Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit: A single-center audit of 30 patients.

Abstract

In refractory status epilepticus (SE), γ-aminobutyric acidergic drugs become less effective and glutamate plays a major role in seizure perpetuation. Data on the efficacy of perampanel (PER) in treatment of refractory SE in humans are limited. Here, we present a single-center case series of patients with refractory SE who received PER orally in an intensive care unit. We retrospectively analyzed treatment response, outcome, and adverse effects of all patients with refractory SE in our Neurological Intensive Care Unit who received add-on PER between September 2012 and February 2018. Thirty patients with refractory SE (median = 72years, range = 18-91, 77% women) were included. In 14 patients (47%), a high-dose approach was used, with a median initial dose of 24mg (range = 16-32). In five patients (17%), SE could be terminated after PER administration (median dose = 6mg, range = 6-20mg, 2/5 patients in high-dose group). Clinical response was observed after a median of 24hours (range = 8-48hours), whereas electroencephalogram resolved after a median of 60hours (range = 12-72hours). Time to treatment response tended to be shorter in patients receiving high-dose PER (median clinical response = 16hours vs 18hours; electroencephalographic response = 24hours vs 72hours), but groups were too small for statistical analysis. Continuous cardiorespiratory monitoring showed no changes in cardiorespiratory function after "standard" and "high-dose" treatment. Elevated liver enzymes without clinical symptoms were observed after a median of 6days in seven of 30 patients (23%; 57% high dose vs 43% standard dose), of whom six also received treatment with phenytoin (PHT). Outcome was unfavorable (death, persistent vegetative state) in 13 patients (43%; 39% high dose vs 61% standard dose), and good recovery (no significant disability, moderate disability) was achieved in nine patients (56% high dose vs 44% standard dose). Oral PER in loading doses up to 32mg were well tolerated but could terminate SE only in a few patients (5/30; 17%). Long duration of SE, route of administration, and severe underlying brain dysfunction might be responsible for the modest result. An intravenous formulation is highly desired to explore the full clinical utility in the treatment of refractory SE.