AWAKE CRANIOTOMY VERSUS SURGERY UNDER GENERAL ANESTHESIA FOR RESECTION OF ELOQUENT CORTEX GLIOMAS: A SYSTEMATIC REVIEW OF COMPARATIVE OBSERVATIONAL STUDIES

Abstract

Background: Gliomas involving eloquent cerebral cortex and subcortical white matter tracts require a surgical approach that balances maximal cytoreduction against neurological function preservation. Awake craniotomy (AC) with intraoperative direct electrical stimulation (DES) mapping is frequently advocated for this indication. However, the comparative evidence base against surgery under general anesthesia (GA) is dominated by heterogeneous observational studies, and the conclusions of prior meta-analyses vary substantially depending on how the GA comparator is defined. Objective: To systematically review comparative observational evidence on extent of resection (EOR), neurological outcomes, functional status, and survival between AC and GA for newly diagnosed eloquent cortex gliomas, with explicit stratification of findings by the IOM modality used in the GA comparator arm. Methods: A systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and CENTRAL was conducted from January 2007 through March 2025, following PRISMA 2020 guidelines. Comparative studies enrolling adults with newly diagnosed WHO grade II–IV eloquent cortex gliomas and comparing AC to GA with any IOM modality were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Given substantial clinical and methodological heterogeneity — particularly in GA IOM modality — a narrative synthesis stratified by GA monitoring approach was performed rather than a single pooled meta-analysis. Where prior published meta-analyses are cited, their methodological characteristics and eligibility criteria are explicitly described. Key Results: Thirty-one comparative observational studies and five published systematic reviews or meta-analyses were identified. Findings are critically heterogeneous and depend fundamentally on the GA IOM modality. When GA includes only standard MEP monitoring without subcortical stimulation mapping, comparative studies consistently report higher EOR with AC (mean difference approximately +8 to +14 percentage points) and lower rates of permanent neurological deficit. When GA is supplemented by direct subcortical stimulation mapping, the EOR advantage of AC is substantially attenuated and in several high-quality propensity score-matched studies is not statistically significant. The only published meta-analysis restricted to motor-eloquent gliomas where both AC and GA groups underwent intraoperative stimulation mapping found no statistically significant difference in EOR or neurological deficit rates between approaches (Abo-Elnour et al., Neurosurgical Review, 2024). Conclusions: The comparative effectiveness of AC versus GA for eloquent cortex glioma resection is not a binary question. The available evidence indicates that AC is associated with equivalent or better outcomes compared with GA-only monitoring, but that well-conducted GA surgery with multimodal monitoring — including direct subcortical stimulation — may achieve outcomes comparable to AC in high-volume settings. A well-designed prospective registry study or randomized trial stratifying by GA IOM modality is the highest-priority evidence need in this field.