The expanding knowledge of epilepsy in leukodystrophies

INTRODUCTION: Leukodystrophies are heritable disorders of the white matter of the central nervous system.1 Epilepsy, defined as neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain, is usually linked with disorders mainly involving gray matter, and less commonly white matter. However, epilepsy might be one of the manifestations of leukodystrophies in children.2 The incidence of epilepsy among leukodystrophies and its clinical characteristics is unclear yet,2 although there appears to be good correlation between the severity of electroencephalography (EEG) changes and the severity of the diseases.3 This study aims to investigate epilepsy and EEG across leukodystrophies. METHODS: An electronic database search was conducted in PubMed for peer-reviewed studies that reported data for patients with leukodystrophies and epilepsy. We included retrospective observational cohort studies, case reports and case series. We first reviewed studies based on title and abstract and excluded the studies that were (1) not written in English language, (2) involving animal models, (3) lacking abstracts, (4) presenting inconclusive diagnoses, or indicating comorbidities at the onset of epileptic seizures. Duplicates were eliminated. The PRISMA guidelines for systematic reviews were followed. Data were analysed for age at seizure onset, seizure type, treatment response, and EEG characteristics. Treatment response was categorized as responder and refractory, with the former defined as seizure-free, >50% reduction of seizures, and improvement without specified details. RESULTS: A number of 6341 studies was totaled and a refined dataset of 340 records was retained for analysis. Median age at epilepsy onset was 10.93 y (range 0-61 y). Among the patients, 37% were classified as responder and 62.5% as refractory. We were not able to define a clear correlation between the type of epilepsy and the disease phenotype, as we observed an extreme heterogeneity in seizure semiology both intra and inter-individually. General EEG findings demostrates the presence of multifocal synchronous or asynchronous, spike, sharp and spike-wave complexes and abnormal background activity; some recogniseable pattern were identifiable, such as hypsarrhythmia, burst suppression and electrical status epilepticus. CONCLUSIONS: This review offers an in-depth analysis of the features of epilepsy in white matter disorders, contributing to a thorough understanding of the clinical spectrum of leukodystrophies.