12th European Congress on Epileptology Prague ...

ABSTRACTS

12th European Congress on Epileptology Prague, Czech Republic 11th - 15th September, 2016 Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

0074 MARKED REDUCTION IN SECONDARILY GENERALIZED SEIZURES IN PATIENTS TREATED WITH PERAMPANEL FOR 3 AND 4 YEARS Perucca E1, Krauss GL2, Kwan P3,4, Ben-Menachem E5, Wang X-F6, Shih J7, Williams B8, Laurenza A8, Yang H9 1 Department of Internal Medicine and Therapeutics, National Neurological Institute, IRCSS C Mondino Foundation, Pavia, Italy, 2Johns Hopkins School of Medicine, Baltimore, MD, United States, 3Royal Melbourne Hospital, University of Melbourne, Parkville, Vic., Australia, 4The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China, 5 Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 6Chongqing Key Laboratory of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, 7Mayo Clinic, Jacksonville, FL, United States, 8Eisai Inc, Woodcliff Lake, NJ, United States, 9Formerly: Eisai Inc, Woodcliff Lake, NJ, United States

Platform Session 1: Antiepileptic Drugs 1 Monday 12th September 0001 PRESCRIBING TRENDS FOR SODIUM VALPROATE IN IRELAND Murphy S1,2, Bennett K3, Doherty C4,5 1 Neurology Department, Beaumont Hospital, Dublin, Ireland, 2 Epilepsy Ireland, Dublin, Ireland, 3Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, Trinity College, Dublin, Ireland, 4Regional Epilepsy Service, St James’s Hospital, Dublin, Ireland, 5Academic Unit of Neurology, Trinity Biomedical Institute, Trinity College, Dublin, Ireland Purpose: This study was undertaken to describe prescribing practice for the anti-convulsant drug (AED) Sodium Valproate (VPA) in an Irish population of woman of childbearing age during the period of the emergence of new data showing a high rate of developmental abnormalities in offspring of women who took VPA during pregnancy.

Purpose: Perampanel is approved for adjunctive treatment of partial seizures with/without secondarily generalized seizures (SGS) and primary generalized tonic-clonic seizures in patients with epilepsy aged ≥12 years. Here we evaluate seizure outcomes in patients with partial seizures receiving perampanel for 3 and 4 years.

Method: All prescriptions dispensed from community pharmacies in Ireland between 2008 and 2013 inclusive were examined for women aged 16–44 years from all three drug reimbursement schemes in Ireland. Numbers of prescriptions and patients on AEDs were identified, as were co-prescription with folic acid and the oral contraceptive pill. All data analysis was conducted using SAS v9.3.

Method: 1,480 subjects enrolled in the prospective, placebo-controlled, double-blind (DB) Phase III studies (Studies 304/305/306) were randomized to placebo or perampanel for 19 weeks (6-week titration+13-week maintenance). On completion, subjects were eligible for open-label extension (OLE, Study 307) study enrollment (16-week blinded conversion+OLE maintenance period). Seizure outcomes included median percent reduction in seizure frequency/28d relative to pre-perampanel baseline and responder rate. Safety outcomes were also evaluated.

Results: In 2008 3.5 per 1,000 women between 16 and 44 were prescribed VPA and VPA accounted for 28% of all AEDs prescribed in 2008. By 2013 the rate the rate of prescribing had dropped to 3.14 per 1,000 while VPA accounted for 20% of all AEDs prescribed. The largest decline in VPA prescribing was in the Drug Payment Scheme (DPS) and which fell from 14.5% to 4.7%. While rates of prescribing fell for epilepsy, there appeared to be a rise in prescription for other indications of VPA. In 2013, co-prescription of folic acid or oral contraceptives was relatively low across all community schemes.

Results: Of 1,480 subjects randomized in the DB studies, 1,218 enrolled in the OLE. The last daily dose for most subjects with at least 3 years (N = 436) and at least 4 years (N = 78) of perampanel treatment was 12 mg. Median percent seizure reductions during the last year of perampanel treatment for subjects with at least 3 and 4 years of exposure were 61.98% and 70.63%, respectively. Corresponding responder rates were 59.6% and 67.9%, respectively. The largest median percent decrease during the last year of perampanel treatment occurred in SGS: 87.96% and 100% in subjects with 3 and 4 years, respectively. During the OLE, there were 11 deaths: 10 occurred during perampanel treatment or within 30d after the last perampanel dose; 2 were classified as sudden unexplained death in epilepsy; none resulted from suicidality. Ten of the 11 deaths were investigator assessed as unrelated to perampanel; a death due to convulsions was considered possibly related. No new safety signals were seen during long-term perampanel exposure.

Conclusion: Recently the European Medicine’s Agency suggested that alternatives to VPA be considered before prescribing to women of childbearing age. Despite this, the rate of VPA prescribing in Ireland appears to be increasing for indications other than epilepsy. It may be necessary to improve the dissemination of information about the potential negative effects of VPA in this population.

Conclusion: This analysis demonstrated that long-term adjunctive treatment with perampanel for up to 4 years was well tolerated and associated

© 2016 The Authors. © 2016 The International League Against Epilepsy

6

7 Abstracts with markedly improved seizure control, particularly in subjects with SGS at baseline. Support: Eisai Inc.

0003 EFFICACY AND TOLERABILITY OF LACOSAMIDE MONOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED EPILEPSY: A PROSPECTIVE RANDOMIZED DOUBLE-BLIND NON-INFERIORITY TRIAL VS. CONTROLLED-RELEASE CARBAMAZEPINE Baulac M1, Rosenow F2, Toledo M3, Terada K4, Li T5, De Backer M6, Brock M5, Werhahn KJ7 1 Clinique Neurologique, Hôpital de la Pitie-Salpêtriere, Paris, France, 2Epilepsy Center Frankfurt Rhine-Main, Neurocenter, Goethe-University, Frankfurt am Main, Germany, 3Hospital Vall d’Hebron, Barcelona, Spain, 4Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan, 5UCB Pharma, Raleigh, NC, United States, 6UCB Pharma, Brussels, Belgium, 7 UCB Pharma, Monheim am Rhein, Germany Purpose: To compare efficacy and safety of lacosamide (LCM) vs. carbamazepine controlled-release (CBZ-CR) in a double-blind non-inferiority trial (NCT01243177). Methods: Patients (≥16 years) with newly-diagnosed epilepsy and focal (partial-onset) or generalized tonic-clonic seizures randomized 1:1 to twice-daily LCM/CBZ-CR. Flexible up-titration to target dose (LCM:200/400/600 mg/day; CBZ-CR:400/800/1,200 mg/day) was based on seizure control. Primary assessments performed for full-analysis (FAS; patients with ≥1 dose of trial medication) and per-protocol sets (PPS), with subgroup analyses for FAS patients with confirmed focal epilepsy (FE-FAS). Primary variable: 6-month seizure-freedom, following stabilization at last-evaluated-dose. Non-inferiority criteria based on treatment-difference: lower limit of 95%CI > 12%; relative ratio to CBZ-CR (RR) > 20%. Results: Of 888 patients randomized, 886 were included in FAS (LCM: 444; CBZ-CR: 442 [FE-FAS: 405; 405]) and 805 in PPS (408; 397). Kaplan-Meier estimates for proportion of patients with 6-month seizurefreedom indicated non-inferiority of LCM to CBZ-CR for FAS (89.8%; 91.1%)(treatment-difference [95%CI]: 1.3% [5.5%, 2.8%]; RR: 6.0%), PPS (91.5%; 92.8%)(1.3% [5.3%, 2.7%]; 5.7%) and FEFAS subgroup (89.5%; 91.2%)(1.8% [6.1%, 2.6%]; 6.7%). Estimates for 12-month seizure-freedom (FAS) were similar with LCM and CBZ-CR (77.8%; 82.7%)(4.9% [10.9%, 1.1%]; 13.2%). Similar proportions of LCM- and CBZ-CR-treated patients completed 6-months (73.6%; 69.7%) and 12-months (59.5%; 59.3%) on last-evaluated-dose without seizure. Treatment-emergent adverse events (AEs) were reported by 328 [73.9%] LCM-treated and 332 [75.1%] CBZ-CR-treated patients during the overall treatment-period (Drug-related AEs: 165 [37.2%]; 203 [45.9%]). 530 patients (LCM: 266 [59.9%]; CBZ-CR: 264 [59.7%]) completed the trial. Most common reasons for discontinuation: AEs (48 [10.8%]; 69 [15.6%]); consent withdrawn (46 [10.4%]; 38 [8.6%]); lack of efficacy (47 [10.6%]; 31 [7.0%]). Conclusion: In this trial with flexible-dosing (similar to clinical practice), LCM was non-inferior to CBZ-CR as assessed by 6-month seizurefreedom. Similar efficacy of LCM and CBZ-CR was supported by 12month seizure-freedom rates. LCM was generally well tolerated in patients with newly-diagnosed epilepsy. UCB Pharma-sponsored.

0004 POSSIBLE CLINICALLY RELEVANT INTERACTIONS BETWEEN ANTIEPILEPTIC DRUGS AND OTHER PRESCRIPTION MEDICATIONS IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED EPILEPSY Keränen T1, Bruun E2, Virta L3, K€ alvi€ ainen R4 1 National Institute for Health and Welfare, Helsinki, Finland, 2 University of Oulu, Oulu, Finland, 3Research Department, The Social Insurance Institution of Finland, Turku, Finland, 4 Neurocenter, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland Purpose: We aimed to evaluate potentially clinically relevant drug-drug interactions between antiepileptic drugs (AED) and medications used for concomitant disorders in elderly patients with newly diagnosed epilepsy. Method: From the register of the Kuopio University Hospital (KUH) we retrospectively identified community-dwelling patients (n = 529), aged 65 or above, with newly diagnosed epilepsy in whom the first single AED was started. Furthermore, register data of the Social Insurance Institution of Finland were used to assess potential interactions in a nationwide cohort of elderly subjects with newly diagnosed epilepsy. Possible clinically relevant drug interactions at the time of the start of the first AED, as assessed with the help of The SFINX – PHARAO and Micromedex databases, were analyzed. Results: In the KUH population carbamazepine (CBZ) was started in 169 of the patients and in 77 (46%) of these, at least one potentially clinically relevant drug interaction with concomitant medication at the time of CBZ initiation was identified. In the 20 patients started on phenytoin (PHT), potential drug interactions were identified in nine (45%). The most common drugs with potential interactions with CBZ or PHT were dihydropyridine calcium blockers, statins, warfarin, and psychotropic drugs. Among valproic acid users (n = 259), only three cases with potential interactions with other drugs were identified. Conclusion: Our results indicate that potential clinically relevant drug interactions are common in elderly patients with newly diagnosed epilepsy in whom CBZ or PHT is started. In many cases the interaction will lead to reduction in the efficacy of a concomitant medication. Dihydropyridine calcium blockers, statins, selected antipsychotic drugs and warfarin, have the highest risk of interactions with CBZ and PHT.

0005 DISCONTINUATION OF THE FIRST ANTIEPILEPTIC DRUG IN PATIENTS WITH EPILEPSY IN THE GENERAL POPULATION: RATE AND PREDICTORS Beghi E1, Giussani G1, Bianchi E1, Canelli V1, Erba G2, Franchi C1, Nobili A1, EPIRES Group 1 IRCCS-Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milano, Italy, 2Department of Neurology, SEC, University of Rochester, Rochester, NY, United States Purpose: The response to the first antiepileptic drug (AED) is an important indicator of the prognosis of epilepsy. We investigated rate and predictors of discontinuation of the first AED in a well-defined population up to 10 years from the start of treatment. Method: The study population (146,506; year 2008) resided in the province of Lecco, Northern Italy. The medical records of 123 general practitioners were reviewed to identify patients with epilepsy diagnosed by a neurologist during period 2000–2008. The cumulative probability of first AED withdrawal with reasons were calculated at 1, 3, 5 and 10 years from the start of treatment. The role of sex, age at diagnosis, seizure types, disease duration and syndrome was assessed with hazard ratios (HR) and 95% confidence intervals (95%CI).

Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

8 Abstracts Results: 731 patients aged 11 months–94 years were identified and followed for 10,810 person-years. 81 (11.3%) stopped the first AED for ineffectiveness, 20 (2.7%) for adverse events, 117 (16.0%) for seizure freedom, and 45 (6.2%) for other reasons. The probability to withdraw the first AED for ineffectiveness was 2.9% at 1 year, 5.6% at 3 years, 7.6% at five and 10.4% at 10 years. The only predictor was age at diagnosis: compared to patients aged < 15y, those in the 15–34 and 35–54 years groups were less likely to withdraw (HR 0.56, 95% CI 0.32–0.99 and 0.37, 95% CI 0.16–0.87). The probability to withdraw the drug for adverse events was 0.5% at 1 year, 1.3% at 3 years, 2.0% at 5 and 2.5% at 10 years. Due to the small numbers, predictors were not assessed. Conclusion: There is an increasing tendency to withdraw the first AED for ineffectiveness or adverse events up to 10 years from the start of treatment. First AED withdrawal for ineffectiveness can be predicted by age at diagnosis. Study supported by an educational grant from UCBPharma.

0006 PERAMPANEL IN PATIENTS WITH REFRACTORY AND SUPER-REFRACTORY STATUS EPILEPTICUS IN A NEUROLOGICAL INTENSIVE CARE UNIT Rohracher A, Kalss G, Neuray C, Dobesberger J, Kuchukhidze G, H€ofler J, Leitinger M, Trinka E Department of Neurology, Paracelsus Medical University, Salzburg, Austria Purpose: In refractory status epilepticus (SE) GABAergic drugs are no longer effective, and glutamate plays a major role in seizure perpetuation. Perampanel (PER) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. Method: We retrospectively analyzed treatment response, outcome, and adverse effects of add-on treatment with PER in patients with refractory SE in the Neurological Intensive Care Unit, Salzburg, Austria between 09/2012 and 11/2014. Results: Twelve patients (75%women, median age 75 years) with refractory SE were treated with PER administered via nasogastric tube. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). PER was given after a median number of four antiepileptic drugs [2–7] and a median time of 1.5 days [0.8–18.3]. In one patient (8%), clinical improvement was observed within 24 h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [2–12], titrated up to 12 mg [4–12] by 2–4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcome after SE were moderate disability in five (42%), death in three (25%), and persistent vegetative state in two patients (17%). Conclusion: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before administration of PER, the route of administration, as well as relatively low doses, might be responsible for the modest result. PER was well tolerated, and no adverse events were reported.

Platform Session 4: Basic Science 1 Monday 12th September 0007 CORRELATION OF EPILEPTIFORM ACTIVITY AND C-FOS MRNA EXPRESSION IN AN ACUTE IN VITRO MODEL OF EPILEPSY Schlabitz S, Holtkamp M, Fidzinski P Department of Neurology, Charite – Universit€ atsmedizin Berlin, Epilepsy-Center Berlin-Brandenburg, Berlin, Germany Purpose: Intense neuronal activation such as epileptiform activity triggers the expression of the immediate early gene c-fos, whose detection can be used as molecular activity marker. We investigated distribution and time course of c-fos mRNA expression in combined entorhinal cortex-hippocampus brain slices of adult rats (n = 20) in vitro. Our aim was to examine the correlation of c-fos expression with onset and propagation of epileptiform activity. Method: Seizure-like events (SLEs) were induced with 4-aminopyridine (4-AP) and monitored using electrophysiological recordings and imaging of intrinsic optical signals. The amounts of c-fos mRNA were quantified by RT-PCR. Results: SLEs were mainly generated in the neocortex and propagated via the entorhinal cortex to the subiculum without further invading the hippocampal formation. In control slices, a remarkable induction of cfos mRNA occurred due to the slicing procedure. The c-fos expression in untreated slices was highest 2.5 h after slicing (hippocampus 90.5-fold; entorhinal cortex 24.0-fold; neocortex 9.5-fold compared to the basal cfos expression) and showed a continuous decrease at later time points. Following 4-AP exposure, c-fos mRNA levels time-dependently increased within the intervention period of 4 h compared to timematched controls. Correlating with the areas displaying epileptiform activity, the highest levels of c-fos mRNA were measured in the neocortex (8.9-fold) and the lowest in the hippocampus (1.6-fold). As additional signaling pathway with evidence of hyperactivation due to epileptiform acitivity, we determined gene expression of the mammalian target of rapamycin (mTOR). The mRNA levels of mTOR were unchanged in both control and 4-AP treated slices compared to the basal mTOR expression. Conclusion: The previously described stimulation of mTOR signaling by protein phosphorylation seems not to be accompanied by increased gene expression. The results on c-fos expression indicate that acute models of epilepsy are suitable tools to investigate modulation of gene expression by epileptiform activity induced in vitro.

0008 DUAL AND OPPOSING ROLES OF MIR-124 IN EPILEPTOGENESIS ARE MEDIATED THROUGH NRSF AND INFLAMMATORY PATHWAYS Brennan G1,2, Dey D2, Chen Y2, Patterson K3, Magnetta E2, Hall A2, Dube C2, Mei YT2, Henshall D1, Baram TZ2,3 1 Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland, 2Pediatrics, University of California, Irvine, CA, United States, 3Anatomy and Neurobiology, University of California, Irvine, CA, United States Insult-provoked transformation of neuronal networks into epileptic ones involves multiple mechanisms. Intervention studies have identified both dysregulated inflammatory pathways and NRSF-mediated repression of crucial neuronal genes as contributors to epileptogenesis. However, it remains unclear how epilepsy-provoking insults (e.g., prolonged seizures) induce both inflammation and NRSF and whether common mechanisms exist. We examined miR-124 as a candidate dual regulator of NRSF and inflammatory pathways. Status epilepticus (SE) induced by


9 Abstracts kainic acid led to reduced miR-124 expression via SIRT1 – and, in turn, miR-124 repression – via C/EBPa upregulated NRSF. We tested whether augmenting miR-124 using miR-124 mimics/agomirs after SE would abort epileptogenesis by preventing both inflammation and NRSF upregulation. SE-sustaining animals developed epilepsy as detected by 24video EEG monitoring, but supplementing miR-124 did not modify epileptogenesis. Examining this result further, we found that synthetic miR-124 not only effectively blocked NRSF upregulation and rescued NRSF target genes, but also augmented microglia activation and inflammatory cytokines. Thus, miR-124 attenuates epileptogenesis via NRSF while promoting epilepsy via inflammation.

0010 HIPPOCAMPAL CELULAR PRION PROTEIN EXPRESSION IN THE PILOCARPINE MODEL OF TEMPORAL LOBE EPILEPSY Martin KC1, Rockenbach IC2, Soares BL3, Carlotti CG Jr4, Leite JP4, Bianchin MM1,2 1 Hospital de Clınicas de Porto Alegre, Porto Alegre, Brazil, 2 Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 3Universidade Federal do Rio Grande do Norte, Natal, Brazil, 4Universidade de S~ ao Paulo, Ribeir~ ao Preto, Brazil

0009 ACCESSORY b SUBUNITS ARE PROTECTIVE TOWARDS GATING MODIFICATIONS INDUCED BY DRAVET SYNDROME NAV1.1 SODIUM CHANNEL TRUNCATED MUTANTS Terragni B1, Bechi G1, Franceschetti S1, Mantegazza M2 1 Neurophysiology and Clinical Epileptology, Fondazione IRCCS, Istituto Neurologico C. Besta, Milan, Italy, 2CNRS UMR 7275 and University Nice-Sophia Antipolis, Institut of Molecular and Cellular Pharmacology, Valbonne, France

Purpose: Mice lacking cellular prion protein (PrPc) are more sensible to seizures induced by four different pharmacological protocols. The hippocampal formation of these animals disclose supragranular mossy fiber sprouting which resembles those observed in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). These findings suggest that the PrPc may be involved with epileptogenesis in MTLE-HS. Here we investigated the immunohistochemical localization of the PrPc in the hippocampus of animals submitted to the pilocarpine model of temporal lobe epilepsy.

Purpose: Dravet Syndrome (DS) is an epileptic encephalopathy mainly caused by loss of function mutations SCN1A (NaV1.1 Na+ channel a subunit). Truncating mutations are about 50% of DS mutations. We have previously excluded a negative dominance of truncated NaV1.1 mutants on wild type neuronal NaV channels, observing only mild modifications of gating properties, consistent with pure haploinsufficiency as the pathological mechanism of DS. However, a recent study reported that the accessory b1 subunit is necessary for disclosing the negative dominance of a Brugada Syndrome NaV1.5 mutant on wild type NaV1.5. To find out if b subunits are implicated in DS Nav1.1 mutants0 negative dominance, we studied the effect of the truncated mutant NaV1.1R222* on co-expressed wild type NaV1.1, NaV1.2, NaV1.3 Na+ channels in the presence of b1 and b2 subunits. Since NaV1.1 is coexpressed in the heart with NaV1.5, we included this isoform in the study. Methods: We studied the effect of the hNaV1.1R222* truncated mutant on wild type hNaV1.1, hNaV1.2, hNaV1.3 and hNaV1.5, co-expressed with human b1 (hb1) and b2 (hb2) subunits in tsa-201 cells, performing whole-cell patch-clamp recordings. Results: We found no modifications of current amplitude co-expressing hNaV1.1R222* and wild type NaV isoforms in the presence of b subunits, thus confirming that NaV1.1 truncating mutants are not dominant negative. Moreover, we did not observe any modifications of gating properties, except in experiments in which we co-expressed hNaV1.1R222* and hNaV1.5 without b subunits. Conclusion: DS truncated Nav1.1 mutants do not exert a dominant negative effect on wild type NaV channels even in the presence of accessory b subunits, confirming that haploinsufficiency is the pathological mechanism of Dravet Syndrome NaV1.1 mutations. Modifications of gating properties were induced by truncated mutants only when a subunits were expressed alone, consistent with a protective role of b subunits. Funding: EU project DESIRE EFP7-602531.

Method: Status epilepticus was induced using pilocarpine in three different groups of adult Wistar rats. The animals were sacrificed after 18 h, 5 days, and 2 months after the pilocarpine-induced SE. Results were compared with the respective saline-injected controls brains. Slices were processed for hematoxilin-eosin, PrPc imunohistochemistry and neo-Timm Results: PrPc was increased in CA1 and in CA3 regions of hippocampus 18-h after pilocarpine injection. PrPc persisted increased in CA1 region of hippocampus 5 days after pilocarpine injection. In CA2 and granular regions of hippocampus we did not observe significant differences in PrPc expression during acute phase of PMTLE. In the chronic group, PrPc was expressed co-localized with mossy fiber sprouting. Conclusion: Prion protein is differentially expressed at different phases of the pilocarpine model of epilepsy. Transient expression of prion protein during acute phase of pilocarpine model may reflect changes which may render cells more resistant to seizure-induced damage, may be related with apoptosis or may be related with initial phases of neuroplasticity. In the chronic period prion protein is co-expressed in the same regions the mossy fiber sprouting occurs. It might be related with neuroplasticity, epileptogenic processes, neurotransmission, or alternatively, it might be implicated in cellular protection against recurrent seizures. Financial support by CNPq and FAPERGS.

0011 QTC PROLONGATION IN AN EXPERIMENTAL EPILEPSY MODEL Giaka K1, Voulgari N1, Chatzistefanidis D2, Georgiou I1, Markoula S2 1 Laboratory of Human Reproductive Genetics, Medical School, University of Ioannina, Ioannina, Greece, 2Department of Neurology, Medical School, University of Ioannina, Ioannina, Greece Purpose: Sudden unexpected death in epilepsy (SUDEP) has been attributed to lethal arrhythmias due to autonomic imbalance following seizures. The aim of our study is to assess whether epilepsy can result in increased susceptibility to lethal ventricular arrhythmias. We evaluated susceptibility to ventricular arrhythmias in rats, after the induction of Status Epilepticus (SE), using the lithium-pilocarpine model. Method: This is the completion of a study, which includes SpragueDawley rats divided in two groups: The first group included rats, in which Lithium-pilocarpine model was used to induce Status epilepticus (SE), and the second group included saline-control animals. Regarding the first


10 Abstracts group, animals which reached stage 4 and 5 of Racine scale were included in our study. ECG recordings were performed in control and SE rats for evaluation of cardiac electrical activity, 5 months after pilocarpine or saline injection. Ventricular arrhythmias were experimentally induced by the infusion of Beta-adrenergic arrhythmogenic agent isoproterenol in the animals of both groups. An ECG recording was performed during the isoproterenol infusion and QT and RR intervals were measured. QT was corrected for heart rate (QTc) according to Bazett0 s formula normalized to average rat RR. Results: Fifteen SE rats (8males/7females) and 11 control rats (5males/ 6females) were included in the study. There were no differences in terms of gender, age and weight between the two groups. The mean age at pilocarpine or saline infusion was 10 2.7 (SE rats) vs. 11 3.2 weeks (control rats) and the mean weight was 318.7 4.3 vs. 325.2 5.7 g accordingly. The results revealed a significant difference for QTc between epileptic rats (72 7 msec) and controls (60 6 msec) (p = 0.003). Conclusion: Our results imply that the autonomic function of heart is altered in rats with epilepsy, induced by pilocarpine administration. Epilepsy resulted in cardiac dysfunction and increased susceptibility to experimentally induced arrhythmias, as showed by QTc prolongation, following the infusion of arrhythmogenic agent isoproterenol.

0012 DISTRIBUTION OF NEURONAL TISSUE DAMAGE IN EPILEPSY SURGERY SPECIMENS Rossini L1, Garbelli R1, Finardi A1, Tringali G2, Tassi L3, Gozzo F3, de Curtis M1 1 Clinical Epileptology and Experimental Neurophysiology Unit, Neurological Institute Foundation ‘C. Besta’, Milan, Italy, 2 Neurosurgery Department, Neurological Institute Foundation ‘C. Besta’, Milan, Italy, 3Epilepsy Surgery Centre ‘C. Munari’, Niguarda Hospital, Milan, Italy Purpose: Cortical laminar disorganization and the presence of abnormal neuronal and astroglial cell types are histological hallmarks of Focal Cortical Dysplasia type II (FCD-II). A lower cortical neuronal density, the abnormal presence of gliosis and activation of various inflammatory pathways were also described in FCD-II. The present work analyzes the distribution of these neuropathological alterations in the tissue in close proximity to the lesional FCD area, to investigate if seizure activity contributes to tissue damage worsening. Method: We investigated the expression patterns of specific glial, neuronal and inflammatory markers in post-surgical tissue of 16 patients with a neuropathological diagnosis of FCD-II (11 FCD-IIb and 5 FCDIIa). We considered 3 different brain areas identified as epileptogenic by stereo-EEG (in 5 cases): the core of the lesion, the lesion boundary and the peri-lesional area. We also included 4 “epileptogenic” specimens from patients not presenting morphologic/dysplastic alterations (cryptogenic patients). Results: In the core of FCD-IIb lesion we demonstrate: 1 glial activation associated to neuronal loss; 2 activated microglia prevalent in subcortical white matter; 3 peri-vascular CD3-positive T lymphocytes often clustered around balloon cells; 4 changes in BBB permeability identified by fibrinogen extravasation prevalent in the white matter. Little, if any, pathological immunoreactivity was observed in the transition tissue and outside the lesion. Similarly, none or very weak expression of damage biomarkers was observed in FCD-IIa and in cryptogenetic specimens. Conclusion: Our data suggest that brain inflammation is associated to the lesional neuropathological alteration in FCD-IIb. The evidence that tissue around FCD-II lesions and in cryptogenic cases expresses neither Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

lesional nor inflammatory markers, suggests that seizure activity by itself does not contribute to brain damage.

Platform Session 2: Clinical Neurophysiology Monday 12th September 0013 SOURCE LOCALIZATION OF INTERICTAL ACTIVITY IN SUSPECTED EXTRA-TEMPORAL DRUGRESISTANT FOCAL EPILEPSY: A PROSPECTIVE HIGH-DENSITY EEG AND STEREO-EEG STUDY Gibbs SA1,2, Proserpio P2, Rubino A2, Sarasso S3, Tassi L2, Mai R2, Francione S2, Cossu M2, Lo Russo G2, Tononi G4, Nobili L2 1 Neurosciences, Centre d’Etudes Avancees en Medecine du Sommeil, Universite de Montreal, Montreal, QC, Canada, 2‘C. Munari’ Centre for Epilepsy Surgery, Niguarda Hospital, Milan, Italy, 3Universita degli Studi di Milano, Biomedical and Clinical Sciences ‘L. Sacco’, Milan, Italy, 4Psychiatry, University of Wisconsin, Madison, WI, United States Purpose: High-density EEG source imaging (HD-ESI) is an increasingly used approach to non-invasively localize the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). Previous studies report accurate identification of the EZ using HD-ESI, especially in temporal lobe cases. Here, we investigate the clinical validity and added value of localizing interictal discharges (IID) using HD-ESI in patients with suspected extratemporal DRFE, using stereo-EEG as a validating method. Method: Fifty-three consecutive patients with suspected extra-temporal DRFE scheduled to undergo stereo-EEG investigation where enrolled from June 2013 to May 2015. All patients underwent a 60-min 256-electrode EEG recording in addition to standard multimodal presurgical evaluation. IID were marked during offline EEG analysis and exported for HD-ESI. Analysis was performed prior to stereo-EEG interpretation and blinded to its result. We then evaluated whether the anatomical location of the HD-ESI source maximum was in agreement with the stereoEEG-defined EZ. Results: To date, 32 of 53 patients have undergone both HD-ESI and stereo-EEG (age range: 9–50 years). In 4 patients (13%), no IIDs were recorded and therefore, HD-ESI was not performed. HD-ESI localization was in agreement with stereo-EEG findings in 68% of cases (19/28). Analyzing spike-and-wave discharges increased the concordance to 86% (18/21) compared to 43% (3/7) when only focal slow waves were recorded. No differences were observed in regards to lobar localization of the EZ or to histopathological substrate. Interestingly, concordance was higher in MRI-negative patients (86%; 12/14) compared to MRIpositive ones (57%; 8/14). Conclusion: Our results suggest a good concordance between the HDESI source maximum and the SEEG-defined EZ, especially when interictal spikes are recorded. Our protocol suggests that a 60-min high-density EEG recording is sufficient to generate clinically relevant localization results in most patients. In the future, HD-ESI might be useful in improving stereo-EEG electrode placement and stereo-EEG sensitivity, especially in MRI-negative patients.

0014 WHAT DIFFERENT INTRACRANIAL EEG SEIZURE PATTERNS CAN TELL US ABOUT ICTOGENIC MECHANISMS Gnatkovsky V1, Nucci C1, Francione S2, Sartori I2, de Curtis M1 1 IRCCS Istituto Neurologico C. Besta, Milano, Italy, 2Ospedale Niguarda, Centro Chirurgia Epilessia ‘Claudio Munari’, Milano, Italy

11 Abstracts In 30% of patients with pharmaco-resistant focal epilepsy brain areas responsible for seizure generation can be defined exclusively with invasive intracranial recordings. Among them Stereo-EEG intracerebral exploration where neuronal activity recorded from the epileptogenic and the surrounding brain areas can be analyzed to study epileptogenic network. We aimed to develop a computer-assisted system to identify and classify different ictal patterns and markers of the epileptogenic zone (EZ) based on intracranial EEG analysis. To identify different ictal patterns computer-driven intracranial EEG analysis based on time, frequency and space domains was retrospectively applied in parallel with visual inspection in 75 patient with focal epilepsy. Human EEG ictal patterns and electrographic biomarkers were correlated with clinical profile, underlined pathology, neuropathology, location of the EZ and data from the experimental epilepsy models. Based on the ictal transients (pre-ictal events, low-voltage fast activity, slow-wave component, asynchronous activity, bursting activity, post ictal depression and seizure duration) all ictal events from 75 patients were classified in 3 main patterns. Pattern A: long seizures (50–60 s) with low-voltage fast activity onset (125 Hz) and bursting phase with following post-ictal depression at the end. Pattern B: shorter seizures (10– 15 s) with characteristic on-set/off-set high amplitude transients and “higher” low-voltage fast activity (190–200 Hz) onset. Pattern C: Short ictal events (5–10 s) associated with high-amplitude voltage oscillations and 30–60 Hz frequency increase. These patterns were combined with EZ biomarkers low-voltage fast activity at 80–200 Hz and slow transient polarizing shift to improve EZ detection. Similar ictal patterns observed in animal epilepsy models, suggest an important contribution of both inhibitory neuronal component and ion concentration changes during seizure development. The quantified analysis shows a good overlap between contacts within the EZ identified by expert clinicians. Proposed stereo-EEG computerassisted approach can reveal information hidden from visual inspection and help in interpretation of the possible epileptogenic mechanisms.

0015 FREQUENCY-DEPENDENT CHANGES OF NEURAL NETWORKS FROM PRE-ICTAL TO ICTAL STAGES IN CHILDHOOD ABSENCE EPILEPSY Wang X, Huang S, Tang L, Qiu W, Miao A, Wu C Nanjing Brain Hospital, Nanjing, China Purpose: Recent studies have shown that changes of neural networks from interictal to ictal stages in epilepsy may vary with different frequency ranges. The aim of this study was to investigate the frequencydependent changes of neural networks from pre-ictal to ictal stages in typical childhood absence epilepsy (CAE). Method: Ten subjects with newly diagnosed drug-na€ıve CAE were studied using a 275-channel whole-head magnetoencephalography (MEG) system. Neuromagnetic data of each seizure were systematically analyzed from pre-ictal to ictal stages in pre-defined frequency ranges from delta (1–4 Hz) to very high-frequency oscillations (VHFOs, 500– 1,000 Hz). Four parameters including clustering coefficient (C), characteristic path length (L), degree (D) and connectivity strength (S) were calculated to quantify neural network. Results: Significant differences of neural networks were found from pre-ictal to ictal stages in 1–80 Hz. While in 80–1,000 Hz, there were no significant differences of network parameter were found between the two stages.

0016 SEIZURE ONSET PATTERNS IN FOCAL CORTICAL DYSPLASIA AND NEURODEVELOPMENTAL TUMOURS: RELATIONSHIP WITH SURGICAL PROGNOSIS AND NEUROPATHOLOGICAL SUBTYPES Lagarde S1,2, Bonini F1,2, Mcgonigal A1, Chauvel P1,2, Gavaret M1,2, Scavarda D3, Carron R4, Aubert S1, Villeneuve N1, Giusiano B2, Figarella-Branger D5, Trebuchon A1,2, Bartolomei F1,2 1 Epileptology and Clinical Neurophysiology Department, APHM, Timone Hospital, Marseille, France, 2Institut de Neuroscience des Systemes, UMR_S 1106, Aix-Marseille Universite, Marseille, France, 3Paediatric Neurosurgery Department, APHM, Timone Hospital, Marseille, France, 4 Functional and Sterotactical Neurosurgery Department, APHM, Timone Hospital, Marseille, France, 5 Anatomopathology Department, APHM, Timone Hospital, Marseille, France Purpose: The study of intracerebral EEG seizure onset patterns (SOP) is crucial to accurately define the epileptogenic zone and guide successful surgical resection. Until now, several SOP have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. Malformations of cortical development (MCD) are frequent causes of refractory focal epilepsies. Our aim was to describe the SEEG SOP in MCD, and their association with the histological type and the surgical prognosis. Method: We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed MCD (focal cortical dysplasia (FCD) and neurodevelopmental tumours (NDT)). Results: We identified 6 SOP using visual and time-frequency analysis: low voltage fast activity (LVFA); pre-ictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between SOP and histological types was found (p = 0.01). The more prevalent patterns were as follows: in FCD 1: LVFA (23,1%) and slow wave/DC shift followed by LVFA (15.4%) in FCD 2: burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and pre-ictal spiking followed by LVFA (27.6%) in NDT: LVFA (54.5%). Using multivariate analysis, we found that SOP including LVFA was a significant predictive variable of favourable post-surgical outcome (Engel Class I; p = 0.045). Conclusion: LVFA are the most often observed SOP but slow/rhythmic activity may also be seen. In MCD, SOP are linked to the histological type (in FCD 2: pre-ictal spiking & bursts of polyspike followed by LVFA are frequent). Better post-surgical outcome is associated with SOP that incorporate LVFA.

Conclusion: There was a frequency-dependent change of neural networks from pre-ictal to ictal stages in CAE. The neural networks in 1–80 and 80–1,000 Hz play different roles in seizure onset and propagation. The pre-ictal network characters in high frequency bands can be used to better understand the cerebral mechanisms of absence seizures and predict the potential changes of neural networks during the seizures in the future.


12 Abstracts 0018 EPILOG: A FRAMEWORK FOR AUTOMATIC DETECTION OF EPILEPTIC SPIKES AND SUBSEQUENT EEG SOURCE IMAGING TO LOCALIZE THE EPILEPTOGENIC ZONE WITH HIGH SENSITIVITY AND SPECIFICITY Strobbe G1, Keereman V1, Birot G2, Carrette E3, Gadeyne S3, Seeck M2, Meurs A3, Vonck K3, Boon P3, Vulliemoz S2, van Mierlo P1,2 1 Ghent University, ELIS, Ghent, Belgium, 2University Hospital Geneva, Geneva, Switzerland, 3Ghent University Hospital, Ghent, Belgium Purpose: The purpose of the study is to investigate the value of automatic detection of interictal epileptiform discharges and subsequent EEG source imaging to localize the epileptogenic zone during the presurgical evaluation of epilepsy patients. Method: In this study 46 patients who underwent a complete pre-surgical work-up followed by resective surgery were included. Twenty-five patients had long term EEG monitoring recorded with the standard clinical set-up (27 electrodes) in Ghent University Hospital, Belgium. The other 21 patients had 1 h high-density EEG with 128 or 256 electrodes recorded in Geneva University Hospital, Switzerland. Epileptic spike detection was performed using Persyst P13. Afterwards the most prominent spike clusters were localized using in-house EEG source imaging (ESI). For this, a 6-layer patient-specific head model including gray matter, white matter, cerebrospinal fluid, skull, scalp and air, was constructed by segmenting the MRI of each patient. We used LORETA to estimate the localization of the active source in the brain. The localization of the irritative zone was compared to the resection that rendered the patient seizure free (n = 35) or not (n = 11). Sensitivity and specificity of the proposed method to localize the epileptogenic focus were assessed. Results: For the EEG data recorded with standard clinical setup we achieved a sensitivity of 66% and a specificity of 100%. Sensitivity and specificity increased to 94% and 100% when hd-EEG was used. This means that automatic detection followed by ESI has a higher sensitivity and specificity than more established techniques in the pre-surgical evaluation such as ictal SPECT (sens 58% and spec 47%), interictal PET (sens 68% and spec 44%) or structural MRI (sens 76% and spec 53%). Conclusion: EEG source imaging of automatically detected spikes is a non-invasive cost-efficient technique with high sensitivity and specificity that deserves a more prominent role during the presurgical evaluation of epilepsy.

Platform Session 3: Epilepsy in Childhood Monday 12th September 0019 CLINICO-NEUROPHYSIOLOGICAL AND GENETIC FEATURES OF ESES/CSWS IN DENMARK Terney D1, K€olmel MS1, Petersen Khinchi MS1, Grøndahl Olsen T1, Nikanorova M1, Olofsson K1, Brix Kjelgaard D1, Steensbjerre Møller R1,2, Alving J1, Pavlidis E1,3, Rubboli G1,4, Beniczky S1,5, Gardella E1,2 1 Danish Epilepsy Centre, Dianalund, Denmark, 2Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark, 3Child Neuropsychiatry Unit, Neuroscience Department, University of Parma, Parma, Italy, 4 University of Copenhagen, Copenhagen, Denmark, 5 Department of Clinical Neurophysiology, Aarhus University, Aarhus, Denmark Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Background: Encephalopathy with continuous spike and waves during sleep (ESES or CSWS) is a rare, age-related disorder, representing approximately 0.5–0.6% of all childhood epilepsy cases. Diagnosis is based on the clinical features (neuropsychological regression and seizures) and on the typical EEG pattern of almost continuous epileptiform activity during NREM sleep. Objective: To evaluate prevalence and features of patients with ESES/ CSWS at the Danish Epilepsy Center in Dianalund, which is the referring center for diagnosis and treatment of ESES/CSWS in Denmark. Methods: 92 patients with the clinical suspect of ESES/CSWS were monitored with 24-h EEG in 2015. The epileptiform activity was semiautomatically quantified by Brain Electrical Source Analysis (BESA). The diagnosis of ESES was based on clinical and EEG features, using as cut off a minimum spike-and-wave (SWI) index during non-REM sleep of 85%. Results: 50 patients were diagnosed as having ESES/CSWS (27 males, 23 females; mean age 10.5 years). All of them had epilepsy and cognitive decline. Mean number of EEG recordings for each patient was 5.2 (range 1–11). Twenty-four patients met the EEG criteria for ESES/ CSWS (9 idiopathic, 15 cryptogenic/symptomatic) and 2 new patients were classified as possible ESES/CSWS due to low SWI. Seventeen patients presented with diffuse and 7 with focal EEG abnormalities. Based on clinical data and previous EEGs, 24 patient previously diagnosed with ESES/CSWS were furthermore classified as ESES on remission (9 idiopathic, 15 cryptogenic/symptomatic). All cases but 5 (1 possible ESES/CSWS and 4 cases on remission) were on antiepileptic treatment and 6 on cortisone treatment at the time of investigations. Genetic testing was performed in 14 patients, 3 of them showed respectively GRIN2A, SCN2A, HUWE1 mutation. Conclusion: We describe a large cohort of patients with ESES/CSWS, which represents approximately 0.85% of all childhood epilepsy cases (48 out of about 5,850 patients in 2015) in Denmark.

0020 COGNITIVE PROBLEMS AMONG CHILDREN EXPOSED TO ANTIEPILEPTIC DRUGS. PRELIMINARY DATA Elkjær LS1, Bech BH2, Laursen TM3, Christensen J1 1 Department of Neurology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus C, Denmark, 2Department of Epidemiology, Institute of Public Health, Aarhus University, Aarhus C, Denmark, 3National Centre for Register-Based Research, Aarhus University, Aarhus C, Denmark Purpose: Do to relevant concern of cognitive impairment after use of anti-epileptic drugs (AED) in pregnancy women with epilepsy represent a special patient group. This study aims to estimate the long-term effects of prenatal AED-exposure among children aged 9–15 enrolled in Primary and Lower Secondary Education. Method: This prospective population-based cohort study included all children born in Denmark between 1997 and 2007 (n = 721,355). Children were identified and linked across National Registers using the unique Civil Registration System number (CPR) thereby collecting information on outcome, exposure and covariates. The primary outcome was performance in the National Tests, an academic test taken by all students in the Danish Public School. We assessed performance in Danish and Mathematic at different grade levels among AED-exposed and control children. Test scores were standardized and adjusted for risk factors thought to influence cognitive abilities. Results (preliminary): We included (n = 479 021) children in our final analysis. Overall AED-exposed children preformed worse. Valproate exposed children preformed significantly worse in Danish 4th grade MD: 1.36 (2.16; 0.57), 6th grade 1.19 (1.83; 0.55) and in

13 Abstracts Mathematics 6th grade 0.79 (1.27; 0.30). Clonazepam exposed children preformed significantly worse in Danish 6th grade 1.50 (2.33; 0.67) and Mathematics 3th grade 0.85 (1.61; 0.09). Carbamazepine, Lamotrigine and Oxcarbazepine exposed children showed no consistent decrease. Conclusion: Maternal use of AED and especially valproate during pregnancy was associated with a significant decrease in school performance among the offspring.

0021 EMOTIONAL FUNCTIONING, FATIGUE, SLEEP QUALITY AND STRESS IN PARENTS OF CHILDREN WITH EARLY ONSET EPILEPSY: A POPULATIONBASED STUDY Reilly C1,2, Atkinson P3, Memom A3, Scott R4, Gillberg C2, Das K5, Jones C5, Neville B1,6 1 Young Epilepsy, Lingfield, United Kingdom, 2University of Gothenburg, Gillberg Neuropsychiatry Centre, Gothenburg, Sweden, 3Crawley Child Development Centre, Crawley, United Kingdom, 4College of Medicine, University of Vermont, Burlington, VT, United States, 5Young Epilepsy, Research, Lingfield, United Kingdom, 6Institute of Child Health, University College London, London, United Kingdom Purpose: To provide population-based data on emotional functioning, fatigue, sleep quality and stress in parents of children with early onset epilepsy, and to compare findings with those of parents of developmental, age and gender matched children with non-epilepsy related neurodisability. Method: The parents (fathers and mothers) of young children (1– 7 years) with epilepsy (n = 46 to date) in a defined geographical area of the UK are undergoing assessment of depression, anxiety, fatigue, sleep quality and parenting stress. The responses of parents of children with epilepsy are compared with parents of developmental, age and gender matched children with non-epilepsy related neurodisability (n = 36 to date). Alpha level is p < 0.05. Results: Preliminary results indicate that mothers of children with epilepsy report significantly more symptoms of depression (p = 0.018), anxiety (p = 0.002) and fatigue (p = 0.005), but not stress (p = 0.132) or sleep quality (p = 0.172), than fathers of children with epilepsy. Mothers of children with epilepsy reported more difficulties on all measures of functioning than mothers of children with non-epilepsy related neurodisability. However, the difference between mothers of children with epilepsy and the comparison group was only statistically significant for depression (p = 0.001). Fathers of children with epilepsy did not differ significantly from fathers in the comparison group on any of the measures. Conclusion: Mothers of children with epilepsy report higher levels of anxiety, depression and fatigue than fathers, and also report higher levels of depression compared with mothers of children with non-epilepsy related neurodisability. There is a need to identify factors that contribute to parental functioning in early onset epilepsy, and identify why functioning may be more compromised in mothers compared with fathers, but also why depressive symptoms are higher compared with mothers of children with non-epilepsy related neurodisability.

0022 PARENT REPORTED CHILD DEVELOPMENT, QUALITY OF LIFE AND FAMILY STRESS DATA FROM A SCOTTISH POPULATION BASED COHORT OF CHILDREN WITH NEWLY DIAGNOSED EPILEPSY Dorris L1,2, Pownall J2, Waldman J2, McLellan A3, Kirkpatrick M4, Hollands A4, O’Regan M1, MacLeod S1, Zuberi S1 1 Fraser of Allander Neurosciences Unit, Royal Hospital for Children, NHS Greater Glasgow & Clyde, Glasgow, United Kingdom, 2University of Glasgow, Glasgow, United Kingdom, 3 Royal Hospital for Children, Edinburgh, United Kingdom, 4 Tayside Childrens Hospital, Dundee, United Kingdom Purpose: From May 2014 all children 300 cases from 2014 to 2017. This study will compare targeted sequencing of a limited number of genes (11) to a Next Generation Sequencing (NGS) approach (104 gene panel).


Method: Patients are recruited from all 21 centres in the Scottish National Health System. A capture-recapture technique using multiple sources identifies all eligible cases. Eligibility criteria are: children under the age of 3 years ( 50% seizure reduction). Two patients (7.4%) remained seizure free for more than 1 year. Patients with temporal lobe epilepsy showed a better improvement (74.9%) from ATN DBS compared to those with frontal (55.0%) or posterior dominant (56.8%) epilepsy (p < 0.01). However, there were no statistically significant clinical factors affecting favorable outcome after ATN DBS (cognitive derangement before operation, previous surgery, age at onset, duration of epilepsy, number of AED medication before surgery and major structural lesions in MRI). Device removal was performed in three patients because of infection (1 patient, 3.7%) or lack of efficacy (2 patients, 7.4%). There was no major bleeding associated with the operation. Conclusion: Our data suggests that ATN DBS appears to be a safe and efficacious treatment in patients with pharmaco-resistant epilepsy. Especially it may be effective in patients with bilateral temporal lobe epilepsy, which is not applicable to respective surgery.

0094 INCREASED SEIZURE FREQUENCY AFTER EPILEPSY SURGERY: A POPULATION-BASED, OBSERVATIONAL STUDY Bjellvi J, Edelvik A, Rydenhag B, Malmgren K Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden Purpose: Increased seizure frequency occurs rarely after surgery for epilepsy. In one study, extratemporal resections and lower seizure frequency before surgery were associated with an increased risk for seizure worsening (Sarkis et al, Epilepsia 53:1731–1738, 2012). The aim of the present study is to analyze data on unfavorable seizure outcome after epilepsy surgery in a large, prospective series. Method: The Swedish National Epilepsy Register provides prospective, population-based data on all patients (adults and children) operated in Sweden since 1990, including extensive pre-operative data, surgical data including complications, and postoperative follow-up. We have analyzed data on seizure worsening for the period 1990–2013.


40 Abstracts Results: During the period January 1990–December 2013, 1,499 epilepsy surgery procedures were performed. Two year-data were available for 1,300 procedures (86.7%). Of the 1,300 procedures, 773 (59.5%) were temporal lobe resections, and 527 (40.5%) were extratemporal surgeries, including 80 hemispherotomies and 100 callosotomies. The mean age at surgery was 26 years (range 2 months–76 years), and the mean age for the first seizure was 11 years (range 0–57 years). At the 2-year follow-up, 48 patients (3.7%) had increased seizure frequency the last year before follow-up compared to the last year before surgery. Preoperative neurological deficits were significantly associated with postoperative seizure worsening (OR 2.0, 95% CI 1.13–3.7), as were extratemporal resections (OR 3.1, 95% CI 1.7–5.6) and previous epilepsy surgery (OR 2.5, 95% CI 1.4–4.6), while mental retardation (IQ< 70), previous neurosurgical operations in general, or complications at epilepsy surgery were not. Conclusion: Increased seizure frequency after epilepsy surgery is a rare event, which however has to be addressed in presurgical counseling. Persons with preoperative neurological deficits, who have had earlier epilepsy surgery and who undergo extratemporal surgery may be at higher risk for this particular unfavorable outcome.

0095 MEMORY PERFORMANCE AFTER STEREOTACTIC RADIOFREQUENCY AMYGDALOHIPPOCAMPECTOMY – 5 YEARS FOLLOW UP Kramska L1, Malikova H1, Vojtech Z1, Liscak R1, Lukavsky J2, Prochazka T1, Sroubek J1, Kalina M1 1 Na Homolce Hospital, Prague, Czech Republic, 2Academy of Science Czech Republic, Prague, Czech Republic Purpose: To assess memory performance and effect of stereotactic radiofrequency amygdalohippocampectomy (SAHE) in the treatment of mesial temporal lobe epilepsy after 5 years. Method: 30 MTLE patients (mean age 38 years, 14 females/16 males) completed 5 years neuropsychological assessment. 21 patients were treated in the left side, 9 in the right side. We compared Global, Verbal and Visual Memory Quotients (MQ), Attention/Concentration and Delayed Recall by WMS-R before the stereotactic surgery and 5 years after intervention. All patients underwent standard preoperative neurological and neuropsychological evaluation including WADA test. Results: Using paired t-test, patients significantly improved after 5 years since operation in Global MQ, Verbal MQ, Visual MQ, Attention/Concentration and Delayed Recall (p < 0.001). We also compared mean change in right and left sided surgery. Right side operated patients benefitted in Delayed Recall, left side operated patients benefitted in Attention/Concentration. 5 years after surgery 26 patients (87%) were classified as Engel I, 1 patient (3%) as Engel II and 3 patients (10%) as Engel III. Conclusion: We found good neuropsychological and seizure control outcomes after SAHE. This type of epilepsy surgery is minimally invasive intervention, with partial destruction of target structures, sparing the lateral temporal neocortex. We minimized the practice effect by long-term follow up, at least 3 years after previous neuropsychological assessment.

Platform Session 17: Prognosis and Outcome Wednesday 14th September 0096 OUTCOMES OF WEST SYNDROME TREATMENT AT THE LONG-TERM FOLLOW-UP Gamirova R1,2,3, Farnosova M1,3, Zaikova F2,3, Zharikova T3, Sivkova S3 1 Department of Basic and Clinical Pharmacology, Kazan Federal University, Kazan, Russian Federation, 2Department of Pediatric Neurology, Kazan State Medical Academy, Kazan, Russian Federation, 3Kazan Municipal Children’s Hospital No. 8, Kazan, Russian Federation Purpose: To evaluate the long-term outcomes of West syndrome treatment. Method: We retrospectively assessed 150 cases of patients with West syndrome (93 boys and 57 girls). Risk ratios (RR) were calculated with Review Manager 5.3 for favorable outcomes of the therapy after 2 months and more than 3 years from the start of the treatment. We determined as the favorable outcome the clinical remission (the number of seizure-free patients). Results: All patients were separated into 2 groups. 90 infants (60%) in first group received tetracosactide. 60 children (40%), who did not receive tetracosactide, but used different antiepileptic drugs as a monotherapy or combination therapy (valproic acid, levetiracetam, topiramate, vigabatrin, clonazepam, ethosuximide, and barbiturates) were included in the second group. 69 of the 90 infants (77%) in the first group (tetracosactide group) and 13 of 60 subjects (22%) in the second group (non-hormonal antiepileptic group) had no seizures after 2 months of treatment start, RR was 3.54; 95% CI [2.16–5.80], p < 0.00001. However, analysis after 3 years from the treatment beginning showed that 69% (62/90) patients in tetracosactide group and 62% (37/60) in non-hormonal antiepileptic group had clinical remission. RR was 1.12; 95% CI [0.88–1.42], p = 0.37. At that 31% (19/62) of seizure-free children in the first group and 54% (20/37) in the second group had epileptiform activity on electroencephalogram. Transformation of West syndrome into the symptomatic focal epilepsy was identified in 27/90 (30%) in the first group and in 16/60 (27%) in the second group, into the symptomatic multifocal epilepsy in 14/90 (16%) and 12/60 (20%), into the Lennox-Gasto syndrome in 1/90 (1%) and 1/60 (2%), respectively. Conclusion: We found that tetracosactide had more advantages than non-hormonal antiepileptic treatment of West syndrome in the short-term period. But there were no differences in these treatments outcomes in more than 3 years follow up.

0097 LONG-TERM PROGNOSIS OF ADOLESCENT-ONSET IDIOPATHIC GENERALISED EPILEPSIES Vorderwülbecke BJ, Kowski AB, Kirschbaum A, Senf P, Merkle H, Janz D, Holtkamp M Epilepsy-Center Berlin-Brandenburg, Charite – Universit€ atsmedizin Berlin, Berlin, Germany Purpose: Adolescent-onset idiopathic generalised epilepsies (IGE) comprise juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalised tonic-clonic seizures only (EGMO). There is still debate as to whether these subsyndromes represent distinct clinical entities or different aspects of the same neurobiological continuum. Therefore, long-term prognosis of JAE, JME and EGMO patients was compared based on clinical and psychosocial parameters. Method: Medical records of 176 patients (JAE: 53, JME: 66, EGMO: 57) were analysed after a median epilepsy duration of 42.5 years. If still


41 Abstracts alive and within reach, patients were interviewed about comorbidities and biographic variables. Results: Epilepsy onset was significantly later in EGMO (median: 18 years) than in JAE or JME (14 years each; p ≤ 0.001). There were no significant differences with respect to sex distribution or age at last contact. At the end of follow-up, 57% (JAE), 59% (JME), or 63% (EGMO) of patients achieved terminal seizure freedom for at least 5 years. Median duration of terminal seizure freedom was 6 (JAE), 12 (JME) or 8 years (EGMO; not significant). Eighty-five (JAE), 82% (JME), or 77% (EGMO) of patients were still taking anticonvulsants at the end of follow-up. Twenty-nine (JAE, JME) to 48% (EGMO) of patients had tried to discontinue anticonvulsant medication (not significant). Among these, seizure relapse rate was significantly lower among JME patients (21%) than among JAE and EGMO patients (67% and 59%; p ≤ 0.05). Rates of psychiatric comorbidity, higher education entrance qualification and marriage did not differ significantly between groups. Conclusion: At the end of follow-up, three out of five patients achieved a terminal seizure free-period of at least 5 years, but more than four out of five patients were still taking anticonvulsants. Overall, long-term outcome was very similar across all adolescent-onset IGE subsyndrome groups arguing for a neurobiological continuum of IGE.

0098 EPILEPSY WITH AUDITORY FEATURES (EAF): LONGTERM OUTCOME IN A LARGE COHORT Menghi V1,2, Bisulli F1,2, Stipa C1,2, Gizzi M2, Vignatelli L1,2, Licchetta L1,2, Leta C1,2, Tinuper P1,2 1 IRCCS Institute of Neurological Sciences, Bologna, Italy, 2 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy Purpose: Epilepsy with auditory features (EAF), also known as Lateral Temporal Epilepsy (LTE), encompasses an autosomal dominant (ADEAF/ADLTE) form and sporadic cases. Data from sporadic and familial series indicated that EAF is a benign epilepsy syndrome, however there are no studies evaluating the long-term outcome. We aimed to study a large cohort of EAF patients with a 21-year median follow-up to define the outcome of this syndrome in terms of 5-year seizure freedom (Terminal Remission, TR). Method: The study involved retrospective and prospective recruitment of consecutive patients that fulfill criteria of EAF and with a follow-up ≥5 years. TR was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. Survival curves were generated (KaplanMeier method) to evaluate the cumulative time-dependent probability of achieving TR from disease onset. Log-rank test and multivariate analysis (Cox’s regression model) were performed to identify prognostic predictors. Results: We included 108 EAF patients (M/F: 50/58). Mean age at epilepsy onset was 18.6 11.1 years. In the majority of cases (73.1%) family history for epilepsy was negative. Twenty-one patients had structural brain abnormalities (19.8%). At last assessment, 32 patients had achieved TR (“TR group”, 29.6%). Of the remaining 76 cases with no TR (“NTR group”), 24.1% had been in remission for < 5 years and 46.3% still had seizures. The cumulative rate of TR was 30% after 20 years. At log-rank test, age at onset < 11 years and structural brain abnormalities were associated with no TR (p: 0.025 and p: 0.033). Conclusion: Our findings showed that EAF is not a benign focal epilepsy syndrome as previously suggested. Epilepsy outcome appears to be primarily a function of the underlying symptomatic etiology and early epilepsy onset.

0099 POST-STROKE EPILEPSY AND STROKE RECURRENCE IN LONG-TERM FOLLOW-UP AFTER ISCHEMIC STROKE Redfors P1, Jood K1, Holmegaard L1, Malmgren K1, Jern C2 1 Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, 2 Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden Purpose: Post-stroke epilepsy (PSE) is associated with long-term mortality. Less is known about the association between PSE and recurrent stroke. Method: The study is based on the first cohort (n = 1,092) of the Sahlgrenska Study on Ischemic stroke, including patients with first-ever or recurrent ischemic stroke before the age of 70 years. PSE was defined as at least two spontaneous seizures occurring ≥7 days after the index stroke (hence excluding acute symptomatic seizures: AS) or one spontaneous seizure ≥7 days after the stroke if it lead to a decision to start antiepileptic drug medication. Vascular risk factors, socioeconomic factors, etiological subtype of ischemic stroke (TOAST), and stroke severity (NIHSS) were determined at baseline. AS, PSE, recurrent stroke and mortality were assessed through national registers and medical records. Cox regression models were used for identifying predictors of PSE and of mortality. Results: After a median follow-up of 6.3 (IQR 2.8–10.3) years, 22 (2.0%) developed AS, 71 (6.5%) had PSE, 173 (15.8%) had experienced a recurrent stroke and 170 (15.6%) had died. The cumulative rates of PSE were 3.4% (95% confidence interval 2.3–4.5%), at 1 year, 4.8% (3.5– 6.1%) at 2 years, 6.0% (4.5–7.4%) at 5 years and 8.3% (6.1–10.5%) at 12 years. Stroke recurrence (p < 0.001), stroke severity (p < 0.001), cardioembolic stroke (p < 0.05), cryptogenic stroke (p < 0.05), and other determined stroke underlying the index stroke (p < 0.01), were independent predictors of PSE. Twenty-four (33.8%) of the patients with PSE had a recurrent stroke, and 12 (50%) of them had their first seizure after the stroke recurrence. PSE was not a predictor of long-term mortality. Conclusion: In long-term follow-up after ischemic stroke the risk of epilepsy remains high, partly explained by the increased risk associated with stroke recurrence. Interestingly, we found no association between PSE and mortality.

0100 POSTSTROKE EPILEPSY IN SWEDEN: A POPULATION-BASED REGISTRY STUDY Zelano J1, Asberg S2, Redfors P1, Kumlien E3 1 Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2Medical Sciences, Uppsala University, Uppsala, Sweden, 3Neuroscience, Uppsala University, Uppsala, Sweden Purpose: Recently, the incidence of poststroke epilepsy has been assessed in a number of publications on smaller single-center or regional cohorts. We wanted to validate these findings in a population-based manner and used the Swedish Stroke Register (Riksstroke), a national quality registry for stroke with a high coverage (> 90%) both in the acute setting and at 3-months follow-up. Method: Data from all patients with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) during the years 2005–2010 were crossreferenced to the Swedish National Patient Register, a mandatory registry of all hospitalized patients, for information on seizure diagnoses. The study cohort consisted of all patients that survived the first 2 months after stroke without a prior epilepsy diagnosis. A total of 106,520 patients were included and followed until the end of 2014. Poststroke epilepsy was defined as an epilepsy-related diagnosis registered more than one week after the stroke date. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

42 Abstracts Results: The total cumulative incidence of poststroke epilepsy was 7.3%. The cumulative incidence of poststroke epilepsy for infarctions and ICH were 6.7% and 12.4%, respectively. Conclusion: These population-based data provide current estimates of the incidence of poststroke epilepsy in Sweden. Future data analyses on the identified cohort will be conducted to elucidate treatment, prognosis and comorbidities.

0101 VNS IN PATIENTS WITH DRUG RESISTANT EPILEPSY: YOUNGER AGE AT IMPLANTATION MAY RESULT IN BETTER EFFICACY Rener Primec Z1,2, Kajdic N1, Kavcic A1, Krajnc N2, Perkovic Benedik M2, Krzan M2, Korosec M3, Zgur T3 1 Medical Faculty, University of Ljubljana, Ljubljana, Slovenia, 2 Department of Child Neurology, University Children Hospital, Ljubljana, Slovenia, 3Medical Centre Ljubljana, University Institute of Clinical Neurophysiology, Ljubljana, Slovenia Purpose: To assess the results of VNS therapy in all Slovenian patients. Methods: Data were collected from medical records of all Slovenian patients with a VNS device, implanted between 2001 and 2015, regarding seizure frequency, duration, ictal severity; a questionnaire was sent to all patients in 2015 to adress behaviour, language disorders, effects on quality of life (QOL) parameters and side effects . Results: A total of 48 patients received VNS; 37 patients responded to questionnaire, 20 were males (54%). Mean age at seizure onset was 5 years (range 0–24 years), mean age at VNS implantation 18.66 years. Seizure frequency was importantly reduced in 18 patients (48.65%), ictal severity improved in 20 patients (54.05%), seizure duration shortened in 16 (43.24%) and post-ictal recovery time decreased in 19 patients (51.35%). A significat difference was noted between pediatric and adult patients in favour of the former. Positive correlation between longer VNS treatment and responsiveness was observed, when it comes to seizure frequency, ictal severity, seizure duration and post ictal recovery time. Favorable results were also evident in quality of life (QOL) parameters: 12 patients (32.43%) reported improved alertness benefit in concentration, energy and mood was seen in 15 patients (40.54%) and 7 patients (18.92%) reported progress with school work and improvement of memory. Conclusions: VNS remains a safe adjunctive treatment for patients with drug resistant epilepsy and is also generally well tolerated. According to this study VNS therapy positively effects quality of life and is more effective in pediatric patients.

Platform Session 18: Varia Wednesday 14th September 0102 ICTAL DYSTONIC POSTURING WITH TREMOR AND IPSILATERAL TONIC LEG EXTENSION AFTER THE FIGURE OF FOUR SIGN – NEW LATERALIZING AND LOCALIZING SEMIOLOGIC SIGNS Kalss G1, Fr€uhwald U2, Unterberger I2, Walser G2, Luef G2, Bauer G2, Trinka E1 1 Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University Salzburg, Salzburg, Austria, 2 Medical University of Innsbruck, Innsbruck, Austria Purpose: The basal ganglia form circuits with the frontal and temporal neocortices. Unilateral dystonic limb posturing and gyratory movements are ictal extrapyramidal motor signs (iEPMS) arising from the basal ganglia. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

The aim of this investigation was to further delineate seizure semiology and seizure propagation pathways in frontal- (FLE) and temporal lobe epilepsy (TLE) and assess a possible lateralizing and localizing value of iEPMS. Method: The authors analyzed 119 seizures of 38 patients with medically refractory TLE or FLE. We focussed on frequency, order and lateralization of established iEPMS and searched for new semiologic signs. Results: Dystonic posturing (p = 0.002) or seizure propagation from dystonic posturing to version (p = 0.038) were predominantly observed in seizures with temporal lobe origin. Seizure propagation pathways exclusively documented in TLE seizures were aura to head turn (p = 0.028) or dystonic posturing to a generalized seizure (p = 0.005). “Dystonic posturing with tremor” was observed in 5/62 TLE seizures, in 4/21 TLE patients, and was contralateral to the seizure onset zone in 100%. “Unilateral tonic leg extension after the figure-4-sign” (TEAF4) was ipsilateral in all (n = 6) of observed seizures in three TLE patients. Immobile limb (p = 0.028), “dystonic posturing with tremor” (p = 0.012) and TEAF4 (p = 0.014) were exclusively found in the TLE group. Post operative outcome was 73.68% seizure freedom (Wieser 1, n = 15), 21.05% only auras (Wieser 2, n = 4), and 5.26% (one patient) with one to three seizure days per year (Wieser 3, n = 1) in the TLE group. Forced blinking (p = 0.034) and grimacing (p = 0.002) were exclusively found in FLE seizures. Conclusion: Basal ganglia seem to be an important propagation pathway as documented by the various semiologic signs following dystonic posturing in TLE but not in FLE seizures. The sequence of iEPMS in TLE had strong lateralizing value. Unilateral dystonic posturing with tremor lateralized contralaterally and TEAF4 ipsilaterally to the seizure onset zone.

0103 MOTOR PHENOMENA IN VASOVAGAL SYNCOPE: CLINICAL ASPECTS AND COMPARISON WITH CONVULSIVE SEIZURES Shmuely S1,2, van Dijk JG3, Thijs RD1,2,3 1 Stichting Epilepsie Instellingen Nederland (SEIN), Research, Heemstede, The Netherlands, 2UCL Institute of Neurology, NIHR University College London Hospitals Biomedical Research Centre, London, United Kingdom, 3Department of Neurology, LUMC Leiden University Medical Center, Leiden, The Netherlands Purpose: Limb movements occur frequently in vasovagal syncope (VVS). We assessed motor phenomena in VVS and convulsive seizures (CS) to aid differential diagnosis. Method: We studied video-EEG tilt table test results of subjects >12 years. We studied phasic myoclonus (PM) and tonic postures (TP) of the arms and for each movement noted the time of occurrence, laterality and synchronicity. PM were likewise studied in video-EEG records of 48 CS. ICI variability was quantified by calculating mean consecutive differences (MCD) of ICI. Results: Of 410 tilt table tests events occurred in 255 cases, of which 52 were VVS. Six cases were excluded because of insufficient video quality, leaving 46 VVS records. All VVS movements were accompanied by loss of tone. TP occurred in 31 cases (67%), PM in 25 cases (54%), and both in 20 (43%). TP was bilateral 21 cases and synchronous in 14; elbow flexion was seen in 30 and extension in two cases. PM was bilateral in 19 cases and synchronous in 10. The median number PM was two in VVS (range 1–7), whereas in CS the median was 51 (range 20–191; Mann– Whitney p < 0.001). MCD of ICI showed higher variability in VVS compared to CS (Mann-Whitney p < 0.001).

43 Abstracts Conclusion: PM and TP were common in VVS, but semiology differed from that of CS. In VVS, PM were fewer in number, less rhythmic, and coincided with loss of tone. The lack of any overlap in the number of PM suggests that 8 mM). Field potentials from the hippocampal CA1 and CA3 regions were recorded using multiple extracellular electrodes. To study the effect of CA3 activity on CA1, further measurements were taken from isolated CA1 slices. Results: Spontaneous seizure-like events were generated within the CA1 region with a mean inter-seizure interval of 60.4 4.4 s. Seizures did not occur abruptly, but were preceded by a progressive buildup of high-frequency activity at 200 Hz. The CA3 region generated interictal discharges propagating to CA1 and interfering with the high-frequency activity. Recorded data motivated a minimal mathematical model, with state space defined by mean firing rate and excitability. For intermediate excitability, model contains a bistability of low-firing rate and high-firing rate state. Slow excitability dynamics lead to emergence of cyclic regime shifts between the two states. However, random noise or external perturbation also affect state switching. Simulations demonstrate that during stable part of the interictal period excitatory input reversed transition to seizure, while in low stability states it could induce seizure. Conclusion: This study demonstrates the dual nature of the effect of excitatory synaptic on input seizure initiation. The impact of the excitatory perturbation depended on the spontaneously slowly changing state of the system. These observation represent plausible explanation for dual, both proconvulsive and anticonvulsive, effect of interictal epileptiform activity.

P110 A NEW RAT MODEL OF INFANTILE SPASMS BASED ON METHYLAZOXYLMETHANOL (MAM)-INDUCED CORTICAL DYSPLASIA Kim E-H1, Yum M-S2, Lee M2, Ko T-S2 1 CHA Gangnam Medical Center, Seoul, Korea, 2Asan Medical Center, Seoul, Korea Purpose: Cortical dysplasia (CD) is a well-established etiology of medically intractable epilepsies and cognitive disabilities in children. We develop a new rat model of infantile spasms using postnatal N-methyl-Daspartate (NMDA) provocation in rats with prenatal methylazoxymethanol acetate (MAM)-exposed CD and determine the structural and electrophysiological features of this model.

P109 EFFECT OF EXTERNAL PERTURBATIONS ON SEIZURE DYNAMICS – IN VITRO RESULTS AND COMPUTATIONAL MODELLING Hlinka J1, Chang W-C2, Palus M1, Jefferys JGR2,3, Jiruska P4 1 Institute of Computer Science, Czech Academy of Sciences, Prague, Czech Republic, 2University of Birmingham, Birmingham, United Kingdom, 3University of Oxford, Oxford, United Kingdom, 4Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

Method: To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, IP) were injected to pregnant rats at gestational day 15. The structural changes of the prenatally MAM-exposed rat brain were validated using magnetic resonance imaging. In prenatally MAMexposed rats and the controls, spasms were triggered by single (15 mg/kg on postnatal day 15 [P15]) or multiple doses (6 mg/kg on P12, 10 mg/kg on P13, and 15 mg/kg on P15) of NMDA and the data of spasms expression were monitored. In prenatally MAM-exposed rats with single NMDA-induced spasms, we obtain the intracranial electroencephalography (EEG) and examine the pre-treatment response to adrenocorticotropic hormone (ACTH) or vigabatrin.

Purpose: Understanding of the mechanisms of transition to seizures represents key prerequisite for their successful control. Previously we have demonstrated in vitro that seizures are preceded by detectable changes in

Results: Compared to saline-exposed controls, the prenatally MAMexposed rats showed thinning of entire cortex and reduced size of both hippocampi. The prenatally MAM-exposed rats showed significantly increased EEG powers (lV2) of gamma frequency (25–80 Hz) and 80–


45 Abstracts 100 Hz ripples during spasms compared to controls (p = 0.029) and shorter latency to onset of spasms compared to the controls during the multiple NMDA-triggered spasms. Vigabatrin pretreatment significantly suppressed the development of spasms in prenatally MAM-triggered rats compared to the controls (p < 0.05), while ACTH did not. Conclusion: This study demonstrates that the prenatally MAM-exposed rats with cortical malformation showed increased susceptibility to spasms with denser high frequency oscillations during spasms and relevant response to vigabatrin. This model can be considered as a model of infantile spasms based on CD.

P111 ALISKIREN, A DIRECT RENIN INHIBITOR, PROTECTS AGAINST PENTYLENETETRAZOLE-INDUCED SEIZURES IN MICE Łukawski K1, Raszewski G1, Czuczwar SJ1,2 1 Department of Physiopathology, Institute of Rural Health, Lublin, Poland, 2Department of Pathophysiology, Medical University of Lublin, Lublin, Poland Purpose: The experimental studies show that the brain renin-angiotensin system could be involved in the regulation of seizure susceptibility and that certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin AT1 receptor antagonists can possess anticonvulsant activity. The purpose of this study was to examine the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, against pentylenetetrazole (PTZ)-induced seizures in mice, which is an animal model of myoclonic convulsions. Method: Both, effects of aliskiren on the PTZ threshold and the protective efficacy of antiepileptic drugs (AEDs) such as valproate (VPA), phenobarbital (PB) and ethosuximide (ETX), against clonic convulsions induced by PTZ were evaluated. Additionally, the rota-rod and passive avoidance test were used to assess the adverse effects of the combined treatment with aliskiren and AEDs. Aliskiren and AEDs were administered intraperitoneally (i.p.) while PTZ was injected subcutaneously (s.c.). Results: Aliskiren at the dose of 75 mg/kg significantly raised the PTZ threshold, raising the median convulsive dose of PTZ from 63.0 to 80.0 mg/ kg (p < 0.05). Aliskiren at the lower dose (50 mg/kg) was ineffective. Moreover, aliskiren at the subthreshold dose of 50 mg/kg enhanced the protective action of VPA and PB against PTZ-induced convulsions, decreasing their ED50 values from 170.7 to 128.8 mg/kg (p < 0.01) and from 13.0 to 9.7 mg/kg (p < 0.01), respectively. When combined with ETX, aliskiren (50 mg/kg) reduced its ED50 value from 138.2 to 108.6 mg/kg, however, it was not statistically significant. Motor coordination in the rota-rod test and long-term memory in the passive avoidance task were not impaired by the combined treatment with aliskiren and AEDs. Conclusion: This is the first study to suggest that aliskiren might be considered as an adjuvant in hypertensive patients with myoclonic seizures. Certainly, a clinical verification of using aliskiren in such patients would be necessary.

P112 EFFECT OF GABA-B DRUGS ON SEIZURES AND MOTOR PERFORMANCE IN IMMATURE RATS Mares P1, Kratka M1, Burchfiel J2 1 Inst. Physiology Czech Academy of Sciences, Prague, Czech Republic, 2University of Rochester Medical Center, Rochester, NY, United States Purpose: An agonist of GABA-B receptors baclofen is used clinically in the treatment of spasticity but its use in epilepsy is contraindicated. We described mixed anti- and proconvulsant action of baclofen in immature

rats and the aim of the present study was to check possible changes of cortical epileptic afterdischarges and motor performance after repeated administration at an early stage of development. Method: Nests formed by 10 male pups were always divided into group injected repeatedly at P7-P11 with baclofen (3 mg/kg i.p.), an antagonist of GABA-B receptors CGP35348 (50 mg/kg i.p.) or saline. A number of nests used was calculated to have ten animals in each age and dose group. The first series studied postnatal development of sensitivity to cortical epileptic afterdischarges, the second series studied maturation of motor abilities of the above mentioned three groups of rats up to adulthood. Results: There were no significant differences among the three groups in the cortical epileptic afterdischarges. On the contrary, motor development was markedly but transitory affected by previous treatment. Spontaneous locomotion was affected in either GABA-B group (more after baclofen than after CGP35348) – there was a shorter distance and slower locomotion especially two weeks after administration of the drugs. Rat pups injected with either GABA-Bergic drug were worse than control animals in some motor tests used. Most marked change was in the test of horizontal ladder in CGP35348 group. The differences were minimal at the age of 31 days and no longer present in young adult rats (60 days old). Conclusion: Our data demonstrated different development of physiological motor performance and pathological epileptic seizures.

P114 A NEW RAT MODEL OF SUSTAINED CORTICAL SPIKE-AND-WAVE SEIZURES Sevcencu C1, Jiao J1,2, Harreby K1, Jensen W1 1 Department of Health Science and Technology, Aalborg University, Aalborg, Denmark, 2Department of Pain and Rehabilitation, Jilin University, Changchun, China Purpose: Although many animal models of seizures exist, new models more suitable for specific purposes are still needed. For example, the antiepileptic effects of neuromodulation therapies depend critically on the stimulation parameters, including the pulse duration, frequency and intensity. Consequently, optimization of such therapies requires many animals for testing such parameters alone or combined, which is costly and time consuming. Such drawbacks could be reduced using models which allow repetitive testing in one and the same animal. This study was performed to develop an acute animal model of seizures suitable for such tasks. Method: This study was performed on 11 Sprague Dawley rats (250– 450 g) anesthetized with a ketamine/xylazine combination. The electrocorticogram and intracortical signals were simultaneously recorded using a custom made electrode placed on the somatosensory cortex. A protocol of controlled IV infusion of pentylenetetrazol (PTZ) was developed to induce and maintain stable spike-and-wave (SW) discharges for as long as needed. Results: SW discharges were induced and maintained stable for 2 h in all rats through a 2-stage infusion of PTZ. During the first stage, a transition from normal to SW discharges was elicited by 2.5 min infusion of 10 mg/kg/min PTZ up to a total dose of 25 mg/kg. During the second stage, a stable PTZ dose of around 25 mg/kg was maintained for 2 h via a 0.21 mg/kg/min PTZ infusion rate. This resulted in consistent SW discharges in the frequency range of 2–3 Hz and with similar morphology for 2 h. Conclusion: The present model of SW seizures allows repetitive testing of neuromodulation parameters or combinations of such parameters in one and the same animal. Besides being suitable for such tests, this SW model of sustained cortical seizures can also be used in pharmacological studies for investigating e.g. the action mode and stability of antiepileptic drugs.


46 Abstracts P115 ACUTE ELECTROPHYSIOLOGICAL CHANGES INDUCED BY CORTICAL PHOTOCHEMICAL ISCHEMIA IN ADULT RAT Svoboda J, Posusta A, Litvinec A, Jiruska P, Otahal J Developmental Epileptology, Institute of Physiology CAS, Prague, Czech Republic Purpose: Stroke is the most commonly identified cause of epilepsy in adults older than 35 years and accounts for more than 50% of all new cases of epilepsy in the elderly population. Although stroke is the second most frequent cause of death worldwide approximately three times higher is a number of people who suffer stroke per year and remain alive. Occurrence of acute symptomatic seizure raises morbidity and mortality. The risk of symptomatic seizure in patients after stroke is approximately 9% with higher risk during first two weeks. The aim of the study is to characterize and quantify epileptiform graphoelements occurring early after photothrombic induction of focal cerebral ischemia in motor cortex in adult rats. Method: Silver wire electrodes were bilaterally implanted over sensorimotor cortices and into the contralateral hippocampus in adult Wistar rats. 24 h after the implantation the focal cortical ischemia was induced by photohrombosis. Briefly, desired cortical area was illuminated through skull with high power green laser for 10 min immediately after intravenous application of photosensitive dye Rose Bengal. EEG was recorded at least for 3 h since stroke induction. To evaluate extension of ischemic lesion a tetrazolium staining was performed 24 h later. Results: In all animals photothrombosis induced consistent ischemic lesion of sensorimotor cortex with diameter 4–6 mm penetrating all cortical layers leaving subcortical white matter intact. Video-EEG monitoring revealed occurrence of epileptiform graphoelements arising mainly from peri-infarct area. Those events were accompanied by jerks of forelimbs. Conclusion: Photothrombosis of sensorimotor cortex in adult rat is reliable model of acute symptomatic seizures and is thus suitable for research of post-stroke epileptogenesis. Acknowledgement: The study was supported by grant project no. 1533115A from Czech Health Research Council.

P116 COMPUTATIONAL ASSESSMENT OF HIPPOCAMPAL SCLEROSIS IN MESIAL TEMPORAL LOBE EPILEPSY Toeglhofer AM1, Kimiwada T2, Fuchs T3, Frei K4, Yonekawa Y4, Haybaeck J1 1 Department of Neuropathology, Medical University of Graz, Graz, Austria, 2Department of Neurosurgery, Miyagi Children’s Hospital, Sendai, Japan, 3Memorial Sloan Kettering Cancer Center, New York, NY, United States, 4Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland Purpose: The hallmarks of hippocampal sclerosis (HS) in mesial temporal lobe epilepsy (mTLE) are neuronal cell loss, granule cell dispersion and mossy fiber sprouting. The underlying molecular mechanisms of those structural alterations are still poorly understood. For preventing permanent neurological deficits in mTLE patients, resection of the epileptogenic area is the most effective treatment. Altered cellular and molecular hippocampal sclerosis patterns might predict seizure history or outcome after hippocampal resection. To avoid interpretation biases during manual HS grading, we developed a novel method to assess HS computationally. Method: For computational HS illustration, resected hippocampal tissue of 22 drug-resistant mTLE patients with HS (mean age 32.8 10.5 years, 59% females) and five post-mortem control samples (mean age 55.8 6.7, 10% females) were obtained. Tissue slides were Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

immunohistochemically stained with an antibody against the DNA-binding, neuron-specific protein NeuN and digitalized for computational analysis. The hippocampal cellular band was tagged manually on digitalized images. Depth, appearance and edges of neurons on the hippocampal cellular band were integrated for this approach. Results: Neurons of the hippocampal cellular band were automatically detected by this novel algorithm on digitalized slides of resected hippocampal tissue. The intensity of each computed data point was plotted against the position on the hippocampal cellular band. The generated linearized profile of the cellular band represents the neuronal cell density with respect to the band location. Conclusion: By the usage of this new method, it might be possible to evaluate the grade of HS in mTLE patients computationally and without interpretation biases. The reliability of linearized site dependent neuronal cell density, obtained by the developed computational approach, in HS of mTLE patients has to be validated. The correlation of the neuronal cell density with regard to the band location and common non-computational grading systems, like Wyler or Bl€umcke scoring, has to be evaluated.

P117 NEUROCHEMICAL CHANGES IN THE ENDOTHELIN-1 MODEL OF FOCAL CEREBRAL ISCHEMIA IN IMMATURE RATS Vondráková K1,2, Vales K1, Kubov a H1, Kacer P3, Tsenov G1 1 Institute of Physiology, v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic, 2Faculty of Science, Charles University in Prague, Prague, Czech Republic, 3Department of Organic Technology, Institute of Chemical Technology, Prague, Czech Republic Purpose: Focal cerebral ischemia (FCI) triggers cascade of events and pathways, which lead to seizure generation and neurodegeneration in immature brain. These can be modulated in the animal model by intracerebral infusion of endothelin-1 (ET-1). Endothelin-1 acts via ETA and ETB receptors. As demonstrated, activation either ETA or ETB receptors lead to the seizures development while neurodegeneration is associated with ETA receptors activation. Aims of this study were to investigate ischemia-induced neurochemical changes in immature brain and to clarify possible causes of following seizures development. Method: P12 rats were stereotaxically implanted with cannula and microdialysis probe into the right dorsal hippocampus under isoflurane anesthesia (1.5%). FCI was induced by the infusion of ET-1 (40pmol/ uL), controls received a corresponding volume of the vehicle. Group of animals was infused with the selective ETB receptors agonist (4-Ala-ET1; 40pmol/uL). Microdialysate was collected during 2 h after infusion. Results: ET-1 caused decrease (p < 0.05) of extracellular concentration of glutamate by ~48%, GABA by ~82% and pyruvate by ~39%. However, lactate and dopamine levels were increased by ~570% and 176% respectively. Similar findings were found after selective activation of ETB receptors. Analysis of inflammatory markers (Leukotriene B4 and Prostaglandin E2) showed increased (p < 0.05) concentrations by ~136% and ~68% respectively after ischemia. Furthermore, increased concentrations of both markers were detected after 4-Ala-ET-1 infusion. Conclusion: Our results pointed that inflammatory process plays a crucial role in the development of seizures followed intrahippocampal infusion of the ET-1 in immature brain. However, other factors (lactic acidosis, glutamate-GABA ratio, oxidative stress, etc.) should not be excluded. This study was supported by research grants GACR P304/12/G069 and P304/14/20613S. Supported by CZ.2.16/3.1.00/22197, NPUI(LO) MSMT-34870/2013) and GAUK No.165115.

47 Abstracts

Basic Science 2 Monday 12th September P118 TRAINING IN NOVELTY EXPLORATION TASKS PREVENTS COGNITIVE DECLINE IN A RAT MODEL OF TEMPORAL LOBE EPILEPSY ^ 1,2, Rocha I2, Cunha-Reis D1,2 Amaro-Leal A 1 Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal, 2Cardiovascular Autonomic Function Lab, Institute of Physiology & CCUL, Faculty of Medicine, Universidade de Lisboa, Lisboa, Portugal Temporal lobe epilepsy (TLE), characterized by recurrent seizures with origin in the temporal lobe, is highly refractory and associated with severe cognitive impairment. Since we previously showed that novelty training improves cognitive performance, we now tested if a novelty training program based on novel spatial distribution of objects can prevent cognitive decline in an animal model of TLE. Male Wistar rats exhibiting spontaneous recurrent seizures (SRSs) (Li2 + -pilocarpine) and Sham rats were either subjected to a training program or were without any training (na€ıve, N group). SRSs and Sham novelty trained (NT) animals were exposed to three objects always presented in a different spatial configuration in a holeboard for two weeks. As control for novelty training, SRSs and Sham animals were also trained by exposure to either a fixed object’s spatial configuration (FT), or to the holeboard without any object (HT). All animals (trained and na€ıve; SRSs or Sham) were subjected to radial arm maze (RAM) test to evaluate hippocampal-dependent spatial learning. Regarding the training program, all trained SRSs rats had lower spatial exploratory activity (rearings) and exploration of objects (nose-pokes) but a longer traveled distance when compared to Sham rats. NT SRSs and Sham rats showed a higher exploration ability (nose-pokes) when compared to FT and HT animals. All trained animal groups (SRSs and Sham) were more efficient (committed less total failures) in finding the baited arms when compared to the respective N group. NT SRSs were more efficient in finding the baited arms than FT and HT SRSs. No differences were observed between different trained Sham groups. Our data shows that a training routine based on novel spatial distribution of objects can improve SRSs rat cognitive performance in spatial learning tasks suggesting that novelty exposure may be useful for cognitive recovery in TLE. Supported by FCT (PTDC/SAU-NEU/103639/2008, SFRH/BPD/ 81358/2011, SFRH/BD/88350/2012).

P119 ABERRANT NEURONAL ACTIVITY AND BEHAVIOR IS UNDERLINED BY THE LOSS OF CONSTITUTIVE ANDROSTANE RECEPTOR Boussadia B1, Gangarossa G2, Lakhal L3, Rousset M-C1, Pascussi J-M1, Ghosh C4, Janigro D5, Marchi N1 1 IGF Montpellier, Montpellier, France, 2College de France, Paris, France, 3INRA Toxalim, Toulouse, France, 4Cleveland Clinic, Cleveland, OH, United States, 5Flocel Inc, Cleveland, OH, United States Introduction: Nuclear receptors (NR) are a group of transcription factors emerging as key players in normal and pathological CNS development. Clinically, an association between the constitutive androstane NR (CAR) seizures and cognitive impairment was proposed, however never experimentally investigated. Methods: We have used CAR/ C57BL/6 and wild type mice and performed longitudinal video-electroencephalographic recordings (Video-EEG) to characterize frequency spectra distribution (0.5– 30 Hz), spontaneous spike activity or seizures, and behavioral tests (recognition, memory, motor coordination, learning and anxiety). We

evaluated whether neuronal in vivo changes were associated with existent neuro-vascular defects. Brain cell morphology was assessed using 2-photon or electron microscopy and fluorescent immunohistochemistry. Results: Video-EEG monitoring revealed a decrease in 3.5–7 Hz theta waves during the awake/exploration and sleep periods. Consistent with EEG read-outs we reported recognition memory impairment and increased anxiety in CAR/ mice, while locomotor activity was not affected. EEG and behavioral abnormalities in CAR/ mice mirrored structural changes, including tortuous fronto-parietal penetrating vessels and localized vascular micro-leakages. At the cellular level we found reduced ZO-1, but not CLDN5, tight junction protein expression in cortical and hippocampal isolated microvessel preparations. Interestingly, the neurotoxin kainic acid, when injected peripherally, provoked a rapid onset of generalized convulsions in CAR/ as compared to WT mice, supporting the hypothesis of vascular permeability. The morphological phenotype of CAR/ mice also included modifications of GFAP/IBA1 glial cells in the parenchymal or adjacent to collagen-IV+ or FITC+ microvessels. Neuronal defects were subtle, although increased cortical NEUN+ cell density, hippocampal granule cell dispersion and increased NPY immunoreactivity in the CA1 region were detected in CAR/ mice. The latter may contribute to the in vivo phenotype. Conclusions: Our results indicate electroencephalographic and behavioral changes in adult CAR/ mice are associated to developmental structural brain defects. The latter could also contribute to the increased vulnerability to neurotoxins and seizures.

P120 THE PECULIARITIES OF EPILEPTIFORM ACTIVITY FORMATION IN RATS DURING SUBCONVULSIVE DOSES PICROTOXIN AND PENTYLENETETRAZOLE REPETITIVE INJECTIONS Denysenko O1,2, Denysenko O1, Kaschenko O1, Lyashenko S1, Onufrienko O1, Shandra A1 1 Normal Physiology Department, Odessa State Medical University, Odessa, Ukraine, 2Human and Animal Physiology Department, Odessa National University, Odessa, Ukraine Purpose: Aim of the study was to investigate the differences in the formation of epileptiform activity (EFA) after repetitive injections of picrotoxin (PTX) and pentylenetetrazole (PTZ) in subconvulsive doses during several hours. Method: Experiments were carried out on 33 male albino rats (180– 250 g). Electrodes were stereotaxically implanted bilaterally in the frontal cortex, ventral hippocampus, and mediodorsal thalamus. EEG registration and behavioral alterations were observed within 60 min prior to injection of the convulsant and 5–6 h after. EFA was induced by repeated i.p. injections of covulsants each 30 min. The total dose of PTX and PTZ (Sigma, USA) received by rats in the experiment did not exceed 6.5 and 85 mg/kg, respectively. PTZ administered in doses of 0.9 mg/kg in the first injection and 0.7 mg/kg in subsequent injections (n = 19). PTX administered in doses of 25 mg/kg in the first injection and 10 mg/kg in subsequent injections (n = 14). Results: According to the peculiarities of EFA, we could divide into two types. The first type corresponded to the development of only SWDs (68.4% animals with PTX and 100% – with PTZ). The second type were recoded only after injections of PTX (31.6%) – regular cortical spike activity with generation of separate short-lasting SWDs. Animals with the first type of EFA showed clonic seizures of different intensity gradual development. 10.5% rats after injections of PTX and 57% – after injections of PTZ showed intensive generalized clonic-tonic seizures development. There were less prolonged SWDs with less expressed clonic seizures in the rats with the second type of EFA.


48 Abstracts Conclusion: Development of only SWDs were observed in animals with PTZ. After PTX injections two types of EPA were recorded. Results show the relationship between the frequency of cortical spike activity and the ability to generation ictal events.

P121 ANTIEPILEPTIC POTENTIAL OF K+-CHANNELS IN ACUTE AND CHRONIC MODELS OF EPILEPSY Köhling R, Kirschstein T Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany Purpose: The vast majority of ictal epileptic events terminate spontaneously. However, the mechanisms that counteract ictal activity and thus stop seizures are poorly understood. Here, we investigated the role of K+channels in both acute models and in chronic epileptic tissue. Method: We used both electrophysiological and biochemical approaches to investigate the role of K+-channels in acute epileptic hippocampal slices, as well as in slices from pilocarpine-treated chronically epileptic animals. Results: In the Gabazine acute model of epilepsy, the afterhyperpolarizing potential following a train of action potentials is lost due to a protein kinase A-dependent process. In chronic epileptic tissue, in turn, the expression of the Ca2+-activated K+-channel KCa2.2 is down-regulated and consequently, the tail currents after prolonged depolarization are critically reduced ins such a way that further pharmacological inhibition of these channels markedly facilitates epileptic discharges in the acute 0Mg2+-model of epilepsy. Moreover, chronic inhibition of casein kinase 2 in vivo enhanced the currents mediating the slow afterhyperpolarizing potential, rendering slices practically resistant to induction of acute epileptiform discharges. Conclusion: In various epilepsy models, K+ channels are altered, resulting in impaired capability of repolarization/hyperpolarization. Thus, K+ channels appear to play a major role in counteracting hyperexcitability. Our results further show that casein kinase 2 could be a promising novel target to facilitate K+ channel function and suppress seizures.

P122 DO SEIZURES EFFECT CEREBRAL UPTAKE MECHANISMS FOR ESSENTIAL COMPOUNDS? PRELIMINARY RESULTS FROM RAT LITHIUM PILOCARPINE MODEL Mann A1, Ekstein D2, Benifla M3, Ben Hur T2, Eyal S1 1 Institute for Drug Research, School of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel, 2Department of Neurology, Hadassah Hebrew University Medical center, Jerusalem, Israel, 3Department of Neurosurgery, Hadassah Hebrew University Medical Center, Jerusalem, Israel Purpose: While clear evidence suggests disruption of the electrolytes and neurotransmitter balance in the epileptic brain, the effect of the disease on entry mechanisms of essential compounds, such as folic acid, thyroid hormones and monocarboxylates, are yet to be elucidated. These compounds are known to play an important role in proper cellular function and metabolism and their deprivation is associated with numerous CNS disorders and could potentially even contribute, either directly or indirectly, to pharmacoresistance. It was therefore our goal to characterize the effect of epileptic seizures on major essential compounds transport pathways into the brain. Method: Studies were conducted using the rat lithium-pilocarpine model of temporal lobe epilepsy. Brains were harvested 8–10 weeks


after pilocarpine injection, when rats develop spontaneous seizures. Transporter expression was evaluated using immunohistochemistry. Results: Initial histological analysis demonstrated upregulation of five uptake carriers for essential compounds in the CA1 of rats with pilocarpine-induced chronic epilepsy compared to controls: the reduced folate carrier, folate receptor a, organic anion transporting polypeptide 1C1, L-type amino acid transporter 1 and monocarboxylate transporter 1 (MCT1) were elevated 8-fold, 4-fold, 3-fold, 6-fold, and 3-fold (p < 0.05 for all carriers except MCT1). Conclusion: The altered expression of folate, thyroid, monocarboxylate fuels and amino acid transport mechanisms suggests an effect of seizures on the transport of essential compounds and drugs into cerebral cells. Further studies are now being conducted in order to validate these results using other techniques, in addition to characterization in rats which were treated with antiepileptic drugs.

P123 ANALYSIS OF HFOS DURING MICROSEIZURES IN HUMANS WITH EPILEPSY Martinez-Lizana E, Aiple F, Brandt A, D€ umpelmann M, Ball T, Schulze-Bonhage A Universit€ atsklinikum, Freiburg, Germany Purpose: Both HFO and microseizures are epileptic patterns reported at submillimeter scales. Whereas HFO display a sinusoidal pattern with fixed frequency and spectral power above 80 Hz, microseizures show temporal- and spectral-evolution. We study interactions between HFO and microseizures using microwire-recordings. Method: One patient with suspected FCD and possible seizure generation in hippocampi underwent stereotactic implantation of Behnke-Fried electrodes into medialtemporal structures. Each contained 8 microwires. Signals were recorded with 30.000 Hz sampling-rate. Data were analyzed in the time/frequency domain. Results: Ripple, fast-ripple and sigma oscillations were detected in amygdala and hippocampus. Oscillatory activity overlapped and evolved in and between different frequency bands, and in different brain areas forming microseizures. They were recorded from hippocampal subregions, often restricted to few microwires of a given bundle, not visible in adjacent macrocontacts. This phenomenon coexisted with high frequency oscillatory activity in a subregion of the amygdala. Conclusion: This example illustrates the complexity behind microseizure generation. In the temporal dimension, frequency changes within a HFO episode preceded different patterns with amplitude, morphology and frequency evolution, affecting highly focal source locations. In the anatomical dimension, these events affect simultaneously non-contiguous regions in mesiotemporal structures, connected as part of a network. The role that these events may play as an epileptic biomarker is still under investigation, but local architecture may be remodeled by the process of epileptogenesis or by repeated seizures, with new or strengthened connections that serve to speed up the development and propagation of microseizures. This observation needs further corroboration in larger patient samples.

P124 DIFFERENTIAL EPILEPTIFORM ACTIVITY RESULTS IN DISPARATE RESPONSES IN INTERNEURONS Parrish RR, Codadu N, Racca C, Trevelyan A Newcastle University, Institute of Neuroscienc, Newcastle Upon Tyne, United Kingdom Purpose: Genes expressed by a neuron determine its excitability, and the neuron’s activity also influences these expression patterns. This two-way interaction regulates key homeostatic mechanisms in

49 Abstracts the brain. Various brain insults can trigger non-homeostatic changes, leading to epileptogenesis. Epileptogenesis can be triggered in vivo by periods of status epilepticus. It is not known though what roles are played by the different elements within the network, namely the pyramidal cells, glia and the different classes of interneurons. We set out to explore this utilizing several different in vitro models of epileptiform event. This likely holds clues as to the role homeostasis plays in the development of epilepsy. Method: We used several different in vitro models of epilepsy, induced by different acute pharmacological manipulations, to induce a range of cortical activations: one involve activation of all cells in tandem and another caused an almost purely interneuronal activation. We present patch clamp and Ca2+ network imaging data, along with a novel immunohistochemical analysis, to illustrate how these in vitro models can be used to generate stable patterns of epileptiform activity involving very different subsets of the cortical network. Tissue was collected from the activity paradigms and gene expression patterns were explored. Results: Interictal events and preictal events show disproportionate activity in the interneuronal population. Disparate forms of epileptiform activity induce different acute changes in gene expression in the interneurons and also show intriguing differences in the pattern of gene regulation in different cortical subfields. Conclusion: These data suggest that induced expression of genes is dependent on type of epileptiform activity and cortical structure. This opens up several questions into how the differential expression patterns may impact the balance of neuronal homeostasis and the development of epilepsy, both of which we are actively exploring.

P125 THE PROGRESSION OF EEG ABNORMALITIES DURING EPILEPTOGENESIS AFTER LATERAL FLUID PERCUSSION INJURY Reid A1,2, Bragin A3, Staba R3, Engel Jr J3 1 University of Toronto, Toronto, ON, Canada, 2University Health Network, Toronto, ON, Canada, 3University of California, Los Angeles, CA, United States Purpose: Post-traumatic epilepsy (PTE) occurs in up to 50% of survivors of severe traumatic brain injury. Experimental models of trauma, such as fluid percussion injury (FPI), are important for studying epileptogenesis. We have previously reported repetitive high frequency oscillations with spikes (rHFOSs) occur early after lateral FPI and may be a biomarker for experimental PTE. The objective of this study was to use multiple electrodes in rat hippocampal and neocortical regions to describe the long-term electroencephalographic and behavioral evolution of rHFOSs and epileptic seizures after lateral FPI. Method: Adult male rats underwent mild, moderate, or severe lateral FPI or sham injury followed by video-EEG recordings with a combination of 16 neocortical and hippocampal electrodes at an early, intermediate, or late time-point after injury. Recordings were analyzed for the presence of rHFOSs and seizures. Results: 28 rats with FPI and 7 shams were analyzed. Peri-lesional rHFOSs were recorded in significantly more rats after severe (70.3%) than mild (20%) injury or shams (14.3%). They occurred more frequently in the early (10.8/h) vs. late (3.2/h) recording group. Focal seizures originating from the same electrodes were recorded in significantly more rats in the late (87.5%) vs. early period (22.2%), occurring almost exclusively in injured rats. Average seizure duration increased significantly over time, from 19 sec at the beginning of the early period to 27 sec at the end of the late period. Seizure frequency also increased over time, from 4.4/week in the early group to 26.4/week in the late group. Generalized seizures were rare.

Conclusion: Lateral FPI results in early rHFOSs which decrease in frequency with the later appearance of spontaneous focal seizures. Epilepsy severity is related to injury severity, and also increases over time, making this a clinically relevant model for studying PTE and epileptogenesis.

P126 CHRONIC DEFICIENCY IN THE BRAIN ENERGY SUPPLY IS A TRIGGERING MECHANISM IN THE EARLY STAGE OF EPILEPTOGENESIS Samokhina E1, Osypov A2, Molchanov M1, Popova I1 1 Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Russian Federation, 2 Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino, Russian Federation Epileptogenesis is a process by which a healthy brain develops epilepsy. A search for pathways of epileptogenesis may provide a foundation for the development of antiepileptogenic and thus a kind of a preventive therapies. Glucose hypometabolism in the brain is one of a characteristic features of the epileptogenesis of both animal and human epilepsy. So, we aimed to support the model of chronic low brain glucose in seizures development. Method: Wistar rats (male, 350–450 g weight, n = 18) were used for the study. Glucose hypometabolism in the rat brain was created by administration of 2-deoxy-D-glucose (2-DG, 2.5 mkL, 20 mM) in the ventricles through the guide cannula daily for 4 weeks. During the entire period of administration of 2-DG the registration of the local field potentials (LFP) of the hippocampus was carried out. After that, the brain was removed for biochemical analysis by 1H-NMR and histological staining. Animals with 0.9% NaCl administration into the cerebral ventricles were used as a control. Result: Hippocampal LFP analysis showed that chronic glucose hypometabolism in the brain leads to pathological activity: there was a significant increase in frequency and duration of ripples (high-frequency oscillations) – (480% and 200%, respectively), as well as twice increase of the frequency of epileptic spikes. In some rats with 2-DG we observed spontaneous seizures accompanied by behavioral manifestations. The total number of neurons per slice was gradually reduced in CA1 region of hippocampus when compared to the controls. Biochemical analysis confirmed glucose hypometabolism (decrease of the levels of adenosine and glycogen in the nervous tissue). Conclusion: These results indicate that the lack of glucose utilization in the brain may be a triggering mechanism in the early stage of epileptogenesis. The work was supported by RFBR (No. 14-44-03682).

P127 UNCOMPLETE RECOVERY FROM MG2+ SUPPRESSION OF NONSYNAPTIC EPILEPTIFORM ACTIVITY ON AN INVERTEBRATE MODEL SYSTEM Stanojević M1, Lopicic S1, Spasic S1, Nedeljkov V1, Mihaljev I1, Jovanovic V2, Djurovic B2, Bulajic P3, Prostran M4 1 Institute for Pathological Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia, 2Clinic for Neurosurgery, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia, 3Health Center, Vranje, Serbia, 4Institute for Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia Purpose: Magnesium is a bioessential cation important for the function of excitable cells both in health and disease, and also one of the potential Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

50 Abstracts simple antiepileptic and antiepileptogenic agents. The object of this study was to examine the neuroprotective effect of MgCl2 against epilepsy on an invertebrate experimental model of epileptiform activity induced nonsynaptically in leech Retzius neurons by Ca2+ channel blockade with 3 mM NiCl2. Method: Classical intracellular electrophysiological recording was used. Epileptiform activity induced by Ni2+ was characterized by rhythmical generation of paroxysmal depolarization shifts (PDSs). The PDS parameters were measured prior to Mg2+ exposure and after flushing Mg2+ from the system early in the recovery period (first 5–10 min). Student’s t-test was used for comparisons. Results: With respect to our previous findings of the effectiveness of Mg2+ in the suppression of Ni2+-induced epileptiform activity on this model in a range of increasing Mg2+ concentrations (1, 3, 7, 10 and 20 mM Mg2+) in separate series of experiments (Stanojevic M et al. Folia Biol (Krakow) 2015; 63:301–306.), here we tested for the characteristics of the epileptiform activity recovered after Mg2+ washout in an overall view, regardless of Mg2+ concentration previously applied. A signifficant reduction of recovery parameters was found comparing to control, as follows: PDS frequency was reduced from 5.92 0.28 to 4.79 0.25/min (n = 49, p < 0.01), PDS duration decreased from 4.81 0.14 to 4.45 0.09 s (n = 39, p < 0.05), PDS amplitude from 12.35 0.43 to 10.41 0.70 mV (n = 43, p < 0.05), and the number of spikes/PDS decreased from 7.17 0.50 to 5.12 0.57 (n = 42, p < 0.01). Conclusion: An overall neuroprotective effect of Mg2+ against nonsynaptic epileptogenesis was found on our model, as seen by prolonged Mg2+-induced suppression with uncomplete recovery of epileptiform activity. Acknowledgement: Serbian Ministry of Education, Science and Technological Development, grant number 175023.

P128 A NOVEL FOCAL SEIZURE PATTERN ASSOCIATED WITH BLOCKADE OF SYNAPTIC TRANSMISSION Uva L1, Saccucci S2, Morbin M2, Chikhladze M3, Tassi L4, de Curtis M1 1 Epileptology and Experimental Neurophysiology Unit, Fondazione Istituto Neurologico Carlo Besta, Milano, Italy, 2 Unit of Neuropathology, Fondazione Istituto Neurologico Carlo Besta, Milano, Italy, 3Unit of Clinical Neurophysiology, Fondazione Istituto Neurologico Carlo Besta, Milano, Italy, 4 Claudio Munari Epilepsy Surgery Center, Ospedale Niguarda Ca’ Granda, Milano, Italy Purpose: Different seizure patterns have been described in patients with focal, pharmacoresistant epilepsies. Arterial application of the potassium channel blocker 4-aminopyridine (4AP) in the isolated guinea-pig brain induces distinctive seizure-like events (SLEs) in the olfactory cortex (Carriero et al., 2010) characterized by runs of fast activity (20–60 Hz) that progress with the recruitment of synchronous spiking discharges (Uva et al., 2013). The mechanisms underlying the onset of this peculiar SLE pattern are here analysed. To evaluate if the seizure pattern observed in piriform cortex (PC) during 4AP administration has a relevance to human epilepsy, we analyzed seizure patterns recorded in patients explored with intracranial depth electrodes. Method: 4-AP (50 lM) was arterially applied in the isolated guinea-pig brain maintained in vitro to induce SLEs. Field potentials (FPs), intracellular activities and [K+]o changes have been recorded in PC. FPs were recorded also in guinea-pig PC slices after 4AP bath-application. Myelin distribution in PC layer I was assessed with black-gold II staining and electron microscopy. Stereo-EEG recordings were performed in patients with focal pharmacoresistant epilepsy candidate to epilepsy surgery.


Results: The analysis of FPs, intracellular activities and [K+]o changes demonstrate that SLEs 1 initiate with a fast increase of [K+]o in the a-cellular superficial layer I, which is composed of a net of unmyelinated axons, 2 correlate with a blockade of synaptic transmission, 3 evolve with the progressive entrainment of deeper cortical layers. The pattern observed in the whole brain was confirmed in tangential slices where the most superficial layers are preserved. The pattern here described mimics a pattern observed in patients with focal pharmacoresistant epilepsy. Conclusion: We propose a novel seizure pattern independent on synaptic transmission, triggered by a [K+]o increase that relies on the peculiar organization of the superficial layers of the olfactory cortex, characterized by unmyelinated axons.

Basic Science 3 Tuesday 13th September P131 OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION IN IMMATURE BRAIN DURING EPILEPTOGENESIS Folbegrová J, Jesina P, Kubov a H, Ot ahal J Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic Purpose: We have demonstrated recently that status epilepticus (SE) in immature rats is in the acute phase associated with oxidative stress and mitochondrial dysfunction. The aim of the present study was to examine their potential role during the long period of survival (up to 5 weeks) following SE, i.e. during the period of epileptogenesis. Method: Seizures (having a character of SE) were induced in immature 12-day-old male Wistar rats by Li-pilocarpine (i.p. LiCl 127 mg/kg and the next day i.p. pilocarpine 35 mg/kg). Dihydroethidium (Het) method was used for detection of superoxide anion production in brain in situ. The determination of the oxidized products of Het (reflecting superoxide production) was assessed microscopically by fluorescence (>600 nm). Mitochondrial function was evaluated by measuring activity of respiratory chain complexes in isolated mitochondria. SOD mimetic MnTMPYP and natural polyphenol Resveratrol were employed for assessing their potential protective effect. Both scavengers were given i.p., at selected time intervals both before and after the induction of SE. Results: The increase of superoxide formation was detected in several brain regions in situ (CA1, CA3 and dentate gyrus of hippocampus, cerebral cortex and thalamus) during long periods following SE. A marked decrease of complex I activity (~ 50%) persisted during the whole period studied. The treatment with both scavengers provided a clear protective effect. They prevented or significantly reduced the increase of superoxide formation and substantially attenuated the inhibition of complex I activity. Conclusion: The present findings suggest that substances with antioxidant properties combined with conventional therapies may provide a beneficial effect in treatment of epilepsy. Supported by the Czech Science Foundation (grant No. 15-08565S).

51 Abstracts P132 NEOCORTICAL GAMMA-OSCILLATIONS BEFORE STIMULUS PRESENTATION PREDICT SUCCESSFUL MEMORY ENCODING IN HUMANS – AN INTRACRANIAL EEG-STUDY Gollwitzer S1, Rampp S2, Fellner M-C3, Gernot K2, Diehl B4, Wehner T4, Walker M4, Bush D5, Bisby J5, Burgess N5, Hagge M2, Lang J2, Schwab S2, R€ossler K2, Hanslmayr S6, Hamer H2 1 Neurology, University Hospital Erlangen, Erlangen, Germany, 2 University Hospital Erlangen, Erlangen, Germany, 3Ruhr University Bochum, Bochum, Germany, 4Institute of Neurology, University College London, London, United Kingdom, 5 University College London, London, United Kingdom, 6 University of Birmingham, Birmingham, United Kingdom Purpose: Brain oscillations following presentation of to-be-remembered items play a vital role in successful memory encoding. Less is known about the influence of different brain states preceding stimulus presentation on memory formation. In this study, we focused on oscillatory patterns appearing up to one second before item presentation during a memory task in patients with invasive EEG recordings. Method: 16 patients with medically refractory focal epilepsy who underwent invasive EEG with subdural or depth electrodes for pre-surgical epilepsy assessment were included (left: 9, right: 6, bilateral: 1). The memory paradigm comprised encoding, distraction and recognition of 100 regular nouns and faces. Encoding trials (1 s before and 2 s after item presentation) were classified as hit (=later remembered) or miss (=later forgotten) trials. For post-processing, we performed time frequency analyses of spike-free raw EEG for each trial and electrode and ztransformed power values using mean and standard deviation drawn from all complete trials. A permutation procedure was applied to evaluate significant differences between conditions (hit/miss). The significance threshold was set at 0.05. Results: Short lasting (< 100 ms) changes in spectral gamma power appearing predominantly around 500 ms pre-stimulus were significantly associated with successful memory encoding. This was seen in 44/1,387 electrodes (3.2%) of 14/16 patients. The subsequent memory effect presented as gamma desynchronization in 38 and as gamma synchronization in 6 electrodes. Pre-stimulus gamma changes occurred in single contacts in all cortical regions. However, clusters of these electrodes appeared predominantly in the bilateral inferior temporal gyrus, right fusiform gyrus and right insula. The power fluctuations were independent of type of stimulus (verbal, non-verbal). Conclusion: Bilateral inferior temporal and right insular changes in spectral gamma power preceding item presentation predict later recall. The subsequent memory effect is mainly characterized by power decreases, whereas power increases are less commonly observed.

P134 EFFECTIVE CONNECTIVITY CHANGES REVEAL NEURONAL POPULATION ACTIVITY DURING SEIZURES IN HUMANS Janca R1, Jezdik P1, Cmejla R1, Tomasek M2, Marusic P2, Krsek P3, Jiruska P4 1 Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic, 2Department of Neurology, 2nd Faculty of Medicine, Motol University Hospital, Charles University, Prague, Czech Republic, 3Department of Paediatric Neurology, 2nd Faculty of Medicine, Motol University Hospital, Charles University, Prague, Czech Republic, 4Department of Developmental

Epileptology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic Purpose: Studies examining the connectivity have potential to bring new insights into the mechanisms of ictogenesis. Recent data have demonstrated dynamical reconfiguration of functional network connectivity at the seizure onset. The reconfiguration is characterized mainly by disconnection of the seizure onset zone (SOZ). In our study we have examined effective connectivity changes during seizures in humans. Method: We have explored the pre-ictal and ictal dynamics of the effective connectivity in intracranial EEG recordings from eight patients with refractory neocortical epilepsy. The connectivity was estimated in 36 seizures using direct Directed Transfer Function (dDTF) which was optimized to determine the connectivity within short time windows and with high frequency resolution. The dynamics of the connectivity was examined from global (between the whole SOZ and surrounding network) and local (between pairs of contacts within the SOZ) perspective. Results: From global perspective, seizures onsets were characterized by decrease in effective connectivity in 50–150 Hz frequency range. The contacts where this decrease was observed co-localized with seizure onset zone marked by clinicians. During advanced stages of seizures the frequency specific drop of connectivity was present only in proportion of channels involved in seizures. On the local scale, connectivity within SOZ increased and correlated with increase in coherence and increased signal energy. Conclusion: Obtained results suggest that regions with decreased of connectivity in high-frequency range represent brain areas which are actively involved in generating of the ictal activity. This network parameter is able to localize SOZ and discriminate areas with passive synaptic propagation of ictal activity. On the local scale, increased connectivity corresponds to traditional phenomenon of increased synchronization of neuronal activity. Supported by grants from the Ministry of Health of the Czech Republic (AZV 15-29835A), Czech Science Foundation (14-02634S) and by Neuron Fund for Support of Science (NFKJ 001/2012).

P135 FOCAL 4-AMINOPYRIDINE-INDUCED SEIZURE-LIKE EVENTS INITIATED BY INHIBITORY NETWORK ACTIVITY INDUCE [K+]0 INCREASE, BUT ARE NOT DEPENDENT ON KCC2 CHANNELS Librizzi L1, Losi G2, Marcon I2, Sessolo M2, Carmignoto G2, de Curtis M1 1 Neurological Institute Foundation ‘C. Besta’, Milano, Italy, 2 National Research Council (CNR) and University of Padova, Padova, Italy Purpose: It has been demonstrated that focal seizures are heralded by an increase of inhibitory network activity. The functional implication of enhanced inhibition ahead of a focal seizure has been interpreted either as inhibitory restraint to seizure propagation (Cammarota et al., 2013) or as a pro-ictogenic event related with seizure onset (de Curtis and Gnatkovsky, 2009). Since extracellular potassium level has also been related to seizure generation, we here investigated the correlation between interneuron network activity, [K+]0 and seizure generation and progression. Method: We performed patch-clamp recordings from Pyramidal neurons (Pyr) and Fast Spiking (FS) interneurons in layer V of the mEC in brain slice preparations. Simultaneous [K+]0 recordings were performed in the same area with ion sensitive capillaries. Focal ictal discharges were induced by perfusion with the potassium channel blocker 4-aminopyridine (4AP; 50 lM) in low Mg++ solution. Results: Few minutes after perfusion with 4AP, inhibitory post synaptic currents (IPSCs) time-locked with [K+]0 changes occurred, followed by Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

52 Abstracts focal ictal discharges. Dual recordings revealed that IPSCs anticipating seizure-like events in Pyr neurons correlated to an intense FS interneurons firing activity. These events were associated with a long lasting, even if moderate, increase in [K+]0, followed by a more abrupt rise of K+ level as a result of the excitatory network recruitment. In order to investigate the role of potassium on seizure onset and progression, blockers of the potassium-chloride co-trasporter (KCC2) were used. Unexpectedly, the KCC2 blockers failed in abolish 4AP- induced seizure. On the contrary, KCC2 antagonists changed the pattern of epileptiform discharge increasing the duration of the seizure. Conclusion: We demonstrate that inhibitory network is an active player in seizure onset, correlating with extracellular potassium changes and promoting seizure generation. We also reveal that in the 4-AP model KCC2 trasporters are not involved in controlling extracellular potassium levels.

P136 NEURONAL FIRING ANALYSIS OF EPILEPTIC INTERICTAL ACTIVITY IN HUMANS Martinez-Lizana E, Brandt A, Aiple F, D€umpelmann M, Ball T, Schulze-Bonhage A Universit€atsklinikum, Freiburg, Germany Purpose: Despite the importance of epileptic interictal activity (EIA) for diagnosis and treatment of epilepsy, little is known about the neurophysiological mechanisms generating these events in the human brain, but abnormal neuronal synchronization may play an important role in their generation. The study of neuronal behavior during these events with microwires can give new insights into the generation of these abnormalities. Method: Six patients with medically intractable epilepsy were implanted with hybrid depth-electrodes, composed of microwires and clinical macroelectrodes. Rate patterns of neuronal action potentials (AP) recorded during EIA were classified and characterized. Results: Two modulation patterns of neuronal activity were observed in three patients: 1 The “burst-suppression” pattern showed an increase in the rate of AP during the interictal spike-phase (50–100 ms), followed by a decrease below the baseline rate during the slow-wave phase (400–600 ms). This pattern was observed during spike-waves in the amygdala (A) and in the anterior hippocampus (AH). 2 The “burst-only” pattern showed a sudden increase in NAP during the burst-phase. It lasted 1–1.5 s, with a maximum firing rate in the first 500 ms. This pattern was observed during polyspike-bursts in the parahippocampal gyrus (PHG) and during sharp waves in the anterior temporal lobe (ATL). Conclusion: We have found different types of neuronal modulation in different regions of the temporal lobe during different types of EIA. The burst-suppression response was observed in regions corresponding to seizure onset zone (SOZ), while the burst-only response was observed inside and outside the SOZ. Whether the suppression is related with the seizure generation remains unknown. Previous works associated the slow wave component with the development of seizures. Further studies should be done to confirm these hypotheses.

P137 GENE EXPRESSION ANALYSIS OF DRUG TRANSPORTERS AND BIOTRANSFORMATION ENZYME IN PATIENTS WITH MESIAL TEMPORAL LOBE EPILEPSY AND FOCAL CORTICAL DYSPLASIA: A COMPARATIVE STUDY Sharma D1, Shrivastava A2, Banerjee Dixit A1, Banerjee J1, Tripathi M2, Chandra PS2 1 National Brain Research Center, Gurgaon, India, 2All India Institute of Medical Sciences, New Delhi, India Purpose: One of the many hypotheses proposed to explain pharmacoresistance in epilepsy is Drug Transporter Hypothesis which suggests decreased antiepileptic drugs (AEDs) uptake into the brain by intrinsic or acquired over-expression of multidrug transporters and biotransformation enzymes in the blood-brain barrier (BBB) (L€oscher W et al. J Pharmacol 2002; 301(1):7–14). To validate this hypothesis, we analyse alteration in expression levels of efflux transporters– Multidrug Resistance Protein 1 (MRP1), Major Vault Protein (MVP), Breast Cancer Resistance Protein (BCRP), and biotransformation enzyme UDP-glucuronosyltransferase 1 (UGT1A4), in resected human brain tissues of the mesial temporal lobe epilepsy (MTLE) and focal cortical dysplasia (FCD) patients compared with non-epileptic controls (C). The selected genes are specific to majority of the AEDs administered to patients except MVP which has no specific substrates. Method: RNA extracted and cDNA was prepared from resected brain specimens of 11 MTLE, 9 FCD and 8C. Real time polymerase chain reaction (qPCR) was performed to study differential gene expression. Hypoxanthine Phosphoribosyltransferase (HPRT) gene was used as a reference for normalisation. Expression results were quantified by Bio-Rad CFX Manager Software. Results: Quantitative analysis showed 5fold over expression of BCRP in MTLE & 2.50 in FCD (p < 0.05). MVP was 3 fold higher in MTLE and 5 times in FCD (p < 0.05). UGT1A4 was 4 fold increased in MTLE (p < 0.05) however no change was seen in FCD group. MRP1 alteration was not statistically significant. Conclusion: Our results suggest a broad upregulation in mRNA expression of the selected genes BCRP, MVP, UGT1A4 in epileptic tissues. Enhanced brain expression of efflux transporters and biotransformation enzyme is thus likely to reduce the amount of drug reaching epileptic neurons which may be an explanation for intractability in epilepsy. Further studies are needed to substantiate this finding.

P138 EPILEPSY MAY CAUSE INCREASED PAIN SENSITIVITY: PRELIMINARY DATA FROM ABSENCE EPILEPTIC WAG/RIJ RATS NOCICEPTIVE THRESHOLD Velioglu SK1, Gedik O2, Yıldırım M2, Ayar A2 1 Clinical Neurophysiology Unit, Neurology Department, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey, 2Department of Physiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey Purpose: Thalamocortical circuits are responsible for generalized absence epilepsy and also related to central pathways of nociception. This raises the question of whether or not there are differences in interictal nociceptive sensitivity in epilepsy. We aimed to study the thermal nociception in the inter-ictal period in a model of genetic absence epilepsy. Methods: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, which are an established model for absence epilepsy. Pain sensitivity was


53 Abstracts assessed by heat-induced behavioral nociceptive tests (plantar test). The epileptic group consisted of 8 adult (8 months old) male WAG/Rij rats and eight age and sex -matched Wistar served as control. All animals were undervent a stereotaxic surgery for placement of cranial electrodes and after at least 10 days of postoperative recovery the plantar tests were performed. Recordings were performed in freely moving rats in the plantar test platform. All protocols were approved by the Ethical Committee on Animal Experimentation of Karadeniz Technical University Trabzon (KTU-ECAE). Results: In the interictal period, significantly shorter plantar test latencies were found in WAG/Rij rats, as compared to controls (respectively epilepsy and control groups: 3.0 and 4.5 s; p = 0.001). Conclusion: Our data, even if preliminary, suggests that there is a decrease in thermal nociceptive thresholds in the inter-ictal period in rats with genetically absence epilepsy.

P139 MECHANISMS UNDERLYING DIFFERENT ONSET PATTERNS OF FOCAL SEIZURES Wang Y1, Trevelyan A2, Taylor PN1,2, Valentin A3, Alarcon G3,4, Kaiser M1,2 1 School of Computing Science, Newcastle University, Newcastle upon Tyne, United Kingdom, 2Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom, 3 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom, 4Hamad Medical Corporation, Comprehensive Epilepsy Center Neuroscience Institute, Academic Health Systems, Doha, Qatar Purpose: Focal seizures typically begin with an electrographic onset pattern that is highly stereotyped in individual patients. Qualitative classifications of these onset patterns describe two frequently occurring waveforms – low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Interestingly, only the former of the patterns is associated with a good surgical outcome. Given the importance of this clinical distinction, we therefore explored whether these two patterns arise from fundamentally different spatio-temporal dynamics. Method: We used a computational model of neocortical tissue to replicate these different onset patterns. Results: We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in excitability of the surrounding tissue, essentially creating a seizure supporting surrounding. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically observed difference in surgical outcomes. Finally, we demonstrate how changes in tissue excitability can be elucidated using active stimulation. Conclusion: The excitability of the tissue surrounding the seizure core is shown to play a determining role in the seizure onset pattern, as well as in the surgical outcome in our model.

Basic Science 4 Tuesday 13th September P140 SIRT3 MEDIATES ANTIOXIDANT DEFENSE VIA REGULATING MNSOD ACTIVITY IN MOUSE HIPPOCAMPUS AFTER PILOCARPINE-INDUCED STATUS EPILEPTICUS Cho I1,2, Kim H1, Cho Y-J1, Cho KH1, Heo K1, Lee BI3, Kim WJ1,2 1 Department of Neurology and Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea, 2Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea, 3Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea Purpose: Excessive production of reactive oxygen species (ROS) results in extensive neuronal cell death, the initial molecular process of seizureinduced brain injury leading to development of epileptogenesis. The NAD+-dependent protein deacetylase, Sirtuin 3 (Sirt3) has been implicated in the various mitochondrial functions; however, the function and localization of this enzyme has been still debated. Recent studies have suggested that Sirt3 upregulates the activity of Manganese superoxide dismutase (MnSOD), the enzyme converts superoxide to hydrogen peroxide, through its deacetylation activity, but the role of this enzyme in association with MnSOD in the ROS-induced cell death during status epilepticus (SE) remains unclear. We investigated the location and role of Sirt3 on the regulation of MnSOD activity against oxidative stress after SE in hippocampus. Method: Adult male C57BL/6J mice were given injections of pilocarpine 30 min after scopolamine treatment. Hippocampal neuronal death was assessed by cresyl-violet and TUNEL staining. Co-immunoprecipitation was performed to confirm the interaction between MnSOD and Sirt3. After the subcellular fraction of hippocampus, the expression of MnSOD and Sirt3 were analyzed by both Western blot analysis and semi-quantitative immunofluorescent staining, respectively. Results: Hippocampal neuronal cell death was evident by both cresylviolet and TUNEL staining after SE. In addition, the amount of superoxide anion significantly increased after pilocarpine-induced SE compared to the normal control. Increase of interaction between MnSOD and Sirt3 was detected at 4 h after SE, and returned to basal level at 24 h after SE. MnSOD activity significantly elevated and reached peak at 4 h after SE, but it was decreased in to basal level. Conclusion: Sirt3 might have neuronal protective property through activation of MnSOD against oxidative stress after SE, and it might be important that the localization of enzyme in the cell components. The strategy enhancing Sirt3 against seizure-induced cell death should be investigated in the future.

P141 THE RHYTHM SPECIFICITY OF DMN DURING TEMPORAL LOBE EPILEPSY SEIZURE Cui Y, Ma T, Wang T, Guo D, Xia Y, Yao D School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China Purpose: As a chronic brain disorder in clinical, the temporal lobe epilepsy can be characterized by recurrent and unprovoked seizures. The default mode network (DMN) has been believed to be associated with many neuropsychological disorders. The purpose of this study is to assess how the DMN changes during TLE seizure. Method: In the present study, we recorded the local field potentials of DMN from 10 Pilocarpine-induced TEL rats. First, we discovered the specific frequency bands with power spectrum density and coherence


54 Abstracts network analysis. Then we emphasized the relationship of these frequency bands during the TLE seizure with cross-frequency coupling. Lastly, we clarified the propagation path of epileptic discharges in the DMN in different frequency bands. Results: We observed that before the onset of the epileptic discharge, the power and network density of the delta frequency band increased while they decreased in the alpha frequency band. And the stage of epileptic discharge propagation is dominated by the increase of alpha band and the decrease of delta frequency band. Meanwhile, the change of the coupling between the delta band and the alpha band was familiar with the changes of delta band power and network density. Moreover, we found that the DMN can be divided into two modules: the prefrontal cortex module including the PrL, CG, OFC and the parietal cortex module, which includes HIP, TE, PPC and RSC. The epileptic discharges initially originated in the parietal cortex module in the delta band and then spread to the prefrontal cortex module in the alpha band. Conclusion: Our results demonstrated that the DMN dynamically changed during the epileptic discharge process in different rhythms, and the rhythm specificity of DMN may result from the co-operation of them.

P142 SINGLE MICROVASCULAR PERICYTE TRACKING DURING EPILEPTIFORM ACTIVITY IN VITRO de Bock F, Schaeffer M, Perroy J, Marchi N INSERM U 1191, CNRS UMR 5203, UM, Institut de Genomique Fonctionnelle, Montpellier, France Purpose: Cerebrovascular damage is reported in human and experimental epilepsy. Recent evidence indicates that perivascular mural cells may participate in the vascular remodeling of the epileptic brain. Post-mortem histology indicates microvascular pericytes redistribution in response to seizures in vivo. The determinants of pericyte changes in the epileptic brain remain understudied. Method: In vitro hippocampal slices were obtained from transgenic NG2DsRed mice (n = 14; female PN21-PN35). Single-pericyte structural modifications occurring in response to various epileptiform activities (0 Mg++, 5 mM K+ or 200 lM 4-aminopyridine) were tracked. Field potential recording was continuous throughout all confocal microscope acquisitions. Time-lapse confocal Z-stacks (20–25 lm depth) were obtained for individually selected NG2DsRed microvascular pericytes (control; 30, 60, 90 and 120 min) within targeted regions of interest (CA1). 3-dimentional reconstructions and volume quantification (lm3) of single NG2DsRed pericytes was performed using Imaris 8.0, while field potential activity was analyzed using pClamp 8.2. Results: NG2DsRed microvascular pericytes were discernable from smooth muscle cells owing to their characteristic morphology. Pericyte changes related to the in vitro preparation and the absence of spike activity were quantified and set as a baseline. Perfusion with 0 Mg++/5 mM K+ produced epileptiform activity (15 7 spikes/min) associated with a trend decrease of pericytes volume (15%) as compared to untreated control. 4AP provoked abundant and repetitive burst activity (53 19 spikes/min) lasting >120 min and lead to a significant NG2DsRed pericytes volume decrease (27%) as compared to control. 3D image reconstruction indicated qualitative structural changes mainly at the NG2DsRed perivascular ramifications, while pericyte soma appeared to be less affected. Conclusion: Our initial results indicate a dose-dependent effect of epileptiform activity in vitro on NG2DsRed pericyte volume. The impact of other pathophysiological determinants of seizures on single pericytes is currently being investigated.


P143 SPONTANEOUSLY HYPERTENSIVE RATS WITH CEREBRAL SMALL VESSEL DISEASE ARE PRONE TO TEMPORAL LOBE EPILEPSY Russo E1, Citraro R1, Leo A1, Ferlazzo E2, Gasparini S2, Aguglia U2, De Sarro G1 1 Science of Health, University of Catanzaro, Catanzaro, Italy, 2 Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy Purpose: Chronic hypertension represents a risk factor for cerebrovascular disease and, consequently, it can lead to late-onset seizures and epilepsy in the elderly1. It is a risk factor for human Cerebral Small Vessel Disease (CSVD). The existence of a cause-effect relationship between hypertension and epilepsy, and between CSVD and Temporal Lobe Epilepsy (TLE), is questionable and physiopathologic mechanisms are unknown2.3. We studied if spontaneously hypertensive rats (SHRs), a well-established animal model of hypertension and CSVD, have a higher propensity to develop TLE or generalized epilepsy in comparison to control WistarKyoto rats (WKY)4. Method: We induced amygdala kindling, an animal model of TLE, and Pentylenetetrazole (PTZ)-induced kindling, a model of generalized seizures, in both SHRs and WKY rats. We also evaluated if enalapril, an angiotensin converting enzyme (ACE) inhibitor, treatment would protect SHR in the animal model of TLE. Results: SHRs (6 weeks old), with only hypertension and treated or untreated with enalapril 10 mg/kg/day in amygdala kindling model do not kindle before control group, while kindling rate in SHRs (16 weeks old and CSVD) was more rapid than in WKY rats, requiring fewer afterdischarges to achieve 3 consecutive stage-5 seizures. In the PTZ kindling model, there is no difference between SHRs and WKY rats (both at 6 or 16 weeks of age) independently from enalapril (10 mg/kg) treatment. Conclusion: These results indicate that SHR rats have a higher susceptibility through the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region in comparison with Wistar Kyoto control rats, while they do not differ in the development of generalized seizures. References1. Gibson et al. Journal of Cerebral Blood Flow & Metabolism 2014;34:564–570. 2. Pereira et al. Clinical science 2010;19:477– 482. 3. Tchekalarova et al., Cellular and molecular neurobiology 2015. 4. Tchekalarova et al., Epilepsy & behavior 2015;46:66–71.

P144 THE ROLE OF OXIDATIVE STRESS IN NEURODEGENERATION IN THE IMMATURE BRAIN FOLLOWING STATUS EPILEPTICUS Demeterova L, Folbergrova J, Kubova H, Druga R, Jiruska P, Otahal J Department of Developmental Epileptology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic Purpose: There exists a large body of evidence that free radicals and oxidative stress are implicated as an important factor in many neurodegenerative disorders, including epilepsy. Oxidative stress is also involved in acute and late neuronal cell death, long lasting molecular alterations and altered gene expression, the processes which all accompany epileptogenesis. The main aim of the study was to examine whether targeting oxidative stress in acute and early latent period can influence the process of neurodegeneration in the immature brain following status epilepticus.

55 Abstracts Method: Seizures was induced by i.p. injection of aqueous solution of pilocarpine (35 mg/kg) in LiCl (127 mg/kg, 24H prior) pre-treated immature 12-day-old rats. A potent super oxide dismutase mimetic MnTMPYP was employed to minimize harmful effect of reactive oxygen species. MnTMPYP dissolved in saline was administered i.p. in three different application regimens covering acute treatment (30 min before and 30 and 60 min. after SE), posttreatment (60, 180 min. and 1 day after SE) and full treatment (the combination of both). Animals were sacrificed 1 day after the induction of SE and the extent and character of neuronal degeneration was evaluated by FluoroJade B staining using semiquantitative scale.

P146 A LOW-NOISE AMPLIFIER IMPROVES AUTOMATED FAST RIPPLE (FR) DETECTION IN INTRAOPERATIVE ECOG Fedele T1, Krayenb€ uhl N1, Curio G2, Hilfiker P3, Grunwald T3, Sarnthein J1 1 University Hospital Zurich, Z€ urich, Switzerland, 2Charite – Universit€ atsmedizin Berlin, Berlin, Germany, 3Swiss Epilepsy Centre, Z€ urich, Switzerland

Results: FluoroJade B staining revealed degenerating neurons spread across the whole body of hippocampus and hippocampal subfields. Most prominent damage was visible in pyramidal cell layer of dorsal CA1 and ventral CA3 of the hippocampus. Those two regions were also protected by MnTMPYP when applied after the SE and compared to saline treated controls. The most protective effect of MnTMPYP was manifested in ventral CA3 hippocampal area in post treatment group.

Purpose: Fast ripples (FR) in the intraoperative ECoG have recently been shown to be specific predictors of surgical outcome. FR detection is restricted by their low Signal-to-Noise Ratio (SNR) and their time consuming visual marking. We present here the combination of a low-noise recording system with automatic detection of high-frequency oscillations (HFO).

Conclusion: Our data suggest that oxidative stress plays an important role in neurodegeneration in the immature brain following status epilepticus. The study was supported by grant project no. 15-08565S from Czech Science Foundation.

P145 THE ROLE OF ADENOSINE IN HIPPOCAMPAL EXCITABILITY AFTER STATUS EPILEPTICUS IN IMMATURE AND ADULT RATS Fabera P1,2, Kubova H1, Mares P1 1 Department of Developmental Epileptology, Institute of Physiology of Czech Academy of Sciences, Prague, Czech Republic, 22nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic Purpose: Status epilepticus (SE) induced in immature rats lead after a long latency to development of spontaneous seizures. Majority of spontaneous seizures is generated in hippocampus therefore we started to study hippocampal excitability after SE. The severity of functional alteration after SE was correlated with the levels of adenosine in hippocampus during brain development. Method: LiCl-pilocarpine SE was elicited in 12-day-old rats and hippocampal epileptic afterdischarges were studied in 15-, 18-, 25-, 32-, 60day and 90-day-old rats with electrodes implanted into dorsal hippocampus. Control animals received saline instead of pilocarpine. All age groups were formed by 10–14 animals. Threshold intensities were found and the rats were stimulated (2-s series of 60 Hz pulses of 1-ms duration) at 20-min intervals six times. Thresholds and duration of ADs were evaluated. The dorsal hippocampus was analyzed for levels of adenosine by using HPL chromatography and microdialysis. Results: Threshold for elicitation of hippocampal ADs was significantly higher in 15-day-old SE rats in comparison with controls. The two older groups did not exhibit a difference between SE and control group but 32day-old rats revealed significantly lower threshold intensity for SE rats than for control animals. Corresponding changes were found in AD duration after repeated stimulations – shorter ADs were recorded in P15 SE rats whereas duration of ADs was significantly longer in P32 SE rats in comparison with appropriate controls. These findings correspond to significantly increased level of adenosine in P15 and P32 rats as the consequence of SE. Conclusion: Our data demonstrated that after SE complex changes of hippocampal excitability took place but did not persist in adults. P32 rats demonstrated higher excitability of dorsal hippocampus than their agematched controls. These changes in hippocampal excitability might correspond to adenosine level after SE in this structure.

Method: Intraoperative ECoG data (7 patients, 14 9 1 min recordings, 77 channels) were collected in parallel by commercial device recordings (CD, input noise level 21 nV/√Hz) and by low-noise recordings with a custom-made amplifier (LN, input noise level 2.3 nV/√Hz). Electrode impedances were below 2 kΩ. The HFO analysis was conducted separately for ripples (80–250 Hz) and FR (250–500 Hz). The automatic detector performed first entropy-based computation of baseline amplitude and then validation of events in the time-frequency domain. Results: The baseline amplitude was 2.9 1.0 lV for Ripples and 1.2 0.4 lV for FR in CD and 2.4 1.1 lV for Ripples and 0.8 0.6 lV for FR in LN. Ripple rates were 2.3 2.6 events/min in CD and 4.2 5.0 in LN (p = 0.002). FR rates were 6.9 4.9 in CD and 17.8 13.7 in LN (p = 10–11). Across patients, the similarity of spatial patterns between CD and LN was 0.77 0.2 for Ripples and 0.93 0.1 for FR. Conclusion: Low-noise technology enhances the SNR in the FR spectral range. The combination of an optimized acquisition system with an unsupervised HFO detector improves FR detection. Improved automatic access to FR at enhanced rates represents a critical advance to analyze FR in clinical application.

P147 ASYMMETRY IN TEMPORAL LOBE CORTEX ORGANISATION Kalina A, Martinkovic L, Marusic P Department of Neurology, Charles University in Prague, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic Background and purpose: Temporal lobe is taking part in great number of brain functions such as hearing, speech, memory, spatial navigation or emotion recognition. Structural changes (atrophy, asymmetry) of temporal lobe are seen in patients with epilepsy, dementia or some psychiatric disorders. We targeted our project to assess temporal lobe cortex organisation asymmetry in comparison to pPlanum temporale as the most discussed temporolobar area concerning variability. Materials and methods: 47 right-handed healthy volunteers – 24 women, 23 men – were included into the study. MRI images were manually segmented to create temporal lobe masks. The masks were automatically segmented in three groups of voxels (grey and white matter, cerebrospinal fluid-CSF). After removal of voxels representing CSF the masks were transferred into aligned 3D models using spherical harmonization. Resulting 3D models were statistically compared using MANCOVA algorithm. Results: Right-left asymmetry of whole temporal lobe volume was assessed (right larger than left, in average 1.82 cm3, p = 0.005). Following spatial analysis using average 3D model of temporal lobes showed Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

56 Abstracts significant (p < 0.05) difference in cortex organization: grey matter increase in the left anterior mesiotemporal area, anterior part of left planum temporale and on contrary posterior part of right temporal lobe. In gender comparison, temporal lobe was generally smaller in women and also the asymmetry was less pronounced. Conclusions: The spherical harmonization method is unbiased – not burdened by subjective visual assessment – and its use in temporal lobe volumetry is unique. Our work shows significant side asymmetry of temporal lobe in healthy controls. Right lobe is larger, but cortex organisation asymmetry is noticeable, especially in advantage for the left anterior side. This can correspond to the left sided speech dominance in righthanded subjects.

P148 THE IMPLICATION OF CAV1 AND CA2+-DEPENDENT CATION CHANNELS IN PDS FORMATION Kubista H, Stiglbauer V, Ruiß M, Hilber K, Boehm S Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Vienna, Austria Purpose: There is considerable evidence in support of an involvement of L-type voltage-gated calcium channels (LTCCs) in the formation of paroxysmal depolarization shifts (PDS), but the role of the two central LTCC isoforms, Cav1.2 and Cav1.3, has not been addressed so far. An implication of Ca2+-dependent cation (CAN) channels in PDS formation has also been widely disseminated in textbooks, but this hypothesis has never obtained direct experimental evidence. Recently, we have shown using mice expressing a dihydropyridine-insensitive Cav1.2 mutant (Cav1.2DHP/ mice) and Cav1.3/ knockout mice that of the two neuronal LTCC isoforms Cav1.2 and Cav1.3, only the Cav1.2 isoform is coupled functionally to CAN channels in primary neurons of rat hippocampus (Hasreiter J et al. Am J Physiol Cell Physiol. 2014, 306: C1200-C1213.). Therefore, these mice represent excellent models to investigate the role of Cav1.2 and Cav1.3, as well as the implication of CAN channels in PDS. Method: Electrophysiological recordings were made using the perforated patch clamp technique. PDS were induced using bicuculline or caffeine and LTCC activity was modulated using the dihydropyridines Bay K8644 (agonist) and isradipine (antagonist). Results: Distinct PDS could be elicited by Bay K8644 in Cav1.2DHP/ neurons but not in Cav1.3/ neurons. PDS in Cav1.2DHP/ neurons had the characteristic shape of similar events originally described in epileptic foci of cats (Matsumoto H and Ajmone Marsan C Exp Neurol. 1964, 9:286–304). In Cav1.3/ neurons, augmentation of LTCC activity by Bay K8644 only increased suprathreshold excitatory postsynaptic potentials. Conclusion: Hence, the LTCC requirement of PDS mainly relates to Cav1.3 channels rather than to Cav1.2 channels and CAN channels in hippocampal neurons. These results add to the increasing evidence of a pathologic potential of the Cav1.3 isoform. Moreover, Cav1.3 channels provide a promising target for therapeutic PDS elimination. This study was supported by a grant from the Herzfelder’sche Familienstiftung.

P149 ALLOPREGNANOLONE IS REDUCED IN PATIENTS WITH PCDH19-RELATED EPILEPSY Trivisano M1, Lucchi C2,3, Terracciano A4, Rustichelli C5, Cusmai R1, Ubertini G6, Giannone G7, Bertini E4, Vigevano F1, Gecz J8, Biagini G2,3, Specchio N1 1 Department of Neuroscience, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 2Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy, 3Department of Neurosciences, NOCSAE Hospital, AUSL Modena, Modena, Italy, 4Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, Department of Neurosciences, Bambino Gesu’ Children’s Hospital, IRCCS, Rome, Italy, 5Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy, 6Unit of Endocrinology and Diabetes, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 7Department of Chemistry, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 8University of Adelaide, Adelaide, SA, Australia Purpose: The inherit base of PCDH19-related epilepsy suggests a hormonal involvement due to de-regulation of AKR1C1-3 genes, which encode for crucial steroid hormone-metabolizing enzymes. Both mRNA and protein levels of AKR1C3 have been reported to be decreased in a small number of PCDH19 mutated patients. Aim of this study is to verify allopregnanolone and other neuroactive steroids serum levels in PCDH19 mutated patients. Methods: We performed a prospective case-control study. We enrolled 12 patients affected by PCDH19-related epilepsy and 15 controls, ageand sex-matched. Controls were recruited among subjects evaluated for praecox puberty or hyperandrogenism. In both groups blood samples were taken at basal (T0) and 60 min after (ACTH) administration (T1). Quantitative analysis of neuroactive steroids in serum was performed by liquid chromatography-electrospray tandem mass spectrometry. Study population: median age of PCDH19-mutated patients was 8.3 5.7 years (range 2.5–18.9). Other than epilepsy, 6 patients had mental retardation. Controls were all females, age 9.2 4.0 years (range 6.1–17.9). All controls had a normal cognitive profile. Nine patients had a diagnosis of praecox puberty and 6 hyperandrogenism. Results: All neuroactive steroids resulted down produced in patients with PCDH19-related epilepsy rather than controls. At basal assessment (T0), allopregnanolone was 0.9 0.5 vs. 0.18 0.9 ng/ml (p < 0.05); pregnanolone was 0.0 0.5 vs. 0.3 0.5 ng/ml (p > 0.05), but pregnanolone sulfate was 7.39 5.53 vs. 75.41 52.69 ng/ml (p < 0.05). Also cortisol, progesterone and 17-OH progesterone resulted to be lowered in PCDH19-mutated patients compared with controls. After ACTH injection (T1), both neuroactive steroids and the other peripheral steroids were confirmed to be lower compared with controls. ACTH test demonstrated a normal functioning of peripheral glands. Conclusion: We documented a down regulation of all steroidogenesis in PCDH19-related epilepsy. Particularly, we found allopregnanolone and pregnenolone sulfate deficiency. Allopregnanolone is a GABA-A receptor modulator influencing neuronal excitability, thus representing a realistic therapeutic target for PCDH19-related epilepsy.

P150 THE CORRELATION STUDY BETWEEN ELECTROPHYSIOLOGICAL DMN AND COGNITIVE IMPAIRMENT BASED ON EXPERIMENTAL TLE RATS Wang J, Zhang T, Chen W, Guo D, Xia Y, Yao D School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China Purpose: Cognitive impairment is a common complication in patients with temporal lobe epilepsy (TLE). It is found that the default mode Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

57 Abstracts network (DMN) involved in some neurological and psychotic disorders. However, the correlation between DMN and the cognitive impairment due to epilepsy is poorly known. The purpose of current study is to assess the correlation between the cognitive impairment and DMN. Method: In this work, 15 electrodes were implemented into the DMN regions of rat defined by fMRI. The changes of cognitive ability based on the spatial memory task and non-spatial memory task and electrophysiological DMN were evaluated in pilocarpine-induced TLE rats by the power spectrum and the coherence methods. Results: The results showed that there were the cognitive impairment both spatial and non-spatial memory in TLE rats. Through the power spectrum analysis, we found that the power of Beta frequency in hippocampus had a significant decreased under spatial and non-spatial task state in epileptic rats. And it is also found that the network connectivity between the hippocampus with other brain regions of DMN was significant decreased in Beta frequency only in spatial memory task. Conclusion: These results suggest that DMN might mainly participate in spatial memory processing. The cognitive impairment might be related to the connectivity reduction of DMN in TLE rats. Keywords: Default mode network, electrophysiological network, cognitive ability, TLE rats.

Basic Science 5 Wednesday 14th September P151 USING AUTOMATED ALGORITHMS TO ANALYZE CIRCADIAN CHANGES OF EEG BIOMARKERS PROPERTIES IN PATIENTS WITH EPILEPSY Balach J, Jezdik P, Janca R, Cmejla R Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic Purpose: Visual assessment of EEG biomarkers dynamics is highly time consuming and very subjective. We developed algorithms for high frequency oscillations and interictal discharges (spike) detection. With these methods we can process large amount of data in reasonable time and with objective results. With this methods the long term analysis can bring few more information for the more precise epilepsy diagnosis and surgery. Method: Both algorithms were used on set of 6 patients invasive EEG recordings. Recordings have length of 17.9 5.7 h and were recorded with 114 22 channels. Results of quantitative analysis were processed in respect to sleep/wake cycle. We compare output of automated detection algorithms with results of studies where were biomarkers labelled visually. Results: The trends in detected biomarkers from the automated algorithms follow circadian dynamics. In respect to the sleep/wake cycle phases occurrence of the high frequency oscillations is significantly more frequent in non-REM sleep phase as it was presented in previous studies. Conclusion: The automatic detection shows ability to monitor trends in the occurrence of EEG biomarkers during circadian rhythms. When we experimentally use detectors to several days long recordings were revealed ultradian changes in trends detected by automated methods. Our next aim will be analysis of circadian and ultradian changes on dataset of patients with focal cortical dysplasia. We try to distinguish type I and II on behalf of these changes and biomarkers parameters.

P152 IDENTIFICATION OF MIRNA EXPRESSION PROFILES IN HUMAN MESIAL TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL SCLEROSIS Bencúrová P1,2, Baloun J1,2, Musilov a K1,3,4, P al K1,3,4, Tom N1,3,4, Hynst J1,3,4, Radov a L1, Pail M2, Brichtov a E2, 2 1,3,4 1,3,4 Hermanov a M , Pospısilov a S , Mr az M , Br azdil M1,2 1 CEITEC – Central European Institute of Technology, Masaryk University, Brno, Czech Republic, 2St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, 3University Hospital Brno, Masaryk University, Brno, Czech Republic, 4Medical Faculty of Masaryk University, Brno, Czech Republic Purpose: The primary aim of this study was to identify specific miRNAs with aberrant expression in hippocampal tissue of mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS). Method: We analyzed miRNA isolated from paraffin embedded tissue slices of hippocampal complex from 22 mTLE +HS patients (14 leftsided, 8 right-sided) and 9 post mortem controls. To characterize the miRNAs highly prone to be involved in the pathological changes in the mTLE+HS brain tissue we performed the expression analysis combining the next generation sequencing (NGS) and novel specific technique for miRNA quantification miQPCR. Results: By both methodical approaches we confirmed significant upregulation of miR-129-1-3p, 129-2-3p, 142-3p, 191-5p, 193b-3p, 1955p, 374b-5p, 451a, and 490-3p in mTLE+HS patients. The levels of miRNA-184 were significantly higher in control subjects. Differential expression levels in mTLE+ HS patients were identified also in the case of 10 miRNA species never considered to play a role in epilepsy before. Conclusion: Analytical approach combining NGS with miQPCR used for the first time for analysis of human epileptic foci led to reliable identification of miRNA with altered expression in mTLE +HS patients. Acknowledgement: This work was supported by GACR (GAP1604726S), CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II, European Union’s Horizon 2020 grant progremme (grant agreement No 692298) and by MUNI/A/1044/ 2015 and MUNI/A/1028/2015.

P153 BLOOD-BRAIN BARRIER MARKERS AFTER TONICCLONIC SEIZURES Cudna A1,2, Jopowicz A1, Bronisz E1, Kurkowska-Jastrzez bska I1 1 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland, 2Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland Inflammation is suggested to be one of the factors stimulating abnormal discharge in the nerve cells, and thus contribute to recurrence of epileptic seizures. Damaged blood-brain barrier is a part of the on-going inflammatory process responsible for an increase of neuronal excitability and intensification of the inflammation and can participate in the creation of the epileptic focus as well as enhance the already existing ones. The aim of the present study was to investigate changes in the expression of markers of the activation of the blood-brain barrier (BBB) in patients with previously diagnosed epilepsy. We examined 50 patients with generalised tonic-clonic seizures, hospitalized in the 2nd Department of Neurology, Institute of Psychiatry and Neurology in Warsaw. The control group comprised nonepileptic, noninflammatory adult patients and healthy volunteers. The blood sample were taken from patients 1 h, 24 h and 72 h after seizures, in order to follow the variations of the studied parameters in Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

58 Abstracts time. The markers of endothelial activation (ICAM-1, E- and P-selectins), markers of endothelial injury (thrombomodulin), markers of increased permeability (metaloproteinase 9- MMP9, S100B), and inhibitor of metaloproteinase 9 (TIMP-1) were studied. It has been shown that the levels of MMP9, S100b and MMP9/TIMP1 ratio were significantly increased in 1 and 24 h after seizures, and then returned to the control level. The expression of ICAM- 1 was increased only 1 h after the onset of seizures. There were no significant changes in the level of E-selectin, P-selectin, and thrombomodulin. The expression of TIMP1 was increased 24 and 72 h after seizures. Increased expression of ICAM-1, MMP9, and S100B after seizures suggests stimulation of endothelial cells and increased permeability of blood-brain barrier Reducing the level of MMP9 and the increase of TIMP1 indicates an inhibition of MMP9 and, therefore, can contribute to improving tightness of the blood-brain barrier.

P154 HIGH-FREQUENCY OSCILLATION ABILITY TO LOCALIZE EPILEPTOGENIC TISSUE IN ANIMAL EPILEPSY MODEL Havel T1, Kudlacek J1,2, Jiruska P2, Jezdik P1, Cmejla R1 1 Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic, 2Department of Developmental Epileptology, Czech Academy of Sciences, Institute of Physiology, Prague, Czech Republic Purpose: Recently, high-frequency oscillations (HFOs) have been reported to be a specific marker of the epileptogenic tissue. According to these findings, we explored the HFOs ability to localize epileptogenic lesion in the tetanus toxin model of epilepsy in the rat. To test this ability, we analyzed multi-channel intracranial electroencephalograms (iEEG) recorded in the epileptic animals. Methods: Four adult male rats (Wistar) were implanted bipolar macro-electrodes into the limbic structures, treated by the tetanus toxin injected in the CA3 area of the right dorsal hippocampus and long-term monitored. Overall 880 (4 9 220) min of iEEG were processed by the automatic HFO detector and further analyzed. The dominant frequency of HFOs was determined from the spectrogram and the occurrence of ipsilateral and contralateral events was compared for each subject separately. Furthermore, we examined the occurrence of ripples (Rip, 80–250 Hz) and fast ripples (FR, 250– 800 Hz) within ipsilateral structures. Results: The predominant occurrence of HFOs corresponds with the laterality of the epileptic focus in 3 of 4 subjects. The most active region in the ipsilateral hemisphere of all subjects was the ventral hippocampus, according to the ripple occurrence. The occurrence of FRs varies between subjects. The unique subject which demonstrate the anomalous pattern differed also with the significantly higher incidence of the high frequency events without any apparent cause. Conclusion: In most cases, the HFOs could be used to identify the laterality of the epileptic focus. The findings suggests the frequency of ripple occurrence in the long-term recordings points to the injected structure in all of examined animals. Similar result was expected also with FRs but was not confirmed. Another conclusion is, that the structures which do not express any HFO activity do not need to be considered a possible location of epileptic focus in further evaluation.

P155 MICROSEIZURES RELIABLY LOCALIZE PRIMARY EPILEPTOGENIC AREAS IN TETANUS TOXIN MODEL OF TEMPORAL LOBE EPILEPSY Kudlacek J1,2, Vlk P1,2, Demeterova L1, Posusta A1, Otahal J1, Jiruska P1 1 Department of Developmental Epileptology, Institute of Physiology of Czech Academy of Sciences, Prague, Czech Republic, 2Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic Purpose: There is a continuous search for highly specific electrographic marker which would allow precise delineation of the epileptogenic tissue. Microseizures were observed in seizure initiating areas in humans and represent spatially limited ictal-like discharge confined to single microelectrode contact. In this study we explored properties and localizing features of microseizures in tetanus toxin model of temporal lobe epilepsy. Method: TLE was induced in seven adult rats by injection of 10 ng of tetanus toxin into the right dorsal hippocampus. Following the injection, animals were implanted with bipolar recording electrodes in the following structures of both hemispheres: amygdala, dorsal hippocampus, ventral hippocampus and piriform, perirhinal and entorhinal cortices. The animals were video-EEG monitored for four weeks. To analyse microseizures we developed a semi-automatic algorithm, which detects microseizures using their energy and frequency features. Results: In the tetanus toxin syndrome, seizures initiated in multiple limbic structures, mainly in ipsilateral (48%) and contralateral (27%) hippocampus. Microseizures were present between seizures in all animals. They are characterized as high-amplitude, rhythmic ictal-like EEG activity lasting 1–8 s (3.6 0.2), often with superimposed high-frequency oscillations. We have extracted 210 microseizures (30 per animal) in order to evaluate their spatial distribution. Occurrence and magnitude of microseizure in each limbic structure was determined from the ratio of signal power during microseizure to power of background signal. The highest mean power ratio 27.5 2.1 was in the injected dorsal hippocampus. The second highest 6.9 0.6 was in the contralateral dorsal hippocampus. Conclusion: This study demonstrates that microseizures represent reliable electrographic marker which is able to localize the primary epileptogenic tissue and to lateralize the epileptogenic limbic structures. Supported by grants from the Ministry of Health of the Czech Republic (AZV 15-29835A, 15-33115A), Czech Science Foundation (14-02634S, 14-11345S) and by Neuron Fund for Support of Science (NFKJ 001/ 2012).

P156 GENOME-WIDE MICRORNA EXPRESSION PROFILE AND REGULATORY SIGNALING PATHWAYS IN GANGLIOGLIOMA Majumdar A1, Kakkar A1, Kumar A1, Pathak P1, Sharma MC1, Suri V1, Chandra SP2, Sarkar C1 1 Pathology, All India Institute of Medical Sciences, New Delhi, New Delhi, India, 2Neurosurgery, All India Institute of Medical Sciences, New Delhi, New Delhi, India Purpose: Ganglioglioma (GG) is a low-grade glioneuronal tumor associated with intractable epilepsy. MicroRNAs (miRNAs) regulate gene transcription; have the potential to serve as indicators in the diagnosis and progression of various cancers; yet role of miRNAs in GGs remains unexplored. Hence, we studied the genome-wide expression profile of miRNAs to identify their regulatory role in GGs.


59 Abstracts Method: We analysed expression of 5,214 miRNAs in 9 GGs and 3 normal brain controls using Affymetrix, GeneChip miRNA 4.0 Array. Significantly altered miRNAs were further validated in 20 GGs with quantitative real-time PCR (qPCR). MiRNA target genes and their functional enrichment were determined using mirsystem and Enrichr software and candidate genes validated by qPCR. Sensitivity and specificity of most differentially expressed miRNAs was determined with Receiver Operating Characteristic (ROC) curve analysis. Result: A total 66 miRNAs (32 upregulated and 34 downregulated) were found to exhibit significantly different expression in GGs (fold change ≥2 or ≤2 and p < 0.05). MiR-187-3p, miR-23a-5p, miR-217, miR-216a3p were the top deregulated miRNAs and in-silico target analysis of these revealed HTRC2, FGF9 and IL6 among the top target genes showing inverse correlation with miRNA expression, both confirmed and validated by qRT-PCR. Enrichr ranked pathways in cancer, axon guidance, focal adhesion, MAPK signaling and mTOR among many significant pathways affected by our set of deregulated miRNAs. ROC curve revealed an area under curve≥0.7 and p < 0.05 for validated miRNAs, thus establishing a diagnostic significance. Conclusion: This study is the first to report the genome-wide miRNA profile of GGs. The miRNAs signature revealed MAPK/mTOR pathway as potential promoter for GG tumorigenesis. Activation of mTOR is known in epileptogenesis or maintaining seizures and our finding of activation of this pathway in GGs further establishes their link with epilepsy. In addition, we also established diagnostic utility of few miRNAs in GGs.

P157 COGNITIVE DEFICITS AND BRAIN MYO-INOSITOL ARE EARLY BIOMARKERS OF EPILEPTOGENESIS IN A RAT MODEL OF EPILEPSY Pascente R1, Frigerio F1, Rizzi M1, Porcu L1, Boido M2, Davis J3, Zaben M3, Tolomeo D1, Filibian M1, Gray WP3, Vezzani A1, Ravizza T1 1 IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy, 2Neuroscience Institute ‘Cavalieri Ottolenghi’, Torino, Italy, 3Neuroscience and Mental Health Research Institute, Cardiff, United Kingdom Purpose: To test the predictive value of cognitive deficits and brain astrocyte activation for the development of epilepsy following a potential epileptogenic injury. Method: We used a model of epilepsy induced by pilocarpine-evoked status epilepticus (SE) in 21-day old rats where only 70% of animals developed spontaneous seizures after around 70 days, although SE was similar in all rats. Learning was evaluated in the Morris water-maze at days 15 and 65 post-SE, each time followed by proton magnetic resonance spectroscopy for measuring hippocampal myo-Inositol levels, a marker of astrocyte activation. Rats were video-EEG monitored for 2 weeks at 7 months post-SE to detect spontaneous seizures, then brain histology was done. Behavioral and imaging data were retrospectively analysed in epileptic rats and compared with non epileptic and control animals. Results: Rats displayed spatial learning deficits within three weeks from SE. However, only epilepsy-prone rats showed accelerated forgetting and reduced learning rate compared to both rats not developing epilepsy and controls. These deficits were associated with reduced hippocampal neurogenesis. myo-Inositol levels increased transiently in the hippocampus of SE-rats not developing epilepsy while this increase persisted until spontaneous seizures onset in epilepsy-prone rats, being associated with a local increase in S100beta-positive astrocytes. Neuronal cell loss was similar in all SE-rats. Conclusion: Behavioral deficits, together with a non-invasive marker of astrocyte activation, predict which rats develop epilepsy after an acute injury. These measures have potential clinical relevance for identifying

individuals at-risk for developing epilepsy, and consequently, for designing adequately powered antiepileptogenesis trials.

P158 RETROSPECTIVE ANALYSIS OF SEIZURE-RELATED HEART RATE CHANGE Ravan M, McGuire RM, Sabesan S, Begnaud J Neuromodulation Division, LivaNova PLC, Houston, TX, United States Purpose: Heart rate increase is associated with seizures in a large proportion of epilepsy patients (82%). Video EEG and ECG data were acquired from 171 investigator-annotated seizures during the E-36 and E-37 clinical trials (NCT01325623 and NCT01846741, respectively). The purpose of the present analysis is to characterize the magnitude and timing of seizure-related heart rate changes relative to ictal onset. Method: Previously (Boon 2015, Fisher 2016), heart rate change was measured using fixed time intervals during the early portion of the ictal period (first 30 s). This approach was taken since heart rate change early within the ictal period presents an improved opportunity for intervention through automated vagus nerve stimulation (VNS), compared to heart rate increases with delayed onset. The present analysis uses a new method to characterize the global maximum heart rate change due to a seizure. A phase space de-spiking algorithm, and a pseudo-Gaussian smoothing window, were used to reduce the influence of recording artifacts. Then, the maximum seizure-related heart rate was identified within 2 min of ictal onset, and compared with the pre-seizure baseline heart rate. Results: Seventy-one percent of seizures were associated with a peak heart rate increase of at least 20% from baseline. A 20% increase in heart rate corresponds with the most sensitive detection setting in the Model 106 VNS Therapy System, which automatically triggers stimulation in response to rapid increases in heart rate. The proportion of seizures with at least 30%, 40%, 50%, 60%, and 70% peak relative heart rate increase (corresponding with other programmable device settings) was 57%, 43%, 25%, 18%, and 15%, respectively. On average the maximum heart rate increase occurred 18 s following seizure onset (SD: 50 s). Conclusion: The prevalence, magnitude, and timing of seizure-related heart rate increase, all support the utility of cardiac based seizure detection.

Basic Science 6 Wednesday 14th September P159 N-PALMITOYLETHANOLAMINE ENHANCES ANTICONVULSANT EFFECTS OF SOME ANTIEPILEPTIC DRUGS AGAINST AUDIOGENIC SEIZURES IN DBA/2 MICE Citraro R, Leo A, De Sarro G, Russo E Science of Health, University of Catanzaro, Catanzaro, Italy Purpose: The endogenous cannabinoid system plays a role in several central nervous system disorders, particularly those associated with neuronal hyperexcitability including epilepsy1,2. We studied the effects of N-palmitoylethanolamine (PEA), an endogenous fatty acid of ethanolamide, in DBA/2 mice, a genetic animal model of reflex generalized tonic-clonic seizures. In order to study the role of CB receptors and peroxisome proliferator-activated receptors (PPAR)-a, we also studied the effects of PEA after co-administration with vehicle or 1-(2,4-Dichlorophenyl)-5-(4-methoxyphenyl)-4-methyl-N-(1-piperidinyl)-1H-pyrazole3-carboxamide (NIDA-41020), a CB1 receptor antagonist, or N-((2S)-2Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

60 Abstracts (((1Z)-1-methyl-3-oxo-3-(4-(trifluoromethyl)phenyl)prop-1-enyl) amino)-3-(4-(2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy)phenyl)propyl)propanamide (GW6471), a PPAR-a antagonist. Co-administration of ineffective doses of PEA with some antiepileptic drugs (AEDs) was studied in order to identify possible pharmacological interactions using the DBA/2 mouse model. Method: DBA/2 mice were treated with PEA (5–40 mg/kg, i.p.) or coadministered with AEDs before auditory stimulation, as previously descrived3,4.

Conclusion: SWD of the myelin mutant rats are susceptible to antiabsence drugs in humans, as well as in GAERS and WAG/Rij rats supporting common neurophysiological mechanisms. Further studies are necessary to determine cortical focus and thalamo-cortical activity during SWD in the myelin mutant taiep rats. Partly funded by CONACYT grants 243247 and 243333 to MCC and JRE, respectively and also by VIEP-BUAP 2016, PROFOCIE 2016 and CA Neuroendocrinologıa BUAP-CA-288 through PRODEP-SEP.

Results: PEA intraperitoneal (i.p.) administration was able to significantly and dose-dependently decrease the severity of audiogenic seizures. PEA acts as an anticonvulsant in DBA/2 mice mainly through PPAR-a and likely indirectly on CB1 receptors. We found that the co-administration of PEA potentiated the efficacy of diazepam, felbamate, gabapentin, phenobarbital, topiramate and valproate whereas, the co-administrations with the other AEDs did not have effects; PEA administration did not significantly affect the total plasma and brain levels of AEDs.

P161 EFFECTS OF KETOGENIC DIET ON HIPPOCAMPAL CALBINDIN-D28K EXPRESSION IN MICE WITH KAINIC ACID-INDUCED SEIZURES Kim DW, Shin Y Pediatrics, Inje University Ilsan Paik Hospital, Goyang, Korea

Conclusion: PEA showed an additive anticonvulsant effect when coadministered with some AEDs without affecting their brain/blood/ plasma levels; therefore, we can exclude pharmacokinetic interactions and conclude that for the most of AEDs, potentiation was of pharmacodynamic nature. PEA mainly acts through PPAR-a suggesting a possible therapeutic importance of this target also in light of beneficial drug-drug combinations.

Purpose: Ketogenic Diet (KD) was reported to have a neuroprotective effect on kainic acid (KA)-induced hippocampal cell death in mice. Calbindin-D28k (CB) is a Ca2+-binding protein, which has the capacity to buffer intracellular Ca2+ and is extensively distributed in the CA1/2 pyramidal cells and interneurons of the hippocampus. Numerous studies suggested that CB plays a neuroprotective function against various central nerve system insults by buffering intracellular Ca2+ levels. In the present study, we examined the effects of KD on hippocampal CB expression in the KA-induced seizure mouse model.

References1. Friedman, O. Devinsky. N Engl J Med. 2015;373:1048– 1058. 2. Mattace Raso et al. Pharmacol Res. 2014;86:32–41. 3. De Sarro et al. Pharmacol Res. 2012;65:285–296. 4. Russo et al. Pharmacol Res. 2013;70:1–12.

P160 ABSENCE CRISIS ARE SUSCEPTIBLE TO LAMOTRIGINE AND ETHOSUXIMIDE IN MALE TAIEP RATS Cortes C1, Corona J1, Callejas C1, Eguibar JR1,2 1 Benemerita Autonoma de Puebla, Institute of Physiology, Puebla, Mexico, 2Direccion General de Investigacion, Vicerrectorıa de Investigacion y Estudios de Posgrado, Puebla, Mexico Purpose: The aim to this study was to analyze the effects of well know antiabsence drugs on the spike-wave discharge (SWD) in the male myelin mutant taiep rats at 9 month of age when the frequency is the highest. Taiep rats had an initial hypomyelinatioin followed by a progressive demyelination in the central nervous system due to an accumulation of microtubules in the cytoplasm and the processes of the oligodendrocytes that disrupt the transporting mechanisms and a general reduction of the myelin proteins. Method: All subjects (Ss) were maintained under standard animal room conditions. We implanted cortical and hippocampus electrodes, and additional electrodes to record EMG and EOG. All signal was recording using the Harmonie system with a sampling rate of 200 Hz and in 5 sec epochs using Sensa module. The Ss were adapted by 3 days to recording conditions and the following days control and after drug recordings were did. Results: We measured offline the number, duration and latency of SWD in control conditions and after the administration of lamotrigine and ethoxusimide. Our results showed that ethosuximide 100 mg/Kg i.p. significantly reduced the number and mean duration of SWD (p < 0.05) by a 5 h period. On the other hand, intragastric administration of lamotrigine 10 mg/Kg also significantly diminished the frequency of SWD (p < 0.05) during the following 8 h suggesting stronger effect respect to that obtained with ethosuximide.


Method: Normal male ICR mice were used for all the experiments. For four weeks, the KD group was fed a KD, whilst the normal diet (ND) group was fed a standard rodent chow (each n = 10). Thereafter, half of both groups (each n = 5) were sacrificed to investigate the change in CB expression by the KD itself. And the seizures were induced by KA (25 mg/kg. i.p.) in the remainder (each n = 5). Two days following KA administration, animals were sacrificed and their brains were removed for immunohistochemistry of CB expression in the hippocampus. Results: Without KA administration, the number of CB-positive interneurons was significantly increased in the KD-fed mice compared with the ND-fed mice (21.9 3.8 vs. 13.4 1.5, P < 0.05). Two days after KA administration, CB immunoreactivity in the CA1/2 and interneurons was almost lost in the ND-fed mice (0.6 0.4). But, in the KD-fed mice, CB immunoreactivity was preserved although decreased (15.1 1.2). Conclusion: These results demonstrate that KD increases hippocampal CB expression and suggest that increased CB may result in the protection of hippocampal neurons via Ca2+ buffering in the KA-induced seizure mouse model.

P162 ISOBOLOGRAPHIC ANALYSIS OF INTERACTIONS OF LACOSAMIDE WITH SELECTED ANTIEPILEPTIC DRUGS IN THREE-DRUG COMBINATIONS AGAINST MAXIMAL ELECTROSHOCK-INDUCED SEIZURES IN MICE Luszczki J1,2, Kondrat-Wrobel M1, Zaluska K1, Marzeda P1, Florek-Luszczki M3 1 Department of Pathophysiology, Medical University of Lublin, Lublin, Poland, 2Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland, 3Centre of Public Health and Health Promotion, Institute of Rural Health, Lublin, Poland Purpose: Treatment of pharmacoresistant epilepsy is still a challenging issue for neurologists and epileptologists throughout the world. In spite of advances in the understanding of physiopathological processes of epileptogenesis, a number of currently available antiepileptic drugs and

61 Abstracts several novel drugs undergoing preclinical and clinical assessment with respect to their efficacy in particular types of epilepsy, about 30% of epilepsy patients have still seizures and require more intensive treatment, including application of antiepileptic drugs in dual or triple combinations. For these patients, new treatment strategies are elaborated to stop or considerably reduce their seizure attacks. This study was aimed at determining the type of interactions of lacosamide with some selected antiepileptic drugs (valproate, carbamazepine and lamotrigine) in threedrug combinations (lacosamide+valproate+carbamazepine, lacosamide+valproate+lamotrigine and lacosamide+carbamazepine+ lamotrigine) in the mouse maximal electroshock-induced seizure model. Method: Type I isobolographic analysis for parallel and non-parallel dose-response relationship curves was used to precisely characterize the interactions among the antiepileptics in three-drug combinations. Tonic hind limb extension (seizure activity) was evoked in male albino Swiss mice with current (25 mA, 500 V, 50 Hz, 0.2 s of stimulus duration) delivered via auricular electrodes. Results: The combinations of lacosamide+valproate+carbamazepine and lacosamide+valproate+lamotrigine at the fixed-ratio of 1:1:1 exerted sub-additive (antagonistic) interaction in the maximal electroshockinduced seizure test in mice. Only the combination of lacosamide+carbamazepine+lamotrigine (fixed-ratio of 1:1:1) was additive, offering protection of the animals against maximal electroshock-induced seizures. Conclusion: The combinations of lacosamide+valproate+carbamazepine and lacosamide+valproate+lamotrigine should be avoided in epileptic patients due to their antagonistic interaction in mice subjected to the maximal electroshock-induced seizure test. In contrast, the combination of lacosamide+carbamazepine+lamotrigine at the fixed-ratio of 1:1:1 is worth recommendation to further clinical settings because of the additive interaction among the antiepileptic drugs.

P164 DYNAMIC S1PR SUBUNIT EXPRESSION PATTERNS AND IN VIVO EEG ANALYSIS SUGGEST FINGOLIMOD AS PROMISING THERAPY OPTION IN FOCAL EPILEPSIES Pitsch J1, Gnatkovsky V2, M€uller JA1, de Curtis M2, Schoch S1, Becker AJ1 1 Neuropathology, Bonn Medical Center, Bonn, Germany, 2Unit of Epileptology and Experimental Neurophysiology, Fondazione Istituto Neurologico Carlo Besta, Milano, Italy We have studied the expression of target structures as therapy rationale of Fingolimod (FTY720) in temporal lobe epilepsy (TLE), i.e. the most frequent epilepsy syndrome with focal seizure onset. About 30% of TLE patients are pharmacoresistant to antiepileptic drugs and therefore there is a pressing need for improved therapy development. Sphingolipids represent a class of biologically active lipids that have key roles in multiple physio- and pathological processes particularly in inflammation. They signal through specific receptors (S1Pr1-5) which are the binding site for the drug Fingolimod. We analyzed the mRNA-expression and protein abundance of the Fingolimod target molecules S1Pr1-5 is altered in hippocampal brain tissue samples of mice after induced status epilepticus (SE) and whether Fingolimod treatment has anti-convulsive and/or neuroprotective effects in TLE. After induced SE a strong transient increase in mRNA-expression of S1Pr3 with a peak at the 36 h time point in the CA1 subfield was found in the pilocarpine as well as in the kainate model of epilepsy. Additionally, we observed a similar expression pattern in CA3 and DG compared to CA1. Protein expression levels and localization of S1Pr3 in the hippocampus showed a strong abundance of S1Pr3 after SE, reflecting the corresponding mRNA dynamics with the strongest expression in CA1 at day 4 after SE. Additionally, S1Pr3 shows a co-localization with GFAP resembling an astrocytic expression-pattern. We further examined the impact of Fingolimod on seizure frequency, severity and electroencephalographic power band changes in vivo.

Our project clearly demonstrates substantial expression levels as well as distinct dynamic expression changes in the epileptic hippocampal formation of Fingolimod target molecules. Furthermore, Fingolimod appears to have anti-epileptogenic and anti-convulsive effects in TLE in vivo. We hope these analyses will contribute to provide the urgently required improved treatments for chronic epilepsy patients. This work was generally supported by Novartis and SFB1089.

P167 ACUTE POST-STATUS ADMINISTRATION OF ENDOCANNABINOID RECEPTOR AGONIST WIN55,212-2 HAS A NEUROPROTECTIVE EFFECT BUT DOES NOT PREVENT EPILEPTOGENESIS Suleymanova EM1, van Rijn CM2, Vinogradova LV1 1 Institute of Higher Nervous Activity and Neurophysiology RAS, Moscow, Russian Federation, 2Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands Purpose: We have previously shown that single administration of endocannabinoid receptor agonist WIN-55,212-2 early after status epilepticus (SE) has an anticonvulsive effect and suppresses the development of nonconvulsive cortical spike-and-wave discharges during the latent period of epileptogenesis. In this study, we have investigated the effect of early stimulation of endocannabinoid system after SE on the occurrence of spontaneous recurrent seizures (SRSs) in the chronic period after SE and SE-induced neuronal loss. Method: The study was carried out on the lithium-pilocarpine model of temporal lobe epilepsy. SE lasted for 90 min and was stopped by injection of pentobarbital. WIN-55,212-2 (5 mg/kg) or vehicle (5% DMSO and 1% Tween-80) was administered 4 h after the end of SE. Cortical and hippocampal EEG was recorded in freely moving rats. Behavior was video-monitored. Rats were sacrificed 5 months after SE; brains were sectioned and stained with cresyl violet to evaluate the number of cells in the hippocampal CA1-CA3 fields and hilus. Results: 1–4 months after SE, 50% of control rats developed spontaneous recurrent seizures (SRSs). Administration of WIN-55,212-2 did not affect the development of spontaneous seizures. The mean daily frequency of SRSs in vehicle- and WIN-treated rats did not differ significantly (2.25 0.9 and 2.06 0.9 respectively). The number of cells in the dentate hilar region but not in the CA1 and CA3 fields was higher in WIN-treated rats in comparison with vehicle-treated animals (p = 0.048). The 5month survival rate of WIN-treated rats was significantly greater in comparison with vehicle-treated rats (93% and 44% respectively, p = 0.0049). Conclusion: Post-SE administration of the agonist of endocannabinoid receptors WIN-55,212-2 had a partial neuroprotective effect, significantly decreased post-SE mortality, but did not prevent the development of spontaneous seizures in the chronic period. This study was supported by the Russian Foundation for Basic Research, projects no. 14-04-01184, 16-34-01282.

P168 INHIBITION OF MONOACYLGLYCEROL LIPASE (MAGL) BY PF-4645 PROTECTS MICE AGAINST REFRACTORY SE Terrone G1, Pauletti A1, Villa BR1, Salamone A1, Guilmette E2, Piro J2, Samad T2, Vezzani A1 1 IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 2Pfizer Global Research and Development, Cambridge, MA, United States Purpose: MAGL is a key enzyme in the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG), representing the major source of Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

62 Abstracts brain arachidonic acid (AA) and proinflammatory eicosanoids. We investigated if MAGL inhibition affects the development of refractory status epilepticus (SE) in mice. Method: We induced SE by intraamygdala injection of kainic acid in electrode- and guide cannula-implanted freely-moving C57/BL6N adult male mice. Forty min after SE onset diazepam (10 mg/kg i.p.) was injected: motor seizures were reduced but EEG SE was unaltered. Under EEG monitoring, mice were injected with PF4645 (10 mg/kg, s.c.) a potent and selective MAGL inhibitor, or its vehicle, 1 and 7 h after SE onset. This protocol increased 2-AG and decreased AA in brain for >8 h. SE was defined by continuous spikes in the g band (amplitude >29 baseline; frequency >5 Hz). The end of SE was set as the time the inter-spike interval becomes consistently >2 s. We reckoned the number of spikes/h and their total number during 12 h from SE onset, and the total SE duration. At the end of experiment, mice were killed for Fluoro-Jade analysis of hippocampal cell loss. Results: PF-4645 progressively reduced the number of spikes/h reaching a maximal 2-fold reduction at 3 h after injection compared to vehicleinjected mice (p < 0.01). SE duration was shortened: vehicle, 9.0 0.3 h, n = 13; PF-4645, 7.4 0.5 h, n = 17; p < 0.05). The reduction in spikes was accompanied by a decrease in inflammatory cytokines, including interleukin-1beta (p < 0.05). Moreover, the number of degenerating neurons was reduced by 2.5-fold in CA1 pyramidal layer (p < 0.05) vs. vehicle-injected mice. Conclusion: MAGL is a promising target for controlling refractory SE since PF-4645 reduced diazepam-resistant SE in mice, resulting in significant neuroprotection and attenuation of neuroinflammation. PF-4645 therapeutic effects are associated with increased 2-AG brain levels and reduced AA availability for eicosanoid biosynthesis.

P169 OPTOGENETIC CONTROL OF HUMAN NEURONS IN HIPPOCAMPAL TISSUE CULTURES Andersson M1, Avaliani N1, Svensson A2, Wickham J1, Pinborg LH3, Jespersen B4, Christiansen SH5, Bengzon J2, Woldbye DPD5, Kokaia M1 1 Department of Clinical Sciences, Epilepsy Centre, Lund University Hospital, Lund, Sweden, 2Department of Neurosurgery, Lund Stem Cell Center, Lund University Hospital, Lund, Sweden, 3Epilepsy Clinic & Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark, 4Department of Neurosurgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, 5 Department of Neuroscience and Pharmacology, Laboratory of Neural Plasticity, University of Copenhagen, Copenhagen, Denmark Purpose: Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. The aim of this project was to investigate if optogenetic tools can be used to modulate neurons in human brain tissue. Method: A lenti-viral vector containing channelrhodopsin-2 (ChR2) under the synapsin promoter was applied to human hippocampal and neocortical slices and incubated for 14 days. Verification of expression was done with immunohistochemistry. With a whole-cell patch-clamp electrophysiological setup the function of the expressed opsin as well as the intrinsic properties of the cells were recorded. Results: With immunohistochemistry we show that the ChR2 is widespread and mostly localised in neurons. Whole-cell patch-clamp electrophysiological recordings from individual neurons show that the intrinsic properties in most of the cells are comparable to human neurons recorded in acute hippocampal and neocortical slices. When exposing the cells to Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

460 nm blue light action potentials were recorded in current-clamp mode. Our data show that neurons in cultured human epileptic tissue slices can survive for prolonged periods, up to 14 days with relatively normal physiological function and that these neurons can effectively express ChR2 and respond to light stimulation by generation of action potentials. Conclusion: The successful application of optogenetic tools to human brain tissue provide a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies.

Clinical Epilepsy 1 Monday 12th September P172 EVALUATION OF 11 CASES WITH EPILEPTIC NYSTAGMUS Aydogdu I, Ekinci A, Gulluoglu H, Tabakoglu A, Cıftcı S, Guler A, Bademkiran F, Arac N € _ Ege Universitesi Tıp Fak€ ultesi N€ oroloji AD, Izmir, Turkey Purpose: Epileptic nystagmus is a rare ictal phenomenon, characterized by rapid, repetitive eye movements. It was usually seen as a horizontal nystagmus and rapid phase of the nistagmus is contralateral to the ictal activity. Ictal nystagmus is typically arise from parieto-temporo-occipital region Method: The study included 11 patients with epileptic nystagmus cases observed between 2004 and 2014 at our institution. Patients were aged between 18 and 67 years with isolated ictal nystagmus or accompanied by other seizures types. Demographic data, clinical history, ictal EEG and video images, and neuroimaging studies of patients were evaluated. Results: In all patients, horizontal nystagmus was observed with the rapid phase contralateral to the ictal activity. Accompanying findings to the nystagmus were conjugate eye deviation (72%), blinking (36%), homonymous hemianopia (27%), head deviation (27%), light flashes (18%) and focal motor seizures (36%, in face, arm, abdomen). The level of consciousness of the patients was depended on the underlying of pathology and confused in eight cases. The etiology of patients was determined as cerebrovascular disease (n = 3), trauma (n = 2), encephalitis (n = 3), temporal sclerosis (n:1) and MELAS (n:1, with two attack). There was history of epilepsy in 7 cases. _ Ictal activity in EEG were observed parieto-occipital (n:5) temporooccipital (n: 1), sentroparietal (n: 2), frontosentral (n: 1), temporal (n: 2) region. EEG findings were mostly compatible with the localization of lesions in cranial imaging. Conclusion: Epileptic nystagmus is a rare condition that result from different etiologies but very valuable ictal phenomenon giving important clues about the epileptic focus and lateralizing the underlying lesions. It was often observed with focal seizures. A careful examination should be done for the seize on of this phenomenon during seizure activity.

63 Abstracts P174 USE OF THE DISCOVER FORM (A STRUCTURED DIAGNOSTIC INTERVIEW) TO ENSURE CORRECT CLASSIFICATION IN A STUDY OF DISEASE IMPACT French J1, Williams B2, Friedman D1, Hegde M3, Thio KLL4, Hennessy R1, Louik J1 1 NYU Comprehensive Epilepsy Center, New York, NY, United States, 2Eisai Inc, Woodcliff Lake, NJ, United States, 3Epilepsy Center, University of California, San Francisco, CA, United States, 4Washington University School of Medicine, St. Louis, MO, United States Purpose: A qualitative patient interview study is being conducted to understand and document epilepsy disease impacts of relevance to patients. To ensure proper understanding of enrolled patients, site coordinators administered a structured interview: DISCOVER (Diagnostic Interview for Seizure Classification Outside of Video EEG Recording). Independent reviewers were used to determine if the DISCOVER form could be used remotely to classify patients. Method: Patients were recruited if investigators believed they had confirmed focal epilepsy. Once enrolled, coordinators administered the DISCOVER form to patients and, when available, to an observer who had witnessed seizures. The forms, with demographic information, were sent to two independent reviewers to determine seizure type: simple partial (SPS), complex partial (CPS), and partial-onset with secondary generalization (SGTCC). Results: Thirty-one patients have been recruited. An investigator/clinician onsite classified each patient’s seizures (patients could have >1) as SPS (n = 18), CPS (n = 22), and/or SGTCC (n = 18). Two remote reviewers agreed with clinician’s seizure classifications 52% of the time (N = 16); reviewers agreed with each other 87% of the time (N = 27) and disagreed on four cases. Where reviewers disagreed with the clinician (N = 11), the seizure types in question were primarily SPS (n = 9) and CPS (n = 6), with only one disagreement over presence of SGTCC. In 5 cases where the reviewers and clinician disagreed, the DISCOVER form provided patient-derived information supporting the reviewers. In several cases there was subtle alteration of awareness, subject to interpretation. Conclusion: A structured diagnostic interview may be useful to confirm seizure type remotely, for research and clinical purposes. Independent external reviewers had high correlation with each other. The best agreement was for SGTCC and the worst for SPS. Although clinical judgment is important, the DISCOVER form can likely contribute to better diagnostic accuracy.

P175 PRONE SLEEPING AND SUDEP RISK: THE DYNAMICS OF BODY POSITIONS IN NON-FATAL CONVULSIVE SEIZURES Shmuely S1,2, Surges R3, Sander JW1,2, Thijs RD1,2,4 1 Research, Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands, 2UCL Institute of Neurology, NIHR University College London Hospitals Biomedical Research Centre, London, United Kingdom, 3Department of Epileptology, University Medical Center, University of Bonn, Bonn, Germany, 4Department of Neurology, LUMC Leiden University Medical Center, Leiden, The Netherlands

Method: We retrospectively reviewed video EEG data and assessed body positions during the course of the CSs, until there was a physical interaction by nursing staff with the subject. Results: We identified 180 CSs in 90 individuals. In 16 of the 180 CSs (9%) the subject started in or turned to the prone position. Of the 7 CSs that started in prone position, 3 turned to a lateral position during the CS. In 13 CSs the subject was in prone position at time of nursing intervention; nine (69%) of these started in a non-prone position. Conclusion: Our data suggest that the prone position occurs rarely during non-fatal and closely supervised CSs, thus strengthening the association between prone position and SUDEP. Whether prone sleeping prior to CSs increases SUDEP risk, however, remains speculative as body position during the course of a CS appeared to be dynamic.

P176 CLASSIFICATION AND THERAPEUTIC OUTCOME IN 96 CASES WITH STURGE-WEBER SYNDROME Suzuki H, Nakajima M, Sugano H, Higo T, Iimura Y Neurosurgery, Juntendo University, Tokyo, Japan Purpose: Sturge-Weber syndrome (SWS) is a rare disease and its epileptic mechanisms are still poorly understood. We used multiple modalities to investigate SWS characteristics and we present our results in relation to patient’s outcome. Method: We classified 96 cases with SWS at Juntendo University 1990– 2014 according to intracranial leptomeningeal angioma extent into six groups: Gr.1-bilateral, Gr.2-hemispherical, Gr.3-posterior quadrant, Gr.4-anterior quadrant, Gr.5-single lobe and Gr.6-others, for a/epilepsy onset age, b/seizure type, c/seizure frequency, d/surgical method and e/ results. Results: Leptomeningeal angioma area was defined on MRI FLAIR (Gd) and SWI imaging. FDG-PET demonstrated high uptake in 56.8%, and EEG showed low amplitude changes in 87.7% and paroxysms-in only 21.8% of the cases. The six groups showed the following results (Gr.1–9 cases had first occurrence of epileptic seizures (FES) at an average age of 3.8 months continuing at least once per month. Six complete callosotomy cases had improvement to at least Engel class 3. Gr.2–29 cases had FES at an age average 4.9 months with frequency at least once a month in 68% of patients. Nineteen hemispherotomy cases had 89.5% seizure disappearance rate. Gr.3–36 cases with FES at 10.1 months, and 71.0% of them had seizure frequency of less than once per year. For 13 disconnection procedure cases seizure disappeared, but after lesion excision seizures remained. Gr.4–11 cases with FES average age of 18.9 months and in 77.8% seizure frequency less than once per year. Two disconnection procedure cases had seizures disappeared, but in another three lesion excision cases seizures remained. Gr.5–8 cases not operated. (6)3cases. Conclusion: The wider the range of the leptomeningeal angioma, the younger was the age of seizure onset and the more refractory seizures became. Lesion excision was ineffective in frequent epileptic seizures, requiring a radical disconnection procedure.

Purpose: Most victims of sudden unexpected death in epilepsy (SUDEP) are found prone with signs suggestive of an unwitnessed convulsive seizure (CS). Prone sleeping has been proposed as a risk factor for SUDEP. Little is known, however, about the change of body position during the course of CSs.


64 Abstracts P177 USING RANDOM FOREST FOR DIAGNOSIS AND LATERALIZATION OF TEMPORAL LOBE EPILEPSY FROM EEG-BASED DIRECTED FUNCTIONAL CONNECTIVITY Verhoeven T1, Coito A2, van Mierlo P1, Seeck M3, Michel C2, Plomp G4, Dambre J1, Vulliemoz S3 1 Electronics and Information Systems, Ghent University, Ghent, Belgium, 2Functional Brain Mapping Lab, University of Geneva, Geneva, Switzerland, 3Epilepsy Unit, University Hospital Geneva, Geneva, Switzerland, 4Department of Psychology, University of Fribourg, Fribourg, Switzerland Purpose: We aimed to build a classification system that uses restingstate (no visible scalp epileptic activity) EEG-based directed functional connectivity values to assign a patient to one of three classes: left TLE (LTLE), right TLE (RTLE) or healthy control. Method: Twenty LTLE, 20 RTLE and 35 healthy controls underwent resting-state high-density EEG. For each subject, sixty 1-s epochs free of artifacts or interictal spikes were selected. The source activity was obtained for 82 regions of interest using an individual head model and distributed linear inverse solution. The summed outflow and whole-brain directed functional connectivity were estimated in the theta, alpha and beta frequency bands using Granger-causal modeling. A Random Forest classifier (an ensemble of decision tree classifiers) was then used to assign the subject to one of three classes. The mean classification accuracy was computed with a leave-one-out procedure. We selected a maximum of six connectivity values for classification, using a greedy forward selection algorithm. Finally, three classifiers were built: “Control vs. LTLE,” “Control vs. RTLE” and “LTLE vs. RTLE.” In the final classification system, a new subject is assigned to the class that was most voted by these three classifiers. Results: The “Control vs. RTLE” classifier achieved an accuracy of 78.2% (sensitivity: 80.0%, specificity 77.2%), “Control vs. LTLE” an accuracy of 83.6% (sensitivity 85.0%, specificity 82.9%) and “LTLE vs. RTLE” an accuracy of 85.0% (sensitivity 85.0%, specificity 85.0%). Combining these classifiers into one system yielded that 16, 15 and 27 subjects were correctly classified as being, respectively, RTLE, LTLE and control. Conclusion: The high accuracy achieved demonstrates the potential of resting-state EEG-based directed functional connectivity for the diagnosis and lateralization of TLE. This could constitute a new clinical biomarker for surgical candidates and earlier in the course of the disease.

P178 NON-CONVULSIVE STATUS EPILEPTICUS IN CHILDREN AND YOUNG ADULTS AT A RESIDENTIAL EPILEPSY CENTRE Yusef D1, Venkatachalam G1, Dragoumi P1, Chivers F1, Brady M1, Jayal A2, Das KB1,3 1 Young Epilepsy, Lingfield, United Kingdom, 2Department of Computing & Information Systems, Cardiff Metropolitan University, Cardiff, United Kingdom, 3Great Ormond Street Hospital for Children, London, United Kingdom Purpose: We describe a cohort of patients with EEG confirmed NCSE at a specialised residential centre for children and young adults in UK. Method: Information from all patients with confirmed NCSE identified between 2000 and 2015 were gathered to look at demographics, aetiology, clinical features, co-morbidities and trigger factors. Results: Of 2,947 EEGs undertaken during this period, we identified 116 referrals for suspected NCSE. There were 21 (18.1%) confirmed Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

episodes of NCSE in 15 patients. One patient had 3 episodes and two patients had 2 episodes. The median age was 13 (range 7–22 years). A male preponderance was seen (M: F ratio 1.6:1). Aetiologies: 27.8% (5) had a genetic aetiology (1 was Ring 20 positive, 1 Trisomy 21, 1 partial trisomy 9, 1 Weaver syndrome and 1 was 47 XY +MAR); 22.2% (4) Lennox-Gastaut Syndrome. Structural lesions 16.7% (3) and 33.3% (6) had generalised, unclassified epilepsy. All patients had intellectual disability (moderate in 17, mild in 1). Seven patients (38.8%) had Autism spectrum disorder and behavioural problems were reported in 6 (33.3%). The commonest presentation was reduced responsiveness in 81% (17) of cases, slow processing in 33.3% (7). Confusion and drooling was noted in 6 patients (28.6%) and twitching of limbs in 5 (23.8%). Twitching of face and staring were noticed in 3 patients each; nystagmus, ataxia and aphasia was noted in 2 patients each. In 38.1% (8) of cases there had been a convulsive seizure in the preceding 12 h. A recent change in antiepileptic drug was identified in in 47.6% (10) of cases. Conclusion: NCSE is seen a wide range of epilepsies with diverse aetiologies. This should be suspected when there is altered awareness, slow processing, confusion and drooling in a previously well individual with epilepsy. History of a recent drug change should raise the index of suspicion.

Clinical Epilepsy 2 Monday 12th September P179 SUPERFICIAL HEMOSIDEROSIS OF THE CENTRAL NERVOUS SYSTEM: A RARE CAUSE OF EPILEPSY Derke F1, Milat D2, Petelin Gadze Z3, Hajnsek S3, Zurak N4 1 School of Medicine, University of Zagreb, Zagreb, Croatia, 2 ‘Sveti Rok’ Polyclinic, Zagreb, Croatia, 3Department of Neurology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Referral Centre for Epilepsy of the Ministry of Health of the Republic of Croatia, Zagreb, Croatia, 4Department of Neurology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia Introduction: Superficial hemosiderosis of the central nervous system is a rare disorder induced by chronic subarachnoidal bleeding. A triad of symptoms including deafness, cerebellar ataxia and pyramidal syndrome is classic, but this syndrome is rarely connected with epilepsy. The source of chronic or recurrent bleeding into the subarachnoid space is detected in only 50% of cases. T2-weighted gradient echo magnetic resonance imaging constitutes the diagnostic method of choice. Case presentation: We report a case of 70- year old retired senior medical nurse, with a history of arterial hypertension and cerebellar stroke at the age of 45, as well as head contusion and brain concussion in a traffic accident at the age of 46. In the past 10 years patient developed sensorineural hearing loss, gait ataxia, hyposmia, spastic paraparesis, urinary incontinence and typical occipital lobe seizures with secondary generalization confirmed with video-EEG monitoring. MRI provided the etiologic diagnosis based on typical low-density signals from the brain, brainstem, cerebellar and spinal cord surfaces on T1, T2 and gradientecho weighted sequences (T2*) -hemosiderosis as a consequence of a previous subarachnoid haemorrhage. MSCT angiography of the head and neck blood vessels and well as spinal cord DSA did not reveal signs of aneurysms of arteriovenous malformation, what is a diagnostic challenge for clinicians. Conclusion: By observing clinical neurological, audiological and neuroradiological changes in this patient, the diagnosis of idiopathic superficial hemosiderosis of the central nervous system has been performed. We also want to poit out that this clinical entity should be considered as a cause of epilepsy.

65 Abstracts P180 ANTIEPILEPTIC DRUG TREATMENT IN ELDERLY PATIENTS WITH EPILEPSY Theitler J1,2, Berkovitch M2,3, Gandelman-Marton R1,2 1 Neurology, Assaf Harofeh Medical Center, Zerifin, Israel, 2 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 3Clinical Pharmacology Unit, Assaf Harofeh Medical Center, Zerifin, Israel

during REM sleep in accordance with the known “antiepileptic” effect of REM sleep; supported by our results as well. Epileptiform potentials may cause fragmentation of stage 3 sleep, contributing to the cognitive decline of AD patients. Our study provides new information to the relation of sleep structure changes and epileptiform activity in AD. Further research is necessary to determine whether sleep structure changes are consequences of epileptiform activity; or are independent complications of neurodegeneration, having an impact on epileptic activity. Acknowledgement: Our research was supported by the National Brain Research Program (KTIA_NAP_13-1 2013-0001).

Purpose: To evaluate AED use and the rate of adverse events in an outpatient cohort of elderly patients with epilepsy. Method: We retrospectively reviewed the computerized database and the medical records of all the patients aged ≥ 60 who visited our epilepsy outpatient clinic during a 4-year period from February 2012 to February 2016. Results: The study group included 115 patients aged 60–90 years (mean- 70.5 7.8 years), 70 (61%) men. Twenty-two (19%) patients had focal seizures without – and 63 (55%) had focal seizures with secondary generalization. Epilepsy etiology was vascular in 40 (35%) patients, tumor-related in 12 (10%), trauma-related in 8 (7%), and unknown in 48 (42%) patients. Past treatment with new-generation AEDs as mono- or polytherapy was reported in 12 (10%) and 22 (19%) of the patients, respectively. Present AEDs included an old-generation AED in 41 (36%) patients, a new-generation AED in 51 (44%), and polytherapy with both old- and new-generation AEDs in 21 (18%) patients. Adverse events were present in 9/41 (22%), 24/51 (47%) and 7/21 (33%), respectively (p = 0.043). Conclusion: New-generation AEDs were administered to most of the patients in this outpatient clinic based cohort of elderly patients with epilepsy. Adverse events were most common in patients treated with newgeneration AEDs compared to patients treated with old-generation AED as mono- or polytherapy. Further research is underway to identify possible contributing factors to this finding.

P181 SLEEP-CHANGES AND EPILEPSY IN ALZHEIMER’S: CAUSES OR COMPLICATIONS? Horváth A, Virag M, Barcs G, Kamondi A, Sz}ucs A National Institute of Clinical Neurosciences, Budapest, Hungary Purpose: There is a growing evidence suggesting that people with Alzheimer’s disease (AD) have high risk to develop epileptic seizures. Based on animal studies, epileptiform activity may have an impact on the progression of AD via the elevated amyloid deposition. Impaired sleep – reduction of rapid eye movement (REM) and slow wave sleep- are additional major features of AD. We aimed to analyze the relation of epileptiform activity and sleep stages in AD. Method: Thirty-three patients matching the criteria for probable AD underwent neuropsychology testing, MRI brain-scan and 24 h EEG. We scored sleep based on the Rechtschaffen-Kales criteria, and calculated the prevalence and distribution of seizures and epileptiform activity during wakefulness and each sleep-stage. Results: Thirty percent of the patients had clinically identified epileptic seizures mainly temporal ones with no motor activity; 39% had interictal epileptiform discharges typically over the dominant temporal lobe. Eighty-two percent of all epileptiform activity occurred in sleep; 55% during stage 3. Only 10% of discharges occurred during REM sleep; less than in wakefulness (18%). The length of REM and stage 3 sleep was significantly reduced while the duration of superficial sleep stages were normal. Conclusion: Epileptiform activity and seizures are prominent features of AD. Discharges cumulate in deep slowwave sleep and are less frequent

P182 CLINICAL FEATURES AND PROGNOSIS OF EPILEPSY IN THE ELDERLY IN WESTERN CHINA Huang C, Feng L, Li Y, Zhou D, Chen L Department of Neurology, West China Hospital of Sichuan University, Chengdu, China Purpose: To investigate the characteristics and prognosis of epilepsy amongst older people hospitalized in southwestern China with newly diagnosed epilepsy. Method: We prospectively enrolled people older than 65 years who were admitted to a tertiary epilepsy center in West China between January 2008 and January 2013. Participants were divided into early-onset group (those who had a first seizure before age of 65) and late-onset group (those in whom the first seizure occurred after age of 65). Clinical data was collected and all participants were followed for 2 years. Results: Of 340 people enrolled, focal seizure (84%) was the most frequent seizure type. Status epilepticus (64.4% vs. 46.7%, p = 0.022) and structural epilepsy (59.3% vs. 40.0%, p = 0.015) were more prevalent in late-onset group than early-onset group. Ischemic stroke was the leading putative cause (22.6%) in elderly epilepsies. Around 80% were given anti-epileptic drugs (AEDs) for treatment. Forty-two people didn’t not complete the study, of whom 26 were lost to follow-up and 16 died for causes other than epilepsy. Of the 298 who completed the follow-up, 240 (80.5%) achieved significant seizure reduction. Logistic regression analysis indicated that late-onset epilepsies and AEDs treatment were associated with more favorable seizure outcome at 2-year follow-up (OR = 4.029 and 92.007, respectively). The number of AEDs intake exerted no significant impact on seizure outcome. Conclusion: In older people, late-onset epilepsies differed in several aspects from early-onset epilepsies. The overall effectiveness of AEDs treatment in older people was satisfactory.

P183 LACOSAMIDE AS CONVERSION TO MONOTHERAPY IN OLDER ADULTS WITH EPILEPSY: A RETROSPECTIVE STUDY Izzi F1, Liguori C1, Romigi A2, Pisani A1, Mercuri NB1, Placidi F1 1 Department of Neuroscience- Epilepsy Center, Policlinico Tor Vergata, University of Rome Tor Vergata, Rome, Italy, 2Azienda Ospedaliera San Giovanni Addolorata, UOC Neurologia, Rome, Italy Purpose: Although epilepsy represents the third most common neurological condition in elderly, older patients are frequently excluded from clinical trials. Lacosamide (LCM) has been authorized as monotherapy for partial-onset seizures in adults in the US, but not yet in the EU. The efficacy of LCM as conversion to monotherapy was established in recent studies but its effects in elderly remain largely unknown. This study aims


66 Abstracts at assessing efficacy and tolerability of LCM as conversion to monotherapy over 12 months in older patients. Method: A retrospective chart review of patients aged ≥65 years suffering from partial onset seizures with or without secondary generalization, who were treated with LCM as conversion monotherapy was performed. Data regarding demographics, seizure type and etiology, LCM dose, number of lifetime AEDs, previous AEDs prior to LCM monotherapy, seizure frequency, seizure free percentage at 12 months follow-up and comorbidities were reported. Results: In this retrospective study 19 patients (9 males, 10 females, mean age 75.53 70.26 y.o., range 65–89; age at epilepsy onset 70.26 7.69 y.o.) were enrolled. LCM was prescribed to all patients as first add-on with a mean dose of 200 79.93 mg/d. Mean number of lifetime AEDs was 1.63 1.1. All patients had at least two comorbidities on chronic treatment. Median monthly seizure frequency reduced from 4.82 8.44 to 0.18 0.37 (p < 0.01) and 13 patients remained seizure free at 12 months follow-up with good tolerability. Conclusion: Epilepsy management in elderly is often challenging. In this retrospective real-life study LCM efficacy and tolerability was favorable even at low doses in older patients and seizure freedom was obtained in 68% of patients at 12 months follow-up. Considering the high rate of comorbidities and the risk of drug-drug interactions, LCM monotherapy may be a valuable option for elderly patients with partial epilepsy due to its favorable pharmacokinetics and safety profile.

P184 ACUTE SYMPTOMATIC SEIZURES AND EPILEPSY IN STROKE PATIENTS; ETIOLOGICAL SUBTYPES AND CLINICAL CHARACTERISTICS Jansky P1, Sulc V1, Magerova H1, Otahal J2, Jiruska P3, Tomek A3, Marusic P1 1 Department of Neurology, Motol University Hospital, Praha, Czech Republic, 2Institute of Physiology CAS, Praha, Czech Republic, 3Motol University Hospital, Praha, Czech Republic Purpose: In our study we set to investigate etiological subtypes and clinical characteristics in patients suffering from acute symptomatic seizures (AS) in ischemic stroke and patients with vascular epilepsy. Method: Patients with both arterial ischemic stroke and epilepsy (G40.x) were retrospectively identified in hospital database in years 2012–2015. Based on chart review 42 patients were identified with AS and 35 with vascular epilepsy (remote unprovoked seizure/s). Stroke etiology was defined according to TOAST criteria. The infarction territory was classified as anterior or posterior. Seizures were labeled as focal convulsive, focal nonconvulsive and generalized (convulsive). Occurrence of status epilepticus was recorded. Results: 42 patients (52.6% female, mean age 72.3; 12.5 SD) had AS. Seizures were most frequently focal convulsive (45.2%) and focal nonconvulsive (38.1%). Status epilepticus occurred in 31%. The most frequent etiology was cardioembolic (47.6%) followed by large vessel disease (LVD, 28.6%), unidentified (14.3%), small vessel disease (SVD, 7.1%) and other (2.4%). Anterior circulation was affected in 88.1%. Hemorrhagic transformation occurred in 4.8% patients. Vascular epilepsy was identified in 35 patients (47.4% female, mean age 65.8;14.9 SD). Seizures were most frequently focal nonconvulsive (40%) and focal convulsive (31.4%). Status epilepticus occurred in 8.6%. The most frequent stroke type was cardioembolic (57.1%) followed by unidentified cause (22.9%), LVD (14.3%), SVD (2.9%) and other (2.9%). The anterior circulation was affected in 74.3%. Hemorrhagic transformation occurred in 11.4% patients. Patients with AS were older (72.3 vs. 65.8 years, p = 0.04) and more often developed status epilepticus (31% vs. 8.6%, p = 0.02). In other characteristics the statistically significant difference was not found.


Conclusion: In our study patients with acute symptomatic seizures in stroke were older and more often presented with status epilepticus in comparison to patients with vascular epilepsy. Study was supported by Czech Health Research Council grant 1533115A.

P185 STATUS EPILEPTICUS IN THE ELDERLY PATIENTS: A NATIONAL DATA STUDY IN THAILAND Tiamkao S1,2, Pranboon S3, Thepsuthammarat K4, Sawanyawisuth K5 1 Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 2Integrated Epilepsy Research Group, Khon Kaen, Thailand, 3Nursing Division, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, 4Clinical Epidemiology Unit, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 5Research Center in Back, Neck Other Joint Pain and Human Performance (BNOJPH), Khon Kaen University, Khon Kaen, Thailand Purpose: There are limited data in term of incidence, characterize the demographics, comorbidity, outcome and prognostic factor and in-hospitalized mortality of status epilepticus (SE) in the elderly patients in Thailand. Method: We retrospectively explored national data for reimbursement of all SE in elderly patients admitted in the fiscal year 2004–2012. SE in elderly (age more than 60 years) were diagnosed on ICD 10 (G41) from the national database with Universal Health Coverage Insurance. Results: There were 3,326 SE. The incidence of SE was lowest at 1.83 patients/100,000/year in 2004 and highest at 8.78 patients/100,000/year in 2012. The average age was 72.02 years and most were males (1,379 patients; 58.8%). At discharge, 66% of patients were improved, while 18.94% were not improved, and in-hospital mortality rate was 14.5%. The first three common co-morbid conditions were hypertension (1,072 patients; 32.2%), diabetes mellitus (543 patients; 16.3%), and previous stroke (423 patients; 12.7%). The common complications were respiratory failure (1,556 patients; 46.8%), pneumonia (569 patients; 17.1%) and septicemia (387 patients; 11.6%). The mean (SD) hospital stay was 7.74 (16.36) days. Predictor of poor outcome were older age > 80 years (odd ratio (OR) = 1.67, 95% CI 1.33–2.10), female (OR = 1.53, 95% CI 1.29–1.80) and hospitals level; secondary care (OR = 0.30, 95%CI 0.24– 0.39) and tertiary care (OR = 0.23, 95%CI 0.18–0.29). Out of 11 co-morbid conditions, three of them including chronic renal failure previous stroke and CNS infection were significantly associated with poor outcomes. Additionally, complications including respiratory failure, pneumonia, septicemia, shock and procedure intervention by cardiopulmonary resuscitation and retained Foley0 s catheter were significant factors of poor outcomes. Conclusion: SE in elderly patients in Thailand were increasing annually .Factors associated with poor outcome in admitted elderly SE patients were age, gender, hospital level, co-morbid conditions, complications of SE, and procedural interventions.

67 Abstracts

Clinical Epilepsy 3 Tuesday 13th September P186 PREGNANCY AND PERINATAL OUTCOME IN CHINESE EPILEPTIC WOMEN: PROSPECTIVE CONTINUOUS HOSPITAL BASED REGISTRATION STUDY He S1, Zhu H2, Zhu X1, Zhou D1, Chen L1 1 Neurology, West China Hospital in Sichuan University, Chengdu, China, 2West China Women’s and Children’s Hospital, Chengdu, China Purpose: Find pregnancy and perinatal outcome in Chinese pregnant women with epilepsy (PWWE) and management gap between China and Western countries. Method: Prospectively registered recent 5 years PWWE in multidisciplinary consultation system (obstetrics, pediatrics and epilepsy doctors) of Sichuan University affiliated Hospital, including seizure frequency, pregnancy complications, delivery mode, etc. All data were analysed by SAS 9.3. Results: 137 PWWE (155 pregnancies) with average gestational age of 26 years were included. Patients selected cesarean section in 103 pregnancies and natural childbirth in 52 pregnancies. Most offspring were healthy on born and received artificial feeding. PWWE never took AEDs or withdrawed AEDs in 55 pregnancies, supplemented with 0.4 mg/d folate in 116 pregnancies, 2 mg/d in 30 pregnancies, only in 9 pregnancies, folate supplement achieved the dose of 5 mg/d recommend by ILAE. For seizure frequency, 67 pregnancies did not changed, 15 reduced, 73 increased and mainly increased in the first and last trimester. By logistical regression analysis, it shows that distance from last seizure to the beginning of pregnancy, pregnancy complications and topiramate or valproate using would significantly affect seizure frequency (p < 0.05). Conclusion: Europe and USA have established PWWE registration system for a long time and contributed much for the international PWWE guideline form. We still lack of clinical data of Chinese PWWE and want to know whether there is some difference outcome of PWWE between China and Western countries. This study showed us the similar pregnancy and perinatal outcome of PWWE in west China, but obvious treatment gap from Europe and USA. More patients here received caesarean section than natural delivery, many patients withdrawed AEDs and supplemented with low dose folate. Therefore, it is necessary to pay more attention to PWWE and establish registration system for Chinese PWWE, which may contribute to the improvement of offpring health level in epileptic women.

P188 PREGNANCY OUTCOME IN WOMEN WITH EPILEPSY BEYOND CHILD AGE OF 1 YEAR Kiteva-Trenchevska G Unversity Clinic of Neurology, Skopje, Macedonia Purpose: There are reports of congenital malformation detected immediately after birth or during the first year of life in children whose mothers with epilepsy were on AEDs during pregnancy and breast feeding period. The aim is to evaluate different defects and deficits appearing after the age of 1 year in children whose pregnant mothers were taking AEDs during pregnancy and breast feeding period of 1 year.

topoiramat. Cryptorchismus in a child whose mother was taking carbamazepine 800 mg daily. Dyslexia in a child whose mother was taking carbamazepine 800 mg daily during pregnancy and breast feeding period. Conclusion: Despite valproat is considered as an AED that could cause the greatest percentage of congenital malformation in a child whose mother is taking AEDs during pregnancy and breast feeding period, there are detected deficits in children after the age of 1 year, whose mothers were taking AEDs during pregnancy and breast feeding period that are considered safer then valproat. It is useful to follow the children of mothers with epilepsy far beyond the age of 1 year for better understanding pregnancy outcome in mothers with epilepsy.

P189 GENDER FEATURES OF DRUG RESISTANCE IN FEMALE EPILEPSY Odintsova G1, Chugunova A1, Figol A1, Saykova L2 1 Epileptology, Federal Almazov North-West Medical Research Centre, St. Petersburg, Russian Federation, 2Neurology, NorthWestern State Medical University n.a. I/I/Mechnicov, St. Petersburg, Rwanda Purpose: To study gender features of drug resistance in female epilepsy. Method: The real work was the part of prospective observation research of antiepileptic drugs (AEDs) side effects on reproductive health (RH) at 155 women at the age of 16–45. 3 groups were allocated: 1gr. – AEDs monotherapy, 2gr. – polytherapy, 3gr. – without AEDs. Epilepsy onset, catamenial epilepsy, reproductive complications were investigated. Results: Average age of the surveyed women made 25 years. 1gr. included 68 patients (44%), 2gr. – 67 (43%), 3gr. -20 women (13%). Resistant epilepsy prevailed in 2gr. with disability in 40% (p < 0.001). Epilepsy onset before puberty- 1–9y.o.were in 15%, in puberty- 10– 18y.o- 59%, after puberty- older 18- 26%. Differences were statistically significant above in puberty (p < 0.001). Prevalence of epilepsy onset in the integrated age range of 12–16 years was statistically reliable (p < 0.001). Disease onset was early in 2gr. The general indicator of catamenial epilepsy in cohort made 32% above in 2gr. (43%) in comparison with 1 (24%) and 2 (25%) groups (p < 0.001). The frequency of reproductive endocrine complications made 53%. Reproductive disturbances due to AEDs made 40%. AEDs polytherapy enlarged the frequency of reproductive disturbances and made 60% in 2gr. (p < 0.001). Conclusion: Gender aspects of resistant epilepsy were caused by influence of sexual hormones in pathogenesis. The epilepsy onset often occurred in periods of oestradiolum production beginning and its ovulatory peaks. It confirms estrogens proconvulsive effect. Catamenial epilepsy has to be considered as predictor of drug resistance. Reproductive complications were frequent side effect of antiepileptic therapy and took part in disease resistant. Adverse events management decreased severe disease. The reported study was funded by the Russian Foundation for Humanities research (RFHR) according to the research project No. 15-0610816.

Method: 106 women with epilepsy who were taking AEDs during pregnancy and breast feeding period gave birth to 119 children older than 1 year. Results: After the age of 1 year several defect and deficit were detected in 3 children. ADHD in a child of a mother taking valproat and


68 Abstracts P190 EFFECT OF UGT1A4 AND UGT2B7 POLYMORPHISM ON LAMOTRIGINE METABOLISM DURING PREGNANCY € Petrenaite V1, Ohman I2, Ekstr€om L2, Bertilsson L2, Sæbye D3, Tomson T2, Sabers A4 1 Neurology, Rigshospitalet-Glostrup, Glostrup, Denmark, 2 Karolinska University Hospital, Stockholm, Sweden, 3Institute of Preventive Medicine, Copenhagen, Denmark, 4 Rigshospitalet-Blegdamsvej, Copenhagen, Denmark Purpose: Genetic polymorphism of UGT has been suggested to have an influence on individual variability of lamotrigine (LTG) metabolism during pregnancy. Our purpose was to evaluate the effect of UGT1A4 and UGT2B7 polymorphism on lamotrigine (LTG) blood level changes during pregnancy and postpartum. Methods: Forty-seven pregnancies in 40 women on LTG treatment were analysed retrospectively. Data included LTG dosage and LTG plasma level changes during pregnancy and postpartum. All women were part of a prospective study of 337 Danish epilepsy patients on LTG treatment for determination of single nucleotide polymorphism UGT1A4*3(L48V), UGT1A4 *2(P24T) and UGT2B7*2. Results: Ten pregnancies were identified among ten women heterozygous for UGT1A4*1/*3. Further 37 pregnancies were registered among 30 women homozygous for the wild type allele (UGT1A4*1/*1). In the wild type group, reductions from prepregnancy plasma concentration to dose ratio (C/D) were significant during pregnancy (p < 0.0001) and postpartum (p = 0.04), but significant only in second and third trimester (p < 0.008) in patients with mutation. Reduction of the ratio in third trimester was significantly higher in wild type than in the mutation group (p = 0. 04).The significant reduction (p < 0.0001) of the C/D ratio during pregnancy was identified in three of patients heterozygous for UGT1A4 1/*2, with no difference in comparing with wild type.Twenty five pregnancies in 21 women heterozygous for UGT2B7*1/*2 and 13 pregnancies in 12 homozygous for UGT2B7*2/*2 were identified, with significantly reduced C/D during pregnancy in both. Significant difference (p = 0.04) between wild type, heterozygous and homozygous groups was only seen postpartum. Conclusion: The significant reduction of the ratio C/D of lamotrigine during pregnancy is to a minor degree dependent of UGT1A4*3, but not on other genotypes.

P191 THE USE OF LACOSAMIDE IN ELDERLY PATIENTS Rainesalo S, M€ akinen J, Peltola J Neurology and Rehabilitation, Tampere University Hospital, Tampere, Finland Purpose: Lacosamide (LCM) is a third-generation AED with limited data on elderly patients with epilepsy. This study was performed for evaluation of the use of LCM in this particular patient group regarding its tolerability and effectiveness. Method: We retrospectively identified all patients aged sixty or more treated for epilepsy in Tampere University Hospital Neurological Unit between January 2010 and May 2015 with LCM. Altogether 237 patient documents were reanalyzed. A substantial number of patients had started LCM in acute settings for short term use ( 0.05, n = 6). A tendency towards decreased expression was also observed for FRa, but the number of placentae were too small to draw conclusions. No clear trend was observed for RFC. Conclusion: Our results suggest that VPA may affect the expression of carriers important for the transplacental transfer of folic acid and those involved in protecting the fetus against xenobiotics. Ongoing studies with additional placentae are aimed at obtaining a better picture of VPA concentration-effect relationships with regard to carrier expression. If validated, these results may point at novel mechanisms through which VPA affect fetal development. The knowledge gained through these studies will hopefully contribute to improved outcome of children born to mothers with epilepsy.

69 Abstracts P193 PLASMA AND BREAST MILK LEVELS OF LACOSAMIDE BEFORE, DURING AND POST PREGNANCY Zárubová J1, Kremlackova V2, Bor ecka K2, Marusic P1 1 Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic, 2Department of Clinical Chemistry, Thomayer0 s Hospital, Prague, Czech Republic Purpose: Lacosamide (LCM) is an antiepileptic drug approved as adjunctive therapy for partial-onset seizures. In women with epilepsy monotherapy is recommended as safer option in comparison to polytherapy and switch to LCM monotherapy has been already published. The data about LCM plasma levels before and during pregnancy, the rate of umbilical cord/maternal plasma levels and the concentration in the breast milk are of outstanding clinical interest. Method: We have investigated LCM plasma levels in 27 years old patient with focal epilepsy taking the dose of 200 mg/day before pregnancy and at every trimester. Moreover, we assessed LCM levels in the umbilical cord and at the breast milk before taking the LCM, 2 and 6 h after taking the regular dose. We used a simple HPLC method with UV detection, which was developed and validated for the quantification of lacosamide in human plasma. Results: Plasma level before pregnancy on 200 mg/day was 19.7 lmol/l (reference range 8–40). During pregnancy the level was 10.11 lmol/l (51.3% of pre-pregnancy value) in the first trimestr, 12.35 lmol/l (62.7%) in the second trimester, 11.45 lmol/l (58.1%) in the third trimester, 9.58 lmol/l (48.6%) 6 weeks before delivery and 15.36 lmol/l (78.0%) at the delivery. As she was seizure free the dose of LCM was not increased. The umbilical cord: maternal ratio was close to 1:1. The concentration in the breast milk 20 days after delivery was 14.27, 21.8, 16.92 lmol/l measured before taking the regular dose of LCM and 2 and 6 h after the administration respectively. Conclusion: In our patient, LCM plasma levels decreased approximately by 50% during pregnancy without breakthrough seizures. The ratio of umbilical and maternal concentrations suggests full transplacental transfer of LCM. The concentration in the breast milk suggests full transfer of LCM from maternal blood to the breast milk.

Clinical Epilepsy 4 Tuesday 13th September P194 THE RATE OF CONGENITAL MALFORMATIONS IN EPILEPTIC PREGNANT PATIENTS: A PROSPECTIVE STUDY € Bozdemir H1, Tantik Pak A1, Aslan K1, B€uy€ukkurt S2, Unal I_ 3 1 Neurology, C ukurova University Faculty of Medicine, Adana, Turkey, 2Gynecology and Obstetric, C ukurova University Faculty of Medicine, Adana, Turkey, 3Biostatistic, C ukurova University Faculty of Medicine, Adana, Turkey

Results: Eighteen patients (41.8%) have had partial epileps, 25 (58.2%) of them have had primary generalized epilepsy. Of these patients 74% of them were on monotheraphy, 20% of them on polytheraphy medication. There is an increase in seizure frequency in 16% of the patients. The rate of congenital malformations (MCMS) among the newborns of all AEDs exposed mothers was 11.6%. Only one newborn from monotheraphy group, and 2 newborn from politheraphy group have malformation. Conclusion: In this prospective study, we found that, the pregnancy is not a risk for increase of seizure frequency. The risk for congenital malformations was higher with high dose valproic acid and with politheraphy-exposed pregnancies.

P195 PREGNANCY-RELATED KNOWLEDGE OF WOMEN WITH EPILEPSY – AN INTERNET BASED SURVEY IN GERMAN SPEAKING COUNTRIES Dierking C1, R€ osche J2, Porschen T3 1 Department of Neurology, University of Rostock, Rostock, Germany, 2Klinik Lengg, Zurich, Switzerland, 3Landesverband f€ ur Epilepsie Selbsthilfe Nordrhein-Westfalen e.V., Colongne, Germany Purpose: We tried to determine the level of pregnancy-related knowledge of women with epilepsy and their informational needs concerning pregnancy and childbirth issues in German speaking countries. Methods: A questionnaire was placed on the internet platform of a patient’s organisation from 4th August 2015 to 31st to December 2015. The questionnaire consisted of 18 questions addressing the characteristics of the syndromes of epilepsy, the patients experience with pregnancy and the sources of their pregnancy-related knowledge. Another 20 items addressed the level of pregnancy-related knowledge. Each of these items consisted of a 5-point Likert scale. We considered Likert scale answers of 1 and 2 as equivalent to disagreement and of 4 and 5 as agreement with the statement in question. Results: 192 women (179 patients, 13 relatives) aged 30.5 years on average (SD 10.8) participated. 69 (=35.9%) had a child and another 9 (=4.69%) had been pregnant without live birth. 80.7% agreed that women with epilepsy should visit their neurologist when planning to get pregnant. Apart from this the knowledge concerning pregnancy related issues was fairly low. For instance: Only 17.2% knew that seizure freedom in the last 9 month before pregnancy implies a very low risk to suffer a seizure during pregnancy. Only 22.9% disagreed that women taking antiepileptic drugs generally have an increased risk of complications in pregnancy like premature birth, emergency caesarean birth, dead birth. Only 31.3% disagreed that fetal exposure to valproic acid does no harm to cognitive development of the child. Conclusion: There are huge information needs concerning pregnancy related issues of women with epilepsy in German speaking countries.

Purpose: The women wiht epileplepsy could have 2–3 times more problem than normal pregnant women. The rate of normal childbear in general pop€ ulation is 98% whereas 92–96% in epileptic patients. The aim of this study was to analyse the effects of epilepsy and antiepileptic drug (AED) treatment on pregnancy and the perinatal outcome, prospectively.

P196 DEVELOPMENT AND VALIDATION OF MODIFIED INCLEN DIAGNOSTIC INSTRUMENT FOR EPILEPSY IN CHILDREN AGED UP TO 18 YEARS Gulati S, Patel H, Chakrabarty B, Dubey R, Arora NK, K Paul V, M Pandey R All India Institute of Medical Sciences, New Delhi, India

Methods: We examined the obstetric and fetal outcomes among women with epilepsy (WWE), who were followed-up at the Department of Neurology and who delivered at the Department of Obstetrics and Gynaecology (n = 43) between 01th January 2013 and 31th December 2015. The mean age of the patients were 28.9 12 (17–40) years.

Purpose: There is shortage of specialists for the diagnosis of children with epilepsy, especially in resource limited settings. Existing INCLEN (International Clinical Epidemiology Network) instruments were validated for children aged 2–9 years. The current study validated modifications of the same including wider symptomatology and age group. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

70 Abstracts Methods: The Modified INCLEN tools were validated by a team of experts by modifying the existing tools (2–9 years) to widen the age range from birth to 18 years and include broader symptomatology in a tertiary care teaching hospital of North India between January and June 2015. A qualified medical graduate applied the candidate tool which was followed by gold standard evaluation by a Pediatric Neurologist (both blinded to each other). Results: A total of 197 children {128 boys (65%) and 69 girls (35%)} with a median age of 62.5 months (IQR: 20–106 months), completed the study. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio of the modified epilepsy tool were 91.5% (84.5–96.1), 88.6% (80.0–93.5), 89.7% (81.9–95.3), 90.8% (83.7–95.7), 8 (6.6–9.8) and 0.09 (0.07–0.12) respectively. Conclusion: The new modified diagnostic instruments for epilepsy is simple, structured and valid instruments covering the entire pediatric age (from birth to 18 years) for use in resource limited settings with acceptable diagnostic accuracy. It covers the entire spectrum of epilepsy upto 18 years of age except neonates. All seizure semiologies as well as common seizure mimics like breath-holding spells are included in the tool. It also provides for identification of acute symptomatic and febrile seizures.

P198 CHARACTERISTICS AND HEALTH CARE OF ADULT TUBEROUS SCLEROSIS VOMPLEX (TSC) PATIENTS IN GERMAN EPILEPSY CENTERS Hamer H1, Kasper BS1, May T2, Mayer T3, Straub H-B4, Steinhoff B5, B€osebeck F6, Baier H7, Kurlemann G8, Holtkamp M9, Weber YG10, Franz M11, Brandt C2 1 Epilepsiezentrum, Neurologische Universit€atsklinik Erlangen, Erlangen, Germany, 2Bethel – Gesellschaft f€ur Epilepsieforschung, Bielefeld, Germany, 3Epilepsiezentrum Kleinwachau, Radeberg, Germany, 4Epilepsieklinik Tabor, Bernau, Germany, 5Epilepsiezentrum Kork, Kork, Germany, 6 Epilepsiezentrum Rotenburg, Rotenburg, Germany, 7 Epilepsiezentrum Bodensee-Weissenau, Ravensburg, Germany, 8 Universit€atsklinikum M€unster, M€unster, Germany, 9EpilepsieZentrum Berlin-Brandenburg am Ev. KH K€onigin Elisabeth Herzberge, Berlin, Germany, 10Abteilung Neurologie mit Schwerpunkt Epileptologie, Hertie Institute f€ur klinische Hirnforschung, Universit€at T€ubingen, T€ubingen, Germany, 11 Novartis Oncology, Nuremberg, Germany Purpose: Little is known about the characteristics of adult TSC patients and their treatment setting after transition to adult health care in Germany. Therefore, we conducted a survey in epilepsy centers throughout Germany focusing on their care of this patient group.

specialized TSC centers. 48.0% underwent diagnostic renal screening within the last 3 years. Conclusion: The survey revealed a high percentage of drug refractory focal/multifocal epilepsies in adult TSC patients requiring frequently polytherapy. There was low utilization of epilepsy surgery which was successful in nearly half of the patients when applied. As AML is a major concern in adult TSC patients, follow-up included renal screening in many patients.

P200 WOMEN AND EPILEPSY: A REVIEW OF PRACTICES IN THE PUBLIC AND PRIVATE SETTING IN JAMAICA, 2012–2015 Menon U1, Williams M2,3,4, Grindley T4, Morgan O3, Ali A2,4 1 Comprehensive Epilepsy Center, Yale New Haven Hospital, New Haven, CT, United States, 2Kingston Public Hospital, Medicine, Kingston, Jamaica, 3Obstetrics and Gynecology, Victoria Jubilee Maternity Hospital, Kingston, Jamaica, 4 Andrews Memorial Hospital, Kingston, Jamaica Purpose: Limited information is available regarding care of women with epilepsy (WWE), particularly in developing countries with scant resources. Jamaica has a population of about 2.8 million with 0.41 physicians per 1,000, and only six adult neurologists. Method: Retrospective chart review of WWE seen in the private and public setting during 2012–2015 to assess the practices according to accepted standards of care. Results: 32 WWE in private and 25 WWE in public setting were identified. The common seizure types were generalized tonic clonic, followed by complex partial. 60% of private and 4% of public patients were above age 35 years. Seizure duration was 1- 4 years in the majority (52%) of public patients and more than 10 years (59%) for most private patients. 47% of private and 28% of public patients were seizure-free for more than 6 months. At last visit, 68.8% of private patients were on newer AEDs vs. 18.8% on initial referral. In contrast, only 24% of public patients were on newer AEDs at last visit. 12.5% of private and 40% of public patients had neuro-psychiatric comorbidities. 1 out of 32 private and 2 out of 25 public patients had documented cannabis use. 59% of private and 72% of public patients were documented to be on folate. EEG was done only in 3 and MRI brain was done only on 5 public patients, whereas all private patients had at least one EEG and MRI brain.

Method: A retrospective survey was performed in eight major German epilepsy centers about their TSC patients’ characteristics (including state of living), epilepsy syndrome, treatment details and health care setting (including follow-up schedules).

Conclusion: Significant disparities exist in epilepsy care provision to women with differing economic circumstances in Jamaica.

Results: A total of 194 adult TSC patients were included (91 female (48%); age 36 8 years, legal representative in 56%). In addition to epilepsy, the most frequently reported TSC signs or symptoms included cerebral tubers (81%), cognitive impairment (70%), facial angiofibromas (60%), subependymal nodules (44%), and renal angiomyolipome (AML) (41%).In 53% of the patients, epilepsy onset was before 3 years of age. Focal/multifocal epilepsy syndromes prevailed (focal epilepsy: 59%; multifocal epilepsy: 30%) with dyscognitive seizures in 70% and generalized tonic-clonic seizures in 63% of the patients. Twenty percent of the patients were on monotherapy while 45% received 2 and 32% 3 or more antiepileptic drugs. 15% of the patients were seizure free. 10% underwent epilepsy surgery rendering 45% of them seizure free.37% of the patients were additionally seen by an urologists/nephrologists and 17% visited

P201 YES YOU CAN: A VIDEO FOR WOMEN WITH EPILEPSY PLANNING A FAMILY Picton C1, Jones A2, O’Donoghue M1,2, Wallace S3 1 Neurology, Nottingham University Hospitals, Nottingham, United Kingdom, 2Nottingham University Hospitals, Nottingham, United Kingdom, 3Obstetrics, Nottingham University Hospitals, Nottingham, United Kingdom


Purpose: To develop a short web-based video to empower women with epilepsy to plan a safe pregnancy.

71 Abstracts Method: Following patient and professional focus groups to develop themes; 5 women were filmed at home speaking about their experiences before, during and after pregnancy. Results: Women spoke movingly about their fears of the effects of drugs and seizures on the unborn child. Women were also concerned about seizures during delivery and the ability to have a normal birth and breast feed. They valued a dedicated feto-maternal/epilepsy team who followed them closely during the pregnancy. They strongly recommended a planned approach to pregnancy to other women with epilepsy. Conclusion: We hope the video is of value to any woman with epilepsy thinking of starting a family.

P202 SERVICE AVAILABILITY OF PHENYTOIN PRODUCTS FOR TREATMENT OF EPILEPSY IN GOVERNMENT HOSPITALS IN THAILAND Suansanae T, Suebjakin T, Poomkumarn N Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand Purpose: The objective of this study was to assess the distribution of phenytoin in term of brand name and formulation in government hospitals in Thailand. Method: Hospital pharmacists of university hospitals, regional hospitals, general hospitals and community hospitals in Thailand were interviewed by telephone during December 2015 to January 2016. Product information of phenytoin including brand name, preparation, strength which was available to use in their hospitals was collected. Results: There were 653 hospitals responded to this survey which accounted for 73% of all government hospitals in Thailand. Phenytoin was available in all hospitals. In 265 hospitals (41%), most of them were regional hospitals, general hospitals and university hospitals had the original brand (Dilantinâ) while the rest of them which mostly were community hospitals had various generic products of phenytoin. Conclusion: There was heterogeneity of phenytoin product brands available in government hospitals in Thailand. Thus, epileptic patients may have a chance to be switched the brands of phenytoin products unintentionally which may have an impact on seizure control, tolerability and quality of patients’ life.

P203 SURVEY OF THE AWARENESS AND CLINICAL PRACTICE OF MEDICAL ASSOCIATION MEMBERS REGARDING COMPREHENSIVE MANAGEMENT OF EPILEPSY IN THE SAN-IN REGION OF JAPAN Yoshioka S-I Faculty of Medicine, School of Health Science, Tottori University, Yonago-Shi, Japan Purpose: Comprehensive management of epilepsy is an important issue. The purpose of this study was to investigate the awareness and clinical practice of medical doctors in relation to the comprehensive treatment of people with epilepsy (PWE). Method: A questionnaire about the respondent’s clinical department, workplace, engagement in clinical management of epilepsy, performance of medical examinations, and use of visiting nurses and home care services for PWE was distributed to members of the Tottori and Shimane medical associations in 2014, and a total of 641 (25.5%) responses were collected.

Results: Of the respondents, 542 (84.6%) had experience with treating PWE. It was found that 81.9% and 62.6% of the doctors thought that neurologists, etc. experienced in managing epilepsy or only epilepsy specialists should treat PWE, respectively. Of the respondents, 238 (37.1%) were engaged in managing epilepsy and they accounted for the highest proportion of personnel working in internal medicine and clinics among the respondents from clinical departments. It was found that biochemical tests of blood/urine, monitoring of the blood levels of anticonvulsants, electroencephalography, and imaging studies of the head were regularly performed in the PWE under their treatment by 50.4%, 50.4%, 18.5%, and 5.0% of the doctors, respectively. There were 106 doctors (44.5%) who had issued medical certificates for the medical care and welfare of patients under their management and 150 doctors (63.0%) who had referred patients with intractable epilepsy to epilepsy specialists. Patients of 12.6% and 16.4% of the doctors received the services of visiting nurses and home care, respectively. Conclusion: These results indicate that only a few doctors currently utilize visiting nurses or home care services for PWE, suggesting that the promotion of these services is important for the comprehensive management of epilepsy. This study was supported by JSPS KAKENHI Grant Number 26463485.

Clinical Epilepsy 5 Wednesday 14th September P204 DIFFERENCES IN QUALITY OF LIFE OF WOMEN AND MEN WITH DRUG RESISTANT EPILEPSY IN POLAND Bala A1,2, Szantroch M2, Rysz A2, Marchel A2 1 Faculty of Psychology, University of Warsaw, Warsaw, Poland, 2 Department of Neurosurgery, Medical University of Warsaw, Warsaw, Poland Purpose: We aimed at assessing the differences in health related quality of life (HRQoL) in groups of women and men with intractable epilepsy and determining which factors influence this quality. Method: The group consisted of 64 subjects with drug resistant temporal lobe epilepsy – 33 women and 31 men. The average duration of epilepsy was 19 9.56 and 17.56 8.92 years respectively. For the assessment purposes a set of psychological tools was used, containing: QOLIE-31-P, Wechsler Adult Intelligence Scale – Revised (WAIS-R(PL)), Hamilton Rating Scale for Depression (HRSD). Results: We did not find any differences in QOLIE-31-P’s total and subscales’ scores between groups of women and men, however, after detailed analysis some differences arouse. Multiple regression analyses indicated that distinct factors were associated with quality of life in each sex. In group of women, depression intensity was associated with QOLIE-31-P’s Emotional Well-Being (R2 = 0.14), age was a significant predictor of Medication Effects subscale (R2 = 0.11) and number of seizures (monthly) predicted score in Cognitive Functioning subscale (R2 = 0.09). In group of men depression intensity was a strongest and most important QoL predictor. It was negatively related with the following QOLIE-31-P’s subscales: Total Quality of Life (R2 = 0.16), Overall Quality of Life (R2 = 0.05), Energy/Fatigue (R2 = 0.12), Emotional Well-Being (R2 = 0.22), Social Functioning (R2 = 0.28), Seizures Worry (R2 = 0.08), Overall Health Level (R2 = 0.24) andDistress (R2 = 0.18). Moreover, younger age at epilepsy onset predicted better QoL in Emotional Well-Being (R2 = 0.07) and Distress (R2 = 0.08) and worse in Medication Effects (R2 = 0.07) subscales. Higher IQ was associated with better QoL in Medication Effects (R2 = 0.05) and Distress (R2 = 0.11) subscales. Distress level was also partially predicted by age (R2 = 0.04). Conclusion: The level of quality of life as measured by QOLIE-31-P does not differ between men and women in Poland, however in each sex it is predicted by different factors.


72 Abstracts P205 EDUCATIONAL VIDEO AND STORY AS EFFECTIVE INTERVENTIONS REDUCING EPILEPSY-RELATED STIGMA AMONG CHILDREN MEASURED BY THE VERIFIED CZECH VERSION OF STIGMA SCALE OF EPILEPSY Brabcová D1, Kohout J2, Weberova V1, Potuzak D1, Kom arek V3 1 Department of Psychology, Faculty of Education, University of West Bohemia, Plzen, Czech Republic, 2Department of Physics, Faculty of Education, University of West Bohemia, Plzen, Czech Republic, 3Department of Child Neurology, 2nd Faculty of Medicine, University Hospital Motol, Praha, Czech Republic Purpose: The aim of this contribution was to verify psychometric properties of the Czech version of the Stigma scale of epilepsy (SSE). Subsequently, the verified questionnaire was used for evaluation of effectiveness of two interventions focused on reduction of epilepsyrelated stigma among children aged 9–11 years. Method: The verification of the SSE questionnaire was carried out in the group of 207 pupils who completed it twice in interval of 3–6 months for the test-retest evaluation. In the intervention study, the first group of children involved in the study (n1 = 89) completed the SSE questionnaire, then watched a video and completed the same questionnaire immediately after the intervention. The same procedure was used for the second group (n2 = 93) where a story based on the content of video was read by instructor. The both groups came from the general population (no children with epilepsy were involved) and were retested 6 months later by the same questionnaire. Results: It was proved that the Czech version of the SSE questionnaire exhibited very good psychometric properties including high internal consistency (Cronbach0 s alpha of 0.856) and a clear and easy-to-interpret 4factorial structure. Subsequently, we showed that the both interventions resulted in a decrease of epilepsy-related stigma immediately after the interventions (the average value on SSE decreased from 55.15 points before the video intervention to 46.84 points immediately after it and from 48.68 points to 45.38 points in the case of the story). Surprisingly, a further significant decrease was observed during the 6 months between the intervention and the retest (to 43.28 points in the case of the video and to 36.97 points in the case of the story). Conclusion: The results show that the both interventions described are significant and effective ways to reduce epilepsy-related stigma in the given age group.

P206 ASSESSMENT OF PATIENTS’ AND CAREGIVER’S PERCEIVED NEED TO START ACTIVELY PARTICIPATED OUTCOME MEASURES IN EPILEPSY RESEARCH Celani MG1,2, Baiocco L1, Bignamini A3, Macone S2, Papetti R1, Cantisani TA1,2 1 Neuroscienze, Neurofisiopatologia, Azienda Ospedaliera Universitaria di Perugia, Perugia, Italy, 2Cochrane Neurosciences, Health Autority in Umbria Region, Perugia, Italy, 3 Pharmaceutical Sciences, Universita di Milano, Milano, Italy Purpose: To collect “end-user of treatments” perspectives, ideas and values to reach an agreement between different stakeholders needs. Method: The study was conducted in Umbria (Italy) on adult population affected by Epilepsy. It was structured through the use of Focus Groups. Patients and carers were recruited by telephone calls from the patients lists maintained by hospital wards, outpatients clinics and charities. From the respondents, two groups of patients and two groups of carers were formed for each level of severity of the disease based on three levels: Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

severe, moderate and mild (mRankin Scale 0–2; 3; 4–5).Two psychologists conducted recruitment, used predetermined semi-structured questions to interview attendees, and moderated group discussions. These were digitally recorded and transcribed into text-files, blindly analyzed and elaborated into key semantic meanings expressing perceived needs and emotions.Codes were analyzed using «Concordance» software, to identify the key semantic significants expressing the perceived needs and emotions in relation to the disease and its consequences. Results: 61 patients and carers participated (40% of people contacted), organized into 5 groups of patients, and 6 groups of Caregivers. Most frequently expressed needs were “assistance”, expressed 3 times more frequently by carers than patients, “Experience sharing” and “need for knowledge” expressed 2 times more frequently by patients. The need for assistance was directly proportional with disease severity, while the need for knowledge inversely proportional with disease severity.Emotions most frequently expressed were anger and fear, proportional with disease severity, but also hope, resignation and acceptance. These two were 2 and 5 times each more frequently expressed by patients. Anger and hope were equally distributed among patients and carers. Conclusion: Patient and carers’ priorities are based on intense personal insight, representing a starting point to work for shared outcome measures in clinical trials and shared agenda in research.

P207 HIGH RATES OF NICOTINE USE AND UNEMPLOYMENT AMONG PREGNANT WOMEN WITH EPILEPSY Farmen AH1,2, Nakken KO1, Lossius MI1 1 SSE Epilepsy Hospital, Oslo University Hospital, Oslo, Norway, 2Neurology, Innlandet Trust Hospital, Lillehammer, Norway Purpose: Psychosocial problems are prevalent in patients with epilepsy. This is the case even in seizure free patients off medication. We wanted to explore this further by comparing pregnant women with epilepsy to a reference population in Oppland County, Norway. Method: Information on 95% of all pregnant women who gave birth at one of the two obstetric departments in Oppland County, Norway, and their newborn children were prospectively registered in the Oppland Perinatal Database (OPD) since 1989. The database contains more than 40 000 pregnancies and births. All diagnoses of epilepsy were thoroughly validated. Nicotine use, drug abuse, employment- and marital status were analyzed in the epilepsy cohort and compared to the controls. Results: 303 pregnancies in 166 women with epilepsy were identified and compared to 40,481 controls. The women with epilepsy used nicotine more frequently in the start of pregnancy compared to the controls (34% vs. 24%, p = 0.001). At the end of pregnancy the nicotine use was almost equal between the two groups. Marital status was almost equal in the two groups, and same applied to the rate of drug abuse (0.6% vs. 0.2%, p = 0.20). 28% of the women with epilepsy on drug treatment were not employed vs. 20.1% in the reference group (p = 0.04). Conclusion: We found increased prevalence of nicotine use among women with epilepsy at the start of pregnancy. The rate of unemployment was significantly higher among the women with epilepsy who were on drug treatment compared to controls.

73 Abstracts P208 THE ADDED VALUE OF EPILEPSY EXPERTS IN THE EMERGENCY ROOM AFTER A FIRST UNPROVOKED SEIZURE Fisch L1, Girardin F2, Vernaz Hegi N3, Vargas M1, HeritierBarras AC2, Picard F1, Vulliemoz S1, Seeck M1 1 University Hospital of Geneva, Geneva, Switzerland, 2Unite Medico-chirurgicale de l’Epilepsie, Pôle Neurosciences Tête et Cou, CHU Montpellier, Geneva, Switzerland, 3Universidad Autonoma de San Luis Potosı, Geneva, Switzerland Purpose: The first seizure or seizure-like event is an emergency with significant morbidity and mortality requiring work-up in the emergency department (ED), including usually basic exams such as CT and neurological assessment. The aim of our study is to assess the yield of an earlycomprehensive patient care (ECPC) by an epilepsy expert after a first unprovoked event, compared to standard care (SPC), similar to what is offered nowadays for stroke patients. Method: From April 2012 to June 2013, patients presenting a first unprovoked epileptic seizure were included ECPC including a consultation by an epileptologist in the ED, a routine or long-term monitoring electroencephalogram (LTM-EEG), a magnetic resonance imaging and two follow-up consultations at 3 weeks and 3 months. We compared this protocol to the SPC, which included a standard neurology consultation in the ED, an EEG and a CT-scan in the ED. Follow-ups were notified to the patient. Results: 183 patients were included (113 patients in the ECPC, 70 in the SPC group). LTM-EEG and MRI were more often carried out in the ECPC group (LTM-EEG: 51% vs. 85%; MRI; 7% and 52% in the SPC (p < 0.001)). A final diagnosis was obtained in 64% (ECPC) vs. 43% (SPC; p = 0.002.) Patients attendance at 3-months significantly higher in the ECPC vs. SPC-group (p < 0.001). Delay until the first recurrence was longer in the ECPC group (p = 0.008). Costs were higher in the ECPC than SPC group (direct medical costs: 1,431 $ vs. 1,035 $ and global management costs 2,573 $ vs. 2,065 $). Conclusion: An early-epileptologist-driven protocol is associated with significant clinical benefit regarding diagnosis accuracy, follow-up and recurrence. We speculate that higher costs of initial patient care will be counterbalanced by fewer seizure recurrences and lower direct and indirect costs in the following years, but this remains to be determined.

P209 DO WE AVOID TALKING ABOUT SEX? Henning OJ1, Træen B2, Nakken KO1, Lossius M1 1 National Centre for Epilepsy – SSE, Oslo University Hospital, Sandvika, Norway, 2Department of Psychology, University of Oslo, Oslo, Norway Purpose: While it is known that many persons with epilepsy (PWE) suffer from sexual problems (SP), this comorbidity is most often not addressed during a consultation. Method: 171 of 227 consecutive adult patients with epilepsy (response rate 75%) and their physicians at an epilepsy centre participated in a questionnaire based survey about epilepsy and sexual problems. In a follow-up pilot study, 56 Norwegian neurologists answered an internet based questionnaire about type and rate of SP in PWE. Results: Physicians reported having asked 27 (16%) of the patients about SP. 18/27 complained about SP. Two of the remaining 9 patients (22.2%) who had not reported SP to their physician, had nevertheless reported SP when completing the questionnaire.In the follow-up study, 96% of the physicians reported that 5 year, but 75.0% used AED during the time of getting the driver’s licence. Even 41.7% of patients ignored advices given by their physicians. In addition, 62.5% of patients, did not inform Driver medical board about epilepsy and AED therapy. One patient (4.2%) was qualified for the category C, officially not allowed for PWO. Traffic accidents occurred in 20.8% patients and in 24.6% healthy controls (NS, p > 0.05). No accidents with deadly outcome nor severe injury occurred in both groups. The relevant license regulative was found unjust and restrictive on driving privileges significantly more often in patients (91.7%) than in healthy controls (46.1%) (p < 0.05). For 83.3% of patients the driver’s license is necessary for a normal life, while for 37.5% it is prerequisite for employment. Conclusion: The rates of motor vehicle accidents and crashes for both drivers with JME and healthy controls are similar. Procedural omissions, neglects and irregular steps of regulators are recognized. Patients found current driving regulative on compulsory AED freedom, to be inappropriate, unjust and discriminating and tried to evade it. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

76 Abstracts P217 PREMARRIGE COUNCELLING BY NEUROLOGIST, IMPROVES MARRIGE SUSTAINABILITY Mishra VN Neurology, Banaras Hindu University, Varanasi, India

P219 A STUDY OF SYMPTOMATIC EPILEPSY RELATED TO ISCHEMIC STROKE Takase K-I, Mizuno Y, Mukaino T, Nakamura N, Tateishi T Neurology, Iizuka Hospital, Fukuoka, Japan

Purpose: To acertain the imprortance of pre-marrige councelling of partener before marrige to improve the marrige sustainability.

Purpose: Symptomatic epileptic seizure is known as a major late complication of ischemic stroke. The mechanism of this symptom has not been made sufficiently clear. The purpose of our study is to identify the differences between patients with seizures after stroke and those who are without.

Method: Marrige parteners of 56 patients undergone 3 sessions of premarrige councelling by clinical councellors and treating neurologist about epilepsy and its medications. Outcome was compared in 1 year of marrige, with those patients who did not went pre-marrige councelling. Results: In those patients, in which councelling was done, 84 percent of marrige persists at the end of 1 year as compared to those who did not had pre-marrige councelling (29%). Conclusion: Proper Premarrige councelling improves the exixstance of marrige.

P218 THE KNOWLEDGE AND STIGMA FOR EPILEPSY IN JAPAN Nagamori C1, Maehara T2, Hara M3, Sumi Y1, Akaza M1, Hara K1,4 1 Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan, 2Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan, 3Hara Clinic, Yokohama, Japan, 4Hara Cliic, Yokohama, Japan Rationale: The care of epilepsy includes not only proper diagnosis and treatment, but also the management of public attitude toward epilepsy, including stigma, which affects patients’ quality of life. In Japan, a new law to prohibit a discrimination against disabilities including epilepsy will be applied in April 2016. The aim of this study is to investigate the knowledge and stigma in general population in Japan. Methods: A set of questions was selected from questionnaires identified in the literature. The participants experience and knowledge, about epilepsy were included in the questionnaire. In all, 1,080 people (540 female) aged 20–79 years living in variety areas in Japan completed the questionnaires on a Web site. After exploratory factor analysis was conducted to analyze the answers to 38 questions about the attitude/stigma toward epilepsy and stigma score, three scores (sympathy, stigma and social activity) were calculated for each participants. Results: Of the participants, 95% had heard or read about epilepsy; the rate was higher among elderly participants, 33% of participants had experiences to see epilepsy seizure. 18% of them had acquaintances with epilepsy. Although most people thought epilepsy was neither a contagious disease nor a mystical phenomenon, only 32% of participants answered that epilepsy was a neurological disease; 55% answered that epilepsy was treatable by medicine. Participants with family members with epilepsy answered higher level of sympathy for patient with epilepsy and stronger stigma toward epilepsy compared with others. The age, area, education, scores of knowledge about epilepsy did not have any significant effect on any factor. Conclusion: Our results revealed that the knowledge about epilepsy is still limited while the word of èpilepsy` is widely known in the general people, Japan. The personal experience such as having family with epilepsy or seeing seizures effects the attitude/opinion toward epilepsy rather than the knowledge.


Method: We selected retrospectively both patients who showed symptomatic epileptic seizure (SES) while presenting an old cardioembolic cerebral infarction, and a similar stroke without any seizures (SWS) matching age, sex and NIHSS who taken to our hospital from April 2010 to March 2015. The SWS group had no seizures for at least 3 years. Patients were investigated with vital signs, laboratory data, neurological findings and MRI findings. These two groups were compared using statistical analysis. Results: 42 SES and 52 SWS patients were finally analyzed in this study. The SES group showed 75.8 10.4 years old, 13.5 7.7 points of NIHSS and 38.1% of the males. Both groups did not show statistical differences in age, sex, NIHSS and past history. Most of them showed secondary generalized convulsions and infarctions occupying several cortices. Association with infarctions at the temporal lobe, elevation of white blood cells and glucose were significantly more conspicuous in the SES group than the SWS group. However, association with infarction at insula and corona radiata was significantly less in the SES group. Conclusion: Details of SES related to ischemic stroke are quite different from SWS. SES might be related to the focal destruction of temporal cortex, inducing hyperactivity of hippocampus. However, a larger area of cortical damage could not cause epileptic irritability because of destruction of the cortical network.

P220 RELATION OF PERCEIVED STIGMA TO ADVERSE EVENTS OF MEDICATIONS IN PATIENTS WITH EPILEPSY Viteva E Department of Neurology, Medical University – Plovdiv, Plovdiv, Bulgaria Purpose: We aimed to assess the influence of adverse events (AEs) of antiepileptic drugs on perceived stigma of Bulgarian patients with epilepsy. Method: Our study was based on questionnaires (Liverpool Adverse Events Profile and stigma scale), information from medical documentation and a purposeful interview on clinical factors of 153 patients with epilepsy. Results: Perceived stigma was observed in 64.71% of the study participants. There was a significant association between perceived stigma and the total Liverpool Adverse Events Profile score (p < 0.05, F = 13.71). Patients who reported AEs had an increased risk of perceiving stigma than those who did not experience AEs. A significant correlation between perceived stigma and the presence of neurological and psychiatric adverse events (p < 0.001, r = +0.60) and a mild correlation between perceived stigma and the presence of non-neurological adverse events (p < 0.01, r = +0.20) were verified. In a multivariate regression analysis the only predictors of perceived stigma were antiepileptic drug polytherapy and the presence of neurological and psychiatric adverse events. Conclusions: Adverse events of antiepileptic drugs in patients with epilepsy significantly correlate with perceived stigma. Our study results give another reason to pay attention to adverse events of antiepileptic treatment and will be useful in the campaign to overcome stigma predictors.

77 Abstracts P221 PUBLIC AWERNESS, UNDERSTANDING AND ATTITUDES TOWORD EPILEPSY IN MONTENEGRO Vujisic S1, Vodopic S2 1 Neurology, Clinical Center of Montenegro, Podgorica, Montenegro, 2 Clinical Center of Montenegro, Podgorica, Montenegro Purpose: To estimate the Montenegrin public awareness, understanding and attitudes toward epilepsy and to correlate the findings with responder’s social background. Method: This was a population based study. We randomly selected 1,326 adults aged 18–65 and carried out face to face interviews using a 10-item questionnaire, which had been used in similar settings. People with epilepsy or with relatives who had epilepsy were excluded from the survey. Descriptive statistics and Chi square (v2) test were used in order to identify factors associated with negative attitudes. Results: After exclusions and refusals, the questionnaire was administered to 1,000 people, 91% of whom had heard about epilepsy. Less than a half knew someone with epilepsy and 31.5% had witnessed a seizure. One fifth would object if their child played with a person who had epilepsy and three quarters would object if their child married a person with epilepsy. Forty percent believed people with epilepsy should be employed in the same way as everybody else. Fewer than 8% of respondents thought epilepsy was a form of insanity. Over 80% favored brain disease/disorder/injury to be the cause of epilepsy and 95% chose convulsions/shaking to be a major feature of an epileptic attack. Conclusion: General awareness of epilepsy in Montenegro is similar to that in other countries. Understanding of epilepsy is relatively good but the results suggest that there are still negative attitudes toward people with epilepsy.

Clinical Neurophysiology 1 Monday 12th September P222 BLINK REFLEX STUDIES IN GENETIC GENERALIZED EPILEPSY PATIENTS WITH EYELID MYOCLONIA Altıokka Uzun G, Ekizoglu E, Kocasoy Orhan E, Bebek N, € AE, Baykan B G€ urses C, G€okyigit A, Oge Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Purpose: Eyelid myoclonia (EM) with or without absences are a rare type of generalized seizures associated with a variety of epilepsy syndromes with an unknown pathophysiology. In this study, it is aimed to investigate the possible contribution of the brainstem structures in this underrecognized special type of seizures. Method: Sixteen consecutive patients with EM, diagnosed with genetic generalized epilepsy (GGE) according to International League Against Epilepsy 2010 criteria were included. Brainstem excitabilities were examined by blink reflex (BR) studies. The results of BR studies in GGE patients with EM were statistically compared with two control groups; namely age and gender-matched healthy volunteers and juvenile myoclonic epilepsy (JME) patients without any absences and using similar antiepileptic drugs (AEDs). Results: There were no statistical differences between the BR thresholds and the BR recovery curves in terms of amplitudes and areas of healthy subjects, JME patients and GGE patients with EM. Conclusion: Our findings do not support a profound interictal hyperexcitability in the BR-related brainstem structures of the GGE patients with EM. It can be considered that EM may be associated with excitability changes of the occipital cortex and other cortical areas.

P223 ADDED VALUE OF THE INFERIOR TEMPORAL ELECTRODE CHAIN IN THE IDENTIFICATION OF EEG ABNORMALITIES Beniczky S, Justesen AB, Johansen AE, Martinussen N, Kristiansen K Danish Epilepsy Centre – Filadelfia, Dianalund, Denmark The objective of this study was to assess the clinical added value of the inferior temporal electrode chain in identifying and characterizing abnormal graphoelements in standard EEG recordings. We have evaluated 300 consecutive recordings and compared the observed graphoelement in the classical 10–20 electrode array with the extended array that included six electrodes in the inferior temporal chain. One-hundred-ninety-three (64.3%) of the recordings were abnormal, 60 recordings had abnormal slowing, 60 recordings had epileptiform discharges, and 73 recordings had both abnormal slowing and epileptiform discharges. The EEG abnormalities were only identified in the inferior temporal electrodes in 6.9% of the recordings with abnormal slowing, 3.6% of the recordings with epileptiform discharges and in 5.5% of the recordings with both abnormal slowing and epileptiform discharges. Extending the standard electrode array with the electrodes in the inferior temporal chain is not time-consuming, and it contributes to identifying EEG abnormalities in a selected group of patients.

P224 AFTERNOON NAP VS. ALL-NIGHT SLEEP EEG FOR THE DIAGNOSIS OF ESES Gardella E1,2, K€ olmel MS3, Terney D1, Petersen Khinchi MS3, 1,4 Pavlidis E , Olofsson K3, Nikanorova M2,3, Rubboli G5,6, Beniczky S1,7 1 Department of Clinical Neurophysiology, Danish Epilepsy Centre, Dianalund, Denmark, 2University of Southern Denmark, Odense, Denmark, 3Department of Child Neurology, Danish Epilepsy Centre, Dianalund, Denmark, 4Child Neuropsychiatry Unit, Neuroscience Department, University of Parma, Parma, Italy, 5Department of Adult Neurology, Danish Epilepsy Centre, Dianalund, Denmark, 6University of Copenhagen, Copenhagen, Denmark, 7Department of Clinical Neurophysiology, Aarhus University, Aarhus, Denmark Purpose: Encephalopathy with continuous spike and waves during sleep (ESES or CSWS) is an age-related disorder, characterized by typical clinical manifestations (seizures, cognitive regression) and characteristic EEG pattern of continuous epileptiform activity during NREM sleep. Quantitative EEG parameters play a central role in the diagnostic process. However, there is no agreement on the gold standards for EEG collection and quantification. The aim of this study is to evaluate the comparability of afternoon NAP vs. all-night sleep EEG for the diagnosis of ESES/CSWS. Methods: 102 twenty-four-hours EEG recordings in 79 patients with the clinical suspicion of ESES/CSWS have been collected at the Danish Epilepsy Center in 2015. Afternoon sleep has been induced by melatonin administration. A semi-automated quantification of the epileptiform activity during wakefulness, NAP and nocturnal NREM and REM sleep has been performed by means of Brain Electrical Source Analysis (BESA) using an algorithm for assessment of the Spike-Wave Index (SWI) (Larsson). Results: Afternoon sleep was obtained in 34 patients (39 exams). Eighteen patients were diagnosed as having ESES/CSWS (21 recordings). In this group, the concordance in the computation of the SWI during NAP and during nocturnal sleep was 33% (7/21 recordings) and the concordance in the diagnosis of ESES based on NAP or on nocturnal sleep was 81% (17/21 recordings). Sixteen more patients (18 recordings) were diagnosed as not having ESES/CSWS. In this group, the NAP/all-nightEpilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

78 Abstracts sleep concordance in SWI quantification was 22% (4/18 recordings), but the concordance in determining the final diagnosis was 94% (17/18 recordings). Conclusion: The afternoon NAP is a simple and relatively cheap test, which can be suitable for a rapid exclusion of ESES/CSWS. Nevertheless, the assessment of the SWI only based on a NAP EEG might be quite imprecise and, in some cases, can lead to an underestimation of the cases of ESES/CSWS.

P226 SINGLE CALCIFIED NEUROCYSTICERCOSIS LESION AS A TRUE PEDIATRIC EPILEPSY SUBSTRATE IN ENDEMIC REGIONS: A PREVALENCE AND CLINICOELECTROENCEPHALOGRAPHIC-ANATOMICAL CORRELATION STUDY Dubey R, Gulati S, Kumar A, Chakrabarty B, Patel H, Pandey RM All India Institute of Medical Sciences, New Delhi, New Delhi, India Purpose: Calcified neurocysticercosis (NCC) is a common radiological finding in epilepsy patients residing in endemic zones. However, clinicoelectroencephalographic-anatomical correlation is often not the rule and occasionally there is presence of dual pathology. Electroencephalographic (EEG) abnormalities have been seen in upto 50% of NCC cases. Two Indian studies with single calcified cerebral lesions have found around 55% clinico-electroencephalographic-anatomical correlation with focal EEG abnormality only in 1/3rd of the study population. Methods: The study was conducted in a tertiary care teaching hospital in North India. Epilepsy patients, aged 5–18 years, fulfilling epidemiological criteria of single calcified NCC lesion (CNL) and more than 1 year of disease duration were included in the study. In a predesigned format, medical details, EEG and CT scan reports were recorded for 60 patients over 6 months period. Specialists recording clinical details and reporting EEG, CT and MRI were blinded to each other’s observations. Results: The mean age of the study population was 11 2.65 years with a female to male ratio of 1.4. The prevalence of EEG abnormalities was 48% (95% CI: 35.31–61.35). There was clinico-anatomical concordance in 80% (p = 0.001), clinico-electroencephalographic concordance in 78% (p = 0.02) and electroencephalographic-anatomical concordance in 77% (p = 0.003). Dual pathology was seen in only one patient, in form of mesial temporal sclerosis. Conclusion: Upto fifty percent of epilepsy patients with single CNL had surface electroencephalographic abnormalities with significant clinicoelectroencephalographic-anatomical concordance.

P228 CHLORAL HYDRATE IS MORE EFFECTIVE THAN MELATONIN IN INDUCING SLEEP FOR SLEEPDEPRIVED CHILDREN UNDERGOING PAEDIATRIC EEG Ong H-T1,2, Lim K2, Chiam J1, Low P-S1,2, Lin J1, Wang F1, Han V1, Tay S1,2 1 Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore, Singapore, 2Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Purpose: To compare the efficacy of chloral hydrate vs. melatonin in inducing sleep for paediatric patients undergoing electroencephalography (EEG). Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Method: Paediatric patients between 1 and 18 years old who were undergoing elective EEG were studied using 2 different medications to induce sleep. These medications were used when the patients fail to fall asleep after 20 min of trying. Chloral hydrate (40 mg/kg) was given over a 2.5-year period from October 2010 to March 2013, while melatonin (weight- and age- based dosage) was given from April 2013 to September 2015. Prior to the EEG, partial sleep deprivation instructions were provided. Patients who had global developmental delay (GDD), learning disability (LD) or autism were identified. Results: For the sedation, 228 patients had chloral hydrate and 164 had melatonin. Overall, 97% slept with chloral and 91% slept with melatonin; this difference is statistically significant (p = 0.006). A sub-group analysis was then performed for patients who had partial sleep deprivation on the night prior to the EEG test vs. those who did not despite the instructions given. Following partial sleep deprivation, the comparison of the 2 groups showed that chloral was superior and statistically significant (p = 0.018). Without sleep deprivation, the difference between the 2 groups was not statistically significant. Following sleep deprivation, 8 out of the 39 patients who had either GDD/LD/autism did not achieve sleep with melatonin, whilst all 34 patients who had chloral achieved sleep. Conclusion: When used together with partial sleep deprivation, chloral hydrate is more effective than melatonin in inducing sleep for EEG studies in paediatric patients. This superiority with chloral hydrate is also evident in the group with learning or behavioural difficulties.

P229 A PILOT STUDY OF AMBULATORY HOME VIDEO TELEMETRY (AHVT) IN ADULTS AT ST THOMAS’ HOSPITAL, LONDON Pauline JM1, Goyal S2, Koutroumanidis M1 1 Neurophysiology Department, Guy’s and St Thomas’ NHS Trust, London, United Kingdom, 2Neurophysiology Department, Evelina London Children’s Hospital, London, United Kingdom Purpose: Home video telemetry (HVT) is a rapidly developing branch of EEG long term monitoring (LTM). “Video-EEG telemetry has conventionally been regarded as a highly specialised investigation requiring inpatient admission” (F.Brunnhuber et al. Seizure 2014;23:338–343), but in NHS Trusts which do no have the capability for inpatient video-EEG telemetry (IVT) HVT can prove a valid alternative with little reduction in diagnostic value. This is a review of an AHVT pilot study within a NHS Trust. This Trust currently does not offer adult IVT, requiring patients with LTM needs to be re-referred to another tertiary centre. After a successful introduction of AHVT within the paediatric department, it was decided the service should be developed for adults. 2 questions will be considered; firstly, to assess the quality of the EEG and video data during clinical events; secondly, was the clinical question answered or an alternative diagnosis offered. Method: 8 patients triaged by a physiologist and Consultant Neurophysiologist suitable for AHVT were offered home video telemetry recording equipment. On return, the data was analysed considering the following criteria: 1 quality of the camera during the clinical events including night-time illumination, 2 artefactual interference of the electrodes including referential during clinical events, 3 comparison of the referred clinical question with the report conclusion. Results: 6/8 (80%) patients had at least one of their typical events in question with camera and scalp electrode coverage. Further non-typical and electrographic events were recorded in these patients. Of the 2 where typical events were not captured, non-typical and importantly diagnostic clinical events with video and EEG coverage were seen. 100% of patients had their clinical question either confirmed or an alternative or additional diagnosis offered.

79 Abstracts Conclusion: On the foundations of considered triaging and equipment compliance from patients, AHVT is offers a timely service with high diagnostic yield.

P230 AUTOMATED CLASSIFICATION OF EPILEPTIC SPIKES IN ICEEG RECORDED DURING FMRI ACQUISITION FOR IMPROVED BOLD MODELLING Sharma N1, Centeno M1,2, Chaudhary U1, Wehner T1, Yadee D1, Murta T1, Leite M1, Diehl B1, Pedreira C3, Lemieux L1 1 Institute of Neurology, Clinical and Experimental Epilepsy, University College London, London, United Kingdom, 2Institute of Child Health, Developmental Imaging and Biophysics, University College London, London, United Kingdom, 3 Experimental Psychology, University of Oxford, Oxford, United Kingdom Purpose: To implement and validate an automated spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED’s) obtained from human intracranial EEG data acquired during functional MRI (fMRI) scanning. Method: 5 patients that have undergone 10 min of intracranial EEGfMRI were selected for this study. A human EEG observer (H1) initially detected IED’s over the whole EEG time course. For the purpose of validation, three human EEG observers (H2, H3 and H4) and automated classifier WC independently classified a randomly selected set of 100 IED0 s detected by H1, for each patient. Cohen’s Kappa was used to compare pair-wise (Classification pairs: WC-H2, WC-H3, WC-H4, H2-H3, H2H4, and H3-H4) inter-classifier agreement (IED’s vs. Non-IED’s). To compensate for the small sample size, non-parametric bootstrapping was used for each pair. The Variation of Information (VI) was used to quantitatively assess the IED classification between each pair. To compare the automated and human classifications, we merged the VI values for all WC pairs on one hand and all H pairs on the other. The VI values were plotted as histograms and the Bhattacharrya Coefficient was used to calculate the percentage overlap between all WC-H pairs and all H-H pairs. Results: There was good (k > 0.4) to perfect (k = 1.0) inter-classifier agreement for ≥ 2 WC pairs for 3/5 patients. The mean VI values obtained after bootstrapping were significant (p < 0.05) for each pair for all patients. The percentage overlap between all WC-H pairs and all H-H pairs was >80% for 3/5 patients and >58% for 2/5 patients. Conclusion: WC based IED classification is indistinguishable from that of humans for most IED datasets considered and has the potential to reduce the subjectivity of IED marking and classification. Incorporating spike classification algorithms in the classification of IED’s can help create a more objective IED-related BOLD model.

Clinical Neurophysiology 2 Monday 12th September P231 COHERENT ANALYSIS OF INTERCONNECTIONS IN THE DRUG-RESISTANT MULTIFOCAL EPILEPSY PATHOLOGIC SYSTEM Alexandrov M, Abramov K, Chukhlovin A, Pavlovskaya M, Ulitin A, Borovikova V, Toporkova O Polenov Russian Scienific Research Institute of Neurosurgery, St. Petersburg, Russian Federation Purpose: The goal of the research was to define the EEG and electrocorticografic symptoms characteristic of a determinate (initial epileptogenetic) focus in case of drug-resistant multifocal epilepsy.

Method: Research was performed during examination and scheduled neurosurgery of 28 patients (19–49 years old) suffering from drug-resistant epilepsy. Clinical, electrophysiological, neuroimaging, neuropsychology examinations indicated that all the patients suffered from cortex multifocal epilepsy. The initial epileptogenetic focus was verified by installing subdural electrodes registering the bioelectric cortex activity under general narcosis according to a standard procedure. The pre-surgery examination comprised continuous electrocorticografic registration (at least 3 h) of the subdural electrodes data and a simultaneous videoEEG monitoring. The epileptic system interconnections were evaluated by a general coherence calculation (Cho). The discharge activities registered at the various epileptic foci were also analyzed. The surgical treatment was aimed at destruction and excision of the epileptogenetic focus. The post-surgery video-EEG was taken in 10–14 days. Results: The video-EEG sensibility rate in defining the determinate epileptogenetic focus in case of the multifocal epilepsy is 73 12%. The reason is the “power loss” of the discharge activities when performed through scalp. The comparison of the EEG and electrocortigram parameters received simultaneously shows that the epileptogenic activity index registered by the electrocortigram is 7.5 1.5 times lower on EEG. The electrocortigram registration results and calculation of the general coherence allowed to evaluate the foci interconnections. At the lover coherence values (Cho< 0.5) the foci were deemed independent. Conclusion: The stable connection in the system result in the following features of the initial focus: 1 a higher epileptogenic activity index (exceeding the index in the other foci by 30–40%); 2 generation of high-intensity discharge forms (high amplitude, but short complexes). The look back analysis of the epileptogenetic foci surgery results support the reliability of the developed criteria.

P233 FRAMEWORK FOR INTRODUCING HIGHFREQUENCY OSCILLATION ANALYSIS INTO CLINICAL DECISION MAKING PROCESS Cimbalnik J1, Klimes P1,2, Dolezalova I3, Pail M3, Rehulka P3, Halamek J1,2, Jurak P1,2, Brazdil M3,4 1 International Clinical Research Center, St. Anne’s University Hospital (ICRC), Brno, Czech Republic, 2Institute of Scientific Instruments (ISI) of the CAS, v. v. i., Brno, Czech Republic, 3 Brno Epilepsy Center, Medical Faculty of Masaryk University and St. Anne’s University Hospital, Brno, Czech Republic, 4 Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic Purpose: Localization of epileptic foci in pharmacoresistant focal epilepsies is crucial for successful epilepsy surgery. High frequency oscillations (HFO) are perceived as a novel biomarker of epileptic brain. Conducted studies confirmed significantly higher HFO rate in pathological tissue, and correlation of its removal with good surgery outcome. Although some significant challenges, such as distinction between pathological HFO and physiological HFO, prevent complete translation of HFO into clinic the results of HFO analysis can be already taken into account when making clinical decisions. Method: We present a framework for automated HFO detection, analysis and result visualization based on cross-platform and open-source tools. HFO detection is conducted by detectors written in Python or C language and stored in MySQL database for future retrospective analyses. The contact MNI coordinates and the brain structure within which they are localized are stored in the same database allowing for combination of these information. The results of HFO detection are presented in a comprehensive form through web interface or directly in MRI 3D models. Results: The framework provides clinicians with information about HFO intensity, frequency and contact location in the brain within 4–5 h from data acquisition. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

80 Abstracts Conclusion: The proposed solution allows clinicians to quickly assess pathological tissue localization with regard to HFO and add the results to the decision making process of pathological tissue localization. Due to its open-source, modular and cross-platform character, it can be used in any institution.

P234 CONVENIENT AND PORTABLE SUBCUTANEOUS EEG MONITOR FOR ULTRA-LONG TERM OUT-PATIENT USE Duun-Henriksen J, Gangstad SW, Blaabjerg L Hypo-Safe A/S, Lynge, Denmark Purpose: Recent years have shown an increasing need for ambulatory monitoring of epilepsy patients. This has required a technological development of convenient and portable systems for ultra-long term EEG recording. We present a discreet device that can continuously record high quality, two channel, subcutaneous EEG for years. Method: The system consists of an implantable and an external device connected via an inductive link. The external device (measuring 9x4x1.5 cm) powers the implantable device (10 cm long wire with a disc-shaped housing of approximately 2 cm in diameter) and receives the EEG signal through the link. This means that the subcutaneous device can stay implanted for years without being serviced. Three measuring points are available with an inter-electrode distance of 3.5 cm. 12 patients were monitored continuously night and day for more than a month. Visual as well as power and spectral analysis in standard frequency bands were analyzed as evidence of signal quality. Results: The visual analysis showed high-quality EEG with easily distinguishable patterns such as alpha enhancement during closed eyes, delta enhancement during deep sleep, sleep spindles, and K-complexes. Nighttime recordings contain few artefacts, and daytime recordings, which are often more exposed to noise, is mainly dominated by interpretable EEG. The power and spectral analysis showed no significant change over the 1-month period indicating a robust measuring system where signal quality does not degenerate over time. Conclusion: With this novel ultra-long term EEG monitoring device it is made possible to supervise epilepsy patients in ways never seen before. Plans for the future will focus on various application areas where the device will be able to make a difference for the patients as well as the treating physicians. Acknowledgment: We would like to thank The Danish Council for Strategic Research for funding of research leading to this abstract.

P235 DETECTION OF EPILEPTIC SEIZURES USING PHASEAMPLITUDE COUPLING IN INTRACRANIAL ELECTROENCEPHALOGRAPHY Edakawa K, Kishima H, Yanagisawa T, Fukuma R, Khoo HM, Oshino S, Kobayashi M, Tanaka M, Yoshimine T Neurosurgery, Osaka University Medical School, Osaka, Japan Purpose: Seizure detection using intracranial electroencephalography (iEEG) contributes to improved treatment of patients with refractory epilepsy. For that purpose, a feature of iEEG to characterize the ictal state with high specificity and sensitivity is necessary. Recently, it is reported that some rhythmic neural activities with different frequencies occur with certain correlation and those have been observed in hippocampus or visual cortex. This phenomenon is called cross frequency-coupling (CFC) and it attracts attention as the important side of the information processing within a brain. In this study, we investigated the phase-amplitude coupling (PAC) between the iEEG activities during the ictal and interictal state. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Method: The iEEG data of seven temporal lobe epilepsy patients with MRI-negative were studied. We evaluated the use of PAC of iEEG signals over a period of 24 h to detect the ictal and interictal states. PAC was estimated by using a synchronisation index (SI) for iEEG signals. Several combinations of PAC were calculated in all electrodes. To evaluated how accurately PAC differentiated the ictal state from the interictal state, we plotted the receiver-operating characteristic (ROC) curve of PAC to differentiate the ictal state from the interictal state. Results: iEEG signals of the ictal state was characterised by a strong PAC. Especially, the ROC of PAC between the phase of b band and the amplitude of high c band used to classify the ictal state has a significantly larger AUC (AUC, 0.9843) than other PAC. Furthermore, using PAC, the ictal state was successfully detected with significantly higher accuracy. Conclusion: PAC accurately distinguished the ictal state from the interictal state. We think that PAC is useful for seizure detection as a new feature.

P236 ELECTROENCEPHALOGRAM FINDINGS IN PATIENTS WITH UREMIC ENCEPHALOPATHY Milikic D, Vodopic S Neurology, Clinical Centre of Montenegro, Podgorica, Montenegro Purpose: The aim of our investigation was to evaluate the results of clinical, laboratory, neuropsychological and neurophysiologic investigations and their association in a sample of 36 patients undergoing chronic hemodialysis. Method: Patients were divided in two groups. The first group was comprised of patients who had normal electroencephalogram (EEG) findings (control group), and the other group included patients with abnormal EEG findings. During our investigation, all patients underwent the following diagnostic procedures: biochemical analyses, physical and neurological examinations, neuropsychological testing (mini-mental state examination – MMSE) and EEG. Statistical data evaluation was made in order to estimate the degree of correlation and the significance of between-group differences. Results: The level of urea significantly correlated with pathological EEG findings, as well as with the raw score on the MMSE test. findings did not show any significant correlation with EEG changes. Polyneuropathy was the most frequent neurological disorder. Based on the results of video EEG analysis, we concluded that the most common abnormalities were non-epileptiform changes with focal distribution. Conclusion: The results of our work reaffirm the importance of EEG recording and EEG analysis aiming to provide a precise and continuing insight into the functioning of nervous system during the hemodialysis, as well as follow-up, diagnostics and prevention of possible complications.

P237 ELECTRO-CLINICAL FEATURES OF VIDEO-EEG RECORDED SEIZURES IN 51 PATIENTS WITH TSC RELATED EPILEPSY Mingarelli A1,2, Savini M1,2, Vignoli A1,2, La Briola F1,2, Chiesa V1,2, Peron A1,2, Mai R3, Tassi L3, Mastrangelo M4, Canevini MP1,2 1 ASST Santi Paolo e Carlo, Milan, Italy, 2Department of Health Sciences, Child Neuropsychiatric Unit – Epilepsy Center, Milan, Italy, 3Epilepsy Surgery Center C. Munari, Niguarda Hospital, Milan, Italy, 4Pediatric Neurology Unit, V. Buzzi Hospital, A.O. ICP, Milan, Italy

81 Abstracts Purpose: Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystemic disease with variable expression. Epilepsy is the most common neurological symptom occurring in 80–90% of affected individuals, causing significant morbidity and mortality. Despite the large number of patients reported, the electro-clinical phenotype associated with TSC epilepsy is poorly described. We analyzed seizure semiology through ictal video-electroencephalography (EEG) recordings in a large series of patients. Methods: We studied 51 patients with TSC related epilepsy followed in 3 Tertiary Care Centers in Milan and analyzed clinical history and ictal video-EEG recordings obtained in all of them. Results: 51 patients (22F/29M) were included in the study. The median age of onset of epilepsy was 22.55 months (range: 1 day–16 years). Epilepsy started in the first year of life in 36/51 patients (70%). In 10 patients seizures started during the neonatal period. 33/51 patients experienced epileptic spasms in their life, with late-onset (> 2 years) in 5. 37/51 patients showed daily seizure frequency at the time of evaluation. We identified 4 different groups of patients: focal epilepsy (18/51), epileptic spasms and focal seizures (17/51), persisting epileptic spasms only (2/51) and Lennox-Gastaut evolution (14/51). Focal seizure were recorded in 42/51 patients, epileptic spasms in 9/51, tonic seizures in 4/51, atypical absences in 2/51, myoclonic seizures in 2/51, atonic seizures in 1/51. In 10 patients we recorded different seizure types. Focal seizures without generalization result as the most frequent seizure type recorded, with variable foci but predominant involvement of the fronto-temporal regions. Data obtained on seizure semiology analysis showed minimal motor signs in neonatal period. Epileptic spasms were frequently asymmetrical and manifestation had lateralizing features (eye deviation, asymmetric limb involvement, etc.), especially those with late onset. Conclusion: We describe the electro-clinical features of a large series of patients with TSC related epilepsy.

P238 DIFFERENTIATING EPILEPTIC FROM NONEPILEPTIC HIGH FREQUENCY IEEG SIGNALS USING WAVELET ENTROPY Mooij AH1,2, Frauscher B1, Amiri M1, Otte WM2,3, Gotman J1 1 Montreal Neurological Institute and Hospital, Montreal, QC, Canada, 2Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands, 3Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands Purpose: In this study, we quantify rhythmicity in the ripple band (80– 200 Hz) independently of amplitude using measures of wavelet entropy. We aim to assess whether there is a difference in measures of entropy of non-epileptic and epileptic channels, and if there is such a difference, whether it is sufficient for their classification. Method: We selected 637 channels from 50 patients with intracerebral depth electrodes. Channels were classified by independent experts as non-epileptic (303 channels) or epileptic (334 channels); epileptic channels were located in seizure onset zone (SOZ, 208 channels) or irritative zone (IZ, 126 channels). We calculated entropy between 80 and 200 Hz over epochs of one second for 60 s. We then calculated mean and standard deviation of entropy per channel and used these measures as predictors in a logistic regression model that estimated the chance of a channel being epileptic. We chose a probability threshold corresponding to 90% specificity and assessed sensitivity, positive predictive value (PPV) and negative predictive value (NPV). Results: The probability of a channel being classified as epileptic increased with higher mean entropy (p = 0.004) and with higher standard deviation of entropy (p < 0.0001). The overall performance of the prediction model was poor (area under the curve 0.67). Based on the

threshold corresponding to 90% specificity, sensitivity was 37%, PPV was 80%, and NPV was 56%. Conclusion: A channel with a high standard deviation of entropy is likely to be epileptic. This finding reflects that the high frequency iEEG signal of epileptic channels is more variable from second to second than the signal of non-epileptic channels. The overall performance of our model is not sufficient for full classification, but with a probability threshold corresponding to 90% specificity it can be used to select with good confidence a subset of the epileptic channels.

P240 FREQUENCY DOMAIN CONNECTIVITY PATTERNS IN EEG FOCAL AND GENERALIZED INTER-ICTAL EPILEPTOGENIC DISCHARGES AND ITS RELATION TO 3-D SPIKE SOURCE ANALYSIS Pinzon A1,2,3, Cabrerizo M3, Janwattanapong P3, Rajaei H3, Petre A2, Garcia S2, Adjouadi M3 1 Epilepsy Program, Baptist Health Neuroscience Center, Miami, FL, United States, 2Neurology Group, Miami, FL, United States, 3 Electrical and Computer Engineering, Florida International University, Miami, FL, United States Purpose: To have a better understanding of connectivity networks of inter-ictal epileptiform discharge activity. Method: Generalized inter-ictal epileptiform discharges (GEDs) represent rapid bi-hemispheric electrical activation originating from abnormal local neuronal activity at some point in the brain. Focal inter-ictal epileptiform discharges (FEDs) are related to an abnormal site in one hemisphere. Selected GEDs and FEDs discharges with a reasonable time constant pattern were identified for this study. We present a frequency domain cross-correlation analysis of GEDs and FEDs based on the number of connections (significance threshold p < 0.05) identified in the regions of interest (Anterior to Posterior and Left to Right) that belong to potentially activated networks. Using a MATLAB environment, crosscorrelation coefficients were calculated for each electrode pair using a time lag of 500 ms, where the maximum value was selected. Also, Curry 3-D spike source analysis of both FEDs and GEDs are presented showing possible onset activation areas in the studied cases. Results: Results of undirected connectivity matrixes are subdivided in the EEG spectrum of delta, theta, alpha and beta frequencies. GEDs showed strong connections in anterior-posterior axis whereas FEDs presented weaker or no connections at the same thresholds. Similar findings were also found when analyzing left-right connectivity strength where GEDs are significantly higher than FEDs. Conclusion: This study shows that results when placed in context with 3D spike source analysis, it is possible to predict that GEDs, as opposed to FEDs, are more likely related to abnormal long distance networking high conduction properties in the brain.

P241 ELECTROCLINICAL FEATURES OF EPILEPSY ASSOCIATED WITH SYNGAP1 MUTATION Tsirka V1, Konstantoulaki E2, Sparkes M2, Lascelles K2, Hughes E1,2, Goyal S1,2 1 King’s College Hospital, London, United Kingdom, 2Evelina London Children’s Hospital, London, United Kingdom Purpose: The epileptic encephalopathies are mainly characterized by drug-resistant seizures and neurodevelopmental deficits. SYNGAP1 mutations are reported to account for up to 1% of the new causes of epileptic encephalopathies and have been described to associate with non-syndromic intellectual disability and generalised epilepsy. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

82 Abstracts Method: We describe the electroclinical profile of five children (four females) with refractory epileptic seizures, neurocognitive delay and confirmed SYNGAP1 mutation, emphasizing on the EEG features. The children were reviewed in the outpatient clinic of a specialized epilepsy service and had repeated EEGs and/or telemetry recordings. Results: All children appeared with early identified neurodevelopmental deficits and seizure onset reported before the age of 18 months (for three children), with multiple, daily, very brief, stereotypical attacks of myoclonic type seizures, specifically head jerks, eyeblinks and eyelid flickering. These were often clinically related to head drops or falls. The seizures did not conform to the known myoclonic epilepsy syndromes (Benign myoclonic epilepsy of infancy, Absences with eyelid myoclonus, Myoclonic absences or Myoclonic-atonic seizures). Photosensitivity and pattern sensitivity were clinically remarkable in two children. The EEG showed normal or mildly slowed background, with eye closure activated posteriorly (occipital) dominant 3–4 Hz slow waves or irregular spike and wave discharges (SWD). In 80% of cases, generalised SWDs, with occipital emphasis, appeared. The ictal recordings (60% of cases) showed irregular, generalised, posteriorly dominant, 3–4 Hz SWDs, associated with isolated myoclonic head jerks, with or without eyelid myoclonus. These were at times related to head drops. Absences, with subtle, irregular eyelid flickering, were also noted. Photosensitivity with photoconvulsive (photosensitivity induced myoclonus) response was demonstrated in one case. Conclusion: The combination of early onset, drug-resistant generalised epilepsy with myoclonic seizures, neurodevelopmental delay and EEG findings of posteriorly predominant epileptiform abnormalities, on an otherwise preserved background, could be consistent with a SYNGAP1 mutation associated epilepsy.

Clinical Neurophysiology 3 Tuesday 13th September P242 HOW USEFUL IS REPEAT CONTINUOUS EEG MONITORING IN THE INTENSIVE CARE UNIT? Chung JM, Tsimerinov EI, Lee SW Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, United States Purpose: Previous studies have established the utility of continuous EEG monitoring (cEEG) in the Intensive Care Unit (ICU) setting. However, none has evaluated the yield or utility of repeat cEEG. We set out to determine the incidence of convulsive or non-convulsive seizures in ICU patients who underwent repeat cEEG performed during a single hospital admission. Method: We retrospectively identified patients who had undergone repeat cEEG during a single hospital admission. Beside patient characteristics, all cEEG reports were reviewed for the total number of cEEG performed, as well as the total number of hours of cEEG recording (both during an individual cEEG period and cumulatively). Repeat cEEGs were considered useful if subsequent cEEG demonstrated seizures (convulsive or non-convulsive) when the first cEEG did not. Results: A total of 740 patients underwent cEEG monitoring were evaluated in our study. Of these, 57 patients (7.7%) received a repeat cEEG which totaled to128 cEEG recordings and yielded a cumulative of 5,959 h of cEEG data. Three of these 57 patients demonstrated seizures on their repeat cEEG (5.3%), with the mean cumulative of 66 h (range of 44–99 h) of cEEG performed before capturing the significant findings of seizures. Conclusion: With limited resources, careful consideration in appropriate utilization of diagnostic study is ever more crucial to ascertain the Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

delivery of optimal care to patients. Our study demonstrated that the positive yield of repeat cEEG monitoring capturing seizures is 5.3% after a mean cumulative number of monitoring time of 66 h. Furthermore, there was a trend towards decreasing predicted probability of a seizure with each consecutive cEEG monitoring period. Further study with a larger patient population is underway to determine the number of cEEG and/or cEEG hours necessary for optimal yield.

P243 ICTAL PATTERN ON SCALP EEG INDICATES RESECTION AREA IN MESIAL TEMPORAL LOBE EPILEPSY Itabashi I1, Jin K1, Sato S2, Suzuki H3, Iwasaki M4, Kitazawa Y1, Kakisaka Y1, Fujikawa M1, Nakasato N1 1 Department of Epileptology, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Department of Diagnostic Radiology, Tohoku University Graduate School of Medicine, Sendai, Japan, 3Pathology and Laboratory Medicine, National Hospital Organization Sendai Medical Center, Sendai, Japan, 4 Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan Purpose: Surgical treatments for mesial temporal lobe epilepsy (mTLE) include anterior temporal lobectomy (ATL) and selective amygdalohippocampectomy (SelAH). ATL provides superior postoperative seizure outcome, whereas SelAH achieves superior functional preservation. However, procedure selection is difficult in individual patients based on presurgical evaluation. Method: Fifteen patients, 5 men and 10 women aged 13–67 years, were pathologically diagnosed as mTLE with hippocampal sclerosis. Nine patients underwent SelAH and 6 received ATL. Presurgical evaluation included long-term video EEG monitoring and 3-tesla MRI in all patients. MRI demonstrated no abnormalities other than hippocampal atrophy. Ictal EEG findings of 59 complex partial seizures were reviewed retrospectively, particularly delayed 5–9 Hz activity in the anterior temporal region. The relationship was investigated between this delayed activity and postoperative outcome/pathological findings. Results: Five of the 15 patients with hippocampal sclerosis showed delayed 5–9 Hz activity in the anterior temporal region, of whom 3 underwent SelAH and 2 had ATL. All 5 patients became seizure-free after surgery, and the 2 patients treated with ATL showed no pathological abnormality in the neocortical temporal region. Ten of the 15 patients showed no delayed activity, of whom 6 underwent SelAH and 4 had ATL. Three of the 6 patients treated with SelAH had residual seizures, and 2 of the 4 patients treated with ATL showed pathological abnormality in the neocortical temporal region. Conclusion: The presence of delayed 5–9 Hz activity in anterior temporal region indicates that the epileptogenic zone is localized only in the hippocampus. Patients with this activity are likely to be seizure-free after SelAH. Patients without this activity have a higher risk for residual seizures after SelAH, so are indicated for ATL. Ictal findings on scalp EEG are useful to determine the resection area.

P244 PAROXISMAL BRAIN: EPILEPSY AND PANIC ATTACK Karlov VA1, Gnezditskii VV2 1 Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, Russian Federation, 2Research Center of Neurology, Russian Academy of Science, Moscow, Russian Federation

83 Abstracts Purpose: Combination of different types of paroxysms in the same patient is not rare, but the mechanism of this phenomenon is poorly understood. Aim: Investigation of the comorbidity of epileptic seizures with other paroxysmal phenomena: rate and neurophysiologic mechanisms. Method: Analysis of 440 epileptic patients ages 12–50 between 1980 and 2012 in the Moscow hospital № 6 and the “Neuromed Center”. The investigation included ECG monitoring, Doppler method of extra and intracranial vessel study, visual evoked potential (VEP), skin sympathetic evoked potential (SSER), MRI, passive orthostatic test. Results: Association between epileptic seizures and panic attacks was revealed – 63 patients (every seventh patient), including nine migraine patients. Three patient groups were studied: patients with panic attacks (PA), patients with epilepsy (E) and patients presenting with the combination of epileptic seizures and panic attacks (E+) (30 patients in each group). Data of SSER (background, physical loading, psychoemotional tests); EEG (background, paroxysmal index, slow activity, including response to hyperventilation) and QOl-31 were compared. The SSER patterns in all patient groups, while being different from the ones in healthy subjects (№ 30, a control group), were similar in lengthiness, change of A1, A2 and Amax indexes. In patients of the E group, insufficiency of autonomic regulation, and in patients of PA and E+ groups, overstrain of parasympathetic system were revealed. Paroxysmal index and slow activity index increased in the following sequence: E, E+, PA. Indexes of autonomic control increased in a different sequence: E, PA, E+. Maximal changes of these indexes were found in the same patient exhibiting both types of paroxysms – panic attacks and epilepsy. Conclusion: Realization of epileptic seizures and panic attacks in the same patient is determined by common mechanisms: increase in paroxysmal index, indexes of slow activity, and dysfunction of autonomic control.

P245 IMPACT OF VIDEO-AMBULATORY ELECTROENCEPHALOGRAPHY ON THE MEDICAL MANAGEMENT OF EPILEPSY Manfredonia F1, Lawley A2, Cavanna AE3 1 Neurology, Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom, 2Royal Wolverhampton NHS Trust, Wolverhampton, United Kingdom, 3Department of Neuropsychiatry, Barberry National Centre for Mental Health, Birmingham, United Kingdom Purpose: Video-Ambulatory EEG (VAEEG) is a diagnostic tool which is being more and more extensively exploited in secondary care centres and has a role both in diagnostic work-up of new cases of suspected epilepsy and in the review of old cases with active seizures despite medical treatment. We reviewed how the outcome of the test has influenced the medical management of patients who underwent VAEEG at our centre. Method: 171 VAEEG were performed over 2 years and 111 were considered for analysis when all relevant clinical information pre- and posttest was available. Results: In our series a quarter of patients had changes in medical treatment following the outcome of the test. Changes reflected confirmation or modification of the original diagnostic impression and prove the value use of VAEEG as a diagnostic tool which acts as a potential filter for further investigations and appropriate referrals to tertiary centres. When no medical changes followed, it is plausible that the outcome of the test had some bearing. Patients at first presentation with non-epileptic seizures

were not started on treatment, thus avoiding misdiagnosis. When medical treatment of patients with longstanding history of epilepsy and non-epileptic events captured on VAEEG was not offered, we postulated that it might reflect a reluctance to challenge diagnosis that had consolidated with time and endorsed by previous specialists. Conclusion: Overall, our study offers a critical insight on how the outcome of VAEEG may influence the clinical attitude towards complex patients with suspected or longstanding history of epilepsy.

P246 PERAMPANEL IN ADD-ON: EFFECT ON EEG BACKGROUND ACTIVITY AND EFFICACY ON SEIZURE CONTROL IN PATIENTS WITH BRAIN TUMOUR-RELATED EPILEPSY. PRELIMINARY DATA Maschio M1, Zarabla A1, Maialetti A1, Petreri G1, Giannarelli D2, Cantelmi T1 1 National Institute for Cancer Regina Elena, Center for TumorRelated Epilepsy, Rome, Italy, 2National Institute for Cancer Regina Elena, Biostatistics/Scientific Direction, Rome, Italy Purpose: Patients with brain tumor-related epilepsy (BTRE) present difficulties regarding the simultaneous management of two challenging pathologies: epilepsy and brain tumor (BT). Patients are often forced to take polytherapy because in many cases, seizures are drug resistant. Perampanel is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization. The aim of this open pilot study was 1) to evaluate the effect of perampanel on EEG background activity using computerized EEG analysis and 2) to evaluate the efficacy of perampanel, as add-on during 6 months of treatment, in patients with uncontrolled partial-onset seizures related to BT. Methods: At first visit and after 6 months of therapy, patients underwent neurological examination (KPS and BI) and were evaluated according to: seizure frequency (using seizure diary), adverse events (using AEP), spontaneous reports of adverse events and Quantitative EEG. The starting dosage of perampanel was 2 mg/die with a weekly increase of 2 mg/day. Results: To date, we have recruited five patients (mean age 48.4 years), followed for at least 1 month: two high-grade gliomas, two low grade gliomas and one metastasis. Three patients were in chemotherapy. Two patients have simple partial seizures and three have secondary generalized seizures. All patients were in AEDpolytherapy. Mean seizure number in the month prior to administration of perampanel was 9.8. At the last follow-up available, 1 patient was seizure-free, 2 patients have a significant reduction of seizures (≥50%) and 2 were stable. Mean dosage of perampanel was 6 mg/die. No side effects were observed.The evaluation of EEG background activity is ongoing. Conclusions: We present the preliminary data of an ongoing study; despite this limitation, our findings indicate that perampanel seems to have a good efficacy on seizure control in patients with BTRE.

P248 PHOTOSENSITIVITY IS AN EARLY MARKER OF INFANTILE NEURONAL CEROIDLIPOFUSCINOSIS (NCL-2) Pietrafusa N1,2,3,4, Bellusci M5,6, Trivisano M3,4, de Palma L3,4, Vigevano F3,4, Specchio N7 1 University of Bari, Bari, Italy, 2Department of Basic Medical Sciences, Neurosciences and Sense Organs, Bari, Italy, 3 Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 4 Neurology Unit, Rome, Italy, 5Hospital 12 de Octubre, Madrid, Spain, 6Pediatric Neurology, Spain, 7Department of Neurology, Bari, Italy Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

84 Abstracts Purpose: To identify electrophysiological and clinical criteria for early diagnosis of NCL-2.

connectivity strength correctly identified the dominant hemisphere in all cases.

Method: We retrospectively reviewed clinical charts of all patients diagnosed with NCL-2, followed from 2005 to 2015 at “Bambino Gesu” Children’s Hospital, Rome, Italy. We analysed onset of symptoms, including epilepsy, seizure semiology, motor and cognitive dysfunctions, and electrophysiological findings.

Conclusion: Verb generation may present with bilateral Broca MEG activation. Its distribution correlates with the side of language dominance, however seems to suffer from limitations in cases of reorganization. However, theta band connectivity between Broca and the motor/ premotor cortex may be increased on the dominant side, irrespective of total activation. This characteristic could potentially be used for more specific language lateralization and localization.

Results: 14 patient were included, mean follow-up was 4.1 2.6 years. The median age at disease onset was 3.0 0.4 years. Epilepsy (71%) and regression of acquired milestones (29%) were the symptoms that lead to a paediatric neurologist evaluation. All patients acquired independent walk at the mean age of 13.5 2.2 months. First words were pronounced at 13.3 5.6 months however, delayed speech or regression of acquired verbal skills were present in 100% of patients at the age of 3 years old. First brain MR was done at the age of 3.7 0.5 years, with evidence of cerebellar atrophy (100%) and periventricular white matter signal alternation (77%). Semeiology of first seizure was myoclonic or atonic (46%), generalized tonic-clonic (18%) or focal with motor signs (18%). EEG revealed photoparoxysmal response (PPR) in 13/14 cases, since the first EEG in 75% patient. The adoption of standardized procedures for Intermittent photic stimulation (IPS), allowed early identification of PPR (3.60 0.52 vs. 4.46 0.45 years old, p = 0.032). In patients followed since the beginning of the disease in our centre PPR was detected earlier rather than in patients referred from other hospitals (0.17 0.21 vs. 1.30 0.63 years since epilepsy onset) (p = 0.006). PPR was documented at low frequencies of stimulation in 9 out of 13 patients, and flash-per-flash response in was evident in 5/13 patients. Conclusion: Early photosensitivity is a hallmark of patient suffering from NCL-2 disease. PPR typically is evident at low frequencies of stimulations. When it occurs in subject with delayed speech and/or ataxia, NCL-2 should be considered.

P249 MEG CONNECTIVITY FOR THE LATERALIZATION OF LANGUAGE – A PROOF OF CONCEPT Rampp S1, Herfurth K2, Hamer H2, Buchfelder M1, R€ ossler K1 1 Department of Neurosurgery, University Hospital Erlangen, Erlangen, Germany, 2Department of Neurology, Epilepsy Center, University Hospital Erlangen, Erlangen, Germany Purpose: A spectrum of non-invasive methods, based on e.g. fMRI, MEG and TMS, are utilized for the determination of the language dominant hemisphere. However, a number of cases of erroneous lateralization results are frequently reported compared to the invasive Wada-test. Especially cases after reorganization seem to be difficult. Furthermore, noninvasive mapping of language-related areas provide rather conservative results. It is frequently reported that the (partial) resection of these do not necessarily result in functional deficits. Novel computational models of neuronal systems provide hypotheses for language generation and reception. Based on consequent predictions, the presented proof of concept study evaluates functional connectivity in the theta-band as a marker for language dominance. Method: Six patients with pharmacoresistant focal epilepsies underwent presurgical evaluation, including neuropsychological testing and invasive language mapping. Four patients were left language dominant. Two patients presented with right language dominance, one of whom after likely reorganization due to left sided hippocampal sclerosis. MEG language lateralization was investigated using a verb generation paradigm. Analysis evaluated total activity in the Broca region, as well as connectivity strength between Broca and motor/premotor cortex. Results: Distribution of total Broca activity yielded correct lateralization in five patients. In three of these however, significant contralateral activation was observed. In one patient with reorganized language areas, lateralization was incorrect in spite of clear activation patterns. In contrast, Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P250 OLFACTORY DYSFUNCTION IN PATIENTS WITH MESIAL TEMPORAL LOBE EPILEPSY: WHAT IS THE DIFFERENCE OF THE PROBLEM? Samanci B1, Sezgin M1, Karbay M1, Sen C1, Samanci Y2, Kocasoy-Orhan E1, Orhan KS1, Baykan B1 1 Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, 2Istanbul Training and Research Hospital, Istanbul, Turkey Purpose: Olfactory impairments in patients with temporal lobe epilepsy (TLE) are known to include olfactory hallucinations as an aura and chronic impairments in odor discrimination and identification. The mesial temporal lobe is the main area of mammalian brain involved in central olfactory processing. Our aim was to investigate whether 1 there are any differences between patients with mesial TLE (MTLE) and idiopathic intracranial hypertension (IIH) and migraine that are also known to have olfactory complaints, 2 there are any associations between clinical features and olfactory impairment. Method: Seventeen non-operated patients with MTLE, 24 patients with IIH, 51 patients with migraine (14 of 51 with aura), 43 age- and sexmatched healthy controls were included after their written consents. The participants completed a structured questionnaire related to odor dysfunction and underwent an otorhinolaryngological examination. The Sniffin’ Sticks test was performed in order to evaluate odor threshold, discrimination and identification.The results were compared statistically. Results: Our results showed that patients with MTLE exhibited significant impairment in odor identification compared to the IIH, migraine and healthy control groups (p = 0.014, p = 0.003, p = 0.018; respectively). We also detected lower threshold levels in healthy control group compared to MTLE group. There was no difference between MTLE and migraine with aura groups. We also found a negative correlation between the number of anti-epileptic drugs and odor discrimination (r = 0.540, p = 0.025). No statistically significant differences were found in other test subcategories and their correlations with clinical and demographical data. Conclusion: The areas involved in MTLE such as hippocampus, piriform cortex, amygdala and enthorinal cortex are important in central olfactory processing, especially for olfactory memory. Our findings suggested that odor identification might be more closely related with olfactory memory as affected by MTLE and also that odor discrimination might be more affected by drugs compared to threshold and identification. Acknowledgments: This work was supported by the Istanbul University Scientific Research Fund.

85 Abstracts P251 LATERALIZATION OF RECEPTIVE LANGUAGE FUNCTION IN EPILEPSY PATIENTS: A HIGH RESOLUTION SCALP-DERIVED EVENT-RELATED POTENTIAL (ERP) STUDY Trimmel K1, Lindinger G1, Sachsenweger J1, Trimmel M2, Pataraia E1 1 Department of Neurology, Medical University of Vienna, Vienna, Austria, 2Department of Public Health, Institute of Environmental Hygiene, Medical University of Vienna, Vienna, Austria Purpose: The assessment of language lateralization is of utmost importance in presurgical epilepsy evaluation and language fMRI represents the current clinical standard. Still, a significant proportion of patients experience postoperative language or verbal memory deficits. Eventrelated potentials (ERPs) derived from high-resolution scalp EEG, especially the language-related negative component around 400 ms, are related to language processing and were therefore expected to represent a complementary noninvasive method of language lateralization assessment. Method: Scalp EEG was recorded from 64 standard locations in 36 drug-resistant focal epilepsy patients and 37 healthy controls during three visually presented language tasks: A short-term language memory task (differentiation of memorized from new/unknown words), a verbal working memory/phonological task (detection of rhymes in word pairs), and a semantic decision task (differentiation of words from pseudowords). ERPs during tasks were analyzed in the 300– 800 ms epoch by a 2 (Lateralization) 9 3 (Task) 9 2 (Stimulus Type) 9 2 (Group; patients vs. controls) repeated ANOVA design with Group as a between factor. Language fMRI was routinely obtained in 31 of the 36 epilepsy patients. Results: ANOVA showed a significant interaction of Lateralization 9 Task 9 Stimulus (F2,142 = 21.42; p < 0.001), indicating more negative potentials over the left compared to the right hemisphere in all tasks, with a less pronounced effect for unknown compared to memorized words and unrhymed wordpairs compared to wordpairs. This effect was independent of group. Computation of a laterality index showed highest concordance rates with fMRI for the Word/Pseudoword Task (87% Broca, 77% Wernicke). Conclusion: High resolution scalp-derived ERPs of language processing were lateralized to the left hemisphere in the majority of healthy controls and epilepsy patients. In patients, single-subject laterality indices showed high concordance with fMRI results. Results indicate that scalp-derived ERPs are a promising tool to investigate lateralization of receptive language function epilepsy patients.

Clinical Neurophysiology 4 Wednesday 14th September P252 PREDICTORS OF POSTICTAL GENERALIZED EEG SUPPRESSION Dede H, Baysal Kirac L, Bebek N, G€urses C, Baykan B Neurology – Clinical Neurophsiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Purpose: Postictal generalized EEG suppression (PGES) seems to be a pathophysiologic hallmark in ictal recordings of sudden unexpected death in epilepsy (SUDEP).

has been defined as postictal EEG suppression of >2 second duration with an amplitude of 10 lV. Forty-three sGTCSs occurring with PGES were classified as the PGES (+) group. Semiological features including lateralizing signs were compared between the PGES (+) and () groups to determine risk factors for the occurrence of PGES. Results: Left hemispheric seizures were significantly (p < 0.01) more common in the PGES (+) group than in the PGES () group. Preceding “bilateral asymmetric tonic posturing” was significantly (p < 0.0001) less common in the PGES (+) group (41.9%) than in the PGES () group (82.4%). However, preceding “version” occurred in similar numbers in the PGES (+) (65.1%) and PGES () groups (56.9%). Conclusion: Left hemispheric seizure onset and absence of “bilateral asymmetric tonic posturing” may be potential risk factors for PGES. Lateralization of the ictal onset zone and propagation pathways leading to sGTCSs are important for the occurrence of PGES.

P255 THE SAFETY OF AUGMENTED VISUAL STIMULATION: DOES REPEATED, EXTENSIVE VISUAL STIMULATION WITHIN A TIME-FRAME OF 1 H INCREASE SENSITIVITY IN PHOTOSENSITIVE PATIENTS? Kasteleijn-Nolst Trenité D1, Reed RC2 1 Utrecht University, Utrecht, The Netherlands, 2Husson University, Bangor, ME, United States Purpose: MDs, technicians and IRB members inquire about the risk(s) involved with IPS and with protocols that require more extensive visual stimulation in patients for diagnostic or scientific purposes. In a questionnaire-based UK study (Whitehead, 2016), GTCS from IPS was reported to be provoked in 0.04% of patients. An EEG study on IPS evoked signs with PPR range determinations (Angus-Leppan, 2007) did not evoke any GTCS, since they used the “Threshold Sensitivity Method” (Kasteleijn, 2012). However, it is not known whether a more extensive visual stimulation in a short period of time increases the risk of seizures. We sought to answer this query. Methods: In 100 consecutive photosensitive epilepsy patients (62 F; 3– 65 year; 59 with visually induced seizures; 29 AED naive) PPR threshold determinations were performed using a Grass PS 33 before and after standardized black/white striped patterns and TV stimulation with provocative programs. PPR ranges (upper-lower sensitivity limits transformed into Standardized Photoparoxysmal Ranges), then analyzed per Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

patient. An increase of: ≥ 3 SPR in eye closure condition was considered a clinically relevant change and a biomarker of increase of seizure susceptibility. Results: A total of 8 patients (5 F) of the 100 patients (8%) exhibited a change in SPR of 2 or more: 5 a decrease and 3 (2 F) an increase of 2- 4 SPR; yet, a change of 2 SPR is not deemed clinically relevant. Increase of ≥ 3 SPR was seen in 2/8 patients (M; 2%) corresponding to an increase from 18–25 to 8–30 Hz, and from zero to 15–30 Hz (both 4 SPR). None of our patients had a GTCS evoked. Conclusion: Extensive and repeated visual stimulation within a period of an hour does not increase the already very low risk of provoking seizures in the vast majority of patients.

P257 STATISTICAL LEARNING METHODS FOR DETECTION OF GENERALIZED TONIC-CLONIC SEIZURES IN ACCELEROMETER DATA Ohlsson F1, Czarnecki M1, Gustafsson N1, Wipenmyr J1, Krysl D2, Rydenhag B2, Malmgren K2 1 Acreo Swedish ICT AB, Gothenburg, Sweden, 2Institute of Neuroscience and Physiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden Purpose: The objective of the work presented is to evaluate the performance of various statistical learning methods applied to the task of detecting generalized tonic-clonic (GTC) seizures using accelerometer data. Such a comparative setting is a novel and important step towards a systematic evaluation of suitable statistical methods for seizure detection. Method: Data from three-axis accelerometers, one attached to each wrist, was collected at the Epilepsy Monitoring Unit at the Sahlgrenska University Hospital for 55 patients. A total of 27 GTC seizures in three patients were identified using video-EEG recordings. Four 24 h signal segments containing all seizures were selected and band-pass filtered before removing non-motion data using a 0.1 g threshold. To evaluate for robustness against high-frequency voluntary motions (e.g. toothbrushing) example data was separately recorded and introduced in the patient data. A large set of derived quantities, known as features, are computed in both the time and the frequency domain for each of the two sensors. The features are used as predictors in training binary classification models to identify GTC seizures. Feature space reduction is applied and several standard classifiers evaluated. Detection of seizures is based on a decision layer applied to the binary classifier, the output of the layer defining the performance of the method. Results: In a patient specific setting many standard classifiers perform well, with sensitivity and precision both at 100%. When subjected to patient generalisation and robustness tests the best performance is obtained for K-Nearest-Neighbours, Support Vector Machine and Random Forest. All these classifiers display 100% sensitivity and precision above 90% for both types of tests. Conclusion: Our results illustrate the merit of moving beyond the simplest linear classifiers, in particular with respect to the performance in patient general settings and in the presence of high-frequency non-seizure movements.

87 Abstracts P258 VERY HIGH FREQUENCY OSCILLATIONS IN TEMPORAL LOBE EPILEPSY Pail M1, Cimbalnık J2, Plesinger F3, Jurak P3, Chrastina J4, Br azdil M1,5 1 Department of Neurology, Brno Epilepsy Center, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, 2International Clinical Research Center, St. Anne’s University Hospital, Brno, Czech Republic, 3Institute of Scientific Instruments, Czech Academy of Sciences, Brno, Czech Republic, 4Department of Neurosurgery, Brno Epilepsy Center, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University,Brno, Czech Republic, 5 CEITEC – Central European Institute of Technology, Masaryk University, Behavioral and Social Neuroscience Research Group, Brno, Czech Republic

were applied, first visual analysis in the time domain for delayed responses and second time-frequency domain analysis with its responses divided in the frequency bands of spikes, ripples and fast ripples. The comparison of these analytic methods was done by calculating sensitivity, specificity, and positive and negative predictive value for the known seizure-onset-zone. Results: The time domain visual analysis responses showed low sensitivity (11%) but high specificity (98%), while spikes in the time-frequency domain method showed a sensitivity of 94% and specificity of 20%. Sensitivity of ripples was 90% and specificity 42%. Fast ripples showed a sensitivity of 54% and a specificity of 81%. The highest PPV was found for fast ripples (34%). The NPV was the highest for ripples (97%). Conclusion: Time-frequency domain analysis of the spike, ripple and fast ripple bands can yield a much higher sensitivity combined with an acceptable specificity (90% and 42% for ripples) compared to standard visual scoring in the time domain (11% and 98%). Time-frequency domain analysis is suggested as the preferred method for detecting pathological responses in epileptogenic tissue.

Purpose: The purpose of the presented study is to find out whether very high frequency oscillations (VHFO) in intracerebral EEG are specific for epileptogenic zone. Method: Intracranial EEG recordings of 33 epileptic patients were analyzed. The signals were visually screened for noise and artefacts and filtered in 4 frequency bands/(gamma (40–80 Hz), ripples (80– 200 Hz), fast ripples (200–500 Hz) and VHFO (500–1,000 Hz)/. Using Hilbert transform power envelopes were computed. Since pathological channels showed increased high frequency activity, the mean-median was calculated for each channel in artefact free regions. The increased activity in every frequency band was subsequently visually checked to verify that increased high frequency activity is caused by high frequency oscillations. Results: VHFO were detected in 11 out of 33 patients. In the group of patients with favorable postoperative outcome (four patients) all channels with VHFO were localized in the resected area (confirmed using postsurgical magnetic resonance imaging). However, in patients with poor outcome (3 patients), at least one contact with VHFO was presented in nonresected area. Conclusion: Removal of brain tissue generating VHFOs has been related to better postsurgical outcome indicating that VHFOs may mark cortex that needs to be removed to achieve seizure control.

P259 TIME DOMAIN VS. TIME-FREQUENCY DOMAIN AS METHODS OF ANALYSIS OF SINGLE PULSE ELECTRICAL STIMULATION IN PATIENTS WITH FOCAL EPILEPSY Pieters IKG1, Valentın A2, Ferrier CH1, van’t Klooster MA1, Alarcon G2, Zijlmans M1, Huiskamp GJM1 1 University Medical Center Utrecht, Utrecht, The Netherlands, 2 King’s College Hospital, London, United Kingdom Purpose: Resective surgery can cure patients with refractory focal epilepsy. This surgery is sometimes preceded by prolonged electrocorticography to detect the seizure-onset-zone. This zone can help to localize tissue that needs to be surgically removed to render the patient seizure free. Single pulse electrical stimulations can elicit typical epileptiform responses. For this, the standard method of analysis is visual detection of delayed responses in the time domain. Recently a method of analysis in the timefrequency domain was proposed, that also includes high frequency content. The purpose of this study was to compare this new method to the standard method, for prediction of the seizure-onset-zone. Method: Eleven patients with focal epilepsy who underwent grid implantation and single pulse stimulation were analyzed. Two methods

Epilepsy in Childhood 1 Monday 12th September P263 STEREO-EEG RECORDING, RADIOFREQUENCY THERMOCOAGULATION AND NEUROPATHOLOGIC CORRELATIONS IN A PATIENT WITH MRI NEGATIVE TYPE IIB FOCAL CORTICAL DYSPLASIA Garbelli R1, Spreafico R1, Barbaglia A2, Zucca I2, Rossini L1, Milesi G1, Cossu M3, Bramerio M4, Tassi L3 1 Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione IRCCS, Istituto Neurologico C. Besta, Milan, Italy, 2 Scientific Department, Fondazione IRCCS, Istituto Neurologico C. Besta, Milan, Italy, 3Epilepsy Surgery Centre ‘C. Munari’, Ospedale Niguarda, Milan, Italy, 4Department of Pathology, Ospedale Niguarda, Milan, Italy Purpose: Epilepsy surgery is particularly effective in patients presenting FCDIIb with up to 85% of seizure freedom. This success is probably due to the overlapping of the anatomical lesion and the epileptogenic zone (EZ). However, despite continuous improvements in MRI, some cases escape to the conventional imaging detection. We present a case of a woman with drug-resistant epilepsy and negative MRI, admitted to pre surgical invasive Stereo-EEG recording and treated by radiofrequency thermocoagulation (RF-THC). Since this procedure was only partially effective on seizures outcome, a resective surgery was then performed allowing a rare opportunity to correlate the identified EZ with the localization and extent of the RF-THC lesion and the underlying neuropathology. Method: The en bloc temporal lobe specimen, which is part of the resected tissues, containing the electrodes I, A, and T, was submitted to ex-vivo 7T MRI and T2wi were acquired. 3D reconstruction of the electrodes traces was performed and correlated with the extent of the RFTHC lesion and the neuropathology. Results: The traces of the electrodes were clearly recognized at the 7T MRI and the volume of RF-THC of the electrode I was measured on 7T images. On histological sections, dorsally to the RF-THC lesion, a FCDIIb was still present. The electrode I, positioned within the lesion, recorded epileptiform abnormalities consistent with this type of dysplasia. By contrast, the electrode A, localized outside the dysplasia, was still recording an epileptic activity albeit different from that recorded inside the dysplasia.


88 Abstracts Conclusion: This observation suggest that, at least in presence of FCDIIb, the EZ may exceed the neuropathologically defined dysplasia. Whether these epileptic discharges beyond the lesion limits could be due to propagation effects outside that area to be resected for seizure freedom is still an open question and this type of report might help in this respect.

P264 EARLY SEIZURES IN PATIENT WITH ACUTE STROKE IN KOSOVO Govori V1, Koqinaj M2, Hoxha R2, Shala A1, Hasani A1, Haxholli Q1 1 Neurology, University Clinical Center of Kosovo, Pristina, Kosovo, 2National Institute of Public Health of Kosova, Pristina, Kosovo Purpose: Aim of the study was to analyze the clinical data of patients diagnosed as acute stroke with appearance of early seizures. Method: In investigation were involved 1,063 patients, with acute stroke, admitted in Neurology Clinic. ES were defined as seizures occurring within 10 days from acute stroke. The patient with history of epilepsy were excluded. Methodology of the study was developed using clinical anamnesis histories and diagnostic methods, EEG, CT, MRI, for the 1 year period of time. Data were analysed using statistical package Instat 3. and v2-test . Results: A total 1,063 cases were treated with stroke, average age was 69.1 years and 12.1 years SD. Analysed according to the gender patients female were in 51.6% of the cases but without significant difference (P > 0.05).The epileptic seizures in all cases of stroke (1,063) was 4.23% (45). From all cases of stroke, ischemic stroke, were 75%, 13.8% hemorrhagic stroke and 11.2% mixed (mix). Hypertension are the main risk factors of stroke, with a prevalence of 68.9%. Prevalence of ischemic stroke was higher, 75%, compared to hemorrhagic stroke 13.8%, in all patients with stroke, the epileptic seizures among all cases of hemorrhagic stroke was higher (8.8%) comparing with ischemic stroke (4.0%). According to the gender of 45 cases with epileptic attack, 57.8% were male, the average age of cases with epileptic attack was 62.5 years, the average age for men was 60.2 years, slightly younger than women. Conclusion: Early seizure occur in about 4% of patient with acute stroke.In this patient hemorrhagic stroke is a predictive factor for ES. Working towards in increasing the awareness of population is needed too. Keywords: seizures, stroke, Kosova.

P265 ELECTROENCEPHALOGRAPHIC MARKERS OF PREICTAL DISORDERS Korsakova M, Kozlova A, Arkhipova N Burdenko Neurosurgery Institute, Moscow, Russian Federation Purpose: Dynamics of interictal activity are different in patients with temporal and parietal-occipital lesions. We will review the preictal electroencephalographic (EEG) patterns which occur in the patients with pharmacoresistant epilepsy associated with focal cortical dysplasia (FCD) temporal and occipital-parietal lobes. Method: We analyzed epileptiform activity appeared within 15 s for 60, 45, 30, 15, 10, 5, 2 and 1 min before seizure. We reviewed data of 20 patients with diagnosis FCD of different types (10 patients with lesion of temporal lobe and 10 patients with lesion occipital-parietal lobes). All patients underwent long-term scalp-EEG and showed ictal EEG pattern. We followed types of epileptiform activity: single and several sharp waves and sharp-slow-waves below 2 Hz, continuous rhythmic epileptiform activity with regular morphology > 2 Hz. We have assigned a Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

different number of points for patterns: 1 for each pattern sharp wave and/or sharp-slow-wave, 6 for continuous epileptiform activity, no epileptiform activity was assessed as 0. After a quantitative visual analysis of the each time point, the different epoch of analysis were calculated. Results: The significant increase of preictal epileptiform activity (an average of 6–11 points) was observed between 10 and 1 min before seizure in 8 patients from 10 with temporal lesion. In patients with occipital-parietal lesion FCD epileptiform activity was diffused. The increase of preictal epileptiform activity was observed since 6–8 points in 4 patients from 10 at 15 min-epoch before seizure. Another 6 patients had equable distribution of activity during all period of time without significant increase the number of patterns. Conclusion: Appearance of interictal activity before seizure are different depending on the localization of lesion. In patients with focal cortical dysplasia of temporal lesion observed increase of numerous and regularity of epileptiform patterns closer to the seizure in contrast to temporaloccipital lesion.

P266 ELECTROENCEPHALOGRAPHIC CHANGE OF NON-AFFECTED SIDE OF HEMIMEGALENCEPHALY AND DEVELOPMENTAL PROGRESS AFTER HEMISPHEROTOMY Nakagawa E, Takahashi K, Saitoh T, Sugai K, Sasaki M Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan Hemimegalencephaly is characterized by intractable epilepsy and severe psychomotor impairment. Epilepsy is often intractable and requires hemispherotomy. Sometimes epileptic discharges occur from nonaffected side after operation. We studied 5 cases of hemimegalencephaly after hemispherotomy resulted in seizure-free and at least 36 months we could follow including video-electroencephalography. Developmental age (DA) and developmental quotient (DQ) were evaluated with the developmental check list (Kinder Infantile Developmental Scale). The paroxysmal-index (PI) was expressed as the number of one second bins containing one or more intracranial epileptic discharges in the non-affected side, divided by the total number of seconds, and yield a percentage. DQ declined and DA increased in all cases. In respect of verbal DA and PI, 3 cases improved verbal DA when PI declined. Other 2 cases declined verbal DA when PI increased. In benign epilepsy with centrotemporal spikes、electrical status epileptics of sleep、Landau-Kleffner syndrome cases, combination of verbal developmental delay and EEG abnormality during sleep is known. The reason remains unclear, but the possibility is pointed frequent epileptic discharges interrupt the adequate neuronetworks. Similar situation might occur in our cases. In cases of hemimegalencephaly after hemispherotomy, if epileptic discharges appear in the non-affected side, it may show an inverse correlation between PI and verbal development.

P268 ANTI-EPILEPTIC TREATMENT OF FIVE ADULT INSTITUTIONALIZED PATIENTS WITH SUBCORTICAL BAND HETEROTOPIA DUE TO DCX MUTATIONS: A 20-YEAR FOLLOW-UP Mierlo, van P1, Snoeijen-Schouwenaars F1, Sourbron J2, Tan F1, Verhoeven J1, Veendrick M1, Wammes-van der Heijden E1, Willemsen MH3, Schelhaas HJ1 1 Neurology, Academic Centre for Epileptology, Heeze, The Netherlands, 2Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Molecular Biodiscovery, KU Leuven, Neurology, Leuven, Belgium,

89 Abstracts 3 Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, The Netherlands

Purpose: Subcortical band heterotopia (SBH) is a rare congenital brain disorder primarily affecting females. It results from aberrant migration of neurons during development of the cortex. SBH is most often caused by mutations in the doublecortin (DCX) gene. Preclinical studies suggest that the epileptogenesis of SBH is caused by a loss of phasic inhibition, which normally occurs by stimulation of the ɣ-aminobutyric acid A (GABAA) receptor. We wondered whether anti-epileptic drugs with an effect on GABAA phasic inhibition, e.g. benzodiazepines, phenobarbital, stiripentol, topiramate, valproate, and vigabatrin, would be more effective than drugs without this mode of action. Method: We evaluated the electronic medical and pharmacy records of the five institutionalized patients with SBH due to a DCX mutation who are living at Kempenhaeghe, a tertiary care facility for people with epilepsy and intellectual disability (ID). In these five patients we assessed the retention rate of the anti-epileptic drugs and we determined the efficacy and tolerability of the various drugs by studying the notes of the neurologist and the seizure registration of the nursing staff. Results: The retention rate was remarkable high for benzodiazepines. For the other GABA-ergic anti-epileptic drugs, this effect was less clear, certainly as compared to carbamazepine. The subjective analysis of the data did not reveal additional relevant information. Conclusion: In this study we could not find evidence that a specific pharmacological intervention of the GABAergic system in patients with SBH is superior to anti-epileptic treatment with a different mode of action. We conclude that, even at a tertiary care facility, where genetic classification of patients is standard care and anti-epileptic drug treatment and seizures are carefully monitored, it is still difficult to judge the therapeutic relevance of a theory that is based on preclinical studies.

P269 FOCAL CORTICAL DYSPLASIA ASSOCIATED TO BRAIN TUMOR (FCD TYPE IIIB ACCORDING THE ILAE). CLINIC, PATHOLOGICAL AND IMMUNOHISTOCHEMISTRY APPROACHES Tena Suck ML1, Alonso Vanegas MA2, Moreira Holguin JC2, Vergara Lopez S2 1 Neuropathology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico, 2Epilepsy Surgery, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Purpose: The three-tiered ILAE classification system for Focal Cortical Dysplasias (FCD) distinguishes isolated forms (FCD Type I and II) from those cortical layer abnormalities associated with another principal lesion (FCD Type III). (Bl€ umcke I et al. Epilepsia 2011; 52:158–174). The objective is analyze Clinical, pathological, immunohistochemistry and electron microscopic correlation in patients with FCD IIIb. (Bl€umcke I et al. Clinical Neuropathology 2011; 30:164–177). Material and methods: We retrospectively analyzed 18 cases diagnosed as FCD Type IIIb (FCD IIIb) associated to brain tumors and 10 cases of normal brain cortex (CN). Histological and immunohistochemical clinical findings correlated. The following primary antibodies expression was assessed by immunohistochemistry: Glut1, Glut3, Glut 4, GFAP, GFAP delta, NeuN, neurofilament, tubulin, myelin, nestin, and GFRA2 gene.

was negative in the CN. Neurofilament and tubulin expressed in fragmented tangle in FCD IIIb and is limited in the CN. The astrocyte GFAP shows tortuous, FCD IIIb and is segmented into discrete fibril in the CN. GFAP delta, nestin and Gene GFAR2 is negative in the CN and focally positive in FCD IIIb. It is higher in dysembryoplastic neuroepithelial tumor then the other kind of tumors and in small neurons. Ki67 was low in both types of tumor but we can observe positive cells between the white matter and cortex with abnormal migration. Conclusion: The transporters Glut are markers that could be directly related to neuronal brain damage.

P270 FOCAL CORTICAL DYSPLASIA ASSOCIATED WITH CAVERNOMA (FDC TYPE IIIC ACCORDING THE ILAE). CLINICAL, HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY CORRELATION Tena Suck ML1, Alonso Vanegas MA2, Vergara Lopez S2 1 Neuropathology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico, 2Epilepsy Surgery, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Purpose: Focal cortical dysplasia Type III refers to cortical lamination abnormalities associated with a principal lesion, usually adjacent to or affecting the same cortical area/lobe. FCD IIIc subtype corresponding to cortical lamination abnormalities adjacent to vascular Malformation. Cerebral cavernomas are characterized by abnormal sinusoid-like capillaries adjacent to one another with little or no interposed cerebral parenchyma or muscular tissue. (Bl€umcke I et al. Clinical Neuropathology 2011; 30:164–177). The objective is analyze clinical, pathological, immunohistochemistry and electron microscopic correlation in patients with FCD IIIc. (Rosenow F et al. Epilepsia 2013; 54:2025–2035). Material and methods: Twenty-one patients with intracraneal cavernomas were retrospectively analyzed. Clinical pathological, immunohistochemistry and electron microscopic correlation were performed. The primary antibodies used were: CD31, CD34, CD15, nestin, Factor VIII, VEGF, VEGF-R2, beta-FGF, IFIa, vimentin, laminin, GFAP and alphasmooth muscle cell actin. Results: There were 13 females and 8 males with a median age of 45– 57 years. Supratentorial region was the most affected by 91%, however the cerebellum was the most common localization followed the frontal lobe. Headache occurred in 62% of cases, 52% presented altered consciousness, motor and personality disorders, seizure frequency was 38%. Histopathological findings proliferation of endothelial cells (86%), inflammation (71%), hemosiderophages (71%) and dystrophic (71%) calcification. CD15 was highly positive, especially in areas of endothelial proliferation, like intimate and the muscular layer vessel. Nestin was negative in endothelial cells of the bigger vessels and occasional positive vessels in brain tissue and was positive in endothelial cells in proliferating cells and blood vessels. We Observed that there was a major expression of VEGF, VEGF-R2, FGF-b in focal hyaline vessels. Conclusion: Endothelial progenitor cells are circulating progenitor cells that enhance neovascularization in various pathophysiologic conditions.

Results: Glut1, GLUT3, Glut 4, GFAP, GFAP delta, NeuN, neurofilament, tubulin, myelin, nestin, and GFRA2 gene. Glut1 was positive in the blood vessels and in the erythrocytes, FCD IIIb observed that there is greater number of vessels in comparison with CN but also these were tubules vascular lumens. The GLUT3 is expressed mostly in the CN than FCD IIIb. The GLT4 was low in the oligodendrocytes in FCD IIIb and


90 Abstracts

Epilepsy in Childhood 10 Wednesday 14th September P271 PHOTOSENSITIVE EPILEPSY AND HOT WATER EPILEPSY: AN UNSUAL COMBINATION € Yalcın AD, Aydin-Özemir Z, S€urmeli R, Anadol Kelleci U, G€urgen N, Diler Y, Yıldırım F Department of Neurology, University of Health Sciences, € Umraniye Research and Education Hospital, Istanbul, Turkey Purpose: Reflex seizures are epileptic events triggered by specific motor, sensory and cognitive stimulation. According to the features of these stimuli they are divided into two main groups: simple and complex reflex seizures. Among the simple form, seizures that are sensitive to visual stimulation, especially flashing lights, are the most common and longest known. Hot water epilepsy is the most frequent type among the complex group. In this study, we describe the clinical and electroencephalographic features of a patient suffering from photosensitive epilepsy and hot water epilepsy at the same time.

Methods: Genetic test results, clinical description, MRI and EEG as well as laboratory results are summarized. Results: ChAc is a rare genetic disorder characterized by hyperkinetic movements, seizures, cognitive decline, neuropsychiatric symptoms, and acanthocytes on peripheral blood smear. This unique cohort of nine patients is characterized by seizures as a first and prominent symptom. In our patients other features of ChAc appeared later, including tics, other movement disorders, dysarthria and mild to moderate cognitive decline. Significance: Chorea-Acanthocytosis patients carrying the described rare mutation can present with focal, treatment resistant seizures.

P273 PLASMA CATECHOLAMINE LEVELS IN EPILEPTIC SEIZURES Bowman S1, Zonjy B2, Murugesan A2, Lhatoo S2, Rani MRS2 1 University School, Hunting Valley, OH, United States, 2 Neurology, Case Western Reserve University, Cleveland, OH, United States

Method: Our patient is a 17 year old male who was admitted to the epilepsy outpatient department after a generalized seizure during bathing. His history did not reveal any abnormalities. His neurological examination and cranial MR findings were normal. He was complaining about involuntary eye blinking in front of television and computer and had five generalized seizures during bath in total. Despite detailed asking he could not describe any symptom or sign before generalized seizure which could be interpreted as aura. His mother witnessed his typical absence seizures during TV watching. His repeated EEGs showed generalized multiple spike and wave discharges enhanced during intermittant photic stimulation. In the follow-up period lasting longer than 2 years the patient remained seizure free under 1,000 mg valproic acid treatment.

Purpose: Sudden unexpected death in epilepsy (SUDEP) is responsible for approximately 7,000 deaths annually in the United States and Europe with an estimated incidence of 1.16 deaths per 1,000 individuals with epilepsy. Risk factors for SUDEP include poor seizure control, frequent generalized tonic-clonic (GTC) seizures and long-standing epilepsy. Patients experience increased sympathetic activity, including hypertension, tachycardia, and cutaneous vasoconstriction after generalized seizures. Increases in catecholamine levels during GTC seizures may cause cardiac arrhythmias leading to death. We hypothesized the plasma catecholamine levels will differ in patients depending on type of seizure, with greater increases in epinephrine and nor-epinephrine levels in GTC seizures compared to non-GTC seizures.

Conclusion: Reflex epilepsies are relatively rare, occuring in only 5% of all epilepsy cases. According to the recent notion most of them are genetic in origin. Our patient represents a random case including two different types of reflex seizures.

Method: Patients were consented to the study in the epilepsy monitoring unit at University Hospitals, and blood was collected from 25 patients within 5 min after the occurrence of a seizure and baseline blood samples were collected after at least 12 h of seizure-free period. Patients were divided into 2 groups based on type of seizure as GTC or non-GTC.

P272 SEIZURES AS PRESENTING AND PROMINENT SYMPTOM IN CHOREA-ACANTHOCYTOSIS WITH C.2343DEL VPS13A GENE MUTATION Benninger F1, Zaid A2, Korczyn AD3, Oliver KL4, Pendziwiat M5, Nakamura M6, Sano A6, Helbig I5,7, Berkovic SF8, Blatt I9 1 Neurology, Rabin Medical Center, Campus Beilinson, Petach Tikva, Israel, 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 3Neurology, Tel Aviv University, Tel Aviv, Israel, 4Medicine, Epilepsy Research Centre, University of Melbourne, Melbourne, Vic., Australia, 5Neuropediatrics, University Medical Center Schleswig-Holstein, Christian Albrechts University, Kiel, Germany, 6Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan, 7Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States, 8Medicine, Epilepsy Research Centre, Austin Health, The University of Melbourne, Heidelberg, Vic., Australia, 9Neurology, Sheba Medical Center, Tel-Hashomer, Israel Objective: The aim of the study was to characterize the clinical features of nine patients in three families with Chorea-acanthocytosis (ChAc) sharing the same rare c.2343del mutation in the VPS13A gene.


Results: The levels of plasma catecholamines (epinephrine, norepinephrine, dopamine) were compared using paired t-tests. Our results revealed epinephrine was significantly higher both after GTC (p = 0.011) and non-GTC seizures (p = 0.010). However, epinephrine levels increased more drastically after GTC seizures ( x = 1025%) compared to non-GTC seizures ( x = 164%). Norepinephrine was also significantly higher in GTC seizures (p = 0.002) compared to non-GTC seizures (p = 0.741). There was no statistical difference for levels of dopamine between the two groups (GTC, p = 0.066; non-GTC, p = 0.376). Conclusion: The greatest autonomic perturbations are associated with GTC seizures. Marked catecholaminergic excess may cause Takatsubo cardiomyopathy with death due to cardiac compromise. Also, inadequate catecholaminergic responses may result in hypotension and fatality within minutes. Our preliminary data shows a spectrum of variability in catecholamine responses even within GTC patients and a larger number of patients is under study.

P274 TRANSIENT EPILEPTIC AMNESIA – THE ACUTE ANTEROGRADE AMNESIA CHAMELEON Cunha C1,2, Borges DF1,2, Franca S1, Leal A1,2,3, Cruto C1 1 Neurology and Neurophysiology, Hospital Pedro Hispano, Matosinhos, Portugal, 2Clinical Physiology Department, Coimbra Health School, Coimbra, Portugal, 3Neurofisiology

91 Abstracts Unit, Hospital Julio de Matos, Centro Hospitalar Psiquiatrico de Lisboa, Lisboa, Portugal Purpose: Transient Epileptic Amnesia (TEA) is a focal epileptic syndrome characterized by brief recurrent attacks of amnesia with favorable response to antiepileptic drugs. The association between Transient Global Amnesia (TGA) and TEA is not fully understood, as both entities may be a consequence of mesotemporal regional dysfunction Method: We report 3 patients admitted to our emergency room and regularly followed in our outpatient epilepsy clinic. Results: Case 1. A 74 year-old woman presented 3 self-limited witnessed episodes of isolated anterograde memory loss lasting several hours. EEG revealed sporadic sharp waves in the left temporal lobe. The 24-h, 25 channel, ambulatory EEG documented spikes in medial and anterior left temporal lobe areas with focal intermittent slowing and a 7 min electrographic seizure emerging from that region. MRI was unremarkable. Case 2. A 67 year-old woman was admitted for a witnessed anterograde amnesia lasting 2 h. TGA was initially diagnosed, but follow-up indentified a similar episode lasting 15 min. EEG showed scarce sharp wave activity in left temporal regions. MRI was normal. Case 3. A 70 year old woman was diagnosed with TGA after a witnessed 6 h anterograde amnestic episode. Months later, 2 similar episodes preceded of malaise with mild consciousness impairment were reported. EEG documented bitemporal intermittent slowing with epileptic activity on the left side. MRI revealed a left diminished hippocampal volume. Conclusion: Although an initial diagnosis of TGA was established in all patients, criteria for TEA were met after further investigation, with a rare case of documented ictal epileptiform activity. This report highlights that performing an EEG in these seemingly typical cases of TGA, with proficiency for long-term electroencephalographic monitoring, provides improved diagnostic accuracy and discloses a decisive impact on patient management and outcome.

P276 FACIOBRACHIAL DYSTONIC SEIZURES RESULT FROM FRONTO-TEMPORO-BASALGANGLIAL NETWORK INVOLVEMENT Iyer R, Ramakrishnan TCR Neurology, KG Hospitals and Post Graduate Institute, Coimbatore, India Purpose: The exact pathophysiology of Faciobrachial dystonic seizures (FBDS) is not known. Whether they are seizures or movement disorder is an ongoing debate. We present two cases of FBDS with unique features along with 60 patients described till date in literature and propose the network hypothesis to explain FBDS. Method: The first patient presented late after 2 months with full-blown features of limbic encephalitis. PET scan showed hypermetabolism in the bilateral caudate and putamen and amygdalae. On follow-up, hypermetabolism disappeared from the amygdalae and persisted in the BG. Clinically she had events of longer duration associated with jerks, automatisms and speech along with loss of awareness at presentation. At follow-up, only the brief jerks without loss of consciousness were present. The second patient presented with FBDS prodrome. The MRI showed BG involvement including the substantia nigra on the left side which is hitherto undescribed. We analyzed the clinical, electrical and imaging features of 60 other FBDS cases in the literature. Results: Based on the collective data, FBDS is explained by a neural network including bilateral frontal regions, bilateral basal ganglia and bilateral temporal regions mainly the hippocampi and the amygdalae. Asymmetric or strictly unilateral involvement results in contralateral clinical expression. Interruption in any one area of the network will alter the clinical expression as happened in our first case where temporal lobe

involvement stopped after the initial therapy resulting in clinical cessation of loss of consciousness, electrical cessation of spread across the temporal lobe and disappearance of temporal lobe involvement in the follow-up PET studies. The network can be entrained from anywhere within the network. The timing of ictal EEG changes depends on the timing of cortical entrainment. Conclusion: We propose the fronto-temporo-basalganglial network as responsible for the clinical phenomenon of FBDS. Further studies are required to establish the network.

P277 MELAS IN A YOUNG ADULT PATIENT PRESENTING WITH STATUS EPILEPTICUS Baysal-Kirac L1, Kinay D2 1 Neurology Department, Goztepe Research and Training Hospital, Istanbul, Turkey, 2Neurology Department, Okmeydani Research and Training Hospital, Istanbul, Turkey Purpose: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare disabling multisystem neurodegenerative disease affecting children and young adults. Method: We described a patient with hearing loss, seizures and strokelike episodes and discussed his clinical, laboratory and imaging findings. Results: This 24 years-old-male presented with convulsive seizures and right hemiparesia. A few days after his admission he developed convulsive status epilepticus and transferred to intensive care unit. His brain MRI revealed left frontal and parietal cortical hyperintensities on T2weighted images and FLAIR. There was no abnormal contrast enhancement. Cerebrospinal fluid (CSF) analysis revealed mild increase in CSF protein (60 mg/dl) without pleocytosis. The EEG showed generalised slowing and bilateral frontotemporal and left frontocentral focal epileptiform discharges and slow waves. His seizures were treated with levetiracetam and carbamazepine. During his follow he developed gait and swallowing disorders, and loss of independence in daily activities. He continued to have seizures trigerred with fever and infection. Cortical T2 hyperintensities was diminished on repeated follow up MRI 6 months later, while a new lesion reflecting right cerebellar ischemic infarct was disclosed. Further investigation with needle EMG and muscle biopsy showed mild myopathic changes. Further genetic counseling was planned. He was born at term to consanguineous couple. Early growth and development was normal except that he was diagnosed to have sensorineural hearing loss when he was 4 months. The family history revealed hearing deficits in his mother, brother, grandmother and cousins. His brother who was diagnosed with epilepsy at the age of 22 years had died after an episode of status epilepticus. Conclusion: Mitochondrial disorders should be considered in differential diagnosis of young adults presenting with unexplainded stroke episodes and epilepsy.

P279 PHENOTYPES OF JUVENILE MYOCLONIC EPILEPSY AMOUND PATIENTS IN SIBERIA, RUSSIA Shilkina O, Shnayder N, Dmitrenko D, Shapovalova E, Bochanova E, Veselova O The Voyno-Yasenetsky Krasnoyarsk State Medical University of the Health Ministry of Russia, Krasnoyarsk, Russian Federation Purpose: To analyse the frequency of occurrence of clinical phenotypes of JME among residents of the Siberian Federal District. Method: We included 80 patients with JME. All patients underwent preliminary anamnestic and clinical selection using stratified randomization.


92 Abstracts All of the participants were Siberian Federal District’s residents, and had certain diagnosis of JME. After verification of their diagnosis, patients were grouped based on the phenotype classification proposed by Martınez-Juarez et al (Brain, 129 (Pt 5):1269–80, 2006). Gender was also noted for subsequent gender-related analysis. Results: The incidence of JME among males was lower than among females (1: 1.9).In general, the average JME onset age was characteristic for this clinical form of idiopathic generalised epilepsy. Furthermore, JME onset age in males was higher than in females (p < 0.05). In general, the most frequent phenotype was the classical Type I phenotype. At the same time, we revealed gender-related features. The frequency of Type I occurrence in males was significantly higher than that in females (70.4% vs. 58.5%, respectively, p < 0.05). Type II, the least favourable phenotype in terms of stable pharmacological remission, occurred 3.5 times less frequently in males compared to females (3.7% vs. 13.2%, p < 0.01). Types III and IV did not reveal significant gender-related differences. Conclusion: As a result of this study, we recommend video-EEG monitoring in adolescent female patients at a younger age, with mandatory testing of levels of consciousness during induced stress for diagnosis of absences, as well as rare myoclonies of upper limbs, including photosensitive types. Higher frequency of Type II JME in females suggests imminent need for dynamic and lengthy video-EEG monitoring to exclude the chance of pseudo-remission, before a decision can be made about reduction or termination of AEDs.

Epilepsy in Childhood 11 Wednesday 14th September P280 LIVING WTIH LANDAU KLEFFNER SYNDROME Mølmen HS1, Cockerell I2, Årva M2 1 University of Oslo, Oslo, Norway, 2National Centre for Rare Epilepsy-Related Disorders, Oslo University Hospital, Oslo, Norway Purpose: LKS is a rare childhood – onset epileptic encephalopathy belonging to the spectrum of related disorders (BECTS, CSWS). A agedependent epileptic activity increasing during Non – REM sleep causes to a varying extent auditory agnosia and acute or subacute aphasia. Epileptic discharges on EEG are usually normalized in adulthood, but language deficits persist in a large proportion. Knowledge regarding adult0 s perception and experience living with this condition is limited.This study`s object was to assess thoughts and experiences living with LKS and language deficits. Method: In this qualitative descriptive study tree young adults were recruited from the National Centre for Rare Epilepsy – related Disorders in Norway. A semi-structured interview was used and obtained data was categorized, structured and coded with the help of NVivo 10. Results: Tree issues were described: Language deficits and emotional concerns: All subjects had since childhood ongoing language deficits and difficulties with receptive language, memory, word retrieval and attention span. The difficulties are labeled as challenging, frustrating and strenuous. Communication and interaction: Management strategies are important in everyday communication and interaction with family, peers ect. Standing close to, establishing eye contact, lip-reading and asking “please repeat” are frequent used strategies. Communication in groups and environments with surrounding sounds are especially demanding. Marginalization and inclusion: Informants encountered lack of knowledge in the educational system and that marginalization and limitations in school were inflicted by teachers. Retrospectively reading- and writing acquisition are Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

explained as particularly difficult. Self initiated withdrawal from social settings and the feeling of social isolation are described. Subjects have concerns on future employment. Conclusion: In adulthood LKS still affect everyday life. Subjects express emotional and social concerns. They experience difficulties with communication, exhaustion, and marginalization and exclusion in school and work, and that knowledge is still sparse in society today.

P282 TYPOGRAPHIC LEGIBILITY AND ITS PHONOLOGICAL INVOLVEMENT IN READING EPILEPSY Cano Celestino MG1, Rodrıguez Leyva I2, Gayt an Hern andez D3 1 Facultad del H abitat, Universidad Aut onoma de San Luis Potosı, San Luis Potosı, Mexico, 2Facultad de Medicina, Universidad Aut onoma de San Luis Potosı, San Luis Potosı, Mexico, 3Facultad de Enfermerıa, Universidad Aut onoma de San Luis Potosı, San Luis Potosı, Mexico Purpose: This research studies the relationship of the legibility factors with the amount of fixations that occur on content words (Golder, C. et al. Leer y comprender: Psicologıa de la lectura. Siglo XXI, Mexico, 2002; 31) while reading aloud to evaluate the posible participation in readers with Reading Epilepsy (RE). The causes that evoke seizures in RE still study (WEAVER, D. Font specific reading-induced seizures. Clin Neurol Neurosurg 2014; 125: 210–1). Method: Patients with epilepsy (5 juvenile myoclonic; 5 absence) were selected to assess the difference in the brain electrical activity while reading aloud printed fairy tales (two typeface families, two typographical sizes and two column widths) compared with another control population (10). The activity was messure throught electroencephalography (8-channel Grass Model). The content words (noun, verb, adjective, adverb) were counted. Reading was recorded by digital videocamera (DCRHC40 NTSC Sony Model). We used Fisher0 s exact test to check the results of electroencephalograms (EEG) and Independent Samples Student t-test to compare the fixations between groups. Results: Registration of abnormal electrical activity in the brain during reading was higher in the experimental group (p = 0.028). We can appreciate in sample a large number of pauses in nouns (p = 0.049), adjectives (p = 0.031) and adverbs (p = 0.046). They were higher in the experimental group in all cases and directly related with the legibility factors employees. This goes to explain that the factors studied (typeface family, typographical size, column width) are important to modify the electrical brain activity. Conclusion: We found an association of fixations in the content words with the use of Helvetica family, 7 points typographical size in the same family, and narrow columns of 20–28 characters per line in Times New Roman. Further studies are needed to confirm the relationship between typographic legibility factors and RE.

P283 DESCRIBING THE HUMANISTIC BURDEN OF ILLNESS IN DRAVET SYNDROME – CRITICAL METHODOLOGICAL QUESTIONS REMAIN Irwin J1, Pagano K1, Rycroft C2, Sabar U2 1 Zogenix International Ltd, Maidenhead, Berkshire, United Kingdom, 2BresMed Health Solutions Ltd., Sheffield, Yorkshire, United Kingdom Purpose: Dravet syndrome (DS) is an epileptic encephalopathy characterised by long-term refractory epilepsy, cognitive, behavioural and motor impairment. This review sought to identify published literature

93 Abstracts describing the humanistic burden of DS (as experienced by patients and caregivers) and the range of instruments used for its measurement. Method: A comprehensive literature review was conducted to identify articles describing the burden of DS, from literature databases (Medline, Medline In-Process, Embase, EconLit, Cochrane Library), and websites (e.g. patient advocacy groups, registries, conferences). Results: Of 1,426 citations, 80 reported a humanistic burden of DS on patients and families in terms of symptoms and health-related quality of life (HRQoL). Within these articles, 33 different instruments were used to assess symptom/HRQoL burden. Most instruments assessed patient symptoms, namely cognitive impairment (n = 8), behaviour (n = 7), mobility (n = 2), adaptive functioning (n = 2), or a range of symptom domains (n = 2). Some assessed specific symptoms, including autistic features (n = 2), Parkinsonism (n = 1) and sleep (n = 1). One assessed general child development. Three epilepsy-specific instruments were used although no validated instrument specific for DS was found. Four additional instruments (each identified in one article) assessed caregiver burden: Impact of Childhood Neurologic Disability scale (impact on patients and caregivers); Multidimensional Scale of Perceived Social Support (impact on families); a structured interview (impact on families), and an online questionnaire (assessing depression in parents). Impacts on families included: stress of seizures on the parents, negative impacts on parents’ relationships with others, decreased attention and resentment in siblings, difficulties in finding respite care outside the family, and depression in mothers (9%), fathers (9%) and siblings (4.5%). Conclusion: Although the humanistic burden is known to extend beyond DS patients to caregivers and families, it is poorly described and given the lack of a validated DS-specific instrument, likely underestimated. There remains a need for validated instruments to measure this burden.

P284 DRUG RESISTANT OCCIPITAL EPILEPSY: STURGEWEBER VARIANT OR COELIAC DISEASE? A DIAGNOSTIC DILEMMA Kiryttopoulos A1, Spilioti M1, Pippidou N1, Antoniadi E1, Mougios V2, Orologas A1 1 1st Department of Neurology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece Purpose: In this presentation, we discuss the differential diagnosis between the Sturge Weber syndrome variant (type III, without facial port wine nevus) and coeliac disease. Method: A 55 year old male patient presents with refractory occipital epilepsy from early childhood, associated mental retardation, recurrent abdominal pains and lateral gyral cortical calcifications on the left occipital regions, without facial port wine nevus. Results: Brain CT revealed gyral left parieto-occipital calcifications, local parenchymal atrophy and suspected leptomeningeal angiomatosis. CT angiography was negative for arteriovenous malformation. Brain MRI, for confirming leptomeningeal angiomatosis, was not performed because of a metallic prosthetic heart valve, while in functional imaging with brain SPECT a reduction in local cerebral blood flow was observed. Screening for autoantibodies to coeliac disease, such as antibodies against tissue transglutaminase (anti-TTG IgA/IgG), the anti-gliadin antibodies (AGA IgA/IgG) and the DGP/tTG screen were negative. The abdomen ultrasound was normal and the bowel biopsy returned without specific findings for coeliac disease. Ophthalmologic examination was negative for glaucoma. The EEG showed frequent generalized paroxysmal discharges of slow theta and delta waves, predominantly on the left posterior areas.

diagnosis requires a high index of suspicion in patients with pharmacoresistant epilepsy and gyral intracranial calcifications. Coeliac disease and Sturge-Weber syndrome type III may share common clinical and neuroimaging findings such as drug resistant epilepsy and cortical gyral calcifications mainly on the posterior brain regions, creating a differential diagnostic dilemma.

P286 EEF1A2 (EUKARYOTIC ELONGATION FACTOR 1, ALFA-2) RELATED EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY AND MYOCLONIC ASTATIC EPILEPSY Linder I1,2, Nezer-Kanner I3, Eden A2, Kivity S2, Zerem A2, Lev D1,3, Blumkin L2, Lerman-Sagie T1,2 1 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 2Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel, 3Wolfson Medical Center, Institute of Medical Genetics, Holon, Israel Purpose: Description of the first two Israeli patients diagnosed with a heterozygous de novo EEF1A2 (eukaryotic elongation factor 1, alfa-2) mutations and definition of the EEF1A2 related early infantile epileptic encephalopathy based on the current literature. Method: Whole exome sequencing was performed in a two epileptic patients with early infantile epileptic encephalopathy (EIEE) and myoclonic astatic epilepsy (MAE). Results: Both infants are females born to non-consanguineous Jewish parents. The first is 15 mo old presented at 3 months with apneic seizures, progressing to EIEE. Her seizures consisted of focal, dyscognitive, tonic and myoclonic seizures. The second patient is 23 mo old presented at 10 mo with atypical absence & myoclonic seizures. EEG demonstrated multifocal discharges in pt1 and polyspike & wave in pt2. Imaging and an extensive metabolic work-up were uninformative in both. Multiple antiepileptic drugs failed to control pt1 seizures. Phenytoin and the ketogenic diet worsened her seizures while a combination of levetiracetam, valproic acid and phenobarbital had a mild positive effect. Medical cannabis (CBD 20% 24 mg/kg/d CBD; 1.18 mg/kg/d THC) seemed to ameliorate the seizure burden- specifically the myoclonic seizures. At 12 mo she has intractable epilepsy, profound intellectual disability (ID), postnatal microcephaly, hypotonia and mild facial dysmorphism. Pt2 responded to a short course of ACTH and was seizure free for 6 months. Recurring at 18 mo as head drops and myoclonic jerks. She responded to valproic acid. At 23 mo she has mild verbal delay. Two de novo EEF1A2 mutations: pt1 [NM_001958.3:c.374C>A: p.Ala125Glu] pt2 [NM_001958.3:c.370G>A:p.Glu124Lys] were found, both predicted to be damaging. Conclusion: De novo EEF1A2 mutations can cause myoclonic astatic epilepsy and a new neurological syndrome consisting of epileptic encephalopathy, postnatal microcephaly, profound ID, hypotonia and mild dysmorphism. Our two patients (Pt1 being the youngest described so far) exhibit the growing phenotypic spectrum of EEF1A2 mutations.

Conclusion: The patient likely belongs to the rare subset of patients with Sturge Weber variant without facial port wine nevus (type III). This


94 Abstracts P287 A NOVEL DESCRIPTION OF A HOMOZYGOUS PARTIAL DELETION OF RBFOX1 GENE CAUSING EPILEPTIC ENCEPHALOPATHY, SEVERE INTELLECTUAL DISABILITY AND PROGRESSIVE POST-NATAL MICROCEPHALY Linder I1, Nezer-Kaner I2, Leshinski-Silver E2, Kivity S3, Michelson M2, Lev D4, Lerman-Sagie T4 1 Pediatric Neurology Unit, Sackler Faculty of Medicine TelAviv, Wolfson Medical Center, Holon, Israel, 2MetabolicNeurogenetic Clinic, Wolfson Medical Center, Holon, Israel, 3 Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel, 4Sackler Faculty of Medicine Tel-Aviv, MetabolicNeurogenetic Clinic, Wolfson Medical Center, Holon, Israel Purpose: RBFOX1 deletions were described in Rolandic epilepsy (RE), Idiopathic generalized epilepsy (IGE), Autosomal dominant lateralized temporal epilepsy (ADLTE) and in Neurodevelopmental disorders such as mental retardation, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and in schizoaffective disorder and in intracranial arachnoid cysts and malformations of cortical development (MCD). Deletions were also traced in obesity, diabetes and in primary biliary cirrhosis. This is the first case of a homozygous partial deletion of the RBFOX1 gene found in a female toddler suffering from epileptic encephalopathy with profound ID and progressive post-natal microcephaly. Chromosomal micro-array analysis (CMA) revealed a 426 KB homozygous deletion in chromosome 16p13.3 at the 50 UTR end of the RBFOX1 gene. The asymptomatic consanguineous parents are heterozygous for the deletion Method and results: Chromosomal micro-array analysis (CMA) revealed a 426 KB homozygous deletion in chromosome 16p13.3 at the 50 UTR end of the RBFOX1 gene. The asymptomatic consanguineous parents are heterozygous for the deletion. Conclusion: This is the first case of a homozygous partial deletion of the RBFOX1 gene in a toddler suffering from epileptic encephalopathy with profound ID and progressive post-natal microcephaly detected by CMA. Our case strengthens the association of partial RBFOX1 deletions in neurodevelopmental diseases and extends the RBFOX1-related phenotypic spectrum.

P288 DE NOVO KCNB1 MUTATIONS CAUSE INFANTILE EPILEPTIC ENCEPHALOPATHY WITH GENERALIZED EPILEPTIFORM DISCHARGES Tohyama J1,2, Kato M3, Akita T4, Goldberg-Stern H5, Kobayashi Y1, Magara S1, Komatsubara T1, Cohen R5, Ohba C6, Nakashima M6, Fukuda A4, Saitsu H6,7, Matsumoto N6 1 Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan, 2Niigata University Medical and Dental Hospital, Niigata, Japan, 3Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan, 4 Department of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu, Japan, 5Schneider’s Children Medical Center, Epilepsy Center, Petah Tiqwa, Israel, 6Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan, 7Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan Purpose: The voltage-gated Kv2.1 potassium channel encoded by KCNB1 produces the major delayed rectifier potassium current in pyramidal neurons. Recently, de novo missense KCNB1 mutations have been identified in three patients with epileptic encephalopathy and a patient with neurodevelopmental disorder. Whole-exome sequencing analysis of Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

patients with unsolved epileptic encephalopathy identified three novel patients with KCNB1 mutations. The aims of this study are to investigate the phenotypic spectrum of KCNB1 mutations. Method: Three patients with de novo missense KCNB1 mutations were ascertained. Clinical histories, epileptic seizures, neurological examinations, neurophysiological and neuroradiological data and results of genetic analysis were evaluated. Wild-type or mutant Kv2.1 was expressed in Neuro2a cells and primary cortical neurons, and whole-cell patch-clamp analysis was performed. Results: Initial seizures appeared at 12 months in two patients or 17 months old in one patient. All showed psychomotor developmental delay and multiple generalized seizures including clonic seizure (1/3), tonic-clonic seizure (1/3), atonic seizure (1/3) and spasms (2/3). Focal seizures were also observed. EEG showed spike-wave discharges in two patients, and spike-wave discharges with hypsarrhythmia in one patient. Initial MRI revealed no abnormal findings, while subsequently brain atrophy was observed in one patient. The three mutations (p.T210K, p.R306C and p.G401R) were located in the linker between transmembrane S1 and S2 segment, voltage-sensing and pore domains of the channel, respectively. The R306C mutation significantly disrupts sensitivity and movement of the Kv2.1 voltage sensor, while the G401R mutation selectively abolishes endogenous Kv2 currents, indicating a dominantnegative effect on wild-type channels. Both mutants exert loss-of-function effects on production of sufficiently deep interspike voltages, thereby inhibiting repetitive action potential firing. Conclusion: Our findings suggest that de novo KCNB1 mutations are associated with psychomotor developmental delay, multiple generalized seizures including spasms, and spike-wave discharges, highlighting the importance of Kv2.1 for brain development and function in humans.

Epilepsy in Childhood 12 Wednesday 14th September P289 THE USE OF NGS FOR THE DIAGNOSIS OF EARLY ONSET EPILEPTIC ENCEPHALOPATHIES: THE CLINICAL EXPERIENCE OF AN ITALIAN CENTRE Contaldo I, Gambardella ML, Olivieri G, Quintiliani M, Perulli M, Musto E, Battaglia D Child Neurology Unit, Catholic University Rome, Rome, Italy Purpose: To report the clinical experience of an Italian center in achieving the diagnosis of Early Onset Epileptic Encephalopathy (EOEE) using Next Generation Sequencing. Method: NGS has been performed in 50 patients affected by EOEE. All patients underwent detailed clinical analyses, scalp EEG study, MRI, metabolic testing and and array-CGH. Patients underwent NGS only if metabolic, neurodegenerative diseases and recognized epileptic syndromes have been ruled out. 48 out of 50 patients underwent an NGS panel inclusive of 105 genes involved epilepsy; 1 patient uderwent a NGS panel inclusive of 96 genes involved in cerebral malformations. The remainig patient underwent a WES within a clinical research project. Results: Pathogenic mutation or Variant Uncertain Significance(VUS) in 7/48 patients. All mutations are “de novo”: Potentially pathogenic VUS in DOCK7 gene in a male with drug resistant focal seizures and cortical blindness. Potentially pathogenic VUS in TBC1A2 in a female with severe intellectual disability, movement disorders and myoclonic seizures double Potentially pathogenic VUS in both SPTAN1 and NHLRC1 genes in a patient with a vitamine B6 dependent encephalopathy, causative mutation in CDKL5 in a female with a typical phenotype

95 Abstracts causative mutation of STPBX1 in a female with ohtahara syndrome causative mutation in CASK a male with a complex cerebral malformation and ohtahara syndrome (gene panel for malformations) causative mutation in SYT1 gene (WES) in a female with severe intellectual disability and atypical absences. Conclusion: Using NGS is becoming increasingly helpful in routine clinical practice. However, to correlate laboratory data and clinical observations is mandatory to guide the diagnostic approach and to establish treatments for the different EOEEs. Further studies are necessary to explore the potentially pathogenic role of VUS and to describe new correlations genotype-phenotype.

P291 CHANGE OF CYTOKINE LEVELS IN NEONATAL SEIZURES INDUCED BY HYPOXIC ISCHEMIC ENCEPHALOPATHY Lee IG, Youn Y, Yoon DH, Lee JE, Sung IK Pediatrics, Catholic University of Korea/Seoul St. Mary’s Hospital, Seoul, Korea Purpose: We investigated any change of cytokine levels in response to neonatal seizures induced by hypoxic ischemic encephalopathy (HIE) serially to assess any meaningful cytokine levels in relation to neonatal seizures with various parameters. Method: The HIE induced seizure group consisted of 13 patients, and another 15 normal newborns were enrolled as a control group. The initial samples in the seizure groups were obtained within the first 24 h of seizure onset, while the samples in the control group were obtained within the first 24 h of admission. The second samples were obtained between 48 and 72 h in both groups. The third samples were taken only in the seizure group on the 5th day of seizure onset. Results: During neonatal seizures, the levels of cytokines increased within 24 h and the levels of cytokines decreased after 48–72 h of seizure onset. Among the 10 interested cytokines, the levels of IL-8 significantly increased for 72 h in the seizure group (p < 0.05). IL-10 was not significant for the first 24 h, but increased significantly between 48 and 72 h of seizure onset (p < 0.05). Meanwhile, IL-1Ra decreased significantly in the 2nd sample (p < 0.05). Conclusion: Our findings suggest that serial examination of serum cytokine concentrations may serve as a biomarker for brain damage of neonatal seizure when detected within 72 h of the seizure.

P292 EVALUATION OF ETIOLOGY AND PROGNOSTIC FACTORS OF THE DEVELOPMENTAL OUTCOME IN NEONATAL SEIZURES Lee BL Pediatrics, Pusan Paik Hospital, Inje University College of Medicine, Busan, Korea Purpose: The purpose of this study was to investigate the clinical features of neonatal seizures and to identify prognostic factors of neurodevelopmental outcome in term infants who experienced clinical seizures. Methods: A retrospective analysis was performed on 153 full term and preterm infants with seizures from January 2008 to December 2013. Binary logistic regression analysis was applied to assess risk factors associated with neurological adverse outcomes using variables that were found to be significant on univariate analysis.

seizure was the focal clonic seizure, but the generalized tonic seizure was more common observed in preterm than in term infants. Totally 39 out of 56 term infants with at least 12 months of neurologic follow-up showed normal outcomes compared with only one preterm infant with normal development. Prognostic factors related to adverse neurodevelopmental outcomes in term infants were perinatal history of fetal distress, etiology of hypoxic ischemic encephalopathy, a moderately or severely abnormal EEG, evidence of hypoxic ischemic encephalopathy on brain magnetic resonance imaging and the need for multiple antiepileptic drugs for seizure control. Conclusion: Preterm infants showed poor neurodevelopmental outcomes compared with term infants. The etiology of seizures, treatment response, neuroimaging and electroencephalographic findings were important in predicting the developmental outcome in term infants with seizures.

P293 TOWARDS A COMPOSITE CLINICAL ENDPOINT: IDENTIFYING A CORE SET OF PATIENT AND CAREGIVER RELEVANT OUTCOME MEASURES THROUGH QUALITATIVE RESEARCH ON THE GLOBAL IMPACT OF DRAVET SYNDROME Nabbout R1, Auvin S2, Chiron C1, Irwin J3, Mistry A3, Williamson N4 1 Reference Center for Rare Epilepsies, Paris, France, 2Hopital Robert Debre, Paris, France, 3Zogenix International Ltd, Maidenhead, United Kingdom, 4Adelphi Values Ltd, Bollington, United Kingdom Purpose: The programme purpose is to identify a core set of patient and caregiver relevant outcome measures that can be used in clinical trials in Dravet Syndrome (DS). The first step was to explore the global impact of Dravet syndrome on children and their caregivers. Method: Qualitative interviews were conducted with those involved in the care of children (2–18 years) with DS in France. Seven caregivers, three pediatric neurologists with expertise in epilepsy and one nurse were interviewed using a semi-structured interview guide with open-ended questions. The interviews explored a range of concepts, including symptoms, triggers, coping strategies, and impacts on patients and caregivers. Interviews were conducted in French and transcribed and translated into English prior to qualitative analysis (thematic analysis) to identify key DS concepts. A conceptual model was developed based on evidence elicited from the interviews. A short list of potential endpoints was identified by expert consensus using a modified Delphi methodology. Results: The most commonly reported symptom was seizures. A range of impacts on children were identified including cognition (e.g. learning, expressive/receptive communication, attention, gross/fine motor function, emotional experience) and behaviour (e.g. emotional expression). Broader impacts on sleep, school, social and physical functioning were also found. Caregivers described a wider range of impacts on children with DS than clinicians. In addition, caregivers reported a range of impacts not reported by clinicians, including impacts on daily activities, physical, emotions, productivity, leisure and sleep. Caregivers highlighted the impact on their wider family including partners and other children and described home modifications. Conclusion: The impact of DS as experienced by patients and caregivers extends beyond the direct impact of seizures. If the benefit of therapeutic interventions is to be fully understood it is important that a range of patient relevant outcome measures are captured.

Results: During the study period, 102 term (66.7%) and 51 preterm infants (33.3%) were enrolled. The main cause of neonatal seizures was hypoxic ischemic encephalopathy (24.5%) in term infants and intracranial hemorrhage (74.5%) in preterm infants. The most common type of Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

96 Abstracts P295 MANAGEMENT OF SEIZURES SPECIFICALLY IN NEWBORN HYPOXIC ISCHAEMIC ENCEPHALOPATHY (HIE) – REVIEW OF THE LITERATURE AND RESULTS OF A QUESTIONNAIRE ON INTERNATIONAL PRACTICES- TIME FOR A FRESH VIEW? Stanley TV1, Wilkinson S2 1 Paediatrics, University of Otago Wellington, Wellington, New Zealand, 2University of Otago Wellington, Wellington, New Zealand Purpose: Seizures in HIE differ from other causes (a natural history of spontaneous cessation) and treatment is aimed at preventing possible acute seizure injury whilst preventing iatrogenic brain injury. We hoped to design an evidence-based protocol for this purpose using literature on the topic and surveying major centres in Australasia, USA and Europe regarding protocols used specifically for this purpose. Method: 1 Literature review from 1947; 2 email questionnaire to all level II/level III neonatal intensive care units (NICU) in Australasia, all NICU registered with the American Academy of Paediatrics and all centres registered with the European Society of Paediatric and Neonatal Intensive care as having a NICU. Units were asked a did they have a specific protocol for managing seizures in HIE and b if so, which anticonvulsants (AC) they would they prescribe, in which dose and in which order Results: The literature review revealed a startling lack of data, both in experimental animal models, or from comparative drug trials in human infants [one trial is at present under way in Australia/NZ]. Worrying data exists on the potential neurotoxicity of most ACs in common use (marked* below). Overall questionnaire response-rate was 45%.(NZ/ Australia 72% USA/Canada 34%, Europe 38%). 66% did not have a specific protocol for HIE. Those that had a specific protocol used firstline: phenobarbitone*92%, levetiracetam 4%, lorazepam* 4%. Secondline drugs were levetiracetam 25%, phenytoin* 25%, midazolam*25%, phosphenytoin* 17%. Those using a general “neonatal seizure” protocol chose first-line: phenobarbitone* 96%, levetiracetam 4%. Second-line: phenytoin* 45%, levetiracetam 30%, midazolam * 15%. There was a remarkable lack of consistency in loading dosages used (phenobarbitone 20–60 mg/kg, levetiracetam 10–60 mg/kg, phenytoin 10–40 mg/kg etc). Conclusion: There is an urgent need for evidence-based data on AC use in the asphyxiated newborn. This could first be accomplished with an animal model.

Epilepsy in Childhood 2 Monday 12th September P296 A NEW HOMOZYGOUS MUTATION ON NPC2 GENE: AS A CAUSE OF REFRACTORY EPILEPSY IN A CHILD Aydın K, Orgun LT, Arhan E, Akbas Y, Serdaroglu A Gazi University Medical Faculty, Ankara, Turkey Purpose: Niemann-Pick disease type C (NPD-C) is a rare disorder caused by impaired intracellular lipid transport due to mutations in either the NPC1 or the NPC2 gene. Mutations in the NPC1 gene can be identified in approximately 95 percent of NPD-C cases, while mutations in NPC2 account for approximately 4 percent. Ataxia, vertical supranuclear ophthalmoplegia, progressive dystonia, dysarthria, and dysphagia occur and approximately one-third of patients develop seizures. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Method: Case presentation. Results: 8 years old boy was admitted to our hospital complaints with the recurrent seizures to drug resistance for 6 months. On neurological evaluation, cognitive slowing, clumsiness, gait problems and vertical supranuclear gaze palsy were found. Brain MRI showed mild cerebellar atrophy and thin corpus callosum, and EEG showed focal epileptic discharges. Plasma chitotriosidase level was high, and NPC1 gene has no mutation. A new homozygous mutation, IVS3 + 6T>G(c.363 + 6T>G), on NPC2 gene was found, and miglustat was started. Conclusion: A much smaller number of patients suffer from NPC2 disease and present recurrent seizures to drug resistance as one of the most frequent symptom. Here, we present a case with a new homozygous mutation on NPC2 gene suffered from recurrent seizures to drug resistance.

P297 ANTIPHOSPHOLIPID ANTIBODIES IN CHILDREN WITH EPILEPSY Calcii C1, Revenco N2, Iliciuc I2, Hadjiu S2 1 Hospital of Mother and Child Health Care, Chisinau, Moldova, 2 Department of Child Neurology, Hospital of Mother and Child Health Care, Chisinau, Moldova Purpose: Increased prevalence of autoantibodies has been suggested in patients with epilepsy. The effectiveness of immunomodulatory treatments in cases with childhood epilepsies sugest the role of immune mechanisms in the pathogenesis of this desease. The purpose of this study was to determine antiphospholipid antibodies (aPLs, immunoglobulin G class), in children with epilepsy. Method: We studied 60 children (34 boys and 26 girls) with a mean age of 2.1 years (range 0.1–4.2 years).The control group consist of 70 healthy subjects, mean age was 2.4 years.The mean age of onset of epilepsy was 1.2 years (range 0.2–2.2). None of the children had any clinical signs of immune system disorders. The type of epilepsy was partial in 42 patients, primary generalized in 13 cases and unclassified in 5 patients. Results: In the study group, there were higher number (16cases) of aPLs immunoglobulin G class positive subjects (26.6%) compared with controls (4 cases-5.7%) (p = 0.011). These antibodies were common (77– 84%) in children with multiple seizure types associated often with symptomatic etiology, early onset and high frequency of seizures. Conclusion: Even though the significance of these autoantibodies remains unknown, their increased prevalence indicates that immune system mediated mechanisms may have a role in the manifestation of epilepsy in some children, especially in the subgroups of early-onset, highseizure-frequency, therapy-resistant epilepsies with multiple seizure types.

P298 GENETIC SYNDROMES IN CHILDREN WITH EPILEPTIC ENCEPHALOPATHIA Fomina M1,2 1 Neurology, Sanct-Petersburg State Pediatric Medical University, St-Petersburg, Russian Federation, 2SanctPetersburg State Pediatric Medical University, St-Petersburg, Russian Federation Purpose: For the 2015–2016 year in a rehabilitation center for children with developmental delays the study included 162 children who applied about the combination of a significant backlog in the development and epileptic seizures.

97 Abstracts Method: All patients underwent VideoEEG-monitoring, brain MRI and the clinical picture is characteristic if genetic testing (cytogenetic and molecular). Results: One female patient with normal development in the first year of life regression of skills and communicative functions has been celebrated since 12 months. In 3.5 years the debut of epileptic seizures (focal motor). On continued regional EEG epileptiform activity. Starting therapy with Depakine proved ineffective. On the basis of clinical data (deep damage to the expressive and impressive speech, gross psychomotor retardation, stereotyped hand movements, gait disturbance (apraxia and ataxia) aims to genetic test. The diagnosis of Rett syndrome confirmed (T158M MECP2 gene mutation) at the age of 4 years. The second patient0 s development was normal until 22 months. Then there was a stereotyped movements of the hands, gradual loss of speech and motor skills, ataxia. 4 years complex absence seizures. ANTIEPILEPTICS therapy without effect levetiracetam, lamotrigine with clinical and EEG improvement. Genetic testing confirmed the diagnosis (mutation T158M (473C>T) gene MECP2). Patient 3 is designed for rehabilitation regarding the violation of speech and motor functions, behavioural abnormalities (combination of causeless laughter, excitability, hypermotor behavior, reduced concentration). Craniofacial dimorphism. Epileptiform activity on EEG. With 2.5 years of epileptic seizures and prescribed levetiracetam. Revealed microdeletion of chromosome 15 (qll.2-ql3). Diagnosed with Angelman syndrome. Conclusion: Among group of children with behavioural abnormalities and epileptoform pattern on EEG/epileptic seuzires it is necessary to distinguish the genetically determined forms.

P299 SERUM TRACE ELEMENT LEVELS IN CHILDREN WITH EPILEPSY; AN OBSERVATIONAL STUDY Gulati S1, Singh Dogra A1, Chakrabarty B1, Tuteja GS2, K Paul V1, M Pandey R1 1 All India Institute of Medical Sciences, New Delhi, India, 2 Indian Council of Medical Research, New Delhi, India Purpose: Equilibrium of trace elements is essential for a healthy nervous system. They activate specific enzymes that act as anti-oxidants. Epileptic seizures result in free radical production and cellular oxidative damage. Increased production of free radicals leads to increased epileptogenicity. It can thus be postulated that epilepsy leads to altered physiological status of trace elements. The current study was planned to evaluate serum trace element status in children with epilepsy. Methods: The current study was conducted in a tertiary care teaching hospital in north India. Serum levels of selenium, copper, zinc and iron were done in 100 patients with epilepsy and 50 age and gender matched controls aged 2–12 years. Results: Serum zinc levels were not significantly decreased in patients with epilepsy as compared to controls (p = 0.13). Serum selenium levels were significantly decreased in patients with epilepsy as compared to controls (p = 0.0077). Serum copper levesl were significantly decreased in patients with epilepsy as compared to controls (p = 0.0026). Serum iron levels were not significantly decreased in patients with epilepsy as compared to controls (p = 0.44). Conclusion: The current study propose a crucial role for trace elements in the pathogenesis of epilepsy and mandate further research for role of trace element supplementation in epilepsy therapeutics. Clinical trials that compare the frequency of seizure and response to antiepileptic drugs pre- and post-administration of trace elements should be planned.

P300 HIPPOCAMPAL NEUROGENESIS AFTER SEIZURES: A ROLE IN DEVELOPMENT OF CHRONIC EPILEPSY Jain A, Mahdi AA King George Medical University, Lucknow, India Purpose: Altered hippocampal neurogenesis has emerged as one of the most important characteristics in temporal lobe epilepsy (TLE). It is particularly important to understand the role of proliferating cells on subsequent occurrence of seizures or development of chronic epilepsy. Considering this gap, the present work was designed to study how seizures influence cell proliferation and differentiation. Method: Kianic acid (KA) induced status epilepticus (SE) model and pentylene tetrazole (PTZ) induced kindling model in rats were used. After SE or kindling, neurodegenerative changes were studied by Nissel’s staining, fluorojade staining and TUNEL assay. Cell proliferation and differentiation were examined imuunohistochemically using antibodies against BrdU or GFAP (glial marker) or Calbindin (neuronal marker). Changes in GABAergic neurons, Nitrergic neurons, BDNF and NGF expression were also studied. Results: Observations of our study revealed that KA-induced SE resulted in significant neurodegeneration as compared to PTZ-induced kindling. Initial seizures were not the result of neurodegeneration, as seizures were observed in PTZ treated animals, but very few neurodegenerative cells were observed in them. Cell proliferation increased shortly after KA or PTZ treatment. Increased cell proliferation were result of seizures as significant increase in cell proliferation was seen in PTZ treated animals. Increased expression of nNOS, NGF and BDNF levels were observed. Higher rate of cell proliferation in kindled rats after 8 weeks of kindling may be due to hyper-excited state of neurons and establishment of a new ratio between excitatory and inhibitory neurotransmitters. Conclusion: Neuronal loss and ectopic gliogenesis could be the main cause of SRS, as SRS were observed only in KA treated rats which also showed significant increase in gliogenesis. The results allow us to understand and determine the factors involved in onset of seizures and development of chronic epilepsy. Study will also help to develop the strategies for prevention and treatment of epilepsy.

P301 EVALUATION OF COGNITIVE AND BEHAVIORAL FUNCTIONS IN CHILDREN OF EPILEPTIC MOTHERS Kishk N1, El-hasany A1, Madbouly N2, Nawito A3, Heniedy S1 1 Neurology, Cairo University, Cairo, Egypt, 2Psychiatry, Cairo University, Cairo, Egypt, 3Clinical Neurophysiology, Cairo University, Cairo, Egypt Purpose: We examined the effects of AEDs on cognitive development and behavioral characteristics among school age children born to epileptic mothers. Methods: 40 children born to 23 epileptic mothers with mean age 8.68 years 8.5 SD were studied. 40 healthy children born to 34 healthy mothers with matched age, sex and education level were recruited. All mothers underwent Wechsler test to measure IQ. All children underwent Stanford Binet test (fourth version) to measure IQ, child behavior checklist to detect behavioral abnormalities. Results: Children exposed to AEDs showed statistically significant difference in the verbal reasoning (p = 0.006), visual reasoning (p = 0.012) and total IQ (p = 0.002) compared to those children born to healthy mothers. There were significant correlations between children total IQ and maternal total IQ, polytherapy and valproate intake (more with dose > 800 mg/day). While no statistical significant difference was found in behavioral domains between children of epileptic mothers and children of healthy mothers. Using Multiple regression analysis, the most


98 Abstracts independent factor affecting children IQ was valproic acid use and maternal IQ . Conclusion: Valproate have a significant impact on children’s IQ exposed to it in utero therefore it is a poor first choice antiepileptic drug for most women of childbearing potential, also Maternal IQ contributes to affecting the child’s IQ . Keywords: Epilepsy, Pregnancy, Antiepileptic drug, Cognitive development, Behavioral development.

P302 ETIOLOGY OF CONVULSIVE AND NONCONVULSIVE SEIZURES IN PATIENTS WITH SEVERE TBI Krylov V1,2, Guekht A3, Lebedeva A4, Trifonov I1,2, Kaımovskiı I5, Talypov A1, Yakovlev A4, Kochetkova O1 1 Neurosurgery, N.V. Sklifosovsky Research Institute of Emergency Medicine, Moscow, Russian Federation, 2 Neurosurgery, Moscow State University of Medicine and Dentistry, Moscow, Russian Federation, 3Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russian Federation, 4Pirogov Russian National Research Medical University, Moscow, Russian Federation, 5Moscow City Hospital No. 12, Intensive Care, Moscow, Russian Federation Purpose: To evaluate the incidence of convulsive SE and nonconvulsive SE in patients with severe TBI. Method: In a consecutive cohort study, 24 traumatic brain injury patients were evaluated by EEG monitoring, MRI, CT, ICP meaning and followed for 3 months or until death. Results: Seizures were detected in 13 (54%) patients (9 patients with convulsive Sz, 2 with nonconvulsive Sz and 2 with SE). Convulsive Sz occurred immediately after TBI in 2 cases, within 7 days in 3 cases and after 7 days in 3 cases (12–70 days after TBI); 1 patient had early and late seizures. In patients with subdural hematomas (SDH), epidural hematomas (EDH), diffuse axonal injury (DAI) seizures occurred in about 50% of all cases. However, patients with multiple brain injury (MBI) were prone to seizures (80% of all cases with seizures, including 2 noncovulsive Sz). SE occurred in 2 patients: in 1 patient – convulsive SE and in 1 patient -were both convulsive SE and nonconvulsive SE. The mortality rate in all patients was 41% (10/24). Among patients who died, 7 (70%) were with Sz and SE. It was found that the level of consciousness at least 10 points on the GCS at admission increases the risk of late SE in a 47 times (p < 0.05). Increased intracranial pressure at 1 and 7 days from the time of injury, its value is higher than 20 mm Hg are a significant predictor of late EP (7 days from the time of injury) (p < 0.01). Conclusion: The pilot study demonstrate importance of detection convulsive Sz and nonconvulsive Sz, convulsive and nonconvulsive SE in patients with TBI and confirms the rather poor prognosis in TBI patients with Sz.

P303 A REFRACTORY EPILEPSY CASE WITH ICTAL ASYSTOLE Hirfano glu T1, Tekin Orgun L1, Serdao glu A1, C etin II2, 3 4 5 6 € € Ucar M , Akdemir O , Atay O , Aydın K , Arhan E6 1 Child Neurology, Gazi University Medicine Faculty, Ankara, Turkey, 2Pediatric Cardiology Department, Ankara Children’s Diseases Hematology Oncology Training Hospital, Ankara, Turkey, 3Radiology, Gazi University Medical Faculty, Ankara, Turkey, 4Nuclear Medicine, Gazi University Medical Faculty, Ankara, Turkey, 5Nuclear Medicine, Gazi University Medicine Faculty, Ankara, Turkey, 6Child Neurology, Gazi University Medical Faculty,Ankara, Turkey Purpose: Ictal bradycardia and asystole are rare forms of seizures and are supposed to be relevant to the pathogenesis of sudden unexpected death of epilepsy (SUDEP). Ictal asystole accompanies by patients with intractable temporal or frontal lob epilepsy which is related to autonomic nervous system. Ictal asystole is more rarely seen in childhood but it has vital importance. Here in we presented a child with intractable epilepsy and ictal asystole. Case: A10-year-old girl with intractable epilepsy was admitted to our video EEG video EEG unit. Cranial MRI was normal. Seizures, which have an onset of right frontal and parasagittal regions and secondary generalization were recorded. The patients had arrhythmia episodes during seizures. Patient0 s heart rate decreased to 35 beat/min and a few extrasystoles were found at the end of seizures. Rhythm Holter was performed and the patient0 s heart rate was found 15 beats/min with extrasystoles. Additionally she had an asystole duration of 3.8 sec while the seizure was occuring at night. Because of the persistent of interictal spike activity in the right frontal and parasagittal regions on EEG, her MRI was evaluated again. The focal cortical dysplasia (FCD) (closed lip schizencephaly) on right premotor cortex was seen and the localization was supported by PET. The vagal nerve stimulator (VNS) was implanted because she has the risk of SUDEP and her operation has a lot of permanent risks. Conclusion: Ictal asystole is one of the rare autonomic seizures, can frequently be emerged from both temporal and frontal lobes. We presented a child with ictal asystole who has significant risk for SUDEP. We aimed to emphasize that ECG recording during EEG is essential for detecting possible prognosis and importanat risks beyond the seizures.

P304 A RARE FORM OF SEIZURE: EPILEPTIC NYSTAGMUS glu A1, Tekin Orgun L1, Ucar M2, Hirfano glu T1, Serdaro € 3, Atay O € 3, Aydın K4, Arhan E1 Akdemir O 1 Child Neurology, Gazi University Medicine Faculty, Ankara, Turkey, 2Radiology, Gazi University Medicine Faculty, Ankara, Turkey, 3Nucleer Medicine, Gazi University Medicine Faculty, Ankara, Turkey, 4Child Neurology, Gazi University Medical Faculty, Ankara, Turkey Purpose: Epileptic nystagmus (EN) is a quick, repetitive jerky movement of the eyeball caused by seizure activity. EN originating from the cortical areas involved in the generation of eye movements. High-speed phase of nystagmus is valuable to detect localization which is mainly indicated to contralateral hemisphere. Case: A right-handed 13-year-old girl complained of horizontal nystagmus in both eyes for and small and large objects vision for last 2 years. She had denied any other additional symptoms. Seizures occured 10–15 times a day and lasting short time. The family medical history was not remarkable and her EEG and MRI were normal at that time. She was admitted to video EEG unit for differential diagnosis. Thithy nine ictal activity from both parieto-occipital regions were recorded at the same time during her clinical seizures which were characterized by epileptic


99 Abstracts nystagmus with preserved consciousness in both sleep and awake. The focal cortical dysplasia (FCD) was suspicious the posterior parieto occipital region when her previously cranial MRI reviewed again. Therefore, the new 3T MRI was taken. FCD was found in the left hemisphere occipital lobes. The localization was supported by hypometabolic are in the same region in the PET. Tractography was performed to evaluate relations of fasciculus. The patient has became seizure-free since carbamazepine was started. Conclusion: EN is a rare condition. The fast phase of the nystagmus is important for diagnosis of contralateral epileptogenic zone. When the etiology of the nystagmus at conscious patients is not known, epilepsy should consider when the seizure frequency is high and the nystagmus duration is short. Video EEG has an important role for differential diagnosis of nystagmus. Keywords: Epileptic nystagmus, EEG, cortical dysplasia.

Epilepsy in Childhood 3 Monday 12th September P309 CHARACTERISTICS OF POLISH PAEDIATRIC PATIENTS WITH EARLY AND LATE POST-STROKE SEIZURES Kopyta I1, Sarecka-Hujar B2 1 Department of Paediatrics and Developmental Age Neurology, Medical University of Silesia in Katowice, Katowice, Poland, 2 Department of Applied Pharmacy, Medical University of Silesia in Katowice, Sosnowiec, Poland Purpose: Seizures and epilepsy are the serious consequences of arterial ischemic stroke (AIS) both in adults and children but it occur more often in paediatric patients. AIS is considered as risk factor for status epilepticus in adults. Previous studies among children showed quite high prevalence of seizures and epilepsy occurring after AIS (from 26% in Netherlands to 65% in Brazilian population). The aim of the present study was to characterize Polish paediatric patients with early (up to 7 days after AIS onset) and late remote post-stroke seizures (between 7 days and 2 years after AIS onset). Method: The study population consisted of 20 children (white Polish Caucasians): 13 children having early post-seizures (mean age 7.61 5.35) and 7 children suffering with late remote pos-stroke seizures (mean age 2.71 2.36). Data were analyzed using STATISTICA 10.1 and EpiInfo 7 softwares. Results: In the group of patients with late remote seizures, the most common stroke subtype was TACI (71% vs. 39% in early post-stroke seizures group, p = 0.274). All of the participants with late remote seizures had FCA while in the subgroup with early seizures, 85% had FCA (p = 0.159). In two of the patients with late seizures antiphospholipid syndrome was found whereas in early seizures group none of the patients had APS (p = 0.042). Late remote seizures (mostly focal in nature) evolved into epilepsy in all of the participants and only three patients with early seizures (23%) developed epilepsy (p = 0.001). Analysed patients had different post-stroke neurological deficits. Only prevalence of intellectual delay differed both groups; 57% children with late remote seizures and 8% children with early seizures had intellectual delay (p = 0.015). Conclusion: Late remote seizures are predictors of post-stroke epilepsy in the Polish paediatric patients. Funded: 3PO5E 135 23, KNW-1-062/P/1/0 and KNW-1-065/09.

P310 CROHN’S DISEASE ASSOCIATED WITH FOCAL EPILEPSY AND NEUROIMAGING FINDINGS OF HIPPOCAMPAL SCLEROSIS AND CEREBRAL HEMIATROPHY Martin KC1, Paulo PAF1, Batista CEA1, Torres CM1, Duarte JA1, Bianchin MM1,2 1 Hospital de Clınicas de Porto Alegre, Porto Alegre, Brazil, 2 Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Purpose: Immunological abnormalities are emerging as important causes of epilepsy. Two examples are hippocampal sclerosis (HS) and Rasmussen’s encephalitis (RE). We present a case report of a patient with Crohn’s disease associated with HS and concomitant cerebral hemiatrophy. Case report: A 16 year-old female was diagnosed with Crohn’s disease in 2011. She was medicated with prednisone and mesalazine, without disease control. In 2014, she presented with episodes of sudden conscience impairment, without any aura, followed by staring and repetitive swallowing. Initially rare, these episodes became more frequent, occurring 3 times/month. Her family doctor began treatment with valproic acid, and later with topiramate, without seizure control. In 2015, she was referred to our service after first presentation of a focal motor seizure in right arm, with secondary generalization. She had normal neurological development, good performance at school and her neurological examination was normal. MRI showed left hemisphere atrophy with left hippocampal sclerosis. EEG showed left temporal slowing with rare spikes. Cerebrospinal fluid exam was normal. Epilepsy was controlled with carbamazepine. Azathioprine and adalimumab were initiated for Crohn’s disease. Discussion: This patient has focal seizures, temporal slowing on EEG, and hemispheric cortical and subcortical atrophy on MRI. Neuroimaging also showed HS. Cerebral hemiatrophy has been associated with prenatal and perinatal events, trauma, tumors, status epilepticus, infections and chronic inflammation, as is the case of RE. Some authors have reported an association of febrile seizures with HS and cerebral hemiatrophy. Crohn’s Disease has been associated with RE and temporal lobe epilepsy. We are tempted to suggest that HS and hemispheric atrophy might both be caused by immunological processes associated with Crohn’s disease. Conclusion: This case represents an interesting association of mesial temporal lobe epilepsy and hemispherical brain disease, both possibly mediated by common autoimmune mechanisms associated with Crohn0 s disease. Financial support: CNPq, FAPERGS.

P311 COMPARISON OF POLISH PAEDIATRIC PATIENTS WITH AND WITHOUT DIAGNOSED POST-STROKE EPILEPSY Sarecka-Hujar B1, Kopyta I2 1 Department of Applied Pharmacy, Medical University of Silesia, Sosnowiec, Poland, 2Department of Paediatrics and Developmental Age Neurology, Medical University of Silesia, Katowice, Poland Purpose: Arterial ischaemic stroke (AIS) occurs in approximately 3 per 100 000 children per year. Several neurological complications (e.g. motor impairment, speech impairment, seizures and intellectual delay) are the consequences of this disease. The prevalence of post-stroke epilepsy in quite high and has great impact on daily activity of little patients. The aim of the present study was to compare Polish paediatric patients suffering from AIS and post-stroke epilepsy with post-stroke epilepsyfree patients.


100 Abstracts Method: The study population consisted of 68 children (white Polish Caucasians): 10 patients with post-stroke epilepsy (mean age 3.50 2.55) and 58 children suffering with AIS but epilepsy-free (mean age 8.96 5.42). Data were analyzed using STATISTICA 10.1 and EpiInfo 7 softwares. Results: Focal cerebral arteriopathy (FCA) was observed in 90% of patients with post-stroke epilepsy and in 51% epilepsy-free patients (Relative risk 1.74 (1.26–2.40), p < 0.001). In seven of the participants poststroke epilepsy evolved from late remote seizures (occurring between 7 days and 2 years after AIS onset) and three of the patients had early post-stroke seizures (occurring up to 7 days after AIS onset). In 30% of post-stroke cases and in 14% of epilepsy-free patients heart diseases were observed (Relative risk 2.74 (0.69–6.83), p = 0.183). Conclusion: FCA is risk factor for post-stroke epilepsy in the Polish paediatric patients. Funded3PO5E 135 23, KNW-1-062/P/1/0 and KNW-1-065/09.

P313 INITIAL TREATMENT OF EPILEPTIC DISINTEGRATIVE DISORDERS IN CHILDREN Zaytsev D1, Titov N2, Zaytsev I1 1 Psychiatry, Zaytsev’s Psichoneurological Center, St.Petersburg, Russian Federation, 2Neurology, Zaytsev’s Psichoneurological Center, St.Petersburg, Russian Federation Purpose: Find a way to optimize the initial treatment of epileptic desintegrative disorders. Method: The study included 25 children (mean age 6 years 2 months). All children were divided into 2 groups according to age of onset of clinical manifestations of disintegration. Group I consisted of 9 persons (age 1–9 years old, the average age 5 years 1 month), Group II included 16 children (the average age of 6 years 10). Group I included children who had delayed development of motor and/or mental/speech skills detected at birth. The second group included children whose mental and speech retardation and/or motor skills was observed at the age of 1.5–2 years after the harmonious development of the previous period. All the children had examined by a psychiatrist-epileptologist, neurologist-epileptologist to assess the mental, speech and motor status; perfemed long term sleep EEG 1 time in half a year within 3–5 years. Results: All children initially had rolandic spikes of varying degrees and severity. After that initial treatment with carboanhydraze inhibitors administered. The dynamics in 8 of the 9 children of group I mentioned preserving bits of morphology as well as their migration was observed on the cerebral cortex, in spite of the mental and neurological improvement. In Group II, all 16 children mentioned reducing EEG abnormalities. In 8 of them noted a transient modification of complexes of rolandic spikes in spike-slow wave with their subsequent reduction. All children of group II, after the detection of non-specific EEG disturbances conducted combined therapy with Valproic acid and Lamotrigine. On the background of the therapy we noted improvement in motor and mental/speech status of all the children in both groups. Conclusion: Antiepileptic therapy of disintegtive disorders in children must be modified when morphology of underlying epileptic discharges changes.

Epilepsy in Childhood 4 Monday 12th September P358 EPILEPSY, CUTIS VERTICIS GYRATA, DYSPHAGIA, SEVERE INTELLECTUAL DISABILITY, AND OTHER FEATURES: A NEW EPILEPSY SYNDROME? Balestrini S1,2, Tortora G3,4, Schneider N1, Sisodiya S1 1 Clinical and Experimental Epilepsy, Institute of Neurology, UCL, London, United Kingdom, 2Neuroscience Department, Polytechnic University of Marche, Ancona, Italy, 3North West Thames Regional Genetics Service, North West London Hospitals NHS Trust, Harrow, United Kingdom, 4Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy Purpose: Cutis verticis gyrata (CVG) is a rare cutaneous disorder in which excessive growth of the scalp skin leads to the formation of furrows that resemble a cerebriform pattern and cannot be corrected by external pressure. Primary CVG is relatively rare. It is considered a genetic disorder and has been associated with various chromosomal and genetic abnormalities. We conducted a review of the literature on primary CVG and we report three unrelated cases with CVG as part of a novel complex syndrome. Method: Demographic and clinical information were gathered. Previous brain CT or MRI scans were reviewed, where available. ECG, EEG and video-EEG monitoring were performed. Results: We present three cases sharing a complex set of features including CVG, epilepsy, microcephaly, developmental delay, profound intellectual disability, quadriparesis, dysphagia, visual impairment, facial dysmorphism, and acral abnormalities. There was no evidence of any of the known causes for secondary CVG. Whilst our cases all have features of primary non-essential CVG, they also share additional unusual features. Conclusion: We postulate an underlying genetic condition in the three cases that we have reported here. Dysphagia is a common feature in our cases, and this has not previously reported in primary non-essential CVG cases, to our knowledge. This might be explained either by the severity of the phenotype with a low chance of long-term survival (i.e., without percutaneous endoscopic gastrostomy insertion), or might represent a new syndrome. Further genetic analysis is planned.

P315 ELECTROENCEPHALOGRAM REQUESTS IN PAEDIATRICS: ARE PAEDIATRICIANS FOLLOWING NICE (NATIONAL INSTITUTE OF CLINICAL EXCELLENCE) GUIDANCE? Glenday E, Killian L, Das K Young Epilepsy, Lingfield, United Kingdom Purpose: The diagnosis of epilepsy is made by accurate clinical history. The misuse of EEG is well documented historically. NICE (National Institute of Clinical Excellence) guidance gives clear guidance on the appropriate use of EEG. This study looks at the effectiveness of these guidelines on appropriate EEG use. Method: A retrospective audit over a 4 month period of EEG requests from a single District General Hospital in the United Kingdom. NICE guidance was used to assess appropriateness of EEG by 2 blinded raters, and the clinical usefulness of these results. Results: 40% of EEGs were requested inappropriately. 25% requestors requested EEGs to diagnose epilepsy. 70% of abnormal appropriately requested EEGs were clinically useful for diagnosis and management


101 Abstracts compared with 18% of abnormal inappropriately requested EEGs. There was fair but not strong agreement between the raters (k = 0.381). Conclusion: Following NICE guidelines on EEG use the amount of inappropriately requested EEGs has not decreased. Fewer EEGs are requested to diagnose epilepsy. Trained raters using guidelines do not strongly agree on appropriateness of EEG, highlighting the difficulty of requesting tests appropriately even with guidance. Careful use of guidance could reduce unnecessary EEGs with more useful results.

P316 ETIOLOGY AND CLINICAL CHARACTERISTICS OF SEIZURES IN THE FIRST YEAR OF LIFE TREATAD IN TERTIARY CENTER: A COHORT OF 127 INFANTS Kravljanac R1,2, Grkinic Jovanovic M2, Kovacevic G2, Ostojic S2, Vucetic B2 1 Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 2Neurology, Instutute for Mother and Child Healthcare, Belgrade, Serbia Purpose: Evaluation of etiology, clinical course and outcome of seizures in the first year of life in infants treated in Institute. Method: The retrospective study included infants aged 1–12 months hospitalized in Neurology Department of Institute due to convulsions in period from January 2012 to January 2016. The etiology was summarized in categories: idiopathic/cryptogenic, remote symptomatic, febrile SE, acute symptomatic and progressive encephalopathy. The type of seizure was classified as generalized including infantile spasms, and partial seizures. Duration was divided in four categories: 30 min. The same hospital protocol for acute seizure treatment was used in all cases. The outcome was defined by persistence of seizures after follow up period. Results: The study included 127 infants with mean age 5.2 months at the time of first seizures. Etiology was: cryptogenic in 40 (31.5%), acute symptomatic in 29 (22.8%) including 18 infants with acute infections, remote symptomatic in 9 (7.1%) febrile in 29 (22.8%) and progressive encephalopathy in 20 (15.7%). Duration of convulsions was 50/year, n = 26) PACS in the past year. In these subgroups, investigators reported learning disabilities in 67.3%, 89.9% and 84.6% of children, respectively; and impairment of typical day-to-day activities in 41.0%, 64.6% and 76.9%, respectively (n = 156, 99 and 26). For their most recent PACS, rescue medication was given at the seizure location to 70.6%, 78.2% and 60.9% of children with infrequent, frequent and very frequent PACS, respectively; an ambulance was called for 32.9%, 12.6% and 4.3%, respectively; and 35.7%, 14.9% and 4.3%, respectively, were admitted to hospital (n = 143, 87 and 23).


108 Abstracts Conclusion: Among children with epilepsy and prescribed rescue medication, children who often experienced PACS were less likely to use healthcare services following a seizure, but more likely to have learning disabilities and day-to-day impairments, compared with those who seldom experienced PACS. Study funded by ViroPharma (part of the Shire Group of Companies).

P344 TREATMENT OF PEDIATRIC INTRACTABLE EPILEPSY WITH VAPORIZED CANNABIDIOL (CBD) AND D9-TETRAHYDROCANNABINOL (THC)PRELIMINARY FINDINGS OF THE ISRAELI PEDIATRIC MEDICAL CANNABIS (MC) COHORT Linder I1, Tzadok M2, Menascu S3, Ben-Zeev B2, LermanSagie T1, Kramer U3 1 Pediatric Neurology Unit, Wolfson Medical Center, Sackler Faculty of Medicine Tel-Aviv,Holon, Israel, 2Pediatric Neurology, Sheba Medical Center, Ramat Gan, Israel, 3 Pediatric Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Purpose: Description of the clinical characteristics of twenty four Israeli pediatric patients with intractable epilepsy treated with vaporized Medical Cannabis. Method: CBD & THC treatment by mobile & immobile vaporizers was administered to epileptic patients fulfilling inclusion criteria. All patients were initially treated with 1:20 CBD:THC oil extract with a uniform gradual dosage increase. Patients eligible for vaporization either failed to respond to the target MC dosage, exhibited tolerance to it, presented with cluster seizures or with intense and abrupt seizures. Contra-indications (CI) were divided to absolute CI -any respiratory disease or hypersensitivity reaction to the oil extract of MC or relative CI such as a known cardio-vascular disease or family history of mental illness. Patients were considered responders if the seizure cluster abated or if the seizure burden decreased according to parental report. Results: Twenty four epileptic patients (16 male 8 female) with a diverse range of etiologies were treated with MC vaporization. Sixteen responded (two substantially, eight mildly and six shortened seizure clusters) while six had no response whatsoever. two patients had low compliance to treatment. Conclusion: Our preliminary findings regarding MC vaporization treatment for pediatric epileptic patients suggest a new and promising MC treatment modality, expanding the MC treatment options. Lack of uniformity in the treatment protocol, due to scarcity of relevant data, especially the immediate and long term effects of THC on the developing brain, render MC vaporization a promising -yet to be better defined option before implementing it as a routine treatment option for intractable epilepsy in the pediatric population.

P346 THE EXPERIENCE OF USING ZONEGRAN TO TREAT RESISTANT EPILEPSY IN CHILDREN OF EARLY PRESCHOOL AGE Perunova N Melbcal Centre ‘Alpha-Rythm’, Ekaterinburg, Russian Federation Purpose: Study the efficacy and tolerability of Zonegran as an adjuvant therapy for resistant epilepsy in children of 3–5 years of age. Method: 23 patients aged 3–5 years with resistant forms of epilepsy, including 9 girls and 14 boys, were monitored for 12–18 months. All Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

patients passed a neurological examination, magnetic resonance imaging, and repeated EEG-videomonitoring. Results: 7 patients had glial-cystic changes in the brain, 9 – periventricular leukomalacia, 3 – cerebral dysgenesis. Microdeletion syndromes were verified in 3 patients. 13 patients had uncontrolled focal epilepsy, with multifocal epilepsy observed in 4 patients and 6 patients having epileptic encephalopathies. Tonic seizures were observed in 10 patients, partial seizures – in 9 patients, polymorphic seizures – in 4 patients, and serial seizures and status epilepticus – in 8 patients. Zonegran was administered in doses of 6–8 mg/kg to 15 patients as a second drug and to 8 patients as a third drug. The most frequently used combination was that with valproates (12 observations) and levetiracetam (11 observations). 5 patients who demonstrated a good therapeutic effect and had adverse events during administration of topiramate were prescribed Zonegran, with topiramate discontinued. 21 patients (91%) continued therapy with Zonegran during the monitoring period. Adverse events were reported in 2 patients (2%), which included a moderate decrease of appetite and weight, and nausea. Remission was achieved in 4 patients (18%), and the frequency of seizure decreased by 75% in 4 patients and by 50% in 9 patients. Positive EEG dynamics were observed in 8 patients (38%). Conclusion: The administration of Zonegran to children aged 3–5 years with resistant epilepsy demonstrates an adequate efficacy and a good tolerability.

P347 SEIZURE DURATION WITH AND WITHOUT RESCUE MEDICATION IN A EUROPEAN STUDY OF CHILDREN WHO EXPERIENCE PROLONGED ACUTE CONVULSIVE SEIZURES Vigevano F1, Kirkham F2,3, Wilken B4, Raspall Chaure M5, Grebla R6, Lee D7, Werner-Kiechle T8, Lagae L9 1 Department of Neuroscience, Bambino Ges u Children’s Hospital, Rome, Italy, 2Department of Child Health, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, 3Institute of Child Health, University College London, London, United Kingdom, 4Neuropaediatrics, Klinikum Kassel, Kassel, Germany, 5Department of Paediatric Neurology, Vall d’Hebron University Hospital, Barcelona, Spain, 6Global Health Economics and Outcomes Research, Shire, Lexington, MA, United States, 7BresMed Health Solutions, Sheffield, United Kingdom, 8Global Medical Affairs, Shire, Zug, Switzerland, 9 Pediatric Neurology, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium Purpose: Rescue medication for prolonged acute convulsive seizures (PACS) is widely prescribed for community administration to children with epilepsy, despite limited evidence that it reduces seizure duration and prevents status epilepticus. Method: A cross-sectional study in four European countries enrolled non-institutionalized children with epilepsy (aged 3–16 years) who had experienced ≥ 1 PACS within the past 12 months and had currently prescribed PACS rescue medication(s). Web-based questionnaires asked parents/guardians how long on average each child’s PACS lasted without rescue medication and when rescue medication was given. Statistical tests were post hoc; p values are descriptive. Results: At study entry, most of the 286 enrolled patients had prescriptions for diazepam (69.2%) and/or midazolam (55.9%), and some had two (26.6%) or three (2.4%) prescribed rescue medications. According to parents (n = 258), average seizures lasted 0 to T) and intron 13 (2416-36A>C) were found in all subjects. These five variants are not pathogenic and represent two common haplotypes spanning a 14-kb region of linkage disequilibrium. Conclusion: Although, no candidate disorder allele was identified in the coding region of SCN1A, this study suggests that other regions of the gene, like, untranslated regions (UTRs) or other possible genes need to be investigated. Using more sensitive methods such as next-generation sequencing could be helpful in identifying the causative genetic factors for MTLE.

P387 NOVEL PHENOTYPIC- AND FUNCTIONAL ASPECTS OF HETEROZYGOUS DE NOVO MUTATIONS IN GRIN2B Platzer K1, Yuan H2, Traynelis S2, Lemke J1, GRIN2B Study Group 1 Institute of Human Genetics, University of Leipzig, Leipzig, Germany, 2Department of Pharmacology, Emory University School of Medicine Rollins Research Center, Atlanta, GA, United States N-methyl-D-aspartate receptors (NMDAR) are ligand-gated ion channels mediating excitatory neurotransmission via cation influx through the postsynaptic membrane. NMDAR are obligatory heterotetramers composed of two glycine-binding GluN1 and two glutamate-binding GluN2

121 Abstracts subunits, encoded by the genes GRIN1 and GRIN2A-D. Mutations in GRIN2B have been associated with intellectual disability, autism spectrum disorders and epilepsy. We identified 32 novel patients with heterozygous GRIN2B de novo mutations. Combined with 28 previously reported cases, we thus collectively review 60 patients and delineate the associated phenotypic spectrum. In addition to known and common symptoms, such as intellectual disability and epilepsy, we also revealed novel features comprising cortical visual impairment and movement disorders. Four patients presented with a striking MRI of a marked neuronal migration disorder. Inspired by an isolated report of successful precision medicine in GRIN2A-associated encephalopathy, we performed in vitro functional analysis for several GRIN2B mutations in Xenopus laevis oocytes followed by in vitro application of the NMDAR blocker memantine. Translating these results into clinics may have led to improvements of vigilance, behavior, sleep, EEG and development in the treated patients. In some patients these improvements were rather mild, and carefully controlled trials will be required to determine whether memantine is a useful treatment for these patients. The distribution of mutations, expansion and delineation of the phenotype, functional investigations and treatment responses observed in our study give a comprehensive insight into GRIN2B-associated encephalopathy.

P388 LOSS-OF-FUNCTION OF THE RETINOID-RELATED NUCLEAR RECEPTOR (RORB) GENE AND EPILEPSY Rudolf G1,2,3, Lesca G4,5,6, Mehrjouy MM7, Labalme A4, Salmi M8,9,10, Bache I7,11, Bruneau N8,9,10, Pendziwiat M12, Fluss J13, de Bellescize J14, Scholly J3, Møller RS15,16, Craiu D17, Tommerup N7, Valenti-Hirsch MP3, SchluthBolard C4,5,6, Sloan-Bena F18, Helbig KL19, Weckhuysen S20,21,22, Edery P4,5,6, Coulbaut S23, Abbas M23, Scheffer IE24, Tang S19, Myers CT25, Stamberger H20,22,26, Carvill GL25, Shinde DN19, Mefford HC27, Neagu E28, Huether R29, Lu H-M29, Dica A17, Cohen JS30, Iliescu C17, Pomeran C17, Rubenstein J30,31, Helbig I12,32, Sanlaville D4,5,6, Hirsch E1,2,3, Szepetowski P8,9,10 1 IGBMC, CNRS UMR7104, INSERM U964, Strasbourg University, Strasbourg, France, 2Federation of Translational Medicine, Strasbourg, France, 3Department of Neurology, Strasbourg University Hospital, France, 4Service de genetique, Hospices Civils de Lyon, Lyon, France, 5Universite Claude Bernard Lyon 1, Lyon, France, 6Lyon Neuroscience Research Centre, CNRS UMR5292, INSERM U1028, Lyon, France, 7 Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark, 8Inserm U901, Marseille, France, 9Aix-Marseille University, UMR S901, Marseille, France, 10Mediterranean Institute of Neurobiology (INMED), Marseille, France, 11Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 12Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany, 13Child and Adolescent Department, Geneva University Hospitals, Pediatric Neurology, Geneva, Switzerland, 14Epilepsy, Sleep and Pediatric Neurophysiology Department, Lyon University Hospitals, Lyon, France, 15Danish Epilepsy Centre, Dianalund, Denmark, 16Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark, 17Department of Clinical Neurosciences (No.6), Pediatric Neurology Clinic, “Carol Davila” University of Medicine Bucharest, Alexandru Obregia Hospital, Bucharest, Romania, 18Department of

Medical Genetics, University Hospitals of Geneva, Geneva, Switzerland, 19Division of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, United States, 20Department of Molecular Genetics, Neurogenetics Group, VIB, Antwerp, Belgium, 21 Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium, 22Division of Neurology, University Hospital Antwerp (UZA), Antwerp, Belgium, 23UCBPharma, Colombes, France, 24Florey Institute, University of Melbourne, Austin Health and Royal Children’s Hospital, Melbourne, VIC, Australia, 25Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seatle, WA, United States, 26Laboratory of Neurogenetics, Institute BornBunge, Antwerp, Belgium, 27Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, France, 28“Mina Minovici” National Institute of Forensic

Medicine, Human Genetics Laboratory, Bucharest, Romania, 29Department of Bioinformatics, Ambry Genetics, Aliso Viejo, CA, United States, 30Division of Neurogenetics, Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD, United States, 31 Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 32 Division of Neurology, The Children’s Hospital of Philadel-

phia, Philadelphia, PA, United States Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy (IGE) is the most common form of epilepsies and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic (EEG) pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the last few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta Retinoid-related orphan nuclear receptor (RORb), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Phe); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5–10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB, and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.

P389 NEXT GENERATION SEQUENCING IN RARE CHILDHOOD EPILEPSY OF SUSPECTED GENETIC ETIOLOGY Ragona F1, Salis B1, Freri E1, Piazza E1, Santi M2, Castellotti B2, DiFrancesco JC3, Canafoglia L4, Franceschetti S4, Gellera C2, Granata T1 1 Pediatric Neuroscience, I.R.C.C.S Foundation, Neurological Institute C. Besta, Milan, Italy, 2Genetics of Neurodegenerative and Metabolic Diseases Unit, I.R.C.C.S Foundation, Neurological Institute C. Besta, Milan, Italy, 3San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy, 4Clinical


122 Abstracts Neurophysiology and Epilepsy Center, I.R.C.C.S. Foundation Neurological Institute C. Besta, Milan, Italy

of homozygous carriers of low-producing allelic variant 511TT/ 3954TT (5/62) were more common in girls (3/5) (p > 0.05).

Purpose: To identify, by next generation sequencing, potentially causative genetic variants in a selected group of patients with rare childhood epilepsies.

Conclusion: Our analysis of the etiological deciphering the molecular genetic study confirms the feasibility of a personalized approach for the management of children with development of FS. Work is carried out with financial support of “Krasnoyarsk Regional Fund of Support of Scientific and Scientific and Technical Activity” a grant №03/15 of 12.05.2015.

Method: A panel targeting known epilepsy genes was developed for next generation sequencing by a team composed by clinicians, neurophysiologists and geneticists. We selected 55 patients affected by epileptic encephalopathy (32 patients), generalized epilepsy (11 patients) and focal epilepsy (12 patients), who had been already investigated by cytogenetic and single gene analysis.The DNA of 37 patients was analyzed by TruSeq Custom Amplicon (Illumina), which included 57 genes. Then, the team designed a new panel which included 93 genes to be analyzed by Nextera Rapid Capture; 21 patients underwent the new panel. Results: Pathogenic variants were found in 4 out of 37 patients, analysed by TruSeq. All patients were affected by severe epileptic encephalopathy. The causative genes were CDKL5 (two cases), FOXG1 and KCNQ3. Nextera has identified 49 variants, that were compared with literature data, discussed with clinicians and analyzed by segregation analysis and in silico studies. In 5 out of the 21 patients (24%) pathogenic mutations were identified in the following genes: GABRB3 in a patient with myoclonic epilepsy and in a patient with generalized epilepsy and cortical myoclonus, SCN1A, associated with a SCN2A mutation, in a patient with Dravet syndrome, TBC1D24 in a patient with focal epilepsy, cortical myoclonus, and recurrent plegic attacks, and SLC2A1 in a patient with focal epilepsy and periventricular heterotopia. Conclusion: In our selected cohort of patients, the diagnostic rate of next generation sequencing using TruSeq and Nextera, was 11% and 24%, respectively. These data confirm the role of these new techniques in the diagnostic workup of childhood epilepsy, highlighting that a discussion between clinicians and geneticists is crucial in evaluating and reading into new genetic results.

P390 GENE IL-1B POLYMORPHISM AND RECURRENT FEBRILE SEIZURES AT CHILDREN Stroganova M, Shnaider N, Martynova G, Dmitrenko D, Diuzhakova A Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk, Russian Federation Purpose: To investigate the frequency of carriers of the gene IL1-B polymorphisms in children with recurrent febrile seizures (FS) as a risk factor for recurrence of the disease. Method: We observed 62 patients with FS in the Krasnoyarsk Inter-District Children0 s Hospital №1 (10/2013–02/2014). In addition to the routine laboratory techniques, we performed molecular biological research on the carriage of polymorphic allelic variants of IL-1B gene. The identification of carriers for polymorphic allelic variants of the gene IL-1B (511C>T, 3954C>T) on chromosome 2q13-q21 was done by real time PCR. Results: It was determined by real time PCR that 27.4% of patients (17/ 62) are carriers of the association of homozygous genotypes in two highproducing allelic variants of the gene IL-1B (511CC/3954CC), and the frequency of corresponding association in boys was higher (53%; 9/17) than in girls (47%; 8/17). It is also noted, that in this group of patients repeated cases of FS were the most frequent (47%). Association 511CC/3954CT was observed in 24.2% of cases (15/62) and was statistically significant higher in boys (73.3%; 11/15, p < 0.05). The frequency of 511CT/3954CC and 511CT/3954CT associations constituted to 21% (13/62) and 16.1% (10/62), respectively, and was statistically significant in boys (p < 0.05). At the same time, the frequency


Genetics 4 Wednesday 14th September P391 SYSTEMATIC RECRUITMENT AND ANALYSIS OF EPILEPSY FAMILIES IN PALESTINE Abu-Rayyn A1, Afawi Z2, Canavati C1, Pendziwiat M3, Helbig I3,4,5, Klein KM6,7, Kanaan M1, on behalf of the IsraeliPalestinian Epilepsy Family Consortium 1 Hereditary Research Lab, Bethlehem University, Bethlehem, Palestine, 2Tel Aviv University Medical School, Ramat Aviv, Israel, 3Department of Neuropediatrics, Christian-AlbrechtsUniversity of Kiel, Kiel, Germany, 4Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States, 5Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel, 6Epilepsy Center Frankfurt RhineMain, Goethe-University Frankfurt, Frankfurt, Germany, 7 Epilepsy Center Hessen, Philipps-University Marburg, Marburg, Germany Purpose: Multiplex families provide an excellent opportunity for the identification of genes of major effect and are particularly frequent in founder populations with a high degree of consanguinity. Here, we present our recruitment and analysis pipeline of epilepsy families in Palestine and report the first Palestinian family with benign familial neonatal seizures (BFNS). Individuals with BFNS typically develop multiple seizures per day between the second and eighth day of life followed by remission within 1 year. Method: Multiplex families with epilepsy in Palestine are recruited by referral from neurologists, pediatricians and general practitioners. The families are phenotyped and a hypothesis on the possible mode of inheritance is devised. Families are analyzed by homozygosity mapping, linkage analysis, exome sequencing and candidate gene approach as appropriate. Results: Ten multiplex families with 3–10 affected individuals were ascertained. Three families had focal epilepsy, two genetic generalized epilepsy, two genetic epilepsy with febrile seizures plus, one BFNS and two showed mixed phenotypes. The BFNS family consisted of two affected siblings resulting from a consanguineous marriage between the affected father and the unaffected mother. Sequencing analysis of the candidate gene KCNQ2 revealed a IVS2-1 (C to T) splice site mutation which segregated in the affected family members. The mutation was absent among 500 Palestinian normal controls and bioinformatics evaluation of the mutation showed that it is a damaging mutation. Molecular analysis of the other families is ongoing. Conclusion: The analysis of multiplex families in the Palestinian population with a high degree of consanguinity is a rich source for the identification of epilepsy genes. Systematic recruitment of such families will likely result in new gene discoveries.

123 Abstracts P392 NTRK2, THE TKRB GENE, IS ASSOCIATED WITH MOOD DISORDERS IN TEMPORAL LOBE EPILEPSY Bianchin MM, Torres CM, Siebert M, Bock H, Martin K, Mota SM, Saraiva-Pereira ML Universidade Federal do Rio Grande do Sul, Laboratory BRAIN/HCPA., Porto Alegre, Brazil Purpose: Psychiatric comorbidities are very prevalent in epilepsy, adding important burden to the disease and profoundly affecting quality of life in these individuals. Patients with temporal lobe epilepsy (TLE) are especially at risk to develop depression and diverse evidences suggest that the association of depression with epilepsy might be related to common biological substrates. In this study we test if NTRK2 allele variants are associated with mood disorders or depression in patients with temporal lobe epilepsy. Methods: Association study of 163 patients with TLE of the Epilepsy Outpatient Clinic of Hospital de Clınicas de Porto Alegre (HCPA). NTRK2 allele variants studied were rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. All patients were submitted to the Structured Clinical Interview for DSM-IV (SCID) and patients with mood disorders were compared with patients without these comorbidities. Results: In our TLE cohort, seventy six patients (46.6%) showed mood disorders. Female sex, anxiety disorders, and A/A genotype in rs1867283 NTRK2, and C/C genotype in the rs10868235 NTRK2 gene were all independently associated with mood disorders in these patients. Depressive disorders mostly accounted for these results. After logistic regression, independent risk factors for depressive disorder in TLE were female sex (OR = 2.54; 95%CI = 1.18–5.47; p = 0.017), presence of concomitant anxiety disorders (OR = 3.30; 95%CI = 1.58–6.68; p = 0.001), A/A genotype in rs1867283 NTRK2 (OR = 2.84; 95%CI = 1.19–6.80; p = 0.019), and C/C genotype in rs10868235 NTRK2 gene (OR = 2.74; 1.28–5.88; p = 0.010). Conclusion: Female sex, anxiety disorders, and allelic variations in NTRK2 gene were all independent risk factors for mood disorder or depressive disorders in TLE. If our results were confirmed, NTRK2 gene allele variants could be used as a biomarker for depressive disorders in patients with temporal lobe epilepsy. Work supported by HCPA/FIPE, FAPERGS and CNPq.

P393 SINGLE NUCLEOTIDE POLYMORPHISMS OF ANTIOXIDANT ENZYMES IN PROGRESSIVE MYOCLONUS EPILEPSY Ercegovac M1, Jovic N2, Sokic D1, Simic T3, Savic-Radojevic A3, Coric V3, Smiljic J4, Nikolic D5, Kecmanovic M6, PljesaErcegovac M3 1 Clinic of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 2Clinic of Neurology and Psychiatry for Children and Youth, Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 3Faculty of Medicine, Institute of Medical and Clinical Biochemistry, University of Belgrade, Belgrade, Serbia, 4Institute of Medical and Clinical Biochemistry, Belgrade, Serbia, 5Faculty of Medicine, University of Belgrade, University Childrens Hospital, Belgrade, Serbia, 6Faculty of Biology, University of Belgrade, Belgrade, Serbia Purpose: It has been shown that activities of the key antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPX), are upregulated in patients with progressive myoclonus epilepsy (PME). The question that arises is whether this increase represents a

compensatory mechanism to increased reactive oxygen species production, or might be a consequence of genetic polymorphism in antioxidant enzymes, resulting in altered enzyme activity, which might modulate individual tendency towards PME development. In order to elucidate in which way polymorphic expression of antioxidant enzymes contributes to oxidative phenotype in patients with PME, we determined SOD2 and GPX1 single nucleotide polymorphisms in these patients. Method: Genomic DNA was isolated from 29 patients with PME (Unverricht-Lundborg disease, Lafora body diesease, Myoclonic Epilepsy with Ragged Red Fibers and late infantile neuronal ceroid lipofuscinosis) and 120 matched controls. Genetic polymorphism of SOD2 was determined by qPCR assay, while GPX1 polymorphism was determined by PCR-RFLP method. Results: Examined SOD2 rs5746136 polymorphism results from an A>G substitution. We found that 6% of PME patients were carriers of A/ A, 71% of A/G and 23% of G/G genotype compared to 23% of A/A, 47% of A/G and 30% of G/G genotype in control subjects (p < 0.001). Regarding examined GPX1 rs1050450 single nucleotide polymorphism, which is a consequence of C>T mutation, changing proline to leucine at position 197, the frequencies were 60% of C/C, 24% of C/T and 16% of T/T genotype in patients with PME in comparison to frequencies found in healthy population of 48%, 42% and 10%, respectively (p = 0.022). Conclusion: Based on our preliminary results, it can be concluded that certain changes in expression profiles of SOD2 and GPX1 exist in patients with PME, possibly affecting their ability to mount antioxidant defense mechanisms.

P394 THE PHENOTYPIC SPECTRUM OF THE RECURRENT SCN2A R1319Q MUTATION Helbig I1,2,3, Johannesen KM4,5, Pendziwiat M1, Bissan H6, Kivity S7, Lemke JR8, Riesch E9,10,11, Kanaan M12, Afawi Z13, Klein KM14,15, Møller RS4,5, on behalf of the Israeli-Palestinian Epilepsy Family Consortium 1 Department of Neuropediatrics, University of SchleswigHolstein Medical Center, Kiel, Germany, 2Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States, 3Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel, 4Danish Epilepsy Centre, Dianalund, Denmark, 5Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark, 6 Tel Aviv Sourasky Medical Center, The Institute for Child Development and Pediatric Neurology Unit, Tel Aviv, Israel, 7 Epilepsy Unit, Schneider Children’s Medical Center of Israel, Petach Tikvah, Israel, 8Department of Diagnostics, Institute of Human Genetics, University of Leipzig, Leipzig, Germany, 9 Center for Genomics and Transcriptomics (CeGaT), T€ ubingen, Germany, 10Division of Human Genetics, University Children’s Hospital Inselspital, Bern, Switzerland, 11Swiss Epilepsy Center, Z€ urich, Switzerland, 12Hereditary Research Lab, Bethlehem University, Bethlehem, Palestine, 13Tel Aviv University Medical School, Ramat Aviv, Israel, 14Epilepsy Center Frankfurt RhineMain, Goethe-University Frankfurt, Frankfurt, Germany, 15 Epilepsy Center Hessen, Philipps-University Marburg, Marburg, Germany Purpose: Mutations in the SCN2A gene have been identified in various genetic epilepsies including benign familial epilepsies and sporadic epileptic encephalopathies. However, in contrast to an constantly emerging spectrum of SCN2A variants identified in sporadic epileptic encephalopathies, our knowledge with regards to variants in familial epilepsies is Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

124 Abstracts limited. To further explore the phenotypic spectrum of familial SCN2A variants, we examined the clinical presentation of families with an R1319Q mutation in the SCN2A gene. Method: We reviewed data from the Israeli-Palestinian Epilepsy Family Consortium and the Danish Epilepsy Center for patients with SCN2A R1319Q mutations as well as data from published families with this variant. In patients with identified mutations, we assessed parental segregation and reviewed the phenotypes of mutation carriers and other affected family members. Results: We identified two Israeli families with R1319Q SCN2A mutations. One family (#14) had three affected mutation carriers with benign neonatal seizures inherited in a dominant fashion. The family was negative for mutations in KCNQ2 or KCNQ3. A second family (#16) had two affected boys. A boy with benign infantile seizures carried a R1319Q SCN2A de novo mutation, while his brother with benign myoclonic epilepsy of infancy did not carry the mutation. We identified one additional sporadic patient with early infantile epileptic encephalopathy. A further patient with a R1319W mutation had West Syndrome evolving to Lennox-Gastaut Syndrome. Review of the literature identified one family with three individuals with Benign Familial-Infantile Seizures. Conclusion: The phenotypic spectrum of the SCN2A R1319Q mutation includes mild infantile epilepsies, but has also been observed in a patient with epileptic encephalopathy, resulting in an unexpectedly broad phenotypic range. SCN2A R1319Q represents a rare example of an epilepsyrelated variant that is found to be inherited in familial cases and de novo in sporadic cases.

P395 PURA MUTATIONS: INTELLECTUAL DISABILITY WITH SEIZURES OR EPILEPTIC ENCEPHALOPATHY? Hjalgrim H1, Johannesen K1, Rubboli G2, Møller R1, Helbig I3, Helbig K4, Ortiz-Gonzalez X3, Brandsema J3, Dubbs H3, Radtke K4, Brilstra E5, Tang S6, Grebe T7, Isidor B8, Smith W9, Bick D10 1 Danish Epilepsy Center, Filadelfia/University of Southern Denmark, Dianalund, Denmark, 2Danish Epilepsy Center, Filadelfia/University of Copenhagen, Dianalund, Denmark, 3 Childrens Hospital, Philadelphia, PA, United States, 4Ambry Genetics, Aliso Viejo, CA, United States, 5University Medical Center, Utrecht, The Netherlands, 6Ambry Genetics, Aliso Viejo, PA, United States, 7Childrens Hospital, Phoenix, AZ, United States, 8Centre Hospitalier Universitaire de Nantes, Nantes, France, 9Barbara Bush Childrens Hospital, Portland, ME, United States, 10Childrens Hospital, Milwaukee, WI, United States Purpose: Neurodevelopmental disorders including epileptic encephalopathy are common, but the etiology is unknown in a significant number of patients. Recently, two studies identified de novo PURA alterations in patients with similar clinical presentations. The majority of these patients presented with neonatal hypotonia, feeding difficulty, and respiratory distress, as well as significant developmental delay. Several patients had clinically confirmed seizures. Some patients also had dysmorphic features including a tall, narrow forehead, narrow palate with tented mouth, and micrognathia. We aimed to further investigate the phenotype, especially regarding seizures and epilepsy. Method: Patients were recruited from genetic and epilepsy clinics in USA and Europe. A standardized phenotyping sheet was provided for the treating clinicians, we collected data on neuroimaging, clinical- and neurophysiological features.


Results: A total of 13 new cases were identified, thereby doubling the known number of PURA patients. Six cases had confirmed seizures, with varying seizure types, including tonic seizures (three patients) and myoclonic seizures (three patients). Ten patients were described with dysmorphic features, typically an elongated and hypotonic face. Neonatally, ten patients had severe hypotonia, seven had feeding problems and seven had respiratory issues. All 13 patients have severe intellectual disability, and no spoken language. Conclusion: We confirm the phenotypic spectrum that has previously been described. PURA patients typically have severe intellectual disability, without spoken language. The neonatal period can be complicated by hypotonia. Dysmorphic features are common. Approximately half of the patients will have seizures, but the semiology and severity is variable. In conclusion, intellectual disability and neonatal hypotonia are constant features in PURA, where as seizures patterns vary between patients.

P396 TARGETED NEXT GENERATION SEQUENCING AS A DIAGNOSTIC TOOL IN 230 PATIENTS WITH EPILEPTIC ENCEPHALOPATHIES Larsen LHG1, Dahl HA1, Olofsson K2, Miranda M3, Nielsen JEK4, Jensen UB5, Petersen MB6, Hao Q1, Lavard L7, Linnet K8, Uldall P2,9, Talvik T10, Talvik I10, Frangu M11, Born AP12, Gellert P2, Nikanorova M2,13, Jepsen B2, Marjanovic D2, Kragh-Olsen B14, Brusgaard K1, Pal D15, Hjalgrim H2,13, Møller R2,13 1 Amplexa Genetics, Odense, Denmark, 2Danish Epilepsy Centre, Dianalund, Denmark, 3Department of Pediatrics, Herlev University Hospital, Herlev, Denmark, 4Section of Gynaecology, Obstetrics and Pediatrics, Department of Clinical Medicine, Roskilde Hospital, Roskilde, Denmark, 5Aarhus Universitetshospital, Klinisk Genetisk Afdeling, Aarhus, Denmark, 6Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark, 7Hvidovre Hospital, Børneafdelingen, Hvidovre, Denmark, 8Aarhus Universitetshospital, Børneafdelingen, Aarhus, Denmark, 9 Pediatric Clinic, Copenhagen University Hospital, Copenhagen, Denmark, 10Childrens Clinic, Tartu University Hospital, Tartu, Estonia, 11Department of Pediatrics, Holbæk Hospital, Holbæk, Denmark, 12Department of Pediatrics, Copenhagen University Hospital, Copenhagen, Denmark, 13 Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark, 14Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark, 15Department of Basic and Clinical Neuroscience, King’s College London, London, United Kingdom Purpose: Epilepsy is one of the most common neurological disorders, and is known to have a very heterogeneous background with a strong genetic contribution. In recent years several genes have been associated with epilepsy. However, making a genetic diagnosis in a patient can still be challenging as there is both genetic heterogeneity for a given epilepsy syndrome and phenotypic heterogeneity for a specific gene. The aim of this study was to develop a diagnostic screening method to analyze the genetic basis of childhood epilepsies. Method: A gene panel targeting 85 known epilepsy genes was developed for next generation sequencing. Potentially causative variants were evaluated by literature and database searches and submitted to bioinformatic prediction algorithms. Variants were verified by Sanger sequencing and parents were included for segregation analysis when possible. We used this panel on an unselected cohort of 230 patients, sequentially

125 Abstracts referred for panel testing. The majority of the patients had a range of epileptic encephalopathies or childhood epilepsies. Results: We identified a presumed disease-causing mutation in 45 of 230 patients and a variation of unknown significance in additional 16 patients. The aberrations encompassed known and unknown point mutations in several different genes. In only a few genes pathogenic variations were observed in more than one patient, such as SCN1A (7), GRIN2A (2), KCNQ2 (2), SCN2A (2) and STXBP1 (2). Genes with only one hit included e.g. PIGA, PURA, ATP1A2, HNRNPU and STX1B. All mutations were confirmed by conventional Sanger sequencing and, when possible, validated by parental testing and segregation analysis. Conclusion: We have developed a rapid and cost-efficient screening panel for the analysis of the genetic basis of childhood epilepsies. With this panel we were able to find a disease-causing genetic variation in 20% of the analyzed patients.

P397 THE PHENOTYPIC SPECTRUM OF A FAMILIAL GRIN2A TRUNCATION MUTATION Muhle H1, Boor R1, Walther B2, Pendziwiat M1, J€ahn J1, von Spiczak S1,3, Stephani U1, Helbig I1,4 1 Department of Neuropediatrics, University of SchleswigHolstein Medical Center, Kiel, Germany, 2Department of Child and Adolescent Psychiatry, HELIOS Klinikum Schleswig, Schleswig, Germany, 3Northern German Epilepsy Center for Children and Adolescents, Schwentinental-Raisdorf, Germany, 4 Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, United States Purpose: Mutations in GRIN2A are known causes of epilepsy aphasia syndromes and related conditions. In some cases, the mutations are transmitted within families and result in a range of phenotypic features. We describe the phenotypic spectrum of a family with three affected boys carrying a truncation GRIN2A mutation. Method: A novel GRIN2A c.594G>A (p.W198X, hg19: chr16: 10032229) mutation was initially identified in the index patient. We performed segregation analysis of the GRIN2A variant in two affected brothers of the proband and reviewed the phenotypes including neuroimaging and serial routine EEG recordings. Parents were not available for segregation testing or phenotyping. Results: All three siblings had epilepsies within the epilepsy aphasia spectrum including atypical benign partial epilepsy (Pseudo-Lennox Syndrome) in sib 1, and single rolandic seizures in sibs 2–3. All brothers had developmental delay and speech apraxia, often with orofacial hypotonia. EEG recording demonstrated frequent centro-temporal spikes that responded intermittently to therapy with sulthiame and ethosuximide. Neuroimaging was unremarkable in sibs 1–2. The youngest brother had hypoplasia of corpus callosum and a midline lipoma. Conclusion: We describe the familial spectrum of a truncation mutation in GRIN2A, confirming that GRIN2A phenotypes have a strong propensity toward epilepsy aphasia syndromes. We also highlight the prominence of developmental delay, speech apraxia and the characteristic EEG features, suggesting that in addition to epileptic seizures these features may be constant clinical features in GRIN2A encephalopathy.

P398 SYSTEMATIC LARGE SCALE GENOME-WIDE ANALYSIS OF CNVS IN PATIENTS WITH “EPILEPSY PLUS” Stamberger H1,2,3, Coppola A4,5,6, Djemie T1,2, Cellini E7, Cetica V7, Mefford H8, Guerrini R7, De Jonghe P1,2,3, Lal D9,10,11, Sisodiya S5,6, Marini C12 1 Department of Molecular Genetics, VIB, Antwerp, Belgium, 2 Institute Born-Bunge, Laboratory of Neurogenetics, Antwerp, Belgium, 3Department of Neurology, Antwerp University Hospital, Antwerp, Belgium, 4Department of Neuroscience, Reproductive and Odontostomatological Sciences, Epilepsy Centre, Federico II University, Naples, Italy, 5Department of Clinical and Experimental Epilepsy, NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, London, United Kingdom, 6The Epilepsy Society, Chalfont-St-Peter, United Kingdom, 7Meyer Children’s Hospital, Neurology Unit and Neurogenetic Laboratories, Florence, Italy, 8Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, United States, 9Center for Genomics (CCG), University of Cologne, Cologne, Germany, 10Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, 11Stanley Center for Psychiatric Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, United States, 12Neurology Unit and Neurogenetic Laboratories, Meyer Children’s Hospital, Florence, Italy Purpose: Copy number variations (CNVs) are an important risk factor for epilepsy in particular when comorbid with intellectual disability. In this study we aimed to unravel the role and frequency of CNVs across the whole genome and to discover novel disease loci and genes in a group of patients with epilepsy plus. Method: We assembled a cohort of 1,258 patients for whom pre-existing array-CGH or single nucleotide polymorphism array (SNP) CNV data were available. All patients had “epilepsy plus,” defined as epilepsy and at least one additional feature, e.g. intellectual disability or dysmorphism. Classification was conducted through a systematic filtering procedure specifically adapted to the epilepsy phenotype and taking into account established guidelines, literature, gene content and inheritance. Results: Out of 1,105 patients that remained after data quality control, 25.7% carried at least one CNV classified as pathogenic and 6.3% carried a duplication or deletion >3 Mb. Approximately 3% carried microdeletions in known loci. Seven percent had a pathogenic duplication or deletion not located in known, pathogenic, CNV loci. Our preliminary results show new recurrent (possibly) pathogenic deletions and duplications and point to epilepsy candidate genes including HNRNPU and RORB. Conclusion: CNV analysis is a valuable diagnostic tool in patients with epilepsy and can lead to the identification of explanatory or novel loci and candidate genes underlying neurodevelopmental disorders including epilepsy. Our identification of rare, disease-associated CNVs underscores the importance of large datasets: collaboration should be seen as the start of an international consortium for CNVs in epilepsy (EpiCNV) in which data sharing on a large scale becomes an important new tool for gene identification.


126 Abstracts P399 VARIABLE PHENOTYPES IN INDIVIDUALS WITH GRIN2A SEQUENCE VARIANTS OR DELETIONS Vlaskamp DRM1, Callenbach PMC1, Rump P1, van PinxterenNagler E2, Willemsen MH3, Gunning B4, de Geus C1, VeenstraKnol HE1, Lunsing RJ1, Dijkhuizen T1, Vos YJ1, Brouwer OF1, van Ravenswaaij-Arts CMA1 1 University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, 2Medical Center Leeuwarden, Leeuwarden, The Netherlands, 3University of Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands, 4Stichting Epilepsie Instellingen Nederland, Zwolle, The Netherlands Purpose: The GRIN2A gene has been associated with epilepsies ranging from benign focal childhood epilepsies to severe epileptic encephalopathies. The aim of this study was to evaluate genotypes and phenotypes in individuals with GRIN2A deletions or variants. Method: We compared genotypes and phenotypes in six newly identified patients with GRIN2A variants with those of 149 individuals with GRIN2A variants from the literature. Results: Six new patients with epilepsy, developmental and/or behavioral problems and GRIN2A deletions (n = 3), missense (n = 2) or splice-site variants (n = 1) are presented. In 125 (84%) of the 149 individuals with GRIN2A variants previously reported, a specific epilepsy syndrome was diagnosed, most often classified as Benign Epilepsy with Centro-Temporal Spikes (BECTS; n = 44) or Landau-Kleffner syndrome/Continuous Spike-and-Waves during Slow-wave sleep (LKS/ CSWS; n = 42). Problems of speech and language development (81%), cognition (68%), motor skills (50%) or behavior (42%) were common. Missense variants were seen in 52% of the patients reported earlier, more often in individuals with BECTS (71%) compared to those with LKS/ CSWS (48%). Certain missense variants in or close to the ligand-gated ion channel domain were associated with a severe phenotype, as was also observed in two of our patients with severe epilepsy and cognitive impairment. Conclusion: Individuals with GRIN2A gene variants or deletions have an extremely variable phenotype without a clear genotype-phenotype correlation. Variants in or close to the ligand-gated ion channel can be associated with a severe phenotype.

Neuroimaging 1 Monday 12th September P401 BILATERAL THALAMIC VOLUME LOSS IN PATIENTS WITH PHARMACORESISTANT TEMPORAL LOBE EPILEPSY WITH AND WITHOUT HIPPOCAMPAL SCLEROSIS Ciolac D1,2, Koirala N3, Muthuraman M3, Chiosa V1,2, Munteanu C1,2, Vataman A1,2, Groppa S3, Groppa SA1,2 1 Institute of Emergency Medicine, Chisinau, Moldova, 2State University of Medicine and Pharmacy ‘Nicolae Testemitanu’, Chisinau, Moldova, 3Johannes Gutenberg University Mainz, Mainz, Germany Purpose: There is growing evidence of extratemporal volume changes associated with pharmacoresistant temporal lobe epilepsy (TLE). The aim of the present study was to characterize the volume changes of thalamus in patients with pharmacoresistant TLE in comparison with healthy controls. Further dependencies of thalamic volumes, seizure focus and duration of epilepsy will be studied. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Method: T1-weighted images (repetition time [TR] = 2,000 ms, echo time [TE] = 9 ms, 4 mm – slice thickness, flip angle = 150°) were acquired by 3T Magnetic Resonance Imaging (MRI) in 15 patients (mean age standard deviation [SD] 25 1.8 years, 9 male) with pharmacoresistant TLE (disease duration 15.2 8.8 years). Nine patients (60%) presented on MRI signs of hippocampal sclerosis (HS). Thalamic volumes were extracted from Freesurfer analytical pipeline and compared with a group of 15 controls (mean age 27.9 4.0 years, 7 male). There was no difference between the groups regarding age (p > 0.1) and sex (p = 0.46). Volumes of thalami were correlated with duration of epilepsy. Results: Patients with TLE presented significantly smaller thalamic volumes both ipsilateral to the seizure focus (7362.1 848.3 mm3, p = 0.00005) and contralaterally (7,186 848.3 mm3, p = 0.0037) in comparison with healthy controls (right thalamus 8088.7 683 mm3, left thalamus 9360.5 1,382 mm3). We found a negative correlation between the duration of pharmacoresistant TLE and the volume of ipsilateral thalamus (r = 0.12, p < 0.05) and contralateral thalamus (r = 0.13, p < 0.05). There was no correlation between age and thalamic volumes both in patients and controls. Conclusion: Our data show a bilateral thalamic atrophy in patients with pharmacoresistant TLE, that correlates with the disease duration. The present study provides insight into alterations of extrahippocampal morphology induced by recurrent seizures of pharmacoresistant TLE.

P402 DIRECTED FUNCTIONAL CONNECTIVITY DURING INTERICTAL SPIKES: A SIMULTANEOUS INTRACRANIAL AND HIGH-DENSITY SCALP EEG STUDY Coito A1, Pittau F2, Spinelli L2, van Mierlo P3, Seeck M2, Michel C1, Plomp G4, Vulliemoz S2 1 Functional Brain Mapping Lab, University of Geneva, Geneva, Switzerland, 2Epilepsy Unit, University Hospital of Geneva, Geneva, Switzerland, 3Electronics and Information System, Ghent University, Gent, Belgium, 4Department of Psychology, Perceptual Networks Group, University of Fribourg, Fribourg, Switzerland Purpose: We aimed to investigate whether directed functional connectivity of interictal spikes seen at both scalp and intracranial EEG revealed the same sources and connectivity pattern using simultaneous intracranial and high-density EEG recordings. Method: Intracranial (iEEG) and scalp EEG (256 electrodes) were recorded simultaneously during rest. For iEEG, depth electrodes were implanted in the right orbito-frontal (FOD), amygdala (AD), anterior hippocampus (HAD), posterior hippocampus (HPD), temporal pole (TPD) and posterior temporal gyrus (TPSD). We here present the results of 1 patient (drug-resistant right Temporal Lobe Epilepsy). Fifteen interictal spikes in the right lateral temporal cortex were identified in the scalp and epochs containing 300 ms before and after the spike were extracted. The corresponding iEEG epochs were then extracted. From the scalp EEG, source activity was estimated for 5,000 solution points (SPs) distributed in the grey matter, using an individual head model and distributed linear inverse solution. Only SPs closest to each iEEG electrode were selected for further analyses. Granger-causal modeling was separately applied to SPs and intracranial activity to estimate directed functional connectivity. The summed outflow across time and region-to-region connectivity at the spike peak were investigated in the alpha band. Results: The SP with the strongest source activity was in the right lateral temporal cortex (HPD6), which was the same depicted by iEEG. For the iEEG, the highest summed outflow (driving) was from the right lateral temporal cortex, which was concordant with the strongest summed outflow from the EEG sources. The strongest region-to-region connections for both iEEG and SPs were between lateral temporal contacts.

127 Abstracts Conclusion: Source activity, summed outflow and region-to-region connections were concordant between both modalities. This shows the potential of source localization and connectivity analysis to non-invasively determine the epileptogenic zone and study epileptic networks.

P403 DIFFUSION TENSOR IMAGING AND MRI TRACTOGRAPHY OF THE BRAIN IN PATIENT WITH EPILEPSY AND DEPRESSION Kapustina T1, Lipatova L1, Savintseva Z2 1 St. Petersburg V. M. Bekhterev Psychoneurological Research Institute, St. Petersburg, Russian Federation, 2Institute of Human Brain of N. P. Bekhtereva, St. Petersburg, Russian Federation Purpose: Modern methods of imaging a fine structure, in particular, diffusion tensor imaging (DTI), giving an idea of the structural integrity pathways of thewhite matter of the brain used for the study of various CNS disorders including epilepsy and affective disorders. Morpho-functionalcomparisons allow clarify the involvement of different brain regions to the formation of pathological processes. Method: We studied 90 patients aged 34 4.2 years: 30 with epilepsy (PE), 30 – patient with epilepsy and depression (PED), 30 patient with depression (PD) and 30 healthy volunteers (HV) – control group. Results: In all groups of patients were identified structural changes in the brain in the form of lower crust density (gray matter) and fractional anisotropy different parts of the brain, deficiency of fornix tracts, corpus callosum and cingulate gyrus, compared with healthy.In the group of PE and PED showed reduced fractional anisotropy, mainly in the anterior corpus callosum, similar changes in the thalamus, bilateral atrophy of the cortical divisions insula, striatal involvement (in the PE group – the right caudate nucleus, to PED – bilaterally), and a reduction in the density of gray matter in the right cerebellar tonsils and the left visual cortex. In the group of PD there are special microstructural changes: reduced fractional anisotropy, mainly in the middle part of the corpus callosum, reduction in the density of gray matter in the anterior part of the left cingulate, dorsolateral prefrontal and visual cortex on the left, bilaterally – in the orbitofrontal and inferior temporal cortical areas as well as anterior – ventral parts of the thalamus, left-sided cortical atrophy insula Conclusion: With DTI of the brain in patients of all groups identified changes in the structures of the limbic-reticular complex and corticostrio-thalamo-cortical tracts, dysfunction, which is likely to be a common “neurobiological substrate” of epilepsy and depression.

P404 ALTERED BASAL GANGLIA-CORTICAL CONNECTIONS IN FRONTAL LOBE EPILEPSY USING RESTING-STATE FMRI FUNCTIONAL CONNECITITY ANALYSIS Peng R, He Z, Dong L, Jiang S, Luo C, Guo D, Liu T, Yao D School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China

test was used to determine the differences between patients and controls, while controlling the age, gender and head motions. Results: Compared with controls, FLE patients showed the significantly increased FCs between the right putamen and the left precuneus/middle cingulum, as well as connections between the left thalamus and antetior cingulum. Decreased FCs between the basal ganglia and the bilateral inferior frontal operculum/bilateral putamen/bilateral precuneus and left caudate were also found in the patients. Conclusion: Our study implied that alterations of functional connections within basal ganglia, as well connections from the basal ganglia to distant regions, may be associated with FLE. Keywords: Frontal lobe epilepsy, basal ganglia-cortical connections, Functional connectivity, Resting-state, fMRI.

P405 BEAMFORMING IMPROVES RIPPLE VISIBILITY IN SCALP EEG Mol A1,2, van Klink N2, Huiskamp GJM2, Zijlmans M2,3 1 Faculty of Medicine, Utrecht University, Utrecht, The Netherlands, 2Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands, 3Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands Purpose: High frequency oscillations (HFOs) in the electrocorticogram have been shown to correlate with epileptogenic brain tissue. Detection of ripples (80–250 Hz) in scalp EEG is limited by signal attenuation and muscle artifacts. Beamforming was reported to improve ripple detection in magnetoencephalography. We applied beamforming to optimize ripple visibility and to localize scalp EEG ripples. Method: We analyzed 10–15 min of EEG of ten persons with focal epilepsy who had an EEG with at least 60 channels. We positioned virtual electrodes 3.5 cm apart in two layers, parallel to the inner skull and computed virtual signals at these electrodes using a SAM beamformer. We visually marked spikes and ripples co-occurring with spikes in physical and virtual channels. Patients who had right TLE showed a significantly decreased FC from the left hippocampal ROI than controls, primary within the left hemisphere. FC from ROIs in the language relevant regions in the left frontal lobe was reduced in left TLE patients, within the left but also to the right hemisphere, which was not observed in right TLE, who showed a similar frontal FC pattern as controls. These findings were corroborated by graph-based network analysis (efficiency, density), demonstrating impaired network structure in left TLE.


130 Abstracts Conclusion: FC analysis revealed that in left TLE the left fronto-hippocampal language network was disrupted, suggesting a critical role for the left medial temporal lobe in language tasks. Additionally, the left frontal network within the ipsi- and to the contralateral hemisphere was impaired. Language function depends on the integrity of the hippocampus and the connecting fronto-temporal networks, providing evidence of multiple systems supporting language function.

P414 OBJECTIVE BACKGROUND OF THE REFRACTORY EPILEPSY DEVELOPMENT FOUNDED ON STRUCTURAL-METABOLIC ALTERATIONS OF BRAIN Kistsen V, Evstigneev V Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus Purpose: The aim of this study was to assess the impact of the extent of brain white matter lesions and neurometabolic disturbances on the development of refractory epilepsy. Method: 49 patients with pharmacoresistant epilepsy (FRE), 26 remission patients and 23 normal volunteers were examined. To evaluate DTI findings, the index of fractional anisotropy (FA) and index of apparent diffusion coefficient (ADC) were used. Temporal brain regions were investigated by multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Results: A significant difference was noted in the ADC data on the epileptic focus side in the remission patients as compared to the FRE (p < 0.05). No differences were found between the patient groups’ FA data. Decreases in the tracts appearing in brain temporal lobes was typical of FRE patients (r = 0.46, p = 0.0005). Analyses of the EEG patterns and FA data demonstrated a correlation between the existence of epileptic activity and a decrease in FA (r = 0.7, t = 2.44, p = 0.01). All FRE patients had a reduction of NAA/(Cho+Cr) ratio into hippocampal voxels bilaterally, which correlated with frequent complex partial paroxysms (r = 0.68, p = 0.041). Conclusion: Microstructural-neurometabolic brain changes make it possible to assess the course of epilepsy and to predict the outcomes of medicamental correction of paroxysmal states.

P415 MORPHOLOGICAL CHANGES OF CEREBELLUM IN EPILEPSY: HYPERTROPHY OF SELECTED VERMIAN SEGMENTS IN PATIENTS WITH TEMPORAL LOBE EPILEPSY Marcián V1,2, Marecek R1,3, Janousova E4, Brazdil M1,3 1 1st Department of Neurology, St. Anne’s University Hospital and Medical Faculty, Brno Epilepsy Center, Masaryk University, Brno, Czech Republic, 2Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic, 3 Behavioral and Social Neuroscience Research Group, CEITEC (Central European Institute of Technology), Masaryk University, Brno, Czech Republic, 4Faculty of Medicine, Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic Purpose: The goal of this work is to determine the presence and degree of cerebellar atrophy within cerebellar substructures compared to healthy controls in temporal lobe epilepsy patients.


Method: Study participants were 36 patients suffering from temporal lobe epilepsy and 38 healthy controls. All patients in this study later underwent temporal lobe resection: 28 seizure-free patients (Engel class I) and 8 patients with persistent seizures after the surgery (Engel class IIIV). All subjects were examined using 1.5T MRI. Cerebellar volume was adjusted for total intracranial volume, age and gender and measured by means of voxel based morphometry. Cerebellar substructures were defined using Automated Anatomical Labeling (AAL) atlas. Results: There was no significant difference in total cerebellar volume between epileptics and controls. Total cerebellar volume appears nonsignificantly smaller in epileptics. Analyzed within substructures using Mann-Whitney non-parametric testing and False Discovery Rate Correction for multiple comparison there was significant difference in volumes of two frontmost (Vermis_1_2, Vermis_3 according do AAL) and the rearmost (Vermis_10 according to AAL) structures of cerebellar vermis compared to controls. Listed structures were of larger volume in epileptics. Conclusion: Cerebellar atrophy is probably more complex phenomenon, the character of changes differs significantly within the cerebellar substructures. Total cerebellar volume tends to be smaller in temporal lobe epilepsy patients compared to controls, nevertheless some parts of vermis are significantly larger in epileptics.

P416 MRI VOLUMETRY OF TEMPORAL LOBES AND ITS SUBSTRUCTURES IN PHARMACORESISTANT TEMPORAL LOBE EPILEPSY PATIENTS Martinkovic L1, Kalina A1, Stepan-Buksakowska I2, Vrana J3, Sulc V1, Horinek D4,5, Marusic P1 1 Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, 2Department of Radiology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, 3Department of Radiodiagnostics, University Central Military Hospital, Prague, Czech Republic, 4Department of Neurosurgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, 5Department of Neurosurgery, Masaryk Hospital, Usti nad Labem, Czech Republic Purpose: Temporal lobe and its substructures volume is a clinical tool to identify pathological changes in epilepsy patients. Ipsilateral hippocampal, amygdala and temporolobar atrophy (including temporopolar atrophy) has been reported in temporal lobe epilepsy patients. The aim of the study was to assess variability of temporal lobe and its substructures volume in patients with farmacoresistant temporal lobe epilepsy. Method: 24 temporal lobe epilepsy (TLE) patients with typical language dominance and 12 right-handed healthy adults were enrolled into the study. High-resolution MRI (3T, T1- weighted images) was performed. Left and right temporal pole, temporal lobe, hippocampus and amygdala were outlined and measured manually in coronal plane by ITK-SNAP. Automatic procedure was used to gain hippocampal and amygdalar volumetry. Obtained volumetric data were normalized to total intracranial volume (performed by FSL software) and statistically analyzed to compare for left-right asymmetry and volume variability. Results: Temporal lobe volumes were significantly reduced ipsilaterally to the side of epilepsy in comparison to healthy subjects. In right TLE patients significant reduction of both temporal pole volumes (and anterior part of temporal lobes) in comparison to healthy participants was observed. However, temporal poles were not significantly reduced in left TLE patients. Ipsilateral hippocampal volumes in patients were

131 Abstracts significantly reduced. Amygdala volumes did not show significant volume reduction. Automatic volumetry of hippocampal volumes differed against manual procedure in absolute numbers. Conclusion: Ipsilateral temporal lobe is atrophic in TLE patients. Anterior temporal lobe volumes are highly variable and show different pattern of atrophy; bilateral in right TLE and no atrophy in left TLE patients. This finding can reflect more pronounced bilateral network involvement in right TLE.

P417 NODULAR HETEROTOPIA: INTEGRATION OF MULTIMODAL NEUROIMAGING AND NEUROPHYSIOLOGICAL METHODS Pappalardo I1, Deleo F1, Schiaffi E2, Visani E2, Rossi D2, Duran D2, Gozzo F3, Tassi L3, Panzica F2, Villani F1, de Curtis M1 1 Unit of Epileptology and Experimental Neurophysiology, IRCCS Foundation Neurological Institute ‘C. Besta’, Milano, Italy, 2Clinical Neurophysiology Unit, IRCCS Foundation Neurological Institute ‘C. Besta’, Milano, Italy, 3‘C. Munari’ Epilepsy Surgery Center, Niguarda Hospital, Milano, Italy Purpose: Grey matter heterotopias are malformations of cortical development frequently associated with refractory epilepsy. The role of the nodules and the overlying cortex in epileptogenesis is still under debate. It is believed that both are involved in a complex epileptogenic network. We executed EEG-functional MRI (EEG-fMRI), Magnetoencephalography (MEG), 18-FDG PET and Voxel based morphometry (VBM) techniques to study patients with nodular heterotopia and refractory epilepsy. The integration of multimodal neuroimaging and neurophysiological methods may identify peculiar morfo-functional features of the epileptogenic network associated to nodular heterotopia. Method: 13 patients with nodular heterotopia and drug-resistant epilepsy have been selected. All patients underwent a complete clinical evaluation including video-EEG. High-resolution volumetric 3T brain MRI was acquired and VBM analysis was performed in all cases. All patients showed florid interictal EEG activity and underwent EEG-fMRI and MEG evaluation. In seven patients was performed PET study. Results: Mean age was 40 (range 25–57) years; mean epilepsy duration was 17 (range 1–34) years. Six patients had bilateral nodular heterotopia, seven patients unilateral nodular heterotopia. EEG-fMRI, MEG and VBM analysis were performed in all cases. Functional analysis (MEG and EEG-fMRI) showed a complex epileptogenic pattern involving mostly both nodules and the surrounding cortex. VBM analysis in unilateral nodular heterotopias confirmed morphological alterations in ipsilateral cortex often remote from the nodules. PET showed a variable metabolism into the nodules. Conclusion: Our data confirm the complex relation between nodular heterotopia and the surrounding cortex and may explain why selective ablation or Radiofrequency Thermo-Coagulation of the nodules can be insufficient to achieve seizure freedom. The integration of multimodal neuroimaging and neurophysiological techniques can improve the knowledge of epileptogenic network involved in nodular heterotopia and may be useful in the non-invasive pre-surgical work-up for the assessment of this group of patients.

P418 DOES AUTOMATED MORPHOMETRIC SCREENING SUPPORT MRI DIAGNOSTICS IN TEMPORAL LOBE EPILEPSY PATIENTS? Rummel C1, Slavova N1, Seiler A2, Abela E1, Hauf M3, Burren Y4, Weisstanner C1, Schindler K2, Wiest R1 1 Inselspital, University Institute for Diagnostic and Interventional Neuroradiology, Bern, Switzerland, 2Department of Neurology, Inselspital, Bern, Switzerland, 3Epilepsy Clinic Tschugg, Tschugg, Switzerland, 4Psychiatric University Clinic, Bern, Switzerland Purpose: Morphometric and volumetric group analyses of T1-weighted MRIs have provided in-depth insight about structural alterations in the epileptic brain. To render these observations useful for clinical practice the question arises to which extent morphometric abnormalities may be inferred in individual patients and if they may contribute to syndrome classification and diagnostics. Method: We developed a fully automatic analysis pipeline based on the free software packages FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/) and FreeSurfer (https://surfer.nmr.mgh.harvard.edu) to evaluate nine morphometric parameters regionally. Individual patient MRIs were compared to a data base of 322 healthy controls. The framework was evaluated on 47 MRIs of 37 electro-clinically confirmed temporal lobe epilepsy (TLE) patients by two experienced raters specialized on imaging of epilepsy. Results: The agreement of automatically detected abnormality patterns with the human raters and with syndromal templates both showed characteristics of typical screening tests (large negative predictive values and small to moderate positive predictive values). Morphometric analysis in individual patients and statistical comparison to large control data sets does not outperform expert assessment in general. However, there is a considerable subset of inconclusive cases where complementary diagnostic information is provided. Additional findings encompass morphometric abnormalities of the folded cortical band (especially surface areas and curvatures, which can hardly be assessed by visual interpretation of cross-sectional images). Conclusion: As the automated morphometric analysis does not allocate human time and resources and can help to exclude unsuspicious brain regions, this tool should be used to support the neuroradiologist in the identification of structural abnormalities associated with epileptic lesions.

P419 INVESTIGATION OF GLOBAL NETWORK SYNCHRONY IN RESTING-STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING OF PATIENTS WITH MESIAL TEMPORAL LOBE EPILEPSY: A PILOT STUDY Yaakub SN, Tangwiriyasakul C, Richardson M Basic & Clinical Neuroscience, King’s College London, London, United Kingdom Purpose: Recent electrophysiological and neuroimaging evidence suggest focal seizures may arise from large-scale brain networks rather than a seizure focus (Richardson MP. J Neurol Neurosurg Psychiatry 2012;83:1238–1248). To investigate whether whole-brain functional magnetic resonance imaging (fMRI) networks in patients with mesial temporal lobe epilepsy (mTLE) show higher global synchrony than controls, we estimated the order parameter, a measure of network synchrony, using tensor decomposition and Kuramoto-based simulation methods (Ponce-Alvarez A et al. PLOS Comp Biol 2015;11(2):e1004100).


132 Abstracts Method: 10 right-sided mTLE and 25 control participants underwent 10 min eyes-closed resting-state fMRI and high-resolution structural scans. fMRI data were pre-processed, co-registered to the standard MNI template and divided into 1 min sliding windows with 90% overlap. Ninety brain regions were defined from the Automated Anatomical Labelling (AAL) atlas (Tzourio-Mazoyer N et al. NeuroImage 2002;15:273–289) and Pearson correlation coefficients were computed between the average timeseries from each pair of regions to obtain a 90x90 adjacency matrix per window. Tensor decomposition was used to extract sub-networks, resulting in 9 major components (90x90 matrices). We overlaid the 9 components to form a single representative adjacency matrix for each subject. To estimate the level of synchrony in this network, we calculated the average order parameter from the results of a Kuramoto-based simulation across a range of simulation parameters (delays and coupling factors). Results: Within the same range of simulation parameters, patients with right mTLE had significantly higher average order parameters (0.204 0.047) than controls (0.138 0.018). Conclusion: The results suggest that whole-brain networks derived from tensor decomposition of fMRI data show higher levels of synchrony in mTLE patients. Tensor decomposition may be a method to identify differences in brain networks between mTLE patients and controls.

Neuroimaging 3 Wednesday 14th September P421 REVERSIBLE MRI FINDINGS IN A NONCONVULSIVE STATUS EPILEPTICUS PATIENT WITH HYPERAMMONEMIC ENCEPHALOPATHY Akyol AG1, Genc E1, Ozkara C2, Dogan EA3, Emlik D4 1 Neurology, Necmettin Erbakan University Meram School of Medicine, Konya, Turkey, 2Neurology, Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey, 3Neurology, Akdeniz University School of Medicine, Antalya, Turkey, 4 Radiology, Necmettin Erbakan University Meram School of Medicine, Konya, Turkey Temporary cortical and/or subcortical signal changes on MRI are well established in status epilepticus and usually these cannot be discriminated from imaging correlates of the underlying etiology. Reports on early MRI findings of hyperammonemic encephalopathy in adults are scarce. In a peviously published report on four cases, symmetric involvement of cingulate or insular cortices was suggested to be highly specific imaging features of an acute hyperammonemic encephalopathy. Here we report the case of a 37-year old male patient who presented with nonconvulsive status epilepticus and was later found to have hyperammonemic encephalopathy. At presentation he had a comatose mental state with subtle twitching movements in the limbs. Repeated EEGs demonstrated a diffusely slowed background activity comprising of irregular slow waves, superimposed with intermittent slow sharp epileptiform discharges. He also developed asymmetric weakness in both upper and left lower extremities. His MRI (T2, FLAIR and DWI) revealed cortical and subcortical signal intensity changes in temporal and frontal lobes including the cingulate gyrus and insular cortex. Involvement of the cingulate gyrus was remarkable on each of the abovementioned MRI sequences while involvement of other regions was more variable. Our patient clinically improved and regained consciousness after treatment of hyperammonemia. Motor deficits in the limbs were also resolved. A follow up MRI obtained 2 months later demonstrated resolution of the abnormal signal intensities. In a comatose or stuporous patient, cingulate gyrus signal abnormality along with additional cortical involvement on MRI should be recognized as early signs of a hyperammonemic encephalopathy to prevent unnecessary further investigations. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P422 PREDICTORS OF CORTICAL REPRESENTATION IN PATIENTS WITH LESIONAL EPILEPSY: AN FMRI STUDY Barba C1, Montanaro D2, Pellacani S1,3, Grisotto L4, Cavalli A1, Aghakhanyan G2, Lenge M1, Frijia F2, Guerrini R1,3 1 Pediatric Neurology Unit, Children’s Hospital MeyerUniversity of Florence, Florence, Italy, 2Neuroradiology, Fondazione CNR/Regione Toscana G. Monasterio, Pisa, Italy, 3 IRCCS Stella Maris, Calambrone, Italy, 4Department of Statistics, Computer Science, University of Florence, Applications ‘G. Parenti’, Florence, Italy Purpose: To characterize the pattern of cortical representation in patients with lesional epilepsy and to identify its clinical predictors. Method: Twenty-six patients (mean age at the study 12.1 6.3 years) operated on for lesional epilepsy were consecutively enrolled at Pediatric Neurology Unit, Children’s Hospital Meyer, Florence, Italy. All patients underwent extensive presurgical evaluation including history, videoEEG recordings, neuropsychological assessment, preoperative 3T anatomical and functional MRI (fMRI) study for language (fluency, rhyme generation and comprehension) and/or motor tasks. To define the pattern of functional activation during the language and motor tasks we assessed the lateralization and localization of the activated areas and the relationship with the epileptogenic lesion as evaluated on MRI and histopathological findings. Several clinical variables and histopathology were analysed to assess if they correlated with the pattern of cortical representation. Results: We found that the distribution of the ictal and interictal EEG, the extent of the epileptogenic zone (EZ), the duration of the epilepsy before surgery and backward digit span task correlated with the topography of the activated areas during the language tasks. Concerning histopathology, we found that FCD type II and DNET were activated during either motor or language tasks, while other type of tumours were not activated. FCD type I and IIa did not show a consistent pattern of activation. Conclusion: The pattern of cortical activation in patients with lesional epilepsy is influenced by the duration of epilepsy, histopathology and the topography of the EZ. These findings should be taken in account when planning surgery in order to avoid post-surgical deficits. Funding: This research was supported by the Italian Ministry of Health and Tuscany Region (RF-2010 -2309954) “Reorganization of cortical function after surgery for lesional epilepsy in children.”

P423 RELIABILITY AND REPRODUCIBILITY OF SINGLEVOXEL SPECTROSCOPY OF THE HIPPOCAMPUS IN 1,342 CONSECUTIVE STUDIES OF 670 PATIENTS WITH EPILEPSY Hoshida T, Sawai Y, Shimokawara T, Hirabayashi H National Hospital Organization, Nara Medical Center, Epilepsy Center, Nara, Japan Purpose: Proton magnetic resonance spectroscopy (MRS) of the hippocampus has demonstrated neuronal dysfunction in patients with epilepsy. Our aim was to evaluate the reliability and reproducibility of single-voxel spectroscopy of the hippocampus. Method: A total 1,342 consecutive MRS studies performed on 670 patients with epilepsy and associated disorders from May 2010 to November 2015 were evaluated. Quantitative single-voxel MRS was conducted at 1.5 Tesla with a sequence of TR/TE = 1,323/136 ms and a voxel size of 30 9 15 9 15 mm in both hippocampi. LC-Model was

133 Abstracts used to estimate the absolute concentrations of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr), and the ratio of NAA to Cho + Cr (NAA ratio). Results: The NAA value and ratio were evaluated in 641 patients (96%) on the right hippocampus, and in 638 patients (95%) on the left hippocampus. Of these patients, bilateral NAA, Cho, and Cr values were the same in 1 patient in studies 2.5 years apart. Among patients who had more than 3 MRS studies over more than 3 years, both sides of the hippocampus were simultaneously evaluated in 86 patients. Patients with idiopathic generalized epilepsy were selected. In 28 of 86 patients, no remarkable change (mean < 10%) in NAA values or NAA ratios in the final compared with the initial MRS study were observed in 22 and 21 on the right, and 18 and 22 on the left side, respectively. Conclusion: Our study, showed that NAA values and ratios using MRS measurement methods were reliable, and were able to evaluate hippocampal metabolic function in 95% of patients. Longitudinal MRS data after more than 3 years revealed 75% reproducibility with this method. Differences between initial and final MRS data might be attributed to epilepsy pathogenesis, natural course, or individual variations within each measurement.

P424 REVERSIBLE MRI ABNORMALITIES IN PATIENTS PRESENTING WITH EPILEPTIC SEIZURES Kazis D, Theodoridou V, Tsolaki M, Ntantos D, Bostantjopoulou S 3rd Neurology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece Purpose: To underpin the importance of reversible MRI findings in the management of patients presenting with a seizure. Method: We present three patients (P1: male, 18yo; P2: female, 64yo; P3: female, 21yo) with epileptic seizures (P1&2 focal with secondary generalization, while P3 with focal status epilepticus). Routine blood tests, EEGs, videoEEG monitoring and MRI imaging (T1, T2, FLAIR, DWI) were performed. Results: EEG showed intermittent polymorphic and rhythmic slowing over the left temporal region in P1&P2. In P3 evolving rhythmic slowing with spikes were recorded over the right posterior temporal and occipital region. MRI abnormalities were localized over the left temporal lobe in P1 and P2 and on the right posterior temporal and occipital region in P3. Routine blood tests, examination for paraneoplastic and autoimmune antibodies were normal. P1 and P2 were started on Carbamazepine while P3 was treated with IV Levetiracetam and Lacosamide. Second MRI performed after 73 days, 75 days and 14 days respectively, were normal. All patients had an excellent response to AEDs. In the follow up there were no seizures (P1-4 months, P2-2 years, P32 months). Conclusion: Our patients with seizures had reversible MRI findings. EEG and MRI findings were in concordance with EEG having a great localizing value. Most published cases have shown that postictal edema is more likely in patients with cluster seizures and status epilepticus. Additionally, this finding resolved in most cases after weeks or months. Two of our patients had a focal seizure with secondary generalization of short duration (up to a minute) while the third patient with prolonged status epilepticus had surprisingly complete resolution of the postictal edema 14 days later. A second MRI helped to avoid unnecessary diagnostic tests however it is unknown when is the right time to perform it.

P425 RESECTION EXTENT OF THE UNCINATE FASCICULUS AND POSTOPERATIVE SEIZURE OUTCOME IN TEMPORAL LOBE EPILEPSY Keller SS1, Glenn GR2, Weber B3, Kreilkamp B1, Jensen J2, Richardson MP4, Bonilha L2 1 University of Liverpool, Liverpool, United Kingdom, 2Medical University of South Carolina, Charleston, SC, United States, 3 Medical University Bonn, Bonn, Germany, 4Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom Introduction: Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy (TLE) will not be rendered completely seizure free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. One possibility is that an insufficient extent of pathological mesial temporal lobe is resected, permitting remnant epileptogenic tissue the capability of contributing to postoperative seizures. In the present study, we investigated whether the extent of resection of important temporal lobe white matter tracts were related to postoperative seizure outcome. Methods: We studied 33 patients with medically intractable TLE with unilateral hippocampal sclerosis who underwent preoperative diffusion tensor imaging (DTI), amygdalohippocampectomy, postoperative structural MRI and postoperative seizure outcome assessment. Outcome assessment was performed using the ILAE classification scale. From preoperative DTI, the fimbria-fornix (FF), parahippocampal white matter bundle (PWMB) and uncinate fasciculus (UF) were reconstructed using Automated Fibre Quantification (AFQ). The surgical lacuna was manually segmented on postoperative MRIs of each patient, and co-registered with the preoperative DTI AFQ maps to generate resection maps of the three white matter tract bundles. Results: Hippocampal sclerosis was histologically confirmed in all patients. 17 (52%) patients were rendered completely seizure free (ILAE 1) and 16 (48%) patients had persistent postoperative symptoms (ILAE 2–5). There were slight differences in the resection extent of the FF (ILAE 1: 20.8 12.6%, ILAE 2–5: 18.3 8.9%; p = 0.54) and PWMB (44.8 27.2%, 33.2 16.8%; p = 0.23) between outcome groups. However, the extent of resection of the UF was significantly greater in ILAE 1 patients relative to ILAE 2–5 patients (41.7 20.9%, 19.7 23.1%; p = 0.02). Discussion: This study indicates that resection extent of the UF is related to persistent postoperative seizures. Smaller UF resections may represent insufficient disconnection of an anterior temporal epileptogenic network.

P426 ROLE OF POSITRON EMISSION TOMOGRAPHY (PET) OF THE BRAIN IN THE DIAGNOSIS OF EPILEPSY Lipatova L, Kapustina T St. Petersburg V.M. Bekhterev Psychoneurological Research Institute, St. Petersburg, Russian Federation Purpose: Numerous clinical and experimental studies have shown that complex interaction structures involved in the generation of epileptic activity and it suppression. Antiepileptic system of the brain includes the caudate nucleus, the reticular nucleus of the pons, some structures of the thalamus, posterior part of the hypothalamus, the dorsal seam core, upper hills of corpus quadrigemina, cerebellum and other structures. Through these structures, by means of a negative feedback mechanism, it is an inhibitory effect on epileptogenesis. A special role in the regulation of processes of excitation and inhibition of neurons belongs to the cerebellum. According to the literature, atrophic changes of the cerebellum in patients with epilepsy (PE) correlated with the frequency of convulsive phenomena (J. Doyon, 2002) and EEG changes (R. Ventura, et al., 2006). Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

134 Abstracts The effectiveness of the surgical treatment of epilepsy is also largely depends on the functional state of the cerebellum and the degree of atrophy of the cerebellum (Mewasingh L.D., et al., 2002).

highlight the nature of such findings along with the associated estimated epidemiology of such and to determine whether or not such associated changes or findings had significance in subsequent clinical management.

Method: Aim of the study to investigate the metabolism of fluorodesoxyglucose (FDG) in the brain of a PE in interictal period by the method of positron emission tomography (PET). We examined 35 patients with drug-resistant epilepsy using MRI and FDG PET of the brain, EEG and EEG-VM.

Method: In a clinical practice of an academic epileptologist in an urban and suburban Level III and IV Epilepsy center in the United States, a retrospective series of patients who presented for EEG monitoring that contained peri-ictal changes were noted and retrospective analysis of these cases are noted.

Results: Hypometabolism of FDG in the brain stem and cerebellum was found in 28 (80%) PE and focal hypometabolism of FDG in different lobes of the brain hemispheres – in 21 (60%) PE. Identified focus of FDG hypometabolism usually corresponded with dominant epileptic focus established by EEG-VM.

Results: Among the cases presented, diverse findings were noted including reversible changes in cortical structures, transient effects in white matter, meningeal involvement, hippocampal swelling, focal enhancement(s) with gadolinium that reverse, and 3 cases of de novo hippocampal sclerosis are noted in adult patients. The presence of such changes was concordant with ictal lateralization, and were seen in patients with frequent seizures or status epilepticus. Findings were noted with patients with partial onset seizures with or without secondary generalization. The cases of de novo Mesial Temporal Sclerosis (MTS) specifically seemed to be associated with frequent both clinical and subclinical seizure activity and morphologic changes occur with a range of 20 months to several years and will be specifically highlighted in this series. One such case of de novo MTS may have an iatrogenic component.

Conclusion: Thus, our findings allowed reveal FDG hypometabolism of the brain of EP in epileptic focus and in the structures of the posterior cranial fossa (brainstem and cerebellum) which can be considered as a functional failure and probable cause insolvency of antiepileptic system of the brain.

P427 RESTING-STATE FMRI SHOWED ABNORMAL LOCAL SPATIOTEMPORAL CONSISTENCY IN FRONTAL LOBE EPILEPSY Li H, He Z, Dong L, Jiang S, Shi Q, Yao D, Luo C School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China

Conclusion: Peri-ictal changes on MRI and other neuroimaging modalities may be detected during the clinical evaluations of epilepsy patients. De Novo MTS occurring in the adult patient population is a unique clinical entity and its occurrence and clinical features as suggested in this report indicate a unique subset in this population in this retrospective series having ramifications for future study.

Purpose: Frontal lobe epilepsy (FLE) is the second most frequent type of focal epilepsy. The purpose of current study is to assess the local spatio-temporal consistency in FLE patients.

P429 PREVALENCE AND IMPORTANCE OF THE INTRACRANIAL CYSTS IN FOCAL EPILEPSY PATIENTS: A TERTIARY REFERRAL CENTER STUDY Ristic A1, Nikolic I2, Bascarevic V3, Vojvodic N1, Jankovic S1, Sokic D1 1 Neurology Clinic, Clinical Center of Serbia, Belgrade, Serbia, 2 MRI Center, Clinical Center of Serbia, Belgrade, Serbia, 3 Neurosurgery Cliinic, Belgrade, Serbia

Method: Resting-state fMRI data were collected from 19 FLE patients and 19 age and gender-matched healthy controls. A new measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA), which characterized the local consistency by integrating temporal and spatial information in the local region, was calculated for the fMRI data. Then, the FOCA differences between patients and controls were investigated using two-sample t-test. And, partial correlation analysis was also conducted to detect relationships between the altered FOCA values and durations of epilepsy in patients group. Results: Compared with healthy controls, significantly increased FOCA values mainly found in the left precentral gyrus, left middle frontal gyrus and left caudate in FLE patients. And patients with FLE showed the decreased FOCA values in the bilateral cerebellum and precuneus. In addition, FOCA in the left caudate was significantly negative correlation with durations of epilepsy. Conclusion: These findings implied that the altered local spatio-temporal consistency in FLE patients may be related with cognitive dysfunction experienced by patients. And FOCA may have potential to provide important insights into understanding the pathophysiological mechanism of FLE. Keywords: Frontal lobe epilepsy, FOur-dimensional (spatiotemporal) Consistency of local neural Activities, Resting-state, fMRI.

P428 PERI-ICTAL CHANGES ON MRI NEUROIMAGING Oster J Neurology, Tufts University School of Medicine, Boston, MA, United States Purpose: The purpose of this paper is to review peri-ictal changes on MRI neuroimaging in patients monitored with Video EEG monitoring to Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Purpose: Intracranial cysts (ICs) are common findings at brain MRI, with broad hystopathological spectrum. Based on origin they are differentiated to normal variants, congenital cysts, traumatic, vascular or infectious cysts, and tumor-associated nonneoplastic cysts. Except for neurocysticercosis, relationship of all other cysts and epilepsy is erratic. We analyzed associations of the overall ICs and focal epilepsy. Method: We studied 180/310 patients (58.04%) selected from the database of the Epilepsy Center video EEG Monitoring Unit at the Neurology Clinical Center of Serbia covering the period from August 2009 to May 2012, who underwent long-term vEEG monitoring in whom focal epileptic seizures were recorded. Electro-clinical data of the patients were collected. In all patients we performed brain MRI (Achieva Phillips 1.5T) with unique protocol: T1W-3D, T1W-sagittal (5 mm), FLAIR/T2W-coronal (3 mm), FLAIR/T2W-axial (5 mm), GradientEchoImage-axial (5 mm), and InversionRecovery-coronal slices (5 mm), with proper angulations. Quality and location of the epileptogenic lesion and ICs were visually analyzed by experienced neuroradiologist. Results: Our patients were 34.2 1.0 years old (48.9% female) with mean epilepsy onset at 14.2 10.1 years of age. Epileptogenic lesion was determined in 126/180, hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) being most prevalent (46%; 23%). ICs were present in 56/180 (31.1%). Cyst types were determend as: arachnoidal (AC) (30.4%), perivascular (16.1%), DNET (12.5%), choroid plexus (8.9%), pineal/neuroglial (5.4% each), choroid fissure (3.6%), FCD, porencephalic/unicameral bone (1.8% each), and multiple cyst types (10.7). ICs were unilateral (left of right) in 80.4%. ACs were seen in 5/17

135 Abstracts temporal and 12/17 retrocebellar region and associated with HS and FCD in 83.7%. When detected in temporal region ACs were concordant in 3 patients with side of temporal ictal EEG recorded (one MRI negative). Conclusion: Brain cysts are common in focal epilepsy. Only ACs in temporal region could potentially contribute to epileptogenesis.

P430 POSTICTAL ARTERIAL SPIN LABELLING (ASL) MRI FOR THE LOCALIZATION OF SEIZURE ONSET ZONE (SOZ): COMPARISON WITH INTRACRANIAL EEGLOCALIZATION AND POST-SURGICAL OUTCOME Singh S1, Gaxiola-Valdez I2, Federico P1,2 1 Neurosciences, University of Calgary, Calgary, AB, Canada, 2 Radiology, University of Calgary, Calgary, AB, Canada Purpose: The existence of post-ictal vascular changes and their value in localizing the seizure onset zone (SOZ) in patients with refractory focal epilepsy has been documented in humans by our group. We have presented data on postictal and interictal ASL MRI where 12/16 patients demonstrated focal post-ictal hypoperfusion that co-localized to the presumed SOZ. We sought to compare these findings with the gold standard, considered to be intracranial EEG or post-surgical seizure freedom. Method: ASL MR images were obtained in 23 patients with refractory focal epilepsy undergoing scalp video-EEG monitoring within 90 min of seizure termination. Baseline ASL scans were obtained for comparison. Epilepsy history, seizure details (duration, type, semiology) and imaging data were documented. The presumed SOZ was compared to the ASL data. Six of these patients went on to have further work-up, four underwent intracranial monitoring, and two underwent surgical resection based on scalp VEM data. We compared the final SOZ with localization provided by ASL. Results: ASL scans were obtained 45–83 min following seizure termination. Three patients were nonlesional, one had mesial temporal sclerosis (MTS), bilateral frontal encephalomalacia and bilateral subependymal heterotopia each. Four patients underwent intracranial monitoring, three of whom were not recommended surgery, one due to seizures arising from eloquent cortex and two because of complex SOZ localization. Two patients proceeded to surgery based on noninvasive data, with pathologically confirmed MTS in both cases, one patient has been seizure free for 6 months. ASL data co-localized to the SOZ in 5 out of 6 patients, showing hypoperfusion in the region of the proven seizure focus. The sixth patient had profound global hypoperfusion, which may have been related to a prolonged secondarily generalized seizure prior to scanning. Conclusion: Post-ictal vascular imaging may be a useful tool to assist in localizing the SOZ.

P431 POSTSURGICAL EFFECTS ON FUNCTIONAL CONNECTIVITY WITHIN THE LIMBIC SYSTEM IN MESIAL TEMPORAL LOBE EPILEPSY Weisstanner C1, Abela E1, Hauf M1,2, Rummel C1, Verma R1, Kasprian G3, Schindler K4, Wiest R1 1 Support Center for Advanced Neuroimaging (SCAN), University Institute for Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland, 2 Epilepsy Clinic, Tschugg, Switzerland, 3Division of Neuro- and Musculoskeletal Radiology, Department of Radiology, Medical University of Vienna, Vienna, Austria, 4Department of Neurology, University Hospital Bern, Bern, Switzerland

Purpose: Temporal lobe epilepsy affects large-scale functional networks within and beyond the limbic system. We aimed to investigate the effects of epilepsy surgery on functional connectivity between these core structures, affected by epilepsy. Method: Seven patients with refractory mesial temporal lobe epilepsy (mTLE) underwent resting state fMRI during a phase I evaluation and after surgery. We applied a seed to voxel analysis to compare functional connectivity between the core structures of the limbic system (i.e. the hippocampus) and their interconnected hubs within the epileptic network. Results: Seven patients with mTLE (4 right mTLE, 3 left mTLE, mean age 31 years) were included, with left mTLE patients images flipped for comparison. Widespread reductions in functional connectivity were observed within limbic and motor networks. Predominant reductions within the limbic system were observed in the anterior cingulate gyrus, right and left paracingulate gyrus, right parahippocampal gyrus, right amygdala, right hippocampus; within the motor network in right and left precentral gyrus, right and left supplementary motor cortex, right cerebellum, right and left pars opercularis of the inferior frontal gyrus. Reductions in functional connectivity were also observed in right thalamus, right and left middle and superior frontal gyrus, left frontal pole, right temporal pole, inferior middle and superior temporal gyrus, planum polare, angular gyrus, right temporal and right and left occipital fusiform cortex, left inferior temporal gyrus, right and left occipital pole, right and left lateral occipital cortex. Conclusion: Downreguation of functional connectivity within the limbic and motor networks are observed after resective surgery. We assume that these changes reflect a trend towards normalization of abnormally interconnected brain areas due to continuous seizure spread.

Neuroimaging 4 Wednesday 14th September P434 SOURCE LOCALIZATION OF ICTAL EPILEPTIC ACTIVITY IN PATIENTS WITH FOCAL EPILEPSY VALIDATED WITH INVASIVE EEG Epitashvili N1,2, Schulze-Bonhage A1, D€ umpelmann M1 1 Epilepsy Center, University Medical Center, Freiburg, Germany, 2MediClubGeorgia, Tbilisi, Georgia Purpose: Source localization and source imaging methods are increasingly applied in presurgical evaluation. So far their use is mainly restricted for the source imaging of spikes.The aim of this study was to investigate the accuracy of the EEG source localization (ESL) models: MUSIC, sLORETA in the frequency domain, DICS in defining the region involved in the seizure onset zone (SOZ) utilising ictal scalp EEG data. Method: 8 patients were selected at Epilepsy Center Freiburg with drug resistant partial epilepsy who underwent invasive EEG (iEEG) monitoring and subsequent resective surgery (n = 7). 6/7 were seizure free, 17 seizures were extracted from pre- and invasive parts of presurgical evaluation. All but one were recorded with low density scalp EEG during iEEG. For the ESL analysis the first interval with rhythmic activity after seizure onset was selected. Distance between the ESL maximum and the first intracranial electrode involved in ictal activity was calculated. Results: The median distance between the ESL maximum and the intracranial electrode was for MUSIC, sLORETA, sLORETA constrained to the grey matter and DICS: 48.79 mm, 34.91 mm, 37.61 mm and 54, 65 mm respectively. Statistically significant difference was observed between sLORETA and DICS (p = 0.038). Time lag between invasive and simultaneously recorded surface EEG seizure onsets ranged from 1 to 20 s. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

136 Abstracts Conclusion: Compared with the results from the source localization studies for interictal spikes a lower accuracy in our study can be explained with by low density EEG, time difference between simultaneously recorded intra- and extracranial EEG seizure onsets and validating the ESL results against one intracranial electrode contact and not the volume representing the seizure onset zone. sLORETA maximum comes closest to the first seizure onset electrode contact.

P436 THE CORTICOSPINAL TRACT IN UNILATERAL POLYMICROGYRIA – A MULTIPARAMETRIC MRI STUDY Fösleitner O1, Samueli S2, Bonelli S3, Feucht M2, Pataraia E3, Czech T4, Prayer D1, Kasprian G1 1 Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria, 2 Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria, 3Department of Neurology, Medical University of Vienna, Vienna, Austria, 4 Department of Neurosurgery, Medical University of Vienna, Vienna, Austria Purpose: Due to the extreme divergence from normal brain anatomy in cases of unilateral polymicrogyria (PMG), standard MR imaging fails to localize the primary motor cortex. Functional MRI (fMRI) is the gold standard in localizing motor representation, but is dependent on patient compliance. This study used corticospinal tract (CST) diffusion tensor (DTI) based tractography as guidance to localize the primary motor cortex in unilateral PMG patients. Method: 1.5 and 3 Tesla MR imaging data (axial T2-TSE, DTI, block design motor BOLD fMRI – in 3/9 cases) were retrospectively reviewed in 9 patients. An asymmetry index (AI) of the pyramidal tract was calculated by adding the grade of asymmetry (symmetrical = 0, slightly = 1, moderately = 2 or severely = 3) at the level of the internal capsule, midbrain, medulla and spinal cord on axial T2-TSE images. Deterministic tractography was used to visualize the CST by placing two ROIs – at the internal capsule and lateral to the lateral ventricle. In all patients clinical assessment of motor function was available. Results: Tractography visualized the CST bilaterally in 9/9 cases. Using the CST as guidance, the presumed primary motor cortex could be identified within PMG. FMRI and DTI were equally efficient in motor cortex localization. The severity of motor deficits correlated well with imaging: mean AI = 1.0 in 2 patients with minimal deficits, mean AI = 9.3 in 7 patients with distinct deficits. 2/2 patients with minimal deficits demonstrated symmetrical CST at tractography, whereas 6/7 patients with distinct deficits showed markedly asymmetrical CST.

Purpose: Voxel-based morphometry (VBM) has been used to identify group-wise gray matter (GM) changes [Scanlon et al. Journal of Neurology 2013;260:9,2320–2329] in patients with non-lesional (MRI-negative) temporal lobe epilepsy (TLE). However, the underlying biological characterisation of these changes has remained elusive. The objective of this work was to apply Arterial Spin Labelling (ASL) to evaluate whether this may yield important additional clinical information in patients with intractable non-lesional left TLE. Method: We studied 39 healthy controls and 9 patients with left TLE who showed no lesion on previous MR scans. Each participant received 3D T1-weighted (T1-w) and pseudo-continous ASL scans. We performed automated GM segmentation of T1-w data using VBM8 in SPM8. The CBF maps were computed through GE Functool. Control ASL images were normalized to SPM8 positron density template and CBF maps were written to ICBM space. In VBM8, CBF maps were corrected for partial volume [Johnson et al. Radiology 2005;234(3),851– 859]. Effects due to cortical atrophy were thus removed. An isotropic 8 mm FWHM Gaussian smoothing Kernel was applied and patient-control differences in CBF maps were determined. GM segmentations were tested in the same way. A statistical threshold of p < 0.001 (uncorrected) with a voxel cluster of 50 was used. Results: No GM structural changes were found. However, patients demonstrated numerous left sided regions with significantly decreased CBF, including the temporal pole, insula and sensorimotor association cortex. Individual statistical testing on patients0 maps (p < 0.01, uncorrected) showed reduced CBF in locations consistent with EEG lateralization in 3 cases. Conclusion: We show that regions likely involved in temporal lobe seizure onset and propagation reveal ipsilateral blood perfusion alterations in patients with non-lesional left TLE while being unremarkable in terms of GM atrophy. In the absence of a structural abnormality, these results could have clinical implications for localization.

P438 SOCIAL COGNITION IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY: AN FMRI STUDY Kuchukhidze G1,2, Schmid E1, Kronbichler M3,4, H€ ofler J1, 3 1 1,4 Mayrhauser L , Thalhammer J , Trinka E 1 Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria, 2Department of Neurology, Innsbruck Medical University, Innsbruck, Austria, 3 Neuroscience Institute, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria, 4Centre for Cognitive Neuroscience, Salzburg, Austria

Conclusion: In non-compliant patients with unilateral PMG, localization of the presumed motor area can be achieved by using tractography as guidance tool. The severity of motor deficit correlates well with the grade of CST asymmetry at different cross sectional levels. Symmetry of the CST in PMG may indicate a high risk for loss of motor function after epilepsy surgery.

Purpose: Juvenile myoclonic epilepsy (JME) is the most common agerelated idiopathic generalized epilepsy. Poor social adjustment and behavioral disturbances are often observed in JME. In recent advanced brain imaging studies on JME patients, emotional and behavioral problems have been associated to subtle structural and functional alterations mainly in frontal cortex and thalamus. Morphological and functional abnormalities may extend beyond thalamo-cortical circuitry involving cingulate, occipital and insular cortices, hippocampi and cerebellum.

P437 STATISTICAL CEREBRAL BLOOD FLOW MAPPING IN PATIENTS WITH TEMPORAL LOBE EPILEPSY Kreilkamp BAK1,2, Das K2, Parkes LM3, Wieshmann U2, Tyler K2, Kiel S2, Gould S2, Marson AG1,2, Keller SS1,2 1 University of Liverpool, Liverpool, United Kingdom, 2The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom, 3Centre for Imaging Sciences, University of Manchester, Manchester, United Kingdom

Method: We performed a pilot fMRI study with a Theory of Mind (ToM) paradigm in order to determine differences in activation patterns in JME patients (n = 6; 3 women; mean age 30 11) and healthy controls (n = 6; 3 women; mean age 30 4). All study participants were also tested by the Structured Clinical Interviews for DSM-IV Axis I (SCID-I) and Axis II (SCID-II) personality disorders, respectively. In the scanner, all participants were presented with 20 short stories describing a character who acquired a false belief (Belief stories, n = 10) or a physical representation that became false, such as an outdated photograph or map (Physical stories, n = 10). The stories were presented visually as a text on a screen in a block design. A fixation cross at the end of each story separated


137 Abstracts different trials. After reading each story, participants chose either “True” or “False” by pressing a button with right or left hand respectively. Results: In JME patients compared to controls, fMRI ToM paradigm showed reduced activations in anterior cingulate cortex bilaterally, temporo-parietal junction bilaterally, right anterior superior temporal sulcus, medial precuneus and medial prefrontal cortex.These differences, however, were not statistically significant in this small sample. JME patients showed obvious deficits in the SCID I&II (in 43% of patients vs. 0% in healthy controls). Conclusion: Poor social adjustment and behavioral disturbances in JME patients may be associated with reduced fMRI activations in ToM paradigm.

P439 VISUALISATION OF BLOOD BRAIN BARRIER IMPAIRMENT AS EARLY MARKER OF POST STROKE EPILEPTOGENESIS Otáhal J1, Kala D1, Svoboda J1, Litvinec A1, Posusta A1, Dammer J1, Lisy J2, Sulc V3, Tomek A3, Marusic P3, Jiruska P1 1 Institute of Physiology CAS, Prague, Czech Republic, 2 Department of Radiology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, 3Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic Purpose: Emerging evidence suggest important role of the blood brain barrier (BBB) impairment in pathophysiology of post-stroke epilepsy. During period of BBB opening various blood derived compounds penetrate the brain tissue. They have been shown previously to have potential to induce acute symptomatic seizures, neuroinflammation and epileptogenesis. BBB assessment algorithms based on dynamic perfusion imaging are time and computationally demanding and inapplicable in preclinical CT imaging where dynamic scans are restricted by low speed acquisition. The aim of present study is to visualize regions of BBB impairment in both preclinical rodent models and human stroke patients using simple post-pre comparison. Method: To detect BBB impairment in patients suffering the stroke a T1 weighted MRI imaging was performed 7–10 days after the stroke without and with Gadolinium contrast. Visualization of BBB impairment in rat intraluminal MCAO model with reperfusion (90 min.) was performed using microCT scanner without and with application of nonionic iodine contrast 24 a 48 h after the reperfusion. Evans blue and tetrazolium staining was used to assess infarcted and albumin permeable area. CT and MRI datasets were processed using adapted post-pre comparison. Briefly, after the registration of images a statistically different pixels were found and the difference was weighted to signal levels of tissue with and without known blood tissue barrier (muscle and eye ball). Results: The post-pre comparison detected areas with significantly different signal which corresponded to those positive for Evans blue in rat MCAO. In majority of human MRI scans an area overlapping ischemic region and its surrounding was detected as region with enhanced Gd extravasation. Conclusion: The present study confirmed post-pre contrast comparison suitable for both clinical and preclinical visualization of BBB impairment after the stroke. The study was supported by grant project no. 15-33115A from Czech Health Research Council.

P440 VARIABLE THRESHOLD IN SPM ANALYSIS OF ICTAL SPECT IN EPILEPSY SURGERY PATIENTS Sulc V1, Tomasek M1, Martinkovic L1, Kudr M2, Jahodova A2, Krijtova H1, Krsek P2, Marusic P1 1 Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic, 2Department of Pediatric Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic Purpose: In patients with medically refractory focal epilepsy a SPECT co-registered to MRI is often useful in seizure onset zone localization visualized as increase in perfusion in a given area. Different factors can influence localization value of SPECT study. Statistical parametric mapping can be used to localize seizure onset based on ictal-interictal difference between patients and paired repeated images from control group (ISAS). Reading rules for this type of analysis were previously published with good sensitivity and specificity but results from using this healthy database with data different SPECT acquisition systems are limited. We aimed to evaluate localizing value of various Z scores (1, 1.5, 2, and 2.5) in patients undergoing resective epilepsy surgery Methods: Ten patients with neocortical focal epilepsy who underwent resective epilepsy surgery were identified to have ictal and interictal study available. SPM analysis of SPECT data was performed using control group and then blindly reviewed for localization of hyperperfused regions. To eliminate bias caused by lesion on MRI data in MRI lesional patients, perfusion maps thresholded with Z score of 1, 1.5, 2 and 2.5 were displayed on standard MRI T1 template in axial, sagittal and coronal plane in randomized order. Results: In SPM SPECT analysis using freely available control group acquired with different SPECT system optimal Z score threshold for correct seizure onset zone localization was two. Conclusion: The present study shows importance of using different thresholds in SPECT data analysis when searching for epileptogenic zone in epilepsy surgery candidates.

Neuropsychology and Psychiatry in Epilepsy 1 Monday 12th September P442 EPILEPSY AND DEPRESSION: RECOGNIZING THE DOUBLE BURDEN IN ALBANIA Grabova S1, Alimehmeti I2, C ibuku O1, Kurmaku E1, Rraklli E1, 1 1,3 Mijo S , Kruja J 1 Service of Neurology, University Hospital Centre ‘Mother Theresa’, Tirana, Albania, 2Department of International Health, School for Public Health and Primary Care (CAPHRI), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands, 3Department of Neurology, Faculty of Medicine, University of Medicine, Tirana, Albania Purpose: Epilepsy is a chronic neurological disorders often complicated not only by recurrent seizures, but also from mood disorders. Nevertheless, mental health, including depression, is not routinely being assessed in patients diagnosed with epilepsy. Up to date, no former study has assessed the prevalence and severity of depression among epilepsy patients in Albania.


138 Abstracts Method: Twenty-nine consecutive epilepsy outpatients were enrolled at the University Hospital Center “Mother Theresa” together with fortyseven healthy controls. To assess depression, both patients and controls were interviewed by trained neurologists using the Beck Depression Inventory II (BDI-II). Differences were tested using the independent samples t-test for total BDI-II scores, and chi-squared test for categorical levels of depression. Results: Epilepsy patients (55.2% males, mean age 36.9 years old) showed no statistically significant gender or age difference with the healthy controls (55.3% males, mean age 42.1 years old). Nevertheless, epilepsy patients scored higher than controls on the BDI-II (mean score 16.4 vs. 8.3, p < 0.001). In epilepsy patients, prevalence of minimal, mild, moderate and severe depression were 48.3%, 20.7%, 20.7% and 10.3% respectively, showing a more severe distribution of depression levels (Pearson v2 8.914, p = 0.03) compared to controls, which showed minimal, mild, moderate and severe depression in 80.8%, 8.5%, 6.4% and 4.3% of the cases respectively. Conclusion: This study depicts for the first time the double burden of epilepsy and depression in Albanian patients, recognizing a higher prevalence and severity of depression in epilepsy. Therefore, in order for the need of mental health care to be met, a more careful and patient-oriented treatment strategy may be warranted.

P443 LONG TERM FOLLOW-UP OF NEUROPSYCHOLOGICAL OUTCOME IN PATIENTS WITH TEMPORAL LOBE EPILEPSY Gurses C1, Marufoglu F2, Tumac A3, Bebek N1, Baykan B2, G€okyigit A2 1 Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, 2Neurology, Istanbul University, Istanbul, Turkey, 3Neuropsychology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Purpose: The purpose of this study is to determine the cognitive functions, psychiatric comorbitidies/symptoms, sociodemografic properties and their effects on quality of life in medically and surgically treated TLE patients who have a long term follow up. Method: We analyzed 65 structural/metabolic TLE patients (30 medical/35 surgical) whose diagnosis were based on clinicand electrophysiological properties and imaging technique. Mean epilepsy duration was 24.6 10.9 years (range 4–46). Standardized assessments included the Neuropsychologic Tests (NPT), psychiatric consultation, Hospital Anxiety Depression Measure (HAD), State-Trait Anxiety Inventory (STAI), Temperament and Character Inventory (TCI) and Quality of Life in Epilepsy Inventory (QOLIE-89). Results: Sixty-five percent of the surgically and 16% of the medically treated patients were seizure free (p < 0.000). Post operative seizure freedom was associated with better attention and verbal fluency (p < 0.05). Seventeen percent-57% of surgical patients showed recovery on various cognitive domains. In long term follow up, memory deficits were (mild to severe) determined in 86% of medical patients, 74% of surgical patients. Visual memory and attention were indicators for a better quality of life (p = 0.000 ve p < 0.05). Overall quality of life (QOL) scores were higher in seizure free (medical/surgery) patients (p = 0.001). However, postsurgical patients’, QOL subscores for emotional well being, seizure worry and medication effects were higher (p < 0.05). Conclusion: In TLE, surgery is superior to medical therapy at providing seizure freedom. Postoperative seizure freedom is associated with improvement in nonmemory functions. Cognitive profile is similar at the end of long term follow up for both medical and surgical TLE patients, nonetheless important individiual gains after surgery should be considered. Gains in memory and nonmemory functions are not only observed Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

in seizure free patients but also in patients who have seizure reduction. QOL subdomains for emotional wellbeing, seizure worry and medication effects are better in post surgical patients.

P444 COGNITIVE PROBLEMS IN CHILDREN AND ADOLESCENTS WITH EPILEPSY: VALIDITY OF A STANDARDIZED PROXY REPORT MEASURE (KOPKIJ) Helmstaedter C, Faz-Pandolofo R, Hoppe C, Witt J-A Epileptology, University Clinic Bonn, Bonn, Germany Purpose: This study evaluated the concurrent and external validity of the Cognitive Problems in Children and Adolescents questionnaire (KOPKIJ, German: Kognitive Probleme bei Kinder und Jugendlichen), a proxy report measure for recognizing cognitive problems in pediatric patients with epilepsy. Method: Data from 279 pediatric patients with epilepsy were analyzed. The KOPKIJ was related to the results of the objective routine neuropsychological assessment (NPY), and to two subjective measures, the Child Behavior Checklist questionnaire (CBCL), and a questionnaire for measuring Health-Related Quality of Life in Children and Adolescents (KINDL). Results: Two KOPKIJ subscales “cognition” and “school” and a total score were differentiated, which indicated problems in 35%, 33%, and 32% of the children. Low IQ was evident in 23%, objective impairments in at least one major cognitive domain in 65% of the patients. Behavior (CBCL) and quality of life (KINDL) were impaired in 40% and 21% of the patients. Stepwise regression analyses revealed that objective cognitive performance (IQ, language, visual-spatial functions) explained ~30%, behavior (CBCL) and coping with the disease (KINDL) about ~40%, and clinical features (age at onset) 5–8% of the variance of the KOPKIJ scales. Conclusion: The parents0 impressions of children’s behavior obtained via the KOPKIJ can at best provide a rough estimate of the cognitive status of children and adolescents with epilepsy. The KOPKIJ appears to be even more sensitive to behavioral problems, which in real life situations indeed often co-occure with cognitive impairments. Aspects of the epilepsy did only marginally affect the parents ratings of their children.

P445 COMPLEXITY OF ICTAL-ONSET ECOG PATTERNS IN PATIENTS WITH TYPE II CORTICAL DYSPLASIA Kozlova A1, Korsakova M1, Arkhipova N1, Broutyan A2 1 Burdenko Neurosurgery Institute, Moscow, Russian Federation, 2Burnazyan FMBC, Moscow, Russian Federation Purpose: The objective of this study was to identify the optimal resection margins in extratemporal epilepsy guided by subdural recordings. We analyzed significance of different initial ictal ECoG changes and there combinations. Method: We evaluated the spatial and temporal profiles of ictal-onset ECoG patterns in 10 patients with histopathologically confirmed focal cortical dysplasia type II and focal or regional seizure onset zone. Seizure onset was determined by visually identifying an electrographic seizure pattern and then looking backward in the record for the earliest ECoG change from background activity associated with the seizure. The earliest ECoG change during the first 3 sec was selected as the seizure onset pattern. Results: We observed diverse ictal onset patterns during the first 3 sec: rhythmic slow wave activity, rhythmic waves and spikes, low-amplitude

139 Abstracts gamma range activity, rhythmic sinusoidal activity >10 Hz. In 6 of 10 patients we registered combination of low-amplitude fast activity and rhythmic slow wave or spike – slow wave activity. Focal pattern of isolated rhythmic beta-activity was revealed In 3 patients, in 1 patient there was combination of slow waves and rhythmic spike – slow waves. In most cases the greatest interictal abnormalities were observed in the same locations as initial ictal patterns. Conclusion: Evaluation of the ictal onset zone on ECoG has to take into account complexity of seizure onset pattern. Different patterns may occur simultaneously under adjacent electrodes of subdural grids. Reliable determination of seizure onset zone requires to include all types of initial electrographic changes during first seconds of seizure.

P446 COMPARATIVE DESCRIPTION OF PSYCHIC AND EMOTIONAL STATE OF PARENTS BRINGING UP CHILDREN WITH CHRONIC NEUROLOGIC PATHOLOGY Shalkeich L1, Kudlatch A2 1 Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus, 2Children Neurology, Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus Purpose: Psychoemotional state of parents with children who have chronic neurological disorders has a direct impact on the effectiveness of their treatment and rehabilitation. Method: 23 parent0 s of children with epilepsy psychoemotional state (mean age 30.34 years) (study group – SG) was studied. The control group (CG) consisted of 19 parents of children with cerebral palsy (CP) without symptomatic seizures (mean age 34.35 years). Families were comparable in composition, age of parents and children, social and economic state. Psychoemotional terms of parents were determined by SF36 questionnaire. Results: MCS (mental components scale) middle score was 34 (Me 31.3, r 9.11, m 1.9) for the IG and 47.6 (Me 46.1, r 9.52, m 1.77) for CG. Thus, the difference in points of MCS was 13.6 points (p < 0.05). The following average scores in the IG and CG for MCS and its components – VT, SF, RE, MH – were revealed: 34 (Me 31.3, r 9.11, m 1.9) and 47.6 (Me 50.3, r 8.98, m 2.1), 49.3 (Me 51.4, r 8.43, 1.76 m) and 55.7 (56.2 Me, r 7.98, 1.83 m), 59.1 (me 62.5, r 22.42, m 4.68) and 87.5 (Me 87.5, r 15.6, m 3.58), 39.4 (Me 40.9, r 9.73, 2.03 m) and 51.7 (51.7 Me, r 6.75, 1.55 m), 30.3 (Me 0, r 40.7, 8.49 m) and 70 2 (Me 100, r 36.68, 8 m, 42), respectively. Conclusion: Psychoemotional state of parents in SG is exposed to certain violations to a greater extent than that of parents in CG.

P447 GENERALIZED EPILEPTIFORM ACTIVITY IN SLEEP DISRUPTS COGNITIVE FUNCTIONS IN CHILDREN WITH INTRACTABLE EXTRATEMPORAL EPILEPSY Novák V1,2, Maulisova A3,4, Jezdık P5, Komarek V6,7, Krsek P6,7 1 Department of Pediatric Neurology, University Hospital Ostrava, Ostrava, Czech Republic, 2Faculty of Medicine, Univesity of Ostrava, Ostrava, Czech Republic, 3Department of Psychology, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, 4Department of Psychology, Faculty of Arts, Charles University in Prague, Prague, Czech Republic, 5Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic, 6Department of Pediatric Neurology, 2nd

Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, 7Department of Pediatric Neurology, Motol University Hospital, Prague, Czech Republic Purpose: Sleep is important for learning and memory consolidation as well as for other psychological functions. Interictal epileptiform discharges (IED) can disrupt cognition by various mechanisms. The direct pathophysiological link between electrical status epilepticus during slow-wave sleep (ESESS) and cognitive deficits is established in children with Landau-Kleffner and related syndromes. However, scarce studies analyzed direct impact of IED on cognition in children with focal (especially extratemporal) epilepsy. Method: We analysed retrospectively 48 children who underwent presurgical evaluation due to intractable extratemporal epilepsy at the Motol Epilepsy Center, Prague. All the patients had long-term videoEEG recording, brain MRI and thorough neuropsychological evaluation. Sleep EEG was evaluated both visually and by using a spike detector with dynamic thresholding implemented in the Matlab environment (Janca et al., Brain Topography, 2015). The patients were divided to two groups according to the type of sleep epileptiform activity (presence or absence of generalized semi-periodical IED in NREM sleep markedly disrupting sleep organization). Psychological domains from both groups were compared. Statistical analysis was performed by the SPSS 15.0 software. Results: 24 patients had marked sleep disorganization caused by the presence of generalized semi-periodical IED (we call this pattern „hurdles”). 24 controls diagnosed as well with intractable extratemporal epilepsy but without „hurdles” did not differ from the previous group in gender, age at seizure onset, age at sleep EEG and psychological evaluation, type of epileptic syndrome, etiology and extent of lesions. The general intellectual ability (measured using the age-appropriate standardized tests) was significantly lower in the “hurdles” group (p < 0.01). Autistic spectrum disorder occured in 3 subjects from the „hurdles” and none from the control group. Conclusion: Electrophysiological disruption of sleep caused by epileptiform activity, especially by generalized and periodic IED is an independent predictive factor for intellectual disability in children with focal intractable epilepsy.

P448 ARE THE NEUROPSYCHOLOGICAL PROFILES OF TEMPORAL LOBE EPILEPSY PATIENTS WITH NEURONAL AUTO-ANTIBODIES DIFFERENT? Sezgin M1, Vanlı Yavuz EN2,3, Bilgic B1, Tuzun E4, Hanagası H1, Bebek N2, Gurses C2, Oktem Tanor O1, Baykan B2 1 Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, 2Departments of Neurology and Clinical Neurophysiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, 3Koc University, School of Medicine, Istanbul, Turkey, 4Department of Neuroscience, Istanbul Faculty of Medicine, Institute of Experimental Medical Research, Istanbul University, Istanbul, Turkey Purpose: Neuronal auto-antibodies (NAA) were first recognized in limbic encephalitis and their presence was shown in chronic epilepsy patients. Our aim was to investigate the neuropsychological profile of temporal lobe epilepsy (TLE) patients with NAA in comparison to the seronegative patients Method: We investigated our epilepsy center’s database and selected the TLE patients who were screened for the presence of NAA and who had undergone a neuropsychological evaluation between 2010 and 2014. TLE diagnosis was based on the presence of typical aura originating from the temporal lobe and/or history of focal seizures with loss Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

140 Abstracts of consciousness and temporal spikes/sharp waves during electroencephalography (EEG) investigation. The sera of TLE patients were tested for antibodies against voltage gated potassium channel (VGKC) complex antigens, contactin-associated protein-like 2 (CASPR-2), leucine-rich glioma inactivated 1 (LGI1), anti-glutamate decarboxylase (GAD), N-Methyl-D-Aspartate (NMDA) receptor, glycine receptor (GLY-R), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPAR), type A gamma aminobutyric acid receptor (GABAAR). Standard neuropsychological evaluation performed in the patients included 15-word verbal memory process test, Weschsler Memory Scale (WMS) visual reproduction subtest, digit span test, phonemic and semantic fluency tests, Stroop test and facial recognition test. Descriptive statistics were applied and the seropositive and seronegative patient groups were compared using Mann–Whitney U test. Results: We found NAA against CASPR-2 in eight, uncharacterized VGKC-complex antigens in six, GLY-R in six, NMDA-R in eight, GAD in two and GABAAR in one patient out of 98 TLE patients; so there were 31 seropositive patients and 67 seropositive patients. There were no significant difference in any test included in the neuropsychological test battery between the seronegative and seropositive TLE groups. Conclusion: Neuropsychological profile of TLE patients with NAA were found to be similar to TLE patients without any known NAA in their sera. Our findings did not support a more severe cognitive impairment in the seropositive group.

P449 A 7 YEAR NEUROPSYCHOLOGICAL FOLLOW-UP OF A WELL FUNCTIONING GIRL WITH AICARDI SYNDROME Tuft M1, Lund C2 1 Oslo University Hospital, National Centre for Rare Epilepsy Related Disorders, Oslo, Norway, 2Oslo University Hospital, National Centre for Epilepsy, Oslo, Norway Aicardi syndrome is a rare neurodevelopmental disorder, defined by Jean Aicardi in 1965. The main diagnostic features are agenesis of corpus callosum, chorioretinal lacunae, and infantile spasms. The outcome is in general severe, with poor cognitive development and refractory epilepsy. With a few exceptions, it affects only girls. The etiology is thought to be genetic, but a causative gene has not yet been revealed. Purpose: In an epidemiological study in Norway, the Aicardi population was cognitively investigated. One of the participants differed from the others, in that she had no epileptic seizures and had a better cognitive level of functioning. She was previously investigated at the age of 6 years and retested at the age of 13. Method: The initial testing at 6 years: Wechsler Preschool Scale of Intelligence-R was used. At age 13: Wechsler Intelligence Scale for Children, fourth ed was used, as well as selected tests from Leiter International Performance Scale-R and single tests from NEPSY. Results: At 6 years she had a verbal IQ of 55, performance IQ of 72 and a full scale IQ of 61. At age 13 she had a verbal IQ of 50, perceptual reasoning IQ of 76, working memory IQ of 54, processing speed of 60 and a full scale IQ of 56. Conclusion: The results at age six were similar compared to 7 years later. At the age of 13, the girl developed well according to her previous results. This is unlike most individuals with Aicardi syndrome, who in general perform at a lower level as they grow older. At age 13, this girl could follow normal conversations on a simple level, although with short sentences and a limited vocabulary. She could also read and write. She was diagnosed with F 70, mild mental retardation. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P450 DEVELOPMENTAL DELAY IN VERBAL WORKING MEMORY (WM) AT THE START OF PRIMARY SCHOOL IN CHILDREN WITH EPILEPSY COMPARED TO CONTROLS MATCHED FOR VERBAL SHORT TERM MEMORY (STM) van Iterson L SEIN/De Waterlelie, Cruquius, The Netherlands Purpose: Working Memory (WM), the ability to mentally hold and manipulate information, is understood to be crucial already in the early school years. The present study focused on the development of WM in young children with epilepsy. Specifically, the research question was whether young children with epilepsy show a deficit in early WM development. Method: Participants were 35 five- and six- year olds with epilepsy. Mean age = 6.3 years (SD = 0.5), Mean age at epilepsy onset = 3.1 years (1.7); mean duration of epilepsy to test = 3.1 years (SD = 1.6), FS-IQ = 96.7 (SD = 14.0), Epilepsy syndrome severity = 5.4 (SD = 1.8). Number of AEDs tried (n) zero 7; one 7; two or more 19, unknown 2. Seizures (n): generalized 3; focal 22; uncertain/unknown 10; (also) frontal 1; (also) temporal 11. Participants were matched for age and identical scores on STM (maximum number of digits repeated forwards, mean = 4.1; SD = 0.7) to 35 typically developing controls (FS-IQ = 101.6; SD = 11.7). WM was assessed as maximum number of digit repeated backwards, mean = 2.1 (SD = 1.3) in epilepsy and 2.6 (SD = 1.2) in controls. With linear regression analysis and ANCOVA’s, the contribution of age, sex, group and STM to WM was assessed. Results: STM (p = 0.035), age (p < 0.001), group (p = 0.041), but not sex, significantly contributed to WM, explaining 33% of the variance in WM. Independent of group, a substantial number of 5-year olds were still unable to perform the task. Controls showed significant age gains (p = 0.001) not (yet) seen in epilepsy (p = 0.068) and outperformed children with epilepsy at age 6 (p = 0.015). No significant contribution was found for distinct epilepsy variables. Conclusion: Given identical STM scores, 6-year olds with epilepsy lag behind in WM development relative to controls. At the start of primary school, teachers should account for reduced WM capacity in children with epilepsy.

P451 NEUROPSYCHOLOGICAL OUTCOME AFTER TEMPOROBASAL VS. TRANSSYLVIAN APPROACH FOR SELECTIVE AMYGDALOHIPPOCAMPECTOMY IN PATIENTS WITH TEMPORAL LOBE EPILEPSY – A RANDOMIZED PROSPECTIVE CLINICAL TRIAL Vogt VL1, Delev D2, Grote A2, Schramm J2, Elger CE1, Helmstaedter C1 1 Department of Epileptology, University of Bonn, Bonn, Germany, 2Department of Neurosurgery, University of Bonn, Bonn, Germany Purpose: To compare the effects of different surgical approaches for selective amygdalohippocampectomy (SAH) in patients with drug-resistent temporal lobe epilepsy on the neuropsychological outcome. Method: Fourty-seven patients were prospectively randomized to temporobasal (13 left, 9 right) vs. transsylvian (13 left, 12 right) approaches for SAH. Memory, language, attentional and executive functions were assessed before and approximately 1 year (M = 17.7 months) after surgery. MANOVAs with “surgery” (pre-/postsurgical assessment) as within subject variable and “approach” and “side” as between subject factors were calculated for each cognitive domain.

141 Abstracts Results: There were no baseline differences in demographic, clinical or cognitive variables. Complete seizure freedom (Engel I A) was achieved in 62% of all patients without a group difference. MANOVA revealed a main effect of side for verbal memory and language only and no significant interactions with approach. Post hoc tests nevertheless revealed worse verbal memory and semantic fluency after temporobasal approach irrespective of the side of surgery. No effects were obtained for changes in figural memory, attention or executive functions. Conclusion: Our results indicate mostly no differential cognitive outcomes dependent on surgical approach alone or in interaction with the side of surgery. Apart from a negative effect of a temporobasal approach on semantic fluency the study fails to replicate our previous study working with matched pairs. Overlap of patients from both investigations was minimal. Presumably sample sizes were too small to control for all relevant variables in a randomized study design.

P452 EMOTION RECOGNITION IN PATIENTS WITH MESIAL TEMPORAL LOBE EPILEPSY Zaborowska O1, Bala A1,2, Szantroch M2, Rysz A2, Marchel A2 1 Faculty of Psychology, University of Warsaw, Warsaw, Poland, 2 Department of Neurosurgery, Medical University of Warsaw, Warsaw, Poland Purpose: There is a relation between the occurrence of epileptic focus in the mesial temporal lobe and lower ability of emotion analysis by limbic structures. The aim of this study was to investigate how patients with mesial temporal lobe epilepsy (MTLE) recognize and understand emotions based on the Salovey and Mayer’s emotional intelligence model. Method: The study involved patients with intractable MTLE (n = 15) and a control group (n = 15) consisting of healthy subjects. In group of patients the average number of years from epilepsy onset was 16.6 (SD = 7.8) and the average number of seizures (monthly) was 6.7 (SD = 5.4). Groups were matched in terms of age, sex, handedness and level of education. The subjects from both groups were examined with two tests evaluating: ability of recognition of emotions on photographs of faces (SIE-T test) and knowledge about emotions and metaemotional processes (TRE test). Results: The results of the research supported the hypothesis about the lowered ability of emotion recognition on faces (t = 2.37; p < 0.05) as well as lowered level of theoretical understanding of emotional processes (t = 4.68; p < 0.001) in patients with MTLE, which is in line with previous findings. Conclusions: Temporal lobe epilepsy can affect the ability of recognizing and understanding emotions. Considering the low number of subjects in the groups the research requires to be replicated.

Neuropsychology and Psychiatry in Epilepsy 2 Tuesday 13th September P453 SEIZURE COUNTING OF CLINICAL DRUG TRIAL PARTICIPANTS Blachut B, Hoppe C, Surges R, Elger CE, Helmstaedter C Epileptology, University of Bonn, Bonn, Germany Purpose: Patients0 self-reported seizure counts provide essential information for individual treatment regimes and they represent the major and often primary outcome parameter of clinical drug trials. This study evaluated seizure counting and documentation behavior of former clinical drug

study patients as compared to historical data from patients having not participated in any drug trial. Methods: 100 adult patients (drug trial group DTG) from twenty-two phase II, III or IV studies investigating safety and efficacy of antiepileptic drugs were contacted by phone and interviewed in a structured way in regard to their seizure documentation behavior, their clinical and demographic characteristics. Answers were retrospectively compared to those from 132 patients who did not participate in drug trials (NDTG) and answered the same questions as part of a recently published study (Blachut et al., Seizure 2015; 29:97–103). Results: DTG were older and lower educated compared to NDTG patients but reported comparable seizure frequencies. The estimated rates of documentation (49.55% vs. 43.75%) were similar as were the motives for documenting (own overview & for the physician). DTG patients reported less frequently that they “don0 t want” (7.8% vs. 29.6%) or “forget” to document (3.9% vs. 36.4%). Conclusion: The same high rate of ~50% underreporting in both study groups seriously questions the validity and reliability of the outcome parameter seizure count. In light of the growing digital healthcare monitoring market, an automated and reliable seizure detection device for use in clinical drug trials and other scientific epilepsy related investigations would be highly appreciated. Acknowledgement: This study was generously supported by the Marga and Walter Boll-Stiftung, Kerpen and the Verein zur F€orderung der Epilepsieforschung e.V., Bonn.

P454 EPILEPSY IN ELDERLY PEOPLE AND AFFECTIVE DISORDERS Druzhinin A1, Mikhailov VA2, Kissin MY3 1 Psychosomatyc Neurorehabilitation, St.Petersburg V.M. Bekhterev Psychoneurological Research Institute, Sankt Peterburg, Russian Federation, 2St.Petersburg V.M. Bekhterev Psychoneurological Research Institute, Sankt Petersburg, Russian Federation, 3Centre Epileptology, First St. Petersburg I.P. Pavlov State Medical University, Sankt Peterburg, Russian Federation Purpose: The objectives of this research were: (1) to study non-psychotic disorders (NPD) in patients with symptomatic epilepsy and in elderly post-stroke seizure-free patients. Method: Two patient groups (141 persons) were studied. In Group 1 (101 patients: 31 men and 34 women), the disease course was complicated by the development of symptomatic localization-related epilepsy. In Group 2 (control group of 40 patients: 28 men and 12 women), no clinical manifestations of epilepsy were found. The average age in Groups was 63.0 years. Results: The prevalence of affective disorders of the depressive spectrum was higher in Group 1 (Group 1 – 78.9% of the patients; Group 2 – 33.3%), whereas the prevalence of affective disorders of the anxiety spectrum was higher in Group 2 (Group 1 – 21.1%; Group 2 – 66.7%). The average depression scores in the groups were 34.81 2.72 and 28.57 3.07 points, respectively, on the BDI scale; and 21.84 1.50 and 13.79 1.36 points (p ≤ 0.01), respectively, on the HDRS scale. In Group 1, a marked intra-structural correlation between depression and anxiety scores, on the one hand, and other psychopathological factors (up to 0.819**) and the Global Severity Index (GSI), on the other hand, was found. In Group 2, only a weak correlation between anxiety and GSI scores (up to 0.828*) was found. Analyzing the group of patients with epilepsy, we found multiple reciprocal correlations between depression and anxiety scores (according Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

142 Abstracts to the HDRS, SCL-90-R and STAI inventories) on the one hand, and quality-of-life domains, on the other hand. Conclusion: The study results have revealed a high intensity of depression and anxiety in elderly patients with symptomatic epilepsy, which, undoubtedly, determines their health-related quality of life. Thus, emotional affective disorders in the pathogenesis of epilepsy in elderly people play a significant part in the changes in their quality of life.

P455 AUTOIMMUNE (LIMBIC AND EXTRALIMBIC) ENCEPHALITIS – OUR RECENT EXPERIENCE WITH THE NEW ETIOLOGY OF EPILEPSY Jakubčiaková V, Slonkova J Department of Neurology, University Hospital Ostrava, Ostrava, Czech Republic Introduction: The limbic encephalitis is quite a new unit of disorders manifested by the acute onset of epileptic seizures accompanied by an acute onset of the cognitive impairment and various psychiatric symptoms. Methodology: A retrospective analysis of the case studies of five patients admitted to the Teaching Hospital in Ostrava within the years 2011–2015 diagnosed by autoimmune encephalitis. The diagnosis was conducted through neurological assessment, electroencephalography, the cerebrospinal fluid analysis, paraneoplastic antibodies assay, specific autoimmune encephalitis antibodies assay, brain MR imaging and response to the therapy. Conclusion and discussion: Patients with an acute onset of epileptic seizures accompanied by the cognitive impairment should be primarily directed to the neurological assessment, cerebrospinal fluid analysis including the specific autoimmune antibodies assay and to the brain MR imaging. Some patients are possibly initially treated at psychiatric wards for the acute psychosis or at the infectious diseases wards for the viral/ herpetic encephalitis. Early diagnosis and treatment is crucial. Diagnosis can be conducted through the electroencephalography, brain MRI and cerebrospinal fluid analysis. The immunotherapy (administration of methylprednisolone, plasma exchange or intravenous immunoglobulins) should be initiated immediately after suspecting autoimmune encephalitis. Negative cerebrospinal fluid analysis finding does not eliminate the autoimmune brain inflammation. In case of paraneoplastic brain affection, the tumour removal and oncological treatment is the first line therapy. Three of our patients are continuously treated for the secondary epilepsy and are well compensated. The decision to terminate the corticosteroid therapy should be based on the follow-up cerebrospinal fluid analysis with the detection of low titres of specific autoimmune encephalitis antibodies or negative findings. The literature review is showing that the relapses of the disease are possible. We did not yet used the monoclonal antibodies (rituximab) therapy. The cooperation of neurologists, infectionists and psychiatrists is essential.

P456 PRELIMINARY FIRST CZECH VALIDATION OF EPITRACKâ Javůrková A1,2, Zarubova J3,4, Tomasek M4, Raudensk a J1, 4 Marusic P 1 Department of Clinical Psychology, Motol University Hospital, Prague, Czech Republic, 2Department of Clinical Psychology, FNKV University Hospital, Prague, Czech Republic, 3 Department of Neurology, Affidea-Praha, Prague, Czech Republic, 4Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Purpose: Achievement of maximum seizure control with preservation or even improvement of patient0 s cognitive capabilities is the major aim of epilepsy therapy. EpiTrackâ (2nd edition with recently extended and revised norms) is a screening tool for tracking adverse cognitive effects of antiepileptic medication. We set to validate Czech version of this tool. Method: The test, which comprises six subtests (Speed, Flexibility, Planning, Response Inhibition, Word Fluency, Working Memory), was administered to 255 adults aged 19–74 years. For the first clinical Czech preliminary validation 134 patients (45% with focal epilepsy, 55% with generalized epilepsy) were evaluated. Epilepsy patients underwent objective assessment of premorbid intelligence (CRT) and performed subjective ratings of depression (BDI-II), anxiety (BAI), activities of daily living (FAQ) and quality of life (QOLIE-89). Results: According to age-corrected norms, 44% of patients (n = 134) and 4% of healthy controls (n = 121) demonstrated deficits in executive functions. Objectively assessed executive functions correlated in patient group negatively with premorbid IQ, years of education, psychiatric comorbidities, seizure frequency, polytherapy, earlier age at onset and employment rate. Subjectively evaluated activities of daily living and quality of life (subscales Physical function, Emotional well-being, Pain, Language) made a difference in EpiTrack test performance. We did not found any correlation between EpiTrack scores and overall subjective evaluation of quality of life, depression and anxiety. Conclusion: Czech version of EpiTrackâ seems to be a sensitive tool to screen for possible adverse cognitive effects. Further studies with testretest and criterion validity are needed to confirm validity and reliability.

P457 CLINICAL COURSE OF PERSONALITY DISORDER ASSOCIATED WITH EPILEPSY Lee S-Y1, Lee K-U2 1 Neurology, Kangwon National University School of Medicine, Chuncheon, Korea, 2Psychiatry, Kangwon National University School of Medicine, Chuncheon, Korea Purpose: Personality disorder (PD) often occurs in the people with longstanding and intractable epilepsy, with characteristic features of viscosity, lability, hyperreligiousity and aggression. Epilepsy patients with PD are often referred to psychiatry clinic, prescribed antipsychotics and sometimes diagnosed as schizophrenia or mania. We purposed to review the clinical course of epilepsy patients with PD. Method: We reviewed clinical records of the patients with typical epileptic PD who needed psychiatric intervention and were followed up more than 1 year, identified from the registry of epilepsy clinic. Results: We identified four patients with typical epileptic PD. They were all women with intractable epilepsy for more than 20 years before they were referred to our epilepsy clinic. After optimization of antiepileptic drugs, one patient became seizure free and emotionally stable for recent 6 years with reduced dose of antipsychotics. Two other patients had better but incomplete control of seizures. They still have epileptic PD but their behavior is acceptable for family life with or without maintenance of antipsychotics. The other patient was reluctant to take medication because of religious delusion. Severity of epilepsy and PD didn’t change and she is at risk of divorce. Conclusion: Epileptic PD correlates with the severity of epilepsy. Their delusion and hyperreligiosity often disturb the treatment of epilepsy. Therefore, initial psychiatric intervention is helpful to control not only PD but also epilepsy. After seizure control, antipsychotics can be tapered carefully.

143 Abstracts P458 RISK FOR VERBAL MEMORY DEFICITS CAUSED BY DEPTH HIPPOCAMPAL ELECTRODES: AN EXPLORATIVE STUDY Ljung H1, Nordlund A2, Strandberg M1, Bengzon J1, K€allen K1 1 Sk ane University Hospital, Lund, Sweden, 2Sahlgrenska Academy at University of Gothenburg, Institute of Neuroscience and Physiology, Gothenburg, Sweden Purpose: To study the possible long-term impact of depth hippocampal electrodes on memory function. Methods: 32 drug-refractory patients suffering from temporal lobe epilepsy (TLE) were recruited. All patients had undergone evaluation for epilepsy surgery followed by either right temporal lobe resection (TLR; n = 8) or rejection from resective surgery (n = 24). The study group, G1 (n = 16), consisted of patients evaluated with longitudinally placed depth electrodes in the hippocampus of the dominant hemisphere during presurgical work-up. The control group (G2), evaluated without depth electrodes, was matched against G1 for: right TLR/no TLR, degree of seizure control, age at seizure onset, biological age, education, handedness and baseline memory function. All patients underwent repeated neuropsychological testing: once during the pre-surgical work up (T1) and once at longterm follow up (T2; median = 60 months). A battery of six memory tests was used to assess verbal and non-verbal memory. Differences in memory performance between groups were analyzed by the Mann–Whitney U test. Results: At T1, the groups did not differ in any of the variables assessed. At T2, G1 showed a strong tendency (effect size: 0.68) towards performing worse than G2 on a verbal list learning test, although only borderline significance (p = 0.073) was achieved. The risk for verbal memory deterioration (>30%) at T2 was 50% higher in the group having received depth electrodes (relative risk ratio: 1.5). Conclusions: Our study is the first to suggest a possible risk for persistent verbal memory deficits caused by longitudinal depth hippocampal electrodes during intracranial monitoring for epilepsy surgery. The results imply the need for further investigation, to provide crucial information for choice of electrode placement in pre-surgical evaluation for TLR.

P459 ETHICAL, CLINICAL, AND SOCIAL ASPECTS OF TREATMENT OF EPILEPSY IN PATIENTS WITH COMORBID DEPRESSION Mikhalovska-Karlova EP1, Mikhailova O2 1 N.A. Semashko National Research Institute of Public Health, Moscow, Russian Federation, 2The Institute of Living, Psychiatry, Hartford, CT, United States Purpose: Epilepsy is an illness with a high level of comorbidity. The most common comorbid disorder is depression. Among the reasons is the fact that the diagnosis of epilepsy is stigmatizing, which imposes serious limitations on personal behavior and lifestyle. Yet depression is often left unaddressed. In 54% of comorbid patients, depression was not diagnosed and only 17% were prescribed anti-depressants. Aim: Investigation of physicians’ motivation to apply bioethical principles and of its implications for treatment of comorbid patients.

bioethics, 29% cannot identify the model they use. 70% admit to significant deficits in their knowledge of bioethics. When seeing comorbid patients, many neurologists refer them to psychiatrists for antidepressants. However, in Russia with its history of punitive psychiatry, the patients rarely follow the referrals because of fear of further stigmatization and discrimination. Given the stigma and the fact that anti-depressants, if prescribed without taking into account the neuropathology, can contribute to epileptogenesis, non-psychopharmacological approaches, specifically psychotherapy, become an effective alternative. Conclusion: There is a discrepancy between clinicians’ high level of motivation to apply bioethics and their poor knowledge of the subject, which may lead to failed interventions or even practices reinforcing stigma. To reduce this discrepancy, courses in bioethics for epileptologists should become part of their continuous education. The adherence to bioethical principles (e.g., protection of the most vulnerable groups) will encourage epileptologists to cooperate with other medical and non-medical professions and seek interdisciplinary solutions to their patients’ clinical needs.

P460 SOCIAL COGNITION AND PREFRONTAL FUNCTIONS IN PATIENTS WITH EPILEPSY TREATED WITH ESLICARBAZEPINE Sanabria A1, Abraira L1, Mazuela G1, Ortega G1, Toledo M1, Quintana M1, Gonzalez-Cuevas M1, Santamarina E1, Serrano P2, Ramirez T2, Salas-Puig X1 1 Unidad de Epilepsia, Hospital Universitari Vall0 Hebron, Barcelona, Spain, 2Unidad de Epilepsia, Complejo Hospitalario Torrecardenas, Almeria, Spain Objective: We aimed to evaluate the impact in social cognition and prefrontal functions in adults patients with partial onset seizures who received treatment with Eslicarbazepine. Methods: We prospectively assessed atentional-executive functions and theory of mind tasks in epilepsy patients before starting an antiepileptic drug and after the stabilization of the treatment 3–6 months later. Quality of life, anxiety and depression were also assessed. All patients had the diagnostic of epilepsy and were treated at least with a new antiepileptic drug. Results: From the 38 patients evaluated at baseline, 15 were started on Eslicarbazepine and completed the protocol. In the follow-up, 6 of them converted into sequencial monotherapy. The median age was 47.5 (15.8) years of average and 53% were females. 70% of patients were responders to treatment with ESL median dose of 800 mg [400–1,200] and showed no limiting adverse events. Patients with ESL improved significantly the Faux-Pas task of the theory of mind (p = 0.046), and the direct digits (p = 0.002), inverse digits (p = 0.035) and symbol digit (p = 0.048) tasks in the prefrontal function assessment. The global quality of life also improved (p = 0.048). For values, see Table 1. There were no significant changes in the rest of items, although most of them were more likely to improve. Conclusion: ESL may improve the global quality of life in patients with epilepsy not only due to the effect in the control of seizures in the absence of major adverse events, but for the positive effect over the prefrontal functions and social cognition.

Materials: 25 years of experience of teaching bioethics to medical students and physicians, participating in expert ethics committees, clinical social work with depressed patients. Methods: Sociological surveys, self-administered questionnaires, interviews with epileptologists. Results: Index of motivation (IM) of epileptologists to apply bioethics is high: 0.8–0.95. However, while over 97% try to follow the principles of Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

144 Abstracts P461 SOCIAL COGNITION AND EMOTION PERCEPTION IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY Schmid E1, Kuchukhidze G1,2, H€ofler J1, Trinka E1,3 1 Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University of Salzburg, Salzburg, Austria, 2 Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria, 3Centre for Cognitive Neuroscience, Salzburg, Austria Background: Juvenile myoclonic epilepsy (JME) is the most common age-related idiopathic generalized epilepsy with an elevated prevalence of psychiatric comorbidities, particularly anxiety, mood, and personality disorders. Further, cognitive deficits, mainly implicating the frontal lobes affecting attention and executive functions, poor social adjustment and behavioral disturbance are often observed in JME patients. In recent advanced brain imaging studies on JME patients, emotional and behavioral problems have been associated with subtle structural and functional alterations mainly in the frontal cortex and thalamus. Methods: We performed a pilot study with various neuropsychological Theory of Mind (ToM) tests (Faux Pas Test, Reading the Mind in the Eyes Test, Moving Triangles) in order to examine social cognition and emotion perception in JME patients (n = 6; 3 women; mean age 30 11) and healthy controls (n = 6; 3 women; mean age 30 4). All study participants were also tested by the Structured Clinical Interviews for DSM-IV Axis I (SCID-I) and Axis II (SCID-II) personality disorders. Results: In JME patients, ToM tests revealed a clear tendency of frequent incorrect responses in various ToM tests compared to healthy controls (“Faux Pas Test” – 16% vs. 6%; “Reading the Mind in the Eyes Test” – 42% vs. 28%; “Moving Triangles” – 69% vs. 53%). These differences, however, were not statistically significant in this small sample. JME patients also showed obvious deficits in the SCID Axis I and Axis II personality disorders (in 43% of patients vs. 0% in healthy controls). Conclusion: Personality disorders (Axis I and II) in JME patients may be associated with ToM deficits, in particular social cognition and emotion perception leading to poor social adjustment and behavioral disturbances. Further examination with a bigger study population is needed.

P462 A SYSTEMATIC REVIEW OF NEUROPSYCHIATRIC COMORBIDITIES IN PATIENTS WITH BOTH EPILEPSY AND INTELLECTUAL DISABILITY van Ool JS1, Snoeijen-Schouwenaars FM1, Schelhaas HJ2, Tan IY1, Aldenkamp AP1,3,4,5, Hendriksen JG1 1 Kempenhaeghe Epilepsy Center, Heeze, The Netherlands, 2 Academic Centre for Epileptology Kempenhaeghe, Heeze, The Netherlands, 3Maastricht University Medical Centre, Maastricht, The Netherlands, 4University of Technology, Eindhoven, The Netherlands, 5University Hospital, Gent, Belgium Purpose: Epilepsy is particularly common in people with intellectual disability (ID). The care for people with both epilepsy and ID can be complicated by the presence of co-occurring neuropsychiatric disorders, defined as psychiatric symptoms, psychiatric disorders, and behavioral problems. The aim of this study was to investigate associations between epilepsy or epilepsy-related factors and neuropsychiatric comorbidities in ID patients and between ID and neuropsychiatric comorbidities in epilepsy patients. Method: We performed a systematic review of the literature, published between January 1995 and January 2015, retrieved from PubMed/Medline, PsychInfo, and ERIC. For each study, we assessed the risk of bias using the SIGN-50 methodology. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Results: Fifteen studies were identified that received a low or acceptable risk of bias evaluation. Neuropsychiatric comorbidities were examined in relation to epilepsy in nine studies, to epilepsy-related factors, such as seizure activity, seizure type, and medication, in four studies, and to the presence and degree of ID in five studies. We can conclude that the presence of epilepsy only was not a clear determinant of neuropsychiatric comorbidities in patients with ID, although a tendency towards negative mood symptoms was identified. Epilepsy-related factors indicating a more severe form of epilepsy were associated with neuropsychiatric comorbidity as was the presence of ID as compared to those without ID in patients with epilepsy, although this should be validated in future research. Conclusion: This review emphasizes the relevance of performing systematic and longitudinal studies on neuropsychiatric comorbidities in patients with both epilepsy and ID according to standardized guidelines, in order to acquire generalized conclusions that can help improve the quality of care for this population.

Neuropsychology and Psychiatry in Epilepsy 3 Wednesday 14th September P463 THE RATE OF PSYCHIATRIC COMORBIDITY IN PSYCHOGENIC NONEPILEPTIC SEIZURES COMPARED WITH EPILEPSY IN WHOM HAVE DEMAND FOR WORKING DISABILITY FOR EPILEPSY € Bozdemir H Aslan K, Balal M, Salkım O, Neurology, C ukurova University Faculty of Medicine, Adana, Turkey Background: Epilepsy is a chronic disorder which can be result with working disability. Psychogenic nonepileptic seizures (PNES) commonly misdiagnosed as epilepsy. On the other hand, PNES could be seen in 5–20% of epileptic patients. The aim of this study is to evaluate the frequency of PNES and comorbid psychiatric disorder in epileptic patients in whom have demand of working disability for epilepsy in epilepsy monitoring unit. Method: A total of 89 patients with epilepsy [88.8% male; mean age 39.3 11.3 (18–71)] were admitted in the video-EEG unit in order to confirm an epilepsy diagnosis and determined seizure frequency for evaluation of working disability between 2013 and 2015. The mean hospitalization duration was 11.9 4.2 days for patients. Results: First history of patients revealed PNES or PNES + epilelsy in 34.8% of the patients. According to history, mean drug usage duration were 18.3 12.9 years and seizure frequency were 5.8 5.5 per months. After monitorizastion, the rate of PNES was 21.3%, PNES + epilepsy was 24.7%. Antiepileptic drugs were stoped after PNES decision. Psychiatric evaluation revealed abnormal in 12.7% of epilepsy patients, 63.2% of the PNES patients, 36.4% of the PNES + epilepsy patients. Psychiatric diagnosis were conversion disorder, depression, psychosis, epileptic personality disorder. Conclusion: We found PNES highly comorbid finding in chronic epileptic patients. Its may be because of secondary income for to be retire because of working disability demand of the patients. That is why the monitorization of such patients is important for confirm an epilepsy diagnosis and comorbid condition.

145 Abstracts P464 PREDICTING THE DIAGNOSIS OF PSYCHOGENIC NON EPILEPTIC SEIZURES AND EPILEPTIC SEIZURES BY VIDEORECORDING Beghi E1, Erba G2, Giussani G1, Juersivich A2, Magaudda A3, Chiesa V4, Lagana A3, Di Rosa G5, Bianchi E1, Langfitt J2 1 IRCCS-Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milano, Italy, 2Department of Neurology, SEC, University of Rochester, Rochester, NY, United States, 3Department of Neuroscience, Epilepsy Center, University of Messina, Messina, Italy, 4Neurology Unit 2, Epilepsy Center, San Paolo Hospital, Milano, Italy, 5Department of Pediatric, Gynecological, Microbiological and Biomedical Science, Unit of Infantile Neuropsychiatry, University of Messina, Messina, Italy Purpose: Aim of this study was to investigate if a video-recorded event could predict the diagnosis of psychogenic non epileptic seizures (PNES) and epileptic seizures (ES) without the aid of the EEG. Method: 23 videos of ES, PNES and other non-epileptic events (NES) from 21 consecutive patients admitted for long-term video-EEG monitoring (VEM) were reviewed by five epileptologists in Italy and USA: four were blind to EEG and clinical information; one was not. Raters assessed videos for quality and content and had to choose among four diagnoses (ES; PNES; Other NES; “Cannot Say”); they had to explain in their own words the reasons leading to the diagnosis. Inter-rater agreement was measured with the kappa statistic. Results: The diagnosis of 7/23 videos (all ES or PNES) (30.4%) were predicted correctly by all raters whereas they failed in 5/23 cases (three Other NES, one PNES, one Cannot Say) (21.7%). The conditions facilitating and interfering with a confident diagnosis were predictable: certain types of signs and symptoms, motor and non-motor manifestations, interaction with bystanders. Degree of accuracy among raters was not uniform and was consistently better for three raters. 2/4 blind raters were as accurate as the non-blind rater. For the overall group, interrater agreement was “moderate” (kappa = 0.52): “moderate” for ES (kappa = 0.53); “substantial” for PNES (kappa = 0.63); “fair” for Other NES (kappa = 0.21). These results were similar to a previous study evaluating the reliability of VEM. Conclusion: Video data alone are sufficient to predict a confident diagnosis of PNES and ES in about one third of cases. The results of this study can benefit all affected patients, particularly those with no access to VEM units.

P465 LET0 S DO THE INDUCTION OF PSYCHOGENIC SEIZURES NONEPILEPTIC? Bora I, Bican Demir A, Ceylan D Medical Faculty, Uludag University,Bursa, Turkey Purpose: It has been reported that almost 10- 30% of the patients sent to the epilepsy centers with a diagnosis of refractory epilepsy were diagnosed with psychogenetic nonepileptic seizure (PNES). A wide variety of provocative methods are used to assist PNES diagnosis. In this study we aim to identify the effect of seizure induction on the diagnosis and prognosis of PNES. Method: We studied 67 cases that were administered intravenous saline and 274 cases that were diagnosed with PNES between 2003 and 2016 in order for PNES seizures to be diagnosed and for seizure semeiology to be identified in video-EEG monitoring unit.e effect of seizure induction on the diagnosis and prognosis of PNES. Results: Of the 61 patients, 65% were women and 35% were men with a mean age of 28. Provocation with intravenous saline was given to 61 of

the 274 patients (22%), and 54 (90%) patients gave a positive response to the treatment. ent–> e effect of seizure induction on the diagnosis and prognosis of PNES. Conclusion: In this study we have concluded that provocative methods are practical, cheap and, most of all, effective for patients to accept a diagnosis. It should be remembered that explaining the diagnosis is the first and most important step of the treatment in clinical practice, and careful patientdoctor communication has a certain positive impact on patients0 seizure prognosis.

P466 IMPORTANCE OF LONG TERM EEG/VIDEO MONITORING IN DISTINGUISHING PSYCHOGENIC NON-EPILEPTIC SEIZURES FROM EPILEPTIC SEIZURES Davelaar S1, Gutter T2 1 Clinical Neurophysiology, Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands, 2Clinical Neurophysiology, Stichting Epilepsie Instellingen Nederland, Zwolle, The Netherlands Purpose: To diagnose atypical seizures in people whom are suspected to have psychogenic non-epileptic seizures (PNES) is a precarious matter. Ability to distinguish epileptic seizures from PNES is strongly related to the experience of the clinician. Aim of current study is to highlight the importance of diagnostic work-up, including long-term video/EEG-monitoring to avoid misdiagnoses of atypical epileptic seizures and to define patient characteristics that differentiate epilepsy from PNES. Method: We retrospectively included all 74 patients (male N 21, mean age 36:10, 15:6–68:6) who visited our PNES-diagnostic trajectory during 2014–2015. Reason of referral and following demographic- and clinical characteristics were extracted from medical charts: date of birth, gender, neurological- and psychiatric history and seizure provoking factors. Video-EEG recordings, were classified based on predominant clinical symptoms of the seizures and (onset)location of ictal EEG phenomena. Results: The number of women was significant higher than the number of men (p = 0.001). Reason of PNES-assumption was based in 49% on emotional related features (e.g. anxiety, stress, hyperventilation) and in 51% based on semiology (e.g. atypical semiology, non-responsiveness to AED). During video/EEG-recording 83% of the patients experienced a seizure, in 65% these were classified as PNES, 27% as epileptic. Two percent of the patients showed both, 3% a syncope and 3% as inconclusive. Fisher exact test showed a trend that “reason of referral” was more towards emotional related features over semiological related features in epileptic -group compared to PNES-group (p = 0.08). Conclusion: Our study confirms both female dominance and high prevalence of psychiatric symptoms in the PNES population. However, preconceived ideas of emotional related features within PNES can create a bias by clinicians in assumption of PNES over epilepsy in our patient group. Video/EEG-monitoring remains golden standard in differentiating PNES from epileptic seizure.

P467 QUALITY OF LIFE (QOL) AND DEPRESSION IN PATIENTS DURING VEEG (2005–2014) – WHO SUFFERS THE MOST? Hermsen AM1,2, Andrees A2, Reif PS1, Rosenow F1, Knake S2 1 Epilepsy Center Frankfurt Rhine-Main, Frankfurt, Germany, 2 Epilepsy Center Hesse, Marburg, Germany


146 Abstracts Purpose: Depression is common in People with epilepsy (PWE) and leads to reduced quality of life. Several studies have found high comorbidities in certain subgroups of PWE. Factors contributing to psychopathology in epilepsy are diverse, including seizure frequency, etiology and genetics. We aim to determine risk factors for depression in a well-characterized and large group of PWE. Method: Patients in the VEEG-unit of a tertiary epilepsy center were handed the QOLIE-31 and BDI I/II between 2005 and 2014. Data of 635 patients (89% presurgical candidates, n = 565) was analyzed retrospectively. Clinical data (e.g. diagnosis, seizure onset, seizure types) were drawn from the medical records.

subscales, except with phobia. IDDI specific scales: paroxysmal irritability and euphoric moods didn’t correlate to SCL subscales. QOLIE-31 total score was significantly negatively related to IDDI total score (r = 0.40; p = 0.001). Multiple regression analysis showed QOLIE-31 total score was significantly predicted by IDDI scores, determining 19.8% of its variance (F = 5.43; R = 0.445; p = 0.002), specifically by IDDI affective score (b = 0.332; p = 0.008). Conclusion: IDD can be diagnosed in third of patients with epilepsy, and its specific symptoms – paroxysmal irritability and euphoric moods did not correlate to other psychiatric symptoms. IDDI scores, especially labile affective symptoms have significant influence on quality of life in patients with epilepsy.

Results: In total 26.6% had a psychiatric disorder, the majority were depressed (15%). In total 10.7% showed psychogenic non-epileptic seizures (PNES) during VEEG. BDI and QOLIE-31 correlated strongly (r = 0.702, p < 0.001). Mean raw scores of BDI were 12.96, mean Tscores 44.4 on QOLIE. Patients without psychiatric disorder showed BDI = 10.81 and QOLIE = 46.15. Men reported significantly less symptoms in BDI and scored higher on the QOLIE than women (p < 0.001). “Symptomatic” epilepsy patients were less depressed than patients with the diagnosis “cryptogenic” epilepsy (p = 0.007). Patients on monotherapy had less symptoms than those on polytherapy (BDI p = 0.014, QOLIE p = 0.021). GTCS, number of seizures during the VEEG and epilepsy duration did not influence BDI or QOLIE. Higher school education correlated with less depressive symptoms (r = 0.159, p < 0.001). Patients in relationships did not differ from patients without partner on BDI or QOLIE.

P469 SUICIDAL RISK FACTORS IN PEOPLE WITH EPILEPSY Neznanov NG1, Mikhailov VA1, Druzhinin AK1, Kissin MY2, Bocharov VV1, Lipatova LV1 1 V.M. Bekhterev Psychoneurological Research Institute, St Petersburg, Russian Federation, 2First St. Petersburg State I.P. Pavlov Medical University, St Petersburg, Russian Federation

Conclusion: This is, to our knowledge, the largest patient group of PWE measured with standardized questionnaires on depression and QoL during the VEEG. It confirms the high prevalence of psychiatric comorbidities and demonstrates differences in mood between patient groups. The data stresses the clinical need for a comprehensive management of patients and a psychiatric evaluation of patients with chronic epilepsies.

Method: 119 patients with epilepsy (57 males and 62 females) were included. Patients were investigated using Reasons for Living Inventory (RFL Inventory); Questionnaire of suicidal risk (QSR; developed by Razuvaeva T.N., 2005), SCL-90-R, HAM-D, HAM-A.

Purpose: Proper understanding of the psychological characteristics of patients with epilepsy is necessary for the early identification and prevention of possible suicidal behavior.

Purpose: To assess comorbid prevalence of the Interictal dysphoric disorder (IDD) (Blumer 2000) in patients with epilepsy; to correlate IDD symptoms with other psychopathologic symptoms and to define IDD influence on quality of life (QOL).

Results: Psychological assessments were elevated vs. normal in the investigated group of patients. SCL-90-R mean score: somatization – 1.36; interpersonal sensitivity – 0.96; obsessive compulsions – 1.32; depression – 0.97; anxiety – 0.96; phobic anxiety – 0.89; paranoid ideation – 0.96; psychoticism – 0.63; hostility – 0.71. HAM-A: total score – 20.02; psychic anxiety – 9.14; somatic anxiety – 10.86; HAM-D total score – 9.62. Decreased assessment of reasons for living using RFL Inventory: survival and copping behavior – 4.81; responsibility to family – 4.76; child-related concerns – 5.17; fear of suicide – 2.71; fear of social disapproval – 3.64; moral objections – 3.75; total score – 4.14. Increased magnitude of the suicidal risk factors was revealed by QSR assessments: susceptibility to protest reactions – 2.44; susceptibility to affective reactions – 3.5; uniqueness – 2.7; incapacity – 3.45; social pessimism – 2.94; demolition of the cultural values – 2.08; susceptibility to run to extremes – 2.12; temporal future prospect – 2.65; anti-suicidal factor – 3.58.

Method: Adult patients with definite diagnosis of epilepsy (ILAE criteria, 1989) able to understand and complete the questionnaires were included in the study. Patients were assessed with: Interictal Dysphoric Disorder Inventory (IDDI) (Mula et al. 2008), The Symptom Checklist90-Revised (SCL-90-R) and The Quality of Life in Epilepsy Inventory (QOLIE-31 – Serbian validated version; Seizure, 2010).

Conclusion: The highest suicidal risk in people with epilepsy was observed in case of prominent anxiety and depression. People with epilepsy had generally decreased motivation for living strongly related to their quality of life. Suicide risk established for the investigated group of patients significantly exceeded age-adjusted norm. A range of personality factors are important for predicting the level of suicidal risk in people with epilepsy, which is strongly correlated with certain psychological features.

P468 INTERICTAL DYSPHORIC DISORDER IN PATIENTS WITH EPILEPSY Milovanovic M, Jovanovic M Institute of Mental Health, Epilepsy and Clinical Neurophysiology, Belgrade, Serbia

Results: In the group of 80 patients with epilepsy (mean age 42.3 14.4; Female 57.6%) prevalence of IDD definite diagnosis was 34.3%. There were not significant differences between seizure severity groups according to IDDI scores (F = 1.606, p > 0.05). IDDI labile depressive symptoms scores significantly correlated with SCL-90 Somatisation (r = 0.25; p < 0.05), Obsessive-Compulsive (r = 0.32; p < 0.01), Interpersonal Sensitivity (r = 0.40; p = 0.001), Depression (r = 0.29; p < 0.05), Paranoid Ideation, (r = 0.34; p < 0.01) and Psychoticism (r = 0.28; p < 0.05) scales. IDDI labile affective symptoms significantly correlated to Somatisation (r = 0.25; p < 0.05), ObsessiveCompulsive (r = 0.31; p = 0.01), Interpersonal Sensitivity (r = 0.35; p < 0.01), Depression (r = 0.37; p < 0.01), Anxiety (r = 0.38; p = 0.001), Phobia (r = 0.32; p < 0.01), and Psychoticism scales (r = 0.31; p < 0.01). IDDI total score significantly correlated to all SCL Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P470 PERSONALITY TRAITS IN PATIENTS WITH TEMPORAL LOBE EPILEPSY Parente A, Villani F, Didato G, Giovagnoli AR I.R.C.C.S Foundation, Neurological Institute C. Besta, Milano, Italy Purpose: Epilepsy is the most common neurological disease, and since 1965 is recognized as a “social disease.” It is often accompanied by numerous psychological and social difficulties, which may invalidate to the same extent as the crises. In addition to cognitive deficits, changes of

147 Abstracts psycho-behavioral aspects are often reported. This study aims at assessing the impact of personality traits which, if particularly severe, can affect the quality of life in patients with temporal lobe epilepsy (TLE). Method: 63 patients with left and right TLE were subject to an assessment of personality traits, through the completion of a self-administered questionnaire: Millon Clinical Multiaxial Inventory-III, MCMI-III1. Results: 78% of patients with TLE shows the presence of particularly accentuated personality traits: obsessive-compulsive personality trait (34%), with higher incidence in patients with right TLE (76%), and histrionic personality trait (22%). Conclusion: Among the psychosocial factors that can affect the quality of life of people with epilepsy, an important role is played by concerns about the unpredictability of the crises, by the perceived stigma and discrimination associated with diagnosis of epilepsy. Obsessive-compulsive and histrionic personality trait may express a need for control and a tendency to perfectionism for fear of social disapproval, fear of real autonomy and need to get approval demonstrations and acceptance. Recognizing the importance of the traits could help to implement appropriate and targeted interventions to improve the quality of life of people with epilepsy.

P471 SHOULD EVERY CHILD WITH EPILEPSY UNDERGO SCREENING FOR PSYCHIATRIC COMORBIDITIES? Pula S1, McGowan M2, Koch-Stoecker S3, Albery M2, Mula M4 1 Bristol Royal Hospital for Children, Bristol, United Kingdom, 2 Child Development Centre, St. Georges University Hospital, London, United Kingdom, 3Epilepsiezentrum, Bielefeld, Germany, 4Regional Neuroscience Centre, St. Georges University Hospital, London, United Kingdom Purpose: To audit the early identification of psychiatric problems and related-risk factors (family psychiatric history) in children with epilepsy. Methods: The study was carried out in a district paediatric epilepsy clinic. It was retrospective and we included, from the epilepsy service database, all children aged 5–17 years old, with an established diagnosis of epilepsy, but excluding those with severe cognitive impairment and those with drug resistant epilepsies. Results: We identified 45 patients, 20 females and 25 males. 42% of them had generalised type of epilepsy, 27% focal, 24% were diagnosed with electro-clinical syndromes and 7% had focal epilepsy with secondary generalization. Most of them (58%) had active epilepsy. The majority of our cohort was receiving mono therapy. 4% had a sleep disturbance and 27% have been diagnosed with psychiatric comorbid disorders such as: ASD, ADHD, generalized anxiety disorder and suicidal ideation. 4 children were subsequently diagnosed with learning difficulties and, on further assessment were also diagnosed with psychiatric comorbidities. Conclusion: Children without drug-refractory epilepsy and without intellectual disabilities are not routinely screened for psychiatric comorbidities. However, almost one third of them have been diagnosed with a psychiatric comorbidity.

P472 SHOULD CHILDREN WITH ATTENTION DEFICIT/ HYPERACTIVITY DISORDER (ADHD) AND INTERICTAL EPILEPTIFORM DISCHARGES (IEDS) ON AWAKE EEG BE TREATED WITH ANTIEPILEPTIC DRUGS (AEDS) FOR THEIR ADHD SYMPTOMS? Socanski D1, Herigstad A2, Beneventi H1, Einarsdottir S1 1 Division of Psychiatry, Department of Child and Adolescent Psychiatry, Department of Neuropsychiatry, Stavanger University Hospital, Stavanger, Norway, 2Department of Clinical Neurophysiology, Stavanger University Hospital, Stavanger, Norway Purpose: The purpose of this study was to investigate whether treatment with AEDs reduce significantly ADHD symptoms in children with IEDs recorded on baseline routine EEG at the ADHD assessment. Method: This is a retrospective chart review of 517 children (82.4% male), aged between 6 and 14 years diagnosed with ADHD over a 6 year period (between January 2000 and December 2005). At least one digitized 20 min routine EEG including hyperventilation and photic stimulation during wakefulness without sleep deprivation was conducted in all children at ADHD assessment. IEDs were found in 39 cases, 12 of them had previous epilepsy. The use of AEDs was assessed at baseline, 1 and 2 years follow-up. ADHD symptoms scores were assessed with ADHD IV rating scale, in addition to observation by parents and teachers. Results: Of the 39 patients with IED, 22 (56.4%) cases were treated with AEDs. 12 of them had previous epilepsy and were already treated with AEDs, 10 were on monotherapy and 2 on polytherapy (because of difficult to treat epilepsy). 27 children had no epilepsy comorbidity. At 1 year follow-up, 22 patients were treated with AEDs (10 without previous epilepsy). At 2 years, 12 cases still used AEDs, 2 of them had no epilepsy and 10 patients with previous epilepsy (8 monotherapy, 2 polytherapy). The use of AEDs was not associated with sufficient reduction of ADHD symptoms. Methylphenidate was introduced to 36/39 (92.3%) of our cases, and initial positive response (assessed after 4–8 weeks of treatment) was found in 30/36 (83.3%). Conclusion: The use of AEDs alone in treatment of ADHD symptoms in children with IEDs dos not improve ADHD symptoms significantly. ADHD symptoms in ADHD children with IEDs should be treated as other ADHD cases without IEDs.

Others 1 Monday 12th September P473 CLINICAL RESPONSE TO ORAL CANNABIS EXTRACTS IN SEVERE REFRACTORY EPILEPSY: PRELIMINARY EXPERIENCE IN CHILEAN PATIENTS Kuester G1,2, Gazmuri AM1, Ahumada A1, Bobadilla P1,3 1 Fundaci on Daya, Santiago, Chile, 2Neurology, Universidad de Chile, Santiago, Chile, 3Fundaci on Mam aCultiva, Santiago, Chile Purpose: To report our preliminary findings in a series of patients with different types of refractory epilepsy treated with oral cannabis extracts. Method: We retrospectively reviewed consecutive patients seen between May 2014 and February 2016, treated with oral cannabis extracts with at least a 6-month follow-up period. We reviewed demographic/clinical data, type of seizures/epileptic syndrome, etiology, and number of previously used antiepileptic drugs (AEDs). Type of cannabis strain, CBD:THC ratio, dosage, frequency/severity of seizures before and after treatment, adverse events, and AEDs regimen during cannabis Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

148 Abstracts exposure were documented. Quality of life (QOL) changes were estimated using CAVE scale, and QOLIE-31-P, WHOQOL-BREF subscales. Informed consent was obtained. Results: Nine children and two adult patients were selected. Mean age: 11.5 yo (range: 1–37), six females. Etiologies included brain malformations, perinatal hypoxic-ischemic encephalopathy, autism, and tuberous sclerosis. Mean follow-up was 14 mo. Most patients had significant improvement in seizure frequency and one evolved seizure-free. Three patients did not respond or had seizure aggravation by high-CBD extracts. Adverse events included irritability and insomnia but they were easily solved by changing the strain. Most parents/patients reported improvement in behavior, cognition, sleep, alertness, mood and/or motor function, as well as in QOL with cannabis. Conclusion: In this small series of patients with different forms of intractable epilepsy, oral cannabis extracts were dramatically more effective than conventional AEDs previously used and had good tolerability. This has been also shown in previous surveys and case reports. Interestingly, some of our patients did not have good response or were aggravated by high-CBD strains, so the optimal therapeutic cannabinoid ratio could vary among different patients. Large randomized controlled trials are needed to establish efficacy and safety of cannabis extracts in epilepsy. Our Foundation is currently conducting the first medicinal cannabis clinical trial in children with pharmacoresistant epilepsy in Chile.

P474 PERCEPTION AND USED OF ALTERNATIVE TREATMENT AMONG PATIENTS WITH EPILEPSY Lertsinudom S1, Tiamkao S2, Pranboon S3 1 Division of Clinical Pharmacy, Faculty of Pharmaceutical Science, Khon Kaen University, Khon Kaen, Thailand, 2 Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 3Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand Purpose: Epilepsy is a common neurology disease which affects quality of life of patients on physical, mental and social. We have found the increasing of alternative treatments which have been used in epileptic patients. The objectives of this study to study the alternative treatments have been used in epileptic patients and to know the perception of epileptic patients to alternative treatment. Method: Qualitative descriptive study by using in-depth interviews in patients with epilepsy at epilepsy clinic, university hospital, Thailand. Results: 30 patients with average age 46.9 17.1 years old, 60% were females. The most frequency type of seizure was generalized tonic-clonic; 50%, average frequency of seizure was 1.71 times/month. We found that 56.7% of patients used alternative treatments more than 1 item and 33.3% of patients still use alternative treatment currently. Alternative treatments which patients used the most were dietary supplement products 20 persons (36.4%), secondly, herbs and herb products 17 persons (30.9%), rituals and magic 16 persons (29.1%). The most reasons of using are relating to psychological; 63.3%. On the average, patient spent 38 90 USD/person/month for an alternative treatment. Perception of epileptic patient to dietary supplement products, herbs and herb products, rituals and magic were unsatisfied 40%, 41.2% and 18.8% respectively, satisfied 30%, 35.3% and 50% respectively and indifferent 20%, 5.9% and 31.3% respectively. Conclusion: Most of patients used more than 1 item of alternative treatments. Common reasons were psychological effects and cultural issue probably important role to having faith in alternative treatment to treat their seizures. When health care team recognized perception of patient we could be counsel patient effectiveness to prevent antiepileptic drugherb or antiepileptic drug-food supplement interaction and educate patients about the importance of anti-epilepsy drug use. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P476 STRESS AND SEIZURES: DEVELOPMENT AND PILOTING OF A SELF-HELP STRESS MANAGEMENT INTERVENTION FOR PATIENTS WITH SEIZURES Novakova B1, Harris P2, Reuber M1 1 Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom, 2School of Psychology, University of Sussex, Brighton, United Kingdom Purpose: Many patients with epilepsy and dissociative seizures (DS) experience high levels of stress. Stress is the most frequently self-identified seizure precipitant in patients with epilepsy and thought to be causative in patients with DS – even if they fail to report subjective stress symptoms. Although psychological interventions tackling stress in patients with seizures have been described, only a minority of patients currently have access to such therapies. The main aims of this study were to develop a simple, widely applicable self-help intervention targeting stress in patients with epileptic or dissociative seizures, to assess its acceptability, and to provide preliminary evidence for its effectiveness in a pilot randomised controlled trial. Method: A theory-guided self-help intervention booklet was developed using an integrative stress model framework. 82 patients with seizures recruited from outpatient neurology clinics were randomised to Group A, who received the intervention at baseline, or Group B, who received the intervention after 1 month. All participants completed self-report questionnaires including the Smith Stress Symptoms Inventory, Generalised Anxiety Disorder Scale, Neurological Disorders Depression Inventory for Epilepsy, European Quality of Life and Liverpool Seizure Severity Scale at baseline, and at 1- and 2-month follow-up. Participants also provided telephone feedback. Both groups were combined for analysis of pre- vs. post-intervention outcomes (N = 29). Results: Treatment was associated with a significant reduction in selfreported stress 1 month post-intervention (p = 0.011), with a medium effect size (dz = 0.509). The intervention was acceptable, with the majority rating it as helpful (63.6%), stating they planned to continue using it in the future (82.5%), and that they would recommend it to others with seizures (88.1%). There were no significant changes in any of the other measures. Conclusion: Our intervention could be a useful complementary treatment option for reducing the distress associated with seizures, although confirmation in a larger trial is needed.

P477 QUANTITATIVE BIOMARKER OF VNS THERAPY USING EEG DATA Ravan M, Sabesan S LivaNova, Houston, TX, United States Purpose: Vagus nerve stimulation (VNS) is an adjunctive therapy for patients with medically refractory epilepsy. The primary metric used to assess response to VNS is seizure frequency reduction. Seizure severity reduction is also clinically meaningful to patients and can be measured objectively. In this study we utilized a quantitative feature obtained from EEG data around ictal events to identify if automated delivery of VNS at the time of seizure onset reduces the severity of seizures as assessed by reduction of EEG spatial synchronization. Method: 51 patients were enrolled across two clinical trials (NCT 01325623, NCT 01846741) wherein patients were implanted with the AspireSRâ VNS Therapy System. This system automatically delivers stimulation when an increase in heart rate, which may be associated with a seizure, is detected. EEG data were collected from patients prior to and after implant. A total of 124 pre-implant and 156 post-implant seizures were available for analysis. To quantify the severity of each seizure, we extracted a measure of spatial synchronization from EEG data during a seizure as an objective feature. This feature was used to distinguish

149 Abstracts seizures that occurred during the period of closed-loop VNS from the ones that occurred prior to VNS therapy. Results: Application of closed-loop VNS Therapy reduces ictal spatial synchronization (as measured by an EEG-based feature). The mean values and standard deviations of this feature across seizures pre- and postVNS treatment were 90.91 18.12 and 23.27 35.34, respectively, which was significantly lower (p < 0.05) for post-VNS treatment compared to pre-VNS treatment. Therefore, this feature is able to discriminate seizures that occurred following VNS Therapy as the ones with reduced EEG spatial synchronization compared to seizures that occurred prior to VNS therapy. Conclusion: Using EEG spatial synchronization feature, we demonstrate that the closed-loop AspireSR VNS Therapy System may have the ability to reduce seizure severity.

P479 THE EFFICACY OF AN 8 DAY COMPREHENSIVE CARE PROGRAM FOR INPATIENTS WITH EPILEPSY Seyer F, Witt J-A, Elger CE, Helmstaedter C University Bonn/Epileptology, Bonn, Germany Purpose: Epilepsy is more than having seizures. Comorbidities and the patients coping with the consequences of chronic epilepsy represent a major issue in the care of people with epilepsy. In this regard we evaluated the outcomes of a focused comprehensive care program which is procedure within the German Diagnosis Related Group-system (G-DRG) for epilepsy and which involves occupational-, physiotherapy as well as behavioral medical treatment and/or social work. Method: Between September 2008 and October 2014 a total of 1,339 adult patients were rated by the occupational therapists at the beginning and the end of their inpatient stay at the University clinic of Epileptology Bonn/Germany. The assessed outcome dimensions are response, affect, activity, autonomy, communication, fine motor skills and mobility. The data were related to the information from medical files and the results of the neuropsychological evaluation. Results: Based on a total score comprising all dimensions about 80% of the patients were rated as significantly impaired. Baseline positive ratings correlated with lower number of drugs, lower seizure frequency, lower severity of seizures, lower continuance of epilepsy, better neuropsychological status, higher education, lower status of disability, and lower age. After the treatment about 50% of the patients were rated as individually improved. Improvements were seen in all outcome measures and particularly in “response”, “activity” and “affect” with improvement rates of 30%, 25% and 24% of the patients. Furthermore 22% were rated as individually improved in one dimension, 14% in two, and other 10% in three dimensions. Conclusion: Although not controlled, this first evaluation of a short time comprehensive care program for inpatients with epilepsy proves an overall positive effect of the program. Subsequent research should address sustainability and carry over effects of program contents to every day live.

P480 LOW GLYCEMIC INDEX DIET FOR THE TREATMENT OF REFRACTORY EPILEPSY IN CHILDREN AND YOUNG ADULTS: A SYSTEMATIC REVIEW OF EFFICACY Singh L, Kondekar A Department of Pediatrics, Topiwala National Medical College and B. Y. L. Nair Charitable Hospital, Mumbai, India Purpose: To systematically review and synthesize the available evidence on the efficacy of the low glycemic index diet (LGID) in reducing seizure frequency in children and young adults with refractory epilepsy.

Method: Extensive Medline searches were performed. The Cochrane Central Register of Controlled Trials was also searched. Studies were selected for inclusion in the review that reported the reduction of seizure frequency following treatment with LGID in children with refractory epilepsy. The outcome measures used were the percentage (%) of patients with: 1 complete elimination of seizures, 2 Greater than 90% reduction in seizures, and 3 Greater than 50% reduction in seizures. Combined analysis of percentage of patients achieving the relevant outcome measure was performed using the confidence profile method. Results: The evidence consists majority of uncontrolled studies. Of seven studies identified for this review (totally including 214 patients) four are retrospective series of patients from a single institution, two are prospective studies and one is a randomized control trial. For each outcome measure, a test of homogeneity was first run among the included studies with the following results: complete elimination of seizures (v2 = 76.5; p < 0.001); >90% reduction (v2 = 51.8; p < 0.001); and >50% reduction (v2 = 10.6; p = 0.001). Estimates of the rates of improvement by combined analysis (confidence profile method) are complete cessation of all seizures in 12.5% of total patients (95% confidence interval [CI]: 8.65–16.94); > 90% reduction in seizures in 19.1% (95% CI: 14.22–23.97) and >50% reduction in seizures in 64% (95% CI: 58.04–69.95). It is unlikely that this degree of benefit can result from a placebo response and/or spontaneous remission. Conclusion: Although enough controlled trials are lacking, the evidence is sufficient to determine that LGID is efficacious in reducing seizure frequency in children and young adults with refractory epilepsy.

Others 2 Monday 12th September P482 ZINC TREATMENT IN EPILEPSY DUE TO PIGA MUTATIONS Abi Warde MT, Spitz MA, Koob M, Marteau C, Schaeffer E, Chelly J, De St Martin A Strasbourg University Hospital, Strasbourg, France Purpose: PIGA gene causes early severe epilepsy and visceral involvement. Patients frequently present low alkaline phosphatase. We report normalization of alkaline phosphatase and improvement of seizures by zinc supplementation in a patient with PIGA mutation. Method: We report the clinical, electrophysiological and radiological features of a young boy aged 4 years, followed-up since the age of 4 months. PIGA mutation was found by exome sequencing. Our patient presents with intractable focal seizures, complicated by frequent status epilepticus. His developmental milestones are greatly delayed: at the age of 4 years, he is able to sit and crawl and does not have any verbal communication. MRI shows delayed myelination. Alcaline phosphatase was low in the first biological workup. As pharmacological treatment failed to stabilize the seizures, ketogenic diet was introduced at the age of 2.5 years without a great change in the seizure frequency, and was stopped a year later. Vitamins supplementation used with ketogenic diet was maintained by the family, because of their observation of an increase in seizures frequency at withdrawal. Results: We supposed that vitamin effect on seizures was due to the presence of Zinc in the vitamin mixture. Alcaline phosphatase normalized after the introduction of the Ketogenic diet, and remained normal under sole vitamin supplementation. Vitamin mixture was replaced by Zinc at the dosage of 7.5 mg/day. At this time, the patient experienced serial seizures (up to 20/day). Seizures deceased to a frequency of 5–6/ month during the weaks following the introduction. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

150 Abstracts Conclusion: Physiopathology of seizures in PIGA mutations is yet unknown; it may imply alkaline phosphatase which also plays a role in pyridoxal phosphate synthesis. Zinc supplementation normalizes plasma alkaline phosphatase, and reduces seizure frequency. More clinical research must be performed to prove the role of zinc as an alternative treatment in epilepsy.

P483 INVESTIGATION OF THE EXPRESSION OF CALCIUM BINDING PROTEINS IN SOMATOSENSORIAL CORTEX OF WAG/RIJ RATS Arkan S1, Kasap M2, Akman O3, Ates N1, Karson A1 1 Physiology, Kocaeli University, Izmit, Turkey, 2Medical Biology, Kocaeli University, Izmit, Turkey, 3Physiology, Istanbul Bilim University, Istanbul, Turkey Purpose: Absence epilepsy is idiopathic generalized epilepsy, characterizing by a strong genetic predisposition and age-related onset. Typical absence seizures are predominantly spontaneous, and they are accompanied by spike-wave discharges (SWD) in the electroencephalogram (EEG). WAG/Rij is an inbred genetic rat model that exhibits absence seizures and depressive like behaviour. Recent electrophysiological experiments showed hyperexcitable locus in the somatosensory cortex (SPo1) of these animals. This study investigates the changes of calcium binding proteins, which are the parvalbumin (PV), calretinin (CR) and calbindin (CB) proteins during epileptogenesis. These proteins are GABAergic neuron markers and they bind the intracellular calcium ion in the cortical regions of WAG/Rij rats with genetic absence epilepsy. Method: Two and 8 months male WAG/Rij and Wistar Albino rats were used in this western blot experiments. The rats were deeply anesthetized by intraperitonal injection ketamine (80 mg/kg)/xylazine (10 mg/kg) coctail and perfused transcardially with cold physiological saline. The brain hereafter removed and stored 80°C until used. Proteins were separated by 12% SDS-PAGE and transferred to PVDF membrane protein bands were visualized with and chemiluminescence detection system. Protein band densities was measured by Image J Results: Our results indicate that even though there are no significant changes in PV, CR and CB protein levels, the expression of PV tends to decreasement in the somatosensorial cortex of WAG/Rij rats. Conclusion: There is only limited information regarding the roles of the calcium ion in the mechanism that result in the formation of absence seizures. The modulation of intracellular calcium homeostasis has great importance. CaBPs that serve as intracellular calcium sensor and buffer, control the functional properties of cells via distinct mechanisms. Although our results do not show any significant results as statistically, we plan to extend our studies by using different molecular approaches to clarify relations between CaBPs and absence epilepsy.

P484 EVALUATION OF SYNAPTIC PROTEIN ALTERATIONS DURING THE ACUTE, SUB-ACUTE, AND CHRONIC INFLAMMATORY RESPONSE FOLLOWING STATUS EPILEPTICUS (SE) Avdic U, Ahl M, Chugh D, Ali I, Ekdahl Clementson C Division of Clinical Neurophysiology, Clinical Sciences, Lund University, Lund, Sweden Purpose: Synaptic adhesion molecules are thought to modulate the overall activity within a synapse. Altering the expression of adhesion molecules may therefore be a new way to “tune” the synaptic activity and dampen hyperexcitability in epilepsy. Our objective in this study was to evaluate the expression of synaptic proteins acutely (6 and 24 h), subacutely (1 week), and chronically (4 weeks) following temporal status Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

epilepticus (SE). We also studied whether protein expression differed in rats that developed spontaneous seizures (epileptogenesis) after SE compared to those with only acute symptomatic seizures (seizures occurring within 1 week after a brain insult). Method: Temporal SE was electrically induced in the hippocampus of adult male rats. Electrode-implanted rats with no stimulation served as controls. Animals were continuously video and EEG-monitored. They were sacrificed 6 h, 24 h, 1w, and 4w post-SE. Brains were processed for western blot analysis. Results: In the acute phases (6 h and 24 h) following SE, no changes were observed, except for a decrease in the cortex of PSD-95, a scaffolding protein found predominately on excitatory synapses. At 1 week, protein changes were evident in the hippocampus with decreased expression of both postsynaptic proteins PSD-95, gephyrin (scaffolding protein found on inhibitory synapses), NL-1 (adhesion molecule apposed to excitatory terminals), and the presynaptic protein synapsin II. This decrease was not sustained at 4 weeks post-SE. Instead, we observed a decrease in the excitatory adhesion molecule N-cadherin in the hippocampus of rats that had become epileptogenic. Conclusion: We present both excitatory and inhibitory synaptic protein changes 1 week following temporal SE. However, these changes were transient. Instead, we found the adhesion molecule N-cadherin to be decreased in the hippocampus specifically in rats that experience spontaneous epileptic seizures, in addition to the initial SE insult. Further analyses will be needed to verify whether this decrease may predict epileptogenesis.

P486 EXPRESSION OF MIR22 IN MESIAL TEMPORAL LOBE EPILEPSY PATIENTS- A PRELIMINARY STUDY Leal B1,2, Carvalho C1,3, Chaves J4, Boleixa D3, Bettencourt A1,3, Freitas J4, Lopes J4, Ramalheira J4, Costa PP1,5, Martins da Silva A4, Martins da Silva B1,2 1 UMIB – ICBAS-UPorto, Porto, Portugal, 2Lab. ImunogeneticaICBAS – UPorto, Porto, Portugal, 3Lab. Imunogenetica – ICBAS – UPorto, Porto, Portugal, 4Hospital Santo Ant onio – Centro Hospitalar do Porto, Porto, Portugal, 5Instituto Nacional de Sa ude Dr. Ricardo Jorge, Porto, Portugal Purpose: MiR-22 is a microRNA known for its anti-tumor, anti-inflammatory and neuroprotective role. These effects may be achieved through the regulation of an ATP-gated ionotropic receptor P2X7R. It has been recently demonstrated that inhibition of miR-22 is associated with higher hippocampal levels of P2X7R and inflammatory cytokines. Several clinical and experimental studies have demonstrated that these proteins are overexpressed following epileptic seizures. Nevertheless, the role of miR-22 in epilepsy development is still controversial since studies in animal models of Mesial Temporal Lobe Epilepsy (MTLE) have reported both up and downregulation of this miR in hippocampus after seizure induction. Knowing that miR expression is very stable in biological fluids our aim was to characterize miR-22 expression in serum of MTLE patients. Methods: Expression levels of miR-22 and RNU48 RNA gene (reference gene) were quantified by Real-Time PCR in serum of 18 MTLE patients all with Hippocampal Sclerosis (HS) (9F, 9M, mean age = 44.1 11.7 years, age of onset = 13.5 10.6 years, 8 with Febrile Seizures antecedents). A group of 24 healthy individuals was used as control. Relative expression values were calculated using the 2DDCt method. Results: We observed that expression of miR-22 was 3 fold lower in MTLE-HS patients than in controls (p = 0.008). Conclusion: To the best of our knowledge this is the first study to quantify miR-22 expression in MTLE-HS patients. Our results are supported

151 Abstracts by recent experimental studies (Jimenez- Mateos et al 2015) that have showed that miR-22 lower levels are associated with propagation of epileptic seizures. The regulatory mechanisms involved in this process should be further explored since they may be relevant for the development of new therapeutic strategies. Supported by a BICE Tecnifar Grant 2013.

P487 2-DEOXY-D-GLUCOSE-MEDIATED DECELERATION OF KINDLING-INDUCED EPILEPTOGENESIS IS REFLECTED BY 18-F-FDG BRAIN KINETICS Leiter I1, Bascu~nana Almarcha P2, Peter S1, Bengel FM2, Bankstahl JP2, Bankstahl M1 1 Department of Pharmacology, Toxicology and Pharmacy, and Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany, 2 Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany Purpose: A therapeutic option to hold epileptogenic processes leading to acquired epilepsy is still lacking. Recent studies suggest that modulation of cerebral glucose metabolism by 2-deoxy-D-glucose (2-DG) might exert anti-epileptogenic effects. Here, we applied 18-F-FDG PET to investigate effects of 2-DG treatment during epileptogenesis. Method: 6Hz-corneal kindling was performed in mice by twice daily electrical corneal stimulation for 21 days. Seizure response was scored using a modified Racine scale. Saline (n = 12) or 250 mg/kg 2-DG (n = 18) were injected i.p. 18 h before baseline 18-F-FDG PET scans and subsequently 1 min after each stimulation. Twelve additional mice received 2-DG without kindling. Dynamic 60-min 18-F-FDG PET/CT scans were acquired at baseline and on days 10 and 17. A standard MRIbased brain atlas was used to quantify 18-F-FDG uptake. Kinetic modelling was performed to evaluate glucose metabolic rate MRGlu and uptake rate constant Ki. Expression of glucose transporter 1 (GLUT-1) and activation of astrocytes (GFAP) was immunohistochemically analyzed. Results: Kindling progression was attenuated by 2-DG-treatment, mainly in the early phase (up to 29.3 11.8%, p = 0.0009). Kindling in combination with 2-DG treatment increased 18-F-FDG uptake by up to 36.0 10.3% (p = 0.0016) at day 10 in hippocampus, compared to the unkindled 2-DG treated group. At day 10, the 2-DG treated kindling group showed an up to 1.32 fold increase in influx constant Ki compared to the unkindled group as well as a higher MRGlu at day 17 than the saline-treated kindling group. In saline-treated mice, kindling did neither alter 18-F-FDG uptake nor kinetic parameters, but induced astrocytic activation, which was partially attenuated by 2-DG. GLUT-1 expression remained unaltered by kindling or 2DG treatment. Conclusion: Increases in F-18-FDG brain uptake are present only in mice undergoing both, 2-DG-treatment and corneal kindling. Increased F-18-FDG influx is associated with decelerated kindling progression.

P488 ACTIVATION OF TRANSFORMING GROWTH FACTOR BETA (TGFb) SIGNALLING IN MESIAL TEMPORAL LOBE EPILEPSY (MTLE) PATIENTS Paul D1, Dixit A2, Srivastava A1, Tripathi M1, Tandon V1, Banerjee J2, Chandra PS1 1 All India Institute of Medical Science, New Delhi, India, 2 National Brain Research Centre, Manesar, India Purpose: TGFbs are pleiotropic cytokines which are found to be upregulated in various brain disorders. Experimental evidence show that TGFb

is upregulated in neurons (Plata Salaman et al., Mol Brain Res. 2000; 75:248–258) and astrocytes in animal models of epilepsy (Aronica E et al., Eur J Neurosci. 2000; 12:2333–2344). Recent studies in rats show that following blood brain barrier (BBB) damage, albumin binding leads to TGFb signalling activation and contribution to network excitability in epileptogenesis. (Cacheaux LP et al., Neurosci. 2009; 29:8927–8935). However no translational studies on the role of TGFb signalling in epileptogenesis are reported in MTLE patients. In the present study we aim to investigate the expression level change of TGFb1 and its downstream signalling molecules phosphorylated SMAD 2/3 in MTLE versus non epileptic control patients. Method: Protein was isolated from the resected hippocampal samples from MTLE patients (n = 10) and non epileptic control patients (n = 7). Western blot was done with goat polyclonal antibody against TGFb1 and pSMAD2/3 and appropriate secondary antibody. Antibody labelling was visualized by enhanced chemiluminescence and densitometric analysis done by ImageJ software. Protein expression was normalised to expression of GAPDH (loading control). Results: TGFb1 is upregulated in MTLE (106.3 67.4) in comparison to non epileptic control paients (62.44 7.8). pSMAD 2/3 is upregulated in MTLE (pSMAD2: 77.5 25.7) (pSMAD3: 102.8 40.3) in comparison to non epileptic control patients (pSMAD2: 61.7 12.4) (pSMAD3: 76.91 15.7). Conclusion: Our study demonstrates that TGFb signalling is activated in MTLE patients, through the phosphorylation of SMAD 2/3. TGFb pathway activation is an important aspect of brain inflammation and may be associated with BBB damage. Alterations in BBB may affect excitability of brain and lower the threshold for seizures, enhancing epileptogenesis. Further studies on more number of patients are required to elucidate how this pathway is contributing to epileptogenesis.

P489 THE IMPACT OF MUSIC ON THE BIOELECTRICAL ACTIVITY OF THE BRAIN IN CHILDREN WITH IDIOPATHIC EPILEPSY Sakalauskaitė D1, Praninskiene R2,3, Samaitiene R2,3 1 Faculty of Medicine, Vilnius University, Vilnius, Lithuania, 2 Department of Children’s Neurology, Children’s Hospital, Affiliate of Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania, 3Clinic of Children’s Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania Purpose: Emotional and conduct problems are common in children with idiopathic epilepsy. We aimed to find out, whether listening to the music of W. A. Mozart could increase the amount of theta waves in the electrical activity of the brain and induce sleepiness in patients with idiopathic epilepsy. Method: Data of 15 patients, aged 11.1 3.77, 10 males, 5 females, was analysed. All patients underwent EEG with oculograms, electrocardiograms and auditory stimulation of W. A. Mozart’s Sonata for Two Pianos in D major, K.448. We analysed the occipital ratio of theta/alpha waves during 3 min of silence, 3 min of auditory stimulation and the spike ratio. Demographic data of the patient, antiepileptic drugs and variability of the pulse during the procedure were analysed. Results: Five patients fell asleep during the period of music, in average of 1 min 5 s after the start of the period. Ten patients did not fall asleep. The occipital ratio of theta/alpha waves was analysed only in awake patients. A statistically significant increase of occipital theta activity ratio to overall occipital brain activity during the music period compared to the period of silence was observed (0.29 0.21 vs. 0.18 0.15, p = 0.01, T-test). No correlates to gender, age or used drugs were observed. No significant changes in the variability of the pulse were found.


152 Abstracts Three patients of 10, who did not fall asleep, had centrotemporal spikes during both periods 3 min of silence and 3 min of music. A change in the amount of spikes was observed. For 1 patient it decreased during the music period (went from 30 in silence to 27 during the music), for 2 others it increased (went from 10 to 38 spikes and from 4 to 16 spikes respectively).

the over expression of p-glycoprotein, however, continuous treatment till 30 days results in rise of p-glycoprotein levels in brain, indicating the development of pharmacoresistant model. Conclusion: The over-expression of P-glycoprotein in the brain of mice with pharmacoresistant epilepsy is due to a combination of drug effects and epileptic seizures.

Conclusion: Mozart’s Sonata K448 significantly relaxes children with epilepsy by increasing theta activity and inducing sleepiness.

P490 THE MOZART EFFECT COMPARING IN CHILDREN AND ADULTS WITH INTRACTABLE EPILEPSY Shaafi S, Nikanfar M Tabriz University of Medical Science, Tabriz, Iran Purpose: To compare the mozart effect in children and adults with interactable epilepsy. Method: Twenty children (5–11 years) with unprovoked epilepsy whose seizures were clinically not well controlled with antiepileptic drugs were included and compared with twenty adult patients (18– 32 years) with poorly controlled epilepsy. For each patient, digital EEGs had revealed epileptiform discharges in repeated recordings. Two groups of the patients listened to Mozart K.448 for 10 min once a day three days in a week for 3 months. EEG traces were recorded and compared with each other before and each month after of listening to Mozart K.448. Results: Epileptiform discharges significantly decreased in children in compare of adults 25% more. Gender did not affect the results. In two group clinically seizures were decreased also. Conclusion: We conclude that long-term listening to Mozart K.448 may be effective in decreasing epileptiform discharges in children with epilepsy more than adults but in the two groups epileptiform discharges and clinically epilepsy were decreased. This study reconfirms that an antiepileptic effect of Mozart music.

P491 EXPRESSION OF MRP/P-GLYCOPROTEIN IN PHARMACORESISTANT TEMPORAL LOBE EPILEPSY IN PTZ-KINDLED MICE Tanveer M, Simjee SU HEJ Research Institute of Chemistry, Neuropharmacology, Karachi, Pakistan Purpose: Drug resistant epilepsy (DRE) or Refractory epilepsy (RE) is the major concern in this era. About one-third of the epileptic patients eventually develop refractory epilepsy. One of the main cause of refractory epilepsy is the over expression of multi drug transporter; p-glycoprotein (P-gp). P-gp consists of two proteins: MDR1 (MDR1 in humans, mdr1a and mdr1b in rats and mice) and MDR2 (MDR2 in humans and mdr2 in rodents). Out of these genes, MDR1, mdr1a and mdr1b expression leads to drug resistance. Therefore, need to identify and evaluate the cause and treatment of refractory epilepsy is paramount. In our study we established the pharmacoresistantant epileptic mouse model by incorporating phenobarbital. The expression of p-glycoprotein has been evaluated in the established model. Method: In order to evaluate the expression of p-glycoprotein, we established the pharmacoresistant mouse model by treating the kindled animals with phenobarbital over an extended time period. In addition to behavioral observations and scoring, p-gp levels in brain were evaluated by PCR. Result: P-glycoprotein expression was increased in our pharmacoresistant kindled animals. The treatment with phenobarbital initially suppress Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Others 3 Monday 12th September P492 ANTICONVULSANT AND NEUROPROTECTIVE EFFECTS OF ARGAN OIL ON PILOCARPINE MODEL INDUCED STATUS EPILEPTICUS IN WISTAR RATS Bahbiti Y, Amouri H, El Hessni A, Ouichou A, Nakache R, Berkiks I, Bousalham R, Bekjdaouene L, Akhouayri O, Mesfioui A Laboratory of Genetics Neuroendocrinology and Biotechnology, Faculty of Sciences, University Ibn Tofail, Kenitra, Morocco Temporal lobe epilepsy (TLE) is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures and status epilepticus (SE). Although the number of antiepileptic drugs is increasing, none displays neuroprotective or antiepileptogenic properties that could prevent SE induced drug-resistant epilepsy. In this regard, medicinal plants are considered an important source in the development of new drugs with anticonvulsant activity. Thus, Argan oil (AO) has been chosen, in particular, due to its chemical composition rich in polyunsaturated fatty acids, sterols and antioxidants such as polyphenols and tocopherols. The present study aimed at investigating AO effects on 1 latency to first seizure, seizure severity, mortality rate, weight change as well as 2 lipid peroxidation level, nitric oxide and catalase activity in hippocampus after SE induced by Pilocarpine (PC). Wistar rats (1 month old) were daily administred by oral gavage with AO or with NaCl (1 ml/100 g) during 2 months before receiving PC. After the treatments, all groups were observed for 24 h. The catalase activity as well as the lipid peroxidation and nitric oxide were measured using spectrophotometric methods and the results compared to values obtained from saline and PC treated animals. The pretreatment with AO increased the latency to first seizures and reduced mortality rate after SE. AO pretreatment produces significantly reduction of the lipid peroxidation level and nitric oxide as well as increased the catalase activity in rat hippocampus after seizures, when compared with the PC group. Our results suggest that neuroprotective effects of AO in adult rats can be the result of modulation of brain antioxidant enzyme activities, but further investigations are in progress to confirm this pharmacological property.

153 Abstracts P493 ROLE OF THE RNA-BINDING PROTEINS PUMILIO 2 AND STAUFEN 2 IN EPILEPTOGENESIS - IMPACTS ON NEUROGENESIS AND LONG-TERM MEMORY Demleitner A1, Follwaczny P1, Schieweck R1, Klemm A2, Popper B1, Kiebler M1 1 BioMedical Center, Ludwig-Maximilians-University, Cell Biology, Planegg - Martinsried, Germany, 2BioMedical Center, Ludwig-Maximilians-University, Core Facility Bioimaging, Planegg - Martinsried, Germany Purpose: Various genetic causes for epilepsy exist. Many are associated with alterations in sodium channels and GABA receptors in neuronal circuits. The RNA-binding proteins (RBPs) Pumilio 2 (Pum2) and Staufen 2 (Stau2) are responsible for the local regulation of transcripts in hippocampal neurons. Decreased Pum2 levels have been associated with a complex seizure phenotype in mice and temporal lobe epilepsy (TLE) in humans. The presented study aims to evaluate possible causes in changes of the excitatory levels in knockdown (KD) mouse models as well as alterations of neurogenesis and long-term memory linked to the epileptic phenotype. Method: Microarray analysis of Pum2 and Stau2 KD mice were used to identify epilepsy and learning-associated targets. The most promising ones were further validated via qPCR, Western Blot and immunohistochemistry on brain slices. To evaluate memory in mice, behavioral tests were performed together with investigations on adult neurogenesis and dendritic spine morphology. Results: Pum2 and Stau2 KD mice show a 1.5 fold increase in SCN2A. In contrast, SCN8A and SCN1A show a 0.5 fold decrease. Quantifications on immunohistochemistry on brain slices validate these findings on the protein level. Stau2 KD show an increase in newly generated neurons upon behavioral analysis but impaired long-term memory in comparison to WT littermates. Pum2 and Pum2/Stau2 KD show slightly enhanced long-term memory. At the cellular level, Pum2 show significant reduction in dendritic branching. Conclusion: Our data suggest defective translational regulation of common epilepsy targets in Pum2 KD and Pum2/Stau2 KD mice. Together with decreased adult neurogenesis and impaired long-term memory, our results link epileptogenesis to the translation of selective transcripts at synapses in the hippocampus. Taken together, dysfunctional RBPs, e.g. Pum2 and Stau2, might critically contribute to the development of TLE. Consequently, our results may be applicable for specific preventional, screening and therapy options linked to TLE patients.

P494 THE SELECT SCORE: A NOVEL TOOL TO PREDICT SEIZURES AFTER ISCHEMIC STROKE Galovic M1,2,3, D€ohler N3, Conrad J4,5, Evers S4,6, Winklehner M7, von Oertzen TJ7, Haring H-P7, Serafini A8, K€ agi G3, Koepp M1,2, Sander JW1,2, Tettenborn B3 1 Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, United Kingdom, 2MRI Unit, Epilepsy Society, Chalfont St Peter, United Kingdom, 3Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland, 4Department of Neurology, University of M€ unster, M€unster, Germany, 5Department of Neurology, Ludwig-Maximilians-University Munich, Munich, Germany, 6 Department of Neurology, Krankenhaus Lindenbrunn, Coppenbr€ugge, Germany, 7Department of Neurology 1, Kepler Universit€atsklinikum - Neuromed Campus, Linz, Austria, 8 Department of Neurology, University Hospital Udine, Udine, Italy Purpose: Stroke is the most common cause of acquired epilepsy in adults. The latent period between the initial insult and remote

symptomatic (>7 days) seizures offers time for diagnostic and therapeutic procedures to prevent epileptogenesis. However, an instrument to predict patients who will develop poststroke seizures and would benefit from these procedures is not available. We developed and externally validated a prognostic model of late-onset seizures after stroke. Method: Model development was done in the prospective Stroke and Epilepsy Registry of Eastern Switzerland (SERES). An integer-based score of remote symptomatic seizures occurring within 3 years after stroke was derived with a backward elimination approach. External validation was performed in three independent international cohorts (Austria, Germany, Italy) and performance was assessed with the concordance (c) statistic and calibration plots. Results: The development cohort included 1,200 patients and three external validation cohorts comprised 1,482 patients. Overall, 139 (5%) patients suffered remote symptomatic seizures. The lowest SeLECT value (0 points) was associated with a 5-fold decrease of seizure risk, whereas the highest value (14 points) predicted a 10-fold increase of relative risk. The model had an overall c statistic of 0.76 0.02 (range 0.73–0.78) in validation cohorts. Calibration plots showed high agreement between predicted and observed outcomes with an overall calibration slope of 0.97. SeLECT values of ≥9 points were more than 95% specific for remote symptomatic seizures. Conclusion: This easily applicable instrument was a good predictor of seizures after stroke in triple external validation. The SeLECT score has the potential to individualise clinical care by identifying patients who would benefit from optimal management and appropriate follow-up. It can inform the selection of an enriched population for antiepileptogenic treatment trials and guide the recruitment for biomarker studies of epileptogenesis.

P496 PRESURGICAL DIAGNOSIS AND DIFFERENTIATED SURGICAL TREATMENT OF DRUG-RESISTANT FOCAL AND MULTIFOCAL TEMPORAL LOBE EPILEPSY BASING ON EPILEPTOGENESIS CONCEPTION Kravtsova S, Stepanova T, Kasumov V, Bersnev V Russian A.L. Polenov Neurosurgical Institute, St. Petersburg, Russian Federation Purpose: Optimization of presurgical diagnosis and surgical treatment of drug-resistant temporal lobe epilepsies. Method: Electroclinical examination and surgical treatment of 255 patients (19–50 years old) with resistant post-traumatic temporal epilepsy. An algorithm for local diagnostics of epileptic foci comprising neurophysiological (EEG, ECoG, ESCoG) and neuroimaging (MRI, PET) technologies was developed. Results: A strict-indications protocol to surgical patients selection was developed: drug-resistance, seizure frequency, localized epileptic focus. Based on chronotopology focal EEG-ECoG-ESCoG trait-biomarkers peculiarities temporal (early) and extratemporal (late) epileptogenesis were depicted reflecting clinical-neurophysiologic forms of temporal epilepsy on different stages of the disease depending. It was shown that temporal focal and multifocal epileptogenesis is peculiar for localization of temporal epileptic focus. The majority of patients (79%) demonstrated a vast epileptic zone with combined damage of temporal neocortex and limbic structures (paleocortical and multifocal temporal-frontal epilepsy); isolated foci in temporal neocortex (4% - lateral epilepsy) or limbic formations (17% - mesial epilepsy) were a rare finding. The developed algorithm for presurgical diagnosing of epileptic focus served a basis for a strictly differentiated approach in planning the strategy and volume of adequate surgical intervention with intraoperative ECoG-ESCoG-control. In the lateral epilepsy we used an open surgery: subpial excision of cortical epileptic temporal focus. In the mesial epilepsy we used an open selective transcortical intervention on the deep


154 Abstracts limbic structures. The optimal treatment of paleocortical epilepsy is an anterior temporal lobectomy: excision of 2/3 temporal lobe and subpial excision of the amygdala and hippocampus anterior. The optimized surgery tactics for the multifocal temporo-frontal epilepsy included an anterior temporal lobectomy combined with minimally invasive surgery, s.a. sparing excision of epileptized cortex zones, incision of cortico-cortical links and subpial transection in the near-border eloquent areas of the temporal and frontal lobes. Conclusion: The chronotopology of epileptogenesis optimizes strategy of differentiated surgical treatment of temporal epilepsy.

P497 DIAGNOSTIC CHALLENGES IN NON-EPILEPTIC PSYCHOGENIC SEIZURES Uygur E1, Erdal A1, Genc F1, Gomceli Y1, Kutlu G2 1 Antalya Educational and Research Hospital, Neurology, Antalya, Turkey, 2Mugla University Faculty of Medicine, Neurology, Mugla, Turkey Purpose: Nonepileptic psychogenic seizures (NEPN) is a problem that frequently encountered in patients admitted to the epilepsy centers, and leads to diagnosis and treatment confusion. In this study, NEPN patients who referred to our epilepsy center on the first evaluation due to diagnosis challenge and diagnosed in the follow-up period, were evaluated. Method: 1,140 patients referred to Antalya Education and Research Hospital, Neurology - epilepsy center with the diagnosis of epilepsy, were retrospectively reviewed. Demographic characteristics, risk factors, and diagnostic methods of all patients with NEPN diagnosed, were examined. Results: A total of 70 patients including 54(77.1%) females and 16 (22.9%) males patients, were found to NEPN diagnosis. While in 24 patients (34.3%) just seen NEPN, 46 patients (65.7%) had epilepsy and NEPN association. In pure NEPN patients, abnormal EEG findings in 10 (41.6%) patients, nonspecific changes in cranial MRI of 5(20.8%), risk factors of 6(25%) and 7(29.2%) patients had a family history. Conclusion: In NEPN diagnosis, the patient group that constitutes the most hesitant; those patients with risk factors, EEG or MRI abnormalities. Both in patients with epilepsy diagnosis, as well as the first application, NEPN should always be kept in mind and history of seizure, semiological features and objective data should be carefully evaluated.

P498 NOVEL BIALLELIC MISSENSE MUTATIONS IN CTC1 GENE IDENTIFIED IN A CHINESE FAMILY WITH CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATION AND CYSTS (CRMCC) Lin H Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China Purpose: Cerebroretinal microangiopathy with calcification and cysts (CRMCC) is a recently described, very rare multisystem disorder. The clinical phenotype of CRMCC is wide and variable, making the diagnosis of CRMCC more difficulty. The biallelic heterozygous mutations in CTC1 gene, encoding conserved telomere maintenance component 1, were identified in families with CRMCC from different ancestry (European, American, and African). We report a mutation in CTC1 gene in a family of CRMCC from China. Method: Coding and uncoding regions of the CTC1 gene, covering the promoter, coding exons and exon-intron junctions, were amplified by


polymerase chain reaction (PCR) from genomic DNA of three individuals in the family. Results: We firstly identify a novel biallelic heterozygous missense variants (c.775G>A p.V259M and c.2066A>G p.Y689C) of CTC1 gene in a Chinese family with CRMCC. The c.2066A>G mutation (p.Y689C) in CTC1 is a novel variant. Such variant was not found in any of the 85 healthy individuals in the same community. Conclusion: This is the first report of a genetically confirmed case of CRMCC from China. Targeted sequencing of CTC1 gene is useful for genetic diagnosis in the family with CRMCC and different diagnosis for other patients with similar disease manifestations. Various mutations in CTC1 gene identified from different ancestry CRMCC patients suggest possible genetic heterogeneity.

P499 WHOLE EXOME SEQUENCING REVEALS NOVEL NOV AND DCAF13 MUTATIONS IN A CHINESE PEDIGREE WITH FAMILIAL CORTICAL MYOCLONIC TREMOR WITH EPILEPSY Lin H Xuanwu Hospital Capital Medical University, Beijing, China Objective: We report a large new family of familial cortical myoclonic tremor with epilepsy (FCMTE) from China and identified the possible causative gene(s) for the family. Methods: Whole exome sequencing of blood genomic DNA from 4 patients and 2 unaffected family members were performed. Detected mutations and their cosegregation were confirmed by Sanger sequencing. Results: We identified c.20G>C mutation in the DCAF13 gene and c.983 T>C mutation in the NOV gene cosegregating in the family. There was no additional cross-over in the family to narrow it to one gene. The two DCAF13 and NOV gene mutations are located on 8q23.3 and 8q24.12, which is consistent with the location 8q23.3-q24.13 reported previously for a group of Japanese families. The DCAF13 mutation is located in alterative transcription start site (TSS) and the function of alterative TSS is unkown. The missense NOV mutation is near the C terminus in a site that is highly conserved across species. It was predicted to have deleterious effect on protein function. Conclusion: In this study, we identify two novel mutations in the DCAF13 and NOV genes associated with FCMTE in Asian populations. The interval between two mutations is 15.6 Mb, which is very closed each other. Future studies of additional families with this phenotype are warranted to confirm whether it is the bigenic inheritance or to narrow it to one gene.

P500 ISCHEMIA AND INFLAMMATION ARE INVOLVED IN THE ONSET OF EPILEPSY IN STURGE-WEBER SYNDROME Nakajima M, Sugano H, Suzuki H, Higo T, Iimura Y, Arai H Juntendo University, Neurosurgery, Tokyo, Japan Purpose: In Sturge-Weber syndrome (SWS), seizures affect 75–90% of cases, and approximately 60% of them have refractory epilepsy. However, the mechanism of epilepsy in SWS remains unclear. From an analysis of direct electrophysiological cortical records in SWS in our laboratory, indicated the possibility that cortical ischemia directly under the leptomeningeal angioma is responsible for epileptic discharges. To improve our understanding of these mechanisms, we performed immuno-histostaining of SWS brain tissue obtained during surgical procedures for refractory epilepsy.

155 Abstracts Method: The subjects were 4 cases of SWS with refractory epilepsy (ages 1.8–4 years), and in all of them the seizure symptoms were motionless staring and respiratory distress. Surgical treatment in angiomas confined to the temporal, parietal or occipital lobes was posterior quadrantectomy, but if there was an extension to the frontal lobe then a frontal or hemispheric disconnection was also performed. We used paraffin fixation for the excised brain tissue in epileptic focus areas during the disconnection procedures and performed pathology analysis with immuno-histostaining for MAP2, GFAP, Glut5, HMGB1, TLR4, and ssDNA. Results: Seizure control after surgical treatment was grade 1 (Engel). MAP2 immunostaining showed a tendency of dendrite decrease, eosinophilic changes in neuronal cytoplasm and pyknotic neurons. The activated microglia and TLR4 staining indicated positive immunoreaction in glial cells and interneurons, suggesting the involvement of inflammation mediators (the HGMG1-TLR4 pathway). In elder patients at the time of surgery was found stronger gliosis and a tendency for remarkable proliferation of reactive astrocytes. Conclusion: The many pyknotic neurons found in the SWS makes us infer that mechanisms related to the cause of epilepsy may include the involvement of ischemic processes as well as inflammatory mediators, inducing changes in neural network excitability.

P501 LOW LEVELS OF SECURE ATTACHMENT STYLES IN PATIENTS WITH PSYCHOGENIC NON-EPILEPTIC SEIZURES Villagran A1,2, Torgersen H1, Lund C1, Hessen E1,3, Lossius MI1 1 Division of Clinical Neuroscience, Oslo University Hospital, National Centre for Epilepsy, Oslo, Norway, 2Institute for Clinical Medicine, University of Oslo, Oslo, Norway, 3 Department of Psychology, University of Oslo, Oslo, Norway Purpose: Mechanisms underlying psychogenic non-epileptic seizures (PNES) remain poorly understood. As patients with PNES often come from dysfunctional families and experience interpersonal difficulties, attachment theory may be useful in conceptualizing underlying mechanisms. From the literature it is known that dysfunctional attachment in childhood is associated with maladaptive interpersonal functioning and increases vulnerability to adult psychopathology. In the current study we aimed at investigating current attachment patterns in adult patients with PNES. Method: 30 patients (24 women, age 18–62 years, mean age 34 years) with confirmed PNES completed the Attachment Style Questionnaire (ASQ). We used published data on an adult healthy cohort (Andersson & Perris, 2000) and a cohort of adults with psychosis (Mulligan & Lavender, 2009) for comparison. Results: Our sample of PNES-patients showed significantly lower levels of confidence (security) and higher levels of insecurity on attachment styles than the normative sample. The mean confidence-score for PNES patients was 32.6 (SD = 1.8) compared to a mean score for the controls of 44.8 (SD = 5.1, p > 0.001). There was no statistically significant difference between our PNES-sample and the psychosis-sample for neither secure nor insecure attachment styles; mean confidence-score for psychosis patients was 30.0 (SD = 7.3). Conclusion: Prior studies addressing the question of PNES and attachment have yielded conflicting results. In the present study we found lower levels of secure attachment styles in our patients with PNES compared to a healthy cohort. Attachment patterns found in our PNES patients did not differ from those reported on adult patients with psychosis. This may shed light on the underlying mechanisms of PNES and might also be a factor influencing the prognosis.

Others 4 Tuesday 13th September P502 SLEEP DISORDERED BREATHING IN PATIENTS WITH EPILEPSY - A POLYSOMNOGRAPHIC STUDY Klobučníková K, Siarnik P, Koll ar B, Turc ani P Hospital of Medical Faculty, Comenius University, 1st Department of Neurology, Bratislava, Slovakia Purpose: Epilepsy and sleep-disordered breathing are relatively common disorders. Obstructive sleep apnea syndrome (OSAS) with repetitive episodes of hypoxia and hypercapnia induce repetitive arousals and sleep fragmentation and may cause symptomatic epileptic seizures. Epileptic seizures change the architecture of sleep with an increase of light sleep and reduction of REM sleep. Aim of this study was to evaluate the sleepdisordered breathing in patients with epilepsy. Method: We evaluated 18 patients with epilepsy. All of them underwent EEG and overnight video-EEG-polysomnography using Alice 5 device (Philips Respironics, Netherlands). They filled in the Epworth Sleepiness Scale questionnaire (ESS) and Body Mass Index was measured. Type and etiology of epilepsy was evaluated as well as the actual antiepileptic therapy. Results: Average age was 67 7.5 year, ESS score was 9.4 3 and BMI 34.8 12.5 kg/m2. Nocturnal type of epilepsy was found in 12 patients, 6 patients had diurnal type of epilepsy. 15 patients had OSAS, 8 of them severe with AHI (apnea/hypopnea index) over 30/h. Two patients had central sleep apnea syndrome and one patient had snoring. All patients with OSAS were indicated for therapy with positive airway pressure (CPAP or BiPAP). Benefit of this therapy on reductions of seizures should be observed in the future. Conclusion: Sleep-disordered breathing, especially OSAS is very frequent in patients with epilepsy. We suppose that sleep apnea is a strong activator of epileptic seizures. Patients with epilepsy, nocturnal epilepsy and those with poor control of epilepsy should be referred to the sleep laboratories to be examined for the presence of the sleep apnea syndrome. This work was supported by the Framework Programme for Research and Technology Development, Project: Building of Centre of Excellency for Sudden Cerebral Vascular Events, Comenius University Faculty of Medicine in Bratislava (ITMS:26240120023), co-financed by European Regional Development Fund.

P504 STRESS AND SEIZURES: EXPLORING THE PATTERNS OF IMPLICIT ATTENTIONAL BIASES IN PATIENTS WITH EPILEPSY AND DISSOCIATIVE SEIZURES Novakova B1, Harris P2, Ponnusamy A3, Marques JLB4, Reuber M1 1 Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom, 2School of Psychology, University of Sussex, Brighton, United Kingdom, 3Department of Clinical Neurophysiology, Royal Hallamshire Hospital, Sheffield, United Kingdom, 4Institute of Biomedical Engineering, Federal University of Santa Catarina, Florianopolis-SC, Brazil Purpose: Stress is perceived by patients as one of the main seizure triggers. However, the processes linking stress and seizures are not fully understood. This study aimed to examine implicit attentional responses to threatening stimuli and to explore whether they differ in patients with epilepsy, patients with dissociative seizures (DS) and healthy individuals. We also explored the relationships between attentional, self-perceived and physiological stress responses in patients with seizures.


156 Abstracts Method: Patients with refractory seizure disorders (epilepsy n = 22, DS n = 23) admitted for diagnostic video-telemetry and 21 healthy volunteers completed self-report questionnaires and performed an emotional Stroop test. Implicit attentional biases were explored by comparison of responses to neutral versus threatening stimuli comprising generally threatening and socially threatening as well as somatic symptom and seizure-related words. Salivary cortisol and heart rate variability (HRV) parameters extracted from resting electrocardiogram recordings taken prior to the Stroop test were used as physiological stress markers. Results: Patients with epilepsy showed a significant positive attentional bias towards threatening information, particularly towards seizurerelated threat, compared to healthy controls (p = .036). The response patterns in patients with DS were similar to those found in epilepsy but were not as marked and not significantly different from healthy controls. In patients with epilepsy, the attentional bias towards somatic words was negatively correlated with HRV (r = 0.58). There were no other relationships among the attentional biases, cortisol, HRV or self-reported stress in any of the patient groups. Conclusion: The findings suggest there may be a reciprocally causative relationship between attentional vigilance (stress perception), the autonomic nervous system tone and seizures, at least in some patients with epilepsy. The long-term experience of stress and seizures could lead to exacerbated attentional responses to seizure-related information, which could in turn trigger more frequent physiological stress responses, further increasing the vulnerability to stress and seizures.

P505 MANAGEMENT OF PATIENTS WITH PSYCHOGENIC NONEPILEPTIC SEIZURES IN SOUTH AFRICA: A SURVEY OF HEALTHCARE PROFESSIONALS Pretorius C University of Stellenbosch, Stellenbosch, South Africa Purpose: Psychogenic Nonepileptic Seizures (PNES) is a complex disorder that remains poorly understood and managed in the clinical setting. This study captures the care currently received by patients with PNES in South Africa. Method: The findings are based on 72 responses to an Internet survey of healthcare providers from South Africa (41.7% neurologists and 47.2% psychiatrists). Data were collected using the online software SurveyMonkey. Frequencies and percentages are reported for categorical variables. Medians and ranges are reported for continuous variables. Results: The majority of the participants (54.7%) treat publicly funded patients. While inpatient video EEG monitoring is perceived as the gold standard for confirming a diagnosis of PNES, only 25% of PNES patients have access to this type of diagnostic method. The responses suggest that there is much variability in the approaches to diagnosis of PNES and communication of the diagnosis to the patient. The five main reasons why patients seem to have difficulty to access diagnostic or treatment services for PNES according to the participants consist of: lack of access to information resources about PNES (59%), lack of popular awareness of PNES (57.9%), lack of liaison between traditional healers and health professionals (45.4%), stigma associated with PNES (37.1%) and a lack of accessible healthcare providers who know about PNES (36.9%). Conclusion: Access to video EEG may improve PNES diagnosis and treatment. There seems to be a general lack of awareness about PNES in South Africa. The implementation of continuous education programmes for healthcare providers in particular could contribute positively to the diagnosis and treatment of patients with PNES.

P507 RELAPSING SEIZURES AFTER RESECTIVE EPILEPSY SURGERY - ARE THEY ALWAYS EPILEPTIC? Staack AM, Wendling A-S, Steinhoff BJ Kork Epilepsy Centre, Kehl-Kork, Germany Purpose: Epilepsy surgery is a well-established treatment option for patients with drug-resistant epilepsy. Post-operative seizure freedom rates up to 75% may be achieved depending upon the etiology and the precise localization and delineation of the extent of the epileptic zone and its complete removal. Seizure-recurrence may be reported by patients and relatives but in some cases it remains difficult to explain why patients still suffer from seizures. The question arises which kind of seizures may occur after presumed successful epilepsy surgery. Patients and methods: We assessed pre-and post-operative data including clinical history, video-EEG, MRI, neuropsychological testing, neurological and psychiatric evaluation from patients who underwent epilepsy surgery at the Kork Epilepsy Centre in the last 15 years. Results: Sixty-five percent (n = 267) of 408 patients were free from disabling seizures at the last time of follow-up. Among the 141 (35%) of patients with reported seizure-relapse, 126 patients still had epileptic seizures. Eight patients presented with post-operative de novo psychogenic non epileptic seizures (PNES) whereas PNES but not epileptic seizures persisted in three patients of five who had already suffered from PNES pre-operatively. Four epileptic seizure-free patients had other de novo paroxysmal attacks (one patient with cardiac syncope, three patients with benign paroxysmal positional vertigo). Especially the group of patients with post-operative de novo psychogenic seizures caught our interest. Common features were predominance of female gender, right sided resection, history of pre-operative psychiatric comorbidity, PNES-semiology with pronounced motor signs that was totally different from their pre-operative epileptic seizure semiology. Conclusion: Even if the number of patients who develop post-operative non-epileptic attacks especially PNES is small, the detection of this important differential diagnosis is crucial and requires further therapeutic strategies.

P509 THE MINNESOTA MULTIPHASIC PERSONALITY INVENTORY-2 PROFILE IN PATIENTS WITH PSYCHOGENIC NON-EPILEPTIC SEIZURES Kramska L1, Vojtech Z2, Prochazka T2, Jarosova Z3, Kalina M2 1 Neurocenter, Clinical Psychology, Na Homolce Hospital, Prague, Czech Republic, 2Na Homolce Hospital, Neurology, Prague, Czech Republic, 3Na Homolce Hospital, Clinical Psychology, Prague, Czech Republic Purpose: Differentiating between epileptic and psychogenic seizures is essential for an appropriate treatment. Evaluation of cognitive performance and personality is an integral part of this process. The aim of this study was the assessment of personality profile of patients with psychogenic non-epileptic seizures (PNES) using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Method: We analyzed MMPI-2 personality profiles of 77 patients diagnosed with PNES (55 women, 22 men). The diagnosis was based on clinical assessment by an experienced epileptologist, negative video/EEG monitoring (7 days) and neuropsychological evaluation (clinical interview, personal history, cognitive testing and personality assessment). Results: Using one sample t-test, the majority of clinical scales in the MMPI-2 were significantly increased against the norm. The most elevated scales (T score >65) were: Hs, D, Hy, Pt, Sc. Analysis of Supplemental scales indicated that patients with PNES reported significantly higher scores (T score >65) for: ANX, WRK, D (1, 4), Sc (5, 6), Ma-O,


157 Abstracts Mt, PK, PS, HEA1 and T scores higher than 70 for: HEA, D3, Hy (3, 4), Sc3, D-O, Hy-O, HEA (2, 3). No validity scales were significantly increased except slightly elevated F scale. Conclusion: Patients with PNES are a very specific and heterogeneous group of patients. Beside trauma and stress factors in patient’s history, attachment styles, communication and models in the family, personality traits and psychopathology are important factors associated with PNES. Patients with PNES suffer from emotional and mood problems and symptoms similar to PTSD which can be identified by MMPI-2. Using this method, clinicians can also form hypotheses regarding mental processes such as attention, memory, judgment and motivation. Analysis of validity, clinical and supplemental scales can be helpful in the diagnostic process of PNES and in the planning of adequate psychotherapy according to the dominant psychological problem.

P510 A CRITICAL EVALUATION OF THE ROLE AND EFFECTIVENESS OF THE UK EPILEPSY SPECIALIST NURSE Wright E Leeds Teaching Hospitals NHS Trust, Neurology, Leeds, United Kingdom Purpose: To evaluate the role of the Epilepsy Specialist nurse in Government documentation and establish key roles, then evaluate evidence underpinning these roles to establish if the Epilepsy Nurse is best placed to do so. Method: This study reviews government documents and audits in order to develop a role profile of the adult epilepsy specialist nurse [ESN] in the UK. Each activity of the role profile was then independently examined to establish if there was any evidence supporting or disputing the ESN performing that role. Roles were found to have developed mainly independently of government documents. Paucity of good methodological evidence was recognized early in the study, therefore alternative appropriate sources of evidence had to be used as deemed suitable by an “inclusion weighting criteria” that was specifically devised for this study. Results: Despite previous evidence to the contrary, this study established nine key roles performed by UK ESN’s, and was able to show that the ESN’s strengths lie in roles revolving around communication and their accessibility, both physically and psycho-socially. ESN’s main roles include information/education provision, liaison with other departments, nurse-led clinics and telephone communication. Supporting these roles are audit and research, conducting investigations and medicines management. The ESN role in Accident and Emergency does not require a physical presence and therefore falls under the liaison category. Administration is the only role that was found to have a detrimental effect upon the ESN role by reducing their accessibility. Conclusion: This study is one of the first to link government documents and research to show the practice of the ESN. In doing so it demonstrates that the roles have developed alongside government literature and the needs of the patient. There is a clear need to support the role further in order to provide an appropriate, efficient service.

P511 STEREOTYPY OF PSYCHOGENIC NON EPILEPTIC SEIZURES Herskovitz M1,2 1 Rambam Health Care Campus, Neurology, Haifa, Israel, 2 Faculty of Medicine, Technion, Haifa, Israel Purpose: Psychogenic non epileptic seizures (PNES) are defined as paroxysmal episodes in which epileptic semiology features are

manifested without the characteristic concomitant electrical discharges seen in epileptic seizures. The aim of this study was to measure the amount of consistency of PNES among individual patients with PNES undergoing long term video EEG monitoring. Method: We retrospectively reviewed medical records and video-EEG records of all adult patients who underwent monitoring in our center from August 2013 to May 2015. We included patients with a diagnosis of PNES who had more than one recorded seizure during monitoring. Consistency was checked in several categories including: Type of seizure. The main organ involved. Seizure components and sequence: which included the body parts involved in the seizure and the sequence of their involvement in the seizure. Frequency of movements in the main organs involved in the seizure and duration of seizure. Results: We found 53 patients who had PNES during this period, 29 of them had more than one seizure. All seizures in the same patient were in the same semiology category, In patients with either motor rhythmic or complex motor seizure, the main organ involved was the same in 13 out of 14 patients. Regarding seizure components and sequences: in 9 out of 14 patients with motor manifestations, same organs were involved in both seizures. Regarding movement frequency: there were no significant differences between the first and second seizure in patients with motor involvement. p = 0.512. The length of seizures was significantly different between the first and second seizure p < 0.05. Conclusions: In patients with PNES, most aspects tested were highly similar between the first and second seizure. This shows that seizures in patients with PNES are highly stereotypic. This supports the notion that PNES is an automatic behavior. This supports the notion that PNES is indeed a dissociative disorder.

Others 5 Tuesday 13th September P512 CROSS-CULTURAL ADAPTATION AND VALIDATION OF THE PORTUGUESE VERSION OF THE QUALITY OF LIFE QUESTIONNAIRE IN EPILEPSY (QOLIE-89) Santos C1, Almeida A1, Rosado L2 1 Universidade da Beira Interior, Covilh~ a, Portugal, 2Centro Hospitalar Cova da Beira, Covilh~ a, Portugal Purpose: Epilepsy is a chronic disease that is manifested by the occurrence of epileptic seizures that arise unexpectedly. Epilepsy is recognized for centuries and there were times when the epileptic people were seen as possessed by demonic forces (ILAE, 2003), hence why people with seizures are still suffering the stigma of the disease that causes social exclusion (RS Fisher et al., 2005). Considering the impact of epilepsy on daily life, Devinsky et al have developed in 1995 a questionnaire of quality of life in patients with epilepsy. This instrument allows to assess how the crisis, medication and other limitations affecting the individual, making their daily lives and in which size is this more evident (Devinsky et al., 1995). It is estimated that in Portugal there are about 50,000 patients with epilepsy (Lima, 2005) and there isn’t no validated instrument to specifically assess the quality of life in patients with epilepsy. This work is the opportunity to creating a tool that can assist in evaluating intervention programs in epilepsy. Objectives: Translation, cultural adaptation and validation of the Quality of Life Questionnaire in Epilepsy (QOLIE-89) for the Portuguese population. Method: Once authorized by the authors of the questionnaire, the adaptation of the original version for the Portuguese language was done according to the methodological procedures recommended by Beaton (2000). Subsequently, it is applied to at least 445 patients with epilepsy


158 Abstracts (n = 5 9 K (where K > 15), K is the number of instrument questions) (Pestana & Gageiro, 2005). Expected results and conclusions: It’s expected that the viability of this questionnaire will allow a better understanding of the difficulties and needs of patients with epilepsy as well as the factors relating to the disease that most impact in their daily lives (Devinsky et al. 1995).

P513 DIAGNOSTIC ACCURACY OF AUDIO BASED SEIZURE DETECTION IN PATIENTS WITH SEVERE EPILEPSY AND A MENTAL IMPAIRMENT Arends J1,2, van Dorp J3, van Hoek D1, Kramer N3, van Mierlo P1, van der Vorst D4, Tan F5 1 Epilepsy Centre Kempenhaeghe, D&B, Heeze, Netherlands, 2 Technological University Eindhoven, Electronic Engineering/ Signal Analysis Group, Eindhoven, Netherlands, 3CLB, Raamsdonksveer, Netherlands, 4Sound Intelligence, Amersfoort, Netherlands, 5Epilepsy Centre Kempenhaeghe, CEW, Heeze, Netherlands Objective: Sound-detection performance of nocturnal major seizures (tonic-clonic and long generalized tonic) in adult patients with mental impairment. Methods: 1 Representativess check. A random sample (n = 17, 102 major seizures) to assess the proportion of patients with recognizable sounds. 2 Manual performance Ten patients (major seizures with recognizable sounds) followed for 4 weeks with a CLB acoustic monitoring system (CLB-monitor’) and videocamera. Week 1: choice of sound detection threshold to avoid too many events. Week 2–4: selection of epilepsy related sounds, independent video verification and labeling (‘snoring’, ‘laryngeal contraction’). Video images fully screened for false negatives. 3 Automatic performance: Algorithms in the CLB-monitor detected one specific sound (snoring) to illustrate the automatic sound recognition. Results: 1 Recognizable sounds (louder than whispering) occur in 23 (51%) of the 45 major seizures. 20 (45%) below this threshold, and 2 (4%) without any sound. 2 Analysis of the 112 major seizures (mean 11.2, range 1–30): mean sensitivity (SENS) of 0.81 (range 0.33–1.00) and a mean positive predictive value (PPV) of 0.40 (range 0.06–1.00). All false positive alarms (mean value 1.29 per night) were due to minor seizures. The CLB-monitor missed 4 seizures (3%) due to lack of sound; and 10 (9%) due to sounds below the system threshold. 3 The overall accuracy of the ‘snoring’ detection was 98.3%, SENS 0.95 and PPV 0.96. Significance: 1 Audio detection of major seizures is possible in half of patients. Lower sound detection thresholds may increase the proportion of suitable candidates. 2 Manual selection of seizure related sounds has a high sensitivity and moderate positive predictive value due to minor seizures who do not need intervention. 3 Algorithms in the CLB-monitor detect seizure-related sounds and may be used alone or in multimodal systems.

P514 ESTABLISHMENT OF EPILEPSY GROUP EDUCATION - A LOCAL EXPERIENCE 2 YEARS ON Behan C St James’s Hospital, Department of Neurology, Dublin, Ireland Within the therapeutic management of chronic diseases educational programs for patients are considered extremely important. Educational sessions aim to increase relevant knowledge about a disorder and strengthen a patient’s responsibility for themselves and managing a chronic illness. Purpose: With a growing patient population and restricted resources the objective of this project is: To streamline nurse workload and use nurse time more efficiently. To standardise the education given to patients. To provide a forum for patients to meet and learn from other patients experiences Method: A pilot group was carried out in May 2014. There were six attendees, resulting in a saving of 2.5 h nurse time, 50% less than required by individual sessions. The clinic runs monthly ongoing. Results: Audit year 1: 52 attendees at eight sessions. A total time of 23 h 30 min (48%) saved nurse time if compared with one to one education. All attendees have received a standardised education session with supporting literature. Audit year 2 shows a 12% reduction in clinical encounters by the patients who attended group education versus a 55% increase in the patients who did not attend for education Conclusion: The saved nurse time has been redirected to provide follow up and focused nurse consults for those patients with greater need. Patient safety: A high number of patients are now receiving information triggers, driving regulations, pregnancy planning, medications and SUDEP. An electronic referral system has been established for epilepsy education. Establishment of an electronic education outcome form allowing documentation of the education session, facilitating transparency for other disciplines. Epilepsy education is now a standardised, ever improving process ensuring access and equity for each patient and focus for those requiring additional support. Patients who received education had a reduced need on the service, freeing up resources for those patients with a greater need.

P515 AUTOMATED ASSESSMENT OF ELECTRODE REDUCTION ON DETECTION OF EEG PATTERNS IN INTENSIVE CARE PATIENTS Herta J1, F€ urbass F2, Koren J3, Kluge T2, Gruber A4, Baumgartner C3 1 Medical University Vienna, Neurosurgery, Vienna, Austria, 2 Austrian Institute of Technology GmbH, Digital Safety & Security Department, Vienna, Austria, 3Karl Landsteiner Institute for Clinical Epilepsy Research and Cognitive Neurology, 2nd Neurological Department, General Hospital Hietzing with Neurological Center Rosenhuegel, Vienna, Austria, 4Medical University of Vienna, Neurosurgery, Vienna, Austria Purpose: Many attempts have been made to detect seizures with a reduced electrode array. Results were moderate and similar numbers of leads and montages used. This study investigated the influence of the


159 Abstracts number of electrodes on automatic detection of EEG patterns in intensive care patients. Method: Long-term EEGs of 83 patients (total 6,733 h, mean 73 h) including 19 electrodes were recorded in two intensive care units. Two EEG experts independently annotated periodic discharges (PD), slow rhythmic (SR, =4 Hz), and burst suppression patterns (BSP) in the first minute of each recording hour. A fully automated computer algorithm was used to detect the EEG patterns. We then reduced the number of electrodes available for the automated detection in four different successions (“headband”, “banana”, “crown”, “forehead”) down to six electrodes. These detection results were compared to the consensus annotations of the EEG experts to quantify sensitivity (SE) and the number of electrodes for which SE dropped more than 20% (D20%). Results: “Headband” was the reduction method with the best overall (all patterns) detection SE and used for further analysis. PD were detected with a SE of 87% in the EEGs including 19 electrodes and reached a D20% already at 10 electrodes. SR patterns were detected with a SE of 93%. A D20% was never observed. FR showed a SE of 90% and a D20% at 11 electrodes. BSP were diagnosed with a SE of 85% and a D20% at eight electrodes.

P518 COCHRANE REVIEW OF PSYCHOLOGICAL TREATMENTS FOR PEOPLE WITH EPILEPSY Michaelis R1,2, Tang V3,4, Wagner JL5, Modi A6, LaFrance WC7, Goldstein LH8, Lundgren T9, Reuber M10 1 Witten/Herdecke University, Witten, Germany, 2 Gemeinschaftskrankenhaus Herdecke, Neurology, Herdecke, Germany, 3Chinese University of Hong Kong, Shatin, Hong Kong, 4Prince of Wales Hospital, Shatin, Hong Kong, 5Medical University of South Carolina, Charleston, SC, United States, 6 Division of Behavioral Medicine and Clinical Psychology, University of Cincinnati College of Medicine, Cincinnati, OH, United States, 7Brown University, Providence, RI, United States, 8 Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London, United Kingdom, 9 Center for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, 10Academic Neurology Unit, Royal Hallamshire Hospital, University of Sheffield, Sheffield, United Kingdom

Conclusion: PDs and FRs are most susceptible to electrode reduction. BSPs can be detected adequately even with 8 electrodes while SRs nearly did not show any influence by electrode reduction. This study shows that the number of required EEG electrodes strongly depends on the EEG pattern of interest.

Purpose: Given the substantial impact epilepsy can have on the healthrelated quality of life (HRQOL) of people with epilepsy (PWE), psychological treatments aiming to enhance psychological well-being in PWE are essential. Establishing evidence of the effects of such therapies is methodologically challenging. A review of the current evidence is needed to assess the effects of psychological treatments on HRQOL in order to inform future therapeutic recommendations and research designs.

P516 DEMOGRAPHIC AND CLINICAL FINDINGS OF EPILEPSY PATIENTS WHO UNDERWENT FOLLOWUP AT THE NEWLY ESTABLISHED CLINIC OF MUGLA UNIVERSITY FACULTY OF MEDICINE Unal Y, Ozturk D, Yılmaz M, Kutlu G Mugla University Faculty of Medicine, Neurology, Mugla, Turkey

Methods: For the operational definition of ‘psychological treatments’, we included a broad range of interventions that use psychological or behavioral techniques designed to improve HRQOL, seizure frequency and severity and psychiatric comorbidities for adults and children with epilepsy. The following databases were searched without language restrictions: Cochrane Epilepsy Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid), PsycINFO (EBSCOhost), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP). Randomized controlled trials (RCTs) and quasi-RCTs were considered for this review. HRQOL constituted the main outcome measure. Trials were assessed for inclusion and risk of bias using the Cochrane Collaboration’s recommended domain-based evaluation tool.

Purpose: The aim of the present study was to evaluate demographic and clinical findings of patients who underwent follow-up at the newly established epilepsy outpatient clinic of the Mugla University Faculty of Medicine. Method: Included were 208 patients who underwent follow-up at the clinic between March 2014 and September 2015. Results: Mean age was 29.42 15.86, with a range of 5–84 years. Eighty-three patients were men (39.9%); 125 were women (60.1%). The most common risk factors included head trauma, febrile convulsion, and family history of epilepsy. Seizures of 155 patients (75.5%) were partialonset, those of 22 (10.6%) were generalized, and those of 9 (4.3%) were unclassified. Sixty-seven patients (37.2%) had normal electroencephalogram, 96 patients (53.3%) had partial, and 10 patients (5.6%) had generalized epileptiform abnormalities. Of the 172 patients (28.5%) to whom antiepileptic drugs had been administered, 49 were resistant to medical treatment. Of the patients with modified therapy, 22 (41.5%) were seizure-free, 7 (13.2%) experienced >50% reduction in seizure frequency, and 8 experienced 1 year, with the first seizure having occurred aged 6 months-6 years, with no identifiable cause found). Results: Responses were received from 116 carers, of which 56 were valid. Carers reported that a median of 1 FS per month (25th–75th percentile: 0–2) was acceptable for their dog, compared to 0 GS (0–1). The majority of carers thought that GS caused most damage to their dog’s brain (59.6%) and body (69.4%), and had the greatest impact on quality of life (52.1%). One quarter of carers (27.3%) deemed it acceptable for an AED to decrease the frequency of GS but increase the frequency of FS. Carers perceived that their vet was most concerned by GS (62.0%) compared to FS (8.0%), and were most likely to report a GS to their vet (45.8%), with only 6.3% more likely to report an FS, and 47.9% equally likely to report each type. Conclusion: The relative perceived unimportance of FS compared to GS by carers may lead to inaccurate reports of seizure frequency, which may bias veterinarian perceptions of treatment efficacy, and reduce the accuracy of clinical trials including client-owned dogs.

P520 FREQUENCY AND THE SEVERITY OF COMPLICATIONS DURING THE WADA TEST Szantroch M1, Bala A1,2, Rysz A1, Marchel A1 1 Department of Neurosurgery, Medical University of Warsaw, Warsaw, Poland, 2Faculty of Psychology, University of Warsaw, Warsaw, Poland Purpose: The Wada test is still considered to be a gold standard for determining language lateralization and memory in patients with intractable epilepsy. However, it is also an invasive method, carrying the risk of potential complications. We report our experience on level of safety of Wada procedure. Method: We retrospectively reviewed medical records of the Wada test in 158 patients with drug resistant epilepsy who underwent the procedure in years: 2000–2016 at the Department of Neurosurgery of Medical University of Warsaw. In all patients the procedure was performed bilaterally, so we analyzed 316 cases. The adverse events were divided into three groups: permanent complications related to the procedure, transient adverse events related to the procedure (which passed before the end of the Wada test) and unexpected events not necessarily resulting from the procedure. Results: Permanent complications were observed in two cases (0.6%), transient adverse events - in 190 (60%) and unexpected unrelated events - in 3 (0.9%). The first group included: a one case of carotid artery dissection (0.3%) and pseudoaneurysm at the site of femoral artery puncture - one case (0.3%). Transient adverse events included: tweaking of the eye resulting from the inadvertent injection of a part of the anesthetic to the external carotid artery - which was very common in our patients (186 cases - 58.8%), but did not affect the neuropsychological assessment; and behavioral abnormalities (verbosity, viscosity), which happened in four cases (1.2%) and hindered neuropsychological evaluation of language and memory. Epileptic seizures, which happened in three cases (0.9%), were accounted to the unexpected events. After each seizure it was impossible to proceed so the Wada had to be repeated another time.


Conclusion: As most of the adverse events were transient and mild the Wada test can be considered a safe procedure for candidates for epilepsy surgery.

P521 AN UNUSUAL FEATURE OF ADULT-ONSET FULMINANT SSPE Milikic D, Perunicic S, Vodopic S Clinical Centre of Montenegro, Neurology, Podgorica, Montenegro Purpose: To present an unusal clinical presentation of SSPE in 28 years old female. Method: 28 years old woman was urgently hospitalized due to seizure. Her first delivery was four months prior to admission. Just before the delivery, her family noticed the change in her behaviour, she was upset and her mood was frequently changing. Two months after delivery, sudden jerky movements of the hand appeared and when the neuroradiology examination (CT) was performed, old ischemia was registered. The neurologic examination revealed left hemiparesis as a residue of encephalitis in patient’s childhood. Results: Differential diagnosis include vascular, inflammatory and immune mediated diseases. The following criteria for the SSPE were fulfilled: 1 Oligoclonal bands in cerebrospinal fluid and serum. 2 EEG with stereotyped high amplitude periodic complex. 3 Serum positive to measles IgG antibodies Conclusion: The diagnosis of SSPE may sometimes be overlooked by the clinician due to the very rapid progress of the disease or the presence of another existing neurological disorder. Our patient had cognitive deficits due to her primary neurological disease and thus evaluation of behavioral and cognitive changes of SSPE was difficult at the beginning.

Others 6 Wednesday 14th September P524 LIMBIC ENCEPHALITIS: THE INTRIGUING LINK BETWEEN AUTOIMMUNE PROCESSES, EPILEPTOGENESIS AND NEURODEGENERATION Casciato S1, Morano A1, Fattouch J1, Fanella M1, Albini M1, Di Gennaro G2, Quarato P2, Mascia A2, D’Aniello A2, Giallonardo AT1, Di Bonaventura C1 1 Universit a “Sapienza” Roma, Neurology e Psychiatry, Rome, Italy, 2IRRCS Neuromed, Epilepsy surgery Unit, Pozzilli IS, Italy Purpose: Limbic encephalitis (LE) is an overlooked, potentially treatable condition, typically characterized by subacute amnestic syndrome, psychiatric features (including behavioral/personality changes and mood disturbances) and seizures. Although LE was usually considered a paraneoplastic disease, it is now well acknowledged that in several cases, especially those related to neuronal surface antibodies, there is no association with malignancies and the prognosis is better, if treatment is promptly started. The aim of our study is to describe and analyze the electro-clinical characteristics, serological features, neuroimaging findings and outcome of 18 LE patients in order to further understand this complex condition and to improve its therapeutic strategies.

161 Abstracts Methods: This is a retrospective cohort study including adult patients with electro-clinical features consistent with the diagnosis of LE. Demographics data, seizure semeiology, EEG pattern, MRI features, complete CSF and serum findings were collected and reviewed. Results: 18 patients (10 males, mean age 62 years) were included in the study. All presented seizures at onset (11 complex partial, 5 simple partial); in 14 cases seizures were recorded (left temporal lobe onset in 4, right in 1, bitemporal in 9). 15 subjects had memory deficits; 10 presented behavioural/mood disorders; 6 suffered from insomnia and in 7 hyponatremia was documented. 11 individuals reported recent infections. In 10/ 18 patients autoantibodies were detected (3 anti-VGKC LGI-1, 4 VGKC Caspr-2; 1 anti-NMDAR, 1 anti-SOX-1, 1 anti-Ri/Hu). In 16 subjects brain MRI showed signal alterations in mesial temporal lobe at onset, which evolved to atrophy in 14. All patients received immunomodulating treatment (10 iv/po steroids alone, 5 steroids + intravenous immunoglobulin, 3 steroids + plasma exchange). 6/18 patients developed drug-resistant epilepsy; 15/18 presented memory deficits, psychiatric disturbances or both at follow-up. Conclusions: Early recognition of LE and prompt immunomodulating therapy are of great importance to prevent the development of neurological sequelae, particularly cognitive impairment.

P525 IMPROVEMENT OF INTERICTAL EPILEPTIFORM DISCHARGES DETECTION DURING EEG-FMRI: PULSE ARTEFACTS CORRECTION BASED ON NONLOCAL MEANS FILTERING Iannotti GR1, Jorge J2,3, Matthieu J4, Pittau F5, Michel CM6, Lazeyras F7, Kocher M8, Vulliemoz S5, Grouiller F7,9 1 University of Geneva, Geneve, Switzerland, 2Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 3Department of Bioengineering, Institute for Systems and Robotics, Instituto Superior Tecnico, Universidade de Lisboa, Lisboa, Portugal, 4 HES-SO, Yverdon-les-Bains, Switzerland, 5EEG and Epilepsy Unit, Department of Neurology, Geneva University Hospital, Geneva, Switzerland, 6Functional Brain Mapping Laboratory, Department of Fundamental Neurosciences, University of Geneva, Geneva, Switzerland, 7Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland, 8Biomedical Imaging Group, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 9Swiss Center for Affective Sciences, University of Geneva, Geneva, Switzerland Purpose: Simultaneous EEG-fMRI has become a successful technique in research and in clinical practice to better characterize epileptic brains. One of the main artefacts during simultaneous EEG-fMRI is the Pulse Artefact (PA), deriving from electrodes and wires motion in the magnetic field subsequent to heartbeats. PA removal is usually performed by Averaged Artefact Subtraction (AAS) considering N previous and following PA occurrences. This approach doesn’t account for the beat-to-beat variability of PA and gives rise to important residuals especially at high field that can compromise IED identification. This study aimed to test the performance of a non-local mean (NLM) filtering where all PA occurrences are considered into the moving averaging with a weight depending on their similarity with the PA instance to be corrected. Methods: EEG was acquired at 3T using a high-density MR-compatible system in a healthy subject and a patient with focal epilepsy. For the patient, EEG was also acquired at 7T. PA correction was performed with both NLM and AAS algorithms. The EEG was averaged for the PA occurrences before and after each correction to evaluate the residuals. Moreover, identified IED of the patient were averaged to assess the preservation of the EEG signal after AAS and NLM.

Results: For the subject and the patient, PA residuals were smaller for NLM than for AAS. Finally, in the patient IED were better preserved by NLM. Conclusions: NLM is an efficient method to remove PA with less sensitivity to beat-to-beat variability than AAS while preserving the EEG signal of interest. This is of great interest especially to remove the increased PA residuals at higher magnetic field.

P527 FREQUENT RHABDOMYOLYSIS IN ANTI-NMDA RECEPTOR ENCEPHALITIS Lim J-A1, Lee S-T1, Jun J-S1, Park B1, Moon J1, Rha J-H2, Jung K-H1, Jung K-Y1, Chu K1, Lee SK1 1 Seoul National University Hospital, Seoul, Korea, 2Inha University Hospital, Neurology, Incheon, Korea Purpose: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis causes psychiatric symptoms, seizure, memory disturbance, language dysfunction, dyskinesia, autonomic instability, central hypoventilation, and a decrement of consciousness. During the disease course, some patients present with rhabdomyolysis, which is characterized by elevated creatine kinase (CK) levels and is sometimes fatal. Here, we analyzed the clinical presentation and provocation factors of rhabdomyolysis in antiNMDAR encephalitis. Method: We searched the prospective operative cohort registry for autoimmune encephalitis between Jan 2013 and Nov 2015 at the Seoul National University Hospital, and identified patients with anti-NMDAR encephalitis with rhabdomyolysis. We analyzed the clinical presentation and precipitating factors of rhabdomyolysis. Results: Among the 16 patients with anti-NMDAR encephalitis, nine patients had elevated CK enzyme levels and clinical evidence of rhabdomyolysis. Rhabdomyolysis was more frequent after immunotherapy: among the nine patients, six developed rhabdomyolysis after immunotherapy. The use of dopamine receptor blocker (DRB) increased the risk of rhabdomyolysis: three patients developed rhabdomyolysis after the administration of DRBs after immunotherapy. None of the patients without rhabdomyolysis received DRBs. One patient died due to rhabdomyolysis, and the remaining eight recovered. Conclusion: Rhabdomyolysis is a frequent complication in antiNMDAR encephalitis. It is more common after immunotherapy and the use of DRBs increases the risk. Therefore, DRBs should be administered carefully in patients with anti-NMDAR encephalitis.

P528 INTERICTAL AND POSTICTAL HEADACHE IN OUR EPILEPSY PATIENTS Nežádal T1,2,3, Bajacek M1,2, Hovorka J1, Nemcov a I1 1 Epileptology and Neuropsychiatry Center, Na Frantisku Hospital, Prague, Czech Republic, 2Neurology Department, Military University Hospital, Prague, Czech Republic, 3Institute of Neuropsychiatric Care, Prague, Czech Republic Purpose: Epilepsy and headache share common pathophysiological mechanisms, although the exact processes underlying these conditions are still unknown. Interictal headaches, namely migraine, are in epilepsy patients more frequent than in general population. Postictal headache (PIH) is classified as headache caused by and occurring within 3 h after an epileptic seizure, and remitting spontaneously within 72 h after seizure termination. PIH have a significant impact on the quality of life of people with epilepsy. Method: The aim of our study was to assess the frequency of both interictal and postictal headaches, their characteristics and other parameters


162 Abstracts (age, gender, epilepsy duration, seizure frequency and severity, effect of therapy) at the outpatient clinic during a short period (1 month). We evaluated 96 epilepsy patients (age: 44.2 12 years, men: 51%, epilepsy duration: 26.3 14.8 years). 42.7% patients were seizure free, median: 5.2 years. 13 patients underwent epilepsy surgery, 7 was implanted with VNS.

DV group does not resemble the pattern observed in MTLE any more than that observed in SCH. Nevertheless, the highly similar patterns of the three clinical groups suggest an increased vulnerability of certain hippocampal subfields; namely, CA4 DG, CA 2-3 and subiculum.

Results: We have found any headache in 53 (55.2%) patients. 32 (60.4%) headaches were interictal, 17 (17.8%) postictal, only 1 patient referred both types and ictal headache had 3 patients. The ICHD criteria of migraine fulfilled 24 (25%) patients, interictal were 15, postictal 8 and ictal in 2 cases. Other types of headache were mostly cervicogenic and tension-type. Migraine was only slightly more frequent in women (58.4%), was episodic and not more frequent in younger patients. The prevalence of interictal migraine was almost the same in seizure free and refractory patients (8 vs. 6). PIH occurred in both non-limiting and limiting seizures (8 vs. 9). We have seen retrospective prophylactic effect of AEs: valproate in 3, topiramate in 2 patients, effect of surgery in 1 patient with PIH. Patients referred good effect of analgetics and sleep.

P531 HLA-A, -B, -DRB1 HAPLOTYPIC ASSOCIATION WITH ANTIEPILEPTIC DRUGS INDUCED CUTANEOUS ADVERSE DRUG REACTIONS AMONG PATIENTS FROM MAINLAND OF CHINA Wu X1, Hu F2, Zhou D3 1 West China Hospital, Sichuan University, Neurology, Chengdu, China, 2West China Hospital in Sichuan University, Chengdu, China, 3West China Hospital of Sichuan University, Chengdu, China

Conclusion: Interictal and postictal headache is common epilepsy comorbidity, often underestimated and undertreated.

Purpose: Aims to investigate the association between antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) and human leukocyte antigen (HLA)-A, -B, -DRB1 in patients from mainland of China.

P529 HIPPOCAMPAL INVOLVEMENT IN PHYSIOLOGICAL VU: SUBFIELD VULNERABILITY RATHER A DEJ THAN TEMPORAL LOBE EPILEPSY Pešlová E1, Marecek R2,3, Shaw DJ4, Kasparek T4,5, Pail M3, Brazdil M3,4 1 Masaryk University, Brno, Czech Republic, 2CEITEC - Central European Institute of Technology, Masaryk University, MultiModal and Functional Neuroimaging Research Group, Brno, Czech Republic, 3Brno Epilepsy Center, Medical Faculty of Masaryk University and St. Anne’s University Hospital, Brno, Czech Republic, 4CEITEC - Central European Institute of Technology, Masaryk University, Behavioral and Social Neuroscience Research Group, Brno, Czech Republic, 5Faculty Hospital Brno and Medical Faculty of Masaryk University, Department of Psychiatry, Brno, Czech Republic Purpose: Morphological correlates of physiological deja vu (DV) have been identified recently within the human brain (Brazdil et al., 2012; Labate et al., 2015). Specifically, significantly reduced gray matter volume (GMV) within a set of cortical and subcortical regions reported in subjects experiencing DV mirrors the distribution of GMV reduction in mesial temporal lobe epilepsy (MTLE) patients. These patterns however vary in terms of the hippocampus. Another condition associated with hippocampal GMV reduction is schizophrenia (SCH). Here we tested the hypothesis that hippocampal involvement in physiological DV resembles more closely the pattern of GMV decrease observed in MTLE compared with that occurring in SCH. Methods: We compared the medians of GMV within hippocampal subfields (cornu amonis [CA]1, CA2-3, CA4 dentate gyrus [DG], subiculum and presubiculum) in healthy individuals that do (DV+; n = 87) and do not report deja vu experience (DV; n = 26), and patients with MTLE (n = 47) and SCH (n = 29). By Spearman rank correlation, we then evaluated the resemblance of MTLE and SCH groups to DV+ group with respect to spatial distribution of GMV deviation from DV group. Results: Significant GMV decrease was found in all subfields except CA1 for the DV+, MTLE and SCH groups relative to the DV group. Concerning the spatial distribution of GMV decrease, we found significant correlations both between DV+ and SCH, and DV+ and MTLE groups, with higher correlations between DV+ and SCH. Conclusion: Our findings reveal structural features of hippocampal involvement in physiological DV, MTLE and SCH. Despite our primary expectations, the pattern of GMV reduction in the DV+ relative to the


Method: Seventy-four patients with cADRs, including 13 with StevensJohnson syndrome (SJS), and toxic epidermal necrolysis (TEN); 70 AEDs -tolerant controls and 71 healthy volunteers were recruited. HLA genotyping was performed by the polymerase chain reaction (PCR)sequence-based-typing (SBT) method. Results: twenty-seven HLA-A, 46 HLA-B and 33 HLA-DRB1 alleles were detected in genotyping. Four high frequency haplotypes were reconstructed: HLA-A*3303-B*5801-DRB1*0301, HLA-A*0207B*4601-DRB1*0901, HLA-A*3001-B*1302-DRB1*0701, HLAA*1101-B*1502-DRB1*1202. The former one was found with higher percentage (10/70) among AEDs-tolerant controls than cADRs patients (3/74) with statistic significance (p < 0.05) in whole enrolled population. Two of those tolerant controls also took haplotype HLA-A*1101B*1502-DRB1*1202. No similar phenomenon was found in healthy volunteer and cADRs groups, even among patients with SJS/TEN. The latter and other haplotype HLA-A*1101-B*1502-DRB1*1501 was merely found in seven different patients, who exactly had carbamazepin (CBZ)induced SJS/TEN, in all patients with severe cADRs, both with significant difference in the frequency comparing with CBZ-tolerant controls and healthy volunteers (p < 0.05). Conclusion: These data suggested that haplotype HLA-A*3303B*5801-DRB1*0301 might be one of the protective genetic factors for AEDs-induced cADRs. HLA-A*1101-B*1502-DRB1*1202 and HLAA*1101-B*1502-DRB1*1501 had strong association with CBZ-induced SJS/TEN among patients from mainland of China.

P532 OBJECT AND ACTION NAMING IN RUSSIAN INDIVIDUALS WITH EPILEPSY Yurchenko A1, Golovteev A2,3, Kopachev D2, Dragoy O1,4 1 National Research University Higher School of Economics, Moscow, Russian Federation, 2Burdenko Neurosurgical Institute, Moscow, Russian Federation, 3Epilepsy Center, Moscow, Russian Federation, 4Moscow Research Institute of Psychiatry, Moscow, Russian Federation Purpose: A number of studies show that individuals with temporal lobe epilepsy (TLE) have deficit in object name retrieval. However, action naming is usually not addressed. Our goal was to investigate both object and action naming in Russian individuals with left TLE (LTLE) and to compare them to right TLE (RTLE) individuals.

163 Abstracts Method: 12 people with LTLE, 12 people with RTLE, and 17 healthy controls (all right-handed) were asked to name 40 pictures of objects and 40 pictures of actions using a single word (noun or verb). The two tests were balanced on name agreement and subject complexity of the picture, object/action familiarity, age of word acquisition, word-image agreement and word frequency. Results: T-test for independent samples revealed that, compared with controls, individuals with LTLE performed significantly worse on both tests (95% vs. 90%, p = 0.03 for object naming; 94% vs. 88%, p = 0.04 for action naming). No significant difference was found between individuals with RTLE and healthy people (93% vs. 95%, p > 0.05 for object naming; 92% vs. 94%, p > 0.05 for action naming). None of the groups showed significant difference in performance between object and action naming (p > 0.05). Conclusion: In contrast to individuals with RTLE, in individuals with LTLE a significant deficit in both object naming and action naming was found. Our results are in line with previous research that showed object naming impairment in individuals with LTLE (Alessio A et al Epilepsy Behav 2006;8(3):593–600; Bartha L et al Brain Lang 2003;87(1):194– 195). Critically, our findings reveal that action naming is impaired to the same extent as object naming in individuals with LTLE, in contrast to RTLE people.

P533 EFFECT OF SEIZURES ON SLEEP QUALITY IN PATIENTS WITH CHRONIC EPILEPSY Yoon SS1, Cho S-H2, Hwang KJ3, Yi JH4 1 Kyung Hee University Hospital, Neurology, Seoul, Korea, 2 Pohang Semyung Christianity Hospital, Pohang, Korea, 3 Kyung Hee University, Seoul, Korea, 4Kyung Hee University Hospital, Seoul, Korea Purpose: Epilepsy patients have high prevalence of various sleep disturbance compared to general population. The aim of this study was to investigate sleep quality in epilepsy patients according to the seizure control. Method: We enrolled the consecutive 111 epilepsy patients (M: F 84:27, age 20–65 y) from January 2009 to May 2013. All completed overnight polysomnography (PSG), sleep-habit questionnaire, Epworth Sleepiness Scale, and Beck Depression Inventory. Patients were divided into wellcontrolled group (WC, n = 62, no seizures ≥ recent 6 m) and uncontrolled group (UC, n = 49, seizure persisting ≥1/m). Data was compared between patients and controls and patients with WC and UC. Results: Patients had poorer sleep quality (lower sleep efficiency, higher apnea-hypopnea index & arousal indices) than controls. UC had a longer duration of epilepsy (mean 14.4 10.6 y vs. 6.6 9.5, p < 0.01) and a higher number of antiepileptic drug (2.5 1.1 vs. 1.1 0.7, p < 0.01) than WC. No significant difference was observed in frequency of nocturnal seizure between UC and WC. UC reported significantly longer sleep time during weekday (454.2 100.5 vs. 392.8 70.7 min, p < 0.01) and weekend (479.2 90.4 vs. 428.3 97.3 min, p = 0.01) than WC, however, other sleep habits were not different. Objective sleep time in PSG was longer in UC than WC (382.0 71.8 vs. 366.2 61.6 min, p = 0.04), while sleep efficiency and arousal indices were not significantly different between them. In patients with uncontrolled seizures, BDI seems to be higher than patients with controlled seizures (13.0 vs. 9.8, p = 0.08), but not significant. Conclusion: These findings showed that epilepsy patients had deteriorated sleep compared to controls, however, sleep quality was not remarkably influenced by seizure control.

Others 7 Wednesday 14th September P534 RETINAL NERVE FIBRE LAYER ASYMMETRY ASSOCIATED WITH DIAGNOSIS OF FOCAL EPILEPSY IN A DRUG-RESISTANT POPULATION Bartmann AP, Balestrini S, Schneider N, Clayton L, Sisodiya S, Plant G, Sander JW, Department of Clinical, Experimental Epilepsy UCL - Institute of Neurology, London, United Kingdom Purpose: Previous one-eye analysis studies demonstrated thinning of the retinal nerve fibre layer (RNFL) in people who had previous exposure to vigabatrin, diagnosis of drug-resistant epilepsy or learning disability. Retrograde trans-synaptic degeneration is the likely responsible mechanism for this observation. Given the role of temporal lobe structures in focal epilepsy (either as origin or propagation of seizures) and its close relation to segments of the visual pathway, we hypothesise that localised damage to the white matter could lead to asymmetry of the RNFL measures obtained by spectral-domain optical coherence tomography. Method: Seventy-four people with focal drug-resistant epilepsy (defined by EEG characteristics and/or evidence of hippocampal sclerosis) and 90 controls were recruited for this cross-sectional study. RNFL measures were obtained by spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of obtaining seizure control after adequate trials of two antiepileptic medications. Results: RNFL measures from patients with focal epilepsy had a statistically significant difference of mean measures of the inferior quadrant when compared to normal controls (mean bilateral thickness of inferior quadrant of 113.1 lm in cases and 121 lm in controls, p = 0.009, t-test). Conclusion: People with focal epilepsy were found to have significant asymmetry of the RNFL measures of the inferior quadrant. This suggests that ongoing epileptic activity may generate asymmetric damage to the white matter. Comparisons of different RNFL segments measures may help to clarify epilepsy phenotypes. Studies in larger populations and in people who are not drug-resistant are necessary to confirm this finding.

P535 PERIICTAL CHANGES OF THE INNNATE IMMUNE SYSTEM Proske M, Olmes D-G, Lang J, Hagge M, Schwab S, Linker RA, Hamer HM, Dogan Önügören M University of Erlangen, Neurology, Erlangen, Germany Purpose: Previous work demonstrated increase of leukocytes and natural killer (NK) cells in the immediate postictal state. Whether these changes were due to postictal stress or started already before clinical seizures remains elusive. To address this question, we intended to measure changes in the innate immune system before seizure onset. Method: Patients with frequent seizures undergoing non-invasive EEG monitoring at our institution between 2012 and 2015 were included. Patients with seizures during the sampling period (n = 14) were cases, those without controls (n = 9). Blood samples were obtained every 20 min preictally and directly, 1 and 24 h after a seizure. Peripheral blood-cell populations were measured via FACS analysis using markers for CD3, CD4, CD8, CD25, CD14, CD16, CD19, CD56. Means of cell numbers were used as baseline. Analysis was done for T helper-, cytotoxic T- and NK-cells, B-lymphocytes, activated and inactivated monocytes. Normality was tested using the Shapiro-Wilk test.


164 Abstracts Wilcoxon rank sum test and Wilcoxon signed rank tests were applied for matched pairs. Results: Compared to baseline, we found a rise of activated monocytes 60–180 min before a seizure. Decrease of T helper-cells (p = 0.0051*; median 0.9979 vs. 0.9727) and B-cells (p = 0.003*; median 1.0217 vs. 0.9195) as well as increase of cytotoxic T-cells (p = 0.0396*; median 1.0044 vs. 1.0272) and NK-cells (p < 0.001*; median 0.7802 vs. 1.9485) within the first 15 min after a seizure, normalizing within 2–24 h were significant findings. Reduction of activated monocytes 24 hrs after seizure did not reach significance level. Conclusion: We could not demonstrate significant preictal changes of immune-cells. This might be due to the time interval between blood drawings and subsequent seizure-onset with a time span varying between 2 and 20 min. Our data are in line to previous results, demonstrating postictal decrease of T helper- and increase of NK-cells.

P536 SEIZURES IN COMATOSE CPR SURVIVORS TREATED WITH HYPOTHERMIA Eilam A, Samogalsky V, Bregman G, Gilad R Kaplan Medical Center, Rechovot, Israel There are some reports in the literature indicating the presence of seizures during and after targeted temperature management. On the other hand post anoxic seizures are a sign of unfavorable neurological outcome. Information on seizure incidence in patients treated with hypothermia is scarce. The purpose of our study was to evaluate the occurrence of seizures in comatose survivor patients treated with targeted temperature in respect to seizures in a normal temperature group of comatose patients. Method: This was a retrospective study of unconscious adults post cardiac-pulmonary resuscitation, hospitalized in the intensive care unit during the years 2008–2015. The patients were divided into 2 groups: those treated with hypothermia and those with normal body temperature. Both groups were evaluated for the appearance of seizures during their hospitalization which was the primary outcome of the study. Mortality during hospitalization was the secondary end point. Results: The data of 88 consecutive unconscious patients after out of hospital cardiac arrest were collected. 26 patients were treated with targeted temperature (32–34 degrees) and 62 patients with normal temperature. In the hypothermic group 6 (23%) patients developed seizures during hospitalization. In the normothermic group - 11 (17%). The mortality rate was similar in both groups 16(61%) in the hypothermic group and 38(61%) in the conservative group. Conclusion: In this retrospective study we found a higher rate of seizures in the hypothermic group of comatose patients respect to the patients with normal temperature after resuscitation. Mortality during hospitalization was similar in both groups.

P537 SEIZURE PREVENTION IN ANGIOPLASTY FOR SYMPTOMATIC EXTRACRANIAL CAROTID AND VERTEBRAL ARTERY STENOSIS Elmahdy M1, Alkhamis F2, Boss S3 1 Faculty of Medicine, Cairo University, Neurology, Cairo, Egypt, 2Faculty of Medicine, Dammam University, Neurology, Dammam, Saudi Arabia, 3Saad Specialist Hospital, Neurology, Alkhobar, Saudi Arabia Purpose: Seizure disorder is not uncommon during and after carotid angioplasty, the main predictors for seizure are age of the patient, degree


of stenosis, preexisting cerebral ischemia in the treatment territory has been increasingly reported as a complication of carotid angioplasty and stent placement. The aim of the present study is to evaluate the efficacy of valproic acid in prevention of periprocedural seizure disorder. Methods: A retrospective study was carried out, and it included files of patient undergoing stenting for carotid or vertebra-basilar arteries stenosis the last 3 years from January 2012 to January 2015. Results: Nineteen (19) patients were included. The mean age was 67.6 years (54–80 years), sex ratio male female was 2.8 (14 male, and 5 female). History of hypertension, diabetes, or dyslipemia was recorded in 89% (17/19); combination of at least 2 risk factors was recorded in 89%, and 54% (10/19) of patients had combinations of the three risk factors. The extra-cranial stenosis was symptomatic in 16 patients (84%). it involved carotid arteries in 15 patients (79%), and vertebro-basilar system in the remaining 4 patients (21%). the mean stenosis severity was 79% (50–90%); it was an ulcerated stenosis in 2 patients. All patients received valproic acid 10–15 mg per day starting one day before and 14 days following the procedure. All patients undergo angiography with stenting, and 18 (95%) of them had had additional post stenting stenosis dilatation. after the stenting procedure the mean duration of hospitalization was 8 days (1–28 days). 52% (10/19 had had hospitalization duration less than 7 days. In all patients no seizures were recorded after 3, 6, and 12 months of follow-up. Conclusion: Short course of valproic acid prevents periprocedural seizures in angioplasty and stenting.

P538 PARANEOPLASTIC ANTI-LGI1 LIMBIC ENCEPHALITIS IN A PATIENT WITH RECTAL CANCER - A CASE REPORT Ismail FS1, Wellmer J1, Schmidt R2, Schlegel U3, Bien CG4, Dalmau J5, Gr€ onheit W1 1 University Hospital Knappschaftskrankenhaus Bochum, RuhrEpileptology, Bochum, Germany, 2Department of General and Visceral Surgery, Evangelisches Krankenhaus Herne-Mitte, Herne, Germany, 3Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany, 4Krankenhaus Mara, Epilepsy Center Bethel, Bielefeld, Germany, 5Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain Purpose: Antibodies (Ab) to the leucine-rich glioma inactivated-1 protein (LGI1) are associated with limbic encephalitis (LE), faciobrachial dystonic seizures and hyponatremia. They occur very rarely related to cancer; the association of anti-LGI1 Ab with colorectal cancer has not been previously reported. Case report: Here we present a 68-year-old man with histologically confirmed rectal adenocarcinoma (UICC TNM classification IIIC; ypT3, ypN2b(14/20),L1,V1,R0,M0). Three weeks after beginning of pre-operative chemoradiotherapy with oral capecitabine, he developed severe mnestic deficits and affective lability. Anti-LGI1 Ab were identified in serum (1:4,000) and cerebrospinal fluid (CSF) (1:8), as well as corresponding Ab to voltage-gated potassium channel (VGKC) in serum (392 pmol/l, n < 85 pmol/l). Brain MRI showed high T2/FLAIR signal intensity and contrast medium uptake (CMU) in both hippocampi compatible with bilateral LE. During video-EEG-monitoring, brief multifocal myoclonic-like jerks were recorded. Interictal EEG showed bi-temporal slowing, sharp- and sharp-slow-waves without ictal EEG abnormalities. Neuropsychological testing demonstrated left temporo-mesial cognitive dysfunction. Pulse methylprednisolone and intravenous immunoglobulin were administered for 5 days, but without symptom improvement.

165 Abstracts Because of suspected tumor association of the anti-LGI1 LE, immediate tumor resection was performed before completion of the pre-operative radiotherapy with the aim to prevent progression of the memory deficits. Cognition improved significantly within a few days after tumor resection. On follow-up at 3 months neuropsychological testing confirmed this improvement in neurocognitive function. The T2/FLAIR signal intensity and CMU in both hippocampi disappeared completely. The LGI1- and VGKC-Ab titer decreased in serum (1:250 and 1:194). Immunohistochemical investigation of LGI1 expression in the tumor tissue of the patient showed a mild, but not significant increase of reactivity comparing with control tumor. Conclusion: The clinical, neuropsychological and MRI follow-up suggested a paraneoplastic etiology of the anti-LGI1 LE in association with the rectal adenocarcinoma.

P541 WHAT DOES A NEUROLOGIST ADD TO THE MANAGEMENT OF BRAIN TUMOUR RELATED EPILEPSY (BTRE)? - EXPERIENCES OF SETTING UP A BTRE CLINIC AT THE QUEEN ELIZABETH HOSPITAL, BIRMINGHAM UK Brewster R, Samarasekera S Queen Elizabeth Hospital, Neurosciences, Birmingham, United Kingdom Purpose: The National Institute for Clinical Excellence (NICE) recognises that the care of patients with CNS malignancy needs to be coordinated. However the pathway for managing BTRE differs across hospitals in the UK, with patients presenting to a number of clinicians. We sought to establish a clearer referral pathway, primarily through the neuro-oncology multidisciplinary team. Method: Local guidelines for managing BTRE were established in 2015. Weekly BTRE clinic appointments enabled the neurologist to accept referrals primarily from neuro-oncology and neurosurgery. Results: 42 new referrals were seen over 24 months; 40 patients experienced both focal and generalised seizures. The neurologist modified the AED regime in 18 (42.9%) patients. Addition of a second AED, most commonly Valproate, was recommended by neurology for 6 (14.3%) patients. This was done primarily to manage focal symptoms, which was successful in 50% cases. Withdrawal of an AED, commonly phenytoin or clobazam, was recommended for 12 (28.5%) patients. Co-existing non epileptic attacks were diagnosed in 3 (7.1%) patients. 32 (76.2%) patients had been prescribed Levetiracetam by the referring clinician, reflecting local guidelines. Conclusion: Establishing local guidelines for the management of BTRE has changed practice regarding the choice of AEDs used, with drugs such as Levetiracetam becoming first line. The neurologist’s role is in refining AED regimens and clarifying diagnostic uncertainty. A proportion of seizures, largely focal events, remain refractory to treatment. Balancing multiple treatments with quality of life is essential.

Pharmacology/AEDs 1 Monday 12th September P544 A RETROSPECTIVE STUDY OF LACOSAMIDE EFFICACY AND TOLERABILITY AS EARLY AND LATE ADD-ON TREATMENT IN ADULT PATIENTS WITH FOCAL EPILEPSY Lawley A, Hegde V University Hospital of Coventry and Warwickshire, Coventry, United Kingdom Purpose: We aimed to determine the efficacy and tolerability of Lacosamide as both early and late add-on treatment in a population of adult patients with focal epilepsy. Patients were divided into those who had previously been treated with 2 or fewer antiepileptic medications (group A) versus more than 2 antiepileptic medications (group B). Four outcome measures were identified; responder rate (defined as overall seizure reduction greater than 50%), overall seizure frequency reduction, seizure freedom and discontinuation rate. Method: 35 patients treated in a tertiary referral centre in the United Kingdom over a 5-year period were identified using pharmacy records. Case notes were retrospectively reviewed evaluating seizure control and tolerability prior to and after introduction of Lacosamide. 12 patients were included in group A versus 23 in group B. Average follow-up was over 2 years. Both follow-up duration and Lacosamide dose were similar between groups. Patients in group A tended to have a shorter duration since epilepsy diagnosis (18 vs. 27.1 years). Results: Both responder rate and overall seizure frequency reduction were greater in group A than group B, although not achieving statistical significance (responder rate 58.3% vs. 39.1%, p = 0.31; average seizure frequency reduction of 7.1/month vs. 4.9/month, p = 0.36, respectively). Side effects occurred more frequently in group B with 4 patients experiencing side effects leading to discontinuation of treatment (vs. 0 in group A). Overall, 11 patients achieved seizure freedom of 6 months or longer, with 6 patients achieving a period of seizure freedom of 12 months or longer. Conclusion: Lacosamide was effective as both early and late add-on treatment for focal epilepsy. Tolerability appears to be improved when used as early adjunctive treatment, reflecting adverse effects being more commonly reported when used in combination with multiple anti-epileptic medications. Significant side-effects were not encountered in the early add-on treatment group.

P545 A RANDOMIZED, OPEN-LABEL, PARALLEL GROUP, MULTI-CENTER COMPARATIVE TRIAL OF LEVETIRACETAM AND TOPIRAMATE AS ADJUNCTIVE TREATMENT IN REFRACTORY FOCAL EPILEPSY Lee B1, Loesch C2, Osakabe T3, Lee J4, on behalf of the N01353 study group 1 Haeundae Paik Hospital, Busan, Republic of Korea, 2UCB Pharma, Monheim, Germany, 3UCB Pharma, Tokyo, Japan, 4 UCB Pharma, Seoul, Republic of Korea Purpose: To assess long-term effects of adjunctive levetiracetam (LEV) on retention rate, safety/tolerability and efficacy compared with topiramate (TPM) in patients with refractory focal epilepsy (partial-onset seizures). Methods: The study consisted of baseline (8-week retrospective; 4-week prospective), 4-week up-titration, 20-week dose-finding, and 28-week maintenance periods. Patients aged 16–80 years had ≥2 seizures Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

166 Abstracts (retrospective baseline) and ≥1 seizure (prospective baseline) while taking 1–3 concomitant AEDs at stable dose. Patients were randomized 1:1 to LEV or TPM. During dose-finding, investigators adjusted study drug dosage (LEV ≤3,000 mg/day; TPM ≤400 mg/day). The primary efficacy measure was 52-week retention rate (Full Analysis Set; FAS) with a sensitivity analysis of patients treated with in-label dosages. Secondary efficacy measures were percent reduction from baseline in weekly seizure frequency, ≥50% responder rate and seizure freedom rate (≥6 months); all during 52-week treatment period (FAS). Safety measures were treatment-emergent adverse events (TEAEs) and discontinuation rate due to TEAEs (Safety Set). Results: Overall 343 patients were randomized (LEV 177; TPM 166); 211 patients (61.5%) completed the study. Mean dose: 1,322.4 mg/day (LEV) and 146.1 mg/day (TPM). The 52-week retention rates were 59.1% (LEV) and 56.6% (TPM) (p = 0.7007, confirmatory); and 59.1% and 42.5% in patients treated with in-label dosages. Median percent reduction from baseline in weekly seizure frequency was 74.47% and 67.86% (p = 0.0665), and ≥50% responder rate was 69.0% and 64.8% (p = 0.4205), in LEV and TPM groups, respectively. Seizure freedom rates were 35.8% (LEV) and 22.3% (TPM). TEAEs were reported by 125 (70.6%) and 128 (77.1%) patients; 14 (7.9%) and 21 (12.7%) patients discontinued due to TEAEs in LEV and TPM groups, respectively. Conclusion: The 52-week retention rates for adjunctive LEV and TPM in patients with refractory epilepsy might be comparable. TPM retention rates may have been impacted by lower than recommended TPM doses. No new safety concerns for LEV were identified. UCB Pharma-funded

P547 A VALIDATED HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD FOR LAMOTRIGINE ANALYSIS IN PLASMA SAMPLES Shabbi H1, Soler D1, Duca D2, Grech G3, Mifsud J1 1 Clinical Pharmacology and Therapeutics, University of Malta, Msida, Malta, 2Research & Innovation Facilities Support Unit, University of Malta, Msida, Malta, 3Pathology, University of Malta, Msida, Malta Purpose: Lamotrigine is one of the new AEDs which is widely used as mono or poly-therapy in treatment of epilepsy in Maltese paediatric population. Monitoring of LTG levels in biological fluids is a valuable aid to adjust the administered dose, monitor pharmacokinetic interactions and assess patient compliance. Method: The chromatographic analysis of spiked plasma samples was carried out on a reversed phase Waters Symmetryâ C18 column (250 mm 9 4.6 mm; 5.0 lm particle size), using water, methanol, acetonitrile, and triethylamine (68.7:25:6:0.3, v/v/v/v) as mobile phase. The wavelength detection was set at 237 nm. Results: The developed method was validation for selectivity, linearity, precision, accuracy, limit of detection and quantification, and recovery. At 30°C and a flow rate of 0.8 ml/min, the peak for lamotrigine was symmetrical in shape, with a retention time 20.358 min. lamotrigine analog [2,4-Diamino-6-(4-methoxyphenyl)-1,3,5-triazine] was found to be the best internal standard with good resolution and no interference with endogenous matrix. Conclusion: This analytical method will be used to analyse patient samples for the development of a pharmacokinetic model for lamotrigine. The model will include the influence of covariates such as drug plasma concentrations, age, weight, cytochrome 450 (CYPs) genotypes and coadministered AEDs.

P549 ADVERSE DRUG REACTION OF ANTIEPILEPTIC DRUGS IN EPILEPSY CLINIC, TERTIARY HOSPITAL, THAILAND Nuntasaen T1, Lertsinudom S2, Tiamkao S3, Topark-Ngarm A2, Soontornpas R4 1 Pharmacy Department, Srinagarind Hospital, Khon Kaen University, Muang, Thailand, 2Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khonkaen, Thailand, 3Faculty of Medicine, Department of Medicine, Khon Kaen University, Khonkaen, Thailand, 4 Pharmacy Department, Srinagarind Hospital, Khon Kaen University, Khonkaen, Thailand Purpose: To evaluate the rate of adverse drug reaction (ADR) which were classified as type A reaction (side effect) and type B reaction (hypersensitivity reaction) of antiepileptic drugs (AEDs) and study the influencing factor to adverse drug reaction include management to solving adverse drug reaction. Method: The retrospective study was performed in epileptic outpatients who attended the Epilepsy clinic. The patients who have been treated with at least one AED were included. Data were collected from chart review and an electronic database. Data were analyzed using SPSS Version 20. Results: A total of 382 patients were recruited. The most AEDs used were phenytoin (30.86%) followed by sodium valproate (26.72%). The incidences of side effect and hypersensitivity reaction were 183 cases (47.91%) and 47 cases (12.30%) respectively. The most common side effect was grade 1 gingival overgrowth (44.09%) caused by phenytoin. Polytherapy as a factor related to side effect (OR = 4.25, p = 0.039). The most event of hypersensitivity reaction was maculopapular rash (89.58%) cause by phenytoin (48.21%). Phenytoin induced rashes were more frequent in patients who had drug interactions than patients who did not have (OR = 5.39, p = 0.02). The management to solving side effect and hypersensitivity reaction were counseling by pharmacist and changing to new AEDs groups. Conclusion: The rate of side effect and hypersensitivity reactions were highest in phenytoin so pharmacist should be concern and give closely pharmaceutical care to epileptic patient who take phenytoin.

P550 ADD-ON ANTIEPILEPTIC DRUG TREATMENT IN PATIENTS WITH SEIZURES AFTER EPILEPSY SURGERY Ryzí M1, Oslejskov a H1, Rektor I2,3, Hemza J2, Chrastina J2, 2,3 Br azdil M 1 Brno University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, 2St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, 3Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic Purpose: The main purpose of the study was to evaluate the indications of add-on AED (antiepileptic drug) treatment and whether specific AED influenced long term outcome in patient with persist seizures after resective epilepsy surgery. Method: Our study was a retrospective investigation of 94 patients with seizure recurrence in the first year after surgery. The outcome were classified by ILAE classification. Results: At the last follow-up visit (average of 9.73 3.70 years after surgery), 33 of the 94 patients (35.1%) were completely seizure free


167 Abstracts (ILAE class 1). The add-on AEDs were used in 13 out of 20 (65.0%) ILAE 2, 10 out of 24 (41.7%) ILAE 3, 17 out of 23 (73.9%) ILAE 4 and 23 out of 27 (85.2%) ILAE 5 + 6 patients. The median of the use of the first add-on AED was 5.42 years after surgery in ILAE 2, 1.34 in ILAE 3, 0.75 in ILAE 4 and 1.0 in ILAE 5 + 6 patients. The differences between seizure-free rates were not significant when we compared the most often used AEDs (levetiracetam, carbamazepine, lamotrigine). Conclusion: The application and time of use of add-on AEDs after surgery significantly depends on outcome in first postoperative year. The majority of patients with considerable improvement because of surgery do not use any new add-on AEDs.

Pharmacology/AEDs 10 Wednesday 14th September

P552 A PROSPECTIVE ANALYSIS OF THE EFFECTIVENESS AND TOLERANCE OF LACOSAMIDE IN PATIENTS WITH REFRACTORY PARTIAL EPILEPSY Czapinski P, Czapinska-Ciepiela E Epilepsy and Migraine Treatment Centre, Krakow, Poland Purpose: To assess and analyze the effectiveness and tolerance of lacosamide (LCM) in polytherapy of patients with refractory partial epilepsy, the number of responders, causes of therapeutic failures, the most effective combinations of LCM with other antiepileptic drugs (AED). Method: A prospective analysis of 73 consecutive patients from a single center, in whom current treatment was extended to include LCM up to a minimum dose of 200 mg/day, with subsequent treatment optimization in a 12-month follow-up. The analysis focused on: % of responders (at least a 50% reduction in seizure number), % of seizure-free patients, % of lacosamide monotherapy, % of non-responders remaining under treatment and % of patients excluded from follow-up.

P551 BEHAVIORAL DISINHIBITION AND GABAERGIC TREATMENT IN CHILDHOOD EPILEPSY van Tuijl D1, Groenwold RHH2, Vlaskamp C1, van Campen J3, Braun KPJ3, Jansen FE3, Bruining H1 1 Brain Center Rudolf Magnus, University Medical Center Utrecht, Psychiatry, Utrecht, Netherlands, 2Julius Centre, University Medical Centre Utrecht, Utrecht, Netherlands, 3 Brain Center Rudolf Magnus, University Medical Center Utrecht, Child Neurology, Utrecht, Netherlands

Results: 37 patients (50.7%) were regarded as responders, of which 7 (9.6%) were seizure-free, and 14 (19.2%) demonstrated a >75% seizure number reduction. The mean duration of current therapy in the group was 20.9 years, the mean number of AED therapy - 8.7, the mean LCM dose – 552 mg/day. Six patients (8.2%) received the drug in monotherapy, 31 (42.5%) - in 2, 3 or 4-drug polytherapy. Medications most commonly combined with LCM included levetiracetam (LEV - 37.8%), valproate (VPA - 35.1%), topiramate (TPM - 27.0%) and lamotrigine (LTG 21.6%). In non-responders (n = 18, 24.7%) continuing LCM treatment, the mean current treatment time was longer (22.8 years), the mean number of prior therapies was higher (11.6), while the mean LCM dose was comparable (558.3 mg/day).

Purpose: Chronic childhood epilepsy (CE) has been associated with altered chloride homeostasis leading to depolarizing effects of GABA. Antiepileptic drugs (AEDs) that potentiate GABAergic transmission may exacerbate hyperexcitability in circuits with elevated intraneuronal chloride levels. We aimed to test whether GABAergic AEDs increase the risk for behavioral disinhibition (BDI) as a possible clinical correlate of depolarizing GABA.

Conclusion: More than 50% of patients with refractory epilepsy may be effectively treated with LCM added to current therapy; in 28.8%, the therapeutic effect is excellent, yet the doses need to be higher than recommended. In more than 8% of patients, LCM may be used in monotherapy, if warranted. In combinations, LCM most often works well with LEV, VPA, TPM, LTG.

Method: Retrospective chart analysis of BDI symptoms and AED treatment regimes was performed in children with active epilepsy (n = 146, age 4–17 years) who consulted our pediatric neurology outpatient clinic in the last three years. We used a risk-set approach to analyse whether the presence or addition of a specific AED category was associated with enhanced risk for episodes of BDI. Results: Mean duration of follow-up was 2,343 days (range 218–6,292, SD 1,437). Episodes of BDI were reported in 51 (34.9%) children. Current use of AEDs targeting GABA (odds ratio 1.8, 95% CI 1.02–3.29, p = 0.04) and SV2A-mediated (2.0, 1.13–3.60, p = 0.02) neurotransmitter release was associated with increased risk for BDI. Restricting the analysis to the 90 days before BDI occurrence revealed that only addition of GABAergic AEDs (26.88, 6.71–107.76, p < 0.001) was associated with BDI. In contrast to to our expectations, seizure control was reported to have improved parallel to most BDI episodes. Conclusion: Our findings support the hypothesis that GABA potentiating drugs can trigger paradoxical behavioral effects in CE. BDI often occurred while seizure control improved, which may have reduced alertness for paradoxical behavioral effects of GABAergic AEDs. Our findings further suggest that addition of chloride reducing agents may reduce these adverse behavioral responses.

P553 ADVERSE PSYCHOLOGICAL EFFECTS OF LEVETIRACETAM COMPARED TO SEVEN OTHER COMMON ANTI-EPILEPTIC DRUGS IN ADULTS WITH EPILEPSY IN GENERAL PRACTICE Josephson C1,2,3,4, Engbers J5, Patten S2,3,4,6, Lowerison M2, Sajobi T2,3,4, Jette N1,2,3,4, Wiebe S1,2,3,4 1 Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, AB, Canada, 2 Community Health Sciences, University of Calgary, Calgary, AB, Canada, 3O’Brien Institute of Public Health, Calgary, AB, Canada, 4Hotchkiss Brain Institute, Calgary, AB, Canada, 5Desid Labs Inc., Calgary, AB, Canada, 6University of Calgary Cumming School of Medicine, Psychiatry, Calgary, AB, Canada Purpose: To examine whether treatment with levetiracetam increases the risk of psychiatric adverse effects (PAEs) compared to other common anti-epileptic drugs (AEDs) in a population-based cohort. Method: A cohort of epilepsy was identified in The Health Improvement Network (THIN) database using a modified version of a previously published case definition. A 3-year washout period was used prior to the prescription date to ensure it was incident. We identified codes for PAEs through a systematic review of the READ ontology. Only patients older than 18 years at prescription, with incident prescription after the year 2000, and with no history of a psychiatric disorder prior to meeting the case definition were included. A multivariate Cox Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

168 Abstracts proportional hazards model was used to evaluate time to PAE controlling for age, gender, levetiracetam, and the seven other most commonly used AEDs (medications were treated as time-varying coefficients using 6 month epochs).

another combination may reduce LAEP score and the risk of unfavorable quality of life and potential non-adherence.

Results: We identified 18,864 patients of whom 1,696 experienced PAEs during 2 years of follow-up. The hazard ratio (HR) of PAEs in patients treated with any AED was 1.20 (95% confidence interval [95% CI] 1.03–1.38; p = 0.02). The hazard of a PAE with levetiracetam was higher than for those not prescribed the medication (HR 1.44, 95% CI 1.21–1.71, p < 0.001) when controlling for age, gender, and the seven other most common AEDs. The hazard conveyed by levetiracetam was comparable to the seven other AEDs including that for valproate (HR 1.62, 95% CI 1.45–1.81; p < 0.001).

P555 LONG-TERM SAFETY AND EFFICACY OF ADJUNCTIVE PERAMPANEL IN PATIENTS WITH DRUG-RESISTANT PRIMARY GENERALISED TONICCLONIC SEIZURES IN IDIOPATHIC GENERALISED EPILEPSY: RESULTS OF AN OPEN-LABEL EXTENSION Wechsler RT1, French J2, Trinka E3, Brandt C4, O’Brien TJ5, Bibbiani F6, Patten A7, Laurenza A6 1 Idaho Comprehensive Epilepsy Center, Boise, ID, United States, 2NYU Comprehensive Epilepsy Center, New York, NY, United States, 3Paracelsus Medical University, Salzburg, Austria, 4Bethel Epilepsy Centre, Mara Hospital, Bielefeld, Germany, 5Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia, 6Eisai Inc, Woodcliff Lake, NJ, United States, 7Eisai Ltd, Hatfield, United Kingdom

Conclusion: Levetiracetam was associated with a higher hazard of PAEs during 2-years follow-up. However, a higher hazard was noted for almost all AEDs including valproate. These results, seemingly counterintuitive, likely represent a major caveat with pharmacoepidemiological studies using primary care data as protopathic bias or confounding by severity may result in the spurious interpretation that all AEDs confer increased hazard of PAEs.

P554 ADVERSE EFFECTS OF DUAL ANTICONVULSANT DRUG THERAPY IN EPILEPSY PATIENTS EXPERIENCE OF A TERTIARY EPILEPSY OUTPATIENT CLINIC Kowski A1, Weissinger F2, Gaus V1, Holtkamp M1 1 Charite-Universit€atsmedizin Berlin, Neurology, Berlin, Germany, 2Stroke Unit, Klinik f€ur Neurologie, Vivantes Humboldt-Klinikum Berlin, Zentrum f€ur Epilepsie, Berlin, Germany Purpose: In epilepsy patients, adverse effects (AEs) of antiepileptic drugs (AEDs) potentially lead to unfavorable quality of life, impaired adherence, and discontinuation of treatment. This study aimed to identify prognosticators including AEDs for overall high AE burden and for specific AEs focusing on patients with AED duo-therapy. Method: In our tertiary epilepsy outpatient clinic, patients ≥16 years with epilepsy for ≥12 months routinely complete the Liverpool Adverse Events Profile (LAEP). Demographic, epilepsy and treatment variables originated from our comprehensive outpatient database. All variables were entered into a binary logistic regression model. Results: Out of 1,325 comprehended patients, 341 on AED duo-therapy fulfilled inclusion criteria. Duo-combinations seen in ≥5% of included patients comprised lamotrigine-levetiracetam (n = 66), lamotrigine-valproic acid (n = 38), lacosamide-levetiracetam (n = 29), levetiracetamvalproic acid (n = 21), and lamotrigine-zonisamide (n = 17). We found no independent predictors for high AE burden (LAEP score ≥45) but a non-significant trend for an association with female sex (p = 0.064) and lack of 12-month terminal seizure remission (p = 0.071). The three most commonly reported specific AEs were sleepiness (67%), difficulty concentrating (60%), and memory problems (53%). The AED-combination lamotrigine-levetiracetam was associated with double/blurred vision (OR 4.250), upset stomach (OR 6.068), and difficulty concentrating (OR 4.200); lamotrigine-valproic acid with hair loss (OR 6.057) and difficulty concentrating (OR 4.114), lacosamide-levetiracetam with difficulty concentrating (OR 6.300), and levetiracetam-valproic acid as well as lamotrigine-zonisamide with hair loss (ORs 8.779 and 6.267, resp.). Conclusion: Individual duo-combinations of AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy and common forms of AED duo-therapy who are at high risk for specific AEs. Change to


Purpose: Perampanel is approved for adjunctive treatment of partialonset seizures, with or without secondarily generalised seizures, and for primary generalised tonic-clonic (PGTC) seizures in epilepsy patients aged ≥12 years. Adjunctive perampanel previously demonstrated efficacy in patients with drug-resistant PGTC seizures in idiopathic generalised epilepsy (IGE) in a randomized, double-blind, placebo-controlled Phase III study (French et al. Neurology 2015;85:950–957). Here we report long-term safety and efficacy outcomes from an open-label extension (OLE). Method: Of 140 eligible patients completing the core phase of study 332, 138 received once-daily adjunctive perampanel in the OLE. Following dose optimisation in a 6-week blinded conversion period (maximum 12 mg/day), patients received open-label perampanel for up to 136 weeks. Safety assessments included monitoring adverse events (AEs), discontinuations, laboratory tests and vital signs. Efficacy assessments included changes in seizure frequency and 50% responder rates relative to baseline of the core phase. Results: Most patients received a modal perampanel dose >4 to 8 mg/ day (n = 93) or >8 to 12 mg/day (n = 34); 11 patients received ≤4 mg/ day. Sixty patients discontinued perampanel during the OLE, most (n = 41) due to reasons other than AEs or inadequate therapeutic effect. There were 120 patients (87.0%) with treatment-emergent AEs, 20 (14.5%) with severe AEs, 18 (13.0%) with serious AEs, and 13 (9.4%) with AEs leading to withdrawal. By the end of the conversion period, patients who had received placebo (n = 70) or perampanel (n = 68) in the core phase were achieving similar median changes in PGTC seizure frequency (100.0% and 93.1%, respectively) and 50% responder rates (74.3% and 75.0%, respectively). Seizure control appeared to be sustained throughout the maintenance period in all patients. Conclusion: In this OLE, long-term adjunctive perampanel, administered up to 142 weeks, demonstrated a favourable risk-benefit ratio in IGE patients. Outcomes were consistent with the known safety profile for perampanel.

169 Abstracts P556 ESLI-ATLANTICO: AN OBSERVATIONAL STUDY ON THE USE OF ESLICARBAZEPINE IN NORTH-WEST SPAIN Rodrıguez-Osorio X1, Puente Hernandez M1, Abella J2, Pérez-Lorenzo G1, Puy-Nu~nez A3, Lopez-Ferreiro A3, SaavedraPi~ neiro M1, Corredera-Garcıa E1, Lopez-Gonzalez FJ1 1 Complejo Hospitalario Universitario Santiago, Santiago de Compostela, Spain, 2Hospital Arquitecto Marcide, Ferrol, Spain, 3Complejo Hospitalario de Pontevedra, Pontevedra, Spain Purpose: Eslicarbazepine acetate (ESL) is an antiepileptic drug approved as adjunctive treatment for partial-onset seizures with a good profile of efficacy and tolerability as shown by previous studies. We aim to analyze our experience with adult patients treated on ESL after 3, 6 and 12 months in a daily clinical practice routine. Method: We performed an observational retrospective study in three secondary and tertiary hospitals in Galicia, Spain. Clinical data, efficacy, safety, adverse events (AE) and adherence were analyzed. Responders achieved ≥50% reduction on seizure frequency compared to baseline (3 months period). Data was collected between January 2014 and January 2016. Results: n = 142 patients were included. n = 98, n = 69 and n = 48 completed 3, 6 and 12 months of follow-up. Median age was 46[33,59] years old; 54.9% were men (n = 78). Medium time of evolution of epilepsy was 13[5,31.5] years. n = 58 (40.8%) suffered secondary generalized seizures. Reasons for starting ESL were inefficacy of previous AEDs (70.4%; n = 100) or intolerance (16.2%; n = 23). Efficacy was observed in 51% of patients (n = 50 being n = 28 [56%] seizure-free) after 3 months; 55% (n = 38; 55.26% seizure-free [n = 21]) at 6 months; and 46% (n = 20; 68.18% seizure-free [n = 15]) after 1 year. When only considering early ESL use (first/second adjunctive treatment), efficacy raised at 72.72% (n = 16/22 with 56.25% seizure-free [n = 9]) at 3 months; 69.23% (n = 9/13 with 66.66% seizurefree [n = 6]) at 6 months; and 83.33% (n = 10/12; with 70.0% seizurefree [n = 7]) after 1 year. Secondary generalization significantly diminished. Rate of AE was 21.3% (n = 30) at 3 months being dizziness the most frequent (n = 14). n = 10 and n = 4 patients reported AE after 6 and 12 months. None was life-threatening. Adherence was high (96.77%, 95.45% and 97.77% respectively). Conclusion: Our study shows a high tolerability and adherence of ESL. Considering together with the high efficacy rates when added promptly, ESL should be considered as an early treatment for focal epilepsies.

P557 CBD-ENRICHED MEDICAL CANNABIS FOR INTRACTABLE PEDIATRIC EPILEPSY Tzadok M1, Linder I2, Kramer U3, Menascu S3, LermanSagie T4, Dor M5, Ben Zeev B1 1 Pediatric Nerology, Sheba Medical Center, Ramat Gan, Israel, 2 Pediatric Neurology, Wolfson Medical Center, Holon, Israel, 3 Pediatric Nerology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 4Pediatric Nerology, Wolfson Medical Center, Holon, Israel, 5Medical Cannabis Unit, Ministry of Health, Tel Aviv, Israel

Method: 129 patients (age range 1–25 years) suffering from intractable epilepsy were treated with cannabis oil in three Israeli epilepsy centers from 02/2014 for a period of at least 1 month. The formula chosen contained CBD (cannabidiol) and THC (tetrahydrocannabinol) in a ratio of 20:1 dissolved in olive oil. The CBD dose ranged from 1 to 20 mg/kg/ day. short-term outcome (average of 6 months), side effects and additional effects of the treatment are presented. Results: Significant positive effect on seizure load was found. Adverse reactions were minimal and included: somnolence, fatigue, vomiting, irritability and aggravation of seizures. Conclusion: These results are promising and suggest that further prospective, well-designed clinical trials using enriched CBD medical cannabis should be conducted.

P558 DRIED BLOOD SPOTS- A NOVEL METHOD FOR THERAPEUTIC DRUG MONITORING IN CHILDREN WITH EPILEPSY IN A HOMEBASED SETTING Wide K1, Walander M2, Linder C3, Gustafsson LL4, Pohanka A3 1 Div of Pediatrics, Karolinska Institute, CLINTEC, Stockholm, Sweden, 2Neuropediatrics, Karolinska University Hospital, Stockholm, Sweden, 3Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden, 4 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Purpose: To develop a technique with dried blood spots (DBS) to measure concentrations of antiepileptic drugs (AED) in children with epilepsy in a home-based setting with a guidance from a video. Method: The method with DBS has been validated for concentrations of carbamazepine (CBZ), lamotrigine (LTG) or valproate (VPA). We have now developed a method where the parents take the blood sample on filterpaper by themselves first time at the outpatient clinic and further on in their own homes. The parents are instructed orally by the nurse, when they perform the test they can watch a video with the instructions on a tablet or smart-phone. The video is available on you-tube so the parents can watch it when taking blood tests in their own home. Results: We evaluated the LC-MS/MS method by comparing routine capillary samples with DBS in 46 children (2–18 years) on treatment with CBZ (n = 20), LTG (n = 21), VPA (n = 42) in mono- or polytherapy. We developed the video and written instructions to parents. Conclusion: The methods had strong correlations. Differences between plasma concentrations and DBS concentrations for VPA and CBZ could be corrected with a factor using the ratio between plasma concentrations and DBS concentrations. For LTG the method comparison was not accepted according to EMA’s guidelines even with the use of a correction factor, although the concentrations were acceptable from a medical treatment decision point. The study with blood sampling by caregivers/ children has started and we estimate that a number samples will be available for analyses later this year. A homebased setting for analyses of AED in children may facilitate for the children and improve the treatment of epilepsy especially for children with motor and cognitive disabilities where a visit to the hospital may be very stressful and complicated.

Purpose: There is accumulating information in the basic science and clinical field literature regarding medical cannabis as an add-on anticonvulsant in intractable epilepsy. In addition, there is increasing medical and popular interest in the field. We summarize our preliminary results of CBD-enriched medical cannabis treatment in a cohort of patients.


170 Abstracts

Pharmacology/AEDs 11 Wednesday 14th September P559 FLAVONOIDS AS POTENTIAL REVERSING AGENTS OF THE PHARMACORESISTANCE TO ANTIEPILEPTIC DRUGS MEDIATED BY THE PGLYCOPROTEIN Ferreira AF1,2, Rodrigues M1,3, Fortuna A2,4, Falc~ao A2,4, Alves G1,2 1 Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Covilh~a, Portugal, 2Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal, 3 Research Unit for Inland Development (UDI-IPG), Polytechnic Institute of Guarda, Guarda, Portugal, 4Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal Purpose: To identify P-glycoprotein (P-gp) inhibitors among several flavonoids and investigate those with higher potential to enhance the intracellular accumulation of antiepileptic drugs (AEDs). This strategy of flavonoid/AED combined therapy may be useful to overcome the pharmacoresistance mediated by the P-glycoprotein and improve the access of AEDs to the biophase. Method: Madin-Darby canine kidney II (MDCK II) cells and those overexpressing the human multidrug resistance-1 (MDR1) gene that encodes P-gp (MDCK-MDR1) were obtained from The Netherlands Cancer Institute (NKI-AVL; Amsterdam, Netherlands). The cells were used to perform rhodamine 123 intracellular accumulation assays according to Barthomeuf et al. (1) and also AEDs accumulation assays. Flavonoids were studied at 50, 100 and 200 lM. AEDs were tested at therapeutic concentrations, namely, carbamazepine (50 lM), carbamazepine-10,11epoxide (16 lM), licarbazepine (140 lM), lamotrigine (55 lM), oxcarbazepine (20 lM) and phenytoin (75 lM). Results: Baicalein, (-)-epigallocatechin gallate, kaempferol, quercetin and silymarin at 50, 100 and 200 lM showed a marked inhibitory effect in P-gp activity, increasing the intracellular accumulation of rhodamine 123 in MDCK-MDR1 (p < 0.05). Moreover, it was suggested that these flavonoids could reverse the AEDs efflux induced by P-gp (p < 0.05); at 200 lM the aforementioned flavonoid compounds demonstrated to increase the intracellular concentrations of carbamazepine, carbamazepine-epoxide, licarbazepine, oxcarbazepine and phenytoin into MDCK-MDR1 cells (p < 0.05). Conclusion: These results suggest the interest of some flavonoids [baicalein, (-)-epigallocatechin gallate, kaempferol, quercetin and silymarin] as P-gp inhibitors, as they were able to reverse the P-gp-mediated drug efflux. Thus, these flavonoid compounds may be promising agents to increase the levels of AEDs and their active metabolites into the brain, circumventing at least partially the pharmacoresistance in epilepsy. Acknowledgements: FCT (SFHR/BD/84936/2012), involving the POPH - QREN (co-funded by FSE and MEC); and PEst-OE/SAU/ UI0709/2014 (FCT, COMPETE). 1-Barthomeuf et al. Cancer Chemother Pharmacol. 2005; 56(2): 173–81.

P560 UNRAVELING THE ROLE OF BLOOD-BRAIN PARTITIONING IN THE ANTICONVULSANT AND ANTIEPILEPTOGENIC ACTIONS OF LACOSAMIDE BY IN VITRO PHARMACOKINETIC STUDIES Gáll Z1, Vancea S2, Kolcs ar M1, Szil agyi T3 1 Pharmacology and Clinical Pharmacy, University of Medicine and Pharmacy of Tirgu Mures, Tirgu Mures, Romania, 2Physical Chemistry, University of Medicine and Pharmacy of Tirgu Mures, Tirgu Mures, Romania, 3Physiology, University of Medicine and Pharmacy of Tirgu Mures, Tirgu Mures, Romania Purpose: Lacosamide, one of the newer anticonvulsants, has a specific mode of action: whether it acts only by enhancing the slow inactivation of voltage-gated sodium channels or it has additional mechanisms is still unsure. Anyway, lacosamide showed additive or synergistic interactions unaccompanied by alteration of the plasma concentrations with other antiepileptic drugs (AED), so these interactions were attributed to pharmacodynamic actions. Lacosamide has high bioavailability, but its brainto-plasma partition coefficient (Kp) is only 0.553. As the whole-brain concentrations do not correlate well with pharmacodynamic action and the free fraction in plasma is not a suitable surrogate for unbound brain concentrations, the main objective of this study was to determine the brain disposition of lacosamide. Method: To calculate the fraction of unbound drug in the brain (fu,brain) equilibrium dialysis was implemented by using brain homogenate. However, homogenization may change the binding properties of proteins, so the brain slice method was also used. The drugs were quantified by LCMSn. Vu,brain (ml/g brain) was calculated as the buffer-to-slice ratio. To assess brain penetration and intracellular accumulation of drugs the following parameters were calculated: Kp,uu,cell = fu,brain9Vu,brain; Kp,uu,brain = Kp/(Vu,brain9fu,plasma). Results: The calculated fu,brain was 0.899 0.105, slightly lower than the free fraction in plasma (0.96) while the Vu,brain was 1.37 0.03 ml/g brain (n = 7). The calculated neuropharmacokinetic parameters showed that lacosamide may be subject to active transport across blood-brain barrier (BBB), having a Kp,uu,brain = 0.42. The Kp,uu,cell = 1.233 means that lacosamide is accumulated in the intracellular space which is in accordance with its physicochemical properties. Conclusion: Lacosamide had low brain tissue protein binding, similar to plasma proteins, but an active transport mechanism seems to be present at BBB, which may also be implicated in drug interactions. Acknowledgement: This work was supported by the Internal Grant for Scientific Research of University of Medicine and Pharmacy of T^ırgu Mures, Romania contract no. 17800/11/22.12.2015.

P561 A PHASE 1 OPEN-LABEL CROSSOVER STUDY TO EVALUATE BIOEQUIVALENCE OF ORAL SUSPENSION AND TABLET FORMULATIONS OF PERAMPANEL IN HEALTHY SUBJECTS Laurenza A1, Hall N1, Majid O2, Rege B1 1 Eisai Inc, Woodcliff Lake, NJ, United States, 2Eisai Ltd, Hatfield, United Kingdom Purpose: Perampanel is approved for adjunctive treatment of partialonset seizures, with or without secondarily generalised seizures, and for primary generalised tonic-clonic seizures in patients with epilepsy aged ≥12 years. Study 048 evaluated the bioequivalence of oral suspension and tablet formulations. Method: In this Phase 1 open-label crossover study, healthy adults (18– 55 years) received single doses of perampanel 12 mg as an oral


171 Abstracts suspension and a tablet, separated by a 6-week washout period. Subjects in fasted (n = 50) or fed (n = 50) arms were randomised (1:1) to treatment sequence. Blood samples were collected up to 504 h post-dose. The primary objective was to evaluate bioequivalence of both formulations under fasted conditions, using a mixed linear model. Bioequivalence was concluded if 90% confidence intervals (CI) for the geometric mean ratio of oral suspension/tablet for AUC(0-t), AUC(0-inf) and Cmax fell within 80% to 125%. Results: Under fasted conditions, geometric mean ratios indicated that pharmacokinetic parameters were similar for the oral suspension and tablets (AUC(0-t), 101.3%; AUC(0-inf), 100.5%; Cmax, 90.0%); bioequivalence criteria were met (AUC(0-t), 90% CI: 97.0, 105.8; AUC(0-inf), 90% CI: 96.2, 104.9; Cmax, 90% CI: 84.3, 96.1). Under fed conditions, the oral suspension was associated with a lower Cmax versus tablets (geometric mean ratio, 77.5%); bioequivalence criteria were met for AUC(0-t) (90% CI: 94.6, 105.5) and AUC(0-inf) (90% CI: 93.6, 105.6), but not Cmax (90% CI: 72.4, 82.9). Median Tmax was delayed with the oral suspension versus tablets under fasted (2.0 vs. 1.0 h) and fed conditions (4.0 vs. 2.0 h). Bioequivalence was supported by follow-up modelling of steady-state pharmacokinetics. Adverse events affected 74/100 subjects; the most common was dizziness (41.0%). Conclusion: Single doses of perampanel oral suspension and tablets were bioequivalent under fasted conditions. Under fed conditions, Cmax was lower with the oral suspension than the tablet (not considered clinically meaningful).

P562 ESLICARBAZEPINE ACETATE (ESL) AND CAROTID INTIMA-MEDIA THICKNESS (CIMT) IN MALES: THE ESL-LIPID STUDY Serrano-Castro PJ1, Fernandez-Perez J1, Lopez-Gonzalez J2, Toledo-Argany M3, Estevez-Maria JC4, Arjona-Padillo A1, Bertol-Alegre V5, Mauri-Llerda JA6, Tortosa-Conesa D7, RuizGimenez J8, Querol-Pascual R9, Garcia-Martinez A10, MoltoJorda JM11, Payan-Ortiz M1, Maestre-Moreno JF8, GalvanEspinosa J12, ESL-LIPID Study Group 1 Complejo Hospitalario Torrecardenas, Neurology, Almeria, Spain, 2Complejo Hospitalario Universitario Santiago, Neurology, Santiago de Compostela, Spain, 3Hospital Vall d’Hebron, Neurology, Barcelona, Spain, 4Hospital Universitario Reina Sofıa, Neurology, Cordoba, Spain, 5 Hospital Universitario Miguel Servet, Neurology, Zaragoza, Spain, 6Hospital Clinico Universitario Lozano Blesa, Neurology, Zaragoza, Spain, 7Hospital Universitario Virgen de la Arrixaca, Neurology, Murcia, Spain, 8Hospital Universitario Virgen de las Nieves, Neurology, Granada, Spain, 9 Hospital de Badajoz, Neurology, Badajoz, Spain, 10Hospital Central de Asturias, Neurology, Oviedo, Spain, 11Hospital Virgen de los Lirios, Neurology, Alcoy, Spain, 12Complejo Hospitalario Torrecardenas, Fundacion Investigacion Biosanitaria Andalucia Oriental (FIBAO), Almerıa, Spain Purpose: Eslicarbazepine acetate (ESL), unlike other carboxamides is not an strong enzyme-inducing drug over CYP-450 isoenzymes. So, theoretically it has not influence on the endogenous route of synthesis of cholesterol and homocysteine as biochemical markers of cardiovascular risk. The objective of this study was to determine the influence that ESL has on biochemical and ultrasonographic vascular risk factors compared with enzyme-inducing Antiepileptic Drugs (AEDs). Method: Multicentric, cross-sectional, observational study comparative between two groups of patients with focal epilepsy aged 18–75 years in

clinical practice: (1) Inducers Group: Patients treated with enzyme-inducing AEDs for a minimum period of 2 years. (2) ESL group: Patients treated with ESL without enzyme-inducing AEDs in the previous 2 years. Demographic, clinical, biochemical and ultrasonographic (Carotid Intima-Media Thickness (cIMT) by Mannheim protocol) variables were collected. Results: 155 patients (84 from Inducers Group and 71 from ESL Group) from 11 Epilepsy Units in Spain were included. The two groups were similar in demographic and clinical variables. There were no differences in previous vascular risk factors between groups except by the existence of dyslipidaemia with lipid-lowering therapy, which was more frequent in the Inducers group (38.1% vs. 15.5%; p = 0.02). Nor were significant differences in the biochemical parameters. The mean values of cIMT were higher in the Inducers group versus ESL (0.668 mm vs. 0.621; p = 0.05). Disaggregated by gender, we found no significant differences in women (0.634 mm vs. 0.616 mm; NS) but in males (0.700 mm vs. 0.624 mm; p = 0.02). Conclusion: cIMT values were higher in males of the Inducers group despite no differences in biochemical parameters of vascular risk. Previous studies have shown that inducing AEDs cause a situation of hypoandrogenism in men that correlates with increased values of cIMT. This mechanism could explain our results at least partially.

P563 THE IMPACT OF PHARMACOKINETIC INTERACTIONS WITH ESLICARBAZEPINE ACETATE VERSUS OXCARBAZEPINE AND CARBAMAZEPINE IN CLINICAL PRACTICE Svendsen T1,2, Johannessen Landmark C1,3,4, Brodtkorb E5, Reimers A6,7, Baftiu A3, Burns ML4, Johannessen SI1,4 1 National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway, 2Neurologiacal Department, Innlandet Trust Hospital, Lillehammer, Norway, 3Department of Life Sciences and Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway, 4Department of Pharmacology, Oslo University Hospital, Oslo, Norway, 5Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway, 6Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway, 7Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Background: Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) chemically related to oxcarbazepine (OXC) and carbamazepine (CBZ) and is increasingly used in clinical practice. Purpose: To study two-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ. Methods: Anonymous data regarding age, gender, use of AEDs, daily doses and serum concentration measurements of ESL, OXC, CBZ and lamotrigine (LTG) and other AEDs were retrieved from two therapeutic drug monitoring (TDM)-databases in Norway. Drugs were categorized according to their known potential for interactions. Concentration/dose (C/D)-ratios were calculated. Results: Data from 1,100 patients were available. The C/D-ratios of ESL and OXC were unchanged in combination with enzyme-inducing AEDs or valproate (VPA). The C/D-ratio of CBZ decreased by 40% and 22% in combination with other enzyme-inducing AEDs or VPA, respectively, Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

172 Abstracts pointing to an increased clearance. ESL demonstrated no significant enzyme-inducing effect on LTG metabolism while there was a 20% and 34% decrease in the C/D-ratio of LTG in combination with OXC and CBZ, respectively. Conclusion: Possible pharmacokinetic interactions have been studied for ESL as compared to OXC and CBZ. The pharmacokinetics of ESL is not affected by enzyme-inducing AEDs or VPA and does not affect the metabolism of LTG, in contrast to OXC and CBZ. The study demonstrates the value of using TDM-databases to explore the potential for pharmacokinetic interactions of new AEDs.

P564 TWO-DIMENSIONAL METAL NANOPARTICLE ARRAYS TOWARDS QUANTIFYING CARBAMAZEPINE IN HUMAN PLASMA Tommasini M1, Zanchi C1, Lucotti A1, Bombelli A1, Trusso S2, de Grazia U3, Ciusani E3, Franceschetti S3, Casazza M3, Ossi P1 1 Politecnico di Milano, Milano, Italy, 2CNR-Istituto per i Processi Fisico Chimici, Messina, Italy, 3Fondazione IRCCS, Istituto Neurologico C. Besta, Milano, Italy Purpose: To make available to the epileptologist a technique to determine in a short time (few minutes) the concentration of carbamazepine in human plasma. This allows to improve checking the compliance of the patients to the treatment. Method: We deposited thin gold films whose surface nanostructure is optimized via a strict control of the parameters of a laser-generated plasma that expands through an ambient gas and lands on a suitable (glass, (100) Si) support. The gold films constitute substrates to reveal the presence of analytes (e.g., carbamazepine) in a droplet (typical volume 50 ll) of human plasma absorbed at the substrate surface and then dried. Enhanced intensity of a probe laser radiation (785 nm) scattered by the substrate provides a fingerprint of carbamazepine (Surface Enhanced Raman Spectroscopy - SERS). The intensity of selected peaks in the collected SERS spectrum of carbamazepine is related to the drug concentration in the plasma. Results: Carbamazepine presence was assessed down to 4 9 104 M on standard solutions in methanol. We prepared solutions of carbamazepine in human plasma from a healthy volunteer at the concentrations of 500, 300, 100 mg/l. Notwithstanding background contributions arising from molecular species usually present in plasma, we recorded carbamazepine SERS features around 718, 1,220, 1,305, 1,565, 1,600, 1,620 cm1. Presently carbamazepine features around 1,565 and in the 1,600–1,620 cm1 region are distinguishable in spectra from solutions in serum from a patient treated at the concentration of 11.9 mg/l. Conclusion: The proposed technique is minimally invasive, fast (minutes), cheap (about 1 Euro per exam). It is suitable to be adopted at the point of care. A robust, portable Raman apparatus is available (through an industrial collaboration) and can be adopted in Developing Countries.

P565 KETOGENIC DIET IN REFRACTORY CHILDHOOD EPILEPSY: INTRODUCTION OF AN ALL LIQUID FORMULATION IN AN OUTPATIENT SETTING Weijenberg A1, van Rijn M2, de Koning TJ2, Brouwer OF1 1 Neurology, University Medical Centre Groningen, Groningen, Netherlands, 2Paediatrics, Section of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Centre Groningen, Groningen, Netherlands


Purpose: Ketogenic diet (KD) and its variants have been proven to be effective in childhood epilepsy. Because the diet has a considerable impact on daily life, early and rapid assessment of efficacy is highly desirable. The aim of our study was to evaluate whether this was possible by introducing an all liquid KD in an outpatient setting. Method: In a prospective, observational, open label pilot study children with refractory epilepsy started with classic KD as a ready to use liquid formulation (KetoCal 4:1 LQ©) taken orally or by tube. Efficacy was determined at 6 weeks and, in case of KD-continuation, adaptations to the diet were made from an all liquid diet to meals. To increase carbohydrate and protein content, MCT was added. Primary outcome parameter was time to response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, efficacy, and retention rate at 26 weeks. Results: Sixteen children (2–14 years) participated. The median time to response of the 4 responders (25%) was 14 days (range 7–28 days). Mean time to achieve stable ketosis was 6.9 days. Efficacy did not importantly change after 6 weeks. Retention rate at 26 weeks was 43%. 3/16 children had hypoglycaemia and/or high ketosis during the first week that could be easily controlled. Two children switched from oral to tube feeding during the first 6 weeks on all liquid diet. Conclusion: Introduction of KD in an all liquid formulation is feasible and contributes to fast and stable ketosis. Acceptance of KetoCal 4:1 LQ© was positive. Although the response rate in our study was low, median time to response was 2 weeks. The retention rate of 43% shows that, apart from seizure reduction, also other aspects are important like seizure type, increase of alertness, and physical well-being. Disclosure: Nutricia Research financially supported this study.

Pharmacology/AEDs 2 Monday 12th September P566 ANTIICTOGENIC AND ANTIEPILEPTOGENIC PROPERTIES OF PERAMPANEL IN MATURE AND IMMATURE RATS Dupuis N1, Enderlin J1, Dournaud P1, Auvin S2 1 INSERM U 1141, Paris, France, 2Ped Neurol Dpt, Robert Debre University Hospital & INSERM U 1141, Paris, France Purpose: Perampanel (PER) is a non-competitive AMPA antagonist approved as antiepileptic drug for both focal seizure and primary generalized seizure. We explored anti-ictogenic and anti-epileptogenic effects of PER in rats at different stages of development. Method: Using a rapid kindling model in P14, P21, P28 and P60 rats, we studied two doses of PER: 1 and 2 mg/kg injected intra-peritoneally 30 min before afterdischarge assessment. Results: PER 2 mg/kg significantly increased the afterdischarge threshold (ADT) at P28, P21 and P14 while PER at 1 mg/kg increased ADT in P21 rats only. PER 2m/kg also shortens the afterdischarge duration (ADD) at P28 and P14. At P28, P21 and P14, PER increased the number of stimulations required to develop a stage 4–5 seizure in a dose-dependent manner with almost complete elimination of stage 4–5 seizures in all immature animals (P28, P21 and P14). In contrast, at P60 PER had no effect on the number of stage 4–5 seizures. Conclusion: PER anti-ictogenic and anti-epileptogenic effects differing according to brain maturation. The antiepileptogenic effect of PER was stronger in younger animals.

173 Abstracts P567 ANALYSIS OF ANTIEPILEPTIC DRUG SELECTION BASED ON THE KNOWN MECHANISM OF ACTION IN DIFFICULT-TO-TREAT PARTIAL EPILEPSY Barcs G1, Szucs A1, Horvath A2, Kamondi A2 1 National Institute of Clinical Neurosciences, Neurology, Budapest, Hungary, 2National Institute of Clinical Neurosciences, Budapest, Hungary Purpose: A retrospective analysis of treatment-ways in the antiepileptic drug history of difficult-to-treat adult partial epilepsy patients. We pay special attention to antiepileptic mechanisms of action when drug-change had become necessary. Method: We selected 50 partial (mainly temporal lobe) epilepsy patients from our epilepsy outpatient clinic. They had all been treated by at least 3 antiepileptic drugs without permanent success. We excluded those patients with insufficient epileptology and care data, uncertain drug adherence, psychiatry or addictology issues, progressive brain lesion or epilepsy-surgery during the index period. We retrospectively followed the remaining 22 patients’ drug-response patterns during the last 2– 10 years; to the most frequently used drugs with different mechanism of action: carbamazepine, levetiracetam, topiramate and lacosamide, The above analysed antiepileptic drugs had been added to-, or instead of the ongoing ineffective antiepileptic drug-regime. Results: Six of those 14 patients resistant to carbamazepine (after at least three additional unsuccessful antiepileptic trials) responded to levetiracetam. Those eight patients who proved resistant also to levetiracetam, responded favourably to topiramate later. In the group of carbamazepineresistant patients lacosamide was ineffective as well. Those patients transitorily (for at least 6 months) responsive to carbamazepine, did not respond to levetiracetam, while they reacted well to lacosamide later. Conclusion: Our pilot study suggests that if an antiepileptic drug is not effective in a difficult-to-treat partial epilepsy patient; a drug with basically different mechanism of action may still be effective even after 2–5 additional unsuccessful antiepileptic drug-trials. A good response to lacosamide may be expected just in those patients who previously reacted favourably to the „traditional” sodium channel blocker carbamazepine. Our data emphasize that the consideration of antiepileptic mechanisms of action and drug history should be important aspects of drug-selection in difficult-to treat epilepsy patients. Our project was funded by KTIA_NAP_13-1-2013-0001/II./I.

P568 ALZHEIMER’S DISEASE, EPILEPSY AND ESLICARBAZEPINE Bermejo PE1, Juarez A2, Dorado R2 1 Neurology, Hospital Los Madronos, Madrid, Spain, 2Hospital Los Madronos, Madrid, Spain Purpose: Patients with Alzheimer’s disease (AD) have an increased risk of epilepsy, what seems to be independent of the stage of the disease. In fact, AD cognitive decline and some epileptic seizures seem to have a common origin in the brain b-amyloid toxicity. The experience of the use of antiepileptic drugs (AEDs) in this population group is very scarce. The aim of this study is to evaluate the efficacy and safety of eslicarbazepine (ESL) in patients with epilepsy and AD. Method: Medical charts of patients with epilepsy and AD who had received ESL were retrospectively evaluated. All of them presented AD and had developed some seizures after the diagnosis of AD. Patients with AD and epilepsy from other origins had been ruled out. The efficacy was determined by comparing the frequency of seizures in the month prior to the beginning of the treatment and a month after the maximum dose of ESL.

Results: Twenty five patients, aged between 56 and 81 years (68.1 9.4) were enrolled. The number of AEDs they were taking was 1.3 0.5 and the number of AEDs tested before was 1.8 1.1. The follow-up period was 6.2 2.1 months, and the dose used was 914 104 mg. All patients experienced at least 50 reduction of seizues and 11 of them were seizures free. Only one patient was discontinued due to adverse effects (diziness). Conclusion: According to the results of our study, ESL appears to be effective and well tolerated in patients with refractory epilepsy and AD and could be an important option for this population group.

P569 ANTIEPILEPTIC DRUG-INDUCED SKIN REACTIONS IN POLISH PATIENTS WITH EPILEPSY Bosak M1, Turaj W1, Song BH2 1 Neurology, Jagiellonian University, Cracow, Poland, 2School of Medicine in English, Jagiellonian University, Cracow, Poland Purpose: Cutaneous manifestations of adverse drug reactions are a common occurrence in patients treated with antiepileptic drugs (AEDs). Prevention and early recognition of cutaneous adverse reactions constitute an important aspect of management of epilepsy. The aim of this study was to assess the incidence of skin reactions to AEDs in Polish patients with epilepsy. Method: 753 consecutive patients with epilepsy were studied retrospectively and prospectively. A detailed survey of medical records concerning all treatment with AEDs was performed. Results: A total of 753 patients who were exposed to 18 different AEDs were included. Mean age of patients was 35.8 (14.2), and 417 (55.4%) were females. AED-related skin reactions occurred in 54 patients (7.2%). Mean age at onset of skin reactions was 28.9 (17.8). Patients with adverse skin reactions to AEDs did not differ from patients without skin reactions in terms of age, sex, type of epilepsy, and age at onset of epilepsy. 92.5% of the reactions occurred to patients on lamotrigine (LTG) (27 patients), carbamazepine (CBZ) (20 patients), or oxcarbazepine (OXC) (3 patients). 4 patients developed skin reaction to lacosamide (LCZ), phenytoin (PHT), levetiracetam (LEV), and valproate (VPA) (one patient to each drug). In 26 patients, skin reaction occurred to firstline treatment of new onset epilepsy (16 to CBZ, 10 to LTG); for the remaining 28 patients, to the add-on treatment. In 16 patients, the culprit drug was added to VPA. Six patients with AED-related skin reactions reported history of rash with other AED. The most common type of skin reaction was maculo-papular exathema, one patient developed Drug Reaction with Eosinophilia and Systemic Symptoms and three patients were diagnosed with Stevens-Johnson syndrome. Conclusion: Skin reactions are a common adverse effect of AED use and are reported more frequently with aromatic AEDs.

P570 AVAILABILITY OF ANTIEPILEPTIC DRUGS IN PRIMARY CARE HOSPITALS OF NORTHEASTERN, THAILAND Chainirun N1, Lertsinudom S2, Tiamkao S3, Nuntasaen T1, Sawanyawisuth K3 1 Pharmacy Department, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, 2Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khonkaen, Thailand, 3Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand


174 Abstracts Purpose: This study aimed to evaluate the availability of standard and new antiepileptic drugs in the primary care hospitals in Thailand.

(3.4%). Drop-outs were 14.9% cases (ineffectiveness in 5.7%, AEs in 12.6%).

Method: This study is a survey study by using a questionnaire on availability of antiepileptic drugs. The questionnaire was distributed to the primary care hospitals in the northeastern part of Thailand; the largest region in Thailand. It comprised of a list of available antiepileptic drugs in Thailand both generic and original; 6 intravenous drugs, 15 oral drugs, and 3 syrups. Data were collected via Google form, facsimile, letter, or phone call.

Conclusion: This clinical experience suggests that PER is a promising drug in super-refractory epilepsies. The results help to delineate both the main syndromic context in which PER can be effective and side effects profile in patients with complex polytherapies.

Results: Out of 237 primary care hospitals in the northeastern Thailand, 202 returned the questionnaire (85.23%). The four most common available antiepileptic drugs were phenobarbital (199 hospitals; 98.51%), generic carbamazepine (179 hospitals, 88.61%), generic phenytoin (162 hospitals, 80.20%), and generic valproate (128 hospitals, 63.37%) while original standard antiepileptic drugs were limited available; phenytoin (17.68%), valproate (12.12%), and carbamazepine (2.53%). There were 68 hospitals (33.66%) with at least one new antiepileptic drug. Intravenous standard antiepileptic drugs were available in 133 hospitals (65.84%). Conclusion: Primary care hospitals in the northeastern Thailand have limited original standard antiepileptic drugs, new antiepileptic drugs, and intravenous standard antiepileptic drugs. The most common available antiepileptic drug was generic standard antiepileptic drugs so physician should be aware antiepileptic drug availability in primary care hospitals.

P571 CLINICAL USE OF PER IN REAL-LIFE CLINICAL SETTING: A RETROSPECTIVE STUDY IN PATIENTS WITH “SUPER-REFRACTORY” EPILEPSIES Fattouch J1, Albini M1, Fanella M1, Morano A1, Casciato S1, Basili LM1, Mascia A2, D’Aniello A2, Quarato PP2, Manfredi M2, Giallonardo AT1, Di Gennaro G2, Di Bonaventura C1 1 Department of Neurology and Psychiatry, Sapienza University, Policlinico Umberto 1 Hospital, Rome, Italy, 2IRCCS Neuromed, Pozzilli, Italy Purpose: Perampanel (PER) is approved for adjunctive therapy of drugresistant partial epilepsy. Its efficacy/tolerability were evaluated in clinical trials,1 extension study2 and clinical settings3. PER was also approved for adjunctive treatment of primarily generalized tonic-clonic seizures in IGE4. The objective of this observational retrospective study is to evaluate the effectiveness and tolerability of PER as an adjunctive therapy in patients with super-refractory epilepsies in “real-life”. Method: We retrospectively analyzed data of 175 consecutively enrolled patients (M83/F92; mean age 37.3 years, range 14–70; mean duration of disease 24.6 years) with drug-resistant epilepsy treated with PER as add-on therapy. Clinical data were collected thought charts review. Effectiveness (≥50% reduction in seizures frequency) and safety were evaluated. Results: Epilepsy syndromes included: cryptogenic partial in 40% of patients, symptomatic partial in 31.3%, indeterminate whether focal or generalized in 5.1% and epileptic encephalopathy in 23.4%. Types of seizures included: simple and complex partial seizures (SPS, CPS) in 46% of patients, SPS and CPS with secondarily generalized tonic-clonic seizures in 54%. Mean number of concomitant AEDs was 2.4 (range 1–4); mean number of AED previously used was 9. PER mean target dose, gradually titrated (2 mg weekly), was 7 mg (range 2–12) once daily. Most used concomitant AEDs were CBZ (48%), LEV (30.7%), PB (30.7%). At the end of 6-months follow up a ≥50% reduction in seizure frequency was observed in 30% of patients (seizure-free in 2). 22.3% of cases experienced AEs, the most common being worsening of seizures (8.6% cases), dizziness (6.9%), psychiatric events


P573 CLINICAL EFFECTS AND MRI MORPHOMETRY CHANGES AFTER USING ANTIEPILEPTIC DRUGS IN TEMPORAL LOBE EPILEPSY IN UZBEKISTAN Umarov A, Prokhorova A, Rakhimbaeva G Tashkent Medical Academy, Department of Neurology, Tashkent, Uzbekistan Purpose: To investigate the relationship between brain MRI and clinical characteristics and patterns of antiepileptic drug (AED) response in patients with mesial temporal lobe epilepsy (MTLE). Method: A total of 165 MTLE patients were divided into seizure-free with AED (AED responders, n = 50), pharmacoresistant (n = 87), and remitting-relapsing seizure control group (n = 28). All groups were evaluated regarding age, frequency of seizures, and age at epilepsy onset, duration of epilepsy, febrile seizures, presence and side of hippocampal atrophy (HA), and initial precipitating injuries. For gray matter (GM) MRI voxel-based morphometry (VBM) we selected only patients with unilateral HA on visual MRI analysis (n = 100). Comparisons were made between all groups and 75 healthy controls. Results: Age at epilepsy onset was lower (p = 0.005) and initial frequency of seizures was higher in the pharmacoresistant compared with the other 2 groups (p = 0.018). All groups showed GM atrophy compared to controls in ipsilateral hippocampus, bilateral parahippocampal gyri, frontal, occipital, parietal, and cerebellar areas. In the AED responders group, such findings were more restricted to areas ipsilateral to the epileptic focus and more widespread in the pharmacoresistant and remitting-relapsing groups. VBM pairwise comparisons showed areas with GM volume reduction in the pharmacoresistant and remitting-relapsing groups compared with AED responders in bilateral periorbital frontal (p < 0.01), cingulum (p < 0.05), and temporal lobe contralateral to the epileptic focus (p < 0.05). Conclusion: Pharmacoresistant and remitting-relapsing groups presented a similar pattern of GM atrophy, which was more widespread compared with AED responders. Conversely, age at epilepsy onset was lower and initial seizure frequency was higher in pharmacoresistant patients.

Pharmacology/AEDs 3 Monday 12th September P575 EFFECTIVENESS AND TOLERABILITY OF PERAMPANEL IN CHILDREN AND ADOLESCENTS WITH REFRACTORY EPILEPSIES - AN ITALIAN MULTICENTER STUDY De Liso P1,2, Vigevano F2, De Palma L2, Specchio N2, Bonanni P3, Osanni E3, Coppola G4, Parisi P5, Grosso S6, Verrotti A7, Spalice A1, Nicita F1, Zamponi N8, Siliquini S8, Giordano L9, Martelli P9, Guerrini R10, Rosati A10, Ilvento L10, Belcastro V11, Striano P12, Capovilla G13, Beccaria F13, Bruni O14, Luchetti A14, Gobbi G15, Russo A15, Pruna D16, Cusmai R2 1 Department of Pediatrics, Child Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy, 2Neurology Unit,

175 Abstracts Department of Neurosciences, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy, 3Epilepsy and Clinical Neurophysiology Unit, Scientific Institute Eugenio Medea, IRCCS, Conegliano, Treviso, Italy, 4Department of Child and Adolescent Neuropsychiatry, University of Salerno, Salerno, Italy, 5NESMOS Department, Faculty of Medicine and Psychology, Sant’Andrea Hospital, Sapienza University, Rome, Italy, 6Paediatric Neurology-Immunology and Endocrinology Unit, University of Siena, Siena, Italy, 7Department of Pediatrics, University of L’Aquila, L’Aquila, Italy, 8Child Neuropsychiatry Unit, Polytechnic University of the Marche, Ancona, Italy, 9Paediatric Neuropsychiatric Division, Spedali Civili di Brescia, Brescia, Italy, 10Paediatric Neurology Unit, Children’s Hospital A. Meyer, University of Firenze, Florence, Italy, 11Neurology Unit, Department of Neuroscience, Sant’Anna Hospital, Como, Italy, 12Paediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, ‘G. Gaslini’ Institute, University of Genoa, Genova, Italy, 13Department of Child Neuropsychiatry, Epilepsy Centre, C. Poma Hospital, Mantova, Italy, 14Child Neuropsychiatry Unit, S. Andrea Hospital, Rome, Italy, 15Child Neurology Unit, IRCCS Institute of Neurological Sciences, Bologna, Italy, 16 Epilepsy Unit, Child Neuropsychiatry Department, University Hospital of Cagliari, Cagliari, Italy Purpose: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. Patients and methods: This Italian multicenter retrospective observational study was performed in 16 pediatric epilepsy centers. Children and adolescents ≤18 years of age were included. Pilot data from patients with ≥5-months follow-up were analyzed for this report. The following data were collected: age, gender, cognitive impairment, age at onset of epilepsy, seizure and epilepsy types, aetiology, monthly seizure frequency, neuroimages and EEG data, number of previous anti-epileptic drugs (AEDs), adverse events and concomitant AEDs. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. Results: 62 patients were included in this study, 53% males with a mean age of 14 years (6–18 years), 76% with intellectual disability. Mean age at epilepsy onset was 3.5 and 10.8 years (range 1–16) of epilepsy duration with at least three seizure per-month (up to several per-day). 63% had symptomatic focal epilepsy. Mean number of AEDs used in the past was 7.08 and mean number of concomitant AEDs was 2.48. Mean PER dose was 7.08 (2–12 mg). After an average of 7months of follow-up (5–13 months), 48 patients (77%) continued on PER. The response rate was 50%, 16% with ≥75% seizure frequency reduction and 5% becoming completely seizure free. Seizure aggravation was observed in 10%. Adverse events were experienced in 25/62 (40%) and resulted in withdrawal in 14 (17.4%). The most common adverse events were behavior disturbance (irritability and aggression), dizziness and sedation. Conclusion: PER was found to be a safe and effective treatment when used as adjunctive therapy in pediatric patients with uncontrolled epilepsy.

P576 EFFECTIVENESS OF PERAMPANEL AS ADJUNCTIVE THERAPY IN PATIENTS WITH REFRACTORY FOCAL SEIZURES WITH GCI ASSESSMENT De Maria G1, Rinaldi F2, Milan A3 1 Spedali Civili di Brescia, Epilepsy Unit, Clinical Neurophysiology, Spedali Civili di Brescia, Brescia, Italy, 2 Universit a degli Studi di Brescia, Clinical Neurology, Spedali Civili di Brescia, Brescia, Italy, 3Medical Department Eisai s.r.l., San Donato Milanese, Italy Purpose: To assess efficacy and tolerability of perampanel (PER), a novel, highly selective, non-competitive AMPA receptor antagonist, as add-on treatment in patients (aged ≥12 y) with refractory focal seizures, in a real-life setting. Method: A retrospective study conducted in patients with refractory focal seizures consecutively treated with PER in our Epilepsy Unit. 46 patients were started on PER from May 2015 to October 2015. PER was titrated based on SmPC; patients were followed-up for at least 26 weeks. Efficacy endpoints included: change of seizure frequency; responder rate (seizure frequency reduction ≥50%); Clinical Global Impression scale (CGI); reduction of concomitant antiepileptic drugs (AEDs); EEG improvement. We also evaluated adverse reactions and withdrawal due to adverse reactions. Results: Patients (all Caucasians; 65% females; mean age 38.9 years) were receiving 1–5 concomitant AEDs and had received in their history a mean of 7.7 AEDs (2–18). Mean duration of disease was 27.7 years (6–54 years), with mean age at onset 10.87 years (1– 50 years). 29 patients had structural-metabolic focal epilepsies, 17 focal epilepsies of unknown origin. Baseline seizure frequency was 11.2/month. After 6 months of treatment, 76.5% of patients reported an improvement in seizure frequency, while 23.5% reported no differences or worsening. The responder rate was 58.8%. 11 patients (23.9%) had the dose of at least 1 concomitant AED reduced, while the EEG improved in 3. Eight patients reported side effects (somnolence; vertigo/ataxia) during the first 3 weeks, persisting after 6 months in 7 patients. One patient withdrew perampanel due to adverse effect (ataxia), 6 due to lack of efficacy. According to CGI scale, the 6-months response was good to excellent in 59.3%, and low to moderate in 40.3%. Conclusion: These data showed that once-daily perampanel is effective and well-tolerated as add-on therapy, especially considering the severe refractoriness of patients and numerous AEDs previously used.

P577 EFFECT OF VALPROIC ACID ON THE PLACENTAL BARRIER IN THE PREGNANT MOUSE: OPTICAL IMAGING AND TRANSPORTER EXPRESSION STUDIES Meir M, Bishara A, Mann A, Udi S, Portnoy E, Shmuel M, Eyal S School of Pharmacy, Institute for Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel Purpose: Valproic acid (VPA) has been recently shown to interfere with placental transport mechanisms for hormones, nutrients and medications in vitro. The aim of the current study was to evaluate the effects of VPA on the function of the placental barrier in vivo, in pregnant mice. Method: Indocyanine green (ICG) was used as a marker of the placental barrier permeability. Imaging studies with ICG (0.167 mg, intravenously) were conducted in mice on gestational days 12.5 (mid-gestation) or 17.5 (late-gestation), following 4 days of intraperitoneal treatment with 200 mg/kg VPA or the vehicle. Placental and hepatic transporter expression was evaluated by RT-PCR. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

176 Abstracts Results: In vivo imaging indicated VPA-induced 1.4-fold increase (p < 0.05) in ICG’s accumulation in maternal liver in mid-pregnancy and one fifth decrease (p < 0.05) in hepatic accumulation in late-pregnancy (p < 0.05). Ex vivo analysis demonstrated a 20% increase in fetal ICG emission (p < 0.05) in mid-pregnancy in the absence of change in systemic ICG emission. In the same animals, the placental expression of the L-type amino acid transporter, the organic anion transporting polypeptide-(Oatp)4a1 (thyroid hormone transporters), and the reduced folate carrier were lower than in controls (p < 0.05). In late-pregnancy, placental transporter expression was not significantly affected by VPA, but hepatic Oatp4a1 levels were 40% lesser (p > 0.05) in VPA-treated mice. Conclusion: The observed changes in placental transport function in vivo support further research into the potential role of the placenta in the adverse pregnancy outcomes of VPA. Beyond the placenta, VPA affects the function of hepatic transport mechanisms that control the systemic concentrations of endogenous compounds and medications. Near infrared imaging provides a non-invasive, non-radioactive tool for future studies on the effects of epilepsy and antiepileptic drugs on transport functions.

P578 EFFECTIVENESS OF ESLICARBAZEPINE ACETATE AS ADJUNCTIVE THERAPY FOR PARTIAL EPILEPSY IN CLINICAL PRACTICE: DESIGN OF A EUROPEAN POOLED ANALYSIS OF REAL-WORLD DATA McMurray R1, Karisson C2, Sousa R3, Villanueva V4 1 Eisai Europe Ltd, Hatfield, United Kingdom, 2Eisa AB, Stockholm, Sweden, 3Bial - Portela & Cª S.A., Coronado, Portugal, 4Hospital Universitario y Politecnico La Fe, Valencia, Spain Purpose: Eslicarbazepine acetate (ESL) is approved in Europe as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalisation, and, in the USA, for the treatment of partial-onset seizures as monotherapy or adjunctive therapy. The efficacy and safety/tolerability of ESL were established in a comprehensive programme of clinical trials. In everyday clinical practice, patients are more diverse in terms of clinical characteristics (e.g. age, comorbidities, comedications) than those recruited for clinical trials, and treatment is tailored on a patient-by-patient basis. Therefore, ‘real-world’ data are needed to complement evidence from clinical trials. We present the methodology for a European pooled analysis designed to comprehensively assess ESL’s effectiveness in routine clinical practice. Method: The study will comprise a pooled analysis of ‘real-world’ databases from across Europe, which have collected clinical practice data on adult patients treated with ESL for partial-onset seizures primarily in the adjunctive setting. Patient-level data will be analysed. Efficacy will be assessed as responder rate (≥50% seizure frequency reduction) and seizure freedom rate. Tolerability will be assessed by evaluating adverse events. In addition, information on effects of treatment on quality of life and global improvement, and ESL dosing and treatment duration, will be examined. Subgroup analyses, such as assessment of elderly patients, comorbidities (e.g. depression, cardiovascular disease) and the preferred combinations of antiepileptic drugs employed with ESL, are also proposed. Results: The full dataset will comprise over 1,500 patients from across Europe, including Spain, France, Germany, UK, Ireland, Czech Republic and the Nordic countries. Conclusion: This large pooled analysis of patient-level data will provide valuable information on the effectiveness of ESL in routine clinical practice, thereby complementing evidence from clinical trials. It will also provide pragmatic information on the dosing patterns, combinations and


response in particular populations when ESL is used under real-world conditions. Supported by Eisai

P579 EFFECT OF LACOSAMIDE ON DEPRESSION AND ANXIETY SYMPTOMS IN PATIENTS WITH FOCAL REFRACTORY EPILEPSY: A PROSPECTIVE MULTICENTER STUDY Rocamora R1, Mauri JA2, Molins A3, Toledo M4, Sansa G5, Bertol V6, Becerra JL7, Carre~ no M8, Principe A9, Ley M9 1 Hospital del Mar, Neurology, Barcelona, Spain, 2Hospital Lozano Blesa, Zaragoza, Spain, 3Hospital Trueta, Girona, Spain, 4Hospital Vall de Hebron, Barcelona, Spain, 5Hospital de Parc Tauli, Sabadell, Spain, 6Hospital Miguel de Servet, Zaragoza, Spain, 7Hospital Germans Trias i Pujol, Barcelona, Spain, 8Hospital Clinic Barcelona, Barcelona, Spain, 9Hospital del Mar, Barcelona, Spain Purpose: Depression is the main psychiatric comorbidity in epilepsy with an estimated prevalence between 11% and 60%. The aim of this study is determine the modulating effects of lacosamide (LCS) on symptoms of depression, anxiety and quality of life in patients with focal onset seizures (FOS). The secondary objective was to determine if the potential variations in the variables were related to seizure control or instead with an intrinsic effect of lacosamide. Method: We performed a prospective multicenter study in seven tertiary epilepsy centers in adults with FOS in which LCS was initiated as add-on therapy. Patients were evaluated through BDI-II, STAI-A/B, HADS and QOLIE-10. Initiation of psychotropic medication was not allowed during the observation period. Evaluations were scheduled before use of LCS, 3 and 6 months after. Results: 49 patients were included (51% female) with average age of 39.5 years (range 18–65). In 65.3% LCS was used as first add-on. Based on BDI-II, 38.8% of patients had depressive symptoms and 46.9% according to HADS. 63.3% of patients presented a pathological state of anxiety (STAI-State). QOLIE-10 showed that 57.1% of patients had a relevant reduction in their quality of life. After LCS, the score on the BDI-II depression scale decreased significantly (p < 0.001). In the STAI and HADS-anxiety scales, patients who started from a pathological anxiety baseline significantly improved. The QOLIE-10 decreased significantly over the observation period (p < 0.001). At 6 months, 28.3% of patients were seizure-free (67.4% were responders). The improvements on depression and anxiety scores were not statistically related to seizure control. Conclusion: LCS seems to have a positive effect on depressive and anxiety symptoms. Although the efficacy of LCS in seizure control was demonstrated, the modulating effect on mood and anxiety appears to be an independent factor.

177 Abstracts P580 EFFECT OF PERAMPANEL OVER THE QUALITY OF SLEEP AND DAYTIME SOMNOLENCE IN FOCAL EPILEPSY Gonzalez-Cuevas M1, Romero O2, Toledo M1, Quintana M1, Cambrodı R2, Santamarina E1, Jurado MJ2, Ferrer A2, SalasPuig J3 1 Vall d’Hebron University Hospital, Universitat Autonoma de Barcelona, Neurology, Barcelona, Spain, 2Sleep Unit, Neurophysiology Department, Vall d’Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain, 3Vall d’Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain Purpose: The purpose of this study was to evaluate the effect of Perampanel (PER) as adjunctive therapy on sleep-wake cycle and daytime somnolence in adult patients with focal epilepsy. Method: This is a prospective non-interventional study where the sleep habits of patients planned to be initiated on PER were assessed before starting the treatment and 3 months later. Maintenance of Wakefulness Test (MWT) with a prior 1-week Actigraphy recording was performed at baseline and in the follow-up. Subjective assessments of nocturnal sleep and daytime somnolence were also performed at baseline and after 3 months of treatment with PER by means of Pittsburgh Sleep Quality Index (PSQI) and Epworrh Sleepiness Scale (ESS). Results: Ten out of 13 patients, who were evaluated at baseline, completed the study. (Mean age: 40.10 (23–64) 14.6; 50% male). PER was used as ≥ 2nd AED. With PER 4 mg per day, 80% of patients were responders (>50% of seizure reduction). Two patients reported mild dizziness as adverse event. At baseline mean values of Actigraphy (sleep efficiency: 91.4 3.4%, total sleep time: 431 64 min), PSQI (4.1 3.7), ESS (4.7 3.6) and MWT (24.06 10.7 min) were within normal limits. At 3 month follow up; Perampanel did not induce any significant change in Actigraphy recording variables and in PSQI scores. Also, mean MWT and ESS score were no significantly modified after treatment. Conclusion: Low doses of Perampanel can improve the control of seizures without a deleterious effect over the sleep characteristics or daytime somnolence.

P581 EFFECTIVENESS AND TOLERABILITY OF LACOSAMIDE IN THAI CHILDREN & ADOLESCENTS WITH INTRACTABLE EPILEPSY Thampratankul L, Khongkhatithum C, Boonyobol R, Visudtibhan A Ramathibodi Hospital, Mahidol University, Pediatrics, Bangkok, Thailand Purpose: Lacosamide (LCM) has shown favorable efficacy in children with refractory epilepsy in Western countries. It has been recently available in Thailand since 2015. However, its efficacy and tolerability is yet to be determined in Thai children with intractable epilepsy. Method: A retrospective study was conducted at Department of Pediatrics, Ramathibodi Hospital, Bangkok, Thailand. Patients aged from 1 month to 18 years old received LCM and had been followed at least 6 months were included. Clinical data such as age, underlying illness, seizure-type, etiology of epilepsy, previous and concomitant treatment and adverse effects were collected. LCM efficacy was evaluated on the basis of seizure-reduction rate determined from seizure diary and interview. Respond-to-treatment was classified as seizure-reduction of 50% or more.

Results: Twenty-seven patients (66.7% male) with mean age of 12.4 4.8 years (range 3.5–18) were included. Sixteen (59.3%) and eight (29.6%) patients had focal-onset seizures and generalized seizures, respectively. The rest three had epileptic spasms, myoclonic seizure and multiple seizure types, each. Six patients were diagnosed with LGS. Prior to LCM commencement; all had taken more than three anticonvulsants, 13 patients (48.1%) had epilepsy surgery and 3 patients (11.1%) had VNS placement. There were 1–4 concomitant AEDs when LCM was added to the regimen. At final evaluation, 13 patients continued taking LCM (mean 7.1 3.6, range 1.8–16.1 mg/ kg/day, treatment duration 8.7 2.5 months). There were 3 (11.1%) patients achieved seizure-free and 10 (37%) patients categorized as responder. LCM was discontinued because of fixed-drug eruption observed at 3 weeks post-treatment (1 patient) and the lack of efficacy (13 patients). Adverse effects were drowsiness (22%) improved with dose-reduction, >10% weight gain (11%), irritability (7.4%), fatigue (3.7%) and vomiting (3.7%). Conclusion: LCM is an option for adjunctive treatment with a favorable efficacy for Thai children and adolescent with intractable epilepsy.

Pharmacology/AEDs 4 Tuesday 13th September P582 EFFECTIVENESS OF PERAMPANEL IN REFRACTORY EPILEPSIES: DATA FROM AN APULIAN (ITALY) OPEN LABEL STUDY Boero G1, d’Orsi G2, Intern o S1, Pontrelli G1, Di Claudio T2, 2 3 Mancini D , Francavilla T , Pietrafusa N3, Sambati R4, De Paolis F4, Avolio C2, La Neve A3 1 Complex Structure of Neurology - ‘SS. Annunziata’ Hospital, Taranto, Italy, 2Clinic of Nervous System Diseases, Epilepsy Centre, University of Foggia, Foggia, Italy, 3Department of Neurological and Psychiatric Sciences, Centre for Epilepsy, University of Bari, Bari, Italy, 4ASL Lecce, Lecce, Italy Purpose: To assess effectiveness of perampanel, a new antiepileptic drug (AED) marked in Italy in May 2015, as add-on treatment in patients with refractory epilepsies. Method: Prospective, open label, multicentre study involving epilepsy centres belonging to Apulia region, in Italy; data are collected in a common database including demographic and clinical features of each patient. The study included three periods: baseline (3 months, at stable therapy), drug titration (2 weeks, to 4 mg/day), observation (open), during which perampanel could be increased until the maximum tolerated dose. Inclusion criteria: age >16 years, no response to at least 2 adequate AEDs. Exclusion criteria: poor compliance, history of pseudo-seizures, pregnancy. Efficacy has been evaluated by comparing the mean monthly seizures frequency of the last quarter observation period with baseline frequency, using T-test for dependent sample. Tolerability was evaluated reporting adverse effects. Results: 50 patients were enrolled (23 F, mean age 39 years); 41 were affected by Focal Epilepsy (19 symptomatic, 22 cryptogenic), 5 by Epileptic Encephalopathies, 2 by Idiopathic Generalized Epilepsy, 2 by Lafora Disease. Mean number of previous AEDs was 8 4 (2–18); mean duration of the epilepsy was 29 years. Perampanel was administrated at a daily mean dose of 5.4 mg (4–10), added to 1 (8 patients), 2 (32), 3 (8) or 4 (2) other AEDs; 11 patients were under vagus nerve stimulation. Mean duration of observation was 6.1 months. After perampanel we observed a statistically significant reduction of the mean monthly seizures rate (26.3 28.2 vs. 22.4 32.1, p = 0.03). 16 (32%) patients complained adverse effects (mainly psychiatric), which in 6 cases led to drug discontinuation; 3 patient withdrew for seizure worsening.


178 Abstracts Conclusion: Our data indicate good effectiveness of perampanel as addon therapy, especially considering the very severe refractoriness of patients and the drug administration in polytherapy.

P583 EFFECTIVENESS OF PERAMPANEL AS ADJUNCTIVE THERAPY IN PATIENTS WITH REFRACTORY SEIZURES Bonanni P1, Negrin S1, Danieli A1, Grillo E2, Milan A2, Sarcona V1, Randazzo G1, Osanni E1 1 Epilepsy Unit, IRCCS Eugenio Medea, Conegliano, Italy, 2 Medical Department, Eisai s.r.l., San Donato Milanese, Italy Purpose: To assess in a real-life setting the effectiveness of perampanel (PER), the first antiepileptic drug which acts as a non-competitive AMPA receptor antagonist, when used as add-on treatment in patients (aged ≥12 years) with refractory seizures. Method: A retrospective, open label, single-center study conducted in patients with refractory seizures treated with PER. Patients were receiving 1–4 concomitant antiepileptic drugs (AEDs). PER doses were increased until optimal seizures control was achieved not exceeding 12 mg/die. We followed up patients for at least 24 weeks. Efficacy endpoints included responder rate (percentage of patients who had a 50% or greater reduction in seizure frequency) and percentage of patients who had some reduction in seizure frequency. To assess tolerability, we evaluated the incidence and severity of adverse reactions (ADRs) and the percentage of patients withdrawn due to ADRs. Results: We included 39 patients, 19 (48.7%) were female. Mean age was 30.8 years (SD = 14.3). Nine patients were 2 concomitant AEDs and 8 had vagal nerve stimulation. A reduction in seizure frequency was observed in 56% (22/ 39). 17/39 patients (43%) were responders and 3 patients became seizure free. The most frequent ADRs were somnolence, irritability, and fatigue. ADRs were more frequent in regimens with >2 (11/18) AEDs. Most ADRs were mild/moderate. Four patients (10%) dropped out of treatment, 3 (7.5%) due to AEs, 1 (2.5%) due to lack of efficacy. Conclusion: Our results are consistent with the efficacy and tolerability profile of perampanel emerged from pivotal RCTs. The percentage of seizure free patients (8%) was remarkable considering that our patients had pharmacoresistant epilepsy.

P585 EFFECTIVENESS OF RUFINAMIDE IN ADULTS WITH LENNOX-GASTAUT SYNDROME - A MONOCENTRIC RETROSPECTIVE AUDIT Friedo A-L, Straub H-B Epilepsieklinik Tabor, Bernau, Germany Purpose: Rufinamide (RUF) is indicated as adjunctive therapy of seizures in patients with Lennox-Gastaut-Syndrome (LGS) aged 4 years and older. Here, we report our experiences in a cohort of adult patients with LGS based on retrospective chart review. Methods: Outcomes of adult patients treated with RUF as add-on were retrospectively analyzed for efficacy, tolerability, and long-term retention. Efficacy measures comprised responder rates, seizure freedom, and overall appraisal of the effect on drop attacks. Tolerability was assessed by documentation of TEAEs during the observation period. Results: Ninety adult patients with LGS (median age 29 years, 67.8% male) with a median follow-up period of 6 years were included. All Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

patients received RUF as add-on to an existing regimen of predominantly 2 (52.2%) or 3 (35.6%) AEDs. The median number of previously failed AEDs was 7.5. RUF was titrated slowly to a median dose of 2,000 mg/ day. In the group of patients (54/90, 60%) who did not discontinue RUF therapy within a period of up to 2 years, responder rates were 27.8%, 33.4%, and 42.6% after approximately 6, 12, and 24 months versus baseline, respectively. For one patient, a seizure free interval of at least 3 months was documented at the last visit. For 27.1% of patients with drop attacks, RUF was described as having a positive effect. At least one TEAE was documented for 23 patients (25.6%), most commonly nausea and somnolence (10% each). After 2 years, 57.8% of patients were still on RUF, 40% after 4 years, and 20% after 6 years. Conclusion: RUF was effective as add-on therapy in a cohort of adult patients with LGS, well retained in the longer term, and generally well tolerated in a complex polytherapy. Results are in line with previously reported experiences from our institution and other studies.

P587 EFFECTS OF ADJUNCTIVE PERAMPANEL ON SLEEP QUALITY, DAYTIME SOMNOLENCE AND COGNITION IN REFRACTORY FOCAL EPILEPSY: A QUESTIONNAIRE-BASED STUDY Romigi A1,2, Izzi F1, Liguori C1, Placidi F1, Bove L2, Mercuri N1 1 University of Rome Tor Vergata, Neurophysiopathology Department, Rome, Italy, 2Azienda Ospedaliera San Giovanni Addolorata, Neurology Unit, Rome, Italy Purpose: Sleep disturbances represent a common comorbidity in patients with epilepsy, in addition AEDs may induce negative effects on sleep and sleepiness. The objective of this observational study is to assess effect of perampanel on sleep quality, daytime somnolence and cognition in a small group of adult patients with refractory partial onset epilepsy. Method: We evaluated a small group of adult patients with uncontrolled focal epilepsy consecutively treated with adjunctive PER at our centre with a follow-up of 1 and 6 months. At 1 and 6 months of follow-up ≥50% responder rate, retention rate and seizure freedom were evaluated. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index, Montral Cognitive Assessment (MoCA), and Patient Health Questionnaire 9 and Beck Depression Inventory-II were also administered in each condition. Results: We included 16 adult patients. One patient dropped-out for dizziness, three patients for lack of efficacy. Twelve patients (8 males, 4 females, mean age 43.7, SD 14.9, range: 27–62). At 6 months of followup, ≥50% responder rate was 7 out 12 (58%) with one patient seizure free with a mean dose of PER of 8 mg/day (SD 1.51 mg). No statistical differences were found between basal condition and follow-up regarding ESS score (T0 6.5 4.88 vs. T1 7.3 3.74, T2 8 3.7), PSQI (T0 7.2 4 vs. T1 5.3 2.74, T2 5 2.5); MoCA (T0 24.5 3.9 vs. T1 24.6 3.1, T2 24.8 3.4), PHQ9 (T0 10 4.5 vs. T1 8.2 2.6, T2 7.6 2.5). Conclusion: PER does not affect nocturnal sleep, sleepiness and cognition in our small sample of patients with focal epilepsy. Since some AEDs induce sleep impairment, which is known to trigger EEG abnormalities and seizures and to worsen quality of life, our findings suggest a positive profile of PER.

179 Abstracts P588 EFFICACY OF LACOSAMIDE MONOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED EPILEPSY STRATIFIED BY BASELINE DISEASE SEVERITY: SUBANALYSIS OF DATA FROM A PROSPECTIVE NONINFERIORITY TRIAL VERSUS CONTROLLEDRELEASE CARBAMAZEPINE Toledo M1, Baulac M2, Rosenow F3, Terada K4, Li T5, De Backer M6, Brock M5, Werhahn KJ7 1 Hospital Vall d’Hebron, Barcelona, Spain, 2Clinique Neurologique, Hôpital de la Pitie-Salpêtriere, Paris, France, 3 Epilepsy Center Frankfurt Rhine-Main, Neurocenter, GoetheUniversity, Frankfurt am Main, Germany, 4Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan, 5UCB Pharma, Raleigh, NC, United States, 6UCB Pharma, Brussels, Belgium, 7UCB Pharma, Monheim am Rhein, Germany

P589 EFFICACY AND TOLERABILITY OF MONOTHERAPY WITH LACOSAMIDE VERSUS CONTROLLEDRELEASE CARBAMAZEPINE IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED EPILEPSY: A SUBGROUP ANALYSIS OF A PROSPECTIVE RANDOMIZED DOUBLE-BLIND TRIAL Rosenow F1, Toledo M2, Baulac M3, Terada K4, Li T5, Brock M5, De Backer M6, Werhahn KJ7 1 Epilepsy Center Frankfurt Rhine-Main, Neurocenter, GoetheUniversity, Frankfurt am Main, Germany, 2Hospital Vall d’Hebron, Barcelona, Spain, 3Clinique Neurologique, H^ opital de la Pitie-Salpêtriere, Paris, France, 4Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan, 5UCB Pharma, Raleigh, NC, United States, 6UCB Pharma, Brussels, Belgium, 7UCB Pharma, Monheim am Rhein, Germany

Purpose: To evaluate efficacy and safety of lacosamide (LCM) versus carbamazepine controlled-release (CBZ-CR) based on disease severity (≤2 or >2 seizures during 3-months pre-enrolment).

Purpose: To evaluate efficacy and safety of lacosamide (LCM) and carbamazepine controlled-release (CBZ-CR) monotherapy in elderly patients (≥65 years) with newly-diagnosed epilepsy experiencing focal (partial-onset) or generalized tonic-clonic seizures.

Methods: Double-blind, non-inferiority trial (NCT01243177) enrolled patients (≥16 years) with newly-diagnosed epilepsy experiencing focal (partial-onset) or generalized tonic-clonic seizures. Patients were randomized 1:1 to twice-daily LCM/CBZ-CR, with strata defined by seizure-count (≤2 or >2) during 3-months prior to enrolment. Flexible uptitration to target dose (LCM: 200/400/600 mg/day; CBZ-CR: 400/800/ 1200 mg/day) was based on seizure control. Efficacy outcomes included seizure-freedom during 6 and 12-months of treatment, following stabilization at last-evaluated-dose. Data are reported for the full analysis set (FAS) and per-protocol set (PPS). Results: 886 patients received trial medication (FAS); 448 were in ≤2 prior seizures stratum (LCM: 224; CBZ-CR: 224 [PPS: 204; 202]) and 438 were in >2 prior seizures stratum (220; 218 [PPS: 204; 195]). Among patients with ≤2 prior seizures, Kaplan-Meier estimates for 6-month seizure-freedom were similar for LCM versus CBZ-CR (FAS: 94.3%; 94.1% [PPS: 95.4%; 95.3%]); 78.1% of LCM-treated and 74.1% of CBZCR-treated patients completed 6-months without seizure. Kaplan-Meier estimates for 12-month seizure-freedom (FAS) were 79.8% with LCM versus 86.3% with CBZ-CR. Among patients with >2 prior seizures, Kaplan-Meier estimates for 6-month seizure-freedom (FAS) were 85.2% with LCM versus 88.0% with CBZ-CR (PPS: 87.4%; 90.2%); 69.1% of LCM-treated and 65.1% of CBZ-CR-treated patients completed 6months without seizure. Kaplan-Meier estimates for 12-month seizurefreedom (FAS) were 75.7% with LCM versus 78.9% with CBZ-CR. Overall, 266 (59.9%) LCM-treated and 264 (59.7%) CBZ-CR-treated patients completed the trial. The most common reasons for premature discontinuation were adverse events (LCM: 48 [10.8%]; CBZ-CR: 69 [15.6%]), consent withdrawn (46 [10.4%]; 38 [8.6%]), and lack of efficacy (47 [10.6%]; 31 [7.0%]). Conclusion: LCM showed similar efficacy to CBZ-CR in patients with newly-diagnosed epilepsy, regardless of their baseline disease severity. UCB Pharma-sponsored

Method: Double-blind non-inferiority trial (NCT01243177) randomized patients 1:1 to twice-daily LCM/CBZ-CR. Flexible dosing (LCM: 200/ 400/600 mg/day; CBZ-CR: 400/800/1200 mg/day) was based on seizure control. Outcomes included 6-month seizure-freedom at last-evaluateddose, and adverse events (AEs). Results: 886 patients received trial medication. Data are reported for 119 (LCM: 62; CBZ-CR: 57) patients aged ≥65 years (full-analysis-set [FAS]), of whom 105 (57; 48) had no important protocol deviations (perprotocol-set [PPS]). Kaplan-Meier estimates for proportion of patients with 6-month seizure-freedom were similar with LCM and CBZ-CR (FAS: 93.6%, 92.3%; treatment-difference [95% confidence interval]: 1.4% [8.9%, 11.6%]) (PPS: 96.3%, 96.4%; 0.1% [8.4%, 8.2%]). Overall, 45 (72.6%) LCM-treated and 34 (59.6%) CBZ-CR-treated patients completed 6-months on last-evaluated-dose without experiencing seizure. Treatment-emergent AEs (TEAEs) occurred in 51 (82.3%) LCM-treated and 48 (84.2%) CBZ-CR-treated patients. Incidences of drug-related (LCM: 22 [35.5%]; CBZ-CR: 30 [52.6%]) and serious TEAEs (8 [12.9%]; 12 [21.1%]) were lower with LCM than CBZ-CR. TEAEs in ≥5% of patients with ≥5% difference in incidence for LCM versus CBZ-CR: headache (4 [6.5%]; 8 [14.0%]); somnolence (3 [4.8%]; 7 [12.3%]); fall (6 [9.7%]; 1 [1.8%]); GGT increased (0; 6 [10.5%]); constipation (1 [1.6%]; 5 [8.8%]); eosinophilia (0; 3 [5.3%]). 67 patients (LCM: 38 [61.3%]; CBZ-CR: 29 [50.9%]) completed trial. AEs were the most common reason for premature discontinuation (LCM: 13 patients [21.0%]; CBZ-CR: 15 [26.3%]). Conclusion: Efficacy of LCM (6-month seizure-freedom) was similar to that of CBZ-CR in elderly patients with newly-diagnosed epilepsy, but tolerability profiles differed. Efficacy results for elderly patients were comparable to those for the overall trial population (Baulac et al. ECE 2016 [submitted]). Individualized drug selection based on tolerability profiles is essential for newly-diagnosed patients. UCB Pharma-sponsored


180 Abstracts

Pharmacology/AEDs 5 Tuesday 13th September

have a PPV of 98.4% and, more importantly, the absence of IEDs has a negative predictive value of 98.5% i.e. the probability that unclear attacks were epileptic in the absence of IEDs is only 1.5%.(3) This is believed to hold true even in patients previously treated with antiepileptic drugs this based on the findings of Gotman et al. who showed that in patients with focal epilepsy drug levels of CBZ, PHT, VPA, PRM and PB did not affect spiking rate (4).

P590 EUROPEAN NON-INTERVENTIONAL REGISTRY STUDY OF ANTIEPILEPTIC DRUG USE IN PATIENTS WITH LENNOX-GASTAUT SYNDROME Auvin S1, McMurray R2, Brandt C3, Nikanorova M4 1 Robert Debre University Hospital, Paris, France, 2Eisai Europe Ltd, Hatfield, United Kingdom, 3Bethel Epilepsy Centre, Mara Hospital, Bielefeld, Germany, 4Danish Epilepsy Centre, Dianalund, Denmark

Methods and results: We hypothesised that Levetiracetam (LEV) may influence spiking rate. Therefore, we analysed the frequency of interiktal IEDs in 5 patients pre-treated with LEV during long-term-EEGs with a duration of 72 h. We observed that with high doses of LEV IEDs were completely absent or rare even in recordings in which epileptic seizures were registered. During the same recording LEV was reduced, which led to the appearance of IEDS in all cases.

Purpose: To present the final results from a European registry study, designed to capture long-term data on Lennox-Gastaut syndrome (LGS) patients initiating rufinamide as add-on therapy, or receiving other antiepileptic drugs (AEDs).

Conclusion: The sensitivity of interictal EEGs is massively reduced in patients treated with Levetiracetam. Thererfore, in cases with unclear attacks and negative 72 h recordings a repeat recording is recommended after discontinuation of Levetiracetam.

Method: The registry enrolled LGS patients (age ≥4 years) requiring modification to any AED treatment, including initiation of rufinamide. Its primary objective was to evaluate long-term safety. Seizure control was also assessed using a 7-point generic seizure frequency scale (rated from ‘very much worse’ to ‘very much improved’). Results: A total of 111 patients were enrolled and included in the Safety Analysis Set, of whom 64 (43 male/21 female) initiated rufinamide (‘rufinamide’ group) and 47 (28 male/19 female) were initially allocated other AEDs (‘other AEDs’ group). At baseline, for patients in the rufinamide and other AEDs groups, the mean (standard deviation [SD]) age was 16.1 (9.5) and 15.9 (12.5) years; the mean (SD) time since LGS diagnosis was 5.7 (8.1) and 6.4 (9.3) years; the mean (SD) number of prior AEDs was 5.6 (3.6) and 6.3 (5.5); and the proportion of patients in residential care was 10.9% and 21.3%, respectively. Median (range) follow-up duration was 26.6 (1.3–46.4) and 23.6 (1.7–47.8) months, respectively. At Month 12, the proportion of patients rated as ‘much’ or ‘very much’ improved in control of all seizures was 12/42 (28.6%) and 5/33 (15.2%) for rufinamide and other AEDs, respectively. AED-related adverse events were reported for 40.6% (rufinamide) and 27.7% (other AEDs) patients, and led to discontinuation of 7.8% and 2.1% patients, respectively. The most frequently reported rufinamide-related adverse events (≥5% patients) were somnolence (7.8%) and decreased appetite (6.3%). There were no unexpected safety findings. Conclusion: The registry has provided useful information on LGS and the use of rufinamide and other AEDs in its management. Supported by Eisai:

P592 FOCAL INTER-ICTAL EPILEPTIFORM ACTIVITY IN THE EEG SUPRESSED BY LEVETIRACETAM, A DIAGNOSTIC PROBLEM IN PRE-TREATED PATIENTS Kristina K, Mothersill IW, Bothmann JC, Cenusa M, Schedler A, Grunwald T Klinik Lengg AG, Schweizerische Epilepsieklinik, Z€ urich, Switzerland Introduction: The EEG is the main diagnostic tool for the diagnosis of epilepsy with interictal epileptiform discharges (IED) providing evidence of an epileptogenic abnormality in the brain. IEDs are highly specific, and the probability of unclear attacks being epileptic is high in the presence of IEDs with a positive predictive value (PPV) of over 90% (1). However, even in patients with confirmed epilepsy routine EEGs may show no IEDs and thus have a high false negative rate, which remains high even with repeated recordings including sleep (2). By contrast, ambulatory long-term-EEGs can increase both specificity and sensitivity: Utilising recordings with a duration of 72 h it has been shown that IEDs Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P593 FENFLURAMINE SIGNIFICANTLY REDUCES SEIZURE FREQUENCY IN DRAVET SYNDROME: A PROSPECTIVE STUDY OF A NEW COHORT OF PATIENTS Schoonjans A-S1,2, Gunning B3, Marchau F1, Paelinck B1, Gammaitoni A4, Lagae L5, Ceulemans B1 1 Antwerp University Hospital, Edegem, Belgium, 2University of Antwerp, Antwerp, Belgium, 3Epilepsy Center SEIN, Zwolle, The Netherlands, Zwolle, Netherlands, 4Zogenix, Inc., San Diego, CA, United States, 5University Hospitals Gasthuisberg, Leuven, Belgium Purpose: Dravet syndrome (DS) is a rare, severe and often drug-resistant epilepsy syndrome. Fenfluramine has been reported to have long-term beneficial activity in a cohort of DS patients in Belgium (Ceulemans et al, Epilepsia 2012). Here we describe the results from a prospective, open-label study of low-dose fenfluramine in a new cohort of DS patients with initiation of a standardized protocol of assessments. Method: Patients from 6 months to 50 years of age with a diagnosis of DS and therapy-resistant epilepsy were eligible to enroll. Patients with cardiovascular disease, including drug-treated hypertension and cardiac valvulopathy, were excluded. Following a 3-month run-in period, fenfluramine was added to each patient’s current anti-epileptic drug regimen at a dose of 0.1–0.5 mg/kg/day (max. 20 mg/day). The incidence of major motor seizures (tonic, clonic, tonic-clonic, atonic, and myoclonic seizures lasting >30 s) in both the run-in and treatment periods was assessed via a seizure diary. Periodic echocardiographic examinations during the treatment period were used to assess cardiovascular safety. Results: Nine patients (ages 1.2–29.8 years) enrolled in the study and were treated with fenfluramine for a median duration of 1.5 years (range, 0.30–5.06 years). Median frequency of major motor seizures was 15.0 per month in the run-in period. All patients demonstrated a reduction in seizure frequency during the treatment period with a median reduction of 75% (range, 28–100%). Seven of 9 patients (78%) experienced a ≥50% reduction in major motor seizure frequency. The most common adverse events were somnolence (n = 5 patients) and anorexia (n = 4). No evidence of cardiac valvulpathy or pulmonary hypertension was observed. Conclusion: The effectiveness of low-dose fenfluramine as add-on therapy for Dravet syndrome in this new cohort supports previous findings. Further studies are warranted.

181 Abstracts P594 EFFICACY OF PERAMPANEL BY BASELINE SEIZURE FREQUENCY IN PATIENTS WITH PARTIAL SEIZURES Sperling M1, Williams B2, Laurenza A2, Ma T3, Yang H3 1 Thomas Jefferson University, Philadelphia, PA, United States, 2 Eisai Inc, Woodcliff Lake, NJ, United States, 3Formerly: Eisai Inc, Woodcliff Lake, NJ, United States

the study, patients were taking a mean of 2.3 AEDs. The dose range of lacosamide was 200–600 mg/day with a mean of 310 mg/day. Add-on treatment with lacosamide was associated to >50% seizure reduction in 9 patients (64%), two of whom were seizure free. Nevertheless, we observed 7.5 to ≤19.1; and 417 had baseline seizure frequency >19.1. For those receiving therapeutic doses of perampanel (4–12 mg) during the double-blind studies, subjects with a seizure frequency at baseline ≤7.5 showed a greater median percent reduction than those with a seizure frequency >7.5 to ≤19.1 or >19.1. During the open-label extension, seizure frequency decreased in all subjects, regardless of baseline seizure frequency. Subjects with baseline seizure frequency ≤7.5 had greater seizure improvement from Week 105 of the open-label maintenance period than subjects with baseline seizure frequency >7.5 to ≤19.1 or >19.1. Conclusion: This analysis demonstrates that pre-treatment seizure frequency influences response to perampanel, with lower frequency associated with better response. The mechanism requires elucidation. Support: Eisai Inc.

P595 EXPERIENCE IN THE TREATMENT OF NOCTURNAL SEIZURES WITH LACOSAMIDE Villas M, Gil F, Aparicio J, Donaire A, Carre~no M Hospital Clinic Barcelona, Epilepsy, Barcelona, Spain Purpose: Lacosamide is an antiepileptic drug (AED) that modulates voltage-gated sodium channels by enhancing their slow inactivation. It is indicated as add-on treatment in focal seizures with or without secondary generalization. Some studies have found that sodium channel blockers tend to control seizures during sleep better than other AEDs. Method: We reviewed 174 epileptic patients in whom lacosamide was initiated as add-on treatment from June 2011 to December 2015. Sixty out of 174 patients had sleep seizures in addition to awake seizures. Among those, we identified 14 who had almost exclusively sleep seizures (>80% of seizures happened during nocturnal or diurnal sleep). Our objective was to find out the seizure outcome and the side effects of lacosamide in this group of patients. Results: The mean age was 41.4 years (range 22–68), 50% women; 11 patients had focal epilepsy (4 frontal and 7 temporal) and 3 had multifocal epilepsy. A structural aetiology was found in 10 patients: DNET (2), hippocampal sclerosis (3), temporal atrophy (1), fronto-parieto-occipital calcifications (1) and malformations of cortical development (3). During

Purpose: To evaluate the efficacy and safety of perampanel as an adjunctive treatment of focal epilepsies in routine clinical practice; to identify the target for the drug and the optimal, effective dosage. Method: We followed up 13 patients (7 men and 6 women) with symptomatic or cryptogenic focal epilepsy aged from 21 to 62 years (mean age, 35.7 years) who were receiving Fycompa at a dose of 6, 8, 10 or 12 mg/day as an adjunctive therapy. 7 patients had drug-resistant epilepsy. The duration of follow-up ranged from 6 months to 1.5 years. The baseline frequency rates were 1–7 per month for secondarily generalized seizures and 2–20 per month for partial seizures. Perampanel was administered once daily, at an initial dose of 2 mg that was subsequently gradually increased until a clinical effect was achieved. Results: A complete discontinuation of all types of seizures was observed in five subjects (38.5%) with the frontal epilepsy. Secondarily generalized seizures (SGS) were the predominant type in these patients and occurred primarily during sleep. Two patients were drug-resistant. Seizures stopped to occur at the following perampanel doses: 6 mg/day (in 4 patients) and 8 mg/day (in 1 patient). A reduction of the number of partial seizures (>50%) was observed in 3 subjects (23%). No effect was observed in 5 subjects (38.5%) with drug-resistant symptomatic focal epilepsy; three of them suffered from temporal epilepsy with frequent complex partial seizures, while the other two had frontal epilepsy with hypermotor seizures. Conclusion: The treatment with Perampanel was effective in 8 patients (61.5%). Effect of perampanel was independent of basic anti-epileptic therapy. The drug was well tolerated. There were isolated cases of transient dizziness. No serious adverse events were observed. Single dose administration at bedtime improves compliance.

P597 ESLICARBAZEPINE VS BRIVARACETAM FOR ADULTS WITH REFRACTORY PARTIAL SEIZURES: A META-ANALYSIS Zhang L1, Zou X1, Li S2, Li H2 1 Department of Neurology, West China Hospital, Sichuan University, Chengdu, China, 2Sichuan University, Chengdu, China Purpose: To compare the efficacy and tolerability of eslicarbazepine (ESL) and brivaracetam (BRV) in adults with refractory partial seizures (RPS).


182 Abstracts Method: We systematically queried Medline, Embase, and the Cochrane Library. We looked for additional studies in the references of all identified publications and ClinicalTrials.gov. The cutoff day was January 07, 2016. Randomized, double blind, placebo-controlled trials were included. The indirect comparison for 50% responder rate, free seizure rate, and adverse effects (AEs) were conducted. Results: Ten trials enrolling 1,796 patients in ESL and 1,919 patients in BRV were included. No statistical differences were found in efficacy between ESL and BRV. However, risk ratios (RRs) of seizure free for ESL versus BRV are 4 seizures/month in the last 6 months.

Fourteen patients (6 females) aged 14–25 years (mean 17.8 y) were studied, with a mean follow-up of 3.5 months (range 2–5.5 months). Neuropsychological executive functions and behavior were also monitored by means of Epitrack battery, CPTs assessment, and aggression behavior scale. Characteristics of the patients were: cryptogenic (5) or symptomatic (9) focal or generalized epilepsy; mean age at seizure-onset 27.8 months (range 3–122 months). Neurological examination was normal in half the patients, TIQ was normal (3) or delayed in 11 (mild 4, moderate 2, and severe 5). Type of epilepsy was: focal secondary generalization (10), epileptic encephalopathy (2), LGS (1), and Dravet syndrome (1). Seizure frequency prior to perampanel therapy was 1–6/week (10), and 1–4/day (4). Brain MRI showed hemispheric or bilateral


atrophy (6), migration disorder (1), hypothalamic amartoma (1), and hyppocampal sclerosis (1). Results: After a mean follow-up period of 3.5 months (2–7 months), seizure frequency decreased by 50% in 3, and by 75% in 2 patients; one patient was seizure-free. Seizure number was unchanged in 5 patients and increased in 3. The mean daily dose of perampanel at follow-up was 6.6 mg (4–8 mg). Irritability was reported in 2 patients. Three patients dropped out of treatment because of seizure worsening. Conclusion: In our experience perampanel as adjunctive therapy was overall well tolerated and effective in 42.8% of refractory children and young adults in the short-term period.

P607 PHARMACOVIGILANCE OF LAMOTRIGINE AND VALPROATE IN NORWAY, 2004–2013 Lima M1, Baftiu A2, Svendsen K3, I. Johannessen S4, Johannessen Landmark C2,4 1 Norwegian University of Science and Technology, Trondheim, Norway, 2Oslo and Akershus University College of Applied Sciences, Oslo, Norway, 3University of Tromsø, Tromsø, Norway, 4National Center for Epilepsy, Sandvika, Oslo University Hospital, Oslo, Norway Purpose: Often, there is a fine balance between efficacy and undesirable adverse effects of antiepileptic drugs (AEDs). The aim of this study was to investigate reports of adverse effects of two commonly used AEDs in Norway, lamotrigine and valproate. Method: Data consisted of all prescriptions of AEDs from the Norwegian Prescription Database and aggregated numbers of all adverse effect reports for AEDs from the Eudravigilance-database (2004–2013). Data contained specific reports on adverse effects for lamotrigine and valproate from Norway. Results: The average number of patients using lamotrigine and valproate in Norway each year was 20.564 (50% women) and 13.350 (49% women), respectively. A variety of different types of adverse effects for both AEDs were found, 145 in total. Of the 50 reports for valproate there were 41 different adverse effects, 17 responses were from men and 33 from women. Lamotrigine had 144 reports of which 38 were from men and 106 from women, with a total of 104 different types of adverse effects. The most frequently occurring adverse effects for valproate were: death/sudden unexplained death (8 patients), mental impairment/dementia/memory loss (3 patients). The most frequently reported adverse effects of lamotrigine were rash, eruption and exanthema (9 patients), death/sudden unexplained death (6 patients), febrile disorders (5 patients). Conclusion: Awareness of adverse effects is crucial to effective treatment without impairing the quality of life of the patients. Serious adverse effects are most commonly reported, and most reports are from women. Such studies are important and contribute to improved pharmacovigilance in a national scale.

P608 OWN EXPERIENCE WITH PERAMPANEL, ESLICARBAZEPINE AND ZONISAMIDE IN THE TREATMENT OF PATIENTS WITH EPILEPSY Nurmukhametova S Bashkir State Medical University, Ufa, Russian Federation Purpose: To evaluate the efficacy and safety of perampanel, eslicarbazepine and zonisamide as an additional and initial treatment in patients with focal and generalized seizures.

185 Abstracts Method: Clinical observation of 57 patients with average duration of disease 13.67 years. Idiopathic generalized epilepsy (IGE) was observed in 11 (19.29%) patients; focal forms in 46 (80.70%) patients. There were observed different types of seizures: simple partial seizures in conjunction with the complex seizures, complex partial seizures in combination with secondary generalized tonic-clonic seizures, generalized tonic-clonic, myoclonic seizures, absences. All patients had a high frequency of seizures. Patients were divided in three medication groups: (1) zonisamide-group, its mean dose in mono- and polytherapy was 205 mg/day, with focal epilepsy in monotherapy and polytherapy 257.14 mg/day; (2) perampanel group with the average daily dose as monotherapy was 3.3 mg/day; polytherapy – 6 mg/day; (3) Eslicarbazepine appointed in 8 patients with focal epilepsy, 3 of them took the drug as monotherapy in high dosage of 533 mg/day, in combined therapy dose was - 800 mg/day. Results: Seizure control was achieved in 14 patients (24.56%), significant clinical effect (reduction of seizure frequency by more than 50%) was achieved.

P609 REAL WORLD DATA OF PERAMPANEL AS ADJUNCTIVE THERAPY IN A GERMAN EPILEPSY CENTER Pensel MC, Racz A, von Wrede R, Helmstaedter C, Elger CE Klinik f€ur Epileptologie, Universit€atsklinikum Bonn, Bonn, Germany Purpose: In the class of selective, non-competitive AMPA glutamate receptor antagonists, Perampanel is currently the only approved substance for the adjunctive treatment of partial onset epilepsy. This study aims to evaluate adverse effects, retention rates and efficacy parameters of Perampanel in a real world setting. Method: We performed a retrospective investigation of partial onset epilepsy patients with adjunctive Perampanel medication. Data of n = 214 patients were assessed from first prescription over a period of around 1 year (14.3 12.2 months). Retention rates, adverse effects and efficacy parameters were extracted from medical reports. The study is still in progress and preliminary results are presented here. Results: After the observation period, n = 97 patients were still treated with Perampanel (retention rate 45.3%). Adverse effects alone lead to termination of Perampanel medication in 50 out of 117 cases (42.7%). Other main reasons were insufficient efficacy (n = 31, 26.5%) and supply problems (n = 3, 2.6%). The remaining patients stated a combination of the aforementioned or other reasons for termination. Reported intolerable side effects (n = 64) were predominantly dizziness (n = 20, 31.3%), increased irritablility (n = 18, 28.1%), fatigue (n = 13, 20.3%) and depression (n = 7, 10.9%). Out of 109 cases with sufficient data on seizure control, n = 11 patients (10%) reported freedom of seizures for 9.1 9.7 months. Additional n = 37 patients (34%) stated a positive impact on seizure frequency and/or intensity. Conclusion: Perampanel was shown to be an effective substance in our sample of patients. The results are promising in terms of efficacy, especially regarding the comparably large number of seizure free patients. On the other hand, adverse effects lead to an end of Perampanel medication in a considerable amount of cases. The study is limited by incomplete data on seizure control. Taken together, for the subgroup of patients tolerating the substance, Perampanel adds a viable therapeutic option for the treatment of partial onset epilepsy.

P610 PROMETEO: A PROSPECTIVE OBSERVATIONAL STUDY TO ASSESS THE TREATMENT EFFECT AFTER INTRODUCTION OF A DIFFERENT AED IN PATIENTS WITH PARTIAL EPILEPSY FULFILLING THE 2010 ILAE CRITERIA OF DRUG-RESISTANT EPILEPSY Perucca E1,2, Galimberti CA2, Ferr o B3, on behalf of the SP0992 Study Group 1 Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy, 2IRCCS National Neurological Institute C. Mondino, Pavia, Italy, 3UCB Pharma, Milan, Italy Purpose: This prospective long-term observational study was designed to assess treatment outcomes in adults with focal epilepsy meeting ILAE criteria of pharmacoresistance (Epilepsia 2010;51:1069–77). Methods: Consecutive patients with focal epilepsy considered to be pharmacoresistant by the enrolling physician were followed up for 18 months to assess outcomes after introduction of one or more additional AED, or for 34 months if seizure free for the last 2 months at the 18-month visit. An external Expert Panel (EP) reviewed individual patient data to confirm or refute the classification of drug resistance made by the enrolling physicians and the final categorization of outcome after subsequent treatment changes. The Full Analysis Set (FAS) refers to the classification of pharmacoresistance and outcome categorization made by the enrolling physician. Per Protocol (PP) analysis is currently ongoing. The PP refer to classification/categorization and include those patients confirmed by the EP to be pharmacoresistant at enrolment. Results: 1,063 patients received an additional AED and were enrolled at 45 sites in Italy from 2011 to 2012. In the FAS dataset (n = 1,053) mean age was 44.5 (SD 14.22) years, mean epilepsy duration was 23.3 (SD 15.25) years, median baseline monthly seizure frequency was 5.0 (range 0.1–220.0) and mean number of previously tried AEDs at enrolment was 5.6 (range 1–33). 877 (83.28%) patients completed the study. Of the 1,053 patients included in the FAS and evaluated using ILAE outcome criteria, 92 (8.73%) became seizure-free, 646 (61.34%) were treatment failures, and 315 (29.9%) were undetermined. Conclusion: This analysis confirms that most patients considered to be pharmacoresistant by the enrolling physician remain resistant after introducing another AED. However, almost one out of ten achieved seizure freedom. Further follow-up after EP validation is needed to better characterize the prognostic features of this population. UCB Pharma-sponsored.

P611 PERAMPANEL IN CHILDREN AND ADOLESCENTS WITH REFRACTORY EPILEPSY: PMK HOSPITAL, THAILAND EXPERIENCE Suwanpakdee P, Nabangchang C Department of Pediatric Neurology, Phramongkutklao College of Medicine, Bangkok, Thailand Purpose: To evaluate the safety & efficacy of short-termed perampanel as add-on anti-epileptic therapy in pediatric and adolescent patients with refractory epilepsy. Method: We retrospectively reviewed pediatric and adolescent patients who had refractory partial-onset or generalized epilepsy and were on Perampanel as the last add-on drug to existing anti-epileptic therapy for at least 3 months including patients with vagus nerve stimulator or prior treatment with epilepsy surgery. Patients were evaluated for age at seizure onset, etiology, seizure type, baseline seizure frequency, concomitant anti-epileptic drugs, and dose of perampanel. Primary outcome was reduction in seizure frequency and secondary outcomes were responder rate and seizure freedom.


186 Abstracts Results: There were 21 patients identified. The age was 10 months – 19 years (mean = 7.75 years) and duration of epilepsy prior to perampanel was 4 months to 14 years (mean = 5 years). Eleven patients had symptomatic partial epilepsy, 8 patients had cryptogenic partial epilepsy, one had symptomatic generalized epilepsy and 2 patients had primary generalized epilepsy. The number of previously failed antiepileptic medications (include surgery, KD, B6) was 1–10 (mean = 6). The number of concomitant antiepileptic medications was 1–3 (mean = 2.4). Eight patients had 100% seizure reduction, 7 patients had seizure reduction of more than 50 percent, 1 patient had seizure reduction of less than 50% and 4 patients demonstrated no response to the treatment. Five patients experienced mild adverse effect of the medicine (sedation = 3, gait problem = 2). There was no serious adverse events. Conclusion: Perampanel demonstrated good efficacy and tolerability as add-on treatment in children and adolescence with refractory epilepsy.

P613 PERAMPANEL IN ROUTINE CLINICAL PRACTICE Vlasov P, Karlov VA, Jidkova IA, Belyaev OV, Danilova TV, Dimitrenko DV, Karas AY, Kazennyh TV, Miguskina OI, Moskvicheva AV, Paramonov EN, Ponomareva IV, Chervyakov AV General Medical Faculty of Moscow State University of Dentistry named after A.I. Evdokimov, Department of Neurology, Moscow, Russian Federation Purpose: To study the efficacy/tolerability of perampanel (PER) as a additional antiepileptic drug (AED) in patients with drug-resistant focal epilepsy. The study design: multicentre retrospective. Method: 52 patients older than 12 years were included in the study. The mean age - 28.92 14.02 years, men - 56%, the disease duration more than 10 years - 69.2% patients, symptomatic epilepsy - 76.9% of the frontal - 46.2% and temporal 44.2% localization of epileptic focus. Perampanel was administered after 3 prior lines of therapy in the most of patients - 71.2%. The initial frequency of all seizure types was 127.29 82.29 per month; secondarily generalized - 6.72 1.90 per month. Results: During the first month there was significant frequency reduction of the all types of seizures to 52.06 29.26 per month after adding the PER (Sign test, p = 0.00001), and secondarily generalized seizures to 3.71 1 71 (Sign test, p = 0.00001). In the vast number of observations duration of reception PER was more than 6 months. The frequency of seizers decreased more than 50% in 58% of patients (responders). Lack of seizure types obtained from 8% and 31% of patients - only secondarily generalized. Side effects were reported in 30.1% of patients: aggression - 11.5% and drowsiness - 9.6%, and the rest were observed with a rare frequency. Perampanel dose was decreased due to the development of side effects in 7 patients (13.5%), in 4 patients (7.7%), perampanel was canceled. Average dose of perampanela for adult patients was 6 mg. Conclusions: Perampanel showed high efficiency and predictable safety profile in patients with drug-resistant focal epilepsy. Perampanel average dose for adult patients was 6 mg. The dose of PER more than 4 mg should increase more slowly and monitor side effects.


Pharmacology/AEDs 8 Wednesday 14th September P614 THE ROME STUDY (RETROSPECTIVE OBSERVATIONAL MULTICENTER STUDY ON ESL): ‘EFFICACY AND TOLERABILITY OF ESLICARBAZEPINE ACETATE (ESL) AS ADJUNCTIVE THERAPY FOR ADULT PATIENTS WITH PARTIAL ONSET SEIZURES AND GLOBAL EFFECT ON QUALITY OF LIFE’ Assenza G1, Mecarelli O2, Assenza F1, Tombini M1, Di Lazzaro V1, Pulitano P2 1 Clinical Neurology, Campus Biomedico University of Rome, Rome, Italy, 2Department of Neurology and Psychiatry, Sapienza University, Policlinico Umberto 1 Hospital, Rome, Italy Purpose: The efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy for persons with refractory partial onset seizures (PrPOS) has been demonstrated in three randomized double blind controlled trials. We aimed to confirm ESL efficacy and tolerability as adjunctive therapy in PrPOS, as well as to determine ESL benefits on quality of life in “real-life”. Method: We retrospectively evaluated 50 (48 14 years old) PrPOS (23 males, 46%) treated with adjunctive ESL for ≥2 months. We compared seizure frequency, treatment retention, ADRs/SADRs, concomitant AEDs and scores of Stanford Sleepiness Scale (SSS), Epworth Sleepiness Scale (ESS), QOLIE-31 and Beck Depression Inventory (BDI) scales at baseline and after ≥2 months of ESL. Results: Before ESL, our patients complained 10 21 seizure/months and took 2.0 0.8 drugs in association with ESL. They had 17 13 years of epilepsy history and tried 3 1 drugs before taking ESL. At the end of follow-up (96 28 days of ESL exposure) ESL reduced seizure frequency of ≥50% in 60% of them, with 31% seizure free. 10% had a ≤50% seizure reduction and 29% did not experienced any change. 15 experienced ADRs (the most common were vertigo in 6 and hyponatremia in 4) and of these 12 withdrew treatment due to their effects; 2 presented SADRs (symptomatic hyponatremia). Retention rate was 74%. ESL reduced the number of concomitant drugs (1.5 0.7; v2 = 9.52, df 3, sig. 0.23), sleepiness (SSS: 3.2 1.8 at baseline, 2.5 1.6 after ELS, p = 0.031; ESS: 6.2 3.5 at baseline, 4.0 3.5 after ESL, p = 0.0000002), while ameliorated QOLIE-31 (49.4 17.8 at baseline, 62.6 16.0 after ESL; p = 0.000002) and mood (BDI 13.7 9.2 at baseline, 6.1 7.1 after ESL; p = 0.000012) with a normalization of BDI results in 90% of depressed patients. Conclusion: Preliminary data on our “real-life” experience suggest that ESL is an effective and safe antiepileptic drug when used as adjunctive therapy in adult PrPOS. ESL effectiveness results in an improvement of global quality of life and mood disorders.

P615 SAFETY AND TOLERABILITY OF ESLICARBAZEPINE ACETATE AS MONOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED PARTIAL-ONSET SEIZURES Trinka E1, Kowacs P2, Ben-Menachem E3, Elger C4, Moreira J5, Pinto R6, Ikedo F5, Pereira A5, Rocha J-F5, Soares-da-Silva P5 1 Department of Neurology, Paracelsus Medical University, Salzburg, Austria, 2Hospital das Clınicas, Universidade Federal do Paran a, Curitiba, Brazil, 3Institute for Clinical Neuroscience and Physiology Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 4Department of

187 Abstracts Epileptology, University of Bonn, Bonn, Germany, 5Bial Portela & Cª S.A., R&D, Coronado, Portugal, 6Faculty of Medicine, University of Porto, Porto, Portugal Purpose: To describe the safety of once-daily (QD) eslicarbazepine acetate (ESL) as assessed in a phase-III, randomized, double-blind, active-controlled, non-inferiority monotherapy study in adults with newly diagnosed partial-onset seizures (POS), in comparison with twicedaily (BID) controlled-release carbamazepine (CBZ-CR). Method: Patients (≥18-years) were randomized (1:1) to receive either ESL or CBZ-CR in a 3-step dose-level design. Each dose-level was to be maintained through a 26-week Evaluation-Period (EP) and increased to the next dose-level in the event of seizure during EP. Dose-level A was ESL 800 mg/day or CBZ-CR 400 mg/day, Dose-level B, ESL 1,200 mg/ day or CBZ-CR 800 mg/day, and C was ESL 1,600 mg/day or CBZ-CR 1,200 mg/day. Subjects who remained seizure-free at any dose-level continued through subsequent periods/phases. Safety assessments included treatment-emergent adverse events (TEAEs), laboratory tests, physical/neurological examinations, electrocardiogram, C-SSRS and BL-VAS. Results: From the 815 randomized patients, 813 were included in the safety analyses (ESL, 401; CBZ-CR, 412). A similar percentage of subjects experienced at least 1 TEAE in the ESL group (75.3%) and CBZCR group (77.7%) and the majority of events were of mild intensity. TEAEs considered at least possibly related to treatment were reported by fewer subjects in the ESL group (41.1%) than in the CBZ CR group (49.5%). The most frequently reported possibly-related TEAEs were (ESL; CBZ): headache (6.5%; 5.6%), dizziness (7.2%; 6.8%), nausea (4.5%; 6.8%), fatigue (4.7%; 4.4%), somnolence (5.2%; 7.0%) and increased gamma-glutamyltransferase (2.7%; 12.4%). Fewer subjects discontinued treatment due to a TEAE in the ESL group (13.5%) compared to the CBZ-CR group (18.0%). In 4 subjects reported TEAE led to death; all were considered to be not related to therapy with the exception of suicide in the CBZ-CR group (possibly related). Conclusion: Once-daily ESL monotherapy demonstrated favorable safety in the study population. No new or unexpected safety findings emerged, compared with the adjunctive studies.

P616 REVERSIBLE LIVER DYSFUNCTION ASSOCIATED WITH HIGH DOSE KETAMINE IN REFRACTORY STATUS EPILEPTICUS Chua HC National Neuroscience Institute (Tan Tock Seng Hospital), Neurology, Singapore, Singapore Purpose: Ketamine is a N-methyl-D-aspartate receptor antagonist used to treat refractory status epilepticus (RSE). We report two patients with reversible liver dysfunction (a rare complication) while on ketamine. Method: Both cases were retrieved from the Neurointensive Care Unit records (1.1.15 - 1.12.15). Results: Case 1: A 76 years old man with post-traumatic scar epilepsy was admitted for recurrent seizures. MRI brain showed encephalomalacia. Microbiologic investigations were negative. Treatment with midazolam, valproate, keppra, topamax and propofol failed to abolish seizures. Valproate, propofol/midazalom were discontinued due to hyperammonemia and hypotension respectively. Ketamine was started with 5 mg/kg bolus followed by infusion 1–10 mg/kg/h. This aborted seizures, but serial liver enzymes showed progressive elevation of alanine transaminase (ALT) to 186 U/l (baseline: 23 U/l), alkaline phosphatase (ALP) to 683 U/L (baseline: 76 U/L), and total bilirubin to 400 lmol/l (baseline 9 lmol/l). INR was 1.8. Magnetic resonance cholangiopancreatography was normal. Ketamine was discontinued and liver enzymes progressively improved. Unfortunately patient perished from pneumonia with septic shock.

Case 2: A 39 year old man with epilepsy and mental retardation presented with recurrent seizures due to non-compliance. Despite treatment with midazolam, phenytoin, valproate and phenobarbitone, seizures persisted. Ketamine was started with a 5 mg/kg bolus followed by infusion 1–10 mg/kg/h. This aborted seizures but liver enzymes progressively escalated to ALT 155 U/l (baseline: 28 U/l), ALP 650 U/l (baseline: 144 U/l). Total bilirubin 35 lmol/l. CT scan abdomen showed normal hepatobiliary system. With discontinuation of ketamine, liver enzymes improved, but seizures recurred and patient perished from pneumonia and status epilepticus. Conclusion: Clinicians should be aware of the possibility of reversible liver dysfunction (both hepatitic and cholestatic) with ketamine in RSE.

P617 SURVEILLANCE OF THE ORPHAN DRUG RUFINAMIDE IN NORWAY: PATIENT AND POPULATION ASPECTS Gott as A1,2, Larsen Burns M1,2, Baftiu A3, Johannessen SI1,2, Johannessen Landmark C1,2,3 1 Department of Pharmacology, Oslo University Hospital, Oslo, Norway, 2The National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway, 3Institute of Pharmacy and Biomedical Science, Oslo and Akershus University College, Oslo, Norway Purpose: Rufinamide, one of the newest antiepileptic drugs (AED), was approved in Norway for adjunctive treatment of children (>4 years) and adults with Lennox-Gastaut syndrome in 2009. An analytical method for therapeutic drug monitoring (TDM) of rufinamide was established in our laboratory in 2015. The aim of this study was to demonstrate methods for surveillance of clinical use, prescriptions trends and TDM results for rufinamide from our epilepsy center. Method: Our medical database regarding clinical use of rufinamide and TDM data were utilized (2015–2016). To investigate the total use of rufinamide (2007–2014) the Norwegian Prescription Database (NorPD) was utilized. The Regional Ethics Committee and National Institute of Public Health approved the study. Results: Clinical data from patients admitted to our center revealed that 43 patients received rufinamide (20 women/23 men, average age 20 years, range 5–63). All of the patients had refractory epilepsy and used rufinamide as add-on therapy. 20 patients had generalized epilepsy, 12 had multifocal and 4 patients had focal epilepsy, while 7 were not classified. 14 patients had Lennox Gastaut syndrome, 12 had symptomatic localization-related seizures and 8 had other seizure classifications. NorPD data showed that rufinamide was prescribed to 41 patients in 2007, and increased to around 100 patients per year 2009–2014. The utilization increased from 0.001 to 0.016 DDD/1000 inhabitants/day in the same period. The data show an increasing trend in the usage of rufinamide in adults (>20 years), while there was a decreasing usage in children (5–9 years) after 2009. Details on TDM data will be discussed. Conclusion: The total number of patients using rufinamide increased from 2007 to 2009, thereafter the usage still increased in the adult population but decreased in the younger population. The use of complementary data sources contributes to pharmacovigilance of new AEDs in Norway.


188 Abstracts P618 RETROSPECTIVE STUDY WITH PERAMPANEL IN THE FJORD DISTRICT IN NORWAY FROM 2013 UP TO FEBRUARY 2016. PATIENTS DIAGNOSED WITH POS AND PGTC Kristensen T1,2 1 Neurological Department, Forde Central Hospital, Helse Forde, Forde, Norway, 2Neurological Department, Helse Forde, Forde, Norway Purpose: To evaluate the efficacy and safety in patients treated with perampanel in the use in POS and PGTC patients treated in clinical practice. Method: To perform a retrospective study of the patients treated with perampanel, which mainly are treated for disabling seizures, at Forde Central Hospital, Norway. The study will include baseline data, efficacy data and safety data for patients treated both for POS and PGTC. A sub analysis will look into data regarding combined effect in treatment in GTC treated patients, elderly, combination therapy and psychiatric disability. The outcome is also analyzed with regard to previous AED history. The patients who have used perampanel from introduction on the market will be searched from the electronical medical files. Data will be collected retrospectively. Retrospective study which will include all patients on perampanel since the start. Approximately 55 adults patients will be included in the study. I will use age adjusting and standard deviation. Results: Providing information regarding efficacy and safety of epilepsy with a detailed history of previous AED treatments, combined effect in treatment in GTC treated patients, elderly, combination therapy and psychiatric disability, may help to find clinical implications in different patient groups depending on the outcome, positive or negative. Conclusion: By finding appropriate AED treatment combinations with a positive outcome regards to seizure freedom, seizure reduction, retention rate and safety; this study might be able to provide an experience outcome in different patient selections for perampanel treatment. It is important to escalate perampanel slowly with only 2 mg each 4 week to avoid side effects. For most patients the target dose perampanel should be 4–8 mg.

P619 SEIZURE FREEDOM WITH PERAMPANEL TREATMENT IN PATIENTS WITH REFRACTORY EPILEPSY Peltola J, Rainesalo S, M€akinen J Neurology, Tampere University Hospital, Tampere, Finland Purpose: The chances for seizure freedom diminish substantially after first two AEDs with adequate doses. According to our treatment protocol perampanel has been used as add-on treatment for refractory epilepsy mostly with patients who have failed all previous treatment efforts with available AEDs and continue to have disabling seizures. For the purpose of this study, the number of patients achieving 12 month seizure freedom with perampanel treatment was assessed. Method: We were able to identify 26 patients treated with perampanel from our hospital records. All patients initiated with perampanel treatment had a long duration of epilepsy with numerous previous AED trials. 24 patients had two or three concomitant AEDs, one patient had only one concomitant AED. Three patients had vagus nerve stimulation (VNS) treatment, additional three had deep brain stimulation (DBS) and one patient had both VNS and DBS. Results: Four patients with focal epilepsy became seizure free for more than 12 months with initiation of perampanel therapy, three patients with 8 mg/day and one with 6 mg/day. These patients had a duration of epilepsy without seizure control between 6 and 11 years. Three patients had


only secondarily generalized tonic-clonic seizures (SGTCS), one patient both SGTCS and complex partial seizures (CPS). Before perampanel these patients had used previously 5–11 other AEDs. Conclusion: When taken into consideration the refractory nature of our study population these data suggest that perampanel provides significant clinical usefulness in patients with long standing refractory epilepsy. The predominant seizure type in a group that became seizure free was SGTCS supporting the notion of efficacy of perampanel to prevent generalization of epileptic seizures.

P620 THE FACTORS OF PHARMACORESISTANCE OF FOCAL SEIZURES, THE EFFICACY OF PERAMPANEL Rakhmanina O, Levitina E SBEE HPE Tyumen State Medical University Ministry of Healthcare Russia, Tyumen, Russian Federation Purpose: To determine the contribution of objective and subjective factors of pharmacoresistance at epilepsy and investigate the efficacy of perampanel at resistant focal seizures. Method: At 18 children (10 male, 8 female, 6.7 5.1 years) and 7 adults (4 male, 3 female, 44.5 14.9 years) with pharmacoresistant epilepsy (inefficiency ≥2 use of AEDs in mono/polytherapy for a year or more) factors most likely to influence the outcome of treatment were investigated. In the second phase the efficacy of perampanel in 10 patients (9 male, 1 female, 19.2 9.3 years) with focal seizures (7 symptomatic focal epilepsy, MRI-positive; 3 - probably symptomatic focal epilepsy, MRI-negative) was evaluated. In assessing the efficacy we have considered only attacks with motor phenomena. Results: Objective factors of pharmacoresistance were found at 94% of children; the leading among them: symptomatic focal epilepsy of various etiologies (77%), intolerance to AEP (27.7%), TBR phenomenon (50%). Subjective factors were detected at 33% of children. 71.4% of the adult, unlike the children, had subjective factors of pharmacoresistance. In both groups, the main subjective factor was the low compliance to therapy. 10 patients had perampanel in the treatment. The average length of the disease was 11.8 8.15 years, the amount applied in the past medical history of AED 6 2.05. At the time of adding perampanel 2 patients were on monotherapy, 8 - duotherapy, at 3 - VNS. Perampanel dose was 6– 12 mg (9 1.8 mg). Folow-up: 6.84 5.2 months. Full regression of attacks was at 1patient; slowing for ≥75% - 3; for ≥50% - 3; no effect - 3. Side effects occurred at 7 patients; 2 patients required discontinuation of the drug, 4 patients needed dose reduction. Key side effects were: dizziness - 4, aggression/agitation - 3 patients. Conclusion: The presented clinical experience (retrospective, uncontrolled, observational, open) of application of perampanel confirms its efficacy in refractory focal seizures.

P621 SAFETY AND EFFICACY OF ZONISAMIDE IN REFRACTORY EPILEPSY PATIENTS: A RETROSPECTIVE STUDY BASED ON AN EARLY DATA Senadim S, Alpaydin Baslo S, Atakli D, Tekin G€ uveli B, Sari H Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology, Neurosurgery, Istanbul, Turkey Purpose: In Turkey, Zonisamide (ZNS) was approved in 2008 and has been used for epilepsy patients with partial and generalized seizures. The aim of this study is to investigate safety and efficacy of ZNS in refractory epilepsy patients.

189 Abstracts Method: This study was carried out in refractory epilepsy patients who received ZNS for epilepsy treatment and who were examined at epilepsy outpatient clinics between October 2015 and February 2016. Medical records were re-evaluated retrospectively. Age, gender, parental consanguinity, febrile convulsion history, age of seizure onset, seizure types, neurological and mental examination, magnetic resonance imaging (MRI), EEG features, number of concomitant antiepileptic drugs except ZNS, seizure frequency reduction, and adverse effects were noted. Results: Forty-five patients were eligible. Six patients observed for less than 6 months after the initiation of ZNS treatment, were excluded. ZNS was used as add-on therapy in all patients. 19 out of 39 patients stopped treatment due to; aggravated seizures, unchanged seizure frequency, or side effects. Remaining 20 patients aged between 19 and 56 years were evaluated. Of the patients 4 had parental consanguinity, 4 had history of febrile convulsion and 6 were mentally retarded. Fourteen patients had both complex partial and generalized seizures, 2 patients had only generalized seizures, 2 patients had generalized seizures and myoclonia, 1 patient had generalized seizures, absence seizures and myoclonic jerks and 1 patient had only complex partial seizures. MRI revealed arachnoid cyst in 1, MTS in 6, hypoxic ischemic findings in 1, leukodystrophy in 1, encephalomalacia in 3, and heteroptopia in 1 patient. Patients were using ZNS for 7–80 months at a dose of 100–400 mg/day. Seizure frequency reduction of 25% was noted in 1, 50% in 5, 75% in 7 patients. Three patients became seizure free. Conclusion: ZNS is safe, tolerable and effective alternative for the patients with refractory epilepsy.

Pharmacology/AEDs 9 Wednesday 14th September P622 USE OF RUFINAMIDE AND OTHER ANTIEPILEPTIC DRUGS IN THE MANAGEMENT OF ADULT PATIENTS (≥18 YEARS) WITH LENNOX-GASTAUT SYNDROME Brandt C1, McMurray R2, Auvin S3, Nikanorova M4 1 Bethel Epilepsy Centre, Mara Hospital, Bielefeld, Germany, 2 Eisai Europe Ltd, Hatfield, United Kingdom, 3Robert Debre University Hospital, Paris, France, 4Danish Epilepsy Centre, Dianalund, Denmark Purpose: Management of Lennox-Gastaut syndrome (LGS) is challenging and there are few published reports concerning treatment of adults with LGS. We present long-term data from a patient registry on the use of rufinamide and other antiepileptic drugs (AEDs) for treatment of adults with LGS. Method: LGS patients requiring modification to any AED treatment, including initiation of rufinamide were enrolled. The primary objective was to evaluate long-term safety. Seizure control was also assessed using a 7-point generic seizure frequency scale (rated from ‘very much worse’ to ‘very much improved’). Data on adult patients (≥18 years) were extracted and analysed. Results: Twenty-four adult patients were included; 16 (seven male) initiated rufinamide (‘rufinamide’ group) and eight (six male) were initially allocated other AEDs (‘other AEDs’ group). At baseline, for the rufinamide and other AEDs groups, respectively, the mean (standard deviation [SD]) age was 30.0 (7.5) and 38.6 (14.7) years; the mean (SD) time since LGS diagnosis was 11.4 (13.3) and 20.3 (15.2) years; the mean (SD) number of prior AEDs was 6.4 (3.8) and 7.4 (8.7); and the proportion of patients in residential care was 25.0% and 50.0%. Median (range) follow-up duration was 29.7 (3.2–46.4) and 19.9 (1.7–38.2) months, respectively. At Month 24, the proportion of patients rated as ‘much’ or ‘very much’ improved in control of all seizures was 2/7 (28.6%) and 2/4 (50.0%) for rufinamide and other AEDs, respectively. AED-related

adverse events were reported for 50.0% (rufinamide) and 37.5% (other AEDs) patients, and led to discontinuation of 6.3% and 0% patients, respectively. The only rufinamide-related adverse event reported for more than one adult was somnolence (n = 2). There were no unexpected safety findings. Conclusion: The registry has provided useful information on LGS in adulthood and the use of rufinamide and other AEDs in this setting. Supported by Eisai.

P624 ADDRESSING THE CHALLENGES IN CONDUCTING INTERNATIONAL EUROPEAN MULTICENTER TRIALS IN RARE DISEASES: TIME FOR ACTION? Jansen F1, van den Munckhof B1, Braun K1, Arzimanoglou A2, Perucca E3 1 UMC Utrecht, Pediatric Neurology, Brain Center Rudolf Magnus, Utrecht, Netherlands, 2Department of Epilepsy, Sleep and Paediatric Neurophysiology, University Hospitals of Lyon (HCL), Lyon, France, 3Department of Internal Medicine and Therapeutics, University of Pavia and C. Mondino National Neurological Institute, Pavia, Italy Purpose: International multicenter randomized controlled trials provide the highest quality evidence for safety and effectiveness assessments and have the theoretical advantage of permitting enrolment of many patients within a relatively short period. Methods: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES), is a relatively rare childhood epilepsy syndrome which can lead to serious consequences in terms of poor cognitive outcome if untreated. Evidence on the most effective treatment in ESES is lacking and an institutional trial was designed to reflect existing medical practices. The international European multicenter randomized controlled trial of Steroids versus Clobazam Usage for Encephalopathy with ESES (RESCUE ESES) aims to compare the effects of treatment with corticosteroids and clobazam, for a period of 6 months, in 130 children with ESES aged 2–12 years. Results: To ensure optimal trial conduct and coordination, several bureaucratic challenges had to be addressed. Trial initiation was delayed at many sites by the need to address heterogeneous procedures and requests by ethical committees and competent authorities working under different regulations, technical and cultural conditions. Although in clinical care all study drugs are readily available, the same drugs were not consistently for use in the trial and had to be imported by many study sites. Complying with regulatory requirements to import commercially available formulations from one EU country to another proved to be practically unfeasible in some instances. Approval of the study protocol and documents, and especially approval of the clinical trial agreements between the sponsor and the participating centers, was very time consuming. We strongly feel that simplification of regulations to conduct European non-profit investigator-driven trials is needed to encourage much needed comparative effectiveness research. Conclusion: The lessons learned in this trial are of considerable importance to all centers taking part in international multicenter studies.


190 Abstracts P625 TRANSITIONING PATIENTS FROM OXCARBAZEPINE TO ESLICARBAZEPINE ACETATE Mäkinen J, Rainesalo S, Peltola J University of Tampere, Tampere, Finland Purpose: Some clinical and experimental findings suggest that eslicarbazepine acetate (ESL) might share similar efficacy compared to oxcarbazepine (OXC), but with less adverse-events (AEs) (Peltola J et al. Epilepsy Behav 2015;50:46–49). However, clinical evidence for OXC versus ESL in terms of tolerability or how to execute the transition from OXC to ESL is lacking. We report the process of transitioning patients from previous OXC treatment to ESL due to AEs in a standardized clinical setting. The rationale for change from OXC is reported, and the outcome with respective to this rationale is analyzed in terms of tolerability (the main objective) and efficacy (the secondary objective). Method: Twenty three subjects with localization-related epilepsy were transitioned from OXC to ESL due to OXC-related AEs. After 3 months follow up subjects were classified as responders (significant reduction of AEs and improvement of quality of life) and non-responders. Results: Fifteen subjects (65%) were responders and eight (35%) nonresponders. Noticeably, nearly all AEs presenting in the morning resolved after transition. According to efficacy, none had increased seizure frequency and seizure frequency was decreased 50% in one patients and seizure duration shortened in two patients without change in seizure frequency. The incidence of ESL-related AEs was 39% at 1 month and 13% at 3 month follow up; however, all patients continued ESL throughout the study. Conclusion: Despite retrospective nature of this uncontrolled follow up study and limited number of patients our findings support the notion that patients currently receiving OXC who experience intolerable AEs for switching them to ESL in order to maintain seizure control and improve patients tolerability and quality of life might be appropriate, especially if the AEs are most evident following morning dosing. Research was supported by an investigator-initiated grant awarded by Eisai Ltd to University of Tampere, Finland.

P626 VALPROATE INDUCED SEVERE HYPERAMMONEMIC ENCEPHALOPATHY SUCCESSFULLY TREATED BY CARGLUMIC ACID IN A CHILD Rosdy B, Kollar K, Moser J, Mellar M, Pfliegler A Heim Pal Children’s Hospital, Neurology, Budapest, Hungary Purpose: Valproate induced hyperammonemic encephalopathy is an unpredictable life threatening side effect of valproate treatment. Method: A 10 year old boy has experienced personality changes and suffered from attacks, which were interpreted as panic by his parents. He experienced 14–20 attacks per day as well in awake and in sleep. The attacks were preceded by a falling sensation and bilateral numbness in his body from his head till the toes. He was terrified, began to shout, sometimes obscene words, and tried to escape. Ictal EEG revealed the epileptic origin of the attacks, but could not verify the pacemaker zone. Interictally in 50% of awake and in 70% of sleep EEG bilateralised spike-wave discharges could be found with 2, 5–3 Hz frequency. We diagnosed frontal lobe epilepsy. Cerebrospinal fluid analysis and the serum autoimmune encephalitis antibodies, and cranial MRI did not show any positive results. Intravenous valproate was started with a loading dose of 30 mg/kg/followed by 1 mg/kg/h, till therapeutic serum valproate concentration was reached. Then we switched to oral medication. The seizures ceased for the first 24 h. Two days later the child got sleepy later became comatose, started to vomit, and the seizures reappeared. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Their duration, severity, and number increased. Laboratory investigations revealed hyperammonemia 211 lmol/l without any signs of hepatotoxicity. Results: Valproate was immediately stopped and 2 doses of carglumic acid (100 mg/kg per day) were administered. The seizures ceased, a rapid improvement in his mental state occurred and the serum ammonia level returned to the normal range within 24 h. Conclusion: In the management of valproate induced hyperammonemic encephalopathy discontinuation of valproate treatment is mandatory. A new therapeutic option is administering carglumic acid. To our experience, which is similar to others, it normalises serum ammonia level within 24 h.

P627 TIME-TO-SEIZURE MODELING OF LACOSAMIDE MONOTHERAPY - IMPACT OF DISEASE SEVERITY AND OTHER COVARIATES ON DROPOUTS AND SEIZURE PROBABILITY Stockis A1, Laveille C2, Lindauer A2 1 UCB Pharma, Braine-l’Alleud, Belgium, 2SGS Exprimo NV, Mechelen, Belgium Purpose: To quantify the relationship between exposure to lacosamide and seizure probability, and to assess the impact of different covariates on dropout risk, and the impact of initial target dose on seizure-freedom. Methods: A structural time-to-event model for dropouts and seizures was developed using data from 883 patients with focal epilepsy participating in a trial (SP0993) comparing lacosamide and carbamazepine controlled-release (CBZ-CR) in initial monotherapy. Trough plasma concentrations of lacosamide were analyzed with a previously developed population pharmacokinetic (PK) model. Final PK and dropout/seizure models for lacosamide were then used for simulations assessing the impact of changing the initial target dose on seizure-freedom. Results: Repeated time-to-seizure data were best described by a Weibull distribution with parameters estimated independently for the first and subsequent seizures. Daily AUC was related linearly to the log-hazard. Disease severity, expressed as the number of seizures during the 3 months before the trial, was a strong predictor of seizure probability patients with 7–50 seizures at baseline had a 2.6-fold (90% CI: 2.01– 3.31) higher risk of seizures compared with the reference 2–6 seizures. Simulations suggested that a 400 mg/day initial target dose for patients with >7 seizures at baseline could potentially result in an additional 8% seizure-free for 6 months at the last evaluated dose compared with initial target doses of 200 mg/day. Hazard ratio of a first seizure for a patient aged 65 compared to 41 years (median) was 0.74 (90% CI: 0.59–0.88). Patients receiving lacosamide had a slightly lower dropout risk compared with those receiving CBZ-CR. Conclusion: Baseline disease severity was the most important predictor of seizure probability. Simulations suggest that an initial target dose >200 mg/day could potentially benefit patients with greater disease severity. Clinical data are needed to confirm these simulation findings. UCB-sponsored.

191 Abstracts P628 THERAPEUTIC DRUG MONITORING OF ANTIEPILEPTIC DRUGS AND THE CORRELATION WITH SEIZURE CONTROL Tuntapakul S1, Lertsinudom S1, Topark-Ngarm A1, Tiamkao S2 1 Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand, 2 Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Purpose: This study was aimed to determine correlation between seizure control and TDM of antiepileptic drugs (AEDs). Methods: The retrospective-cohort study was performed in outpatients who were attending the Epilepsy Clinic at Srinagarind Hospital, Khon Kaen University in 2011. The patients who were aged 15 or over, had enrolled in the Epilepsy Clinic for a minimum of 3 months and been treated with at least one AED were included into the study. The follow-up time was 1 year. Data on seizure control and TDM was collected from chart reviews and an electronic database. Data analysis was performed by using Generalized Estimating Equation (GEE) in STATA SE program Version 11.1. Results: A total of 382 patients attending 2,369 visits were included. The mean age was 40.4 0.8 years. There were 7.81% (185 visits from 2,369 visits) of patients who received TDM service. The indication of TDM requests were suspected sub-therapeutic level 79 times (41.80%), routine follow-up 75 times (39.68%), suspected toxicity 34 times (17.99%) and confirming drug level 1 time (0.53%). Plasma Drug Concentrations appeared to be within therapeutic level 134 times (50.19%), sub-therapeutic level 69 times (25.84%), and over therapeutic level 64 times (23.97%). TDM requests was found to be significantly increasing in patients with uncontrolled seizure (OR = 2.45; 95% CI = 1.92–3.13). Conclusion: TDM is the necessary approach in helping multi-disciplinary team to manage use of medications appropriately.

P629 EFFICACY AND TOLERABILITY OF PERAMPANEL IN ADOLESCENT PATIENTS WITH GENERALIZED SEIZURE TYPES: A POOLED ANALYSIS OF SIX RANDOMIZED STUDIES Pi~ na-Garza JE1, Rosenfeld W2, Saeki K3, Villanueva V4, Yoshinaga H5, Bibbiani F6, Yang H7, Patten A8, Williams B6, Laurenza A6 1 The Children’s Hospital at TriStar Centennial, Nashville, TN, United States, 2Comprehensive Epilepsy Center for Children and Adults, St Louis, MO, United States, 3Eisai Co, Ltd, Bunkyoku Tokyo, Japan, 4Hospital Universitario y Politecnico La Fe, Valencia, Spain, 5Okayama University Graduate School of Medicine, Okayama, Japan, 6Eisai Inc, Woodcliff Lake, NJ, United States, 7Formerly, Eisai Inc, Woodcliff Lake, NJ, United States, 8Eisai Ltd, Hatfield, United Kingdom

the six studies (Titration, 4–6 weeks; Maintenance, 13 weeks). Efficacy was assessed in the full analysis set (placebo, n = 46; perampanel, n = 67): median percent change in SG/PGTC seizure frequency per 28 days (Baseline vs. Double-blind Phase); percentage of patients achieving 50% or 75% reduction in SG/PGTC seizure frequency (Baseline vs. Maintenance); and percentage of patients who were study completers and free from SG/PGTC seizures (Maintenance). Adverse events (AEs) were assessed in the safety analysis set (placebo, n = 47; perampanel, n = 68). Results: Compared with placebo, perampanel 8 mg/day improved SG/ PGTC seizure control (median percent change in frequency: 25.5% vs. 75.2%; 50% responder rate: 28.3% vs. 67.2%; 75% responder rate: 19.6% vs. 53.7%; seizure freedom: 8.7% vs. 37.3%). Efficacy outcomes were broadly consistent with those in adults. AEs affected 66.0% of placebo-treated and 76.5% of perampanel-treated adolescents. With perampanel, the most common AEs were dizziness (placebo, 6.4%; perampanel, 19.1%) and headache (placebo, 12.8%; perampanel, 14.7%). The most common psychiatric/behavioral AEs were aggression (placebo, 2.1%; perampanel, 8.8%) and irritability (placebo, 0.0%; perampanel 8.8%). Conclusion: Adjunctive perampanel improved SG/PGTC seizure control in this adolescent population, with outcomes similar to those in adults.

Prognosis/Epidemiology 1 Monday 12th September P630 EPIDEMIOLOGY OF FOCAL AND GENERALIZED ONSET SEIZURES IN ALGERIA Abdellaoui W1, Bahbouh S1, Belabed MR1, Bensemane D2, Sadibelouiz M2, Attal E2, Ait-Kaci-Ahmed M1 1 EEG Laboratory, Department of Neurology, Ait Idir Hospital, Algiers, Algeria, 2Department of Neurology, Ait Idir Hospital, Algiers, Algeria Purpose: To estimate the prevalence of focal and generalized onset seizures in adult and peadiatric Algerian population. Method: 782 patients were screening to identify generalized and focal onset seizures. The data collected from medical records between January 2008 and December 2010. Included age of seizure onset, seizure description. The video-EEGs were evaluated for: clinical seizure description, EEG pattern at ictal onset and interictal discharges. Results: 782 patients were identified with Focal onset seizures (500 of 782 patients-63.93%). Temporal Lobe Epilepsy (122 of 500 patients15.60%). Non Temporal Lobe Epilepsy (378 of 500 patients-48.33%). Generalized onset seizures (282 of 782 patients-36.06%). Conclusion: Focal onset seizures are more frequent compared to generalized onset seizures. The identification of the seizure type may help clinicians choose appropriate medications.

Purpose: Perampanel is approved for adjunctive treatment of partialonset seizures (POS), with or without secondarily generalized (SG) seizures, and primary generalized tonic-clonic (PGTC) seizures in epilepsy patients aged ≥12 years. Perampanel efficacy and tolerability was investigated in adolescents across four Phase III studies involving both adolescents and adults with POS (studies 304, 305, 306, 335), or PGTC seizures and idiopathic generalized epilepsy (332), and a Phase II cognition study in adolescents with POS (235). Method: This post hoc pooled analysis included adolescents (12 to 80 years of age were the classes less investigated (28% and 22% respectively). Concerning the study design, randomisation appeared adequate in 78%, but the sample size calculation was appropriate only in 58% of the studies. Source of funding was not reported in 22% while 38% of trials were clearly for profit studies. Conclusion: We identified weaknesses in design, analysis and conflicts of interest in the low percentage of included RCTs, highlighting research that should be better directed. This approach could provide useful information for clinicians, with the opportunity of a new framework for the production, reporting and critical appraisal of research. These preliminary results give a first indication of how valuable resources are wasted.

P632 CLINICAL AND ETIOLOGICAL PROFILES OF ADULT PATIENTS WITH SYMPTOMATIC EPILEPSY IN BISHKEK Jusupova A Kyrgyz State Medical Academy, Neurology and Medical Genetics, Bishkek, Kyrgyzstan

deficits. The most common identified etiological factors were trauma 73 (39.7%), perinatal incidents - 23 (12.5%), CNS infections - 12 (6.5%), stroke - 33 (17.9%), aneurisms/AVM - 13 (7.1%), brain tumors - 25 (13.6%), metabolic conditions - 5 (2.7%). Status epilepticus was detected in 25 patients. The seizure types were mostly generalized tonic clonic seizures – 131 (71.2%), complex partial seizures - 9 (4.9%), secondary generalized seizures - 13 (7.1%), and simple partial seizures - 31 (16.8%). EEG revealed pathological focal patterns in 47 patients, generalized – 45 patients. Conclusion: The distinction between remote symptomatic epilepsies and seizures provoked by acute symptomatic cause sometimes can be difficult due to multifactorial nature of epilepsy. One of the emergency measures to distinguish the underlying cause and consequences could be EEG available 24 h. We would like to draw attention to this nature of symptomatic epilepsies.

P634 COMPARISON OF PATIENTS WITH STATUS EPILEPTICUS OR EPILEPTIC SEIZURE ADMITTED TO THE EMERGENCY ROOM Reinecke S, Holtkamp M, Kowski A Neurology, Charite - Universit€ atsmedizin Berlin, Berlin, Germany Purpose: Status epilepticus (SE), a symptom of a large variety of disorders, is a common neurologic entity admitted to the emergency room (ER). This retrospective study aims to assess frequency of patients admitted with SE in all epileptic seizure (ES) cases and, its acute management in the ER, and to identify differences between patients with SE and ES. Method: We reviewed all patients ≥18 years admitted in 2014 to the ER of our academic hospital with certain diagnoses of SE or ES. Information on demographics and seizure characteristics, diagnostic procedures and treatment originated from our in-house database. SE was defined as clinical seizure lasting longer than 5 min. Variables of SE and ES patients were compared by univariate analysis. Results: 779 patients (36% female; age 50 19 years) were included. Based on history, 84 patients (44% female) had SE and 695 ES (35% female). 54% had persistent SE when arriving in ER. About half had generalized tonic-clonic SE, 32% complex partial and 19% simple partial SE. Compared to ES patients, those with SE were significantly older (63 20 years vs. 49 19 years, p ≤ 0.001, Mann-Whitney-U). Denovo manifestation was significantly more common in SE compared to ES (43% vs. 31%, p = 0.023, Chi-square). Cerebral imaging within 24 h was performed in 81% with SE (66% with ES) with a proof of acute pathology in 10% and remote pathologies in 85% of SE patients (ES, 10% acute, not significant, and 39% remote, p ≤ 0.001, Chi-square). Anticonvulsants were administered to 61% of patients with SE pre-hospital and in 74% in ER (ES, 13% pre-hospital; 37% in ER, each p ≤ 0.001, Chi-square). Conclusion: Older age and de-novo manifestation seem to be associated with SE, while remote brain pathologies are seen more often in SE. Due to impending acute and long-term complications, pre-hospital and ER management is more rigorous in SE.

Purpose: The purpose of the study was to evaluate the etiological factors and clinicoelektroencephalographic features of patients with symptomatic epilepsy. Method: A prospective analysis was performed to 184 patients with symptomatic epilepsy attending neurology department of City Hospital #6, between January and December 2015. Results: Mean age of 77F: 107M patients were (16–79 years). Age at seizure onset was between the first year of life and 79 years. Neurological examination was unremarkable in 56% cases, 9% patients had mental retardation, 21% - had motor deficits, and the rest had other neurological Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P635 COMORBIDITY OF EPILEPSY Stefanova I, Kolev P, Kuzmanova R Multiprofile Hospital for Active Treatment in Neurology and Psychiatry ‘St. Naum’, Sofia, Bulgaria Purpose: Comorbidity refers to the coexistence of two or more diseases in the same person. Epilepsy and the comorbid disorders can occur and

193 Abstracts exist without causality or interconnection between them. The aim of the research is to determine the type and number of the most common comorbidities among patients with epilepsy, the chronology of their arisal, and thus to estimate the course of epilepsy when comorbid with other diseases. Method: Our research is clinical and epidemiological, retrospective, and covers patients with epilepsy for a period of 10 years. The methods used are a documentary analysis, clinical, laboratory, instrumental, and statistical methods. Results: The results show that more than one third (49.2%) of the examined patients with epilepsy have comorbid diseases and the treatment of the epileptic disorder among patients with comorbid diseases most often includes one or two antiepileptic drugs. In the patients with epilepsy and somatic and/or neurological comorbidity, the partial and secondary generalized tonic-clonic seizures are most frequent. More than one comorbid disease was found among people over 60 years of age and the frequency of somatic comorbiduty increases with age, in contrast to the neurological and phychiatric commorbidity. Neurological disorders (71.2%) are the most common among patients with epilepsy, followed by somatic (58.3%) and psychiatric diseases (15.6%). There is a higher risk of complications and increase of the frequency of epileptic seizures among patients with epilepsy and diabetes. Not well compensated diabetes is a factor for aggravation of the epileptic disease. Conclusion: In conclusion, the most common coexistent diseases in epilepsy have been studied for the first time in Bulgaria and a number of important conclusions which were reached help the adequate therapeutical approach among patients with epilepsy and comorbid disorders.

P636 EPIDEMIOLOGY OF SEIZURES IN CHILDREN WITH NEUROINFECTIONS Surovtseva A, Gorelik E, Skripchenko N Research Institute of Children’s Infections, Saint Petersburg, Russian Federation Purpose: explore the epidemiology of seizures at neuroinfections. Method: The study involved 1,328 patients with seizures arising in the background of an acute infectious disease. All patients performed a neurological monitoring, EEG, MRI, etiological examination of blood and cerebrospinal fluid. Results: The structure of infectious diseases in children with seizures: 79% of febrile seizures, 10% of viral encephalitis, 6% - bacterial meningitis, 3% of the debut of epilepsy. Among the viral encephalitis occurs most frequently herpes encephalitis and tick-borne encephalitis. When herpes encephalitis generalized seizures were more common in children under 2 years of age (68%), and focal seizures in 64% of children older than 2 years, in the period of convalescence symptomatic epilepsy developed in 72–82% of cases. The development of symptomatic epilepsy in the period of convalescence focal forms of tick-borne encephalitis was detected in 46–78% of patients. When analyzing the outcomes of bacterial meningitis - symptomatic epilepsy developed in 5% of children, most often 3–5 times the children had undergone pneumococcal meningitis etiology in contrast to patients with Hib and meningococcal meningitis. In the analysis of the effectiveness of therapy in symptomatic epilepsy neuroinfections outcome in children found that 78% of the seizures were stopped using a single drug, and the most effective drug was valproic acid. Combination therapy was used in 22% of children, most often it was the combination of valproic acid and phenobarbital, topiramate or levetiracetam.

encephalitis, as well as bacterial meningitis pneumococcal etiology. When treating convulsions arrest one drug fails to 78% of cases. In the treatment of combined therapy achieved remission in 14% and 8% in drug-resistant patients.

P637 A COMPARISON FROM MEXICO AND CANADA OF WAITING TIMES FOR ASSESSMENT AND EPILEPSY SURGERY Tellez-Zenteno J1, Funes B1, Moreno J2, BribiescaContreras E2, Martınez-Bustos V2, Zertuche-Ortu~ no L2, 2 1 Hern andez-Vanegas L , Hernandez-Ronquillo L , Wu A3, Mario A4, Martınez-Ju arez I2 1 Saskatchewan Epilepsy Program, Medicine, Saskatoon, SK, Canada, 2National Institute of Neurology and Neurosurgery, Epilepsy, Mexico City, Mexico, 3Saskatchewan Epilepsy Program, Surgery, Saskatoon, SK, Canada, 4National Institute of Neurology and Neurosurgery, Surgery, Mexico City, Mexico Purpose: To determine the waiting times for assessment in an epilepsy center and for epilepsy surgery. Method: We compare the waiting times from the diagnosis of epilepsy till the assessment in an epilepsy center and epilepsy surgery in two referral centers from Mexico and Canada. Both centers have adequate equipment and manpower to provide epilepsy surgery. Results: Waiting times for assessment and epilepsy surgery of 76 cases from the Epilepsy Program of the National Institute of Neurology and Neurosurgery (NINN) in Mexico City and 70 cases from the Epilepsy program of the province of Saskatchewan (SEP), Canada were compared. Patients where assessed in the same period of time (between 2007 and 2015). Mean age of patients at the NINN was 37.4 9 years versus 42.2 13 in the SEP. The times from the diagnosis to the referral to the NINN was 20 and 16 years at the SEP (p 0.27), to the first consult with the epileptologist 237 versus 208 months (p < .001), to the neuropsychology consult 257 versus 201 months (p 0.027), to the video-EEG telemetry 256 versus 219 months (p 0.09), to the first consult to neurosurgery 262 versus 227 months (p 0.29) and finally to the epilepsy surgery was 280 versus 238 months (p 0.29). Conclusion: It has been showed in some studies that the average delay from onset of seizures to surgical procedures is 20 years among adults and 10 years among children, although the reports come mainly from developed countries. This the first study comparing waiting times between two countries with different economical characteristics. Our study shows similar waiting times in both centers suggesting a global problem in the reference of patients to epilepsy programs.

Conclusion: Symptomatic epilepsy in the outcome neuroinfections most often occurs in children undergoing herpes encephalitis or tick-borne Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

194 Abstracts

Prognosis/Epidemiology 2 Tuesday 13th September P638 EXPERIENCE WITH FIRST EPISODE OF CONSCIOUSNESS LOSS ASSESSMENT IN A REGIONAL CENTER OF ROMANIA Cuciureanu DI1,2, Nita A3, Cuciureanu A4, Cuciureanu T5, Moisei Constantinescu I1,2 1 University of Medicine ‘Gr. T. Popa’ Iasi, Neurology, IASI, Romania, 2Emergency Hospital ‘Prof. Dr. N Oblu’ Iasi, Neurology, IASI, Romania, 3University of Medicine ‘Gr. T. Popa’ Iasi, IASI, Romania, 4CMI Neurology, IASI, Romania, 5 University of Medicine ‘Gr. T. Popa’ Iasi, Gastroenterology, IASI, Romania Purpose: The high prevalence of patients admitted to the emergency departments with a first episode of consciousness loss is well established. Although there are studies assessing acute management in patients experiencing consciousness loss, there is still need for more data on clinical and paraclinical characteristics of these patients, especially in countries where unified standards for medical procedures are lacking and access to specific medical care is still limited. The aim of the present work was to review demographic, clinical and paraclinical defining features in adult patients presenting a first episode of consciousness loss and referred to our emergency hospital - a reference center in the Northern-Eastern part of Romania. Method: We performed a retrospective observational study over 12 months, between January 2015 and January 2016, including adult patients addressed for investigation of a first non-syncopal episode of consciousness loss in the neurology department. Results: We included 110 patients (mean age 46.5, SD 15.5, 70 female patients). Epilepsy diagnosis was affirmative in 36% of patients, based on electro-clinical and imagery findings. Initial standard EEG monitoring showed epileptiform abnormalities in only 20% of patients. No co-morbidities were found in 53.44% of patients. Cerebral malformations were found in 7% of patients, while endocrine disorders and psychiatric disturbances were highlighted in an equal proportion (8.62%) of investigated patients. Conclusion: Our data strengthens the need for multidisciplinary protocols at regional level, in order to foster prompt management of a common and often overlooked complaint in the emergency departments. Specific medical procedures, such as sleep EEG monitoring should be more accessible in regional centers, pertaining improved accuracy of evaluation in unclear cases.

P639 EVALUATION OF CLINICAL FEATURES OF PATIENTS WITH OCCIPITAL LOBE EPILEPSY, RETROSPECTIVELY Turk BG1, Akbaba G2, Delil S1, Icellioglu S3, Yeni N1 1 Istanbul Uni/Cerrahpasa Medical Faculty, Neurology, Istanbul, Turkey, 2Istanbul Uni/Cerrahpasa Medical Faculty, Psychiatry, Istanbul, Turkey, 3Istanbul Kultur Universitesi, Istanbul, Turkey Purpose: Occipital lobe epilepsy is not frequent among focal epilepsies. It may be under diagnosed. We report the features of 38 patients with occipital lobe epilepsy (OLE) evaluated in an outpatient clinic retrospectively. Method: We retrospectively evaluated 38 patients with OLE among 2,000 epilepsy patients. Patients were diagnosed as OLE if there is a Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

typical semiology indicating an occipital onset such as visual auras and/ or if there is an EEG (interictal and/or ictal) abnormality pointing occipital electrodes and/or if there is a structural lesion limited to occipital lobes on neuroimaging. We assessed the gender and the age of the patients, onset age of seizures, physical examination, etiology, epileptic auras, etiology. Results: Thirty eight patients with OLE (17 female, 21 male with a mean age 28 at last visit were evaluated. The mean age at onset of seizures was 12 years (1–32 years). Neurologic examination revealed horisontal nystagmus in six of them, visual field defect in two of them and mental retardation in five. From the etiologic point of view; 18 had a structural lesions, 15 were unknown etiology, two were genetically determined and three were uncertain with the available data. Twenty one patients described auras preceding seizures including flashes, blurred vision and visual loss. On the other hand 4 of them had nausea. The frequency of the seizures of the 38 patients with anti-epileptic drug treatment: 5 of them had 1–3 seizures in a week, 13 of them had 1–3 seizures in a month and 20 of them had 1–3 seizures in a year. Conclusion: Occipital lobe epilepsy is probably under-recognized. Visual hallucinations are the key clinical symptoms indicating an occipital focus, but only 50% of patients approximately describe auras. Since the occipital lobe epilepsy is a challenging condition to diagnose and there is no common characteristics of the OLE we want to share the features of our patients.

P640 SECULAR TRENDS IN THE INCIDENCE OF EPILEPSY IN THE PROVINCE OF SASKATCHEWAN, CANADA (2001–2010) Hernandez Ronquillo L1, Thorpe L2, Pahwa P2, Tellez Zenteno JF1 1 University of Saskatchewan, Neurology, Saskatoon, SK, Canada, 2University of Saskatchewan, Community Health and Epidemiology, Saskatoon, SK, Canada Purpose: To measure secular trends in the incidence of epilepsy between 2001 and 2010 in the province of Saskatchewan, Canada. Method: A population-based retrospective cohort was created from an administrative database linked by a unique health services number. This cohort included individuals with the first identification of epilepsy from January 01, 2001 to December 31, 2010, based on case definition of epilepsy met with any one of two administrative health databases (Hospital separation data and Physician’s service data). The case definition was fulfilled if the subject had, at least, one hospital separation with a diagnosis of epilepsy (ICD-9 345 or ICD-10-Ca G40) during the 10 years period or had two physician visits within 730 days before or within the 10-year period of the study. Results: A total of 7,930 incident cases of epilepsy were identified during 2001/2010. The incidence rate between 2001 and 2005 range from 78.27 to 109.14 per 100,000 people but between 2006 and 2010 they range from 43 to 61.84 per 100,000 people. The incidence of epilepsy was higher in elderly, but not in early life. Also was higher in Registered Indian, and slightly more frequent in males than in females. No differences were found between rural and urban areas. Conclusion: This is the first Canadian study of the incidence of epilepsy involving the entire age spectrum. We did not find a classical U shape incidence curve as it has been found in other developed countries, finding only a high incidence in the elderly population. Our new finding are foundational for public awareness and policy recommendations, health promotion and prevention strategies, appropriate health resource planning, and research priorities.

195 Abstracts P641 FIRST EPILEPTIC SEIZURE: INCIDENCE AND MANAGEMENT OF PAROXYSMAL EPISODES IN LJUBLJANA EMERGENCY UNIT FOR NEUROLOGY Pipan E1, Kostadinova V1, Lorber B2, Granda G2 1 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia, 2Department of Neurology, University Medical Center Ljubljana, Ljubljana, Slovenia Purpose: First seizure is a very common clinical entity: approximately 5% of population will have at least one seizure during their lifetime. The diagnosis is clinical so the rate of misdiagnosis can be high. The aim of this study was to assess the incidence and epidemiological data of first epileptic seizure in the catchment area of Ljubljana Emergency Unit for Neurology (EUN) - approximately 1,000,000 people. Method: We retrospectively collected data of all patients that presented to EUN in 1 year (2014), with acute paroxysmal events that were or could mimic epileptic seizures. The inclusion criterion was the referral diagnosis and we included all referrals that could represent a possible epileptic seizure, among others: epilepsy, epileptic seizure, unspecified impairment of consciousness, transient ischemic attack (TIA), syncope, and transient global amnesia. Results: The number of all admissions to EUN was 9,693 and 2,614 were included in the study. For 141 there was insufficient data and were excluded from analysis. 39.5% (1,032 patients) had a diagnosis of epilepsy and that accounts for 10.6% of all yearly referrals to EUN. Probable first epileptic seizure was the cause for 16.7% (414 cases out of 2,473) of admissions and second epileptic seizure for 5.4% (134 cases). Out of those 414 patients with probable first seizure 21.0% (87 patients) were referred to EUN with referral diagnosis other than epileptic seizure, most commonly as TIA or syncope. We also performed further analysis of aetiology, semiology and epidemiological data of first seizures in our sample. Conclusion: EUN is our biggest neurology emergency centre and it covers roughly half of the population of Slovenia. The results of this study thus represent an important insight in epidemiology of first epileptic seizure in Slovenia and will help in planning better epilepsy care in our country.

P642 INJURIES AND ACCIDENTS IN EPILEPSY: A PROSPECTIVE, POPULATION-BASED COHORT STUDY ON INCIDENT CASES Mahler B1,2, Carlsson S3, Andersson T3,4, Tomson T1,2 1 Karolinska University Hospital, Stockholm, Sweden, 2 Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, 3Epidemiology Unit, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, 4Center for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden Purpose: To study the risk of injuries or accidents for people with epilepsy (PWE). Method: Between September 1st 2001 and August 31st 2008, all patients in northern Stockholm with incident unprovoked seizures (n = 2,343) were included in the Stockholm Incidence Register on Epilepsy (SIRE). For every exposed (patient with incident seizure), eight unexposed controls were matched for sex, inclusion year and catchment area (n = 18,672). Patients and controls were followed until December 31st, 2014 in the Swedish Outpatient Register, the Swedish Hospital Discharge Register and the Cause of Death Register for information on accidents and injuries based on ICD codes (in total 13,883 person years in exposed).

Results: There were 1,001 registrations for injuries and accidents among exposed and 6,111 among controls, with an increased risk among exposed cases (Hazard Ratio, HR = 1.60, 95% CI = 1.49–1.71). The risk was increased among women (1,061 exposed, HR = 1.70 95% CI = 1.55–1.91) and men (1,282, HR = 1.52, 95% CI = 1.39–1.67). While the relative risk was not elevated among 713 patients 5 years whereas 19 had persistent seizures. The EEGs were retrospectively categorized into four main groups; normal, slowing, epileptiform discharges or both slowing and epileptiform discharges, with further subclassification. Hyperventilation and photoparoxysmal responses were also evaluated. The scoring of EEG was blinded to outcome. Results: Prolonged >3 s fast (4–5c/s) spike-wave runs was more frequent in patients with persistent seizures compared to the seizure-free group (9/19 (47%) vs. 3/21 (14%); p = 0.04). Significant associations were also found between poor seizure control and photoparoxysmal (n = 6/19 vs. 1/21; p = 0.04,) and hyperventilation-induced epileptiform runs (5/19 vs. 0/21; p = 0.04). Other epileptiform features (polyspikewaves, spikes, spike-waves, brief photoparoxysmal and hyperventilation-induced discharges) occurred equally in the two prognostic groups. Conclusion: Prolonged (>3 s) fast spikes, photoparoxysmal and epileptiform hyperventilation-induced runs were associated with persistent seizures in JME. Focal EEG abnormalities were not associated with clinical outcome. These results from our blinded retrospective study suggest that a lack of intracortical inhibition, not interictal epileptiform activation per se, is the essential feature that predicts recurring seizures in AED-treated JME patients.

P648 CLINICAL EXPERIENCES IN PSYCHOGENETIC NONEPILEPTIC SEIZURES BETWEEN 2003 AND 2016 XPLAINING THE DIAGNOSIS IS THE FIRST AND MOST IMPORTANT STEP OF THE TREATMENT IN CLINICAL PRACTICE, AND CAREFUL PATIENTDOCTOR COMMUNICATION HAS A CERTAIN POSITIVE IMPACT ON PATIENTS’ SEIZURE PROGNOSIS Bican Demir A, Bora I, Sarıdas F Uludag University Medical Faculty, Bursa, Turkey

Results: The mean length of stay in VEM was 4 days. 30% of the patients we taking antidepresants while 72% were taking antiepileptic drugs prior to VEM. Of the 274 patients, 68% were women and 32% were men with a mean age of 39. 9 patients were observed PNES-status. Provocation with intravenous saline were applied to 61/274 (22%) patients, and 90% of them were observed to give a pozitive response to treatment. Conclusion: It is stated that the period between the first seizure and diagnosis is 7.2 years on average though several clues have been identified to distinguish PNES from real epileptic seizures. This delay in the diagnosis causes patients to be exposed to unnecessary antiepileptic treatment over a long period of time as well as a number of social and financial problems in addition to the delay in the treatment of the real illness.

P649 THE SURGERY FOR DRUG-RESISTANT EPILEPSY AND QUALITY OF LIFE Dolezalova I1, Sklenarova B2, Kocvarov a J1, Pail M1, 1,3 1,3 Rekotr I , Brazdil M 1 Brno Epilepsy Center, Medical Faculty of Masaryk University and St. Anne’s University Hospital, Brno, Czech Republic, 2 Medical Faculty of Masaryk University, Brno, Czech Republic, 3 Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic Purpose: The main aim of our study was to determine the change in quality of life in patients who underwent respective surgery for drugresistant epilepsy. Methods: The quality of life was determined by Quality of Life in Epilepsy Inventory-89 (QOLIE-89) questionnaire before surgery and 1 year after surgery. We included the total number of 95 patients - 79 (89%) patients with temporal lobe epilepsy and 16 (17%) patients with extra temporal lobe epilepsy. The seizure freedom rate in year 1 after surgery was 69 (67%), the seizures persisted in the rest 31 (33%) patients. Results: When the questionnaires were evaluated, the improvement of global quality of life measured by total score of QOLIE-89 was found (p = 0.008). When evaluated individual subcategories of QUALIE-89, the improvement was present in followings: Health perception (p < 0.001); Overall Quality of Life (p = 0.001); Work, driving and social functioning (p < 0.001); Health discouragement (p = 0.049); Seizure worry (p < 0.001); Medication effect (p < 0.002) and Change in Health (p < 0.001). We did not managed to identified clinical variables which would be associated with improvement of total score of QOLIE-89 when analyzing following clinical variables: age at epilepsy onset, duration of epilepsy, age at surgery, type of epilepsy, seizurefreedom, psychiatric and somatic co-morbidities, and intellectual functions. Conclusion: There is improvement of global quality of life after surgery measured by total score of QOLIE-89 at year 1 after surgery when compared to patients’ pre-surgical data.

Purpose: Psychogenetic nonepileptic seizures (PNES) constitute the majority of the cases in epilepsy centers. Long term video-EEG monitoring is still considered as a gold standard for the detection of PNES. Besides clinical tests, psyhiatric assessment, laboratory examinations and provocative tests are also helpful for diagnosis. Method: Provocation tests, including long term VEM, neuropsychometric test, psychiatric consultation, serum prolaction levels and regular saline injection have been conducted. In this study, 912 seizures of 274 patients who were diagnosed with PNES after having been observed with long term video-EEG monitoring unit in the Neurology Department of Uludag University, the Faculty of Medicine between January, 2003 and January, 2016 were analyzed retrospectively.


198 Abstracts P650 THE RESULTS OF THE COMPARISON OF STATISTICAL DATA ON EPILEPSY IN UKRAINE, OBTAINED IN DIFFERENT WAYS Dubenko A1, Sazonov S2, Suhonosova O3, Sergienko O2, Litovchenko T4 1 SI ‘INPN NAMS of Ukraine’, Kharkiv, Ukraine, 2SI ‘INPN NAMS of Ukraine’, Scientific Organisation of Neurologic, Psychiatric and Narcologic Aid, Kharkiv, Ukraine, 3Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine, 4 Kharkiv Medical Academy of Postgraduate Education, Chair of Neurology, Kharkiv, Ukraine The profiles of obtained information were very different. The official statistics of the Ministry of Health of Ukraine concern mainly epidemiological, geographical and socio-demographical aspects, disability and mortality. The advantages of official medical statistics are high verity and coverage, because every registered case is considered. Particular properties of electronic register are: bigger differentiation of case’s clinical peculiarities (epilepsy’s form, seizures type, frequency), genesis of disease, history of the case and treatment; the data of EEG and MRI examination; psychiatric aspects etc. Of course, these data are collected in addition to the stated above (with exact age, educational level, employed or disabled status, observation status). For this moment 820 epilepsy cases are fixed in Kharkiv region by the register as opposed to 1,389 patients, recorded by medical institutions of MOH. This fact points that the project is just at the beginning of its development. The comparison of these data with the prevalence of epilepsy in the world (0.7%) shows that the significant part of cases in Ukraine is not registered. The prevalence of epilepsy among children is almost twice bigger than among adults that cannot be only explained by existing of benign “child” form of epilepsy. The epilepsy takes the first place among the reasons of children’s disability (invalidity) in Ukraine – 15.4% of all cases. Also in different regions of Ukraine the epilepsy prevalence is very different that can only be explained by subjective factor.

P652 DIFFERENCES IN LONG-TERM OUTCOMES IN PATIENTS WITH FOCAL CORTICAL DYSPLASIA TYPE IIB WITH AND WITHOUT SOMATIC MTOR MUTATIONS Komatsubara T1, Magara S1, Kobayashi Y1, Okazaki K1, Kato M2, Shirozu H3, Masuda H3, Nakashima M4, Saitsu H4,5, Matsumoto N4, Kakita A6, Fukuda M3, Tohyama J1 1 Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan, 2Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan, 3 Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Japan, 4Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan, 5Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan, 6 Department of Pathology, University of Niigata/Brain Research Institute, Niigata, Japan Purpose: Recent research suggests that somatic MTOR mutations in the developing brain may be a major genetic cause of focal cortical dysplasia (FCD) type IIb. This study aims to investigate long-term outcomes following surgical resection in patients with FCD type IIb, comparing those with and without somatic MTOR mutations. Methods: We recruited 13 patients with FCD type IIb (diagnosed according to new guidelines from the International League Against Epilepsy), who underwent surgical resection in Nishi-Niigata Chuo National Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

Hospital between 1996 and 2013. Patients’ tissue specimens underwent genetic analysis. Six had somatic MTOR mutations and seven did not have MTOR mutations. Retrospectively, we evaluated patients’ clinical history, seizures, electroencephalography and neuroimaging assessments, neuropsychological tests and post-surgical outcomes (classified according to Engel’s schema). The mean follow-up period after surgery was 7.9 years (range 3–20 years). Results: Mean age at epilepsy onset was 4.5 years (range 0–13 years), mean duration of follow-up was 10.2 years (range 3–20 years), and mean age at epilepsy surgery was 17.2 years (range 3–58 years). One year after surgery, 12 patients (92%) were seizure free (Engel Class I outcome), but 10 patients (77%) remained seizure free at last follow-up time. In the six patients with somatic MTOR mutations, five (83%) were seizure free at 1 year, but seizures recurred after this in additional two patients. In contrast, seven patients without the MTOR mutation remained seizure free at final follow-up. Conclusion: Long-term seizure outcomes in patients with somatic MTOR mutations are not as good as expected. This may be due to not only the location and size of FCD, but also its pathogenesis. Establishing pathogenesis-specific therapies could reduce seizures for patients with FCD.

P653 MORTALITY IN A COHORT OF 831 PATIENTS AFTER NONINVASIVE VIDEO-EEG TELEMETRY Sokic D1,2, Bascarevic V2,3, Ristic A1,2, Parojcic A1, Vojvodic N1,2, Brajkovic L4, Djukic T1, Damjanovic D5 1 Department of Epileptology, Clinic of Neurology, Clinical Centre of Serbia, Belgrade, Serbia, 2Department of Neurology, Medical Faculty University of Belgrade, Belgrade, Serbia, 3 Clinic of Neurosurgery, Clinical Centre of Serbia, Belgrade, Serbia, 4Department for Nuclear Medicine in Neurology, Center for Nuclear Medicine, Clinical Centre of Serbia, Belgrade, Serbia, 5Department for Neuroradiology, Center for MRI, Clinical Centre of Serbia, Belgrade, Serbia Purpose: To determine the mortality in patients subjected to noninvasive video-EEG telemetry (VEEGT). Method: During the period of 6 years (between 01.01.2010. and 31.12.2015) we subjected 831 patients to noninvasive VEEG. VEEGT lasted 5 days in 747, 10 days in 71, 15 days in 11 and 25 days in 1 patient. Results for 49 (6%) patients were not analyzed. In 159 (19%) patients no seizures were recorded although diagnosis of epilepsy was confirmed. In 49 (6%) patients the diagnosis of generalized, and in 243 (29%) the diagnosis of focal epileptic syndromes (with no defined epileptogenic zone) were established. In 108 (13%) patients only nonepileptic seizures were recorded. We selected 85 (10%) patients for epilepsy surgery but this was denied or postponed by patients. Vagal nerve stimulator was implanted in 10 (1%) patients and 5 patients chose to perform epilepsy surgery abroad. Finally, we performed resective epilepsy surgery in 111 (13.5%) patients. Follow-up data were obtained for 789 (95%) subjects between 01.09.2015. and 31.12.2015 from patients, family members, their doctors or nurses. Results: We found that 11 (1.3%) patients died 2 weeks to 4 years after VEEG. The causes of death were: gastric cancer (1), malignant melanoma (1), glioblastoma multiform (1), myocardial infarction (2), suicide (2), SUDEP in patient with MS and epilepsy (1), ill-treated status epilepticicus (SE), sepsis during prolonged SE (1), and traffic accident (1). Suicide was the cause of death in one patient 1.5 year after VNS implantation (significant improvement in seizure control) and in another patient 2 years after epilepsy surgery (seizure free, aggravation of previous psychosis). The average age of deceased patients was 40.2 12.8 (range: 10–84) and of the rest of patients 34.7 12.1 (range: 22–61) years (p = 0.02).

199 Abstracts Conclusion: Mortality after VEEGT occurs rarely and is usually associated with causes not directly related to epilepsy.

P654 THE ROLE OF EPILEPSY SURGERY TREATMENT IN QUALITY OF LIFE OF THE PATIENT WITH REFRACTORY EPILEPSY-EXPERIENCE FROM LOCAL OUTPATIENT CARE Togtokhjargal A, Slonkova J University Hospital Ostrava, Neurology, Ostrava, Czech Republic Purpose: To evaluate quality of life of the patients who underwent epilepsy surgery treatment before and after procedure in 6 months follow up in epileptologist outpatient care. Methods: The Czech 1.0 version of the QOLIE-31 questionnaire has been used as a method of evaluation the quality of life of the patient with refractory epilepsy before and 6 months after epilepsy surgery. Descriptive statistics and a two-tailed p-value less than 0.05 was considered statistically significant. Results: We have prospectivelly used the QOLIE-31 questionnaire Czech version 1.0 before the epilepsy surgery and 6 months after in 17 patients. One patient was excluded from the analysis as he did not come to follow up visit, but remained seizure free after the surgery. We have a group of 16 patients, 7 men, 9 women. Mean age while operation perfomed in men group was 36.25 8.12, median 35 years. Women had mean age in operation procedure 36.33 9.24, median 36 years. Mean QOLIE-31 mean total score before the operation was 39.75 17.89, median 37.75 out of maximum of 100 points. After the operation mean total score value was 81.76 21.38, median 91.10. Difference mean was 42.01 22.27, median 46.56 points. p value < 0.001. 14 patients were seizure free or had sporadic seizure (Engel I.). One patient was only slightly improved due to new independent malignity with seizure reoccurence while on chemotherapy with lowering the AED blood levels due to negative drug interactions. One patient was worse with 3.4 points difference. To this patient with the most poor quality of life outcome after epilepsy surgery (Engel IV) vagal nerve stimulation and ketogenic diet was later administered. Conclusion: We conclude epilepsy surgery as highly effective treatment of refractory epilepsy patients with significant improvement of quality of life.

Status Epilepticus 1 Monday 12th September P655 EMERGENT VAGAL NERVE STIMULATOR IMPLANT DURING PAEDIATRIC REFRACTORY STATUS EPILEPTICUS: REPORT OF THREE CASES Landi A1, Gagliardi E2, Trezza A2, Grioni D1 1 San Gerardo Hospital University of Milan Bicocca, Monza, Italy, 2University of Milan Bicocca, Monza, Italy Purpose: To establish the efficacy of Vagal Nerve Stimulator (VNS) implant during refractory Status Epilepticus (SE). Method: Three paediatric cases implanted during refractory SE. Results: 1 Macrocrania and delay of motor milestones. The child presented with focal seizures at age of 3 months; MRI showed left hemimegalencephaly; seizures became drug resistant till a focal motor refractory SE, requiring admission to ICU; after discharge seizures remained uncontrolled (up to 90 seizures/day) worsening the neurological status

dramatically; VNS started at this time (17 months) switching the device on immediately after surgery. Seizures decreased (4 seizures a day), until the last follow-up (33 months). 2 Delay of motor and psychomotor milestones due to a partial deletion of chromosome 1. Onset of partial seizures at age of 7 months; in the following months the child presented with three episodes of SE, the last one refractory, requiring admission to ICU. After discharge the child presented with drug resistant jerks localized at limbs occurring every 3 min. At this time, we implanted VNS (17 months), switching the device on immediately after surgery. The jerks disappeared at once. At the last follow-up (12 months) the parents reported only sporadic spasms during awake. 3 Born after artificial insemination by sperm and ovule donors. The child developed few weeks after birth focal seizures. The EEG showed migrating epilepsy, possibly genetic, which became severe and intractable in 3 months. The MRI was normal. The child underwent VNS implant at age of 6 months. The stimulation obtained only a transient reduction of the seizures. The child death for intractable SE at age of 8 months. Conclusion: We suggest the indication to a precocious VNS implant in refractory SE at least in some cases. In our experience, VNS stopped structural refractory SE whereas in the genetic case was unsuccessful.

P656 DIAGNOSTIC ACCURACY OF SALZBURG-CRITERIA FOR NONCONVULSIVE STATUS EPILEPTICUS Leitinger M1, Trinka E1, Gardella E2,3, Rohracher A1, Kalss G1, ofler J1, Hess A3, Zimmermann G1, Qerama E3, H€ Kuchukhidze G1,4, Dobesberger J1, Langthaler PB1, Beniczky S2,5 1 Department of Neurology, Paracelsus Medical University, Salzburg, Austria, 2Department of Clinical Neurophysiology, Danish Epilepsy Centre, Dianalund, Denmark, 3Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark, 4Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria, 5Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark Purpose: Several EEG-criteria for nonconvulsive status epilepticus (NCSE) have been proposed, but none of them has been clinically validated yet. We assessed diagnostic accuracy of the EEG-criteria proposed by a panel of experts at the 4th London-Innsbruck-Colloquium on Status Epilepticus in Salzburg, 2013 (Salzburg-criteria for NCSE). Method: We analyzed data from 220 patients recorded in three centers. The clinical validation group consisted of 120 consecutive patients with clinical suspicion of NCSE referred to EEG. Reference standard was the final clinical diagnosis in the medical reports, based on all clinical and para-clinical data. We calculated sensitivity, specificity, positive and negative predictive value, and overall diagnostic accuracy. We also analyzed a group of 100 consecutive recordings with abnormal EEG-findings, but without clinical suspicion of NCSE (controls) to further evaluate the specificity of the criteria. Results: In the clinical validation group, sensitivity was 97.6% and specificity was 88.6% (overall accuracy: 91.7%). PPV was 81.6% and NPV was 98.6%. In the control group, specificity was 97.0%. Therapeutic changes were seen significantly more often in the group of patients fulfilling the Salzburg-criteria (83.7%) as compared to patients who did not (15%) (p < 0.001). Conclusion: Salzburg-criteria for NCSE have high diagnostic accuracy, are useful tool in clinical practice, and can help standardizing further research on NCSE. This is the first clinical validation study of diagnostic criteria for NCSE, and it was done in a multicenter approach.


200 Abstracts

P657 CORRELATION OF INFLAMMATORY CYTOKINES, SYNAPTIC PROTEINS AND GROWTH FACTORS IN THE IMMUNOPATHOGENESIS OF TEMPORAL LOBE EPILEPSY Mehta VK1, Bhatnagar M1, Khamesara R2 1 Mohanlal Sukhadia University, Udaipur, India, 2RNT Medical College and Government Hospital, Udaipur, India Purpose: A growing body of data suggests that hyperactivation of the immune system has been implicated in the pathophysiology of temporal lobe epilepsy (TLE). The pathophysiological mechanisms behind seizures are yet to be untangled. The main objective of this study was to investigate associations between pro-inflammatory cytokines, synaptic proteins and growth factors in patients with TLE. Methods: We measured interleukin (IL)-6, IL-2, interleukin (IL)-1beta, and tumor necrosis factor-alpha (TNF-a) in CSF and serum. We also measured BDNF, GFAP, a-synuclein in CSF from TLE patients (n = 56) and healthy controls (n = 40). Symptoms of fatigue, depression, anxiety and sleeping difficulties were also assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT), the Hospital Anxiety and Depression Scale (HAD), and the Scales for outcome in TLE-Sleep Scale respectively. Results: IL-6, IL-2 and a-synuclein were significantly higher in TLE patients than in healthy controls. TLE patients displayed significantly higher mean scores on HAD and lower scores on FACIT, thus indicating more severe symptoms as measured with these scales, as compared to healthy controls. Within the TLE samples, high levels of both syn-a and TNF-a were significantly associated with more severe symptoms assessed by means of FACIT and HAD (depression and anxiety subscales). SIL-2-R levels were able to significantly predict FACIT and HAD scores after the effects of age, gender, anti-epileptic and seizures were controlled for. Discussion: We suggest that symptoms in TLE patients, such as fatigue and depression might be generated via inflammatory mechanisms. This knowledge might contribute to the development of novel treatment options in TLE, specifically targeting non-seizure symptoms.

P658 ELECTROCLINICAL FEATURES AND OUTCOMES IN NEW ONSET REFRACTORY STATUS EPILEPTICUS WITH CLAUSTRUM DAMAGE Meletti S1,2, d’Orsi G3, Toran L4, Lapenta L5, Specchio N6, Guha R7, Monti G1, Giovannini G1, Vaudano AE1, Pascarella MG3, Martino T3, Slonkova J8 1 Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy, 2AUSL Modena, Neurology, Modena, Italy, 3Riuniti Hospital, Clinic of Nervous System Diseases, University of Foggia, Foggia, Italy, 4 Department of Neurology, University of Virginia, Charlottesville, VA, United States, 5Institute of Neurology, Catholic University, Rome, Italy, 6Division of Neurology, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy, 7 Department of Neurology, University of Virginia, Charlottesville, Italy, 8Clinic of Neurology, University Hospital Ostrava, Ostrava, Czech Republic Purpose: New-onset refractory status epilepticus (NORSE) is a rare but challenging condition, characterized by the occurrence of refractory seizures with no identifiable cause. We recently described a subgroup of Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

NORSE patients with a typical MRI sign characterized by bilateral hyperintense lesions of the claustrum (Neurology 2015;85:1224–32). Here, we characterize the electroclinical findings and outcomes of these cases. Method: Patients fulfilling the following inclusion criteria were investigated: 1 previously healthy adults (>16 years of age) with new-onset SE; 2 MRI evidence of the “claustrum sign”. A PubMed search to identify previously reported cases from 1990 to 2015 was also performed. Results: 9 personal and 19 previous cases fulfilled inclusion criteria, for a total of 28 patients (15 females). Mean age was 25 years. Fever preceded SE in 82% of cases by a mean of 6 days. Headache, malaise, confusion were the presenting symptoms in 75% of cases. SE was considered refractory/super-refractory in 72% of the patients, requiring third lines agents and ICU stays (median of 15 days). Focal motor seizures and tonic-clonic seizures were observed in 85%, complex partial seizures in 18%, and myoclonic seizures in 11% of the cases. Often more than one seizure type was observed in one patient, and with alternating hemispheric origin. MRI showed hyperintense claustri after SE onset (range 3–21 days; mean of 9.5 days post-SE onset). Other limbic (bilateral hippocampus, insula) alterations were observed in 33% of the patients. Extensive search for known auto-antibodies was inconclusive. 10% of the patients died in the acute phase. Of the surviving, 85% developed drug-resistant epilepsy and more than half suffered from behavioral and cognitive deficits. Conclusion: Febrile-illness related SE with claustrum hyperintensity represents a homogeneous condition with defined electro-clinical features. A better characterization of de novo SE is mandatory for the search of specific etiologies.

P659 ENDOGENOUS NEUROSTEROIDS LEVELS ARE DECREASED IN CSF DURING STATUS EPILEPTICUS Monti G1, Lucchi C2, Rustichelli C2, Giovannini G1, Meletti S1, Biagini G2 1 Department of Neuroscience, NOCSE Hospital, AUSL Modena, University of Modena e Reggio Emilia, Modena, Italy, 2 Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy Purpose: Neuroactive steroids, such as allopregnanolone (AP), are positive allosteric modulators of GABAA receptors enhancing both synaptic and extrasynaptic GABAA mediated inhibition and might be effective in the treatment of benzodiazepine-resistant status epilepticus (SE). No data are available on AP levels in central nervous system (CNS) of patients suffering from SE. This lack of information hampers the possibility to correctly design a rational therapeutic approach to SE. We designed a study to evaluate AP in serum and cerebrospinal fluid (CSF) of patients affected by SE. Method: We retrospectively (2007–2015) evaluated blood and CSF samples from 41 adult patients with diagnosis of SE who received lumbar puncture at SE onset (median of 4 days) for clinical purposes and for whom a CNS infection was finally excluded. 41 subjects (matched for age and sex) that had negative results after lumbar puncture for suspected idiopathic intracranial hypertension, CNS infection, or inflammatory disease served as control group. Quantitative analysis of neurosteroids was performed by liquid chromatography-electrospray tandem mass spectrometry. Results: Serum AP levels did not revealed significant differences between controls and SE patients. However, CSF AP levels were decreased by approximately 30% (p < 0.05, Mann-Whitney test) in patients compared with controls. Interestingly, linear regression did not reveal a relationship between serum and CSF levels for AP in controls

201 Abstracts (R2 = 0.06, p = 0.27). On the contrary, a significant relationship (R2 = 0.57, p = 0.003) was present in patients affected by SE. Conclusion: We demonstrated that endogenous allopregnenolone is significantly reduced during SE in CSF. Administration of AP to patients suffering of SE could be useful to reestablish AP level in the CNS. In addition, exogenously administered AP may result to have a privileged access to brain tissue by virtue of the higher permeability of the bloodbrain barrier during SE.

P660 DID NEW DEFINITION OF STATUS EPILEPTICUS HAVE IMPACT ON ITS INCIDENCE IN OLDER PATIENTS WITH ACUTE STROKE? Nikic P1, Grkic I1, Georgievski B2 1 Special Hospital for Cerebrovascular Diseases ‘Sveti Sava’, Belgrade, Serbia, 2Special Hospital for Cerebrovascular Diseases ‘Sveti Sava’, Neuroradiology, Belgrade, Serbia Purpose: Stroke is the most common cause of acute symptomatic seizures, epilepsy and status epilepticus (SE) in the elderly population. Recently new operational definition of SE has been proposed by the International League Against Epilepsy (ILAE). The objective of this study is to investigate the frequency of SE, in older people with acute stroke, comparing the time criteria proposed by new definition of SE with those stated in the older one. Method: We retrospectively studied the occurrence of seizures, within 14 days after acute stroke, in 1,456 consecutive patients, older than 60 years, admitted to our hospital. Those with clinical and electroencephalographic SE were identified and the duration of their seizures analyzed. The time frame for SE was defined as a seizure or series of seizures, without recovery of consciousness, lasting more than 30 or more than 5 min by the old and the new definition retrospectively. Results: Within the group of 146 patients (10%) with post-stroke seizures, thirty-eight patients (26%) developed SEs that lasted more than 30 min compared to forty-four patients (30.5%) that had seizures lasting more than 5 min. There were no statistically significant differences between the number of patients with SE and the type of seizures comparing the old and the new definition of SE. Conclusion: The new time frame for diagnosis of SE has modest impact on incidence of SE. Using the new criteria for SE might facilitate the diagnosis and treatment of SE in the population of older patients with acute post-stroke seizures.

Results: 11/18 patients (6 CPSE, 5 NCSE) showed EEG improvement after about 5 min having started IV-LCM and disappearance of both continuous epileptic activity and clinical picture at the end of infusion. Of these 6/11 (4 with CPSE and 2 with NCSE) had received diazepam 10 mg before iv LCS without clinical and EEG response. None patient showed severe adverse events. At third hour EEG evaluation, only 1/11 patient treated with only IV-LCM showed recurrence of continuous PLEDs and clonic seizure that disappeared after 10 min the start of a further IV-LCS 200 mg. In all 18 patients we performed an EEG 24 h after LCM administration and it resulted normal at all. Conclusion: Tolerability of IV-LCS in any of 18 SE was good. IVLCM resulted effective in 11/18 patients regardless they had been treated with iv diazepam before IV-LCM. To treat patients before 3 h after the SE onset seems to be a favorable risk factor for the clinical efficacy of IV-DZP + IV-LCM (6/11) and IV-LCM alone (5/8) regardless they were CPSE or NCSE. Each patient has been treated in follow up with AED: 6/18 increasing previous dosage, 12/18 with two drugs and second one was lacosamide 100 mg bid. All patients were seizure-free at 6 months.

P662 COMPARISON OF THE EFFECTIVENESS OF FOUR ANTIEPILEPTIC DRUGS IN TREATMENT OF STATUS EPILEPTICUS ACCORDING TO FOUR DIFFERENT EFFICACY CRITERIA Redecker J1, Wittstock M1, Rösche J1,2 1 Department of Neurology, University of Rostock, Rostock, Germany, 2Klinik Lengg, Z€ urich, Switzerland Purpose: We investigate whether different criteria of identification for an antiepileptic drug (AED) with a possible or certain treatment effect influence the results of retrospective case series. Method: We present the data from all treatment episodes of SE at the neurological department of the University of Rostock hospital from January 2010 to June 2013. We compare the results of four different efficacy criteria for the effectiveness of Phenytoin (PHT), Valproate (VPA), Levetiracetame (LEV) and Lacosamide (LCM). Criterium 1 = the last AED administered before SE termination. Criterium 2 = the last drug introduced into the antiepileptic therapy within 72 h before the cease of the SE and without changes in the co-medication. Criterium 3 = the last drug introduced into the antiepileptic therapy or increased in dose within 24 h before termination of the SE without changes in the co-medication. Criterium 4 = the last drug introduced into the antiepileptic therapy within 72 h before the cease of the SE even allowing changes in the comedication.

P661 EFFICACY AND TOLERABILITY OF INTRAVENOUS LACOSAMIDE IN TREATMENT OF STATUS EPILEPTICUS IN ELDERLY EPILEPTIC PATIENTS Paciello N1, Cervellino A1, Sica U2 1 Neurology Unit, San Carlo Hospital, Potenza, Italy, 2Stroke Unit, San Carlo Hospital, Potenza, Italy

Results: 145 treatment episodes in 124 patients (44 male, 77 female, mean age at last episode 68.9 years SD 18) could be analysed. According to criterium 1 LEV was more effective than PHT (p < 0.0007) and VPA (p < 0.02). When considering criterium 3 PHT was less effective than VPA (p < 0.04), LEV (p < 0.002) and LCM (p < 0.02). Concerning single AEDs, VPA was more effective according to criterium 1 and 4 than 2 (p < 0.008; p < 0.05), LEV was most effective if related to criterium 1 (p < 0.0000004–0.05) and more effective in accordance with criterium 3 than 2 (p < 0.002).

Purpose: We describe efficacy and tolerability of intravenous lacosamide (IV-LCS) in treatment of status epilepticus in elderly patients.

Conclusion: Efficacy criteria for the effectiveness of AEDs in the treatment of SE should be standardized.

Method: We administered IV-LCS in 18 consecutive epileptic elderly patients, all treated with oral monortherapy, referred to our epilepsy center because of convulsive partial (10) and non convulsive (8) SE. Each patient performed standard EEG once admitted and along the IV-LCS (200 mg/10–15 min). All patients performed an EEG 3 and 24 h after IV-LCM. 10/18 (6 CPSE and 4 NCSE) patients had received diazepam 10 mg iv (IV-DZP) before lacosamide introduction without any clinical response.


202 Abstracts P663 CRYPTOGENIC FOCAL EPILEPSY PRESENTING AS NEW ONSET REFRACTORY STATUS EPILEPTICUS (NORSE): IMPLICATION OF AUTOIMMUNITY? Spilioti M1, Kiryttopoulos A1, Alexopoulos H2, Notas K1, Karafyles G1, Antoniadi E1, Orologas A1 1 1st Department of Neurology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, 2 Neuroimmunology Unit, Department of Pathophysiology, Medical School, University of Athens, Athens, Greece Purpose: We present the case of a patient with cryptogenic focal epilepsy presenting as new onset refractory status epilepticus (NORSE). Method: The patient was a 19 year old female with no priory history of epilepsy. She developed pyrexia and headache for 3 and 2 days later was admitted to the Neurology department with refractory complex partial status epilepticus. An empirical treatment with acyclovir, antibiotics and antiepileptic drugs was initiated for probable viral encephalitis. Despite the antiepileptic treatment with multiple anticonvulsants, the seizures were refractory and the patient required admission to the intensive care unit and administration of general anesthesia. Results: MR imaging, CSF examination and serological tests for viral, autoimmune and paraneoplastic etiologies were normal. The neuralspecific autoantibodies for autoimmune encephalitis in serum and CSF (VGKC, NMDAR, LGI1, CASPR2, GABAb1R, AMPA1R, AMPA2R, GAD) were negative. During her hospitalization in the intensive care unit she received steroids IV. After extubation the patient’s partial seizures resumed and a trial with immunoglobulin IV was administered. The patient made a good recovery being discharged 1 month after her admission. However, the patient over the last 2 years developed refractory temporal lobe epilepsy that remains cryptogenic in origin despite repeated and detailed examinations. Preliminary data of immunofluorescent staining of hippocampal neuron cells cultures with patient’s CSF and sera suggests a likely antibody binding, yet to be identified. Conclusion: We believe that this is a case of cryptogenic focal temporal lobe epilepsy presenting as new onset refractory status epilepticus probably of an autoimmune, unidentified cause. Suspected autoimmune etiology was based on cryptogenic refractory temporal epilepsy (high seizure frequency, multifocality, AED resistance), history of viral prodrome before NORSE, response to an immunotherapy trial and the preliminary findings of hippocampal cell cultures. The suspicion for implication of autoimmunity in this case is high and remains to be confirmed.

Status Epilepticus 2 Tuesday 13th September P664 NEUROBRUCELLOSIS PRESENTING WITH STATUS EPILEPTICUS AS AN INITIAL SYMPTOM Akyol A, Ozkul A, Tataroglu C, Eskici M Faculty of Medicine, Neurology, Adnan Menderes University, Aydin, Turkey Purpose: Brucellosis is a multisystem disease with different clinical presentations. Occasionally the central nervous system may be involved causing varied neurological manifestations. Neurological complications, including meningitis, meningoencephalitis, myelitis-radiculoneuritis, brain abscess, epidural abscess and meningovascular syndromes, are rarely encountered.


Case: We present a 65 years old male patient with chronic neurobrucellosis of 3 years duration. The initial clinical manifestation was status epilepticus which responded well to benzodiazepines. Conclusion: The diagnosis of neurobrucellosis should be considered in patients presenting with recurrent seizures or status epilepticus especially in endemic areas for brucellosis.

P666 LATERALIZED PERIODIC DISCHARGES ASSOCIATED WITH STATUS EPILEPTICUS IN THE FIRST YEAR AFTER STROKE Bebek N, Dede HO, Gelisin O, Atmaca MM, Yesilot Barlas N, Gurses C, Baykan B, Gokyigit A Istanbul Faculty of Medicine, Neurology-Clinical Neurophsiology, Istanbul University, Istanbul, Turkey Background: Lateralized periodic discharges (LPDs) are infrequent electroencephalograph (EEG) findings, and may present in ictal or interictal form. They are regarded as a potential electrophysiologic signs of convulsive or nonconvulsive status epilepticus (NCSE). We aimed to report four patients who presented with NCSE and one who presented with convulsive status epilepticus in the postictal period, characterized by LPDs in EEG recordings in the first year after stroke. Material and methods: We prospectively evaluated patients who clinically presented with status epilepticus associated LPDs between March 2014 and March 2015. We studied the patient presented like a new stroke attack. We excluded the other LPD etiologies. EEG studies of five patients (two men) who were admitted to our emergency unit with confusion, three of whom had visual symptoms; four were treated for NCSE as diagnosed with LPDs. The fifth patient had convulsive status epilepticus with LPD in the postictal period. Results and discussion: None of the five patients, who were aged between 68 and 92 years, showed any etiologic factor other than a history of cerebrovascular disease (CVD). Magnetic resonance imaging (MRI) studies of the patients revealed old infarcts and transitional diffusion restrictions. The clinical and EEG findings reduced substantially with antiepileptic treatment. Herein, we illustrate the first patient who had confusion, visual hallucinations, and ictal and interictal LPD in her consecutive EEGs. Conclusion: CVDs may pave the way for LPDs in patients with a history of stroke because CVDs cause structural brain damage. Patients who present with a similar clinical profile and imaging signs of stroke should be checked for NCSE, particularly in the presence of LPDs in EEGs.

P667 INTERLEUKIN 17A IS ASSOCIATED WITH THE SEVERITY OF EPILEPSY AND BBB INTERRUPTION IN PILOCARPINE INDUCED STATUS EPILEPTICUS MODEL Ding J, Wang J, Zhao Y, Zhang Q, Peng W, Wang X Zhongshan Hospital, Fudan University, Shanghai, China Purpose: Interleukin 17A (IL-17A) is a newly indentified cytokine secreted by TH17 cells. Previous researches have proved that IL-17A play a critical role in immune related diseases such as multiple sclerosis. It is still unclear that whether IL-17A is involved in epilepsy. Our study was aimed to elucidate that whether IL-17A has an effect on blood-brain barrier (BBB) disturbance in pilocarpine induced epileptic models.

203 Abstracts Method: Male SD rats were divided into five groups according to different observe time course after presented “status epilepticus” (SE) 30 min induced by pilocarpine: 1 SE -0 h; 2 SE -4 h; 3 SE -24 h; 4 SE -72 h; (5) saline-control (negative control) received only saline solution. IL17R knockout (KO) mice and wild-type (WT) mice were divided into four groups: 1 17R-KO SE; 2 17R-KO control; 3 WT SE; 4 WT control. The animals were monitored by a video system. Duration of myoclonic jerks, clonic and tonic convulsions, tonic hindlimb extensions and percentage of tonic convulsion index, as well as recovery latency and duration of attack were investigated. EB dye and brain weighed method were used to assess encephaledema, which reflex the blood brain barrier integrity. The expression of tight junction protein was determined by western blot. Results: The serum IL-17A concentration was increased 4 h after SE, which is coincidence with the disruption of BBB. Compared to wild type mice, IL-17R knockout (KO) mice exhibited significant low mortality and increased latency time, as well as increased tight junction associated proteins expression. Conclusion: Our study results indicated that IL-17A induced BBB interruption may play an important role in severity of epilepsy. The underlying mechanism merits further research.

P668 PREDICTING THE OUTCOME OF STATUS EPILEPTICUS: COMPARISON OF STESS AND EMSE SCORE IN A PROSPECTIVE, MONOCENTRIC, ADULT POPULATION Giovannini G1,2,3, Monti G1,2, Marudi A4, Gessaroli G2, Valzania F2, Nichelli PF1,2, Leitinger M3, Trinka E3,5,6, Meletti S1,2 1 Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy, 2Unit of Neurology, NOCSAE Hospital, AUSL Modena, Modena, Italy, 3 Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria, 4Intensive Care Unit, NOCSAE Hospital, AUSL Modena, Modena, Italy, 5 Center for Cognitive Neuroscience, Salzburg, Austria, 6Medical Informatics and Technology, University for Health Sciences, Hall i.T, Austria Purpose: To assess the prognosis in patients with Status Epilepticus (SE) as early as possible is of paramount importance to avoid either overor under-treatment. So far only two scores are available: Status Epilepticus Severity Score (STESS) and Epidemiology Based Mortality Score (EMSE). Here, we apply and compare them on a population of adult patients with SE. Method: We prospectively collected adult patients (≥14 years old) with SE admitted to our institution from September 2013 to September 2015. We collected all demographic and clinical parameters as well as 30 days follow up. STESS 3 (cut off of 3 points) and EMSE-EACE 64 (EMSEEtiology-Age-Comorbidity-EEG with a cut off of 64 points) scores were calculated for each patient to predict 30 days mortality, morbidity (likelihood to return to baseline conditions) and response to treatment. Results: We identified 175 SE episodes (109 females, median 74, range: 14–94). Among them 103 episodes were acute symptomatic. 67% of the patients were treatment responsive while 22% had a Refractory SE (RSE

and super-RSE). The overall 30 days’ mortality was 30%. 70% worsened their clinical condition after SE. 84% had a STESS ≥ 3 and 49% patients had an EMSE-EACE ≥ 64. 30 days mortality: the negative predictive value (NPV) was 86% for STESS-3 and 94% for EMSE-EACE-64; the positive predictive value (PPV) was 38% for STESS-3 and 57% for EMSE-EACE 64. Response to treatment: NPV was 89% for STESS-3 and 88% for EMSE-EACE-64; the PPV was 31% for STESS-3 and 40% for EMSEEACE 64 Conclusion: STESS and EMSE are both feasible to use for prediction of survival and treatment response, EMSE appeared to be superior to STESS. However, they both appear inferior identifying patients who will die after a SE episode. Both EMSE and STESS predict treatment response: they both equally correctly identified responsive patients.

P669 PROGNOSIS OF STATUS EPILEPTICUS IN ELDERLY PATIENTS Vilella L1, Abraira L2, Santamarina E1, Gonzalez Cuevas M1, Quintana M1, Toledo M1, Sueiras M1, Guzman L1, GarcıaTornel Garcıa-Camba A1, Vila C1, Salas Puig X1 1 Hospital Universitari Vall0 Hebron, Barcelona, Spain, 2Hospital Universitari Vall0 Hebron, Epilepsy Unit, Barcelona, Spain Purpose: To evaluate the clinical features and prognosis of status epilepticus (SE) in elderly patients. Method: We analysed all patients over 70 years old with diagnosis of SE registered prospectively in our centre, from April 2011 to May 2015. Post-anoxic aetiology was ruled out. Results: We evaluated a total of 90 patients. Previous diagnosis of epilepsy was found in 25.6% of patients. Acute symptomatic aetiology was the most common cause, representing 54.4% of all SE. Most of the SE (55.6%) was due to vascular pathology. The mean number of antiepileptic drugs (AEDs) was 2.7 1.2 and 21% of them required sedation. Mean SE duration was 24 h (8–78). Patients were considered to have a poor prognosis in the cases of death (31.1%) or new neurological impairment at discharge (27.8%). Poor outcome was related to higher scores in modified Rankin Scale (mRS) (p = 0.041), aetiology (p = 0.031), level of consciousness (p = 0.003), longer duration of SE (p = 0.003), Status Epilepticus Severity Score (STESS) (p = 0.002) and the development of infectious or metabolic complications (p = 0.004). After performing a logistic regression analysis, four variables predicted a poor outcome: previous mRS (OR: 1,659; IC 95% 1,078–2,553; p = 0.021), STESS over 4 (OR: 9,196; IC 95% 1,006–84,053; p = 0.049), acute symptomatic aetiology (OR: 1,865; IC 95% 1,186–2,931; p = 0.007) and SE duration above 12 h (OR: 6,332; IC 95% 1,926–20,818; p = 0.004). There was no association between sedation or the number of AEDs used and prognosis (p > 0.05). Conclusion: SE above 70 years old has a high morbi-mortality. Higher scores on mRS, STESS > 4, longer duration of SE and acute symptomatic aetiology are associated with a poor outcome. Prognosis is not related to treatment aggressiveness.

P670 PROGNOSIS OF STATUS EPILEPTICUS (SE) PATIENTS REQUIRING INTRAVENOUS ANESTHESIC DRUGS (IVAD) Santamarina E, Gonzalez Cuevas M, Toledo M, Porta I, Gracia RM, Sanchez A, Quintana M, Sueiras M, Guzman L, Salas Puig X Hospital Universitari Vall0 Hebron, Barcelona, Spain Different studies have raised some concern about the safety of using IVAD in the management of SE. It would be interesting to know which Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

204 Abstracts factors are associated with poor prognosis in SE patients requiring anesthetics. Method: We analysed all SE patients >16 years who required IVADs between February 2011-December 2015. Demographics, clinical data, etiology, duration of SE, the indication for sedation, EEG features, complications and prognosis at discharge were collected. Results: 73 patients required IVADs and endotracheal intubation. In 43 (58.9%) it was performed as third-line of treatment for SE, in 20 (27.4%) after a decreased level of consciousness due to SE treatment and in 10 (13.7%) it was performed due to the SE etiology itself. 22 patients (30.2%) had a functional decline at discharge and mortality was 26% (n = 19). The outcome was significantly poorer in patients with higher STESS (p = 0.003), a lower level of consciousness at baseline (p = 0.025), if evolving to a non-convulsive SE in coma (p = 0.040), with a potentially fatal aetiology (p = 0.006), a longer duration (p = 0.026), the presence of complications (p = 0.022), when IVADs were performed due to the etiology (p = 0.020) and the finding of PEDs in EEG (p = 0.032). After a multivariate analysis only the duration >12 h (OR = 3.266 [95% CI = 1,077–9,908]; p = 0.037), a STESS ≥ 3 (OR = 4.816 [95% CI = 1,435–16,165]; p = 0.011) and the presence of a potentially fatal aetiology (OR = 3.526 [95% CI = 1,184–10,506]; p = 0.024) were independently associated with a poor prognosis. Regarding mortality, only a SE duration >12 h (OR = 7.07 [95% CI = 1,836–27,220]; p = 0.004), a low level of consciousness (OR = 6.97 [95% CI = 1,194–40,718]; p = 0.031) and the presence of complications (OR = 21.32 [95% CI = 2,440–186,295]; p = 0.006) predicted independently mortality. Conclusion: The longer duration of SE in patients requiring IVADs is associated with a poor prognosis and mortality. A STESS ≥ 3 and the etiology seem to affect mainly the functional status at discharge, while the initial decreased level of consciousness and the complications are related to mortality.

P671 FATAL CEREBRAL EDEMA WITH STATUS EPILEPTICUS IN CHILDREN WITH DRAVET SYNDROME Scheffer I1,2,3, McMahon J1, Mandelstam S2,4,5, Mackay M2,3, Kalnins R6, Leventer R3,4,7, Myers K1,8 1 Epilepsy Research Centre, University of Melbourne, Heidelberg, VIC, Australia, 2The Florey Institute of Neuroscience and Mental Health, Heidleberg, VIC, Australia, 3 Department of Neurology, Royal Children’s Hospital, Parkville, VIC, Australia, 4Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia, 5Department of Radiology, The University of Melbourne, Parkville, VIC, Australia, 6Department of Pathology, Austin Health, Heidelberg, VIC, Australia, 7Murdoch Children’s Research Institute, Parkville, VIC, Australia, 8Alberta Children’s Hospital, University of Calgary, Calgary, AB, Canada Purpose: Febrile status epilepticus is almost universal in patients with Dravet syndrome (DS). Children with this disorder have a high mortality primarily due to sudden unexpected death in epilepsy or multi-organ failure with status epilepticus. Here, we report five children with DS who presented with febrile status epilepticus, and developed profound brain edema that led to their deaths. This previously unrecognised phenomenon may be a preventable cause of death in DS. Method: While patients usually recover from status, we describe five children with DS who presented with febrile convulsive status epilepticus, developed severe brain swelling, and died. Medical history notes and neuroimaging were analysed.

Results: Four children had classical DS and a fifth atypical multifocal DS. All had de novo SCN1A mutations with prior brain magnetic resonance imaging (MRI) showing no significant abnormalities. The only exception was case 3 who had 4 years of seizure freedom following the introduction of stiripentol at age 5.5 years. This ended when she had status epilepticus lasting an estimated 6 h at 9 years of age, after which she developed right hemiparesis, cognitive regression and behavioural change. Acute phase MRI during that event showed diffuse restricted diffusion, primarily in the frontal lobes. Her motor function, development and behaviour returned to baseline within 8 months. At 11 years, she had a 25 min seizure and developed fatal cerebral edema. Conclusion: Cerebral edema causing herniation and death is an important, previously unreported, sequela of status epilepticus in children with DS. Prompt identification of severe cerebral edema may allow urgent potentially life-saving intervention.

P672 INTRAVENOUS LEVETIRACETAM AS SECOND LINE OPTION FOR STATUS EPILEPTICUS AND SEIZURE CLUSTERS Ungureanu A1, Prodan L1, Roman-Filip C2 1 Academic Emergency Hospital, Neurology, Sibiu, Romania, 2 Lucian Blaga University of Sibiu, Neurology, Sibiu, Romania Purpose: To to investigate the efficacy and tolerance of intravenous (IV) administration of levetiracetam (LEV) for status epilepticus (SE) and seizure clusters (SC). Method: We retrospectively analyzed 29 patients admitted in our neurological intensive care unit with SE or SC between December 2011 and January 2015. Indications for IV LEV as second line treatment were SE or SC unresponsive to IV diazepam. Responsiveness within 3 h, relations between variables and adverse events were evaluated. IV LEV was administered as second line therapy immediately after no response of 10 mg of IV diazepam, in a maximum dose of 3,000 mg/day. Unresponsive patients or patients at risk underwent general anaesthesia. Results: In 82.7% of the cases (24 patients), seizures stopped within 3 h. No correlation was observed between age and seizure duration. The seizure duration did not correlate with age (r = 0.12, p = 0.07), seizure type (r = 0.34, p = 0.06), nor with etiology (r = 0.008, p = 0.9). Conclusion: Our study showed that IV LEV is a safe, effective treatment for refractory SE or SC of different etiology.

Status Epilepticus 3 Wednesday 14th September P673 SESA SYNDROME WITH A NOVEL EEG PATTERN Akyol AG, Genc E, Genc BO Necmettin Erbakan University Meram School of Medicine, Neurology, Konya, Turkey Introduction: Subacute encephalopathy with seizures in alcoholism (SESA) syndrome is a rare disorder, seen within the course of chronic alcoholism and abstinence in particular. It is characterized by focal or generalized seizures accompanied by transient neurological deficits, typical EEG features and variable MRI changes. However, few reports indicating permanent neurological sequela as a result of recurrent episodes also exist. Case presentation: 38 year old female with a diagnosis of alcoholic liver cirrhosis was consulted to neurology department because of


205 Abstracts recurrent secondary generalized tonic clonic seizures. Medical history was remarkable for chronic alcoholism and withdrawal for a few weeks. Neurological examination on the twelfth day of hospitalization after several seizures revealed a stuporous state with right gaze deviation, bilateral positive Babinski sign and poor motor response, prominently on the right side. There was no sign of meningeal irritation. Serum AST and bilirubin levels were elevated. Brain MRI detected high signal intensity in the left frontoparietal parasagittal area extending to occipital region on diffusion and T2 weighted images with corresponding decreased signal on ADC. She was started Valproat infusion, however seizure control was insufficient and the antiepileptic treatment was switched to levetiracetam after 24 h. EEG showed lateralized pseudoperiodic pattern mimicking burst suppression morphology, which was dominant on the left hemisphere. Seizures stopped on the 48th hour of levetiracetam infusion. Follow up Brain MRI taken 5 days later showed diminished T2 changes. The patient was lethargic but responsive, however she had persistant right hemiparesis. Conclusion: SESA syndrome is considered to be a subtype of partial non-convulsive status epilepticus, and ongoing subtle seizures after achievement of clinically visible seizure control might contribute to prolonged neurological deficits. To our knowledge, burst-supression mimicking pseudoperiodic lateralized EEG pattern has not been identified in the course of SESA syndrome before.

P674 STATUS EPILEPTICUS IN PEDIATRIC AGE: ETIOLOGY, SEMIOLOGY AND OUTCOME IN 173 CHILDREN Bellusci M1, Benvenga A2, Trivisano M2, de Palma L2, Pietrafusa N2, Cappelletti S2, Fusco L2, Vigevano F2, Specchio N2 1 Hospital 12 de Octubre, Pediatric Neurology, Madrid, Spain, 2 Neurology Unit, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy Purpose: To report the characteristics of paediatric patients suffering from Status Epilepticus (SE) and their outcome. Method: We included 173 children treated at “Bambino Gesu” Children’s Hospital in Rome (4.35 4.85 years old; follow up 2.74 1.9 years). We adopted the definition of SE proposed by ILAE (1993) and the classification by Trinka (2009). Multivariate model was constructed and adjusted ORs were calculated with 95% Confidence interval (OR [95% CI]). Five endpoints were evaluated: worsening of neurological exam and/or cognitive status, development of epilepsy, drug-resistance and recurrence of SE. Results: Fifty percent of SE were symptomatic (32% acute, 18% remote). Acute symptomatic and genetic aetiology were prevalent in patients ≤6 months (OR 8.10 [3.0–21.9]), febrile SE between 6 months and 2 years, OR 10.4 [1.9–56.1]). Non-convulsive SE was associated with Idiopathic aetiology (OR 49.8 [6.4–345.3]), myoclonic SE with metabolic causes (OR 12.0 [3.5–40.7]) and convulsive semeiology with febrile SE (OR 7.2 [1.5–33.9]). After SE patients developed: 67% epilepsy (drug-resistant in half of them);17% recurrent SE; 19% worsening of neurological exam; 15% cognitive deficit; 3% died during the hospitalization and 3.5% during follow-up. At multivariate analysis: SE lasting more than 24 h have increased risk to develop cognitive (OR 6.00 [2.0–17.1]) or neurologic sequelae (OR 8.58 [2.7–27.1]); the same finding was observed for patient younger than 1 months (cognitive OR 4.84 [1.13–17.3] and (neurologic sequelae OR 6.7 [1.17–27.1]). The recurrence of SE was associated with cryptogenic aetiology (OR 11.5 [2.2–61.8]), genetic aetiology (OR 8.87 [2.46–42.63]) and myoclonic seizures (OR 6.1 [1.1–29.4]). Epilepsy after SE was associated with acute symptomatic aetiology (OR 0.12 [0.04–0.40]) and Febrile SE (OR 0.06 [0.008–0.40]). Drug-

resistant epilepsy post SE was associated with Focal non-convulsive SE (OR 0.18 [0.32–0.97]) or acute symptomatic SE (OR 0.04 [0.007–0.26]). Conclusion: Age at onset and duration of SE are critical independent variables associated to worst neurocognitive outcome. The risk to develop epilepsy is lower after acute symptomatic and febrile SE.

P675 SPORADIC CASE OF CREUTZFELT-JACOBS’S DISEASE WITH EEG FEATURES OF NONCONVULSIVE STATUS EPILEPTICUS Arnaoutoglou M1, Spilioti M1, Karafyles G1, Kyriakogianni C1, Kiryttopoulos A1, Xerras C1, Notas K1, Konstantinidis G1, Tziomalos K2, Kimiskidis V3, Orologas A1 1 1st Department of Neurology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, 21st Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, 3Laboratory of Clinical Neurophysiology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Purpose: We report a case of probable sporadic Creutzfeldt-Jakob disease (CJD) presenting with clinical manifestations of subacute diffuse encephalopathy and EEG features of non-convulsive status epilepticus (NCSE). Method: A 68 year old female patient was admitted to our department with subacute onset of ataxia and confusional state. The previous weeks she had vertigo, nausea and vomiting. The neurological examination on admission revealed an impaired mental status with disorientation and delusions, vertical nystagmus and gait ataxia with impaired tandem walk. An extrapyramidal syndrome developed gradually that made the patient bedbound. It initiated with myoclonus and subsequently she presented extrapyramidal rigidity, bilateral pyramidal sings and dystonia. Her overall neurological state rapidly deteriorated to akinetic mutism. Finally the patient died 2 months later. Results: The initial EEG showed a background slowing with diffuse sharp and slow wave complexes of short duration and bursts of triphasic waves in the frontal regions. The subsequent EEGs showed continuous sharp and slow wave complexes intermixed with triphasic waves, which were attenuated after IV injection of clonazepam, without improvement of vigilance. Based on these EEG findings, suggestive of NCSE, an aggressive antiepileptic treatment was administered, without clinical improvement. Brain MRI revealed an increased cortical signal in DWI sequence, in the occipital regions bilaterally. CSF analysis detected high titers of 14-3-3 protein (65,000 IU/ml), supporting the diagnosis of probable CJD. Conclusion: In our case, the initial EEG features and the improvement after the administration of intravenous benzodiazepines were suggestive of NCSE. However, the unmodified clinical state despite the antiepileptic therapy, the rapid deterioration, the high titers of 14-3-3 protein and the neuroimaging findings were supportive of CJD. The EEG features, especially in early stages of CJD may be similar to those of NCSE, but the clinical course, the laboratory investigations and serial EEGs may clarify the differential diagnosis.


206 Abstracts P676 TOPIRAMATE FOR REFRACTORY NONCONVULSIVE STATUS EPILEPTICUS IN ELDERLY Kim J Dongtan Sacred Heart Hospital, Neurology, Hallym University, Hwaseong, Republic of Korea Purpose: We want to describe two cases of refractory nonconvulsive status epilepticus (NCSE) in elderly, dramatically responsive to topiramate (TPM). Method: Two elderly patients (78 & 81-year-old, all females) with NCSE refractory to therapeutic loading doses of two or three antiepileptic medications (fosphenytoin 30 mg/kg and levetiracetam 50 mg/kg in both cases and additional phenobarbital 30 mg/kg in case 1) were given topiramate (TPM) with loading and maintenance dose of 400 mg/day. Results: There were dramatic improvements in EEG and mental status within 24–48 h after TPM loading. Eventually, TPM successfully controlled refractory NCSE and were well tolerated in two elderly patients. Conclusion: Our experience indicates that TPM can be an effective and safe treatment option in refractory NCSE, even in elderly.

P677 SEVEN CASES OF NEW ONSET REFRACTORY STATUS EPILEPTICUS (NORSE) IN QATAR: IMPROVED OUTCOME WITH EARLY IMMUNOTHERAPY Melikyan G1,2, Malki S3, Ibrahim F3, Al Tabouki A3, Haddad N4, Al-Hail H5, Mesraoua B3, Deleu D3,4, Azar N1 1 Hamad Medical Corporation, Neurology/Neuroscience, Doha, Qatar, 2Weil Cornel Medical College, Doha, Qatar, 3Hamad Medical Corporation, Neurology/Medicine, Doha, Qatar, 4Weil Cornel Medical College, Neurology, Doha, Qatar, 5Hamad Medical Corporation, Neurology, Doha, Qatar Purpose: New onset of refractory status epilepticus (NORSE) is a lifethreatening condition, which is characterized by failure to respond to first and second line anticonvulsant therapy. In this case series we show that immunotherapy seems to be a helpful treatment option when conventional therapy fails. Method: This is a descriptive, retrospective review of seven previously normal adult patients (age between 28 and 45 years) with NORSE admitted to Hamad Medical Corporation MICU in Qatar from 2012 to 2015. Results: Seven patients with NORSE syndrome were identified, where a cause was not established despite an exhaustive search with an average duration of 27 days (range 14–32). Characterizing features were male gender, young age, previous good health, cerebrospinal fluid pleocytosis (in 4), antecedent febrile illness (in 5), extraordinarily prolonged status epilepticus, failure of extensive investigations to reveal an underlying cause, catastrophic outcome as well as temporal lobe (in 3) and leptomeningeal enhancement (in 1) on brain magnetic resonance imaging. Treatment modalities included at least 3 antiepileptic drugs (in all patients), anesthetics (in all patients), intravenous immunoglobulin (IVIG, 5 patients), steroids (4 patients), plasmopheresis (1 patient). Three patients improved completely without neurological deficit and two of them survived with severe disability. Two patients who were not given early immunotherapy, died from complications associated with prolonged ICU stay. None of the survivors received long term immunotherapy. Conclusion: The cause of NORSE syndrome may often be difficult to find. NORSE carries a poor prognosis and early recognition and treatment may improve outcomes.


P678 REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME ASSOCIATED WITH NONCONVULSIVE STATUS EPILEPTICUS Milat D1, Petelin Gadze Z2, Hajnsek S2, Ribaric B3, Petravic D3, Mudrovcic M4 1 Sveti Rok Polyclinic, Zagreb, Croatia, 2University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Referral Centre for Epilepsy of the Ministry of Health of the Republic of Croatia, Department of Neurology, Zagreb, Croatia, 3 University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Department of Neurology, Zagreb, Croatia, 4 School of Medicine, University of Zagreb, Zagreb, Croatia Introduction: Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinicoradiologic syndrome characterized by headache, decreased alertness, seizures, visual abnormalities, and white matter changes indicative of cerebral edema. This syndrome frequently occurs in patients with hypertensive encephalopathy, where disruption of cerebral vascular endothelial cells plays a critical role in the pathogenesis of the disease. Initially, this syndrome was believed to be secondary to hypertension, renal disease, or immunosuppressive therapy. However, it has recently been identified in a wide variety of conditions, including eclampsia, hemolytic-uremic syndrome, connective tissue diseases, malignancies, etc. Case report: Authors describe a case of a 72-year-old woman with a history of arterial hypertension, who suddenly developed neurological symptoms associated with high blood pressure: headache, left homonymous hemianopsia and left hemiparesis, followed by confusional state. Her electroencephalography showed right-sided periodic lateralized epileptiform discharges and pointed to nonconvulsive status epilepticus. Brain MRI revealed extensive white matter lesion in the right parietal and occipital lobe, splenium corpus callosum and left occipital lobe, suggestive of expansive process. However, after extensive diagnostic workup, diagnosis of reversible posterior leukoencephalopathy was established, connected with arterial hypertension. Following treatment with levetiracetam intravenously and antihypertensive drugs clinical condition improved. At the moment patient is without neurological symptoms, and control brain MRI revealed resolution of white matter lesion. Conclusion: Early recognizing of this syndrome is of great importance, because prompt medicamentous therapy and distinction from brain tumour can postpone invasive diagnostic procedures (stereotactic brain biopsy). It should be also kept in mind that RPLS is a causative factor of nonconvulsive status epilepticus.

P679 STATUS EPILEPTICUS - CAN DATA FROM THE PAST CHANGE OUR STRATEGY TODAY? Nachmilnerová I, Hor akov a J, Slonkov aJ University Hospital Ostrava, Neurology, Ostrava, Czech Republic Purpose: The evaluation of patients admitted with status epilepticus (SE) to the University Hospital Ostrava in 2010–2015, focused on the semiology, etiology and treatment. Methods: All patients admitted with SE were retrospectively analyzed. Multiparametric assessment was performed using standard statistical methods. Results: We identified 85 hospitalizations 41 men and 44 women cases. The average age was 60.81 20.91, with the median 63 years. The average duration of hospitalization was 11.12 10.09 days, median 8 days. The etiology included poststroke SE (37), lack of efficacy of

207 Abstracts AED (19), chronic alcohol abuse (13), tumor (11), multiple sclerosis (3) autoimmune encephalitis (3). The main semiology was focal onset evolving into bilateral convulsive SE (44). Repeated focal motor seizures, ictal paresis, unknown whether focal or generalized all equally contributed for 7 admissions. The main EEG findings included focal specific ictal activity (47), specific generalized (13) and non-specific findings (13). All patients received diazepam as a first line treatment; the most frequently used drug during the hospitalization was valproic acide (71), followed by levetiracetam and phenytoin (30 and 29 respectively) and thiopental in 8 cases. In 51 cases patients were discharged home, 23 cases after SE were transferred to other hospitals and 11 events were fatal (12.94%, n = 85). We focused on the group of 13 patients who were admitted repeatedly, in regards of their etiology, semiology and treatment. The most severe diagnosis was super refractory SE, type NORSE in 2 cases, of which one patient died and one survived with partial complex epilepsy syndrome. 1 patient died under diagnosis of non specific encephalopathy and cognitive decline, retrospectively anti-NMDAr encephalitis could not be excluded. Conclusion: Status epilepticus is a life threatening condition. A detailed retrospective analysis of each case using etiology, semiology and EEG findings should help predict severity, prognosis and outcome.

P680 REFRACTORY STATUS EPILEPTICUS, ARE WE REFINING TREATMENT PATHWAYS? Brewster R, Samarasekera S Queen Elizabeth Hospital, Neurosciences, Birmingham, United Kingdom Purpose: The diagnosis and management of refractory status epilepticus (RSE), defined as seizures persisting in spite of first line therapy and requiring ITU admission, is evolving. Access to newer anti-epileptic drugs and immunomodulatory therapies is extending treatment options. Nevertheless, RSE remains a condition with high morbidity and mortality; non-convulsive RSE in particular is associated with delays in time to treatment. We conducted an audit of patients admitted to ITU at the Queen Elizabeth Hospital, Birmingham between 2012 and 2014. This tertiary centre benefits from extended access to EEG services at weekends. Method: Data was collected via the QEBH electronic recording system and added to the global registry established by Professor Simon Shorvon and colleagues: the StEp Audit. Results: 25 cases (18 males) were identified. The mean age was 51.5 years (range 23–80 years). 19 patients (76%) did not have a previous diagnosis of epilepsy. Aetiology was established in 22 of 25 (88%) cases. 19 (76%) cases were convulsive SE. 10 of 12 patients in convulsive SE received AEDs within an hour of arrival to hospital, compared with 1 out of 4 patients in non-convulsive SE (p = 0.06). Time to treatment was unavailable in 9 (32%) cases Intensivists preferred choice of anti-epileptic (following first-line benzodiazepines) was Levetiracetam (44%). Propofol was the first choice anaesthetic agent in 23 (92%) cases. Six patients (24%) were treated with immunomodulatory therapies steroids plasma exchange. 13 patients (52%) were discharged home, a further 6 (24%) discharged to rehab. Five patients (20%) died. Conclusion: Refractory Status Epilepticus is a condition with a growing range of causes and outcomes. Hospital guidelines need to encompass both convulsive and non-convulsive RSE; extended access to investigations is needed to help facilitate prompt treatment and improve outcome.

Surgical Treatment and Neuromodulation 1 Monday 12th September P684 PROLONGED SEIZURE REMISSION AFTER ELECTRODE INSERTION IN PATIENTS SUBMITTED TO HIPPOCAMPAL DEEP BRAIN STIMULATION (HIPDBS) FOR REFRACTORY TEMPORAL LOBE EPILEPSY Cukiert A1,2, Cukiert C3,4, Burattini J1, Mariani P1 1 Clinica de Epilepsia de Sao Paulo, Neurosurgery, Sao Paulo, Brazil, 2Faculdade de Medicina do ABC, Neuroscience, Sao Paulo, Brazil, 3Clinica de Epilepsia de Sao Paulo, Neurology, Sao Paulo, Brazil, 4Faculdade de Medicina da Santa Casa de Sao Paulo, Neurology, Sao Paulo, Brazil Purpose: An insertional effect characterized by seizure frequency reduction has already been noted in patients submitted to thalamic or hippocampal deep brain stimulation for refractory epilepsy. It is usually a transient phenomenum, lasting for a month, but might be more prolonged. Method: Eighteen patients submitted to Hip-DBS with at least 12 months of follow-up were studied. Generators were kept off postoperatively until patients got back to their pre-operative seizure frequency. Patients were followed up at least once every 2 months. Results: Two patients had prolonged seizure-free intervals after electrode insertion. One patient has been seizure free for 14 months (generator off); a second patients remained seizure free for 30 months, had a cluster of seizures, and remained seizure free for an additional 13 months (generator off). Both patients had mesial temporal sclerosis. Conclusion: Although infrequent, we observed prolonged insertional effects in patients undergoing Hip-DBS. Although both patients had mesial temporal sclerosis, it is not clear at this point if this patient population is more prone for seizure freedom after electrode insertion. The analysis of the biological characteristics of these patients with prolonged insertional effects might enable us to select patients who would be candidates for minimally invasive procedures.

P685 POST-OPERATIVE CONTACTS’ LOCATION IN PATIENTS SUBMITTED TO HIPPOCAMPAL DEEP BRAIN STIMULATION (HIP-DBS) Cukiert C1,2, Cukiert A1,3, Burattini J1, Mariani P1 1 Clinica de Epilepsia de Sao Paulo, Sao Paulo, Brazil, 2 Faculdade de Medicina da Santa Casa de Sao Paulo, Neurology, Sao Paulo, Brazil, 3Faculdade de Medicina do ABC, Neuroscience, Sao Paulo, Brazil Purpose: Hip-DBS has been used in an increasing frequency to treat patients with refractory temporal lobe epilepsy who are not candidates for temporal lobe resection or are not willing to do so. Adequate electrode’s positioning is crucial for the effectiveness of the procedure. The hippocampus can be sampled using a single occipito-temporal trajectory. On the other hand, the hippocampus is slightly curved and some contacts might miss the structure according to individual brain anatomy. Method: Twenty-two patients submitted to Hip-DBS were studied. Post-operative MRI was performed 2 months after the procedure, with the generator transiently off. Thin T1, T2 and FLAIR coronal slices perpendicular to the hippocampal axis were obtained. The quadripolar electrode’s contacts were rated as being inside the hippocampus, at its periphery (in the hippocampus, but not centered) or outside the hippocampus. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

208 Abstracts Results: At least one contact was considered to be at periphery of the hippocampus in all patients. These contacts were usually located in the lateral and caudal hippocampus. In two patients, the most anterior contact was found to be inside the anterior temporal horn. In three patients, one contact, usually the most posterior, was located in the parahippocampus, immediately under the hippocampus. The other electrodes were located in the middle of the hippocampus. Conclusion: Most of the hippocampal electrodes targeted using a occipito-temporal route were within the hippocampus. It is not clear yet if patients with electrodes located in the hippocampal periphery or within the parahippocampus would have a different outcome regarding seizures.

P686 EFFICACY OF VAGAL NERVE STIMULATION IN A COHORT OF 32 DRUG-RESISTANT EPILEPTIC PAEDIATRIC PATIENTS Grioni D1, Gagliardi E2, Trezza A2, Landi A3 1 Child Neuropsychiatric Clinic, San Gerardo Hospital University of Milan Bicocca, Monza, Italy, 2University of Milan Bicocca, Monza, Italy, 3San Gerardo Hospital, University of MIlan BIcocca, Monza, Italy

Method: We used cortical electrical stimulation in amygadala, hippocampus and orbitofrontal structures in three patients with refractory left temporal lobe epilepsy who were stereotactically implanted with depth electrodes as part of their surgical evaluation for intractable epilepsy in the Epilepsy Monitoring Unit at University Hospital Case Medical Center. 50 Hz biphasic, bipolar, 0.2 ms pulse width, 30 s stimulation trains were used, increasing from 2 mAmp to a maximum of 20 mAmp. EEG, EKG, blood pressure, O2, CO2, breathing rate and nasal thermister measurements were used to assess responses to stimulation. Results: We found central apnea and mild O2 desaturation (to minimum of 91%) consistently occurred immediately with onset of amygdalar stimulation, at a current intensity of ≥4 mAmp. Apnea periods lasted for 10–46 s. Patients were apnea agnostic, despite being awake and alert during stimulation. In all patients seizures were induced at varying intervals after stimulation onset, associated with continuing apnea, tachycardia and modest blood pressure decreases. Conclusion: Sudden Unexpected Death in Epilepsy (SUDEP) mechanisms are currently poorly understood. In part, this is because the site and role of cortical respiration and autonomic control structures have not been well identified. Apnea can occur during and after epileptic seizures. Similarly, a variety of autonomic dysfunctions have been described in seizures. The amygdala is thought to play a role in breathing control. Our study confirms amygdala influence on respiration and furthermore, characterizes autonomic responses to stimulation and seizures.

Purpose: Evaluate the efficacy of Vagal Nerve Stimulation in paediatric patients. Method: Among the patients implanted in our centre since 2007, we selected those implanted during paediatric age. The following parameters were retrospectively collected for each patient: prevalent seizures type, age at the onset of the seizures, aetiology, age at the implant, delay between age at the onset of the seizures and age at the implant, outcome (McHugh scoring) at the last follow-up. All the patients were selected for Vagal Nerve Stimulation (VNS), implanted and followed by the same team in our Institution. Results: Prevalent seizure type were: spasms (31.3%), focal seizures (18.8%), generalized seizures (28.1%) and other (21.9%). The mean age at the onset of the seizures was 1 years (0.6–15). The aetiologies were: structural-methabolic (40.6%), syndromic (18.8%), genetic (9.4%) and unknown cause (31.3%) according with Berg AT et al (2010). The mean age at the implant was 7.9 years (0.6–18 years) and the mean delay was 6.3 years (0.6–17.8 years). The outcome at the last follow-up (mean 3.7 years), according the McHugh scoring, was: IA/B 46.9%, IIA/B 31.3%, IIIAB 3.1% and V 9.4%. Two patients (6.25%) are currently seizures free. Three patients died for the following causes: super-refractory status epilepticus in one case and SUDEP in the others. The better results were obtained in spasms (70% of children in Class IA), in young children implanted with a short delay between age at onset of the seizures and time of the implant (Spearman correlation rs 0.29) and overall in early implants (rs 0.39). In our experience, the efficacy of VNS improve until 2 year after the implant unchanging over the following time. Conclusion: Our data confirm that VNS could be helpful in the treatment of drug-resistant epilepsies of various aetiology in paediatric patients.

P687 CORTICAL AUTONOMIC AND RESPIRATORY CONTROL STRUCTURES IN PATIENTS WITH EPILEPSY Lacuey Lecumberri N1,2, Zonjy B1, Lhatoo S1 1 University Hospitals Case Medical Center, Cleveland, OH, United States, 2Vall d’Hebron Hospital, Neurology, Barcelona, Spain Purpose: To identify cortical structures involved in autonomic and breathing regulation in the human brain. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P688 ALTERED CORTICAL EXCITABILITY IN DRUGNA€IVE EPILEPSY PATIENTS Lee JH1, Joo EY2, Kim HJ3 1 Sungkyunkwan University School of Medicine, Neurology, Changwon, Korea, 2Sungkyunkwan University School of Medicine, Seoul, Neurology, Seoul, Korea, 3Department of Neurology, Konkuk University Medical Center, Seoul, Korea Purpose: Numeroustranscranial magnetic stimulation (TMS) studies have defined the characteristic features of TMS in epilepsy. TME parameters were expected to classify the epilepsy syndrome or drug responses. However, the results such as corticalsilent periods (CSP) are variable according to conditions of patients. Here, we investigate whether specific TMS parameters have localizing or lateralizing values in drug na€ıve epilepsy patients Method: We recruited 148 consecutive untreated patients with epilepsy (idiopathic generalized epilepsy; IGE 38, focal epilepsy; FE 110, mean age 31.4 years) and 38 age- and gender-matched normal subjects. We obtained resting motor threshold (RMT), motor-evoked potential (MEP), cortical silent period (CSP), short interval intracortical inhibition (SICI, inter-stimuli interval 2–5 ms), and intracortical facilitation (ICF, interstimuli interval 10–20 ms). TMS were performed during a seizure-free state of more than 48 h. Results: In IGE, no interhemispheric difference in CSP was found (p > 0.05). However, the mean CSP was longer in IGE patients than in normal controls at all stimulus intensities (p < 0.05). The mean CSP in ipsilateral hemisphere (IH) of FE was significantly longer at all stimulus intensities than that in normal controls (p < 0.001). The CSP in IH was longer than that in CH of FE. There was no significant difference in CSP between FE and IGE. SICI was significantly reduced only in the IH of PE versus normal subjects. RMT, MEP amplitudes, and ICF did not differ among IGE, FE, and normal controls. Conclusion: We found that prolonged CSP and reduced SICI in FE indicate asymmetrically increased cortical inhibition in the epileptic hemispheres. It suggests that CSP among TMS parameters has a crucial role to lateralize the epileptic hemispherein FE.

209 Abstracts P689 HIGH SPECTRAL CHANGES INDUCED BY SPES- A COMPARISON BETWEEN PHYSIOLOGIC AND PATHOLOGIC NETWORK INTERACTION IN SEEG Maliia MD1,2, Donos C3, Barborica A3,4, Mindruta I1,5, Popa I1, Ene M3, Beniczky S2,6 1 University Emergency Hospital, Neurology, Bucharest, Romania, 2Danish Epilepsy Centre- Filadelfia, Neurophysiology, Dianalund, Denmark, 3University of Bucharest, Physics, Bucharest, Romania, 4FHC Inc, Bowdoin, ME, United States, 5University of Medicine and Pharmacy ‘Carol Davila’, Neurology, Bucharest, Romania, 6Aarhus University Hospital, Neurology, Aarhus, Denmark Objective: To investigate functional coupling between brain networks using spectral changes induced by single-pulse electric stimulation (SPES). Method: Data from 20 patients, implanted with depth electrodes for their presurgical evaluation were analyzed. SPES (biphasic pulses, 3 ms pulse duration, 15 s inter-pulse interval, current intensity in the 0.25–5 mA range) were applied to each pair of adjacent contacts, and responses evoked by stimulation were recorded from all other contacts. (Donos et al., 2016) The mean RMS value was quantified in 3 independent time periods (5–60, 60–255, 255–500 ms) for 3 EEG spectra, Gamma 30– 100 Hz, High Frequency Oscillations (HFO) 100–250 Hz, Fast Ripples (FR) 250–500 Hz, both after the stimulation and 1 s before it, in the background period. 31,700 responses were recorded out of which only those significantly different from the background activity (Mann Whitney p < 0.05) were considered. A 3-way ANOVA analysis, Bonferroni adjusted, was performed taking into consideration 3 dichotomous variables (stimulating in primary sensory areas (S1-V1) -physiologic interaction; stimulating in seizure onset zone (SOZ)-pathologic interaction and recording into the default mode network (DMN) vs. non-default brain areas). Results: S1-V1 stimulation produced a higher deactivation in the delayed periods, in gamma (p = 6E9) and FR (p = 3E11) spectra, more so in the DMN, in reverse to SPES applied to non-S1V1 contacts. SOZ produced a higher deactivation in the delayed periods (p = 2E23, 5E20) in both HFO and FR spectra, as compared to non-SOZ stimulation, with a lesser impact on the DMN. Conclusion: This study is a proof of principle demonstrating that physiologic and pathologic interactions can be probed with asymptomatic stimulation paradigms. The increased deactivation induced by SPES in the SOZ suggests increased connectivity of these regions, while failure of deactivating the DMN could play a role in disturbance of consciousness during seizures.

P690 ELECTRICAL CONTINOUS NEUROMODULATION IN THE INTERNAL GLOBUS PALLIDUS FOR TREATMENT OF DRUG-RESISITANT MYOCLONUS (AND REFRACTORY EPILEPSY) IN PATIENTS SUFFERING FROM THE UNVERRICHT-LUNDBORG DISEASE Mercedes Alvarez B1, Crespel A2, Gelisse P2, Cif AL3, Genton P4, Coubes P5 1 Unite Medico-Chirurgicale de l’Epilepsie, Pôle Neurosciences Tête et Cou, CHU Montpellier, Neurochirurgie Fonctionnelle, Montpellier, France, 2Medical-Surgical Epilepsy Unit, Gui de Chauliac University Hospital, Montpellier, France, 3 Department of Neurosurgery (Research Group on Movement Disorders), Gui de Chauliac University Hospital, Montpellier,

France, 4Saint Paul Center - Gastaut Hospital, Marseille, France, 5Medical-Surgical Epilepsy Unit and Research Group on Movement Disorders, Fonctional Neurosurgery Department, Gui de Chauliac University Hospital, Montpellier, France Purpose: We report on the partial effectiveness of the Electrical Continuous Neuromodulation (ECN) in the internal Globus Pallidus (GPi) in patients suffering from Unverricht- Lundborg disease (ULD). It’s an inherited neurodegenerative disorder and the most common form of progressive myoclonus epilepsies, where the drug-refractory myclonus tends to be the most disabling feature of the disease. The occurrence of epileptic seizures can be most often controlled by anti-epileptic drugs (AEDs), whereas the myoclonus is quite resistant to medication. Its worldwide prevalence is unknown. Methods: The four patients were adults and had a medically refractory epilepsy with epileptic seizures (tonic-clonic seizures) and myoclonic jerks with or without some dystonic component. We decided to evaluate GPi modulation on the basis of the effectiveness and safety treating both myoclonus and dystonia in patients with myoclonous-dystonia syndrome (MDS or DYT11). In fact, myolonic jerks have clinical similarities. All patients were implanted bilaterally in the internal globus pallidus and one of them also bilaterally in the anterior nucleus of the thalamus. Results: The two patients with the most severe forms of ULC had initally a great reduction of myoclonus (absence of rest myoclonias, few intention and action myoclonias). Unfortunately, they died within the first year after implantation (dehydration during Canicule and complications of extensive burns), not allowing to conclude the long-term outcome with ECN procedure. Another patient had a moderated-high efficacy, reducing rest myoclonia and CTCG and moderated effect for intention and action myoclonias. However, this effect only lasted a couple of years. In the last patient implanted, it was not useful at all and the stimulators were removed at the time of the first battery replacement. Conclusion: GPi-ECN does not appear to improve myoclonus, in the long-term, in patients suffering from Unverricht-Lundborg disease.

P691 EFFECTS OF VAGAL NERVE STIMULATION ON PEOPLE WITH EPILEPSY AND COGNITIVE DISABILITIES Pipan E1, Brooks P2, Apostolou A2, Bograkou M2, Gauffin H2 1 Faculty of Medicine, University of Ljublana, Ljublana, Slovenia, 2Department of Neurology and Department of Clinical and Experimental Medicine, Link€ oping University, Link€ oping, Sweden Purpose: People with cognitive disabilities have a higher incidence of epilepsy than the general population and more often suffer from therapy resistant epilepsy. They are also more prone to central nervous sideeffects from anti-epileptic drugs. Vagal Nerve Stimulation (VNS) could be an alternative treatment option. However, studies have indicated that VNS treatment has smaller seizure reducing effect in this group than in patients without cognitive problems. (Huf et al. Epilepsy and Behavior 2005; 6: 417–23). The purpose of this study is to evaluate the general effect of VNS for people with cognitive disabilities, including additional effects. Method: All patients treated with VNS for at least 10 months at the department of Neurology, University Hospital in Link€oping were included in this study. Data was collected retrospectively from medical records and with a specially designed questionnaire. Cognitive disability was defined as not having the ability to live independently because of cognitive problems. Those who had none or less than 50% reduction of frequency of their seizures were listed as non-responders.


210 Abstracts Results: 82 participants were included and 46 of those had cognitive disabilities. Effect of VNS on seizure-frequency was lower among participants with cognitive disabilities than the other participants (p < 0.05). However other improvements, such as milder seizures, shorter post-ictal period, improvement of cognitive functions and alertness, were reported by the participants. Among non-responding participants with cognitive disability 69% (25 out of 36) reported other benefits of VNS treatment. Conclusion: VNS had smaller effect on seizure frequency amongst participants with cognitive disabilities than participants without cognitive disabilities. However additional improvements from VNS treatment were observed. It appears that people with cognitive dysfunction often benefit from VNS treatment regardless of poorer seizure control and VNS could therefore be considered as a treatment option for therapy resistant seizures among people with cognitive dysfunction.

Surgical Treatment and Neuromodulation 2 Monday 12th September P692 VAGUS NERVE STIMULATION AND CORPUS CALLOSOTOMY IN REFRACTORY EPILEPSY EXPERIENCE FROM A TERTIARY CENTER IN RIO DE JANEIRO Andrea-Meira DI, Faverett E Paulo Niemeyer Brain Institute, Epilepsy, Rio de Janeiro, Brazil Purpose: Refractory epilepsy is a devastating brain disorder with significant socio economic impact. The use of antiepileptic drugs (AED) is the primary method of treatment of epilepsy. Unfortunately, despite the existence of numerous AED, they are unable to provide adequate seizures control in about 20–40% of patients. Vagus nerve stimulation (VNS) and callosotomy can be used to help seizure control however the role of each method needs to be better defined. This study aim to compare the efficacy of corpus callosotomy and VNS for long-term adjunctive therapy. Method: This is a retrospective analysis of six patients that were submitted to both corpus callosotomy and VNS. All patients had refractory epilepsy and failed at least in three drugs. We evaluated seizure frequency and compare with 3 months prior the procedure and complications for each method. Three patients underwent to callosotomy prior to VNS and the other three was implanted with VNS before. Results: Seizure type among the patients included atonic with drop attacks, atypical absence, generalized tonic clonic seizures and discognitive seizure. All of them had mental deficiency. The mean age was 28.3 years (range 10–56 years) and the mean age of onset of disease was 22.8 months (range 3–60 months). Among the patients initially submitted to callosotomy 1 out 3 (33.3%) had reduction of seizure frequency by around 30% and one patient had worsening of his seizures frequency. In those patients who underwent VNS implantation first, two (66.6%) had seizure reduction around 50%. There was any adverse event related with VNS implantation however one patient presented with local is infarct after callosotomy. Conclusion: In these small series of cases patients with initial VNS implantation had better response in reducing seizure frequency than those who submit to callosotomy first. We also observed that callosotomy had higher morbidity.

P693 A PROSPECTIVE LONG-TERM STUDY OF HEALTHRELATED QUALITY OF LIFE AND MOOD AFTER EPILEPSY SURGERY OR PRE-SURGICAL WORK-UP Edelvik A1, Taft C2, Malmgren K1 1 Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2 Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Purpose: To evaluate health-related quality of life (HRQoL), depression and anxiety at long-term in epilepsy patients after epilepsy surgery or presurgical investigations. Method: Patients with drug-resistant epilepsy who underwent presurgical evaluation between 1995 and 1998 completed the Short Form Health Survey (SF-36) and the Hospital Anxiety and Depression scale (HAD) questionnaires at baseline, after 2 years and at long-term (cross-sectional follow-up, mean 14 years, range 9–17). Previously we reported that at 2year follow-up (Taft et al. Epilepsia 2014;55:878–885) patients who were seizure free after surgery (n = 53) had significantly improved on nearly all SF-36 domains and composites to levels comparable with population norms, as well as on HAD anxiety, whereas no improvements were seen for operated patients with persistent seizures (OpS, n = 42) or non-operated patients (n = 45). Here we compare long-term SF-36 and HAD scores with 2-year scores for the three groups, using Wilcoxon signed rank test and Effect sizes (ES). Results: Long-term data were available for 68/96 surgical patients (8 dead, 4 re-operated) and 24/45 non-surgical patients (4 dead, 1 operated). Compared to 2-year follow-up, no significant differences were seen for any SF-36 domain or composite, HAD anxiety or depression in any of the three groups, except in OpS where a significant, moderate improvement in SF-36 Role Physical (p < 0.024; ES = 0.64) was seen. All other effect sizes were trivial or small. Conclusion: Long-term outcomes of HRQoL, anxiety and depression after epilepsy surgery or presurgical investigations were stable at group level compared to 2-year follow-up. However, improvements as well as worsening in HRQoL were seen in a subset of patients in all three groups.

P694 THE EFFECTIVENESS OF VAGAL NERVE STIMULATION THERAPY IN PATIENTS WITH REFRACTORY EPILEPSY AND MENTAL RETARDATION - A 12-MONTH FOLLOW UP Flicinski J1, Winczewska-Wiktor A1,2, Barciszewska AM3, Liebert W3, Steinborn B1 1 Chair and Department of Developmental Neurology, Poznan University of Medical Sciences Poland, Pozna n, Poland, 2 Outpatient VNS Department, The Heliodor Swiecicki University Hospital in Poznan Poland, Pozna n, Poland, 3Chair and Department of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences Poland, Poznan, Poland Purpose: The aim of our study is to present the efficacy of treatment in 25 patients with drug-resistant epilepsy and mental retardation. Method: We collected data including: demographic, age at epilepsy onset and VNS implantation, duration of epilepsy, seizure type, number of antiepileptic drugs (AEDs), side effects and reduction of seizures after 12-month implantation of VNS. Results: The analysis included 25 patient (aged from 8 to 36 years at the time of implantation). At 12th month after the implantation respectively (15) 60% of patients had ≥50% reduction in baseline seizure frequency of


211 Abstracts the predominant seizure type, three patient were nonresponders. One patient remained seizure-free throughout the 12 months study period. The average amount of AEDs was 3, the maximum was 7. During a 12month study only one patient had a reduction dosage of AED, however, none of the patients withdrew AED after VNS implantation. 40% of patients was diagnosed with primary focal epilepsy, the rest of 15 patients had secondary epilepsy, among others: 7-focal epilepsy, 3-tuberous sclerosis, 1-neurofibromatosis type I, 2-non malignant brain tumor, 1-polymicrogyria, 1-schizencephaly. 80% of patients had mental retardation. The average duration of epilepsy before VNS implantation was 11 years. No major complications or side effects requiring discontinuation of VNS therapy were encountered but in one patient there was a reduction of parameters of VNS due to dizziness and bad feelings. The most frequent adverse events were: hoarseness, cough, sore throat, and anorexia experienced by 25% of patients. Conclusion: Most data about the efficacy of VNS treatment state that the reduction of seizures >50% is observed in 24 months, however, in our observation we concluded that this period of time might be shorter. In addition, the reduction of seizures during the VNS treatment might improve cognitive functions.

P696 TMS COMBINED WITH EEG IN GENETIC GENERALIZED EPILEPSY: A PHASE II DIAGNOSTIC ACCURACY STUDY Kimiskidis VK1, Tsimpiris A1, Ryvlin P2,3, Kalviainen R4, Koutroumanidis M5, Valentin A5,6, Laskaris N1, Kugiumtzis D1 1 Aristotle University of Thessaloniki, Thessaloniki, Greece, 2 Hospices Civils de Lyon, Lyon, France, 3CHUV, Lausanne, Switzerland, 4University of Eastern Finland, Kuopio, Finland, 5 Kings College London, London, United Kingdom, 6Universidad Complutense Madrid, Madrid, Spain Purpose: TMS combined with EEG (TMS-EEG) is a recently introduced neurophysiological technique that holds significant diagnostic potential in the field of epilepsy. No study has investigated the diagnostic accuracy of TMS-EEG in Genetic Generalized Epilepsies (GGE). The present study aims: A) To develop and optimize a TMS-EEG brain stimulation and data analysis protocol in patients with GGE. B) To investigate the diagnostic accuracy of TMS-EEG in patients with GGE. Method: Pilot experiments resulted in the development, testing and validation of an optimal paired-pulse TMS-EEG protocol combined with multi-level data analysis (i.e. descriptive, average & single-trial evoked potential and data mining). Briefly, we employed a paired-pulse stimulation paradigm at rest, during hyperventilation (HV) and post-HV. This protocol was applied in 11 healthy controls and 25 patients with GGE further dichotomized into responders to antiepileptic drugs (n = 13) and non-responders (n = 12). Features (n = 57) extracted from TMS-EEG responses after multi-level analysis were given to a feature selection scheme and further to a Bayesian classifier and the accuracy of assigning participants into two (patients/ controls) and three (responders/ nonresponders/controls) classes was computed. Results: The protocol was well-tolerated. From a descriptive point of view, TMS induced Epileptiform discharges (n = 2, non-responders) and morphologically abnormal TMS-Evoked Potentials (n = 4, non-responders). On the basis of the optimal feature subset, the cross-validated accuracy of TMS-EEG for differentiating GGE patients from controls was 0.862 at rest, 0.814 during HV and 0.916 post-HV. The cross-validated accuracy for differentiating responders from non-responders and controls was 0.655 at rest, 0.555 during HV and 0.416 post-HV. All accuracy levels were statistically significant. Features providing maximal accuracy values varied amongst different conditions indicating that the employed multi-level analysis is a relevant approach.

Conclusion: TMS-EEG can be used for diagnostic purposes as well as to stratify the severity of GGE. Further testing of this promising technique is warranted.

P697 VAGUS NERVE STIMULATION IN EPILEPSY: A LONGTERM ANALYSIS FOR OUTCOME Landré E, Chassoux F, Mann M, Turak B, Devaux B, Champeaux C Sainte-Anne Hospital, Department of Neurosurgery, Paris, France Purpose: To depict the long-term effectiveness and survival of Vagus Nerve Stimulation (VNS) on intractable epilepsy and search for factors that may influence the outcome. Method: We reviewed the clinical and surgical records of the 129 patients who had a VNS implanted between 1996 and 2015. Logistic regression and survival methods were implemented. We considered as responders the patients with at least 50% seizure frequency reduction and minimal 2 years of stimulation. Results: Epilepsy was classified as partial symptomatic in 67 patients (52%), partial cryptogenic in 42, (33%), generalized cryptogenic in 20 (16%) including Lennox-Gastaut syndrome in 12. Half of the patients had daily seizures and 30 underwent a previous neurosurgical procedure. Median time between epilepsy onset and VNS implantation was 25 years, IQR[17–33], median age at VNS implantation was 34 years, IQR[25–43] and median duration of the VNS therapy was 6 years, IQR [3–10]. In 21 patients (16%) the device the electrode was removed; 4 patients had a turned off system, 8 were lost to follow-up and 6 deceased. Among 112 patients having >2 years of stimulation, 54 patients were considered as responders (48%). In addition, 8 patients were not respondeurs but the generator was replaced because of seizure intensity reduction and/or magnet effect utility. No major side effect or complication were observed except in two patients (early postoperative infection in one, vocal cord paralysis in another one). Survival probability of having a functional VNS at 5 years was 82%, IC95%[75,90]. Among the variables studied, short epilepsy duration and young age at VNS implantation were associated with the responder rate. Conclusion: The indication of VNS should be discussed earlier in the course of non-surgical and drug-resistant epilepsy. Surgical complications are rare and probability that the device remains functioning at longterm is high.

P698 A CLINICAL, NEURORADIOLOGICAL, AND NEUROPHYSIOLOGICAL STUDY WITH SURGICAL OUTCOME ON 45 PATIENTS WITH DRUG-RESISTANT PARTIAL EPILEPSY RELATED TO PERIVENTRICULAR NODULAR HETEROTOPIA Mirandola L1, Pelliccia V2, Gozzo F2, Cossu M2, Meletti S1, Tassi L2 1 Department of Biomedical, Metabolic and Neural Sciences, University of Modena e Reggio Emilia, Modena, Italy, 2’C. Munari’ Epilepsy Surgery Centre, Niguarda Hospital, Milano, Italy Purpose: Periventricular nodular heterotopias (PNHs) are malformations of cortical development related to neuronal migration disorders, frequently associated with drug resistant epilepsy (DRE); PNH Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

212 Abstracts epileptogenesis is not clearly understood, namely the precise onset, propagation or maintenance of seizures in this kind of partial epilepsies are not clarified. Stereoelectroencephalography (SEEG) is frequently a necessary step of the presurgical evaluation permitting the recognition of the epileptogenic zone and giving important neurophysiological data of the explored cerebral regions, as the interictal and ictal activities of the heterotopia. The first aim is to investigate the epileptogenic role of PNH trough a clinical, electrical and neuroradiological characterization. The second one is to evaluate the efficacy of thermocoagulation through intracerebral electrodes (THC). Method: Patients with DRE associated with PNH who completed a surgical work-up have been selected: clinical, neurophysiological (SEEG), neuroradiological (PET and MRI) data and surgical outcome were analyzed. Results: 45 patients were selected (23 female, mean age: 32 years): they completed the surgical workup with traditional neurosurgery or with THC (n = 16 patients). Conclusion: The epileptogenic role of PNH and results obtained by the different non-invasive examinations are discussed. THC represents a valuable therapeutic alternative in patients with PNH, even when bilateral PNHs are present (Cossu et al., JNS, 2015).

P699 VAGUS NERVE STIMULATION IN LAFORA BODY DISEASE Petelin Gadze Z1, Hajnsek S1, Milat D2, Borovecki F3, Nankovic S1, Mrak G4, Gotovac K3, Sulentic V1, Mudrovcic M5 1 Department of Neurology, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Referral Centre for Epilepsy of the Ministry of Health of the Republic of Croatia, Zagreb, Croatia, 2Sveti Rok Polyclinic, Zagreb, Croatia, 3 Department for Functional Genomics, Centre for Translational and Clinical Sciences, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia, 4 Department of Neurosurgery, University Hospital Centre Zagreb and School of Medicine, University of Zagreb, Zagreb, Croatia, 5School of Medicine, University of Zagreb, Zagreb, Croatia Introduction: Lafora body disease (LBD) is a rare autosomal recessive disorder characterized by progression to inexorable dementia and frequent occipital seizures, in addition to myoclonus and generalized tonic-clonic seizures (GTCSs). It belongs to the group of progressive myoclonus epilepsies (PMEs), rare inherited neurodegenerative diseases with great clinical and genetic differences, as well as poor prognosis. Since those patients have a pharmacoresistant disease, an adjunctive treatment option is vagus nerve stimulation (VNS). To date, there are four reported cases of the utility of VNS in PME - in Unverricht-Lundborg disease (ULD), myoclonic epilepsy with ragged-red fibers (MERRF), Gaucher’s disease, and in one case that remained unclassified. Case presentation: A 19-year-old male patient had progressive myoclonus, GTCSs that often progressed to status epilepticus (SE), progressive cerebellar and extrapyramidal symptomatology, and dementia, and his disease was pharmacoresistant. We confirmed the diagnosis of LBD by genetic testing. After VNS implantation, in the 3-year followup period, there was a complete reduction of GTCS and SE, significant regression of myoclonus, and moderate regression of cerebellar symptomatology. Conclusion: To our knowledge, this is the first reported case of the utility of VNS in LBD. Vagus nerve stimulation therapy may be considered a treatment option for different clinical entities of PME. Further studies with a larger number of patients are needed. Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

P700 VAGUS NERVE STIMULATION DEVICES CAN BE COMPLETELY REMOVED OR REPLACED SAFELY Turak B, Landre E, Champeaux K, Chassoux F, Devaux B Centre Hospitalier Sainte Anne, Neurosurgery, Paris, France Purpose: Vagus nerve stimulation (VNS) using an implanted device is one option for the treatment of drug refractory epilepsy. Occasionally the need for device lead removal or replacement arises. Removal of the device lead wrapped around the vagus nerve is technically more challenging than implantation. Fearing neurovascular damage, many surgeons hesitate to remove completely the implanted material when indicated. However, retained electrodes and wiring fragments may present an additional source of danger and artefacts for procedures such as magnetic resonance imaging, diathermy and electrocautery. The safety of complete VNS lead removal therefore needs to be assessed. Method: During the last decade, 27 patients (16 males, 17–61 years old) with a VNS device for the treatment of epilepsy underwent a total of 29 procedures for lead removal or replacement in our institution where over 129 such devices have been implanted to date. The most frequent reasons for the procedure were lack of a satisfactory clinical response, discomfort and lead damage, often in combination. The average delay between implantation and lead replacement or removal was 5.9 years (range 0.1–19.7). Standard microsurgical technique was used for all cases and electrophysiological nerve monitoring is now employed on a routine basis. Results: For the 9 lead replacement procedures (including generator replacement for 5) and the 20 complete device removal procedures no complications, serious or otherwise, were encountered. Conclusion: Implanted VNS device complete lead removal and replacement can be performed safely. This point must be taken into consideration by the medical team caring for the patient when confronted by situations where device removal may be preferable. It is also a point to be emphasized during the discussion with patients for whom VNS implantation is indicated, and with their family, and may assist them in their decision.

Surgical Treatment and Neuromodulation 3 Tuesday 13th September P701 EPILEPSY SURGERY OUTCOME - OUR CENTER FINAL RESULTS Nez adal T1,2,3, Mohapl M4, Bajaček M1,2, Hovorka J1,4, Nemcov a I1, Z amecnık J5, Lisc ak R6, Tichy M7, Sroubek J8, Brad ac O4 1 Epileptology and Neuropsychiatry Center, Na Frantisku Hospital, Prague, Czech Republic, 2Neurology Department, Military University Hospital, Prague, Czech Republic, 3Institute of Neuropsychiatric Care, Prague, Czech Republic, 4 Department of Neurosurgery, Military University Hospital, Charles University, 1st Faculty of Medicine, Prague, Czech Republic, 5Department of Pathology and Molecular Medicine, University Hospital Motol, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic, 6Stereotactic and Radioneurosurgery Department, Na Homolce Hospital, Prague, Czech Republic, 7Department of Neurosurgery, University Hospital Motol, Prague, Czech Republic, 8Department of Neurosurgery, Na Homolce Hospital, Prague, Czech Republic Purpose: Epilepsy surgery is at present a substantial part of refractory epilepsy treatment. The aim of our study is to introduce complete surgery

213 Abstracts results of a smaller center working within Prague Epilepsy Surgery Group, which was closed in December 2015 due to hospital restructuring. Method: We evaluated 115 patients (age: 38 10.5 years, men: 55.7%) which underwent surgical procedure between September 1999 and February 2014. Assessed were: outcome at least 2 years (mean folow-up 8.1 years) by Engel criterias, histology in resective cases and antiepileptic drug (AE) withdrawal. The outcome of vagus nerve stimulation (VNS) and deep brain stimulation (DBS) were rated percentually. Results: Temporal lobe resection (mostly anteromesial - AMTR) was performed in 57, extratemporal in 15, stereotactic radiofrequency amygdalohippocampectomy (SAHE) in 5 patients. VNS was implanted in 42 and DBS in 2 patients. In patients with temporal resection met Engel I 40 (70.2%) patients, Engel II 8 (14.0%), III 7 (12.3%) and IV 2 (3.5%). Extratemporal patients were in Engel I 8 (53.3%), II (33.33%) and III (13.33%). Histology of temporal lobe resections was hippocampal sclerosis in 38 cases, focal cortical dysplasia (FCD) by Palmini 1A in 14, 1B in 6, 2A in 1, gliosis in 16, hamartoma in 2, cavernoma and nodular heterotopia in 1 sample. In extratemporal resections we found mostly FCD 2B in 5, 1A, 1B and 2A in 1, hamartoma and ganglioglioma in 1 and gliosis in 6 samples. Two SAHE patients were Engel I(A). VNS responder rate was 66.7%, 3 patients seizure free, DBS has one responder. AE were discontinued in 27 patients (25 after temporal resection). Clinically significant post-surgical motor or cognitive deficit have four patients. VNS was explanted due to low effect in 3 patients. Conclusion: Our results are coherent with other studies and prove benefits of epilepsy surgery.

P702 ENDOSCOPIC ROBOT-GUIDED DISCONNECTION OF HYPOTHALAMIC HAMARTOMAS: RESULTS IN 18 CASES De Benedictis A, de Palma L, Cappelletti S, Messina R, Randi F, Cossu S, Figa Talamanca L, Bernardi B, Pietrafusa N, Delalande O, Specchio N, Marras CE, Vigevano F Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy Purpose: To review our experience on the endoscopic disconnection of drug-resistant epilepsy symptomatic of hypothalamic hamartomas (HHs). Method: Our series includes 18 patients: 13 M. Mean age at epilepsy onset was 11.8 17 months, age at surgery was 9.3 7 years. Each patient received a complete pre-surgical evaluation, including neurological, neurophysiological, neuropsychological, and neuroimaging. HHs were defined according to the Delalande’s classification. In all surgeries, we adopted the RObotized Stereotactic Assistant (ROSA, Medtech) and the disconnection was performed by using monopolar or laser thulium (Revolix) coagulation. In eight patients, we performed intraoperative EEG registration. In 6/8 cases, the invasive monitoring identified repetitive spikes within the lesion. Post-operative evaluation was performed at 1-3-6 months. Results: HH were classified in type II: 9 (50%), type III: 7 (38%), type IV: 2 (11%). All patients presented with multiple per day gelastic seizures, 7 patients presented also multiple per week focal seizures, and 1 patient presented also monthly generalized tonic-clonic and tonic seizure. Neuropsychological evaluation revealed a mean Griffith DQ score of 90 11 (range 79–101). After surgery no permanent deficits were seen. After a mean follow-up period of 10 months, 11/18 patients (61%) were in Engel class I, 3/18 (16%) in class II, 2/18 (11%) in class III, and only 2/ 18 (11%) in class IV. No significant discordances of the neuropsychological status were reported. Due to seizure persistence, six patients underwent a second surgery, with post-operative improvement of the Engel score.

neuropsychological outcome. Neuronavigation stereotactic systems, in association with robotic technology and laser coagulation, allowed to safely manage more difficult cases (e.g. tight ventricles or small lesions). Intra-lesional EEG contributes in localizing the ictal activity. In refractory cases, repeated procedures might be proposed to optimize the outcome.

P703 EPILEPSY SURGERY IN CHILDREN: CLINICAL AND FOLLOW-UP DATA OF THE FIRST 100 OPERATED CHILDREN CASES AT THE BAMBINO GESU HOSPITAL, IRCCS, ROME, ITALY de Palma L1, De Benedictis A1, Pietrafusa N1, Cappelletti S1, Bernardi B2, Diomedi Camassei F3, Maria Carmen G4, Fig a Talamanca L2, Trivisano M1, Fusco L5, Marras CE5, Specchio N1, Vigevano F5 1 Epilepsy Surgery Unit, Department of Neuroscience and Neurorehabilitation, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 2Radiology Unit, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 3Pathology Unit, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 4Nuclear Medicine Unit, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy, 5 Neurosurgery Unit, Bambino Ges u Children’s Hospital, IRCCS, Rome, Italy Purpose: Aim of this study is to collect clinical data and surgical outcome of the first 100 cases operated at the Bambino Gesu Children Hospital from 2009 to 2015 for drug resistant epilepsy. Method: All clinical, neurophysiologic and neuroimaging data and all follow-up visits were prospectively evaluated. One hundred patients were enrolled. Mean age at seizure onset was 4.9 6 years, mean age at surgery was 11.1 9 years, with a mean epilepsy duration of 6.2 7 years. Patients had usually high seizures frequency (49% with daily seizures). All patients had a basal MRI, mostly abnormal (97%) and a neuropsychological evaluation. A video-EEG recording was performed in all patients and in 96% was longer than 24 h. Most patients (80%) had at least one seizure recorded (mean 5.3). FDG-PET and f-MRI were performed in more selected cases (11% and 9% respectively). S-EEG was performed in 27 cases when anatomo-electro-clinical correlations were not clear. Results: Mean follow-up was 23.5 19 months, with 96% who had at least 6 months of follow-up. Of these 73% were in Engel class 1, 12% in Engel class II, 11% in Engel class III while 6% in Engel 4. Thirty-five percent of patients are seizure free without AED. The most common pathology was Focal Cortical Dysplasia (30%), followed by Low Grade Tumors (20%) and Hypothalamic Hamartoma (18%). Seizure free rate changed significantly when considering the pathology: 95% of Low Grade Tumors achieved seizure freedom, while 76% with Focal Cortical Dysplasia and 61% with Hypothalamic Hamartoma. Surgical procedures were mainly resections (59%), followed by multilobar or hemispheric disconnections (24%) and hypothalamic disconnection (18%). Conclusion: Our preliminary results of pediatric epilepsy surgery, show a good overall seizure free rate (73% seizure-free) with a more favorable outcome for Tumors and Focal Cortical Dysplasia.

Conclusion: Endoscopic transventricular disconnection is an effective mini-invasive treatment of HHs, with a positive impact on epilepsy and Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

214 Abstracts P704 CORRELATION OF SURGICAL OUTCOME WITH ICTAL AND INTERICTAL EEG PATTERNS IN TEMPORAL LOBE EPILEPSY Gupta S1, Jayalakshmi S1, Panigrahi M2, B S3 1 Krishna Institute of Medical Sciences, Neurology, Hyderabad, India, 2Krishna Institute of Medical Sciences, Neurosurgery, Hyderabad, India, 3Krishna Institute of Medical Sciences, Neuropathology, Hyderabad, India Purpose: To identify ictal and interictal EEG patterns in patients with temporal lobe epilepsy (TLE) and correlate with surgical outcome. Method: The ictal and interictal EEG data of 375 patients with TLE who underwent surgery and at least 1 year post-surgery follow-up was reviewed. Ictal EEG patterns were classified according to frequency, spatial distribution, duration of persistence of rhythm (16 years) with HS, operated 1995– 2009 in Denmark. Only left hemisphere dominant patients were included (excluding 12 left handed and ambidextrous with right hemisphere dominance or no WADA-test). Additional subjects were excluded due to intelligence level below normal range (9) or not Danish as native language (8). Follow-up was not possible in 17 cases. Thus, 62 patients were analysed. The patients were allocated to SAH (22) or TLR (40), predominantly based on intraoperative electrocorticography (ECoG). Verbal learning and memory was tested before and 1 or 1 years after surgery. After surgery subjective symptoms were assessed using a questionnaire. Results: Verbal memory performance (mistakes before - after) was unchanged in SAH but slightly worsened in TAH, not statistically significant (p = 0.057). Verbal learning was more affected in left sided (dominant hemisphere) operations (p = 0.001). Cognitive subjective memory outcome after operation was better in Engel class I vs. II-IV (p = 0.033). There were no significant correlation between the verbal learning or memory tests and the subjective assessments of language or memory impairment. Conclusion: Our results imply that a more extended resection (TLR vs. SAH) do not cause a worse outcome in verbal learning or memory. However, though no significant difference in mean verbal memory outcome was demonstrated between groups, there was a large variation in outcome in the TLR group. Verbal learning outcome is worse in patients operated on the left side. There was no difference in seizure outcome between TLR and SAH groups.

223 Abstracts P730 THE DANISH EPILEPSY SURGERY PROGRAMME ALIGNS WITH BEST INTERNATIONAL STANDARDS Holm E1, Foged MT1, Brennum J2, Pinborg LH1, Danish Epilepsy Surgery Group 1 Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 2Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Purpose: Despite optimal medical treatment ⅓ of epilepsy patients continues to have seizures. Epilepsy surgery is widely accepted as an effective therapeutic option in a selected subset of patients with drug-resistant focal epilepsy. Here we report the results of the Danish epilepsy surgery programme from 2009 to 2014. Method: One hundred and sixty-nine consecutive patients operated at Rigshospitalet were included. Information was gathered retrospectively from patient records and databases. The Danish Health Authority and the Danish Data Protection Agency approved the study. Results: The pattern of referral differs from region to region in Denmark. On average, patients had been drug-resistant for 15.4 years (SD = 13.3) and tried 5.7 drugs (SD = 2.4) at the time of the surgery. At 1-year follow-up 65% of all patients (n = 162) operated were free from disabling seizures (Engel’s class I), 51% of the patients were completely seizure free since surgery (Engel’s class IA). Only 9% reported no worthwhile improvement (Engel’s class IV). Similar numbers for patients operated in the mesial temporal lobe (n = 128) were 69%, 55% and 7%, respectively. For extratemporal operated patients (n = 34) the outcomes were 50%, 38% and 15%, respectively. Intracranial registrations were done in 52 patients and the outcomes were 60%, 54% and 12%, respectively.

surgery due to different extratemporal lesional and nonlesional causes. Mean postoperative follow-up time was 110 month (range 12– 210 month) after surgery. Overall 290 patients (79%) achieved an excellent postoperative outcome with Class 1a,1 and 2 according to ILAE Classification (Wieser et al.). 45 patients had outcome Class 3, 21 patients Class 4 and 11 patients class 5. 68 patients (45%) out of 154 patients who were absolutely seizure free after operation (Class 1a) were off medication, whereas only 28 patients (24%) of 117 with Class 1 and none of 19 patients with Class 2 (only auras). Conclusion: AED withdrawal increases the risk of breakthrough seizures after epilepsy surgery, but the seizures are usually well controlled after readministration of medication. Large randomized studies are necessary for validation of the data.

P732 TWO-YEAR AND LONG-TERM SEIZURE OUTCOME AFTER RESECTIVE EPILEPSY SURGERY IN PATIENTS WITH LOW IQ Reinholdson J1, Olsson I1, Edelvik A2, Rydenhag B2, Malmgren K2 1 Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Department of Clinical Neuroscience and Rehabilitation, Gothenburg, Sweden Purpose: To describe 2-year and long term seizure outcome after resective epilepsy surgery in patients with low IQ operated in Sweden 1990– 2013.

Conclusion: The outcomes of the Danish epilepsy surgery programme are comparable or better than international standards found in recent meta-analyses. Future patients may be referred to epilepsy surgery evaluation at an earlier stage.

Method: Data on all patients in Sweden undergoing epilepsy surgery are reported to the Swedish National Epilepsy Surgery Register. For this study, data on all patients with IQ < 70 undergoing resective epilepsy surgery were analysed. Variables studied were: seizure frequency, IQ, type of surgery and aetiology.

P731 THE IMPLICATION OF REDUCTION OF ANTIEPILEPTIC MEDICATION ON POSTOPERATIVE OUTCOME AFTER EPILEPSY SURGERY Pataraia E1, Trimmel K1, Jung R1, Czech T2, Dorfer C2, AullWatschinger S1 1 Medical University of Vienna, Neurology, Vienna, Austria, 2 Medical University of Vienna, Neurosurgery, Vienna, Austria

Results: In all 847 patients underwent resective epilepsy surgery in Sweden 1990–2013; 166 had an IQ < 70 (19.6%); 143 of these (43 adults and 100 18 years or younger at operation) had a 2-year follow-up and 82 had a long-term follow-up 5 or 10 years postoperatively. Temporal lobe resection was the most common surgical procedure. The most prevalent aetiologies were gliosis and malformations of cortical development. At the 2-year follow-up, 30% of the children and 35% of the adults were seizure-free. There was no difference in seizure outcome between the patients with IQ 50–69 and those with IQ < 50. Hemispherotomy and tumour aetiology were associated with the best seizure outcomes. At the long-term follow-up, 30% of the 60 patients with IQ 50–69 and 25% of the 16 with IQ < 50 were seizure-free.

Purpose: The aim of the study is to assess the relation between the keeping or stopping of AEDs after epilepsy surgery and long-term seizure outcome. Method: All patients who underwent epilepsy surgery at the Epilepsy Center, Medical University of Vienna, from January 1994 until December 2013 were evaluated for the study. The study was approved by local ethics committee. Prior to surgery, patients had failed at least two AEDs, completed a presurgical work-up and were selected for surgery after a multidisciplinary patient management conference. We collected data on clinical, imaging and electrophysiological patient characteristics. The doses of AEDs used at the time of surgery, at seizure recurrence and at the last available follow-up were recorded.

Conclusion: Our results suggest that seizure freedom is achieved in a significant proportion of patients with low IQ undergoing epilepsy surgery and that the improvement is consistent over time. Contrary to our earlier findings (Malmgren et al Brain, 2008;131(Pt 2):535–542) the degree of intellectual disability was not shown to be predictive of seizure outcome in this larger cohort. Selected patients with low IQ may well benefit from epilepsy surgery, but further investigation is warranted to determine predictors for a favourable seizure outcome in patients with low IQ.

Results: The data of 367 patients were included in final analysis. 308 patients (83.9%) underwent resection on temporal lobe: 137 patients (37.3%) had selective amygdalohippocampectomy with histologically proven hippocampal sclerosis, 119 patients (32.3%) had anteromesial resection and 52 patients (14.1%) underwent resection of epileptogenic tumors localized in temporal lobe. 59 patients (16.1%) had epilepsy Epilepsia, 57(Suppl. 2):6–225, 2016 doi: 10.1111/epi.13609

224 Abstracts P733 THREE-DIMENSIONAL VISUALIZATION OF MORPHOMETRIC BRAIN ANOMALIES IN PATIENTS WITH TEMPORAL LOBE EPILEPSY Rosén J, Krysl D, Strandberg J, Rydenhag B, Malmgren K, Heckemann RA Institute of Neuroscience and Physiology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden Purpose: Brains of patients with temporal lobe epilepsy exhibit morphometric features that distinguish them from brains of healthy persons, and these features can be identified on MR images by computer algorithms, even when they are invisible to the human eye. Visualizing these anomalies in a straightforward, intuitive way would be valuable for identifying biomarkers of interest for prediction of surgical outcome. The purpose of this work is to create a tool that finds the morphometric anomalies and presents them in an easily interpreted way. Method: To visualize brain anomalies, we used the popular MATLAB environment to construct a framework for interpretation and generation of NIFTI files, which is a commonly used format for storing MR images. The program code was made object-oriented to make it possible to easily add functionality and new algorithms. Image segmentation was done with MAPER (multi-atlas propagation with enhanced registration, Heckemann et al. NeuroImage; 2010;51;221–227). Results: The result is a program, taking as input a presurgical MR image. After segmentation, a z-score representing possible anomalies is calculated for 83 brain segments by comparison with a set of 492 healthy subjects. A new synthetic MR image is then constructed for the analyzed patient, where each segment is colored with an intensity proportional to the magnitude of the z-score. The resulting file can be loaded into any NIFTI-compatible image viewer for analysis. Conclusion: We have developed a system that enables visualization of brain anomalies in an intuitive and accessible way. By analyzing multiple MR images with this tool, it will be possible to identify anomaly patterns in a less time-consuming way for clinical research on outcome prediction of epilepsy surgery.

P734 THE ROLE OF REGIONAL EPILEPTOLOGIST - CAN BE THE ESTIMATED TIME OF EPILEPSY ONSET TO EPILEPSY SURGERY EFFECTIVELY SHORTENED? Slonkova J, Bar M University Hospital Ostrava, Clinic of Neurology, Ostrava, Czech Republic Purpose: To analyse the time from epilepsy onset to epilepsy surgery and the timing role of the regional epileptologist. Method: Retrospective study of the patients who have been sent to epilepsy surgery centre. Descriptive statistics of %, mean, median and standard deviation was used. Results: Between 2007 and 2015 we have discussed 36 cases with refractory epilepsy. 16 men and 20 women. 17 (47.2%) had brain surgery, 2 (5.6%) VNS implantation, to 6 (16.7%) no surgery recommended, 9 ((25%) have not resolved yet. 1 (2.7%) possibly refractory-two years since epilepsy onset. 19 patientshad mean age while surgery procedure 36 8.112 years. The mean onset of epilepsy and treatment to the first meeting with epileptologist is 19.68 years 13.75. Median 17 years. The mean time from the first meeting to epilepsy surgery was 34.7 29.38 months (2.89 years) median 18 month. 1 patient was sent repeatedly after first conservative recommendation in the past. 15 patients are Engel I, 1 Engel II. To one of Engel IV, vagal nerve stimulation was added, less than 50% reduction of seizures, now remains on successful ketogenic diet. 2 of all patients have history of childhood epilepsy


with seizure freedom during adolescence and seizures reoccurrence in young adulthood. The onset of epilepsy was counted since adulthood. 2 patients with primary VNS care are responders with more than 50% reduction of seizures. Conclusion: Epilepsy surgery is effective way of treatment. Patient without seizure freedom within 1 year after epilepsy onset should be treated by the specialist to fulfil the timing of at maximum 2 years of ineffective treatment before surgery consultation. Fortunately, long period does not seem to influence the result of the surgery, but the quality of life and social status is a task for the next studies.

P735 VISUAL FIELD DEFECTS IN EPILEPSY PATIENTS TREATED WITH TEMPORAL LOBE RESECTION Steensberg AT1, Olsen AS2, Litman M1, Holm E1, Jespersen B3, Kjaer TW4, Kolko M5, Pinborg LH1 1 Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 2Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 3Department of Neurosurgery, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, 4Department of Neurology, Copenhagen University Hospital, Roskilde, Copenhagen, Denmark, 5 Department of Ophthalmology, Copenhagen University Hospital, Roskilde, Copenhagen, Denmark Purpose: Epilepsy surgery is a well-established treatment in patients with drug-resistant focal epilepsy. It is known that epilepsy patients undergoing resections of the temporal lobe may get a postoperative visual field defect (VFD). The aim of this study was to detect VFD after epilepsy surgery and to determine the risk of VFDs related to the operation. Method: This study included 37 epilepsy patients treated with an anterior temporal lobe resection. All patients were postoperatively tested with the Humphrey Field Analyzer (HFA). The patients completed a questionnaire to determine the subjective symptoms and received a full ophthalmic examination to exclude competing eye diseases. Patients were divided into four groups based upon the number of missed points on the HFA printout (figure 1): No defect: 0–1 missed points, small VFD: 1–6 missed points, moderate VFD: 7–12 missed points and severe VFD: 13– 19 missed points. Results: A VFD was demonstrated in 81% of the patients: 32% had a small VFD, 30% had a moderate VFD and 19% had a severe VFD. 70% of patients with a VFD were not aware of it (figure 2). Two patients having no objective signs of VFD claimed to have abnormal VFs. Three out of 7 patients having a severe VFD reported normal VF in the questionnaire. Conclusion: This study showed a high risk of a VFD after resective surgery for temporal lobe epilepsy. Despite this, only a minority of the patients subjectively recognised any visual fields change after surgery.

225 Abstracts P736 TRANS-SYLVIAN DISCONNECTION SURGERIES FOR MEDICALLY INTRACTABLE EPILEPSY INCLUDING TEMPORAL LOBE Sugano H, Nakajima M, Suzuki H, Arai H Juntendo University/Epilepsy Center, Neurosurgery, Tokyo, Japan Purpose: Disconnection surgeries are indicated for intractable epilepsy, instead of resection. The benefit of disconnection surgeries is reducing surgical insult, but the problematic issue of them is maintaining the surgical orientation during disconnection procedure. We think that shorter distance of disconnection can provide accurate and complete disconnection. In order to do the shorter disconnection, we indicated trans-sylvian approach to the temporal stem for temporal lobe disconnection. Herein, we analyzed our surgical result and complications after trans-sylvian disconnection surgeries.

sylvian approach to temporal stem is one of the choices for temporal lobe disconnection.

P737 UTILITY OF DEPTH ELECTRODES FOR EPILEPSY SURGERY AND SURGICAL OUTCOME Hwang KJ1, Yi JH2, Kim JY3, Yoon SS2, Cho S-H2 1 Kyung Hee University Hospital, Neurology, Seoul, Korea, 2 Kyung Hee University Hospital, Seoul, Korea, 3Pusan University Hospital, Pusan, Korea Purpose: In refractory epilepsy patients, invasive study is performed for epilepsy surgery, when noninvasive presurgical work up was failed. The aim of this study was to evaluate the usefulness of depth electrodes for the epilepsy surgery and surgical outcome.

Method: Trans-sylvian disconnection surgeries were applied for 17 patients whose epileptic focus located in posterior quadrant including temporal lobe. The etiologies were following, Sturge-Weber syndrome in 13, tuberous sclerosis in one, cortical dysphasia in one, post-encephalitis in one, and non-lesional infantile spasm in one, respectively. We carried out the temporo-parieto-occipital disconnection in 10, the temporo-occipital disconnection in 4, and the only temporal disconnection in 3. We evaluated the surgical results and complications.

Method: We reviewed 24 patients who underwent epilepsy surgery between March 1, 2011, and February 28, 2013. All patients were evaluated presurgical work up with combined depth and grid electrode for epilepsy surgery. We defined seizure outcome according to Engel`s classification. Free of seizure or only aura after surgery were assigned to class I. Rare seizures (two or more per year) were assigned to class II. Seizure reduction >75% were assigned to class III. Seizure reduction