A Rohracher1, J Höfler2, G Kalss3, M Leitinger4, G Kuchukhidze5, I Deak6, J Dobesberger7, H Novak8, G Pilz9, A Zerbs10, E Trinka11. 1. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: a.rohracher@salk.at. 2. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: j.hoefler@salk.at. 3. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: g.kalss@salk.at. 4. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: ma.leitinger@salk.at. 5. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: g.kuchukhidze@salk.at. 6. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: i.deak@salk.at. 7. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: j.dobesberger@salk.at. 8. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: h.novak@salk.at. 9. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: georg.pilz@salk.at. 10. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: a.zerbs@salk.at. 11. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria; Centre for Cognitive Neuroscience Salzburg, Ignaz Harrer Straße 79, A-5020 Salzburg, Austria. Electronic address: e.trinka@salk.at.
Abstract
INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: 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 the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.
INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: 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 the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.
Authors: Boulenouar Mesraoua; Dirk Deleu; Hassan Al Hail; Faisal Ibrahim; Gayane Melikyan; Hassan Al Hussein; Rajvir Singh; Basim Uthman; Leopold Streletz; Peter W Kaplan; Heinz Gregor Wieser Journal: J Drug Assess Date: 2017-11-10