Awake Craniotomy Versus General Anesthesia for Resection of High-Grade Gliomas: A Systematic Review and Meta-Analysis

<b>Background</b>: The optimal anesthetic approach for high-grade glioma resection remains controversial. We conducted a systematic review and meta-analysis comparing awake craniotomy with intraoperative brain mapping versus general anesthesia for adults with high-grade gliomas. <b>Methods</b>: We searched PubMed/MEDLINE, Web of Science, Cochrane Library, and Embase databases from January 2000 to August 2025 for comparative studies of awake craniotomy versus general anesthesia in adults with WHO grade III-IV gliomas. Primary outcomes were overall survival and neurological deficits. Meta-analyses used random-effects models with hazard ratios (HR) for survival and risk ratios (RR) for binary outcomes. <b>Results</b>: Eleven studies comprising 2689 patients (854 awake craniotomy, 1835 general anesthesia) were included. One randomized controlled trial and ten observational studies met inclusion criteria. Awake craniotomy was associated with improved overall survival (HR 0.70, 95% CI 0.60-0.82; 4 studies, 1273 patients), representing a 30% reduction in mortality risk and a median survival advantage of approximately 4.1 months (18.5 vs. 14.4 months; low certainty evidence due to predominantly observational data and heterogeneity). Neurological deficits at 3 months were significantly reduced with awake craniotomy (RR 0.62, 95% CI 0.42-0.91; 2 studies, 1111 patients; moderate certainty evidence), with absolute deficit rates of 13% versus 21% (number needed to treat = 13). Awake craniotomy also achieved greater extent of resection (mean difference 4.4%, 95% CI 2.8-6.0%; 5 studies, 1121) and notably shorter hospital stay (mean difference -2.85 days, representing a 41% reduction [4.1 vs. 6.95 days]; 2 studies, 949 patients). Substantial heterogeneity was observed for most outcomes (I² > 50%). Subgroup analysis demonstrated greater benefits for tumors in eloquent areas. Limitations include predominantly observational studies with potential selection bias (including possible differences in baseline performance status), molecular marker heterogeneity due to evolving WHO classification systems, and one small randomized controlled trial showing opposite results. <b>Conclusions</b>: Awake craniotomy may offer survival and functional benefits for selected patients with high-grade gliomas, particularly those with tumors in eloquent areas. However, evidence certainty is limited by the observational nature of most studies and significant heterogeneity. Well-designed randomized trials with molecular stratification and performance status adjustment are needed to establish definitive evidence.