Brain Tumor-Related Epilepsy: A Comprehensive Review of Pathophysiology, Molecular Biomarkers, Surgical Outcome, and What is the New Frontier in Clinical Management

Abstract

Brain Tumor-Related Epilepsy (BTRE) is a complex clinical challenge at the intersection of oncology and neurology, significantly impacting patients' quality of life. Seizure prevalence is estimated between 30% and 50% in adults with brain tumors, reaching up to 80% in specific tumor types. This comprehensive literature review aims to synthesize and analyze the current knowledge on BTRE, focusing on its epidemiology and clinical correlations, molecular and pathophysiological mechanisms, and therapeutic strategies. The analysis revealed that Low-Grade Gliomas (LGGs) and Long-Term Epilepsy-Associated Tumors (LEATs), such as Ganglioglioma (GG) and Dysembryoplastic Neuroepithelial Tumor (DNT), are the most epileptogenic, particularly when localized in the temporal or frontal lobes. The review also underscored the pivotal role of modern molecular classification (WHO 2021), where genetic mutations like BRAF V600E and IDH play a direct role in epileptogenesis. Pathophysiologically, an "Epileptogenic Niche" forms in the peritumoral microenvironment, characterized by neurotransmitter imbalance (glutamate excess and GABA deficiency), neuroinflammation, and Blood-Brain Barrier (BBB) disruption. Shared molecular pathways, including PI3K/AKT/mTOR and RAS-RAF-MAPK, contribute to both tumor growth and neuronal hyperexcitability. In clinical management, drug-drug interactions between Antiseizure Medications (ASMs) and chemotherapy pose a major challenge. Enzyme-Inducing ASMs (EIAEDs) are discouraged in favor of Non-Enzyme-Inducing ASMs (NEIAEDs) like Levetiracetam. Surgical resection of the tumor remains the most effective treatment for seizure control, especially for LEATs, often requiring extended resection to achieve long-term seizure freedom. This review emphasizes the necessity of a multidisciplinary and personalized therapeutic approach to improve outcomes for patients with BTRE.