Ketogenic diet combined with multimodal therapy in drug-resistant epilepsy: a case report

Abstract

Case Presentation: H.A.V., a 7-year-old male, presented with neuropsychomotor developmental (NPMD) delay identified at the age of 2, predominantly affecting language, and associated with behavioral disturbances and attention deficits. At the age of 4, following a COVID-19 infection, he developed afebrile epileptic seizures, which progressed to multiple seizure types, including focal, absence, atonic, and bilateral tonic-clonic seizures. A family history of childhood epilepsy on both the maternal and paternal sides has been reported. The electroencephalogram (EEG) revealed both generalized and focal epileptiform activity, while whole-exome sequencing identified pathogenic variants in the BBS10, CCNO, HFE, PDZD7, TRMU, and DYRK1A genes. Initial monotherapy with sodium valproate was ineffective in controlling seizures, requiring dose optimization and the addition of multiple antiseizure medications (ASMs), along with the implementation of complementary therapeutic strategies, including the ketogenic diet, corpus callosotomy, and Vagus Nerve Stimulation (VNS). Discussion: This case illustrates a presentation of pharmacoresistant epilepsy associated with a genetic abnormality, impacting significantly the patient's quality of life. Given the resistance to isolated pharmacological treatment, a multidisciplinary approach was necessary to optimize seizure control. Over time, the child experienced more than 100 seizures per day, which were reduced to fewer than one seizure per month. Notably, nutritional therapy with the ketogenic diet played a key role in controlling certain seizure types, such as generalized seizures, emphasizing its importance as an adjunctive therapy in cases of drug-resistant epilepsy. Furthermore, the therapeutic combination used highlights the heterogeneity of epilepsy and the need for individualized management. Final Comments: This study underscores the complexity of pharmacoresistant epilepsy and the importance of exploring non-pharmacological treatments when traditional drugs fail. When applied appropriately, considering the patient's profile, monitoring ketosis, and adjusting the dosages of associated antiseizure medications, the ketogenic diet proves to be an essential component of multimodal treatment. The integration of ketogenic therapy, pharmacological management, surgery, and neuromodulation reinforces the significance of a personalized, multidisciplinary approach in managing pharmacoresistant epilepsy.