The clinical and genomic features of seizures in meningiomas

Abstract

Meningiomas are the most common central nervous system tumors. Although these tumors are extra-axial, a relatively high proportion (10%-50%) of meningioma patients have seizures that can substantially impact the quality of life. Meningiomas are believed to cause seizures by inducing cortical hyperexcitability that results from mass effect and cortical irritation, brain invasion, or peritumoral brain edema. In general, meningiomas that are associated with seizures have aggressive features, with risk factors including atypical histology, brain invasion, and higher tumor grade. Somatic NF2 mutated meningiomas are associated with preoperative seizures, but the effect of the driver mutation is mediated through atypical features. While surgical resection is effective in controlling seizures in most patients with meningioma-related epilepsy, a history of seizures and uncontrolled seizures prior to surgery is the most significant predisposing factor for persistent postoperative seizures. Subtotal resection (STR) and relatively larger residual tumor volume are positive predictors of postoperative seizures. Other factors, including higher WHO grade, peritumoral brain edema, and brain invasion, are inconsistently associated with postoperative seizures, suggesting they might be crucial in the development of an epileptogenic focus, but do not appear to play a substantial role after seizure activity has been established. Herein, we review and summarize the current literature surrounding meningioma-related epilepsy and underscore the interaction of multiple factors that relate to seizures in patients with meningioma.

Keywords: NF2; meningioma; seizures.

Figure 1.

Proposed relationships between driver mutations, demographics, tumor characteristics, mechanisms of epileptogenesis, and seizure occurrence. NF2 and KL4 are driver mutations related to demographics and tumor factors that increase preoperative seizure occurrence. KL4 is a driver mutation for secretory histologic subtypes that produce peritumoral brain edema and increase risk of preoperative seizures. NF2 is related to male sex, tumor location in convexity, increasing tumor volume, atypical histology, and higher WHO grade. These factors increase risk of preoperative seizures through brain invasion, peritumoral brain edema, and cortical irritation. The primary risk factor for postoperative seizures is poorly controlled preoperative seizures.

Figure 2.

Mediation analysis investigating the causal pathways between genomic subgroups and preoperative seizures. A significant indirect effect instead of a direct effect of the NF2 subgroup on preoperative seizures through the sequential mediators of atypical histology and peritumoral brain edema was revealed. An indirect effect of the NF2 subgroup on preoperative seizures through the sequential mediators of atypical histology and brain invasion was suggested, but not significant. Figure reproduced from Gupte et al. (2020) with permission from Journal of Neurosurgery.

Figure 3.

Magnetic Resonance Imaging of WHO grade 2 meningioma NF2 mutation in a patient who presented with seizure. T1-weighted image with contrast demonstrating an extra-axial lesion causing compression and mass effect of underlying cortex (a). Fluid Attenuated Inversion Recovery (FLAIR) MRI demonstrating peritumoral brain edema (b). Postresection T1-weighted MRI with contrast, without evidence of residual tumor (c).