Comparison of 1 week versus 4 weeks of albendazole therapy in single small enhancing computed tomography lesion
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
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. , 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. 
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. 
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. ,,,, Albendazole and praziquantel both have been used for nearly two decades in patients with NCC and their benefits have been widely documented. , 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. ,, 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. ,,
The exact duration of albendazole therapy remains unclear. Standard conventional regimens use 28 or 30 days schedule. ,, 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.
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].
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.
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.
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.
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.
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.
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.
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)].
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.
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. ,, 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.  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. ,,
Seizure recurrence rate in different studies with conventional therapy varied between 8 and 22.6%. ,,,,, 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. 
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.
[Table 1], [Table 2]