Background: Ketogenic dietary therapies (KDT) are used as a treatment in childhood epilepsy. However, their mechanism has not yet been established. The main objective of this study was to determine the changes in the transcriptomic profile induced by KDT in children with epilepsy in order to shed light on its possible mechanisms. Methods: Eight children with refractory epilepsy were enrolled in the study. Peripheral blood mononuclear cells were obtained before and after the children were treated with KDT for a minimum of 6 months. RNA was extracted and mRNA and miRNA profiling were performed and analyzed. Results: Our intervention with KDT significantly reduced the seizure number in seven of the eight paediatric patients treated and caused important changes in their gene expression profile. Our study reveals modifications in the transcription of 4630 genes and 230 miRNAs. We found that the genes involved in the protection against epileptic crises were among those mainly changed. These genes collectively encode for ion channels, neurotransmitter receptors, and synapse structural proteins. Conclusions: Together our results explain the possible mechanisms of KDT and reinforce its clinical importance in the treatment of epilepsy.

Ketogenic dietary therapies (KDT) are high-fat and low-carbohydrate diets that may achieve seizure control and improve cognitive state. We describe our KDT experience in infants (children less than two years of age). Research methods & procedures:We conducted a retrospective, descriptive and observational study of 42 infants treated with KDT between 2000-2018.Results: The types of KDT started were: classic ketogenic diet ratio 3:1 (40), ratio 4:1 (1) and modified ketogenic diet with medium-chain triglycerides (1). Four patients switched to a modified Atkins diet. During follow-up, 79%, 57%, 38% and 17% of infants remained on KDT at 3, 6, 12 and 24 months, respectively. Seizure reduction ≥50% compared to baseline was achieved in 50%, 45%, 38% and 17% at 3, 6, 12 and 24 months, respectively. Seizure control was excellent (reduction >90%) in 33%, 31%, 26% and 12%, and seizure-free infants were 9, 9, 10 and 4, at different follow-up intervals, respectively. Sixty-three percent of infants with West syndrome were responders to KDT. Mean length of KDT was 390 days (16 days-4.9 years). Ineffectiveness was the reason for withdrawal in 50% of patients. Early adverse effects (during first month) occurred in 40% of infants. The most frequent early side effects were asymptomatic hypoglycemia and gastrointestinal disturbances. Lateonset side effects occurred in 55-14% of infants during therapy, and most frequent were hypercalciuria and dyslipidaemia. Conclusion: KDT are useful and effective treatments in infancy. Side effects are frequent but mild and easy to manage.