State of the art: glioma-associated epilepsy-bridging tumor biology and epileptogenesis.

Abstract

Background: Glioma-associated epilepsy (GAE) is a frequent and clinically significant complication in neuro-oncological practice. Its prevalence varies across glioma subtypes and is influenced by tumor biology, cortical involvement, tumor size, extent of resection, and disease progression. Despite its substantial impact on quality of life and clinical outcomes, GAE remains underrepresented in neurological and neuro-oncological guidelines. Moreover, novel findings in molecular subtyping and their relevance to tumor biology and GAE pathogenesis are not yet adequately reflected in clinical frameworks. Here, we aim to provide a comprehensive synthesis of epidemiology, pathophysiology, and management strategies for GAE based on the recent advances in glioma biology, cancer neuroscience, and epileptology.

Main body: This review highlights recent insights into the epidemiology, clinical impact, pathophysiology, and therapeutic strategies for GAE. We focus on both lower-grade gliomas, in which GAE is most prevalent over lifetime-particularly in tumors harboring isocitrate dehydrogenase (IDH) mutations-as well as high-grade gliomas where GAE remains a clinically relevant and complex issue. In addition to diffuse glioma subtypes, this review also addresses low-grade epilepsy-associated tumors (LEAT), a distinct and heterogeneous group with an inherently high risk of seizures. The pathomechanisms of GAE are reviewed with regard to glioma subtype-specific alterations of the tumor metabolism, neuroinflammation, increased glutamatergic activity, as well as the interaction between tumor cells and non-neoplastic cells. Key pathways implicated in both GAE and tumor biology include the IDH and mTOR signaling and a range of tumor related somatic mutations. With regard to the prognostic and therapeutic significance of GAE, we highlight the essential importance of accurate molecular tumor classification. In addition to reviewing common and tumor-specific side effects of anti-seizure medication (ASM), the emerging role of therapeutic approaches targeting both tumor growth and epileptogenesis is discussed.

Conclusion: Glioma (subtype) specific mechanisms of epileptogenesis and selection of ASM is an emerging topic with future potential to improve the therapy of GAE and tumor growth alike.