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.

Perifocal edema is a risk factor for preoperative seizures in patients with meningioma WHO grade 2 and 3

“…Pathogenetic mechanisms driving tumor-related epilepsy remain complex and include aberrant neuronal migration, changes in synaptic vesicles and glial gap-junction coupling alterations [ 6 , 9 , 20 , 23 ]. On a cellular level, morphologic changes lead to a higher concentration of excitatory voltage-dependent Na + , Ca ++ and glutamate receptors, diminishing inhibitory synapses and propagating excitatory influences leading to cortical hyperexcitability [ 5 , 6 ]. Moreover, brain invasion has been shown to be associated with preoperative seizures, leading to a disruption of the pial-glial basement membrane, potentially inducing astrocytic responses and altering the tumor microenvironment similar to primarily intra-axial malignancies [ 5 ].…”

“…On a cellular level, morphologic changes lead to a higher concentration of excitatory voltage-dependent Na + , Ca ++ and glutamate receptors, diminishing inhibitory synapses and propagating excitatory influences leading to cortical hyperexcitability [ 5 , 6 ]. Moreover, brain invasion has been shown to be associated with preoperative seizures, leading to a disruption of the pial-glial basement membrane, potentially inducing astrocytic responses and altering the tumor microenvironment similar to primarily intra-axial malignancies [ 5 ]. In our study cohort, brain invasion was not directly associated with preoperative seizures.…”

“…Apart from the peritumoral edema apparent on preoperative imaging, patients without edema were also observed to develop preoperative seizures in selected cases of our patient cohort. Here, slow-growing meningiomas might not induce perifocal edema, yet lead to cortical deafferentation by either mechanically or vascularly isolating brain regions, driving epileptogenesis [ 5 , 9 , 25 ].…”

Factors Predicting Seizure Outcome After Surgical Excision Of Meningioma : A Systematic Review

“…Patients with meningioma who experience seizures have a significantly worse progression-free survival rate compared with those who do not experience seizures, suggesting that meningiomaassociated epilepsy signals the presence of a more aggressive tumor. 1,2 Seizures in meningiomas occur in approximately 30% of patients.…”

“…However, the incidence of post-operative seizures still ranges between 26%-60% in the literature, which includes patients who are not seizure-free, as well as those who are seizure naïve and then experience post-operative seizures. 1,2 In this article, we would like to discuss about the predictors of seizure/epilepsy in postoperative patients. located in the motor cortex of the frontal lobe.…”