Factors associated with preoperative and postoperative seizures in patients undergoing resection of brain metastases

Abstract

OBJECTIVE Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors. METHODS Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non–small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures. RESULTS Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively. CONCLUSIONS Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion–targeting therapeutic interventions on seizure control in these patients.

Wide Dissection Trans-Sulcal Approach for Resection of Deep Intra-Axial Lesions in Eloquent Brain Areas

“…Out of the 6 subjects that experienced post-operative seizures, 5 (83.3% of patients who experienced seizures) were Grade 4 Glioblastoma patients. Seizure rates vary from 1.1% to 48%, if not even higher, for brain tumor resection overall [ 70 , 71 , 72 ]. As a result, the reported number of postoperative seizures in this study may reflect subjects in a high-risk demographic for seizure occurrence.…”

Effect of perioperative seizures on mortality and recurrence in patients with brain metastases

“…Subgroup analyses were also conducted for 30-day preoperative seizures and 30-day postoperative seizures. Known confounders based on existing literature were adjusted for in three separate models ( 2 , 4 , 5 ). In the first model, we adjusted for baseline demographics, including age, gender, and ethnicity.…”

“…Brain metastases are the most common tumors of the central nervous system, with an incidence three to four-fold higher than primary brain tumors ( 1 – 3 ). Among patients with brain metastases, the reported incidence of preoperative seizures ranged from 16.8 to 21.4% ( 2 , 4 , 5 ), while the reported incidence of postoperative seizures ranged from 7.8 to 15.4% ( 4 , 6 ). The incidence of seizures varies across different primary tumor pathologies ( 7 ).…”

“…Risk factors for preoperative seizures among patients with brain metastases include preoperative headache, cognitive deficits, multiple intracranial tumors, bone infiltration by tumor, and presence of metastases in the temporal, occipital, and/or frontal lobe ( 2 , 5 ), while risk factors for postoperative seizures include presence of preoperative seizures, younger age, absence of cerebellar metastases, smaller tumor size, absence of preoperative headache, presence of parietal metastases, and checkpoint inhibitor use ( 2 , 4 , 5 ).…”

“…Data on the effect of perioperative seizures on mortality and tumor recurrence among patients with brain metastases is limited. There was only one study which examined the effect of preoperative seizures on mortality, and the study found no statistically significant association between preoperative seizures and mortality ( 5 ). To our knowledge, there are no studies which examined the association between perioperative seizures and tumor recurrence.…”