Abstracts

Rationale: Use of high-dose benzodiazepines such as diazepam and clonazepam can be an effective treatment in some patients with Continuous Spikes and Waves during Sleep (CSWS). We evaluate the treatment efficacy with high-dose clobazam in reducing seizures and epileptiform activity in CSWS. The impact on cognition and behavioral functioning following treatment is also evaluated.Methods: Patients with CSWS were enrolled prospectively in a 3-month trial at a tertiary pediatric hospital. Patients 2-21 years old with frequent discharges on EEG (at least 50% spike percentage during slow wave sleep) and cognitive regression were identified during long-term EEG (>18 hours) monitoring. Patients underwent neuropsychological assessment prior to treatment. Treatment consisted of 1 mg/kg up to a maximum dose of 30 mg during 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.Results: Seventeen patients (11 males) with a mean age of 6.9 years were enrolled and 12 completed the study. Five patients were excluded from analysis due to early discontinuation of treatment (agitation in 2 patients, 1 showed no treatment response, 1 underwent epilepsy surgery, and 1 did not return for follow-up). Mild adverse events occurred in 3 of the 12 patients that completed the study (23.1%): hyperactivity (2) and drowsiness. Spike percentage improved from a mean of 71% (SD=12.2) at baseline and decreased to 44% (SD=38.6) 3 months after treatment (paired sample t test, t-Test, p < .05). Mean spike frequency decreased from 9 per 10 seconds (SD=2.7) at baseline to 5 per 10 seconds (SD=6.7) 3 months after treatment (paired sample t test, p =0.182 [NS]). At the 3-month follow up evaluation, group means showed evidence of cognitive improvement on tests of Verbal and Spatial IQ, and receptive vocabulary skills but did not show statistical significance. A decrease in affective and behavioral problems was noted (p < 0.05). Reliable change indices were calculated to measure neuropsychological change in the six patients that showed a clear response to treatment with 1 to 3 patients improving in verbal IQ, nonverbal IQ, spatial IQ, and language tests.Conclusions: High-dose clobazam appears to be well-tolerated in patients with CSWS, and was associated with a decrease in both spike frequency and spike percentage with 3 months of treatment in selected patients with CSWS. Disclosure: This research was funded as an investigator-initiated grant by Lundbeck LLC.