Remarkable Phenytoin Sensitivity in 4 Children with SCN8A-related Epilepsy: A Molecular Neuropharmacological Approach

Ragna S. Boerma, Kees P. Braun, Maarten P. H. van de Broek, Frederique M. C. van Berkestijn, Marielle E. Swinkels, Eveline O. Hagebeuk, Dick Lindhout, Marjan van Kempen, Maartje Boon, Joost Nicolai, Carolien G. de Kovel, Eva H. Brilstra, Bobby P. C. Koeleman*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    106 Citaten (Scopus)
    63 Downloads (Pure)


    Mutations in SCN8A are associated with epilepsy and intellectual disability. SCN8A encodes for sodium channel Nav1.6, which is located in the brain. Gain-of-function missense mutations in SCN8A are thought to lead to increased firing of excitatory neurons containing Nav1.6, and therefore to lead to increased seizure susceptibility. We hypothesized that sodium channel blockers could have a beneficial effect in patients with SCN8A-related epilepsy by blocking the over-active Nav1.6 and thereby counteracting the effect of the mutation. Herein, we describe 4 patients with a missense SCN8A mutation and epilepsy who all show a remarkably good response on high doses of phenytoin and loss of seizure control when phenytoin medication was reduced, while side effects were relatively mild. In 2 patients, repeated withdrawal of phenytoin led to the reoccurrence of seizures. Based on the findings in these patients and the underlying molecular mechanism we consider treatment with (high-dose) phenytoin as a possible treatment option in patients with difficult-to-control seizures due to an SCN8A mutation.

    Originele taal-2English
    Pagina's (van-tot)192-197
    Aantal pagina's6
    Nummer van het tijdschrift1
    StatusPublished - jan.-2016

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