Prevalence of Migraine in the Elderly: A Narrated ... - Karger Publishers

Neuroepidemiology of Aging – Review Neuroepidemiology 2019;52:104–110 DOI: 10.1159/000494758

Received: October 19, 2018 Accepted: October 21, 2018 Published online: January 9, 2019

Prevalence of Migraine in the Elderly: A Narrated Review Tissa Wijeratne a, b, d Huiliang Melissa Tang a, c David Crewther b, e Sheila Crewther a, b

a Department of Neurology, Sunshine Hospital, Western Health, St Albans, VIC, Australia; b Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia; c Department of Neurology, Box Hill Hospital, Box Hill, VIC, Australia; d Department of Medicine, AIMSS, Melbourne Medical School, WHCRE, University of Melbourne, Sunshine Hospital, St Albans, VIC, Australia; e Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, VIC, Australia

Keywords Calcitonin gene-related peptide · Migraine · Prevalence · Elderly

Abstract Migraine is one of the most prevalent neurological disorders among all age groups including the elderly, but the incidence and prevalence of migraine tend to decrease with age. The clinical phenotype of migraine also appears to be different in the elderly patient group in comparison to the younger patient group, with elderly migraine appearing to be more often bilateral and associated with what has become known as “late-life migraine accompaniments. Furthermore, difficulty in the differentiation of migraine from vascular insults such as transient ischemic attacks and amyloid angiopathy and other multiple comorbidities, polypharmacy and age-related changes in pharmacodynamics and pharmacokinetics makes treatments for this cohort challenging but necessary, especially given the worldwide increase in life expectancy, and likelihood of migraine continuing to be a major personal and public health problem. © 2019 S. Karger AG, Basel

© 2019 S. Karger AG, Basel E-Mail [email protected] www.karger.com/ned

Migraine (see Table 1 for the diagnostic criteria for migraine) is one of the most prevalent neurological disorders and the most neglected, under-diagnosed medical disorder worldwide [1–4]. Migraine is also the ostensible cause of significant disability worldwide [5]. Migraine generally begins during early childhood with a peak around puberty, (~12 years in boys and 15 years in girls [6] but may first appear at any age [7] with a small number first self-reporting in their sixth, seventh and eighth decades of life [8]. Indeed the literature [9, 10] suggests that migraine is most active between the third and fourth decades of life with the majority of elderly chronic migraine patients indicating an onset of migraine prior to 50 years [11–14]. Importantly, given the worldwide increase in life expectancy, older age migraine is likely to become a far greater personal and public health issue over the next 40 years as management is likely to be confounded by other health problems and consequent association with polypharmacy. Migraine is the second commonest headache disorder after tension type headache in older adults with a one-year prevalence of about 10% [7, 15]. Interestingly, the clinical characteristics of migraine change with age [16] and as comorbidities increase [11]. In a study of 260 consecutive patients with migraine, ranging in age from 3 to 69 years, Prof. Tissa Wijeratne Department of Neurology, AIMSS Melbourne Medical School Sunshine Hospital St Albans, VIC 3021 (Australia) E-Mail Tissa.Wijeratne @ wh.org.au

Table 1. Diagnostic criteria for typical aura without headache and migraine with typical aura IHCD-3 [34]

Typical aura without headache

Migraine with typical aura

A. Fulfils criteria for migraine with typical aura B. No headache accompanies or follows the aura within 60 min

A. At least 2 attacks fulfilling criteria B and C B. Aura consisting of visual, sensory and/or speech/language symptoms, each fully reversible, but no motor, brainstem or retinal symptoms C. At least 3 of the following 6 characteristics: 1. At least 1 aura symptom spreads gradually over ≥5 min 2. Two or more aura symptoms occur in succession 3. Each individual aura symptom lasts 5–60 min 4. At least 1 aura symptom is unilateral 5. At least 1 aura symptom is positive 6. The aura is accompanied, or followed within 60 min, by headache D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded

marked differences in clinical features were observed with age [17]. The percentage of males with migraine decreased markedly from childhood to adulthood. In females, the duration of headache, unilateral pain, pulsating sensation, light sensitivity and noise sensitivity increases with age. In contrast worsening of headache with physical activity decreased with age [17]. Neck pain also increases with acute attacks of migraine in the elderly [18]. Other studies have shown increase in autonomic symptoms (tachycardia, sweating, dry mouth, facial flush), while there was a reduction in sensory sensitivities as well as nausea and vomiting as patients got older [14]. Thus, treatment options for migraine in older individuals are complex and challenging and made more so by the exclusion of older patient groups (>65 years) from the majority of clinical trials in migraine [19, 20]. The prevalence of chronic headaches (chronic migraine, chronic tension type headaches, medication overuse headaches [MOH]) in the elderly ranges from 5 to 22% and occurs more commonly in women [14, 21, 22]. Headache accounts for 14.9% of female patients and 6.1% of male patients general practitioner visits in Australia [2]. Worldwide, headache is the tenth most common symptom in elderly women and fourteenth most common symptom in elderly men [23]. Headache has the potential to adversely affect quality of life and limit domestic and community activities of daily living, and therefore carries a high burden of disability [24]. Although certain primary headaches, such as hypnic headache and primary cough headache, occur more commonly in the elderly, the prevalence and incidence of primary headaches decrease with age [11–14]. Conversely, secondary headache syndromes increase in incidence with aging and important differentials to consider include intracranial space-occupying neoplasms, intracra-

nial haemorrhage, giant cell arteritis, trigeminal neuralgia or post-herpetic neuralgia, cervicogenic and cervical spine related headache and headache associated with comorbidities such as sleep-disordered breathing [13, 25]. Migraine in the elderly also tends to present less classically. In a Brazilian retrospective study on patients presenting to an outpatient headache clinic, migraine patients older than 60 years were more likely to be bilateral and less likely to have migraine associated symptoms (photophobia and phonophobia and/ or nausea or vomiting), compared to younger (aged 20–40 years) migraine patients [14]. Elderly patients may also present with aura only (acephalgic) migraines [23] and shorter attacks of migraine [24]. Fisher et al. [24] point out that concomitant mild cognitive impairment and changes in memory and thinking are not uncommon in the elderly. Therefore, the history of presenting complaint may be limited and therefore, a diagnosis of migraine may be challenging in this cohort. The association between cognition and migraine is controversial – with some evidence that the two are not associated [24, 26]. Another interesting aspect of migraine in the elderly is the onset of late life migraine accompaniments or migraine without aura (noted above), which is more common in the elderly [27–30]. In an important early consideration of migraine in 1980, Fisher [28] described this interesting condition for the first time in 1980 (120 cases in 1980, 85 cases in 1986 and 205 cases in total [27, 28]) proposing the term “late life migraine accompaniments (LLMA)” as a common differential diagnosis occurring in acute stroke population [31–33]. Fifty per cent of the cases experienced headaches with 23% of the cases in patients aged 40–49 years, while 40% were 50–59 years of age, 20% of the cases were patients aged 60–69 years and 16% were patients aged 70 years and over [27, 28]. Sixty five per cent of these pa-

Prevalence of Migraine in the Elderly: A Narrated Review

Neuroepidemiology 2019;52:104–110 DOI: 10.1159/000494758

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tients had been diagnosed with recurrent headaches in the past [27, 28]. Of the 120 patients with “unexplained transient cerebral ischemic attacks” with normal cerebral angiograms in whom the transient episodes of neurological symptoms resembled the neurological accompaniments of migraine reported by Fisher [28] in 1980, 25 of these patients had visual and paraesthesia disturbances, 18 visual and speech disturbances, 7 visual and brain stem symptoms, 14 visual, paraesthesia and speech disturbances, 7 visual, paraesthesia and speech disturbances and paresis, 25 recurrence of old stroke deficit. The late life migraine accompaniments typically include spreading sensory, visual or speech disturbance that can occur suddenly, rarely and generally last for less than an hour [34]. Fisher noted that the neurological deficits of LLMA may occur before, during or after an attack of migraine. Fisher went on to propose the following criteria to support the diagnosis of LLMA [27]. 1. The presence of visual symptoms 2. Gradual build up, expansion or migration of symptoms of the scintillating display 3. A march of paraesthesia 4. The serial progression of one accompaniment to the other (e.g., visual to paraesthesia) 5. The occurrence 2 or more identical spell of symptoms 6. Headache noticed by at least 50% of cases 7. Slightly longer duration than transient ischemic attacks (TIAs) – 15–25 min in LLMA compared to the majority of TIAs that last less than 15 min 8. Benign clinical course trajectory 9. The occurrence of a cluster of LLMA spells in older subgroup (50–60) 10. No evidence of cerebral thrombo-embolism, dissection or prothrombotic status with blood tests 11. No evidence of atherosclerosis 12. Normal cerebral angiography. Fisher later came up with 8 additional observations in 1986 [27]. 1. At least 10 out of 205 patients described episodic horizontal or vertical diplopia which lasted from few seconds to few minutes 2. At least 20 out of 50 patients with numbness of various components of the body went on to describe numbness of the tongue. Fisher felt when the transient numbness is the only symptom in these patients, the diagnosis of migraine was of a prime consideration for him 3. The remarkability of focal distribution of the numbness that may be limited to one toe, one finger, the chin on one side, a small patch of the cheek, tip of the tongue appears to be more suggestive of migraine 106


4. The brevity of symptoms as many patients were quite certain that their numbness in the finger or hand lasted only a second or few seconds 5. Some patients described transient tinnitus, a sound in the ear or head 6. Few patients described sudden severe pain in the head which they described as “struck with a sledgehammer” 7. Few patients described “triggers” from telephone ringing, overwork at income tax time and stress over unresolvable problems 8. Few patients described a feeling of faintness or presyncope. Unfortunately, Fisher [27] provides no details about the associated medical conditions of these patients. It would be very useful to know the number of patients with hypertension, diabetes and all medications being taken concurrently by these patients. Challenges Related to Treatment

Treatment of migraine in the elderly is often difficult due to the multi comorbidities and polypharmacy [35, 36] associated with age, for example, diabetes, hypertension, heart disease and other cerebro-vascular occurrences. In addition, the older population is characterised by general physiological changes such as slowing of gastric emptying, reduced hepatic mass and blood flow (hence the changes in rate of metabolism of drugs in the liver), reduced renal mass and glomerular filtration rate with direct impact on pharmacokinetics and pharmacodynamics [37]. Furthermore, many age-specific pharmacokinetic and pharmacodynamic considerations associated with long-term therapeutic management of blood pressure, cholesterol (statins) diabetes and/or mood have been reported, thus highlighting the special consideration needed to be given to management of geriatric migraine in clinical practice. Furthermore, as many elderly patients may be taking analgesics for other painful conditions, such as arthritis, medication overuse in headache is not uncommon in this age group [23]. Indeed a French study at a tertiary headache centre has recently reported a prevalence of 30% of headache from medication overuse in the elderly [11]. Non-Pharmacological Interventions

Non-pharmacological measures such as good mental health hygiene including proper sleep, regular physical activity such as daily walking, proper hydration, positive Wijeratne/Tang/Crewther/Crewther



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Study design

Cross-sectional population-based face to face interview

Door to door survey

Outpatient clinic survey

Prospective cross sectional study in an outpatient setting

Population-based study

Door-to-door survey with screening semi structured interview and neurological evaluation

Retrospective audit of clinical charts of patients referred to headache centre over 8 years (till 2002)

Population-based study on community-dwelling elderly with neurologist assessment via structured interview (based on ICHD-2 criteria) and follow-up MRIB at 4 years

Retrospective study on patients presenting to headache clinic over 5 years: comparing elderly (60–70 years) to younger (20–40 years) patients with migraines based on ICHD-1 criteria.

Author

Hagen et al. [68], 2018

Zhang et al. [69], 2016

Ruiz et al. [70], 2013

Tai et al. [72], 2012

Schwaiger et al. [71], 2008

Camarda and Monastero [22], 2003

Lisotto et al. [12], 2004

Kurth et al. [73], 2011

Martins et al. [14], 2006

60 years n = 144

60 years n = 780

65 years n = 282

65 years n = 1,031

55–94 years of age n = 574

55 years and above n = 70

65 years and older out patients n = 262

60 years and older n = 5,248

22–89 age groups n = 232

Cut-off age, years and n

Table 2. Prevalence of headache in the elderly: summary of studies

Brazil

Nantes, France

Padua, Italy

Rural Southern Italy

USA

Malaysia

Espana

Tianjin province, China

Norway

Location

Migraine accounted for 25% of presentations. Chronic daily headache, other primary headache, secondary headache and inconclusive diagnosis accounted for 14.5, 15.9, 13.2, and 17.4% presentations, respectively

Overall, the prevalence of severe headache was 20.9%. Of these, 71.2% were migraine and of these, 14.7% of those with migraine was with aura

Primary headaches accounted for 81.6% of presentations, and among these, prevalence for episodic migraine, chronic migraine and tension type-headache was 27.8, 26.1, and 25.7%, respectively

Overall prevalence of recurrent headache was 21.8%. Prevalence of migraine, tension-type headache and another headache were 4.6, 16, and 1.3% respectively

Tension-type headache (40.9%) and migraine (19.3%)

12.9% migraine without aura, 5.7% migraine with aura, 5.7% chronic migraine

23.8% had migraine

1-year prevalence of migraine 0.85%, chronic headaches 3.79%, unclassified headaches 3.63%

Lifetime prevalence of migraine 32.8%

Findings

Migraine patients were more likely to be women. Compared to younger patients with migraine, elderly migraine patients were more atypical in presentation

Compared to those without any headache, migraine was associated with females, never-smokers and lower alcohol intake. severe headache was associated with white matter hyperintensities on MRIB. Migraine with aura was associated with silent infarcts

Females were associated with transformation from episodic to chronic migraine

Women were more likely to have migraine and tension-type headaches. The prevalence of migraine decreased with aging [22]

Lifetime prevalence ofall primary headaches combined and of cranial neuralgias was 51.7 and 1.6% respectively. It emerged as the most common types of headache [71]

47.1% of Malaysian elderly patients suffered from chronic daily headaches. 94.3% reported at least one headache episode per month

51.9% of the patients (136 patients from the older than 65 years of age cohort) , headache began after 65 [70]

Prevalence of all headaches was much lower than that mentioned in other published studies. Respondents with less participation in social activities had a reduced prevalence of primary headaches [69]

120 participants were 60 years or older. Compared to those below 60 years , the 1-year prevalence was 10% for migraine (vs. 26.8% p < 0.0001) [68]

Comments

ICHD-3 version of the International Headache Society Classification of Headache Disorders. MIDAS, The Migraine Disability Assessment Questionnaire; MRIB, magnetic resonance imaging of the brain.

Marseille, France Retrospective review of patients presenting for the first time to a tertiary headache centre clinic with migraine over 9 years. Criteria via ICHD-3beta de Rijk et al. [11], 2017

65 years n = 329

Women were more likely to report migraine. Majority of patients who had previously sought medical advice for their headache did not get a diagnosis. Consonant with previous studies, there was no clear association between headache and cognition Overall, 24.4% had a current history of headaches. Among these, probable migraine accounted for 13.8% and amongst these, 3.2% described migraine with aura. Episodic migraine accounted for 3% of the sample and chronic migraine occurred in 3.6%. Episodic tension type headache and chronic tension-type headache accounted for 3.4% and 0.6% respectively Italy Cross-sectional study on patients presenting to a memory clinic over 8 years. Migraine was defined via ICHD-2 criteria and disability assessed via MIDAS Feleppa et al. [24], 2017

65 years n = 1,237

Comments Findings Location Cut-off age, years and n Study design Author

Table 2 (continued)

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stress management and avoidance of triggers such as hunger must be advised to all elderly migraine patients [38–41]. Acute Treatment

The goal of acute treatment is to achieve sustained pain free response, that is, to be pain free in 2 h time of the acute treatment and also in 24 h [42–46]. Simple analgesics such as paracetamol, acetylsalicylic acid, antiemetic drugs such as metoclopramide, NSAIDs, triptans can be used in acute treatment [45, 47–49]. However, it is also critically important to minimize potential for acute overuse treatment as this would invariably lead to MOH [50]. Longer-Term Preventative Treatments

Tricyclic antidepressants, beta blockers, sodium valproate, topiramate, lisinopril, candesartan, calcium channel blockers, onabotulinum toxin injections, CGRP antagonists or CGRP receptor antagonists are prescription alternatives currently approved for use as migraine prevention [51–66]. However, yet again it is important to use these medications with caution in the elderly – ideally at low doses initially and slow gradual increase [67]. It is also important to individualise the treatment (i.e., a patient with hypertension will be better off with initial preventative medications such as candesartan, which will be helpful for blood pressure control as well as monthly headache day reduction. A patient who is overweight may benefit from a medication such as topiramate that is known to cause weight loss. Conclusion

The prevalence of migraine in older patients who are in their sixties and seventies is significant though less than in younger cohorts with both incidence and prevalence decreasing with age. The clinical phenotype also appears to be different (bilateral rather than hemispheric and MOH), with patient attacks being symptomatically less typical, for example, LLMA, in comparison to the younger patient group [14]. Treatment choices are also more difficult, given the multiple comorbidities and potential polypharmacy associated with increasing age. Furthermore, there are also many fewer published studies in the literature (see Table 2 Wijeratne/Tang/Crewther/Crewther

for those found in PubMed using terms “migraine in elderly,” “Late life migraine accompaniments,” “elderly migraine,” “prevalence of elderly migraine” specifically designed to explore the features of migraine and chronic migraine or clinically trial medications in the elderly [older than 65] from 2002 to 2018). Thus, migraine as a severely neglected disorder, particularly in the el-

derly, needs better recognition and attention, with more extensive exploration of the specific pharmacokinetics and pharmacodynamics in comorbid-illness- induced drug-drug interactions. Lastly, research into evidence-based management, both in terms of acute and preventative treatment, is a matter warranting high priority.

References 1 Stark RJ, Ravishankar K, Siow HC, Lee KS, Pepperle R, Wang SJ: Chronic migraine and chronic daily headache in the Asia-Pacific region: a systematic review. Cephalalgia 2013; 33:266–283. 2 Stark RJ, Valenti L, Miller GC: Management of migraine in Australian general practice. Med J Aust 2007;187:142–146. 3 Buse DC, Scher AI, Dodick DW, Reed ML, Fanning KM, Manack Adams A, et al: Impact of migraine on the family: perspectives of people with migraine and their spouse/domestic partner in the CaMEO study. Mayo Clin Proc 2016;pii:S0025-6196(16)00126-9. 4 Dodick DW, Loder EW, Manack Adams A, Buse DC, Fanning KM, Reed ML, et al. Assessing barriers to chronic migraine consultation, diagnosis, and treatment: results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study. Headache 2016; 56:821–834. 5 Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol 2017;16:877–897. 6 Goadsby PJ: Migraine: diagnosis and management. Intern Med J 2003;33:436–442. 7 Haan J, Hollander J, Ferrari MD: Migraine in the elderly: a review. Cephalalgia 2007;27:97– 106. 8 Stewart WF, Lipton RB, Celentano DD, Reed ML: Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA 1992;267:64–69. 9 Burch R, Rizzoli P, Loder E: The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies. Headache 2018; 58:496–505. 10 Burch RC, Loder S, Loder E, Smitherman TA: The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache 2015;55:21–34. 11 de Rijk P, Resseguier N, Donnet A: Headache characteristics and clinical features of elderly migraine patients. Headache 2018;58:525–533. 12 Lisotto C, Mainardi F, Maggioni F, Zanchin G: Headache in Sturge-Weber syndrome: a


case report and review of the literature. Cephalalgia 2004;24:1001–1004. 13 Lisotto C, Mainardi F, Maggioni F, Zanchin G: Episodic hypnic headache? Cephalalgia 2004;24:681–685. 14 Martins KM, Bordini CA, Bigal ME, Speciali JG: Migraine in the elderly: a comparison with migraine in young adults. Headache 2006;46: 312–316. 15 Prencipe M, Casini AR, Ferretti C, Santini M, Pezzella F, Scaldaferri N, et al: Prevalence of headache in an elderly population: attack frequency, disability, and use of medication. J Neurol Neurosurg Psychiatry 2001; 70: 377– 381. 16 Starling AJ: Diagnosis and management of headache in older adults. Mayo Clin Proc 2018;93:252–262. 17 Wober-Bingol C, Wober C, Karwautz A, Auterith A, Serim M, Zebenholzer K, et al: Clinical features of migraine: a cross-sectional study in patients aged three to sixty-nine. Cephalalgia 2004;24:12–17. 18 Kelman L: Migraine changes with age: IMPACT on migraine classification. Headache 2006;46:1161–1171. 19 Landy S: Migraine throughout the life cycle: treatment through the ages. Neurology 2004; 62(5 suppl 2):S2–S8. 20 Landy SH, Lobo BL: Migraine treatment throughout the lifecycle. Expert Rev Neurother 2005;5:343–353. 21 Linn J, Schwarz F, Reinisch V, Straube A: Ophthalmoplegic migraine with paresis of the sixth nerve: a neurovascular compression syndrome? Cephalalgia 2008;28:667–670. 22 Camarda R, Monastero R: Prevalence of primary headaches in Italian elderly: preliminary data from the Zabut Aging Project. Neurol Sci 2003;24(suppl 2):S122–S124. 23 Sharma TL: Common primary and secondary causes of headache in the elderly. Headache 2018;58:479–484. 24 Feleppa M, Fucci S, Bigal ME: Primary headaches in an elderly population seeking medical care for cognitive decline. Headache 2017; 57:209–216. 25 Reinisch VM, Schankin CJ, Felbinger J, Sostak P, Straube A. [Headache in the elderly]. Schmerz 2008;22(suppl 1):22–30. 26 Jelicic M, van Boxtel MP, Houx PJ, Jolles J: Does migraine headache affect cognitive

function in the elderly? Report from the Maastricht Aging Study (MAAS). Headache 2000;40:715–719. 27 Fisher CM: Late-life migraine accompaniments–further experience. Stroke 1986; 17: 1033–1042. 28 Fisher CM: Late-life migraine accompaniments as a cause of unexplained transient ischemic attacks. Can J Neurol Sci 1980; 7: 9– 17. 29 Manusov EG: Late-life migraine accompaniments: a case presentation and literature review. J Fam Pract 1987;24:591–594. 30 Vongvaivanich K, Lertakyamanee P, Silberstein SD, Dodick DW: Late-life migraine accompaniments: a narrative review. Cephalalgia 2015;35:894–911. 31 Sequeira D, Martin-Gill C, Kesinger MR, Thompson LR, Jovin TG, Massaro LM, et al: Characterizing strokes and stroke mimics transported by helicopter emergency medical services. Prehospital Emergency Care 2016; 20:723–728. 32 Goyal N, Tsivgoulis G, Male S, Metter EJ, Iftikhar S, Kerro A, et al: FABS: an intuitive tool for screening of stroke mimics in the emergency department. Stroke 2016; 47: 2216– 2220. 33 Vroomen PC, Buddingh MK, Luijckx GJ, De Keyser J: The incidence of stroke mimics among stroke department admissions in relation to age group. J Stroke Cerebrovasc Dis 2008;17:418–422. 34 Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1–211. 35 Baranzini F, Poloni N, Diurni M, Ceccon F, Colombo D, Colli C, et al: [Polypharmacy and psychotropic drugs as risk factors for falls in long-term care setting for elderly patients in Lombardy]. Recenti Prog Med 2009; 100: 9– 16. 36 Salwe KJ, Kalyansundaram D, Bahurupi Y: A study on polypharmacy and potential drugdrug interactions among elderly patients admitted in department of medicine of a tertiary care hospital in Puducherry. J Clin Diagn Res 2016;10:FC06–FC10. 37 McLean AJ, Le Couteur DG: Aging biology and geriatric clinical pharmacology. Pharmacol Rev 2004;56:163–184.


109

38 Kroll LS, Sjodahl Hammarlund C, Gard G, Jensen RH, Bendtsen L: Has aerobic exercise effect on pain perception in persons with migraine and coexisting tension-type headache and neck pain? A randomized, controlled, clinical trial. Eur J Pain 2018, Epub ahead of print. 39 Birru EM, Abay Z, Abdelwuhab M, Basazn A, Sirak B, Teni FS: Management of headache and associated factors among undergraduate medicine and health science students of University of Gondar, North West Ethiopia. J Headache Pain 2016;17:56. 40 Suzuki K, Miyamoto M, Miyamoto T, Inoue Y, Matsui K, Nishida S, et al: The prevalence and characteristics of primary headache and dream-enacting behaviour in japanese patients with narcolepsy or idiopathic hypersomnia: a multi-centre cross-sectional study. PLoS One 2015;10:e0139229. 41 Dodick DW: Review of comorbidities and risk factors for the development of migraine complications (infarct and chronic migraine). Cephalalgia 2009;29(suppl 3):7–14. 42 Baron EP, Tepper SJ, Mays M, Cherian N: Acute treatment of basilar-type migraine with greater occipital nerve blockade. Headache 2010;50:1057–1059. 43 Tepper SJ, Rezai A, Narouze S, Steiner C, Mohajer P, Ansarinia M: Acute treatment of intractable migraine with sphenopalatine ganglion electrical stimulation. Headache 2009; 49:983–989. 44 Tepper SJ, Spears RC: Acute treatment of migraine. Neurol Clin 2009;27:417–427. 45 Da Silva AN, Tepper SJ: Acute treatment of migraines. CNS Drugs 2012;26:823–839. 46 Katic BJ, Krause SJ, Tepper SJ, Hu HX, Bigal ME: Adherence to acute migraine medication: what does it mean, why does it matter? Headache 2010;50:117–129. 47 Tepper DE: Non-steroidal anti-inflammatories for the acute treatment of migraine. Headache 2013;53:225–226. 48 Knowles S, Oh P, Gomes T; Ontario Drug Policy Research Network: Triptans for acute migraine: drug class review to help inform policy decisions. Headache 2015;55(suppl 4): 191–198. 49 Rapoport AM, Tepper SJ, Sheftell FD, Kung E, Bigal ME: Which triptan for which patient? Neurol Sci 2006;27(suppl 2):S123–S129. 50 Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB: Transformed migraine and medication overuse in a tertiary headache

110

centre–clinical characteristics and treatment outcomes. Cephalalgia 2004; 24: 483–490. 51 Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB: Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia 2015;35:478–488. 52 Diener HC, Limmroth V: Advances in pharmacological treatment of migraine. Expert Opin Investig Drugs 2001;10:1831–1845. 53 Reinke T: Aimovig for migraine prevention: the new kid may have trouble fitting in. Manag Care 2018;27:10–11. 54 Raffaelli B, Reuter U: The biology of monoclonal antibodies: focus on calcitonin generelated peptide for prophylactic migraine therapy. Neurotherapeutics 2018; 15: 324– 335. 55 Tepper SJ, Bigal ME, Sheftell FD, Rapoport AM: Botulinum neurotoxin type A in the preventive treatment of refractory headache: a review of 100 consecutive cases. Headache 2004;44:794–800. 56 Paemeleire K, MaassenVanDenBrink A: Calcitonin-gene-related peptide pathway mAbs and migraine prevention. Curr Opin Neurol 2018;31:274–280. 57 Israel H, Neeb L, Reuter U: CGRP monoclonal antibodies for the preventative treatment of migraine. Curr Pain Headache Rep 2018; 22:38. 58 Maizels M, Blumenfeld A, Burchette R: A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache 2004;44:885–890. 59 Zhu Y, Liu Y, Zhao J, Han Q, Liu L, Shen X: The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis. Neurol Sci 2018, Epub ahead of print. 60 Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, et al: Fremanezumab as add-on treatment for patients treated with other migraine preventive medicines. Headache 2017;57:1375–1384. 61 Ohlsson L, Kronvall E, Stratton J, Edvinsson L: Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries. J Headache Pain 2018;19:66. 62 Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, et al: Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med 2017;377: 2113–2122.


63 Edvinsson L, Haanes KA, Warfvinge K, Krause DN: CGRP as the target of new migraine therapies – successful translation from bench to clinic. Nat Rev Neurol 2018;14:338– 350. 64 Jin Y, Smith C, Monteith D, Brown R, Camporeale A, McNearney TA, et al: CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial. Osteoarthritis Cartilage 2018;pii :S1063-4584(18)31459-6. 65 Edvinsson L: The CGRP pathway in migraine as a viable target for therapies. Headache 2018;58(suppl 1):33–47. 66 Skljarevski V, Oakes TM, Zhang Q, Ferguson MB, Martinez J, Camporeale A, et al: Effect of different doses of galcanezumab vs placebo for episodic migraine prevention: a randomized clinical trial. JAMA Neurol 2018;75:187– 193. 67 Loder E, Biondi D: General principles of migraine management: the changing role of prevention. Headache 2005; 45(suppl 1):S33– S47. 68 Hagen K, Asberg AN, Uhlig BL, Tronvik E, Brenner E, Stjern M, et al: The epidemiology of headache disorders: a face-to-face interview of participants in HUNT4. J Headache Pain 2018;19:25. 69 Zhang Y, Shi Z, Hock D, Yue W, Liu S, Zhang Y, et al: Prevalence of primary headache disorders in a population aged 60 years and older in a rural area of Northern China. J Headache Pain 2016;17:83. 70 Ruiz M, Pedraza MI, de la Cruz C, Baron J, Munoz I, Rodriguez C, et al: Headache in the elderly: characteristics in a series of 262 patients. Neurologia (Barcelona, Spain) 2014; 29:321–326. 71 Schwaiger J, Kiechl S, Seppi K, Sawires M, Stockner H, Erlacher T, et al: Prevalence of primary headaches and cranial neuralgias in men and women aged 55–94 years (Bruneck Study). Cephalalgia 2009; 29: 179– 187. 72 Tai ML, Jivanadham JS, Tan CT, Sharma VK: Primary headache in the elderly in South-East Asia. J Headache Pain 2012;13:291–297. 73 Kurth T, Mohamed S, Maillard P, Zhu YC, Chabriat H, Mazoyer B, et al: Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study. BMJ 2011; 342: c7357.

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