SCN8A-developmental and epileptic encephalopathy is caused by pathogenic variants in the SCN8A gene encoding the Nav1.6 sodium channel, and is characterized by intractable multivariate seizures and developmental regression. Fenfluramine is a repurposed drug with proven antiseizure efficacy in Dravet syndrome and Lennox–Gastaut syndrome. The effect of fenfluramine treatment was assessed in a retrospective series of three patients with intractable SCN8A epilepsy and severe neurodevelopmental comorbidity (n = 2 females; age 2.8–13 years; 8–16 prior failed antiseizure medications [ASM]; treatment duration: 0.75–4.2 years). In the 6 months prior to receiving fenfluramine, patients experienced multiple seizure types, including generalized tonic–clonic, focal and myoclonic seizures, and status epilepticus. Overall seizure reduction was 60%–90% in the last 3, 6, and 12 months of fenfluramine treatment. Clinically meaningful improvement was noted in ≥1 non-seizure comorbidity per patient after fenfluramine, as assessed by physician-ratings of ≥“Much Improved” on the Clinical Global Impression of Improvement scale. Improvements included ambulation in a previously non-ambulant patient and better attention, sleep, and language. One patient showed mild irritability which resolved; no other treatment-related adverse events were reported. There were no reports of valvular heart disease or pulmonary arterial hypertension. Fenfluramine may be a promising ASM for randomized clinical trials in SCN8A-related disorders.
Bibliographical notePublisher Copyright:
© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
- drug repurposing
- genetic epilepsy
- sodium channelopathy
- Epilepsies, Myoclonic/drug therapy
- Fenfluramine/therapeutic use
- NAV1.6 Voltage-Gated Sodium Channel/genetics
- Child, Preschool
- Retrospective Studies