Abstracts

Rationale: Several small case series have cited high-dose diazepam (DZP) as an effective treatment for electrical status epilepticus in slow-wave sleep (ESES), in the setting of Landau-Kleffner syndrome (LKS) and the syndrome of continuous spike-waves in sleep (CSWS). This retrospective study was designed to evaluate the short-term efficacy of DZP using a larger cohort, with a standardized protocol for dosage and EEG assessment. Methods: In a retrospective analysis, 23 subjects were identified with ESES, which was electrographically defined as spike-wave complexes occupying greater than 50% of slow-wave sleep. 12 subjects were male, 11 were female. Mean age was 8 years (range 4-12). Three had LKS whereas 20 had CSWS. All but one had epilepsy, and six carried an autistic spectrum diagnosis. All patients exhibited either language delay or frank language regression prior to diazepam therapy. Patients were admitted for continuous video-EEG monitoring at the Mattel Children s Hospital at UCLA. After overnight baseline EEG assessment, DZP was administered by mouth in a single bedtime dose of 1 mg/kg, and continued for at least three weeks at a dosage of 0.5-1.0 mg/kg/day and subsequently tapered in most cases. Video-EEG was continued for a second night and patients were observed for adverse events. For each patient, ESES was quantified before and after treatment using the spike-wave index (SWI), defined as the proportion of sleep occupied by spike-wave complexes. The change in mean SWI before and after DZP was assessed using a paired t-test. Results: Mean SWI before DZP was 79.8 (95% CI 75.4-84.3) and mean SWI after DZP was 63.0 (95% CI 55.5-70.6). This represents a statistically significant reduction (p < 0.001). Although no standardized neuropsychological assessment was carried out, subjective language performance was uniformly improved among subjects with LKS. However, only modest language improvement was observed among those with CSWS. There were no adverse events that mandated immediate discontinuation of therapy, but several parents reported fatigue and behavioral problems. Conclusions: Diazepam appears to be a safe and effective means to acutely reduce the severity of ESES, and among patients with LKS, is of at least temporary clinical benefit. Further investigation is necessary to assess the long-term effectiveness of DZP for the treatment of ESES. A blinded and placebo-controlled trial with standardized EEG and clinical outcome measures is necessary to validate these findings.