Clinical and genomic factors associated with seizures in meningiomas

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  • 1 Departments of Neurosurgery,
  • 5 Surgery,
  • 8 Pathology,
  • 11 Radiology and Biomedical Imaging, and
  • 9 Clinical Neurology,
  • 10 Therapeutic Radiology and Pharmacology,
  • 12 Genetics, Yale School of Medicine, New Haven;
  • 2 Yale Brain Tumor Center, Smilow Cancer Hospital, New Haven, Connecticut;
  • 3 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha;
  • 4 The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China;
  • 6 Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut; and
  • 7 Department of Neurological Surgery, Northwestern University, Chicago, Illinois
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OBJECTIVE

The association of seizures with meningiomas is poorly understood. Moreover, any relationship between seizures and the underlying meningioma genomic subgroup has not been studied. Herein, the authors report on their experience with identifying clinical and genomic factors associated with preoperative and postoperative seizure presentation in meningioma patients.

METHODS

Clinical and genomic sequencing data on 394 patients surgically treated for meningioma at Yale New Haven Hospital were reviewed. Correlations between clinical, histological, or genomic variables and the occurrence of preoperative and postoperative seizures were analyzed. Logistic regression models were developed for assessing multiple risk factors for pre- and postoperative seizures. Mediation analyses were also conducted to investigate the causal pathways between genomic subgroups and seizures.

RESULTS

Seventeen percent of the cohort had presented with preoperative seizures. In a univariate analysis, patients with preoperative seizures were more likely to have tumors with a somatic NF2 mutation (p = 0.020), WHO grade II or III tumor (p = 0.029), atypical histology (p = 0.004), edema (p < 0.001), brain invasion (p = 0.009), and worse progression-free survival (HR 2.68, 95% CI 1.30–5.50). In a multivariate analysis, edema (OR 3.11, 95% CI 1.46–6.65, p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03–3.90, p = 0.041) were positive predictors of preoperative seizures, while genomic subgroup was not, such that the effect of an NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort, and only 20.8% of the seizure-free patients, who were more likely to have undergone gross-total resection (p = 0.031), were able to discontinue antiepileptic drug use postoperatively. Preoperative seizures (OR 3.54, 95% CI 1.37–9.12, p = 0.009), recurrent tumors (OR 2.89, 95% CI 1.08–7.74, p = 0.035), and tumors requiring postoperative radiation (OR 2.82, 95% CI 1.09–7.33, p = 0.033) were significant predictors of postoperative seizures in a multivariate analysis.

CONCLUSIONS

Seizures are relatively common at meningioma presentation. While NF2-mutated tumors are significantly associated with preoperative seizures, the association appears to be mediated through edema and atypical histology. Patients who undergo radiation and/or have a recurrence are at risk for postoperative seizures, regardless of the extent of resection. Preoperative seizures may indeed portend a more potentially aggressive molecular entity and challenging clinical course with a higher risk of recurrence.

ABBREVIATIONS AED = antiepileptic drug; CNV = copy number variation; EOR = extent of resection; GTR = gross-total resection; LOH = loss of heterozygosity; PFS = progression-free survival; PTBE = peritumoral brain edema; STR = subtotal resection; WES = whole exome sequencing.

Supplementary Materials

    • Supplemental Tables and Fig (PDF 727 KB)

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Contributor Notes

Correspondence Jennifer Moliterno: Yale School of Medicine, New Haven, CT. jennifer.moliternogunel@yale.edu.

INCLUDE WHEN CITING Published online December 4, 2020; DOI: 10.3171/2020.7.JNS201042.

T.P.G. and C.L. 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.

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