Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management

Abstract

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug–drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials.

Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma

“…Both perampanel and levetiracetam are broad spectrum ASMs and effective clinically for the management of glioma-related epilepsy. 1 However, it is notable that usual doses of perampanel administered are 2-3 orders of magnitude smaller than doses of levetiracetam (i.e., 4-12mg versus 1000-4000mg per day). We observed a similar difference in brain tissue concentrations of the drugs, with perampanel near the limit of detection for MALDI.…”

“…Diffuse gliomas are commonly associated with seizures over the course of disease. 1 The detection of peritumoral hyperexcitability by electrophysiologic brain recording techniques serves as the primary biomarker of tumor-related epileptogenesis. Although multiple mechanisms of tumor-related epileptogenesis exist, a role for increased glutamatergic signaling in the glioma microenvironment appears to be a critical early event in promoting hyperexcitability, 2 mediated in part by glioma cell-autonomous release of glutamate and impaired re-uptake from the extracellular space.…”

Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy

“…On the other hand, no clinical studies have evaluated the effects of LAC on survival during adjuvant GBM therapies. As of the present day, LEV is still the most widely used ASM in BTRE, and LAC is one of the third-generation drugs recommended for monotherapy as first-line treatment in BTRE ( Avila et al, 2023 ). Therefore, the main objective of this study, the first to compare these two ASMs, is to analyze the survival outcomes of patients with surgically treated GBM IDH-WT taking LEV and/or LAC during adjuvant chemoradiation therapy with TMZ.…”