Abstract
BackgroundEpileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterised by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The goal of treatment is to prevent further decline or even improve cognitive functioning. Based on mostly small and retrospective studies, corticosteroids and clobazam are regarded by many clinicians as the most effective pharmacological treatments. This European multicentre randomised controlled trial is designed to compare the effects of corticosteroids and clobazam on cognitive functioning after 6 months. Secondary outcomes include cognitive functioning after 18 months, EEG abnormalities in sleep, safety and tolerability, and seizure frequency. We also aimed at investigating whether treatment response in epileptic encephalopathy with ESES can be predicted by measurement of inflammatory mediators and autoantibodies in serum.MethodsThe pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. A total of 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomised in a 1:1 ratio to receive either corticosteroids (monthly intravenous methylprednisolone pulses or daily oral prednisolone) or oral clobazam for 6 months according to an open-label parallel-group design. Follow-up visits with clinical assessment, EEGs, and neuropsychological testing are scheduled for up to 18 months. Blood samples for cytokine and autoantibody testing are obtained before treatment and 8 months after treatment initiation.DiscussionThe treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomised controlled study will compare the most frequently used treatments, i.e. corticosteroids and clobazam. If the study proves superiority of one treatment over the other or identifies biomarkers of treatment response, results will guide clinicians in the early treatment of this severe epilepsy syndrome.Trial registrationISRCTN, ISRCTN42686094. Registered on 24 May 2013.
Highlights
Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years
The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome
Study setting Study preparations have been initiated in 22 centres with expertise in the treatment of rare paediatric epilepsy syndromes across 12 European countries
Summary
Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is an epilepsy syndrome occurring almost exclusively in children, usually at an age between 4 and 12 years. It is characterised by abundant sleep-induced epileptic activity in the electroencephalogram (EEG) and by acquired cognitive and behavioural deficits. The cognitive deficits are global (often referred to as continuous spikes and waves syndrome, CSWS) or confined to a specific cognitive domain (e.g. acquired aphasia or auditory agnosia in children with Landau-Kleffner syndrome, LKS) [2, 3] These phenotypes are referred to as “typical ESES patients” [4, 5]. In a previous study, we found that several cytokines were significantly higher in blood samples of patients with encephalopathy with ESES compared with healthy controls [16]
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