Perampanel as precision therapy in rare genetic epilepsies
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Perampanel as precision therapy in rare genetic epilepsies. / Nissenkorn, Andreea; Kluger, Gerhard; Schubert-Bast, Susanne; Bayat, Allan; Bobylova, Marya; Bonanni, Paolo; Ceulemans, Berten; Coppola, Antonietta; Di Bonaventura, Carlo; Feucht, Martha; Fuchs, Anne; Gröppel, Gudrun; Heimer, Gali; Herdt, Brigitte; Kulikova, Sviatlana; Mukhin, Konstantin; Nicassio, Stefania; Orsini, Alessandro; Panagiotou, Maria; Pringsheim, Milka; Puest, Burkhard; Pylaeva, Olga; Ramantani, Georgia; Tsekoura, Maria; Ricciardelli, Paolo; Lerman Sagie, Tally; Stark, Brigit; Striano, Pasquale; van Baalen, Andreas; De Wachter, Matthias; Cerulli Irelli, Emanuele; Cuccurullo, Claudia; von Stülpnagel, Celina; Russo, Angelo.
I: Epilepsia, Bind 64, Nr. 4, 04.2023, s. 866-874.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Perampanel as precision therapy in rare genetic epilepsies
AU - Nissenkorn, Andreea
AU - Kluger, Gerhard
AU - Schubert-Bast, Susanne
AU - Bayat, Allan
AU - Bobylova, Marya
AU - Bonanni, Paolo
AU - Ceulemans, Berten
AU - Coppola, Antonietta
AU - Di Bonaventura, Carlo
AU - Feucht, Martha
AU - Fuchs, Anne
AU - Gröppel, Gudrun
AU - Heimer, Gali
AU - Herdt, Brigitte
AU - Kulikova, Sviatlana
AU - Mukhin, Konstantin
AU - Nicassio, Stefania
AU - Orsini, Alessandro
AU - Panagiotou, Maria
AU - Pringsheim, Milka
AU - Puest, Burkhard
AU - Pylaeva, Olga
AU - Ramantani, Georgia
AU - Tsekoura, Maria
AU - Ricciardelli, Paolo
AU - Lerman Sagie, Tally
AU - Stark, Brigit
AU - Striano, Pasquale
AU - van Baalen, Andreas
AU - De Wachter, Matthias
AU - Cerulli Irelli, Emanuele
AU - Cuccurullo, Claudia
AU - von Stülpnagel, Celina
AU - Russo, Angelo
N1 - Publisher Copyright: © 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - genetic epilepsies
KW - perampanel
KW - precision therapy
U2 - 10.1111/epi.17530
DO - 10.1111/epi.17530
M3 - Journal article
C2 - 36734057
AN - SCOPUS:85148533566
VL - 64
SP - 866
EP - 874
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 4
ER -
ID: 389676991