Abstracts

Rationale: Perampanel is the first highly selective, non-competitive AMPA-type glutamate receptor antagonist that is available on the market [Di Bonaventura C et al. AMPA receptors and perampanel behind selected epilepsies: current evidence and future perspectives. Expert Opin Pharmacother. 2017;18(16):1751-64] with a marked effectiveness in focal and generalized seizures. So far, there are no data about PER efficacy on sleep-related seizures. Aim of this study was to evaluate long term efficacy and tolerability of perampanel (PER) as adjunctive therapy in patients with drug-refractory sleep-related hypermotor epilepsy (SHE) through a retrospective study. Methods: We performed a retrospective observational study of patients fulfilling the criteria of SHE [Tinuper P, et al. Definition and diagnostic criteria of sleep-related hypermotor epilepsy. Neurology. 2016:10;86(19):1834-422] receiving PER as add-on therapy for at least 12-months. Only patients who completed diaries concerning the seizures frequency and who underwent to periodic follow-up visits up to 12 months were included. Patients were classified as seizure-free, responders (seizure reduction >50% compared to baseline) or non-responders at 12 months follow-up.  Results: Ten patients (7 males, 3 females, mean age 38.1+-16.1, range 22-59 y.o) were included. All patients reported seizures during nocturnal sleep with a wide clinical spectrum, ranging from repeated stereotypic brief motor attacks to prolonged seizures, occasionally followed by tonic-clonic seizures; some patients also presented sporadic seizures during wakefulness. Furthermore 4 out of 10 patients were affected by structural focal epilepsy. Despite antiepileptic treatment (carbamazepine, phenobarbital, topiramate, levetiracetam, valproic acid and lacosamide as monotherapy or polytherapy) seizures persisted with variable frequency. PER was administered as adjunctive treatment and slowly titrated (2 mg every two weeks) up to 4 or 8 mg daily dose at bedtime. At 12-month follow-up 8 patients were responders and 2 patients were seizure-free; no patient was non-responder or had seizures worsening. The mean maintenance dose of PER was 5.2 mg/day and it was well tolerated at 12 months. Conclusions: We hypothesize that effectiveness of PER on sleep-related seizures may be due to a positive effect on the sleep-wake cycle as previously reported [Romigi A,Izzi F, et al. Effects of adjunctive perampanel on sleep quality, daytime somnolence and cognition in refractory focal epilepsy.Epilepsy Behav.2017;67:137-138]. Although larger samples are needed this study suggests PER as potentially efficacious adjunctive therapy in patients with refractory SHE. Funding: No funding