To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question.

Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic drugs) is necessary to answer the title question.