Predictors of early, recurrent, and intractable seizures in low-grade glioma

Abstract

Background: Seizures are common among patients with low-grade glioma (LGG) and can significantly affect morbidity. We sought to determine the association between the clinical and molecular factors with seizure incidence and refractoriness in LGG patients.

Methods: We conducted a retrospective review at the University of Virginia in patients with LGG (World Health Organization, WHO Grade II) evaluated between 2002 and 2015. Descriptive statistics were calculated for variables of interest, and the Kaplan-Meier method was used to estimate survival curves, which were compared with the log-rank test.

Results: A total of 291 patients were included; 254 had molecular testing performed for presence of an isocitrate dehydrogenase (IDH) mutation and/or 1p/19q codeletion. Sixty-eight percent of patients developed seizures prior to LGG diagnosis; 41% of all patients had intractable seizures. Using WHO 2016 integrated classification, there was no significant difference in seizure frequency during preoperative and postoperative periods or in developing intractable seizures, though a trend toward increased preoperative seizure incidence among patients with the IDH mutation was identified (P = .09). Male sex was significantly associated with higher seizure incidence during preoperative (P < .001) and postoperative periods (P < .001); men were also more likely to develop intractable seizures (P = .01).

Conclusions: Seizures are common among patients with LGG. Differences in preoperative or postoperative and intractable seizure rates by WHO 2016 classification were not detected. Our data showed a trend toward higher seizure incidence preoperatively in patients with IDH-mutant LGG. We describe a unique association between male sex and seizure incidence and intractability that warrants further study.

Keywords: IDH mutation; WHO 2016 classification; low-grade glioma; seizure.

Figure 1.

A, Survival vs seizure presentation. There was no significant difference in survival between patients who presented with a preoperative (pre-op) seizure and those who did not. B, Survival vs World Health Organization (WHO) 2016 integrated glioma classification. Significant differences were detected based on the WHO 2016 classification (1 = diffuse astrocytoma, isocitrate dehydrogenase [IDH] wild-type, grade II, 2 = diffuse astrocytoma, IDH-mutated, 1p/19q intact, grade II, 3 = oligodendroglioma, IDH-mutated, 1p/19q codeleted, grade II, 4 = not tested).