Evidence-based safe stimulation thresholds in subcortical mapping during glioma surgery: a systematic review and...

Intraoperative subcortical electrical stimulation is essential for safe glioma resection near motor pathways, yet minimum safe current thresholds remain controversial, with published recommendations ranging from 1 to 7 mA. This systematic review synthesizes evidence on safe stimulation thresholds in monopolar subcortical mapping during glioma surgery to provide evidence-based recommendations.

Following PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, Web of Science, and Cochrane Library through November 2025 for studies reporting specific threshold values and motor outcomes in glioma surgery with monopolar subcortical monitoring. Study quality was assessed using the Newcastle-Ottawa Scale. Evidence was synthesized narratively and graded using GRADE methodology. Statistical pooling of proportions used random-effects models with Freeman-Tukey double arcsine transformation.

Sixteen studies comprising 1,146 patients were included. Safe threshold recommendations ranged from 1 to 7 mA, with 3 mA applied across the largest patient cohort (seven studies, 728 patients, 63.5%). A clear dose-response relationship emerged: pooled permanent motor deficits increased from 2.1% (95% CI 1.3-3.2%) at thresholds ≥5 mA to 17.8% (95% CI 12.4-24.5%) at thresholds <2 mA. Motor evoked potential (MEP) monitoring significantly reduced permanent deficits from 8.7% to 4.0% (pooled OR 0.43, 95% CI 0.26-0.72, p < 0.001). The threshold-distance relationship approximated 1 mA per 1 mm from the corticospinal tract (r = 0.87, p < 0.001). Low-grade gliomas tolerated lower thresholds better than high-grade gliomas (0-2% vs 7-14% permanent deficits at 2-3 mA, p < 0.01). Importantly, 78% of permanent deficits resulted from ischemic injury rather than direct tract damage, predominantly confirmed on postoperative diffusion-weighted MRI.

Based on moderate-quality evidence (GRADE: ⊕⊕⊕◯), 3 mA represents a clinically important decision threshold for the general glioma population, supported by the largest evidence base. However, 4-5 mA is an equally valid and preferred stopping threshold for high-grade gliomas and patients with preoperative deficits (2.1% permanent deficit rate). Continuation below 3 mA should be reserved for carefully selected low-grade glioma patients with intact preoperative function, stable continuous MEP monitoring, and tractography guidance. Thresholds below 2 mA carry markedly elevated risk (17.8%) based on limited single-study evidence and should generally prompt cessation. Stimulation thresholds are protocol-dependent and should not be compared across institutions using different pulse widths or frequencies. Vascular preservation is paramount given that most permanent deficits arise from ischemia.