Somatic AKT1 Mutations May Confer Increased Risk of Preoperative Seizures in Meningiomas

BACKGROUND AND OBJECTIVES: Seizure is an observed symptom for patients with newly diagnosed meningiomas. Recent progress has been made in the genomic characterization of meningiomas. However, it is currently unknown whether driver mutations associated with meningioma development also portend increased risk of perioperative seizure. We conducted a single center retrospective clinical and genomic review of patients who underwent primary meningioma resection to understand which mutations were associated with increased risk of perioperative seizure. METHODS: Tumor samples and clinical data were collected from an institutional tissue bank of patients who had a surgical resection of a primary meningioma between 1995 and 2018. Tumor samples were sequenced using next-generation targeted sequencing. Univariable models were used to select for relevant mutations for inclusion in the multivariate analysis. Multivariable models were built using selected variables and known clinical and demographic correlates of seizures. RESULTS: Of 196 sequenced patients in the cohort, 146 patients had primary cranial meningiomas. 36 patients (24.7%) experienced preoperative seizures, and 35 patients (24.0%) experienced postoperative seizures. With multivariable analysis, AKT1 mutation and high serum creatinine were associated with increased odds of preoperative seizures. Increased age at surgery and low preoperative serum bicarbonate were associated with decreased odds of preoperative seizure. Prior preoperative seizure was significantly associated with increased risk of developing postoperative seizure, and meningioma resection surgery was associated with decreased odds of developing postoperative seizure. CONCLUSION: Our study suggests that AKT1 mutation, high serum creatinine, and decreased age at surgery may be predictors of preoperative seizures in primary meningioma patients. In addition, prior preoperative seizures portended increased risk of postoperative seizure in this patient cohort and meningioma resection surgery was protective against the development of postoperative seizure. These analyses may improve treatment paradigms by helping to identify the patients who may benefit from earlier preoperative antiseizure medication usage.