Molecular characterization of high-grade glioma-associated seizures

Seizures occur in nearly half of all patients with high-grade gliomas, but few molecular markers have been identified as prognostic for glioma-associated seizures. We sought to examine the relationship between tumor molecular markers and glioma-associated seizures in patients with WHO grade 4 gliomas (glioblastoma, IDH- mutant astrocytoma). Amongst 950 patients diagnosed with grade 4 gliomas between 1999 and 2023, 414 (44%) patients experienced seizures. Tumor genomic characteristics were correlated with seizure incidence (before or after glioma diagnosis) and frequency in multivariable analyses. In multivariable analyses, chromosome 1p deletion (OR = 2.7, 95% CI [1.6, 4.4], p  < 0.001), pathogenic IDH1 variants (OR = 3.1, 95% CI [1.4, 7.1], p  = 0.033), and EGFR amplification (OR = 1.6, 95% CI [1.1, 2.2], p  = 0.039) were all significantly associated with increased odds of seizures before glioma diagnosis. For an exploratory subset of 83 patients, we conducted whole exome sequencing of the tumor, but no specific variants were associated with seizure occurrence. In conclusion, chromosome 1p deletion, pathogenic IDH1 status, and EGFR amplification were significantly associated with seizures before glioma diagnosis. Future work to identify additional molecular markers for patients at greatest risk for tumor-associated epilepsy may improve morbidity in high-grade glioma.