Introduction

Surgical resection of ‘peri-Rolandic’ diffuse gliomas – those involving primary motor and sensory cortex – poses a significant clinical challenge due to the critical role of this cortex. Although extent of resection (EOR) is strongly associated with improved overall survival (OS) in diffuse glioma patients, aggressive resection near eloquent cortex carries a substantial risk of postoperative neurological deficits that can profoundly impact quality of life [1]. Thus, the neurosurgical objective in these cases is to balance oncologic outcome with functional preservation, often through the use of intraoperative mapping techniques.

While preoperative imaging modalities such as functional MRI (fMRI) and diffusion tensor imaging (DTI) offer valuable insights into cortical and subcortical anatomy, they cannot substitute intraoperative motor mapping, the gold standard for functional preservation during glioma resection, given its high sensitivity and specificity in localizing function [2]. Intraoperative mapping via direct cortical stimulation to identify motor regions can be performed through two approaches: awake and asleep motor mapping [3]. In awake craniotomies, patients remain conscious and provide real-time feedback during cortical stimulation, enabling direct functional assessment. This approach is particularly valuable when tumors involve or are adjacent to speech areas or premotor areas, where patient participation can help delineate eloquent cortex with greater precision [4]. In contrast, asleep motor mapping is conducted under general anesthesia using neurophysiological monitoring, most commonly via motor evoked potentials (MEPs) elicited by direct cortical or subcortical stimulation (Fig. 1) [5]. Both techniques are thought of as reasonable standards for guiding safe and maximal resection, and the choice between them typically depends on tumor location, patient suitability, seizure risk, and surgeon preference.

Fig. 1
Fig. 1
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Intraoperative Motor Mapping Protocols and Asleep Stimulation Modalities (A) Functional interpretation of cortical stimulation responses across awake and asleep mapping methodologies. Without stimulation, awake patients demonstrate voluntary movement, while asleep patients show absent Motor Evoked Potentials (MEPs). During active stimulation, arrested movement (awake) or intact MEPs (asleep) identify the motor cortex and guide resection boundaries. (B) The two asleep direct cortical stimulation techniques analyzed in this series: Handheld Probe DCS (HHP-DCS), applied directly to the exposed cortical surface, and Subdural Electrode DCS (SDE-DCS), using a flexible strip electrode positioned over the motor cortex when exposure is limited. Created in BioRender. Trippett, J. (2026) https://BioRender.com/eau56ej

During asleep motor mapping, direct cortical stimulation (DCS) can be accomplished either via a sheet of subdural electrodes delivering direct cortical stimulation (SDE-DCS) or via a bipolar or monopolar handheld probe direct cortical stimulation (HHP-DCS) (Fig. 1) [3, 6]. Strip electrodes are linear arrays used when cortical exposure is limited or when targeted mapping of a specific region is needed [7,8,9]. Although both awake and asleep mapping approaches have been described, most studies have focused on operative methodology rather than outcomes as a function of tumor biology. Older series predate the current molecular classification of diffuse gliomas [10]. The current study aims to compare functional outcomes as a function of mapping strategy and tumor biology in patients undergoing resection of ‘peri-Rolandic’ diffuse gliomas stratified per the 2021 WHO classification. We also evaluated differential advantages between mapping techniques across glioma subtypes.

Methods

Study design and setting

Our retrospective cohort study included all consecutive adult diffuse glioma patients who underwent resection with intraoperative motor mapping at a single institution. All procedures were performed by two attending neurosurgeons. The study was approved by the Institutional Review Board and followed the STROBE guidelines.

Patient identification and data collection

Patients were identified using a comprehensive tumor database to isolate those who underwent surgery between 2008 and 2024 for diffuse glioma requiring intraoperative motor mapping. Inclusion criteria were: (1) histologically confirmed diffuse glioma, (2) peri-Rolandic tumors, and (3) use of intraoperative motor mapping. Clinical data collected included demographics, pathology, surgical details, intraoperative mapping technique, presenting symptoms, neurological deficits, adjuvant therapies, and postoperative follow-up of at least 3 months. Tumor classification was based on the 2021 WHO CNS tumor classification [10]. For analytic purposes, tumors were categorized as IDH-wildtype glioblastoma (GBM) versus IDH-mutant tumors (astrocytoma and oligodendroglioma). We deliberately avoid the loose terms “high-grade” and “low-grade,” as grade 3 IDH-mutant molecular oligodendrogliomas and astrocytomas have markedly different outcomes from glioblastoma.

EOR was radiographically quantified by volumetric analyses using Vitrea Advanced Visualization (Olea Medical–Canon Medical Systems, CA, USA). Contrast-enhancing (CE) tumor burden was segmented on post-contrast T1-weighted images, and non-enhancing tumor burden was outlined on FLAIR (or T2-weighted) sequences. EOR was assessed according to the RANO resect categories for glioblastoma [11,12,13,14] and IDH-mutant grade 2 glioma [15]. For grade 3 and 4 IDH mutant tumors, EOR was classified by the glioblastoma or IDH-mutant category, depending on whether they were T1-CE or not.

Neurological deficits and outcome measures

Permanent postoperative deficits were defined as new or worsening neurological deficits persisting for 3 months postoperatively, a common threshold distinguishing transient from persistent deficits [16]. Functional status was assessed using the Karnofsky Performance Status (KPS) scale both pre- and postoperatively. Additional outcomes included hospital length of stay (LOS), discharge disposition (home, inpatient rehabilitation, skilled nursing facility [SNF]), and 60-day hospital readmission.

Comparison of asleep mapping techniques

Within the asleep cohort, patients were further stratified based on the intraoperative stimulation method: HHP-DCS patients (n = 61) underwent direct handheld probe-based cortical and subcortical mapping, while SDE-DCS patients (n = 12) had flexible electrode arrays placed over the motor cortex surface for stimulation. Three patients missing follow-up data from the SDE-DCS group were excluded from this subanalysis.

Statistical analysis

All statistical analyses were performed using Python (version 3.13.9) in JupyterLab (version 4.4.7). Continuous and ordinal variables (age, KPS, LOS) were summarized as medians with interquartile ranges (IQRs) and compared using the Mann-Whitney U test. Categorical variables were compared using Fisher’s exact test, given the potential for small expected cell counts. Discharge disposition (home, inpatient rehabilitation, SNF) was compared using the chi-squared test. OS and progression-free survival (PFS) were analyzed using Kaplan-Meier estimation with log-rank testing. Univariate Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). No correction for multiple comparisons was applied to analyses of presenting symptoms. Statistical significance was defined as double-sided p < 0.05.

Results

Patient baseline characteristics

Between 2008 and 2024, 130 patients with diffuse gliomas underwent resection with intraoperative motor mapping. Of these, 76 patients (58.5%) underwent asleep and 54 patients (41.5%) underwent awake motor mapping. Baseline characteristics for both groups are summarized in Table 1. Patients in the asleep group were significantly older than those in the awake group (median 53 years, IQR 40–65 vs. 42 years, IQR 34–57; p = 0.016). There were no significant sex differences between groups (asleep: 42.1% female vs. awake: 40.7% female; p = 1.000). Presenting symptoms differed between groups. Emesis (9.2% vs. 0.0%, p = 0.041), motor deficits (57.9% vs. 29.6%, p = 0.002), sensory deficits (32.9% vs. 16.7%, p = 0.044), confusion (32.9% vs. 9.3%, p = 0.002), and gait disturbance (9.2% vs. 0.0%, p = 0.041) were more common in the asleep cohort, suggesting larger masses or greater mass effect. Seizure presentation did not differ significantly between groups (50.0% asleep vs. 63.0% awake; p = 0.156). Preoperative functional status was lower in the asleep cohort, with a lower median KPS (70 vs. 80; p = 0.001), as well as lower postoperative KPS (median 80 vs. 90; p < 0.001). Glioblastomas were significantly more prevalent in the asleep mapping group (68.4% vs. 31.5%; p < 0.001). The use of post-surgical adjuvant chemotherapy and radiation therapy did not differ significantly between groups (p = 0.104 and p = 0.088, respectively). LOS, discharge disposition, and 60-day readmission rates were also similar.

Table 1 Baseline demographics and presenting symptoms (awake vs. asleep)

Postoperative neurological deficits

New or worsened neurological deficits persisting at 3-months occurred in 7 patients (5.4%) overall. It was seen in 4 patients (5.3%) in the asleep group and 3 patients (5.6%) in the awake group (p = 1.000).

Tumor subgroup analysis

Subgroup analysis stratified by tumor type, GBM and IDH-mutant diffuse glioma, was performed (Table 2). The GBM subgroup comprised 52 asleep (75.4%) and 17 awake (24.6%) patients. Pre-operative KPS was significantly higher in the awake group (median 90 [IQR 80–90] vs. 70 [IQR 60–80]; p = 0.0002), as was postoperative KPS (median 90 [IQR 80–90] vs. 80 [IQR 70–90]; p = 0.002). The change in KPS from pre- to postoperative assessment (ΔKPS) did not differ between groups (median 0 [IQR 0–10] vs. 0 [IQR 0–10]; p = 0.780). Three-month deficits occurred in 4 asleep patients (7.7%) and 3 awake patients (17.6%), with no statistical difference (p = 0.352). Hospital LOS, discharge disposition, chemotherapy, and radiation did not differ between subgroups. In the non-GBM subgroup (IDH-mutant astrocytoma and oligodendroglioma), comprised of 24 asleep and 37 awake patients, no permanent deficits occurred at 3 months postoperatively.

Table 2 Clinical outcomes stratified by tumor subgroup — GBM vs. Non-GBM (Awake vs. Asleep)

Volumetric analysis

EOR was evaluated per RANO resect criteria. This was available for 97% of patients (asleep n = 74, awake n = 52). Median EOR as a continuous variable did not differ significantly between groups overall (97.5% vs. 95.4%; p = 0.942), nor within GBM (98.7% vs. 92.8%; p = 0.405) or non-GBM (92.1% vs. 97.9%; p = 0.353) subgroups. After controlling for baseline tumor volume, mapping modality was not an independent predictor of EOR (β = 1.4%, p = 0.680); larger baseline volume was the only significant predictor of lower EOR (p = 0.002). RANO resection class distribution differed significantly between awake and asleep GBM patients (p = 0.001). Class 1 (supramaximal) resection was achieved exclusively in the awake group (25.0% vs. 0%), while class 2 (maximal) resection was more common in the asleep group (62.0% vs. 37.5%), and class 3 (submaximal) rates were similar (38.0% vs. 37.5%). In non-GBM patients, RANO resection class distribution did not differ between groups (p = 0.745). Subgroup volumetric outcomes are presented in Table 2.

Comparison of asleep mapping techniques

Among the 76 patients who underwent asleep motor mapping, 61 underwent HHP-DCS, and 12 underwent SDE-DCS mapping; three patients missing follow-up data from the SDE-DCS group were excluded from this analysis (Table 3). New or worsening deficits at 3 months occurred in 2 patients (3.3%) in the HHP-DCS group and 2 patients (16.7%) in the SDE-DCS group, a difference that did not reach statistical significance (p = 0.124). No significant differences were observed in age, preoperative or postoperative KPS, hospital length of stay, or tumor histology distribution.

Table 3 Asleep subgroup — direct cortical stimulation (DCS) vs. Subdural Strip Electrodes

Survival outcomes in glioblastoma

Survival analysis in GBM patients (n = 69; 52 asleep, 17 awake), is depicted in Fig. 2. Median OS was 19.2 months in the asleep group and 23.5 months in the awake group (log-rank p = 0.674). Median PFS was 9.8 months in the asleep group and 13.4 months in the awake group (log-rank p = 0.223). On univariate Cox proportional hazards regression, mapping modality (awake versus asleep) was not associated with OS (HR = 0.89, 95% CI 0.51–1.58; p = 0.700) or PFS (HR = 0.81, 95% CI 0.50–1.33; p = 0.408).

Fig. 2
Fig. 2
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Kaplan-meier survival analysis in glioblastoma patients by mapping modality. (A) Overall survival for asleep (n = 52) and awake (n = 17) groups; median OS 19.2 vs. 23.5 months (log-rank p = 0.674). (B) Progression-free survival for the same cohorts; median PFS 9.8 vs. 13.4 months (log-rank p = 0.223). Shaded regions represent 95% confidence intervals; numbers at risk and censored patients are shown below each panel

Discussion

In this cohort of 130 patients with peri-Rolandic diffuse gliomas, 3-month deficit rates did not differ between awake and asleep mapping, and this held across GBM and non-GBM subtypes. Within the asleep cohort, HHP-DCS and SDE-DCS showed no significant differences in deficits, KPS change, or survival. These findings address an important question: whether asleep motor mapping can reliably serve as an alternative to awake craniotomy for tumors involving eloquent cortex [16]. In our cohort, patients undergoing asleep mapping were older, had lower baseline KPS, and had a substantially higher proportion of GBM. These differences likely reflect clinical selection patterns in which patients with more aggressive disease or greater neurological impairment are preferentially managed under general anesthesia. Despite these baseline differences, postoperative neurological deficit rates were similar between groups, suggesting that asleep mapping can provide effective functional preservation even in higher-risk patients [17,18,19]. Given the retrospective, non-randomized design and substantial baseline differences between cohorts – including age, preoperative function, and glioblastoma prevalence – the absence of a significant difference does not establish equivalence between these two techniques. Patients selected for asleep mapping could have differed in unmeasured ways, such as cognitive ability, subjectively perceived ability to tolerate an awake procedure, and likelihood of the procedure to result in a deficit that may have influenced the surgeon’s decision-making. Thus, residual confounding and selection bias cannot be excluded. Our findings, therefore, support the feasibility of asleep mapping rather than statistical equivalence.

Beyond motor cortex identification, awake craniotomy offers the ability to map sensory cortex and premotor cortex, which play an important role in motor initiation. In cases where the tumor is in the left hemisphere near the face and speech cortex, where the boundary between motor and language cortex may be uncertain, awake mapping is generally preferred, as it allows patient participation to clarify functional boundaries [4]. This is particularly relevant for dominant-hemisphere peri-Rolandic lesions, where language deficits were common in our cohort (> 20% of patients). For such tumors, awake mapping retains a distinct advantage for preserving language function that motor-focused asleep mapping cannot replicate. As this study centered on motor mapping, our findings should not be interpreted to imply that asleep mapping is an equivalent substitute when protecting language or other higher-order functions is a primary objective. Asleep mapping, in contrast, offers practical advantages in appropriate patients as it is associated with shorter setup times and allows more controlled management of intraoperative seizures. At our center, asleep mapping is more commonly implemented in patients with significant mass effect, with larger tumors, or confusion limiting reliable participation, and may be implicitly considered when advanced age, frailty, or marked anxiety are judged to compromise tolerance of an awake procedure. These factors are best viewed as contributors to individualized selection rather than absolute contraindications. Awake craniotomy can be performed safely in carefully selected elderly patients, including octogenarians and nonagenarians, with high mapping success and acceptable morbidity, and anxiety alone need not preclude an awake approach with adequate counseling and anesthetic support. For lesions involving language or other higher-order networks, awake mapping may aid maximal resection while preserving function, regardless of age (Fig. 3) [3, 20,21,22,23,24]. Some of these preferences have been reflected in larger multi-institutional glioblastoma cohorts [16]. A recognized limitation of asleep mapping, however, is the higher stimulation current required to overcome the suppressive effects of anesthesia, which may narrow the therapeutic window between motor identification and seizure threshold. One strategy to mitigate this is the use of lower-frequency stimulation paradigms with motor evoked potential responses as the readout, an approach that has been described in other asleep mapping series [5, 25].

Fig. 3
Fig. 3
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Decision algorithm for intraoperative motor mapping modality selection in peri-Rolandic diffuse gliomas. Flow chart describing the decision making process for mapping modality selection. SDE-DCS = subdural electrode direct cortical stimulation. Created in BioRender. Trippett, J. (2026) https://BioRender.com/2aj0dt7

Our findings are consistent with prior reports supporting the safety of asleep motor mapping techniques. Large institutional series using a triple-modality asleep approach — combining motor evoked potentials with bipolar and monopolar stimulation and strip electrode — have demonstrated low rates of permanent motor deficits (3.8% at 6 months) in peri-Rolandic glioma surgery [25]. Similarly, large cohorts evaluating subcortical motor pathway mapping have shown that identification of descending motor tracts during asleep surgery is feasible and associated with acceptable neurological morbidity [26]. While previous literature has relied on “low-grade” versus “high-grade” terminology, our results extend these observations by demonstrating comparable outcomes in a molecularly stratified cohort defined by the current WHO classification of diffuse gliomas [7, 25, 27]. In the GBM subgroup, survival analysis revealed no significant differences in OS or PFS between the awake and asleep mapping groups. This supports EOR, molecular biology, and access to adjuvant therapy, rather than mapping modality, as the dominant prognostic factors in GBM [28].

Although the overall percentage of resection was similar between awake and asleep mapping, RANO resect classification revealed a small but statistically significant difference in residual disease patterns, with class 1 resections more common after awake mapping. This difference was not evident when class 1 and 2 resections were analyzed together, suggesting that both approaches achieved comparable rates of maximal or supramaximal resection. Given that the extent of resection is among the strongest determinants of oncologic outcome, the mapping modality itself could possibly have influenced surgical aggressiveness. The exclusive occurrence of class 1 resections in the awake GBM group raises the possibility that real-time feedback enabled more aggressive resection at eloquent margins. This may also explain the numerically higher 3-month deficit rate in the awake GBM subgroup (17.6% vs. 7.7%), which, though not significant given the small sample, likely reflects greater aggressiveness rather than a disadvantage of awake mapping itself. The isolated difference in class 1 resections should be interpreted in the context of treatment and tumor selection. Prior unmatched analyses have reported similar findings, but these differences often disappear after matching or adjustment for baseline characteristics [16]. This likely reflects the close association between preoperative tumor volume and EOR, [12, 16] which was also observed in our cohort. Larger, adjusted studies using standardized RANO resect categories are needed to determine whether mapping modality independently affects the probability of radiographic resection.

Comparing the two asleep stimulation approaches, the SDE-DCS group showed numerically higher rates of postoperative deficits and SNF discharge, but these differences were not significant and likely reflect case complexity, as SDE-DCS was typically reserved for limited cortical exposure or restricted corridors. SDE-DCS may therefore be a reasonable alternative when HHP-DCS is technically challenging [6, 8, 9, 29, 30].

This study has several limitations. Patients were not randomized; mapping was chosen by clinical judgment, favoring awake mapping in younger, higher-functioning patients. Subgroup analyses were limited by small samples, particularly the awake glioblastoma and SDE-DCS cohorts, reducing power to detect modest differences. The absence of formal neurocognitive evaluation also prevents analysis of cognitive outcomes beyond KPS and deficit rates. Detail graded muscle strength data were unavailable. Because the asleep cohort had a higher rate of preoperative motor deficits, some patients may have had limited baseline strength, raising the possibility of a floor effect in which already weak limbs could not meaningfully worsen; the deficit comparison should be interpreted accordingly. Future prospective studies with matched cohorts and standardized outcome instruments are needed.

Conclusion

Awake and asleep intraoperative motor mapping demonstrated comparable functional and oncological outcomes in patients undergoing resection of peri-Rolandic diffuse glioma across molecular subtypes defined by the 2021 WHO classification. Similar rates of persistent postoperative neurological deficits and comparable survival outcomes in glioblastoma support the use of asleep motor mapping as a feasible and safe alternative when awake craniotomy is not feasible, although these retrospective findings should not be interpreted as establishing statistical equivalence between the techniques. Within the asleep cohort, both HHP-DCS and SDE-DCS were associated with acceptable outcomes. Advanced age, frailty, or anxiety should inform an individualized, multidisciplinary decision rather than serve as automatic indications for asleep mapping, and awake mapping retains particular advantages for tumors involving language or other higher-order networks. The choice of mapping technique should therefore be guided by surgeon preferences in individual cases, patient factors, and surgical anatomy while maintaining the goal of maximal safe resection.