Characterizing Epilepsy-Induced Changes in the Glioma Microenvironment

Approximately 30-40% of patients who are diagnosed with glioblastoma (GBM) initially present with an epileptic seizure.1 Epilepsy at presentation is an independent favorable prognostic factor for survival in GBM,2,3 with one series reporting a doubling of survival time (26.8 months vs. 13.1 months, p<0.001).4 This prognostic effect cannot be explained by treatment with anti-epileptic drugs,5,6 a smaller tumor volume at presentation due to earlier detection,5,7 or IDH1 mutations.5,8 Recently, tissue from epileptogenic GBMs was shown to associate with decreased hypoxia/HIF1a, decreased STAT5b, and decreased epithelial to mesenchymal transformation signaling.9 This epilepsy-related downregulation of major oncogenic signaling pathways potentially leads to decreased proliferative and invasive tumor behavior and promotes enhanced chemo- and radiosensitivity, which could account for the improved survival seen in this cohort.