Tag: Glioma

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Relationships Between Surgical Approach, Tumor Classification Scheme, and Early Neurocognitive Outcome After Awake Craniotomy for Resection of Insular Glioma

Operative Neurosurgery 30:880–889, 2026

This study evaluates early postoperative neurocognitive outcomes after awake craniotomy for insular glioma resection, comparing transcortical and transsylvian approaches and examining tumor classification schemes. It reports frequent, domain-specific declines—most notably in memory and verbal fluency—and analyzes relationships with tumor hemisphere, insular zone, and extension.

The authors found similar overall neurocognitive change across surgical corridors but identified higher verbal fluency decline with transcortical approaches and greater domain-specific risk linked to left-sided tumors, extra-insular extension, and anterior or inferior insular involvement.

Study aim: Assessed how surgical approach (transsylvian vs transcortical) and tumor classification/location relate to early postoperative neurocognitive function (NCF) after awake resection of insular glioma.

Cohort & design: Retrospective series of 53 newly diagnosed insular glioma patients (47% high-grade; 75% left hemisphere) treated with awake craniotomy, with neuropsychological testing pre-op and within 60 days post-op.

Classification schemes: Tumors were categorized by Berger–Sanai zones (collapsed to anterior/posterior/superior/inferior) and Pitskhelauri extension groups (insula only; insula + extension; predominantly extra-insular).

Overall NCF change: Postoperative decline occurred across multiple domains, with the largest effects most often in memory and verbal fluency (executive function).

Frequency of clinically meaningful decline: 85% declined on ≥1 test (Δz ≤ −1.0), 52% on ≥2 tests, and 22% on ≥5 tests; decline was most frequent/severe in memory and also common in executive function, attention, and processing speed.

Surgical approach comparison: Mean NCF change generally did not differ by approach, but the transcortical approach showed a higher rate of verbal fluency decline than transsylvian (61% vs 26%).

Tumor hemisphere & localization effects: Left-hemisphere tumors were linked to poorer outcomes on multiple tests (notably memory, verbal fluency, naming, and token comprehension), while anterior tumors had worse executive function (mental flexibility) than posterior, and inferior lesions had worse recognition memory than superior.

Tumor extent/size associations: Predominantly extra-insular tumors had greater fluency reduction than insula-only; more Berger–Sanai quadrants involved correlated with worse executive function change; larger tumor volume and higher postoperative FLAIR volume related to worse processing speed and comprehension outcomes.

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Awake Versus Asleep Craniotomy for Glioma: A Comparison of Survival and Costs Using Time-Driven Activity-Based Costing

Operative Neurosurgery 30:653–667, 2026

Awake versus asleep (general anesthesia) craniotomy are two approaches for glioma resection, and this work compares their intraoperative costs and survival outcomes.

Key Insights and Themes

Clinical question centers on whether awake craniotomy (AC) differs from asleep craniotomy under general anesthesia (GA) in intraoperative cost and in survival for glioma patients.

Cohort identification included all glioma resections at one institution from 2017–2022: 298 GA cases and 67 AC cases.

Awake-craniotomy indication primarily involved tumors in eloquent brain regions to allow intraoperative monitoring of neural function, while noneloquent tumors typically started under GA.

Costing method (TDABC) used process maps plus automated time-stamped extraction from the electronic medical record to capture intraoperative resources and time.

Cost components were dominated by supplies and personnel, with other elements (turnover and overhead) described as relatively minor contributors.

Baseline overall intraoperative cost had a median total of $6600 (IQR $2875), largely driven by supply cost (median $3178) and personnel cost (median $3141).

Operating-room time was longer for AC (median 5.2 hours) than GA (median 4.5 hours), and AC had about 30 additional minutes of incision-to-closure time.

Patient/tumor comparability showed GA patients were older, but there were no differences in WHO grade distribution or extent of resection between groups.

Unadjusted total cost difference showed higher median intraoperative cost for AC ($8506) versus GA ($6033).

Unadjusted subcomponent differences showed AC had higher median supply cost ($4238 vs $2928) and higher median personnel cost ($4111 vs $2962) than GA.

Adjusted total cost effect found AC associated with $2175 additional intraoperative cost versus GA after accounting for confounders.

Adjusted cost drivers attributed the added AC cost to higher supply cost (+$1272) and higher personnel cost (+$970).

Supply subcomponents were higher for AC than GA across consumables, implants, sterilization, and medications in unadjusted comparisons.

Personnel mix differed in that neurology attendings/fellows were included in AC but not GA at this institution, contributing to personnel-cost differences.

Unadjusted survival showed higher overall survival for AC on Kaplan–Meier analysis (log-rank P = .011), while progression-free survival did not significantly differ (log-rank P = .106).

Adjusted survival showed no significant differences between AC and GA in overall survival (HR 0.84, P = .48) or progression-free survival (HR 0.9, P = .66) after multivariable adjustment.

Key limitation (missing GA neuromonitoring costs) is that electrophysiological neuromonitoring personnel costs for GA were not captured due to EMR documentation limits.

Scope limitation (episode-of-care costs) is that the analysis focuses on intraoperative costs, and commenters note postoperative/inpatient costs could change conclusions about overall expense.

Conclusion

Awake craniotomy for glioma resection had higher intraoperative costs than asleep craniotomy, but after adjustment it showed no significant survival advantage in overall or progression-free survival.

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Mapping the Functional Boundaries of the Speech Articulation Network Using Positive and Negative Direct Electrical Stimulation With Resting-State Functional MRI

Neurosurgery 98:577–587, 2026

This clinical research integrates positive and negative direct electrical stimulation (DES) with presurgical resting-state fMRI to refine the speech articulation network (SAN) atlas in glioma patients. Analyzing 25 patients, the study maps DES-positive and DES-negative seed-based connectivity, compares anticorrelated networks, and evaluates sensitivity and specificity across group-frequency thresholds.

Key findings show DES-positive sites robustly identify bilateral SAN regions (rolandic operculum, inferior frontal and superior temporal gyri), while DES-negative points delineate functional borders and improve atlas specificity; a 41% SAN-positive threshold yields approximately 80% sensitivity and specificity for clinical use.

Resting-state fMRI and DES: Resting-state functional MRI (rs-fMRI) is a noninvasive tool for mapping brain networks, while direct electrical stimulation (DES) during awake surgery (AwS) is the gold standard for causally identifying functional brain regions, especially for speech articulation mapping in glioma patients.

Inclusion of DES-negative points: Incorporating both DES-positive (eliciting function) and DES-negative (no function elicited) points enables more precise mapping of the speech articulation network (SAN) and its functional borders, improving specificity and sensitivity compared to using only positive points.

Comprehensive SAN atlas: A new SAN atlas was created from 25 glioma patients using 32 DES-positive and 42 DES-negative points, with presurgical rs-fMRI seed-based connectivity analysis, providing a more accurate and clinically relevant definition of the SAN.

Distinct connectivity patterns: DES-positive points consistently mapped the SAN to bilateral rolandic operculum, inferior frontal gyrus, and superior temporal gyrus, while DES-negative points revealed distinct, only partially overlapping connectivity patterns, helping delineate the SAN’s functional borders.

Threshold for clinical use: A 41% frequency threshold for the SAN-positive network achieves approximately 80% sensitivity and specificity, offering a practical balance for clinical application in presurgical planning.

Functional borders and overlap: Minimal overlap between SAN-positive and SAN-negative networks identifies functional borders, especially in the precentral sulcus and inferior frontal gyrus, aiding neurosurgeons in distinguishing critical from non-critical areas during mapping.

Clinical implications: Defining precise SAN borders improves intraoperative decision-making, reduces irrelevant stimulation, shortens mapping time, and enhances safety in both awake and asleep brain surgeries.

Limitations and future directions: The study’s limitations include sample size, heterogeneity, and MRI field strength; future research should use larger, more homogeneous cohorts and higher-resolution imaging to further refine SAN mapping.

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Indirect cognitive mapping in glioma surgery in patients not eligible for awake craniotomy

Acta Neurochirurgica (2025) 167:289

This article presents a neurosurgical technique for indirectly mapping cognitive subcortical white matter pathways during glioma resection in patients who cannot undergo awake craniotomy. Using preoperative DTI and fMRI to create a 3D functional map, the team employs intraoperative monopolar subcortical motor stimulation as a live landmark to infer and protect nearby cognitive tracts like the arcuate fasciculus and IFOF.

Three illustrative cases demonstrate planning limits based on measured motor stimulation thresholds (approx. 1 mA ≈ 1 mm) and show safe resections with preserved cognitive and motor function. The report discusses indications, limitations versus awake mapping, importance of patient counselling about transient deficits, and integration of neuronavigation, tractography, and intraoperative motor mapping.

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Resectability of White Matter Tracts in Patients With Language-Critical Gliomas

Neurosurgery 00:1–9, 2025 (Published Online, October 15, 2025)

Resection of white matter tracts (WMTs) in language-critical glioma surgery robustly predicts permanent postoperative language deficits, particularly when parietal and temporal segments are involved. Frontal lobe WMTs are often safely resectable. Anatomical stratification enhances prediction, supporting data-driven, segment-specific surgical planning.

Resecting language-associated white matter tracts (WMTs) in glioma surgery robustly predicts permanent postoperative language deficits (PLDs).

• Frontal lobe WMT segments (e.g., arcuate fasciculus, IFOF, UF, SLF, FAT) are often resectable without causing PLDs.

• Resections in the temporoparietal junction (TPJ) and middle temporal lobe (MTL) significantly increase the risk of PLDs.

• Anatomically stratifying resections to parietal and temporal tracts improves prediction accuracy for PLDs (PPV increases to 50%).

• Volume of tract resected does not correlate with risk of PLDs; specific tract location is more important.

• Broca area and underlying white matter can often be resected safely, challenging traditional localizationist models.

• Combining imaging data with intraoperative mapping remains essential due to some nonfunctional tract segments leading to low PPV.

• Study limitations include small sample size, operator variability in tractography, and need for multicenter validation.

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Awake surgery with direct electrical stimulation mapping and real‑time cognitive monitoring for functionally guided tumor resection

Acta Neurochirurgica (2025) 167:239

Awake surgery with direct electrical stimulation and real-time cognitive monitoring enables maximal safe brain tumor resection by mapping individual functional networks, preserving quality of life and cognitive abilities. This multidisciplinary, patient-centered approach is gold standard for low-grade gliomas and is increasingly applied to other brain tumors.

• Awake surgery with direct electrical stimulation (DES) mapping is the gold standard for low-grade glioma resection and can also be applied to other brain tumors.

• This approach uses real-time cognitive monitoring to guide tumor removal based on the patient’s individual brain connectome, preserving neurocognitive functions and quality of life.

• A multidisciplinary team—including neurosurgeons, anesthesiologists, and neuropsychologists or speech therapists—is essential for patient selection, preparation, and intraoperative mapping.

• The asleep–awake–asleep protocol with continuous cognitive testing and tailored tasks optimizes functional mapping and minimizes permanent deficits.

• Subpial dissection and limited coagulation reduce vascular injury and promote better cognitive outcomes.

• Early postoperative rehabilitation is crucial for neuroplasticity and functional recovery.

• Careful patient selection and preparation are vital; conditions impairing intraoperative testing are relative contraindications.

• This personalized surgical philosophy has led to high cognitive preservation, low permanent deficit rates, and high return-to-work rates.

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Feasibility, Safety, and Impact of Awake Resection for Recurrent Insular Diffuse Gliomas in Adults

Neurosurgery 97:399–409, 2025

Function-based transopercular awake resection for recurrent insular diffuse gliomas in adults is feasible and safe, with similar resection rates, complications, and outcomes as first-time surgery, though prior combined treatments may increase intraoperative cooperation difficulties and sick leave, especially in high-grade gliomas.

• Transopercular awake resection for recurrent insular diffuse gliomas is feasible and safe, showing similar resection rates and outcomes to first-time surgery.

• No significant increase in intraoperative adverse events or surgery-related complications was observed for recurrent cases compared to first-line surgeries.

• Patients with previous combined oncological treatments had a higher risk of insufficient intraoperative cooperation, but this did not lead to mapping failure.

• Extent of resection and 6-month postoperative outcomes (Karnofsky Performance Status, seizure control, sick leave) were similar between recurrent and first-line groups.

• Longer sick leave was associated with high-grade gliomas and adjuvant treatments, not with surgery type.

• Shorter awake phase duration was observed in recurrent cases, likely due to easier access from prior surgeries and smaller tumor volumes.

• Study supports careful preoperative counseling and patient selection, especially for those with previous combined treatments.

• Results are specific to adult insular glioma patients treated with transopercular awake surgery and may not generalize to other populations or techniques.

 

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Comparative analysis of intraoperative MRI and early postoperative MRI findings in glioma surgery patients

J Neurosurg 142:1289–1297, 2025

The study compares intraoperative MRI (iMRI) and early postoperative MRI (epMRI) in glioma surgery, highlighting iMRI’s accuracy in extent of resection (EOR) and reduced surgically induced contrast enhancement (SICE). iMRI better detects postoperative neurological deficits, with fewer diffusion-weighted imaging abnormalities than epMRI.

• Objective: The study compares intraoperative MRI (iMRI) and early postoperative MRI (epMRI) findings in glioma surgery to assess the extent of resection (EOR) and postoperative neurological deficits.

• Methods: A retrospective analysis of 43 glioma patients who underwent surgery with iMRI, with no additional resection after iMRI, was conducted.

• Results: Discrepancies in EOR were found in 11.1% of nonenhanced and 4.0% of enhanced lesions. iMRI showed more accurate EOR and less surgically induced contrast enhancement (SICE) compared to epMRI.

• Findings: The positive rate of SICE was higher on epMRI (67.9%) than iMRI (25.0%). The positive rate of diffusion-weighted imaging (DWI) abnormality was also higher on epMRI (89.2%) compared to iMRI (73%).

• Clinical Outcomes: Two patients developed new neurological deficits postoperatively, both showing DWI abnormality on both iMRI and epMRI. No deficits were observed in the late-developing group.

• Conclusion: iMRI is more reliable for assessing accurate EOR and detecting postoperative neurological deficits than epMRI, despite higher late-developing DWI abnormalities on epMRI.

• Significance: The study underscores the importance of iMRI in optimizing glioma surgery outcomes and minimizing misinterpretation of residual tumors.

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Mental fatigue and cognitive functioning in patients presenting with non-enhancing gliomas

Acta Neurochirurgica (2025) 167:63

The study investigates the relationship between mental fatigue and cognitive functioning in patients with lower-grade gliomas (LGG) before surgery. It found a consistent correlation between self-reported mental fatigue and cognitive functioning but no correlation between self-reports and neuropsychological test results, highlighting the complexity of evaluating these symptoms.

• Study Purpose: Investigate mental fatigue and cognitive functioning in LGG patients pre-surgery.

• Patient Cohort: 101 patients with presumed LGG; 71 with confirmed IDH-mutated LGG.

• Methods: Self-reports, neuropsychological tests, and clinical/demographic data collected.

• Key Findings: No strong correlation between self-reports and neuropsychological tests.

• Correlation: A strong link was found between self-reported mental fatigue and cognitive functioning.

• Tumor Localization: Frontal tumors had more oligodendrogliomas; non-frontal had more glioblastomas.

• Neuropsychological Impairment: Higher RAVLT, FAS, and CWT test impairment rates.

• Statistical Analysis: Spearman’s partial correlations assess variable relationships.

• Clinical Implications: Need for a multi-perspective approach in evaluating LGG patient symptoms.

• Research Recommendations: Larger cohort studies and quantitative tumor localization metrics are suggested.

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Genomic Alterations in Molecularly Defined Oligodendrogliomas

Neurosurgery 96:328–337, 2025

• Study Focus: Genomic alterations in oligodendrogliomas using standardized NGS panels.

• Key Genes: CIC, FUBP1, and TERTp are the most frequently altered genes.

• Patient Cohort: Retrospective analysis of 95 patients with NGS reports.

• Methodology: Kaplan-Meier plots and log-rank tests for survival analysis.

• Findings: CIC alterations linked to reduced PFS at earlier time points.

• Additional Genes: NOTCH1 and PIK3CA show potential prognostic value.

• Clinical Implications: Potential integration of genomic alterations into clinical practice.

• Future Research: Larger studies needed to validate findings.

• Seizures: Most common presenting symptom in patients.

• Treatment: Majority underwent surgery followed by observation.

• Tumor Grade: Predominantly WHO grade 2 at first surgery.

• Mutation Analysis: 435 cancer-related genes analyzed.

• Statistical Tools: MATLAB R2022b used for analysis.

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Noninvasive evaluation of the glymphatic system in diffuse gliomas using diffusion tensor image analysis along the perivascular space

J Neurosurg 142:187–196, 2025

The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS).

METHODS In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the logrank test and univariable and multivariable Cox regressions.

RESULTS Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = −0.004, p = 0.026), tumor grade (β = −0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = −0.005, p < 0.001), tumor grade (β = −0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = −0.002, p = 0.001), and peritumoral edema volume (β = −0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = −0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = −0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = −0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001).

CONCLUSIONS GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

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Improvement of diffusion tensor imaging–based tractography by free-water correction in nonedematous gliomas: assessment with brain mapping

J Neurosurg 141:684–694, 2024

The free-water correction algorithm (Freewater Estimator Using Interpolated Initialization [FERNET]) can be applied to standard diffusion tensor imaging (DTI) tractography to improve visualization of subcortical bundles in the peritumoral area of highly edematous brain tumors. Interest in its use for presurgical planning in purely infiltrative gliomas without peritumoral edema has never been evaluated. Using subcortical maps obtained with direct electrostimulation (DES) in awake surgery as a reference standard, the authors sought to 1) assess the accuracy of preoperative DTIbased tractography with FERNET in a series of nonedematous glioma patients, and 2) determine its potential usefulness in presurgical planning.

METHODS Based on DES-induced functional disturbances and tumor topography, the authors retrospectively reconstructed the putatively stimulated bundles and the peritumoral tracts of interest (various associative and projection pathways) of 12 patients. The tractography data obtained with and without FERNET were compared.

RESULTS The authors identified 21 putative tracts from 24 stimulation sites and reconstituted 49 tracts of interest. The number of streamlines of the putative tracts crossing the DES area was 26.8% higher (96.04 vs 75.75, p = 0.016) and their volume 20.4% higher (13.99 cm 3 vs 11.62 cm 3 , p < 0.0001) with FERNET than with standard DTI. Additionally, the volume of the tracts of interest was 22.1% higher (9.69 cm 3 vs 7.93 cm 3 , p < 0.0001).

CONCLUSIONS Free-water correction significantly increased the anatomical plausibility of the stimulated fascicles and the volume of tracts of interest in the peritumoral area of purely infiltrative nonedematous gliomas. Because of the functional importance of the peritumoral zone, applying FERNET to DTI could have potential implications on surgical planning and the safety of glioma resection.

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Evaluation of the extent of resection of intracranial tumors with virtual intraoperative MRI

J Neurosurg 141:695–701, 2024

Intraoperative MRI (iMRI) is the gold-standard technique for intraoperative evaluation of the extent of resection in brain tumor surgery. Unfortunately, it is currently available at only a few neurosurgical centers. A commercially available software, Virtual iMRI Cranial, provides an elastic fusion between preoperative MRI and intraoperative CT (iCT). The aim of this study was to evaluate the accuracy of this software in determining the presence of residual tumor.

METHODS Virtual iMRI was performed in patients who underwent iCT after intracranial tumor resection. The results of the software in terms of presence or absence of tumor residual were then compared with postoperative MRI performed within 48 hours after surgery to evaluate the diagnostic accuracy of virtual iMRI.

RESULTS Sixty-six patients were included in the present study. The virtual iMRI findings were concordant with the postoperative MRI data in 35 cases (53%) in the detection of tumor residual (p = 0.006). No false-negative findings (i.e., presence of residual on postoperative MRI and absence of residual on virtual iMRI) were encountered. Virtual iMRI had a sensitivity of 1 (95% CI 0.86–1), specificity of 0.26 (95% CI 0.14–0.42), positive predictive value of 0.44 (95% CI 0.3–0.58), and negative predictive value of 1 (95% CI 0.72–1). Subgroup analysis revealed that the virtual iMRI findings were concordant with postoperative MRI findings in all cases (n = 9) of lower-grade glioma (LGG) with a sensitivity of 1 (95% CI 0.59–1) and a specificity of 1 (95% CI 0.16–1) (p = 0.003); a statistically significant association was also found for grade 4 gliomas with a sensitivity of 1 (95% CI 0.69–1) and a specificity of 0.33 (95% CI 0.08–0.7) (p = 0.046) (19 patients). No significant association was found when considering meningiomas or metastases.

CONCLUSIONS The commercially available virtual iMRI can predict the presence or absence of tumor residual with high sensitivity. The diagnostic accuracy of this method was higher in LGGs and much lower for meningiomas or metastases; these findings must be evaluated in prospective studies in a larger population.

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Asleep triple-modality motor mapping for perirolandic gliomas: an update on outcomes

J Neurosurg 140:1029–1037, 2024

Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. Here, the authors review their results with triple-modality asleep motor mapping with motor evoked potentials and bipolar and monopolar stimulation for cortical and subcortical mapping during glioma surgery in an expanded cohort.

METHODS This was a retrospective analysis of patients who underwent resection of a perirolandic glioma near motor pathways. Clinical and neuromonitoring data were extracted from the electronic medical records for review. All patients with new or worsened postoperative motor deficits were followed for at least 6 months. Regression analyses were performed to assess factors associated with a persistent motor deficit.

RESULTS Between January 2018 and December 2021, 160 operations were performed in 151 patients with perirolandic glioma. Sixty-four patients (40%) had preoperative motor deficits, and the median extent of resection was 98%. Overall, patients in 38 cases (23.8%) had new or worse immediate postoperative deficits by discharge, and persistent deficits by 6 months were seen in 6 cases (3.8%), all in patients with high-grade gliomas. There were no new persistent deficits in low-grade glioma patients (0%). The risk factors for a persistent deficit included an insular tumor component (OR 8.6, p = 0.01), preoperative motor weakness (OR 8.1, p = 0.03), intraoperative motor evoked potential (MEP) changes (OR 36.5, p < 0.0001), and peri–resection cavity ischemia (OR 7.5, p = 0.04). Most persistent deficits were attributable to ischemic injury despite structural preservation of the descending motor tracts. For patients with persistent motor deficits, there were 3 cases (50%) in which a change in MEP was noted but subsequent subcortical monopolar stimulation still elicited a response in the corresponding muscle groups, suggesting axonal activation distal to a point of injury.

CONCLUSIONS Asleep triple motor mapping results in a low rate of permanent deficits, especially for low-grade gliomas. Peri–resection cavity ischemia continues to be a significant risk factor for permanent deficit despite maintaining appropriate distance for subcortical tracts based on monopolar feedback.

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Sodium fluorescein uptake by the tumor microenvironment in human gliomas and brain metastases

J Neurosurg 140:958–967, 2024

Intravenous sodium fluorescein (SF) is increasingly used during surgery of gliomas and brain metastases to improve tumor resection. Currently, SF is believed to permeate the brain regions where the blood-brain barrier (BBB) is damaged and to accumulate in the extracellular space but not in tumor or healthy cells, making it possible to demarcate tumor margins to guide resection. By evaluating the immune contexture of a number of freshly resected gliomas and brain metastases from patients undergoing SF-guided surgery, the authors recurrently observed fluorescence-positive cells. Therefore, the aim of this study was to determine if SF accumulates inside the cells of the tumor microenvironment (TME), and if so, in which type of cells, and whether incorporation can also be observed in the leukocytes of peripheral blood.

METHODS Freshly resected tumor specimens were dissociated to single cells and analyzed by multiparametric flow cytometry. Peripheral blood leukocytes, macrophages, and a glioma cell line were treated with SF in vitro, and their cell uptake was assessed by multiparametric and imaging flow cytometry and by confocal microscopy.

RESULTS The ex vivo and in vitro analyses revealed that SF accumulates intracellularly in leukocytes as well as in tumor cells, but with a high variability of incorporation in the different cell subsets analyzed. Myeloid cells showed the highest level of fluorescence. In vitro uptake experiments showed that SF accumulation increases over time. The imaging analyses confirmed the internalization of the compound inside the cells.

CONCLUSIONS SF is not just a marker of BBB damage, but its intracellular detection suggests that it selectively accumulates intracellularly. Future efforts should target the mechanisms of its differential uptake by the different TME cell types in depth.

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Minimally invasive keyhole approach for supramaximal frontal glioma resections

J Neurosurg 140:949–957, 2024

The authors aimed to review the frontal lobe’s surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results.

METHODS Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis.

RESULTS Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months.

CONCLUSIONS Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

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Nonenhancing motor eloquent gliomas: navigated transcranial magnetic stimulation oncobiological signature

J Neurosurg 140:909–919, 2024

Preoperative grading of nonenhancing motor eloquent gliomas is hampered by a lack of specific imaging surrogates. Tumor grading is crucial for the informed consent discussion before tumor resection. In this paper, the authors hypothesized that navigated transcranial magnetic stimulation (nTMS)–derived metrics could provide significant information to distinguish between high- and low-grade motor eloquent gliomas that present as nonenhancing tumors and therefore contribute to improving patient counseling, timing of treatment, preoperative planning, and intraoperative strategies.

METHODS The authors conducted a retrospective single-center cohort study of patients admitted for tumor surgery between January 2018 and April 2022 with a nonenhancing motor eloquent glioma and preoperative bilateral nTMS mapping. nTMS data including resting motor threshold (RMT), interhemispheric RMT ratio (iRMTr), Cortical Excitability Score (CES), area and volume of cortical activation, and motor evoked potential (MEP) characteristics were obtained and integrated with demographic and clinical data.

RESULTS Thirty patients met the inclusion criteria, and 10 healthy participants were recruited for comparison. Seizures were the most common presenting symptom (25 patients) and WHO grade 3 the most common tumor grade (21 patients). The area and volume of functional cortical activation of both the abductor pollicis brevis and first dorsal interosseous muscles were decreased in healthy participants compared with patients with WHO grade 3 glioma (p < 0.05). An abnormal iRMTr for the lower limbs (16.7% [1/6] WHO grade 2, 76.2% [16/21] WHO grade 3, 100% [3/3] WHO grade 4; p = 0.015) and a higher CES (maximal abnormal CES: 0% [0/6] WHO grade 2, 38% [8/21] WHO grade 3, 66.7% [2/3] WHO grade 4; p = 0.010) were associated with the prediction of high-grade lesions. A total of 7280 MEPs were analyzed. A significant increase in the amplitude and a significant decrease in latency in the MEPs for the first dorsal interosseous and abductor digiti minimi muscles (p < 0.0001) were identified in healthy participants compared with WHO grade 3 glioma patients.

CONCLUSIONS Nonenhancing motor eloquent gliomas have a different impact on both anatomical and functional reorganization of motor areas according to their WHO grading.

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Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

J Neurosurg 140:357–366, 2024

Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration–cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied.

METHODS Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0–2) and a high tumor probability (HTP) group (scores 3–5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated.

RESULTS Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86–0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40–0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40–0.83]) and HTP group (0.68 [0.39–0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group.

CONCLUSIONS CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

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Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

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Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

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