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ORIGINAL ARTICLE
Year : 2010  |  Volume : 58  |  Issue : 4  |  Page : 560-564

Comparison of 1 week versus 4 weeks of albendazole therapy in single small enhancing computed tomography lesion


1 Department of Pediatrics, Government Multi Speciality Hospital, Sector 16, Chandigarh- 160 015, India
2 Department of Radiology, Government Multi Speciality Hospital, Sector 16, Chandigarh- 160 015, India

Date of Acceptance24-Jun-2010
Date of Web Publication24-Aug-2010

Correspondence Address:
Neeraj Dhawan
H. No. 6144, MHC, Manimajra, Chandigarh- 160 101
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.68677

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 » Abstract 

Background : The appropriate duration of albendazole therapy in neurocysticercosis is uncertain. The observation in small uncontrolled randomized trials in children that short-course therapy (1 week) is as effective as the conventional regimen (4weeks) must be tested. Objective : To compare the efficacy of 1 and 4 weeks of albendazole therapy in children with single small enhancing computed tomographic lesion (SSECTL). Study Design: An open-labeled, randomized, clinical trial. Materials and Methods : One hundred twenty children with SSECTLs presenting with seizure. Intervention: The subjects were assigned to two groups using random tables: group A (n=58) received albendazole for 1 week and group B (n=62) for 4 weeks. All the subjects were followed up for 6 months. Results : The proportions of subjects with complete resolution of lesion in the two groups were similar (group A 63.8% versus group B 51.6%). The proportion of subjects in the two groups in whom the lesion calcified on follow up (group A 19% versus group B 24.2%) also did not differ significantly. The incidence of seizure recurrence during the 6-month follow-up period was also similar in both the groups (group A 9.6% versus group B 3.4%, P > 0.05). Conclusion : One week of albendazole therapy is as effective as 4 weeks of therapy in children with SSECTLs.


Keywords: Albendazole, contrast-enhanced computer tomography, duration, neurocysticercosis, single small enhancing computed tomographic lesions


How to cite this article:
Kaur P, Dhiman P, Dhawan N, Nijhawan R, Pandit S. Comparison of 1 week versus 4 weeks of albendazole therapy in single small enhancing computed tomography lesion. Neurol India 2010;58:560-4

How to cite this URL:
Kaur P, Dhiman P, Dhawan N, Nijhawan R, Pandit S. Comparison of 1 week versus 4 weeks of albendazole therapy in single small enhancing computed tomography lesion. Neurol India [serial online] 2010 [cited 2019 Aug 23];58:560-4. Available from: http://www.neurologyindia.com/text.asp?2010/58/4/560/68677



 » Introduction Top


Neurocysticercosis (NCC) is defined as an infection of the brain and its coverings by the larval stage of the tapeworm. Infection by Taenia solium is the most common helminthic infection of the central nervous system and a leading cause of acquired epilepsy worldwide. [1],[2] Rates of taeniasis, as determined by stool examination for ova, have been reported to range between 0.1 and 6% in the community in India and in other developing countries. [3]

A common but characteristic presentation of NCC is the single cysticercus lesion, also known as solitary cysticercus granuloma. Radiologically, [on contrast-enhanced computed tomography (CECT)], the lesion is typically single, small (<20 mm), well-defined, contrast enhancing (ring/disk) (hence, single, small, enhancing computed tomography lesions or SSECTLs), with or without surrounding edema and associated with minimal mass effect and no midline shift. Usually, there is no evidence of persistent focal neurological deficit and raised intracranial pressure. [4]

During the past 25 years, there have been contrasting opinions on the efficacy of cysticidal drugs in hastening the resolution of NCC and improving the natural course of the disease and this has caused controversy. [5],[6],[7],[8],[9] Albendazole and praziquantel both have been used for nearly two decades in patients with NCC and their benefits have been widely documented. [10],[11] Controversies have surrounded the management of SSECTLs. In view of the frequent spontaneous disappearance of CT lesions, some authors do not recommend the use of cysticidal agents in the management of SSECTLs. [12],[13],[14] However, studies in both adults and children with SSECTLs have demonstrated the benefits of albendazole administration, both in terms of seizure control and resolution of the granuloma on follow-up imaging studies. [5],[7],[15]

The exact duration of albendazole therapy remains unclear. Standard conventional regimens use 28 or 30 days schedule. [5],[11],[16] Many recent studies have employed shorter durations of albendazole treatment, mostly 1 week. There are enormous benefits of short-course therapy in terms of reduction in cost, duration of therapy and total dosage and better compliance. Here, we report the results of a prospective, open-labeled, randomized trial that compared the efficacy of 1 week versus 4 weeks albendazole treatment, in terms of resolution of SSECTLs and seizure recurrence.


 » Materials and Methods Top


A total of 598 children between 1 and 12 years of age with seizures, attending the Pediatric Emergency and Out Patient Department at Government Multi Speciality Hospital, Chandigarh, were screened during the period from March 2007 to February 2008. One hundred twenty children with first episode of seizure/s, without neurological deficit on clinical examination and with a characteristic neuroimaging finding of a single, small (<20 mm), well-defined lesion with contrast enhancement (ring or disk), without midline shift were enrolled in this randomized trial. Four hundred seventy eight patients with meningitis, febrile seizures, multiple and calcified lesions on imaging, ancillary evidence of tuberculosis (history of contact, positive chest X-ray or Mantoux test positive), idiopathic seizures, known old cases of seizure disorders and critically ill children were excluded [Figure 1].
Figure 1 :Flow of participants in study

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After informed consent was obtained, the children were randomized into two groups using computer generated random number tables. A detailed history and complete neurological examination was performed and recorded on a prestructured proforma. Cysticercus serology, Mantoux test, erythrocyte sedimentation rate (ESR), chest X-ray, stool examination and electroencephalogram (EEG) were performed on all the patients. The project was approved by the hospital ethics committee.

Treatment assignment

Group A (short-course group) received albendazole 15 mg/kg/day as a single dose for 7 days and group B (long-course group) received albendazole 15 mg/kg/day as a single dose for 28 days. All the children received oral prednisolone 2 mg/kg/day for the initial 7 days, starting 2 days before giving albendazole therapy. All the patients also received anti-epileptic drugs. All the children were kept under observation for at least 24 hours after starting the therapy.

Follow up

All the patients were followed regularly for at least 6 months. To prevent defaulters and to assure compliance to both anthelminthic drug and antiepileptic drugs, the unused tablet blisters or unused syrup bottles were counted at each follow-up visit. CECT scan was repeated after 3 months (first follow-up CT scan) of completion of albendazole therapy and after 6 months (second follow up CT scan) in all those children in whom the lesion had not completely disappeared on the first follow-up CT scan. Radiological outcome was assessed as complete resolution, partial resolution (reduction in the size of lesion by at least 50% or more of the original size), no resolution/persisting lesion (no or less than 50% decrease in the size of original lesion) and calcification of the lesion. Clinical outcome was recorded as recurrence of seizures based on objective reports from patients at each follow-up visit.

Outcome parameters

The primary outcome parameter was the proportion of subjects in each group in whom either of the follow-up CT scans demonstrated complete resolution of the SSECTL. The secondary outcome parameters included the proportion of subjects in each group that demonstrated resolution with calcification in either of the follow-up CT scans. Another secondary outcome measure was the number of subjects with seizure recurrence in the follow-up period of 6 months. Finally, adverse reactions to treatment were recorded in an open-ended manner from all subjects at each follow-up visit.

Statistical analysis

Analysis was done on an intention-to-treat basis. Baseline parameters and outcome parameters in the two groups were compared. For continuous data, the student's t test was used and for categorical variables, the chi-square test with Yale's correction was used. Intragroup qualitative analysis was done by McNemar's test.


 » Results Top


Patients in groups A and B were comparable with respect to demographic data, clinical profile and baseline investigations as shown in [Table 1]. None of the patients had past history of seizures. Family history of seizures due to NCC was present in two children, one from each group, in whom the elder sibling was also treated for NCC. NCC serology was positive in 10% (12) of patients. The characteristics of lesion in baseline CECT head were similar in both the groups. There was no significant difference between size of SSECTL between groups A and B [Table 1]. A total of nine patients were lost to follow up, six from group A and three from group B.
Table 1 :Comparison of baseline parameters in the two groups in the trial


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Evaluation of computed tomography lesions

Seventeen children in group A and 24 in group B had second follow-up CECT head because of partial or no reduction of lesions. Thirty-seven out of 58 subjects (63.8%) in group A and 32 out of 62 (51.6%) in group B demonstrated complete resolution on follow-up CT scan done at 3 and/or 6 months [Table 2]. This difference was not significant (P = 0.547). Similarly, there was no difference in the proportion of subjects in the two groups with residual calcification on follow-up CT scan [11 (19.0%) in group A and 15 in group B (24.2%) (P = 0.433)].
Table 2 :Imaging outcome on follow-up in the two groups in the trial


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During the follow-up period of 6 months, five subjects (9.6%) in group A and two (3.4%) in group B reported seizure recurrence. This difference in proportion was not significant (P = 0.261). All seizure recurrences responded to increase in dose of antiepileptic drugs. All seizures recurred in the first 3 months in subjects in group B and up to 60% of those in group A had a recurrence in the first 3 months.

Three patients, one in group A and two in group B, had adverse drug reactions due to antiepileptic drugs. They presented with hypersensitivity rash and with  Stevens-Johnson syndrome More Details and were started on an alternative antiepileptic drug. However, no adverse effect related to albendazole therapy was seen in either of the groups.


 » Discussion Top


This randomized, open-labeled trial was designed in order to determine if short course of albendazole treatment (7 days) was as efficacious as the conventional 4 weeks treatment course. No significant differences were found between subjects given albendazole treatment along with corticosteroids for 1 week and 4 weeks, in terms of the proportion of subjects in whom the SSECTL resolved completely on follow-up CT scan at 3 and/or 6 months. Likewise, there was no significant difference in the proportion of subjects in either group in terms of the number of subjects with seizure recurrence over the 6-month follow-up period.

The concept of shorter therapy regimen for NCC is based on the fact that the conventional regimen of albendazole, that is albendazole for 4 weeks, had shown variable results with regard to resolution of lesion. Our study showed that 51.6% of children who received conventional regimen of 4 weeks had complete resolution in 6 months. Previous studies have reported resolution rates between 61 and 86% in children with NCC, with the conventional 4-weeks course of albendazole. [17],[18],[19] In our study, the short-course albendazole (1 week) therapy along with steroid group showed complete resolution in 63.8% of patients as compared to 79% in a previous study. [18] The variability in the percentage of resolution in different studies may be due to different mean size of ring lesion at the start of the therapy, the number of patients enrolled and variable duration of follow up.

Our study further emphasized on the fact that much of the resolution that has to occur is seen within 3 months. In our study, a total of 52 (43.3%) patients showed complete resolution within the first 3 months, which is consistent with the findings of other studies. [6],[17],[18]

Seizure recurrence rate in different studies with conventional therapy varied between 8 and 22.6%. [5],[6],[13],[17],[18],[19] A study by Singhi et al. in 2003 showed recurrence rate of seizures as 8.2% in patients with short-course albendazole therapy in a follow up of 1 year, as compared to 9.6% in our study. [18]

The limitation of our study is follow up of short duration; it should have been of longer duration to see seizure recurrence and any progression or evolution of ring lesion on CT head. In addition, the sample size was small and this could be the reason for lack of any difference between the two groups in terms of the outcome parameters. Finally, the absence of blinding may have introduced a bias in the evaluation of the outcome parameters.

We conclude that a 1-week course of albendazole and steroid is equally efficacious as the conventional 4-week course of albendazole in terms of lesion resolution on follow-up CT scan at 3-6 months and seizure control over a 6-month follow-up period in pediatric subjects with SSECTL. Radiological resolution occurs in the first 3 months in majority of the subjects with SSECTL.

 
 » References Top

1.Ito A, Nakao M, Wandra T. Human taeniasis cysticercosis in Asia. Lancet 2003;362:1918-20.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Garcia HH, Gonzalex AE, Evans CA, Gilman RH. Cysticercosis working group in Peru. Taenia Solium cysticercosis. Lancet 2003;362:547-56.  Back to cited text no. 2      
3.Rajshekhar V, Joshi DD, Doanh NQ, van De N, Xiaonong Z. Taenia solium taeniasis/cysticercosis in Asia: epidemiology, impact and issues. Acta Trop 2003;87:53-60.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Rajshekhar V. Etiology and management of single small CT lesions in patients with seizures: understanding a controversy. Acta Neurol Scand 1991;84:465-70.  Back to cited text no. 4  [PUBMED]    
5.Baranwal AK, Singhi PD, Khandelwal N, Singhi SC. Albendazole therapy in children with focal seizures and single small enhancing computerized tomographic lesions: a randomized, placebo-controlled, double blind trial. Pediatr Infect Dis J 1998;17:696-700.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.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 Pediar 2003;143:111-4.  Back to cited text no. 6      
7.Gracia HH, Pretell EJ, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH, et al. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med 2004;350:249-58.  Back to cited text no. 7      
8.Del Brutto OH, Roos KL, Coffey CS, Garcia HH. Meta analysis: cysticidal drugs for neurocysticercosis: albendazole and praziquantel. Ann Intern Med 2006;145:43-51.  Back to cited text no. 8      
9.Thussu A, Chattopadhyay A, Sawhney IM, Khandelwal N. Albendazole therapy for single small enhancing CT lesions (SSECTL) in the brain in epilepsy. J Neurol Neurosurg Psychiatry 2008;79:272-5.  Back to cited text no. 9      
10.Sotelo J, Torres B, Rubio-Donnadieu F, Escobedo F, Rodriguez-Carbajal J. Praziquantel in treatment of neurocysticercosis: long term follow-up. Neurology 1985;35:752-4.  Back to cited text no. 10  [PUBMED]    
11.Escobedo F, Penagos P, Rodriguez J, Sotelo J. Albendazole therapy for neurocysticercosis. Arch Intern Med 1987;147:738-41.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Ahuja GK, Behari M, Prasad K, Goulatia RK, Jailkhani BL. Disappearing CT lesions in epilepsy: is tuberculosis or cysticercosis the cause? J Neurol Neurosurg Psychiatry 1989;52:915-6.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Sethi PK, Kumar BR, Madan VS, Mohan V. Appearing and disappearing CT scan abnormalities and seizures. J Neurol Neurosurg Psychiatry 1985;48:866-9.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.Rajshekhar V. Solitary cerebral cysticercus granuloma. Epilepsia 2003;44 Suppl 1:25-8.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  
15.Singhi P, Singhi S, Ramanathan RP, Bharti S. Neurocysticercosis in focal epilepsy in North India. Epilepsia 1995;36:156.  Back to cited text no. 15      
16.Sotelo J, Escobedo F, Penagos P. Albendazole versus praziquantel for therapy of neurocysticercosis: a controlled trial. Arch Neurol 1988;45:532-4.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]  
17.Singhi P, Singhi S. Neurocysticercosis in children. J Child Neurol 2004;19:482-92.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Singhi P, Dayal D, Khandelwal N. One week versus four week of albendazole therapy for neurocysticercosis in children: a randomized, placebo-controlled double blind trial. Pediatr Infect Dis J 2003;22:268-72.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  
19.Gogia S, Talukdar B, Chaudhury 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;97:416-22.  Back to cited text no. 19      


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]

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