OBJECTIVE: Epilepsy develops in 70-90% of children with Tuberous Sclerosis Complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.

METHODS: In this multi-center study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At six sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At four sites, treatment allocation was fixed, denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure.

RESULTS: In 54 subjects epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment (RCT: 364 95% CI: 223, 535) vs. 124 days (95% CI: 33, 149); OLT: 426 (95% CI: 258, 628) vs. 106 days (95% CI: 11, 149). At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted.

INTERPRETATION: Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalAnnals of Neurology
Publication statusE-pub ahead of print - 12 Nov 2020

    Research areas

  • Prevention, epilepsy, infants, Tuberous Sclerosis Complex, EPISTOP trial

ID: 54518371