Trisha P Gupte1,2, Chang Li1,2,3,4, Lan Jin1,2,5,6, Kanat Yalcin1,2, Mark W Youngblood7, Danielle F Miyagishima1,2, Ketu Mishra-Gorur1,2, Amy Y Zhao1,2, Joseph Antonios1,2, Anita Huttner2,8, Declan McGuone2,8, Nicholas A Blondin2,9, Joseph N Contessa2,10, Yawei Zhang5,6, Robert K Fulbright2,11, Murat Gunel1,2,12, Zeynep Erson-Omay1,2, Jennifer Moliterno1,2. 1. Departments of1Neurosurgery. 2. 2Yale Brain Tumor Center, Smilow Cancer Hospital, New Haven, Connecticut. 3. 3Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha. 4. 4The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. 5. 5Surgery. 6. 6Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut; and. 7. 7Department of Neurological Surgery, Northwestern University, Chicago, Illinois. 8. 8Pathology. 9. 9Clinical Neurology. 10. 10Therapeutic Radiology and Pharmacology. 11. 11Radiology and Biomedical Imaging, and. 12. 12Genetics, Yale School of Medicine, New Haven.
Abstract
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.
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 meningiomapatients. 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.
Authors: Peter Baumgarten; Mana Sarlak; Daniel Monden; Andrea Spyrantis; Simon Bernatz; Florian Gessler; Daniel Dubinski; Elke Hattingen; Gerhard Marquardt; Adam Strzelczyk; Felix Rosenow; Patrick N Harter; Volker Seifert; Thomas M Freiman Journal: Cancers (Basel) Date: 2021-01-25 Impact factor: 6.639
Authors: Stephanie M Robert; Shaurey Vetsa; Arushii Nadar; Sagar Vasandani; Mark W Youngblood; Evan Gorelick; Lan Jin; Neelan Marianayagam; E Zeynep Erson-Omay; Murat Günel; Jennifer Moliterno Journal: J Neurooncol Date: 2021-11-30 Impact factor: 4.130
Authors: John Lynes; Gabriel Flores-Milan; Sebastian Rubino; John Arrington; Robert Macaulay; James K C Liu; Andre Beer-Furlan; Nam D Tran; Michael A Vogelbaum; Arnold B Etame Journal: Front Oncol Date: 2022-08-12 Impact factor: 5.738