Efficacy and safety of perampanel oral loading in postanoxic super‐refractory status epilepticus: A pilot study

Abstract

Refractory nonconvulsive status epilepticus (NCSE) occurs in 10%-30% of patients following resuscitation after cardiac arrest. Both the optimal treatment and prognosis of postanoxic status epilepticus remain uncertain. We analyzed acute electroencephalographic changes, neurological outcome at 3 months, and adverse effects in consecutive postanoxic patients with super-refractory NCSE treated with add-on oral loading of perampanel. Eight postanoxic patients with super-refractory NCSE were treated with perampanel (dose range = 6-12 mg). All patients had continuous electroencephalographic monitoring showing definite generalized NCSE and favorable multimodal prognostic indicators (presence of brainstem reflexes, presence of bilateral N20 responses, absence of periodic discharges/generalized epileptic periodic discharges). In six patients (75%), status epilepticus resolved within 72 hours after administration of perampanel, without changing the comedication. Neurological outcomes at 3 months were return to normal or minimal disability in four patients (50%). A mild cholestatic liver injury, which required no specific treatment, was observed in five patients (62.5%). Perampanel 6-12 mg oral loading appeared to be an effective option in selected patients with postanoxic super-refractory NCSE with good prognostic indicators. In this patient population, our safety data indicate a risk of cholestasis.

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management

“…Perampanel is used for the adjunctive treatment of epilepsy up to 12 mg/day and acts as an orally active noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist to reduce glutamate-mediated postsynaptic excitation [118][119][120].…”

Super-Refractory Status Epilepticus Treated with High Dose Perampanel: Case Series and Review of the Literature

“…Perampanel is a noncompetitive glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist [10]. It has a terminal half-life of ~105 hours and reaches steady state in 10–19 days [11].…”

“…Clinical response was observed by a median of 24 hours (range 8–48 hours) and EEG response by median of 60 hours (range 12–72 hours) with a shorter time to treatment response in those with high dose loading (16 vs 18 hours for clinical response; 24 vs 72 hours for EEG response) [13]. In ~23–63% of patients, a mild hepatic/cholestatic injury was observed following perampanel [10, 13]. No patient had changes in cardiorespiratory parameters following loading dose of perampanel [10, 13].…”

“…In ~23–63% of patients, a mild hepatic/cholestatic injury was observed following perampanel [10, 13]. No patient had changes in cardiorespiratory parameters following loading dose of perampanel [10, 13]. One patient developed multi-organ failure from the use of high doses of pentobarbital.…”

“…Perampanel may also have a role in the treatment of post-anoxic status epilepticus. In a small pilot study of 8 post-anoxic patients with super-refractory, nonconvulsive status epilepticus (NCSE) and favorable prognostic indicators, the addition of perampanel (median dose of 6 mg; range 6–12 mg) after a median time of 9.5 days (range 4–35 days) from cardiac arrest to the standard of care [median number of 3 AEDs (range 2–5) and 3 anesthetics (range 1–4)] resulted in cessation of NCSE in six (75%) patients by 72 hours [10]. For those patients with postanoxic myoclonic seizures, perampanel has been shown to cause clinically meaningful improvement in myoclonus despite the use of other commonly administered antiepileptic medications [16].…”