Abstracts

Rationale: Studies looking at the effect of anti-epileptic drugs on the sleep microstructure of patients with epilepsy are scarce1,2. The aim of this study was to evaluate the effects of eslicarbazepine (ESL) as add-on therapy on sleep microstructure in focal drug-refractory epilepsy. Methods: Twelve patients affected by focal epilepsy were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) before and after three months of treatment with ESL as add-on therapy. Scoring and analysis of arousals and cyclic alternating pattern (CAP) parameters were performed. Comparison of CAP parameters was performed using the non-parametric Wilcoxon test (p < 0.05). Results: Ten patients completed the study. ESL therapy reduced seizures by >50% in 7 out of 10 patients (5/10 were seizure free). Three patients were non-responders, 1/3 showed a reduction of seizure of less than 50% and 2/3 unchanged frequency. ESL did not induce any significant changes in nocturnal macrostructural polysomnographic variables and PSQI scores. Besides, ESS score was unmodified after treatment. The sleep microstructure analysis showed lower CAP rate in N3 (p=0.03), phase A2 index (p=0.02) and number and mean duration of CAP sequences (both p=0.02) after ESL. A trend toward significance was evident for the decrease of CAP rate in N1 (p=0.09), and N2 (p=0.09) and the increase of B phase mean duration (p=0.07) after ESL. Conclusions: Both subjective and objective sleep parameters showed no detrimental effects on nocturnal sleep and daytime somnolence in patients with focal epilepsy using ESL. We found significant improvement of sleep stability as measured by CAP after ESL. These findings suggest that ESL may positively modulate sleep instability and fragmentation in patients with refractory focal epilepsy, and hence ameliorate sleep quality and continuity. Since some AEDs induce sleep impairment, which is known to trigger EEG abnormalities and seizures and to worsen the quality of life, our findings suggest a favorable sleep profile of ESL3–7. Bibliography1. Sudbrack-Oliveira, P., Lima Najar, L., Foldvary-Schaefer, N. & da Mota Gomes, M. Sleep architecture in adults with epilepsy: a systematic review. Sleep Med. 53, 22–27 (2018).2. Nayak, C. S., Sinha, S., Nagappa, M., Thennarasu, K. & Taly, A. B. Effect of carbamazepine on the sleep microstructure of temporal lobe epilepsy patients: a cyclic alternating pattern-based study. Sleep Med. 27–28, 80–85 (2016).3. Jain, S. V. & Glauser, T. A. Effects of epilepsy treatments on sleep architecture and daytime sleepiness: an evidence-based review of objective sleep metrics. Epilepsia 55, 26–37 (2014).4. Placidi, F. et al. Effect of anticonvulsants on nocturnal sleep in epilepsy. Neurology 54, S25-32 (2000).5. Romigi, A. et al. Effects of epilepsy treatment on sleep architecture and daytime sleepiness: an evidence-based review of objective sleep metrics. Epilepsia 55, 777–778 (2014).6. Romigi, A. et al. Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study. Epilepsy Behav. 26, 170–174 (2013).7. Romigi, A. et al. Effects of adjunctive perampanel on sleep quality, daytime somnolence and cognition in refractory focal epilepsy: further data. Epilepsy Behav. 67, 137–138 (2017). Funding: EISAI Inc funded this study.