Abstracts

Rationale: Antiepileptic drugs (AEDs) control seizures and frequently modify hypnic structure in both animals and humans. Otherwise, the sleep modulates the epileptic activity through different brain synchronizing mechanisms. Both, the amount as well the quality of sleep, are found to be altered in the epileptic population. Potentially, medicaments that block excitatory activity such as perampanel (PER) could have a beneficial role in sleep-regulation and good sleep implies better epilepsy control. Until now, there is scarce information about the effect of GLU-antagonist on sleep physiology and it is based in animal models. The primary objective of this study is to determine for the first time the sleep modulatory properties of PER in patients with focal epilepsy through objective sleep evaluation (PSG). Methods: We performed a prospective, monocentric pilot study in our comprehensive epilepsy centre that included 15 patients aged 18 to 65 meeting criteria for refractory focal onset seizures (FOS). All patients required additional medication due to pharmacoresistence. Patients were evaluated one week before PER-therapy with the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Inventory (PSQI) and a baseline polysomnography (PSG). PER tolerability was examined after titration. Four weeks after PER therapy was maintained at 6-8 mg/day, a 2nd PSG was performed altogether with PSQI and ESS. Results: 13 patients (7 females) finalized the study and performed 2 PSGs each. Two were withdrawn due to adverse events after PER titration. Average age was 36.5 years (range: 23-47). Six patients had frontal lobe epilepsy (40%) and 3 temporal lobe epilepsy (20%). In PSQI, 36% of patients had poor global sleep-quality. The ESS showed that only one patient had increased daily somnolence. In PSQI only 27% of patients reported subjective normal sleep-quality and 36%, normal sleep latency. On PSG, of 13 patients, six had prolonged sleep-latency (>20 min) and five, reduced sleep-efficiency ( < 85%) on the first PSG. After PER-therapy, no patient showed increased somnolence on ESS. On PSQI, no significant changes were observed in the subscales. Based on PSG parameters, in the whole group of 13 patients, PER showed a tendency to reduce the sleep-latency time (59.4%, p=0.221; Wilcoxon). Considering only the patients with a pathological baseline, the improvement was indeed relevant: six of six patients with abnormal sleep-latency showed a significant reduction of 74.3% and 4 reached normal values (p=0.028; Wilcoxon). Moreover, of five patients with reduced sleep-efficiency, three improved their scores, one remained unchanged and one got worse (p=0.345; Wilcoxon). Conclusions: Despite the reduced number of patients analysed in our study, PER demonstrated to show favourable properties on sleep modulation in patients with previous altered sleep structure. More interestingly, these improvements seem not to be associated with daily sleepiness (hangover). Funding: Funding was received from EISAI Co. Ltd.