%0 Multicenter Study
%T Perampanel as precision therapy in rare genetic epilepsies.
%A Nissenkorn A
%A Kluger G
%A Schubert-Bast S
%A Bayat A
%A Bobylova M
%A Bonanni P
%A Ceulemans B
%A Coppola A
%A Di Bonaventura C
%A Feucht M
%A Fuchs A
%A Gröppel G
%A Heimer G
%A Herdt B
%A Kulikova S
%A Mukhin K
%A Nicassio S
%A Orsini A
%A Panagiotou M
%A Pringsheim M
%A Puest B
%A Pylaeva O
%A Ramantani G
%A Tsekoura M
%A Ricciardelli P
%A Lerman Sagie T
%A Stark B
%A Striano P
%A van Baalen A
%A De Wachter M
%A Cerulli Irelli E
%A Cuccurullo C
%A von Stülpnagel C
%A Russo A
%J Epilepsia
%V 64
%N 4
%D 04 2023
%M 36734057
%F 6.74
%R 10.1111/epi.17530
%X Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g., SCN1A), overactive excitatory neurons (e.g., SCN2A, SCN8A), and variants in glutamate receptors (e.g., GRIN2A) hold special interest. We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy.<BR>This multicenter project was based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel were collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified.<BR>A total of 137 patients with 79 different etiologies, aged 2 months to 61 years (mean = 15.48 ± 9.9 years), were enrolled. The mean dosage was 6.45 ± 2.47 mg, and treatment period was 2.0 ± 1.78 years (1.5 months-8 years). Sixty-two patients (44.9%) were treated for >2 years. Ninety-eight patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61% ± 34.36%. Sixty patients (43.5%) sustained >75% reduction in seizure frequency, including 38 (27.5%) with >90% reduction in seizure frequency. The following genes showed high treatment efficacy: SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, and NEU1. Eleven of 17 (64.7%) patients with Dravet syndrome due to an SCN1A pathogenic variant were responders to perampanel treatment; 35.3% of them had >90% seizure reduction. Other etiologies remarkable for >90% reduction in seizures were GNAO1 and PIGA. Fourteen patients had a continuous spike and wave during sleep electroencephalographic pattern, and in six subjects perampanel reduced epileptiform activity.<BR>Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1, and POLG, suggesting a targeted effect related to glutamate transmission.