Corticosteroids versus clobazam in epileptic encephalopathy with ESES: a European multicenter randomized controlled clinical trial (RESCUE ESES*)
Abstract Background: 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 characterized 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 randomized 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 auto-antibodies in serum.Methods: The pragmatic study will be performed in centres with expertise in the treatment of rare paediatric epilepsy syndromes across Europe. 130 patients, 2 to 12 years of age, with epileptic encephalopathy with ESES will be enrolled and randomized 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 auto-antibody testing are obtained before treatment and after 8 months of treatment.Discussion: The treatment of epileptic encephalopathy with ESES aims at improving cognitive outcome. This randomized 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 registration: ISRCTN, ISRCTN42686094, registered 24 May 2013, http://www.isrctn.com/ISRCTN42686094