Electro-clinical analysis of epilepsy patients with generalized seizures on adjunctive perampanel treatment

Abstract

Quantifying epileptiform discharges before and after the initiation of treatment can be useful for evaluating the efficacy of antiepileptic drugs in generalized epilepsy. The aim of this study was to determine if the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist perampanel alters the electroencephalographic signals in patients with drug resistant generalized seizures (primary or secondary). We also assessed the clinical efficacy, safety and tolerability of perampanel as an adjunctive treatment for patients with refractory generalized seizures after 3, 6 and 12 months of treatment to determine if there is an electro-clinical correlation. We carried out a 1-year retrospective, unicentric, observational, descriptive and non-interventional study to analyze changes in epileptiform discharges, seizure frequency and adverse effects in patients with generalized seizures taking perampanel as an add-on treatment. Perampanel significantly reduced the total number, total duration, maximal duration and average duration of epileptiform discharges in patients with primary generalized epilepsy (n = 44). In patients with focal onset epilepsy and secondary generalized seizures (n = 8) significant decreases in the maximal duration and average duration of epileptiform discharges were found. These findings correlate with the significant decrease in seizure frequency and clinical improvement observed after taking perampanel as an adjunctive therapy for 3, 6 and 12 months. To our knowledge, this is the first study to show that perampanel reduces epileptiform activity, and that this effect correlates with patients' clinical improvement. Analysing patients' electroencephalographic activity in response to perampanel could be useful for assessing the drug's efficacy and optimising adjunctive treatments.

Keywords: Epileptiform discharge; Focal onset epilepsy; Generalized seizures; Idiopathic generalized epilepsy; Juvenile myoclonic epilepsy; Perampanel; Primary generalized epilepsy.