Abstract
OBJECTIVE: Developmental and epileptic encephalopathy with spike-wave activation in sleep ((D)EE-SWAS) is associated with acquired cognitive and behavioral deficits. This international multicenter study aimed to compare cognitive and safety outcomes following initial treatment with corticosteroid and clobazam in patients not eligible for the Randomized European trial of Steroids versus Clobazam Usage for Encephalopathy with Electrical Status Epilepticus in Sleep (RESCUE ESES). METHODS: Ten centers participated in this retrospective study. Inclusion criteria were diagnosis of (D)EE-SWAS between 2 and 12 years of age; treatment with either clobazam or corticosteroid for a consecutive period of more than 1 month within 1 year of diagnosis; and no prior treatment with clobazam or corticosteroid. Primary outcome was defined as improvement in daily functioning after 6 months of treatment, as judged by a principal investigator. Spike-wave index (SWI) was measured as secondary outcome and occurrence of adverse events was assessed. Data were analyzed by an intention-to-treat principle. In addition, an as-treated analysis was conducted to compare outcomes between patients who received oral prednisolone and intravenous methylprednisolone at any point during the 6-month treatment course, regardless of their initial selected treatment (corticosteroid or clobazam). RESULTS: Seventy-two patients met eligibility criteria and were initially treated with corticosteroid (n = 24) or clobazam (n = 48) between June 2011 and March 2020. Baseline characteristics did not differ between groups. After 6 months, 84% of patients in the corticosteroid group showed improvement in daily functioning, compared to 51% in the clobazam group (relative risk [RR] 1.6, 95% confidence interval [CI] 1.2-1.8, p = .012). SWI improved in the corticosteroid group (median change from baseline -10, interquartile range [IQR] -26 to -1), but not in the clobazam group (median change 0, IQR -20 to 7, p = .036). Both treatments were well tolerated. In patients treated with corticosteroid, intravenous pulse methylprednisolone therapy was better tolerated than daily oral prednisolone. SIGNIFICANCE: These findings complement the results of the RESCUE ESES trial and are consistent with the superiority of corticosteroid over clobazam in the early management of children with (D)EE-SWAS.