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Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial
Author(s) -
Kotulska Katarzyna,
Kwiatkowski David J.,
Curatolo Paolo,
Weschke Bernhard,
Riney Kate,
Jansen Floor,
Feucht Martha,
Krsek Pavel,
Nabbout Rima,
Jansen Anna C.,
Wojdan Konrad,
Sijko Kamil,
GłowackaWalas Jagoda,
Borkowska Julita,
Sadowski Krzysztof,
DomańskaPakieła Dorota,
Moavero Romina,
Hertzberg Christoph,
Hulshof Hanna,
Scholl Theresa,
Benova Barbora,
Aronica Eleonora,
Ridder Jessie,
Lagae Lieven,
Jóźwiak Sergiusz
Publication year - 2021
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25956
Subject(s) - tuberous sclerosis , medicine , epilepsy , randomized controlled trial , odds ratio , vigabatrin , pediatrics , clinical trial , confidence interval , electroencephalography , clinical endpoint , anesthesia , anticonvulsant , psychiatry
Objective Epilepsy develops in 70 to 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 multicenter 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 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was 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 days (95% confidence interval [CI] = 223–535) vs 124 days (95% CI = 33–149); OLT: 426 days (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. ANN NEUROL 2021;89:304–314