Work

INNV-40. Targeting tumor-related epilepsy: modified Atkins diet therapy in the context of IDH-mutant gliomas

Year: 2025

Type: conference-abstract

Abstract: PURPOSE Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant brain tumors in young adults and commonly present with tumor-related epilepsy. One proposed mechanism for seizure generation in IDH-mutant gliomas is the accumulation of 2-hydroxyglutarate (2-HG), which may promote neuronal hyper-excitability. While ketogenic diet therapy (KDT) is an established adjunct in drug-resistant epilepsy, its use in tumor-related epilepsy remains investigational. Here, we present a case report of two patients with IDH-mutant glioma and drug-resistant epilepsy who were self-referred to the UW Health Adult Neurology KDT Clinic. METHODS A retrospective review was conducted on two patients with IDH-mutant gliomas and drug-resistant epilepsy who elected to start on the modified Atkins diet (MAD) version of KDT following tumor treatment with standard maximal safe resection, radiation, and adjuvant chemotherapy. Both patients had drug-resistant epilepsy, and further adjustments of antiseizure medications failed to provide meaningful seizure control. Seizure frequency was documented before and after initiation of MAD. Ketone levels were tracked while on MAD, indicating adherence. RESULTS Both patients maintained compliance with MAD for an average of 33 months. Patient 1 had a 69% reduction in seizure frequency over 14 months with a mean beta-hydroxybutyrate level of 3.83 mmol/L (ketosis defined as >0.5 mmol/L). Even when seizure frequency was at baseline, the patient reported decreased seizure severity. Patient 2 had a 46% reduction in seizure days per month over 6 months and was in ketosis with moderate to large urine ketones. CONCLUSION These cases suggest that KDT may be an effective treatment for IDH-mutant glioma patients with tumor-related and drug-resistant epilepsy. Both patients demonstrated significant reductions in seizure frequency and/or severity. These data highlight the potential utility of diet interventions in tumor-related epilepsy and emphasizes the need for further investigation of the efficacy, tolerability, and mechanistic role of ketone metabolism in these populations.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/noaf201.0929