Clinical, sociodemographic, radiological profile and ...

[Downloaded free from http://www.jmgims.co.in on Wednesday, September 28, 2016, IP: 85.171.61.208]

Original Article

Clinical, sociodemographic, radiological profile and response to albendazole therapy in children with neurocysticercosis in Uttarakhand Rajnish Kumar, Ritu Rakholia, Ajay Kumar Arya

ABSTRACT Background: Overall neurocysticercosis (NCC) is identified as a major cause of active epilepsy in the developing world. Most of the studies focus on adults with limited studies in children. A pilot study from Garhwal region of Uttarakhand had reported a high incidence. Conflicting reports regarding the clinical presentation and response of cysticidal drugs have created a controversy regarding disease and outcome. This prospective observational study in Kumaon region of Uttarakhand aims to study clinical features, sociodemographic profile, radiological findings and response to 28 days albendazole therapy in children with NCC. Materials and Methods: Seventy nine patients with various neurological complaints, were diagnosed to have NCC on basis of computed tomography scan head. Other differential diagnoses were excluded by chest X-ray, Mantoux, erythrocyte sedimentation rate and magnetic resonance imaging where needed. The clinical, sociodemographic profile was recorded, and radiological and clinical response at 3 months after 28 days albendazole therapy was observed. Results: Seizures (93.9%) followed by vomiting (62%) and headache (30.4%) were the chief complaints. Complex partial seizures (70.3%) and generalized (17.6%) were the main seizure type. Most NCC were single (72.2%) out of which 26.3% disappeared on follow-up, 17.7% were multiple out of which 7% resolved and eight were calcified of which all persisted. Electroencephalography was abnormal in 62% patients. Conclusion: NCC in children is a relatively benign disease in Kumaon region with significant morbidity in the form of epilepsy with no mortality. Better prognosis was seen in single NCC in comparison to multiple or calcified lesions, but response to albendazole therapy was much less than in previous studies.

KEYWORDS: Albendazole therapy, clinic-sociodemographic profile, neurocysticercosis Introduction Neurocysticercosis (NCC) is the most common parasitic disease of the nervous system caused by the larval stage of the tapeworm Taenia solium.[1] Overall, NCC is identified as the cause of active epilepsy in 26.3-53.8% in the developing world.[2] Clinical features may vary and are largely determined Access this article online Quick Response Code: Website: www.jmgims.co.in

DOI: 10.4103/0971-9903.164242

by the location, stage and number of the parasite in the brain. Although NCC affects adults as well as children, there are limited studies on clinical features in children and age-related factors have This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: [email protected]

How to cite this article: Kumar R, Rakholia R, Arya AK. Clinical, sociodemographic, radiological profile and response to albendazole therapy in children with neurocysticercosis in Uttarakhand. J Mahatma Gandhi Inst Med Sci 2015;20:157-62.

Department of Pediatrics, Government Medical College, Haldwani, Nainital, Uttarakhand, India Address for correspondence: Dr. Ritu Rakholia, Type 4, H5, Medical College Campus, Government Medical College, Susheela Tiwari Hospital, Haldwani, Nainital, Uttarakhand, India. E-mail: [email protected]

© 2015 Journal of Mahatma Gandhi Institute of Medical Sciences | Published by Wolters Kluwer - Medknow


158

been inadequately studied.[3-7] The use and duration of cysticidal therapy continue to be debated. Various studies have shown that short course therapy of 7 days is as effective as longer regimes (28 days) with some studies also showing significant improvement without any cysticidal therapy. However, it is now accepted that cysticidal therapy helps in faster and increased resolution.[8-10] Epidemiological studies of epilepsy in Uttarakhand, Garhwal region have calculated the crude prevalence of epilepsy at 10/1000 population with active and inactive cysts contributing 32-35% of unprovoked seizures.[11-13] However, there are no studies from Kumaon region. Against the above background, the present study has been conducted to study the clinico-sociodemographic and radiological profile of children presenting with NCC in Kumaon region of Uttarakhand and to determine the clinical course with 28 days albendazole therapy, short course (5 days) steroid with anticonvulsant therapy.

Materials and Methods This is a prospective clinical based observational study conducted for two years between June 2011-May 2013. Seventy-nine patients are attending outpatient department and admitted in the pediatric ward in a Teaching Hospital which acts as a tertiary referral center in Kumaon region, Uttarakhand, were included in the study. All children 0.05. NCC = Neurocysticercosis

Table 2: Dietary pattern and religion distribution of NCC cases in admitted children Dietary/religious characteristics Number of cases Percentage P value* Type of diet Vegetarian Nonvegetarian Total Religion Hindu Muslims Sikhs Christians Total

58 21 79

73.4 26.6 100

0.001

58 15 4 2 79

73.4 19.0 5.1 2.5 100.0

0.001

*One sample Chi-square test. NCC = Neurocysticercosis

Table 3: Clinical profile of admitted children with NCC Clinical features*

Number of cases

Percentage

Seizure only Seizure+vomiting Seizure+headache Seizure+fever Vomiting only Headache only Fever only Hemi/monoparesis Altered sensorium Blurring of vision

58 9 5 2 40 19 7 8 5 5

73.4 11.4 6.3 2.5 62.0 30.4 11.4 10.1 6.3 6.3

*Multiple responses. NCC = Neurocysticercosis

Table 3a: Type of seizure in children admitted with seizure complaint (n = 74) Type of seizure Partial complex seizure with secondary generalization Generalised Simple partial Status epilepticus Total

Number of cases

Percentage

52

70.3

13 7 2 74 (93.7% of total)

17.6 9.5 2.6 100.0

Journal of Mahatma Gandhi Institute of Medical Sciences


160

Kumar, et al.: Neurocysticercosis in children

(12.5%). Temporal lobe lesions were the least forming 2 (2.8%) cases. Seven cases had multiple site of ring enhancing lesion [Table 4]. Best response with albendazole therapy at 3 months follow-up in the form of resolution of lesion on CT scan was observed in single ring enhancing lesion (26.3%) while only 7.1% cases with multiple ring enhancing lesions resolved completely in 3 months. This difference of outcome between single and multiple ring enhancing lesions has been found to be significant (P = 0.035). In contrast to single and multiple ring enhancing lesions, none of the calcified lesions resolved in 3 months treatment with albendazole [Table 5]. Electroencephalography response was abnormal in 62% children and normal in 38% children. Abnormality was in the form of focal slowing, sharp or spike activity or a combination of the above.

Discussion Ring enhancing lesions are a common neurological problem seen worldwide in all age groups. Studies from Garhwal region of Uttarakhand have shown high endemicity of NCC contributing 32-35% of all cases of epilepsy.[10-12] Seventy nine cases of NCC in 2 years in a single referral Teaching Hospital of Kumaon would also indicate a high prevalence in this region. Further population based studies are needed to throw more light on the matter. The current hospital based study showed that majority of NCC cases (75.9%) belonged to school going children. There were no patients younger than 1 year. Lesser number of NCC (24.1%) in the preschool age Table 4: Radiological profile of children admitted with NCC Side of lesion Right Left Bilateral Total

Number of cases

Percentage

50 22 07 79

63.36 27.86 8.78 100

NCC = Neurocysticercosis

Table 5: Response to albendazole therapy among admitted children with NCC CT lesion Single Multiple Calcified Total

Initial

Resolution after 3 months

n (%)

n (%)

57 (72.2) 14 (17.7) 8 (10.1) 79 (100)

15 (26.3) 1 (7.1) 0 (0) 16 (100)

P value* 0.035

*χ2 = 6.708, P < 0.05. NCC = Neurocysticercosis, CT = Computed tomography


children is because of the prolonged incubation period as long as 5 years of T. solium as well as the dietary habits of young children. This is similar to findings in other studies.[10-12] Our study showed a male preponderance similar to some studies.[7,11] In contrast to others which have shown an equal distribution[3] or a female predilection.[5,6] Most of the studies are hospital based other than Kumar et al.[10] hence it is difficult to attribute sex as an additional risk factor for NCC. The population in this study in Kumaon region of Uttarakhand was predominantly vegetarian (73.4% vs. 26.6%) in contrast to studies from Garhwal region of the state which had a basically nonvegetarian population. Similar to our study pork eaters were insignificant in all studies in Uttarakhand.[10-12] Hence, the current study underlines the important contribution of water sanitation and hygiene in spread of the disease. Seizure (94%) was the most common clinical presentation observed in our study similar to various studies of Uttarakhand, India and abroad[4,10,15-17] with incidence ranging from 77.7%[18] to 100%.[19] As to the seizure type, complex partial seizures were the most common clinical seizure pattern in some studies similar to our study[16,18,20] as opposed to García et al.[13] where simple partial or Kumar et al.[10] and Kuruvilla et al.[19] where generalized convulsions were more. Other presenting complaints recorded in the study included vomiting, fever, hemi/monoparesis, altered sensorium and visual complaints have also been reported by others.[4,10,11,20] In the present study fever was seen in greater percentages of cases that is, 11.4% and hemi/monparesis in only 0.1% cases, which may be due to regional differences and different number of subjects being taken up in different studies. Hemi/ monoparesis results either from the cyst or from Todd’s paralysis after a partial seizure. Life threatening features in the form of cysticercal meningitis, arachnoiditis and uncontrolled raised intracranial pressure as seen in studies from India[10,18] and outside India[5] were not seen in the present study. This may be attributed to difference of the study population, virulence of organism, variation in the pattern of health care delivery and presence of some immunity due to endemicity of tape worm infection. No mortality was recorded during 2 years study period implying benign nature of disease as opposed to other studies,[4,18] which have shown significant mortality due to arachnoiditis, meningo-encephalitis and untreated raised intracranial September 2015 | Vol 20 | Issue 2


161

Kumar, et al.: Neurocysticercosis in children

tension and status epilepticus. No significant morbidity in the form of dementia, hydrocephalus, hyperkinesias or learning disabilities were documented in this study unlike other studies.[5,10,18] NCC thus appears to have a relatively benign clinical outcome. In the current study, it was observed that single ring enhancing lesions [Figure 1] were seen on CT scan in 2/3rd cases and multiple in 1/3rd cases, similar to Dehradun based studies[10,11] however another study in Uttarakhand by Goel et al.[12] found single NCC to be much commoner (96% vs. 4%) and study in other developing countries like Mexico have shown a preponderance of multiple lesions.[19] Regarding the cerebral hemispheres involved radiologically, the present study showed a statistically greater involvement of the right hemisphere with parietal lobe being the commonest site in 59.7%, frontal lobe lesions constituted 25% and occipital lobe lesions in 12.5% cases. Temporal lobe lesions were the least, in 2.8 cases similar to Indian study by Patil and Paithankar.[17] Electroencephalography done after 6 months of discharge showed significant morbidity in the form of epilepsy in 62% of cases (abnormal EEG). Similar findings were reported by Chayasirisobhon et al.[21] (EEG was abnormal in 28%). Although there is controversy about the routine use of cysticidal drugs in single enhancing lesions, cysticidal therapy is helpful in the management of some of these patients. A meta-analysis by Del Brutto et al.[7] favors cysticidal therapy for better resolution and lesser risk of seizure recurrence. A trial by Gogia et al.[22] did not show any benefit of albendazole in hastening resolution

of CT lesions while Singhi et al.[8] in a study in children of Chandigarh show 1 week to be as effective as 4 weeks. In the present study, albendazole as cysticidal drug has been used for 28 days. The response in the form of resolution of NCC was significantly more in single as compared to multiple NCC similar to other studies.[7-9] However rate of improvement was much lesser 26% in this study versus 77-79% in others.[8,9] No comparison has been made regarding the efficacy of 28 days cysticidal therapy using albendazole drug vis-à-vis no cysticidal therapy, praziquental and short duration cysticidal therapy for formulation of treatment protocols in the future. The findings of the study cannot be generalized as it is a hospital based study and no formula has been used for calculating sample size. The treatment seeking behavior depends on the educational level of family head as illiteracy and poverty are common and traditional and religious treatment is commonly practiced in hills of Kumaon. Due to difficult geographic terrain accessibility is another issue due to which many patients are unable to reach the hospital. Hence, the study may have missed patients residing in very remote and inaccessible areas and those who are orthodox and practicing traditional treatment.

Conclusion and Recommendations Neurocysticercosis in this study appears to be a relatively benign disease with no mortality and no significant morbidity other than epilepsy. Single ring enhancing lesions have a good prognosis but the rate of resolution is less (26.3%) for single lesion. Four weeks albendazole cysticidal therapy with anticonvulsants was well tolerated with no significant side effects during study period. The preventive strategy must be customized to the endemic area and be tailor-made to prevent predominant form of transmission in that particular area. In the previous study[23] from this region the drinking water supply was found to be highly contaminated with coliforms indicating fecal contamination and could be responsible for high rate of NCC in this region. Hence, measures like raising public awareness and directing public health spending toward water sanitation and hygiene should go a long way to prevent transmission.

Acknowledgments Figure 1: Computed tomography scan head showing ring enhancing lesion with perilesional edema

September 2015 | Vol 20 | Issue 2

1. Dr. Jha, Assosciate Professor, Department of Community Medicine who helped us in statistical analysis. Journal of Mahatma Gandhi Institute of Medical Sciences


162 2. Dr. Divyashree, Assosciate Professor, Department of Radiodiagnosis, reporting of CT head.

Financial support and sponsorship Nil.

Conflicts of interest There are no conflicts of interest.

References 1.

Del Brutto OH, Sotelo J. Neurocysticercosis: An update. Rev Infect Dis 1988;10:1075-87. 2. Rajshekhar V, Chandy MJ. Incidence of Solitary Cysticercus Granuloma. Solitary Cysticercus Granuloma: The disappearing lesion. Chennai: Orient Longman Ltd.; 2000. p. 12-8. 3. Singhi P, Ray M, Singhi S, Khandelwal N. Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy. J Child Neurol 2000;15:207-13. 4. Shrestha BM. Childhood neurocysticercosis: Clinico-radiological profile. J. Nepal Paediatr 2008;28:14-6. 5. Ruiz-García M, González-Astiazarán A, Rueda-Franco F. Neurocysticercosis in children. Clinical experience in 122 patients. Childs Nerv Syst 1997;13:608-12. 6. Morales NM, Agapejev S, Morales RR, Padula NA, Lima MM. Clinical aspects of neurocysticercosis in children. Pediatr Neurol 2000;22:287-91. 7. Del Brutto OH, Roos KL, Coffey CS, García HH. Meta-analysis: Cysticidal drugs for neurocysticercosis: Albendazole and praziquantel. Ann Intern Med 2006;145:43-51. 8. Singhi P, Dayal D, Khandelwal N. One week versus four weeks of albendazole therapy for neurocysticercosis in children: A randomized, placebo-controlled double blind trial. Pediatr Infect Dis J 2003;22:268-72. 9. Kalra V, Dua T, Kumar V. Efficacy of albendazole and short-course dexamethasone treatment in children with 1 or 2 ring-enhancing lesions of neurocysticercosis: A randomized controlled trial. J Pediatr 2003;143:111-4. 10. Kumar A, Khan SA, Khan S, Das S, Anurag, Negi KS. A study of neurocysticercosis in the foothills of the Himalayas. Int J Infect Dis 2006;10:79-82.


Kumar, et al.: Neurocysticercosis in children 11. Varma A, Gaur KJ. The clinical spectrum of neurocysticercosis in the Uttaranchal region. J Assoc Physicians India 2002;50:1398-400. 12. Goel D, Dhanai JS, Agarwal A, Mehlotra V, Saxena V. Neurocysticercosis and its impact on crude prevalence rate of epilepsy in an Indian community. Neurol India 2011;59:37-40. 13. García HH, Evans CA, Nash THE, Takayanagui ON, White AC Jr, Botero D, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 2002;15:747-56. 14. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 1993;34:592-6. 15. Garg RK. Childhood neurocysticercosis: Issues in diagnosis and management. Indian Pediatr 1995;32:1023-9. 16. Kotokey RK, Lynrah KG, De A. A clinico-serological study of neurocysticercosis in patients with ring enhancing lesions in CT scan of brain. J Assoc Physicians India 2006;54:366-70. 17. Patil TB, Paithankar MM. Clinico-radiological profile and treatment outcomes in neurocysticercosis: A study of 40 patients. Ann Trop Med Public Health 2012;3:58-63. 18. Puri V, Sharma DK, Kumar S, Choudhury V, Gupta RK, Khalil A. Neurocysticercosis in children. Indian Pediatr 1991;28:1309-17. 19. Kuruvilla A, Pandian JD, Nair M, Radhakrishnan VV, Joseph S. Neurocysticercosis: A clinical and radiological appraisal from Kerala State, South India. Singapore Med J 2001;42: 297-303. 20. Sotelo J, Guerrero V, Rubio F. Neurocysticercosis: A new classification based on active and inactive forms. A study of 753 cases. Arch Intern Med 1985;145:442-5. 21. Chayasirisobhon S, Menoni R, Chayasirisobhon W, Locke GE. Correlation of electroencephalography and the active and inactive forms of neurocysticercosis. Clin Electroencephalogr 1999;30:9-11. 22. Gogia S, Talukdar B, Choudhury V, Arora BS. Neurocysticercosis in children: Clinical findings and response to albendazole therapy in a randomized, double-blind, placebo-controlled trial in newly diagnosed cases. Trans R Soc Trop Med Hyg 2003;97:416-21. 23. Rawat V, Jha SK, Bag A, Singhai M, Rawat CM. The bacteriological quality of drinking water in Haldwani block of Nainital district, Uttarakhand, India. J Water Health 2012;10:465-70.

September 2015 | Vol 20 | Issue 2