Abstracts

Rationale: Epileptic encephalopathies with Continuous Spikes and Waves during Sleep (CSWS) have been shown to improve after treatment with high-dose diazepam and clonazepam, but there is limited data on the clinical response to other benzodiazepines. The aim of this study is to evaluate the effect of high-dose clobazam treatment on seizures, epileptiform activity and cognition in patients with CSWS. Methods: We prospectively enrolled patients with CSWS in a 3 month trial with high-dose clobazam at a single tertiary pediatric hospital. Patients 2-21 years old with cognitive regression were identified during long-term EEG (>18 hours) monitoring. Subjects with frequent discharges on EEG (at least 50% spike percentage during slow wave sleep) were enrolled. Treatment consisted of high-dose (1 mg/kg up to a maximum dose of 30 mg) clobazam the first night, followed by 0.5 mg/kg nightly for 3 months. Interictal epileptiform activity during non-REM sleep was evaluated as spike percentage and spike frequency immediately before treatment and 3 months after treatment. Seizure frequency and standardized neuropsychological evaluation were determined at baseline and 3 months. Results: Thirteen patients (9 males) with a median (p25-p75) age of 6.9 (4.9-9.3) years were enrolled and seven completed the study to date. Six patients were excluded from analysis: agitation led to early discontinuation in two patients, one patient failed to respond pharmacological treatment and underwent epilepsy surgery for an underlying lesion before 3 months, one was lost to follow-up and two have not yet completed the three month follow-up at this time. Spike percentage improved from a median (p25-p75) of 73% (30-88) at baseline and decreased to 30% (0-70) 3 months after treatment (Wilcoxon matched-pairs signed-rank test, p = 0.1071). Spike frequency decreased from a median (p25-p75) of 90 per 100 seconds (60-130) at baseline to a median of 40 per 100 seconds (0-90) 3 months after treatment (Wilcoxon matched-pairs signed-rank test, p = 0.0910). The group means for general IQ, verbal IQ, spatial IQ and receptive vocabulary skills improved from baseline to the 3-month follow up. Other areas examined did not demonstrate specific trends (Table 1). Mild adverse events occurred in 3 (23.1%) patients: hyperactivity (2) and mild drowsiness (1). Conclusions: Findings from this interim analysis in patients with CSWS treated with high dose clobazam demonstrate a trend towards a reduction of epileptiform activity and improved cognition. Adverse events were typically mild. These findings suggest high-dose clobazam is a safe option for CSWS and treatment may have short-term benefits on neurobehavioral status in select patients. We are in the process of enrolling more patients to provide additional details in the near future. Disclosure: This research was funded as an investigator-initiated study by Lundbeck LLC.