G302 Comparison of 4-weeks versus 12-weeks anti-convulsant therapy for acute symptomatic seizures in children with acute encephalitis syndrome- an open-label, randomised controlled trial

Abstract

Background There exists poor evidence-base and conflicting literature regarding optimum duration of anti-epileptic drugs for acute symptomatic seizures in central nervous system infections. A duration of one to three-months of anti-epileptic drugs has been suggested for central nervous system infections with parenchymal involvement. The study was designed to compare the effectiveness of 4 weeks versus 12 weeks anti-convulsant treatment in preventing seizure recurrences over a six-month period. Methods Children aged 3 months to 12 years having Acute Encephalitis Syndrome with acute symptomatic seizures receiving single anti-epileptic drug at 4 weeks of illness and without seizure recurrence from day 7 day 28 of illness were included in this comparative, parallel group assignment, open label, randomised control study. The exclusion criteria were included children with chronic meningitis, brain abscess, intracranial space occupying lesion, prior history of seizures, prior focal neurological deficit or any developmental delay, children suffering from HIV, chronic liver/kidney disease, acute hepatic encephalopathy. Children on ≥2 anti-epileptic drugs, severely affected children [Paediatric Cerebral Performance Category Scale (PCPC) Score and Paediatric Overall Performance Category Scale with category score of 5] were also excluded. They were randomly allocated to receive anti-epileptic drugs either for 4 weeks or 12 weeks. Children were followed up at 1, 3, and 6 months of illness. The primary outcome was proportion of children developing seizure recurrence over 6 months follow up. The secondary outcome was to study factor(s) associated with seizure recurrence. Results Out of 232 children with Acute Encephalitis Syndrome, 60 children were found to be eligible for randomization in two groups. Baseline demographics were comparable (except duration of illness) between the groups. None of the children developed any seizure recurrences in the follow up period. Although, 8 children had neurological deficits and 9 children had EEG abnormality, seizure recurrences were not seen in any of these children. Conclusions The present study suggests that a shorter duration (4 weeks) of anti-epileptic drug therapy is comparable with 12 weeks anti-epileptic drugs for preventing seizure recurrences over a six-month follow-up period in this cohort of children with Acute Encephalitis Syndrome. The trial was registered with Clinical Trial Registry of India (CTRI/2017/06/008783) and Clinicaltrial.gov (NCT03181945).