Comparison of 4 weeks versus 12 weeks antiseizure medication for acute symptomatic seizures in children with Acute Encephalitis Syndrome: An open-label, randomized controlled trial

Abstract Objective To compare the proportion of children with seizure recurrence/s during 6-18 months of follow-up among children with acute symptomatic seizures underlying acute encephalitis syndrome (AES) treated with either 4 weeks or 12 weeks of antiseizure medication (ASM). Methods Eligible children aged 3 months to 12 years with acute symptomatic seizures underlying AES, receiving a single ASM at 4 weeks of illness, and without seizure recurrence from day 7–28 of illness were included in this comparative, parallel-group assignment, open-label, randomized control study (either 4 weeks or 12 weeks duration). The primary outcome was to compare proportions of children developing seizure recurrence over six months of follow-up. The secondary outcomes were to study seizure recurrence over 12–18 months follow-up and factor(s) associated with seizure recurrence. Results Of 232 children with AES screened, 60 eligible children were randomized in two groups. Baseline demographics were comparable (except the duration of illness) between the groups. Seizure recurrences at 6, 12 and 18 months were none, two (one in each group, relative risk 1.0, 95% CI 0.06–16.76; p-value >0.99), and six (one and five children in 4 and 12 weeks groups respectively, relative risk 0.17, 95% CI 0.01–1.62; p-value 0.19) respectively. There was no association of seizure recurrences with seizure characteristics, abnormal electroencephalography and neuroradiology. Children with disabilities at randomization had a higher risk of seizure recurrence at 18 months of follow-up (relative risk 7.16, 95% CI 1.1–43.9; p-value 0.049). Significance With limitations of the study design, this study provides Class I evidence that a shorter duration (4 weeks) of ASM is comparable with 12 weeks therapy for preventing seizure recurrences in children with AES. Trial registration Clinical Trials.gov identifier: NCT03181945; Clinical Trial Registry of India identifier: CTRI/2017/06/008783.