Drug resistant epilepsy and ketogenic diet: A narrative review of mechanisms of action

Abstract

Drug-resistant epilepsy (DRE) poses a significant global challenge, impacting the well-being of patients. Anti-epileptic drugs often fail to effectively control seizures in individuals with DRE. This condition not only leads to persistent seizures but also induces neurochemical imbalances, elevating the risk of sudden unexpected death in epilepsy and comorbidities. Moreover, patients experience mood and personality alterations, educational and vocational setbacks, social isolation, and cognitive impairments. Ketogenic diet has emerged as a valuable therapeutic approach for DRE, having been utilized since 1920. Various types of ketogenic diets have demonstrated efficacy in controlling seizures. By having a multimodal mechanism of action, the ketogenic diet reduces neuronal excitability and the frequency of seizure episodes. In our narrative review, we have initially provided a concise overview of the factors contributing to drug resistance in epilepsy. Subsequently, we have discussed the different available ketogenic diets. We have reviewed the underlying mechanisms through which the ketogenic diet operates. These mechanisms encompass decreased neuronal excitability, enhanced mitochondrial function, alterations in sleep patterns, and modulation of the gut microbiome. Understanding the complex mechanisms by which this diet acts is essential as it is a rigorous diet and requires good compliance. Hence knowledge of the mechanisms may help to advance research on achieving similar therapeutic effects through other less stringent approaches.

Graphical abstract