Abstracts

Rationale: In refractory status epilepticus (SE) GABAergic drugs are no longer effective, and glutamate plays a major role in seizure perpetuation. Perampanel (PER) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. Methods: We retrospectively analyzed treatment response, outcome, and adverse effects of add-on treatment with PER in patients with refractory SE in the Neurological Intensive Care Unit, Salzburg, Austria between 09/2012 and 06/2016. Results: Sixteen patients (75%women, median 70 years, range: 21 to 91 years) with refractory SE were treated with PER administered via nasogastric tube. In four of these patients (treated between 01/2015 and 06/2016) an intensified dosage approach was used. The most frequent SE type was nonconvulsive SE (NCSE) with (6/16, 38%) and without coma (7/16, 44%). In eight patients (50%), SE arose de novo, with an acute symptomatic cause in six patients (38%). PER was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 2.3 days [0.8 - 18.3]. In one patient (female, age 60 years), clinical improvement was observed within 24 h and EEG improvement within 60 h after administration of PER 12mg, while in another patient (female, age 66 years), clinical and EEG improvement was observed more than 48 h after administration of PER 6 mg. Median initial dose in the "standard" dose group was 4 mg [2?"12], titrated up to 12 mg [4?"12] by 2 to 4 mg per day. Higher initial doses of PER with a median initial dose of 32 mg (range: 20 to 32 mg) were used in the "ultra high dose" group. In one patient (female, age 21 years), suffering from focal motor SE, clinical and EEG improvement was observed within 24 hours after administration of PER 20 mg. Continuous cardiorespiratory monitoring was performed in all patients, with no changes in cardiorespiratory function associated with administration of "standard" as well as "ultra high dose" PER. Outcome after SE was good recovery in one patient (6%), moderate disability in six (38%), death in five (31%), and persistent vegetative state in two patients (13%). Two of the four patients receiving the intensified dosage scheme, died due to a severe underlying disease (metastatic tumor, cerebral toxoplasmosis). Conclusions: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before administration of PER, the route of administration, as well as relatively low doses in the majority of patients (12/16, 75%), might be responsible for the modest result. By using a high dose approach with administration of PER 32 mg, SE could be terminated in one patient (25%). No cardiorespiratory adverse events or laboratory changes were observed associated with both "standard" and "ultra high dose" PER administration. Funding: No funding was received in Support of this Abstract.