Gjerulfsen, Cathrine E;
Oudin, Madeleine J;
Furia, Francesca;
Gverdtsiteli, Sopio;
Landmark, Cecilie Johannessen;
Trivisano, Marina;
Balestrini, Simona;
... Møller, Rikke S; + view all
(2025)
Cenobamate as add-on treatment for SCN8A developmental and epileptic encephalopathy.
Epilepsia
10.1111/epi.18257.
(In press).
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SCN8A and cenobamate_final141224_no_track.pdf - Accepted Version Access restricted to UCL open access staff until 16 January 2026. Download (372kB) |
Abstract
Objectives: Developmental and epileptic encephalopathies (DEEs) caused by pathogenic variants in SCN8A are associated with difficult-to-treat and early-onset seizures, developmental delay/intellectual disability, impaired quality of life, and increased risk of early mortality. High doses of sodium channel blockers are typically used to treat SCN8A-DEE caused by gain-of-function (GoF) variants. However, seizures are often drug resistant, and only a few patients achieve seizure freedom. In this retrospective study, the effect of cenobamate was assessed in patients with SCN8A-DEE. // Methods: Across multiple centers and through collaborations with SCN8A patient advocacy organizations, patients with SCN8A-DEE treated with cenobamate for ≥6 months were identified. Data were obtained from patients' caregivers or treating physicians through a (Research Electronic Data Capture) REDCap survey. The functional effect of the SCN8A variants was obtained from the literature or assessed by prediction tools. // Results: Twelve patients (3–25 years of age (median 8 years), 9 females) with presumed GoF SCN8A variants were treated with cenobamate for a mean period of 17 months (range 6–42 months). Countable motor seizures were meaningfully reduced in 10 of 12 patients (83%). Six patients experienced a seizure reduction above 70%, of which two achieved seizure freedom. In addition, two patients achieved a reduction in seizures ranging between 50% and 70%. An increase in seizure-free days per patient was also reported. Rescue medication was decreased in six of seven patients (85%) in need. Furthermore, 80% of patients reported non–seizure-related improvements, which included increased alertness, better sleep, and improved muscle tone. Adverse effects were reported by 50% of patients, and half resolved spontaneously or through the reduction of concomitant antiseizure medications. // Significance: Our data suggest that cenobamate is a promising and safe treatment for SCN8A-DEE, even during early childhood. As a potential precision approach to treatment, cenobamate significantly reduced seizure burden and improved non–seizure-related symptoms. These positive outcomes may also be achieved in patient cohorts with GoF variants in other voltage-gated sodium channel genes.
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