Brain invasion and the risk of seizures in patients with meningioma

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Identification of risk factors for perioperative epilepsy remains crucial in the care of patients with meningioma. Moreover, associations of brain invasion with clinical and radiological variables have been largely unexplored. The authors hypothesized that invasion of the cortex and subsequent increased edema facilitate seizures, and they compared radiological data and perioperative seizures in patients with brain-invasive or noninvasive meningioma.


Correlations of brain invasion with tumor and edema volumes and preoperative and postoperative seizures were analyzed in univariate and multivariate analyses.


Totals of 108 (61%) females and 68 (39%) males with a median age of 60 years and harboring totals of 92 (52%) grade I, 79 (45%) grade II, and 5 (3%) grade III tumors were included. Brain invasion was found in 38 (22%) patients and was absent in 138 (78%) patients. The tumors were located at the convexity in 72 (41%) patients, at the falx cerebri in 26 (15%), at the skull base in 69 (39%), in the posterior fossa in 7 (4%), and in the ventricle in 2 (1%); the median tumor and edema volumes were 13.73 cm3 (range 0.81–162.22 cm3) and 1.38 cm3 (range 0.00–355.80 cm3), respectively. As expected, edema volume increased with rising tumor volume (p < 0.001). Brain invasion was independent of tumor volume (p = 0.176) but strongly correlated with edema volume (p < 0.001). The mean edema volume in noninvasive tumors was 33.0 cm3, but in invasive tumors, it was 130.7 cm3 (p = 0.008). The frequency of preoperative seizures was independent of the patients’ age, sex, and tumor location; however, the frequency was 32% (n = 12) in patients with invasive meningioma and 15% (n = 21) in those with noninvasive meningioma (p = 0.033). In contrast, the probability of detecting brain invasion microscopically was increased more than 2-fold in patients with a history of preoperative seizures (OR 2.57, 95% CI 1.13–5.88; p = 0.025). In univariate analyses, the rate of preoperative seizures correlated slightly with tumor volume (p = 0.049) but strongly with edema volume (p = 0.014), whereas seizure semiology was found to be independent of brain invasion (p = 0.211). In multivariate analyses adjusted for age, sex, tumor location, tumor and edema volumes, and WHO grade, rising tumor volume (OR 1.02, 95% CI 1.00–1.03; p = 0.042) and especially brain invasion (OR 5.26, 95% CI 1.52–18.15; p = 0.009) were identified as independent predictors of preoperative seizures. Nine (5%) patients developed new seizures within a median follow-up time of 15 months after surgery. Development of postoperative epilepsy was independent of all clinical variables, including Simpson grade (p = 0.133), tumor location (p = 0.936), brain invasion (p = 0.408), and preoperative edema volume (p = 0.081), but was correlated with increasing preoperative tumor volume (p = 0.004). Postoperative seizure-free rates were similar among patients with invasive and those with noninvasive meningioma (p = 0.372).


Brain invasion was identified as a new and strong predictor for preoperative, but not postoperative, seizures. Although also associated with increased peritumoral edema, seizures in patients with invasive meningioma might be facilitated substantially by cortical invasion itself. Consideration of seizures in consultations between the neurosurgeon and neuropathologist can improve the microscopic detection of brain invasion.

ABBREVIATIONS AED = antiepileptic drug; EI = edema index; PTBE = peritumoral brain edema.

Article Information

Correspondence Benjamin Brokinkel: University Hospital Münster, Münster, Germany.

INCLUDE WHEN CITING Published online April 27, 2018; DOI: 10.3171/2017.11.JNS172265.

K.H. and D.C.S. contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    Cranial MR and histopathological images of brain-invasive and noninvasive meningiomas. Coronal T1-weighted contrast-enhanced (A) and axial T2-weighted (B) MR images show a large convexity meningioma with distinct PTBE in a 79-year-old male patient. Histopathological analyses (C) (elastica van Gieson, original magnification ×100) revealed fingerlike invasion of the tumor (*) into the adjacent brain tissue (**) with disruption of the leptomeninges (arrows, WHO grade II). Also shown are axial T1-weighted gadolinium-enhanced (D) and T2-weighted (E) MR images of a 73-year-old female. In histopathological analyses (F) (elastica van Gieson, original magnification ×100), the tumor (*) had a distinct border (arrow) to the adjacent brain tissue (**). Figure is available in color online only.

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    Box-and-whisker plots illustrating correlations of tumor and edema volumes with brain invasion (A and B) and preoperative seizures (C and D). In univariate analyses, tumor volume was independent of brain invasion (A, p = 0.176) and only slightly correlated with an increased incidence of preoperative seizures (B, p = 0.049). However, edema volume was strongly correlated with both brain invasion (p < 0.001) and preoperative seizures (p = 0.014). In multivariate analyses, the risk of preoperative seizures was independent of the edema volume (OR 1.00, 95% CI 0.99–1.01; p = 0.803) and only slightly increased with rising tumor volume (OR 1.02, 95% CI 1.00–1.03; p = 0.042). In contrast, brain invasion was revealed as a strong predictor for preoperative epilepsy (OR 5.26, 95% CI 1.52–18.15; p = 0.009). Boxes indicate upper and lower 25th quartiles, whiskers indicate the minimum and maximum values, dots indicate the outliers, asterisks indicate the extreme values, and the heavy horizontal line indicates the median. ccm = cubic centimeter.

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    Scatter plots showing the association of tumor and edema volumes (with best-fit straight line). As expected, edema volume generally increased with rising tumor volume (p < 0.001, R2 = 1.01) (A). Similarly, the correlation of edema and tumor volumes was confirmed when invasive (p = 0.015, R2 = 0.43) (B) and noninvasive (p = 0.003, R2 = 0.08) (C) meningiomas were analyzed separately.

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    Bar graphs showing the frequency of seizures in correlation with brain invasion. Brain invasion was detected in 36% of patients with preoperative seizures compared with 18% of those without preoperative seizures (p = 0.033). However, brain invasion was independent of the development of new postoperative seizures (p = 0.408) or persistence of preoperative seizures (p = 0.372). n.s. = not significant.



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