To characterize glioma-associated seizures among primary & secondary glioblastoma and grade 4 astrocytoma.

Many patients with gliomas experience glioma-associated seizures, which are often resistant to anti-seizure medications (ASMs). Low-grade gliomas and IDH1 mutant gliomas are associated with increased seizures versus high-grade gliomas. However, differences in seizure characteristics remain unclear between grade 4 glioma subtypes: 1) IDH1 mutant grade 4 astrocytoma, 2) IDH1 wild-type primary glioblastoma, 3) IDH1 wild-type secondary glioblastoma (progression from low-grade glioma).

We conducted a retrospective cohort study including 598 patients diagnosed with grade 4 glioma (2005-2022) at the Cleveland Clinic. Seizure activity was obtained from review of patient records. Univariable and multivariable analyses examined age, glioma subtype, tumor location, number of ASMs, and ASM use.

Of 598 patients, 37 (6.2%) patients had grade 4 astrocytoma, 535 (89.5%) had primary glioblastoma, and 26 (4.3%) had secondary glioblastoma. Patients with grade 4 astrocytoma were significantly younger than patients with primary or secondary glioblastoma (mean 44 vs. 63 vs. 53 years, respectively; p < 0.001). Patients with grade 4 astrocytoma had significantly greater odds of seizures before glioma diagnosis (OR = 6.7, 95% CI [2.1-25.1], p = 0.002) versus those with primary but not secondary glioblastoma. Additionally, patients with grade 4 astrocytoma had significantly lower odds of any seizures within 6 months after glioma diagnosis (OR = 0.2, 95% CI [0.06-0.76], p = 0.02) versus those with primary but not secondary glioblastoma. Patients with secondary glioblastoma used significantly more ASMs 6 months after glioma diagnosis versus those with primary glioblastoma (p = 0.03).

Overall, patients with grade 4 astrocytoma may experience more seizures before glioma diagnosis but have better seizure control as compared to patients with primary but not secondary glioblastoma. This suggests that patients with secondary glioblastoma may have distinct seizure characteristics from both primary glioblastoma and grade 4 astrocytoma.