Electrical Status Epilepticus in Sleep

Abstract

Encephalopathy with electrical status epilepticus in sleep (ESES) is a childhood epilepsy syndrome characterized by near-continuous epileptic activity in sleep and learning or behavioural problems. Children with ESES may have occasional visible epileptic seizures, but the epileptic activity in sleep is generally invisible. The aim of my PhD program was to 1) improve early recognition of children at risk of developing ESES, 2) to increase our knowledge of the causes of ESES and reveal mechanisms that lead to learning and behavioural problems and 3) to provide evidence on optimal treatment.

Part I. Aetiology and Pathophysiology We found that nearly all children with perinatal injury of the thalamus develop ESES during follow up and higher residual thalamic volume predicts better neurodevelopmental outcome. We also found that several inflammatory mediators are highly activated in people with epilepsy. In children with encephalopathy with ESES, serum levels of several inflammatory mediators are higher than in controls and reduction in IL-6 with treatment is accompanied by clinical improvement. In a sleep EEG study, we found that overnight sleep slow wave homeostasis, reflecting synaptic homeostasis, is impaired in children with ESES and this impairment is most severe in children with behavioural problems.

Part II. Treatment In a systematic review and pooled analysis of cases from literature, we found that benzodiazepines and corticosteroids are more effective than conventional anti-epileptic drugs in improving cognition or EEG in children with encephalopathy with ESES. In cases with a clear unilateral structural lesion, surgery is the most effective treatment. In a study within our own centre, we found that reduction in epileptiform activity (SWI) after treatment is associated with subjective improvement in cognitive functioning, while it is not reflected by significant total IQ change. To assess the best medical treatment for ESES, a randomised controlled trial comparing clobazam and corticosteroid treatment (RESCUE ESES) is currently conducted. Outcome measures include neuropsychological test results, EEG findings and side-effects. Possible predictors (including inflammatory mediators) are analysed.