Perampanel as precision therapy in rare genetic epilepsies.

Autor: Nissenkorn A; Pediatric Neurology Unit, Wolfson Medical Center, Holon and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel., Kluger G; Epilepsy Center for Children and Adolescents, Schön Clinic Vogtareuth, Vogtareuth, Germany.; Research Institute for Rehabilitation, Transition, and Palliation, PMU Salzburg, Salzburg, Austria., Schubert-Bast S; Pediatric Neurology, University Clinic and Epilepsy Center, Frankfurt, Germany., Bayat A; Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Filadelfia, Dianalund, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark., Bobylova M; Svt. Lucka's Institute of Child Neurology and Epilepsy, Moscow, Russian Federation., Bonanni P; Epilepsy and Clinical Neurophysiology Unit, Scientific Institute, Eugenio Medea, Scientific Institute for Research and Health Care, Treviso, Italy., Ceulemans B; Pediatric Neurology, Antwerp University and Antwerp University Hospital, Edegem, Belgium., Coppola A; Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University Naples, Naples, Italy., Di Bonaventura C; Neurology Department, Sapienza University, Rome, Italy., Feucht M; Center for Rare and Complex Epilepsies, full member of EpiCARE, Department of Pediatrics, Medical University Vienna, Vienna, Austria., Fuchs A; SPZ Suhl SRH Central Clinic Suhl, Pediatric Clinic, Suhl, Germany., Gröppel G; Department of Pediatrics and Adolescent Medicine, Kepler University Hospital, Johannes Kepler University, Linz, Austria., Heimer G; Pediatric Neurology Unit, Sheba Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel., Herdt B; Neonatology, Palliative Care, Miltenberg, Germany., Kulikova S; Republican Research and Clinical Center of Neurology and Neurosurgery, Minsk, Belarus., Mukhin K; Svt. Lucka's Institute of Child Neurology and Epilepsy, Moscow, Russian Federation., Nicassio S; IRCCS, Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'età pediatrica, Bologna, Italy., Orsini A; Pediatric Neurology, Pediatric Department, Pisa University Hospital, University Hospital of Pisa, Pisa, Italy., Panagiotou M; Pediatric Office Maria Panagiotou, Larissa, Greece., Pringsheim M; Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Clinic Vogtareuth, Vogtareuth, Germany., Puest B; Department of Neuropediatrics, Wilhelmstift Catholic Children's Hospital, Hamburg, Germany., Pylaeva O; Svt. Lucka's Institute of Child Neurology and Epilepsy, Moscow, Russian Federation., Ramantani G; Department of Neuropediatrics, University Children's Hospital Zurich, Zurich, Switzerland., Tsekoura M; Department of Neuropediatrics, University Children's Hospital Zurich, Zurich, Switzerland., Ricciardelli P; Neurology Service of the Pediatric Unit, Ravenna Hospital, Ravenna, Italy., Lerman Sagie T; Pediatric Neurology Unit, Wolfson Medical Center, Holon and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel., Stark B; Department of Pediatrics and Adolescent Medicine, Kepler University Hospital, Johannes Kepler University, Linz, Austria., Striano P; Giannina Gaslini Institute, Scientific Institute for Research and Health Care, Genoa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy., van Baalen A; Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University (CAU), Kiel, Germany., De Wachter M; Pediatric Neurology, Antwerp University and Antwerp University Hospital, Edegem, Belgium., Cerulli Irelli E; Neurology Department, Sapienza University, Rome, Italy., Cuccurullo C; Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University Naples, Naples, Italy., von Stülpnagel C; Research Institute for Rehabilitation, Transition, and Palliation, PMU Salzburg, Salzburg, Austria.; Pediatric Office Dr. Brückmann, Brannenburg, Germany.; Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics Department of Pediatrics and Epilepsy Center, Dr. von Hauner Children's Hospital, Ludwig Maximilian University, Munich, Germany., Russo A; IRCCS, Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'età pediatrica, Bologna, Italy.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2023 Apr; Vol. 64 (4), pp. 866-874. Date of Electronic Publication: 2023 Feb 20.
DOI: 10.1111/epi.17530
Abstrakt: 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.
(© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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