Nowadays, particularly in countries with high incomes, individual mutations in people affected by genetic
epilepsies are identified, and genetic therapies are being developed. In addition, drugs are being screened to directly target specific mutations, and personalised medicine is possible. However, people with
epilepsy do not yet benefit from these advances, and many types of
epilepsies are medication-resistant, including
Dravet syndrome. Thus, in the meantime, alternative and effective treatment options are needed. There is increasing evidence that metabolic deficits contribute to epileptic
seizures and that such metabolic impairments may be amenable to treatment, with metabolic treatment options like the
ketogenic diet being employed with some success. However, the brain metabolic alterations that occur in
ion channel epilepsies are not well-understood, nor how these may differ from
epilepsies that are of acquired and unknown origins. Here, we provide an overview of studies investigating metabolic alterations in
epilepsies caused by mutations in the SCN1A and KCNA1 genes, which are currently the most studied
ion channel epilepsies in animal models. The metabolic changes found in these models are likely to contribute to
seizures. A metabolic basis of these
ion channel epilepsies is supported by human and/or animal studies that show beneficial effects of the
ketogenic diet, which may be mediated by the provision of auxiliary brain fuel in the form of
ketone bodies. Other potentially more preferred dietary
therapies including medium-chain
triglycerides and
triheptanoin have also been tested in a limited number of studies, but their efficacies remain to be clearly established. The extent to which brain metabolism is affected in people with
Dravet syndrome, KCNA1
epilepsy and the models thereof still requires clarification. This requires more experiments that yield functional insight into metabolism.