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Multicenter Study
. 2023 Apr;64(4):866-874.
doi: 10.1111/epi.17530. Epub 2023 Feb 20.

Perampanel as precision therapy in rare genetic epilepsies

Andreea Nissenkorn  1 , Gerhard Kluger  2   3 , Susanne Schubert-Bast  4 , Allan Bayat  5   6 , Marya Bobylova  7 , Paolo Bonanni  8 , Berten Ceulemans  9 , Antonietta Coppola  10 , Carlo Di Bonaventura  11 , Martha Feucht  12 , Anne Fuchs  13 , Gudrun Gröppel  14 , Gali Heimer  15 , Brigitte Herdt  16 , Sviatlana Kulikova  17 , Konstantin Mukhin  7 , Stefania Nicassio  18 , Alessandro Orsini  19 , Maria Panagiotou  20 , Milka Pringsheim  21 , Burkhard Puest  22 , Olga Pylaeva  7 , Georgia Ramantani  23 , Maria Tsekoura  23 , Paolo Ricciardelli  24 , Tally Lerman Sagie  1 , Brigit Stark  14 , Pasquale Striano  25   26 , Andreas van Baalen  27 , Matthias De Wachter  9 , Emanuele Cerulli Irelli  11 , Claudia Cuccurullo  10 , Celina von Stülpnagel  3   28   29 , Angelo Russo  18
Affiliations
Multicenter Study

Perampanel as precision therapy in rare genetic epilepsies

Andreea Nissenkorn et al. Epilepsia. 2023 Apr.

Erratum in

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Significance: 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.

Keywords: genetic epilepsies; perampanel; precision therapy.

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Comment in

References

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