Effect of fenfluramine on seizures and comorbidities in SCN8A-developmental and epileptic encephalopathy: A case series

Ángel Aledo-Serrano*, Borja Cabal-Paz, Elena Gardella, Pablo Gómez-Porro, Otilia Martínez-Múgica, Alvaro Beltrán-Corbellini, Rafael Toledano, Irene García-Morales, Antonio Gil-Nagel

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


SCN8A-developmental and epileptic encephalopathy is caused by pathogenic variants in the SCN8A gene encoding the Nav 1.6 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.

Sider (fra-til)525-531
Antal sider7
TidsskriftEpilepsia Open
Udgave nummer3
StatusUdgivet - sep. 2022

Bibliografisk note

© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.


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