Tag: tumor

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The role of salvage stereotactic radiosurgery for tumor progression following incomplete microsurgical resection of vestibular schwannoma

J Neurosurg 144:1403–1409, 2026

This clinical study evaluates salvage stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) that progresses after incomplete microsurgical resection, reporting long-term tumor control, freedom from additional treatment (FFAT), and complication rates in a 64-patient cohort. Key outcomes include 10- and 15-year tumor control of 87.5% and 84.4%, and FFAT of 95.3% and 92.2%, respectively.

The methods describe retrospective selection, radiosurgical dosimetry (median margin 12.5 Gy), imaging and follow-up protocols, and statistical analyses using Kaplan–Meier and Cox models; no factors significantly predicted control or FFAT, and common complications included trigeminal neuropathy and hearing worsening.

Objective Assess safety/efficacy of salvage stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) that progresses after incomplete microsurgical resection, including factors affecting tumor control and freedom from additional treatment (FFAT).

Cohort Retrospective series of 64 adults treated with salvage SRS for post-resection tumor progression; median age 51.5 years and 46.9% male.

Treatment parameters Median marginal dose 12.5 Gy (median isodose 50%); median tumor volume 1.6 cm³; median time from surgery to salvage SRS 38.8 months.

Long-term control Tumor control rates after salvage SRS were 87.5% at 10 years and 84.4% at 15 years.

Durability (FFAT) FFAT rates were 95.3% at 10 years and 92.2% at 15 years, indicating most patients avoided further intervention long term.

Predictors No evaluated factors (e.g., Koos grade, age/sex, cranial nerve neuropathies, marginal dose, extent of resection, tumor volume) were significantly associated with tumor control or FFAT in Cox modeling.

Complications Most common post-SRS issue was worsening/new trigeminal neuropathy (15.6% total); hearing worsened in 14.1% (Gardner-Robertson class), and facial nerve function worsened in 4.7% (House-Brackmann).

Conclusion Salvage SRS is a safe and effective long-term strategy for VS tumor progression after incomplete resection, supporting continued monitoring and consideration of SRS once progression is documented.

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Awake surgery for IDH-mutant grade 2 glioma involving the corpus callosum: long-term onco-functional results after callosectomy in 157 consecutive patients

J Neurosurg 143:1280–1289, 2025

This clinical study reports outcomes from 157 consecutive patients with IDH‑mutant grade 2 gliomas infiltrating the corpus callosum who underwent connectome-guided awake surgery with callosectomy. It summarizes surgical technique, extent of resection, complication rates, return-to-work statistics, histology, adjuvant treatments, reoperations, and long-term overall survival.

Comparative analysis contrasts complete (total/supratotal) versus incomplete resections, showing higher extent of resection, greater reoperation potential, and longer median overall survival when callosal tumor was fully removed, while preserved function and a 96.8% return-to-work rate underline favorable onco-functional balance.

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The neuronal reserve in glioma surgery: functional reorganization of the motor network examined by navigated transcranial magnetic stimulation and diffusion tensor imaging tractography

J Neurosurg 143:793–804, 2025

This study demonstrates that glioma-induced reorganization of the motor cortex, measured by navigated transcranial magnetic stimulation and diffusion tensor imaging, is linked to functional recovery. Individual neuronal reserve—reflected in motor area resizing, excitability, and tract integrity—may explain differences in disease progression and surgical outcomes.

• Glioma surgery outcomes vary due to individual differences in motor network compensation and adaptation.

• This study used navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging (DTI) tractography to measure motor cortex reorganization in glioma patients.

• Motor area relocation, resizing, and changes in excitability were observed in both affected and unaffected hemispheres, indicating bilateral reorganization.

• Greater preoperative motor area size and excitability were associated with better postoperative motor function and recovery.

• Reduced integrity of the corticospinal tract correlated with motor impairment and limited reorganization capacity.

• Functional recovery was linked to increased motor area size, excitability, and area relocation, supporting the concept of an individual neuronal reserve.

• Reorganization patterns were independent of tumor grade, highlighting the importance of personalized risk stratification and treatment planning.

• The study recommends using nTMS data for tailored preoperative risk assessment and patient counseling in glioma surgery.

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High-grade glioma: combined use of 5-aminolevulinic acid and intraoperative ultrasound for resection and a predictor algorithm for detection

J Neurosurg 143:323–331, 2025

Combining 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative ultrasound (ioUS) significantly improved the sensitivity and specificity for detecting high-grade glioma during surgery, compared to either technique alone. A machine learning algorithm (HGGPredictor) further enhanced intraoperative tumor margin prediction, suggesting a new standard for safer, more effective resections.

• Combining 5-ALA fluorescence and intraoperative ultrasound (ioUS) improves the accuracy of high-grade glioma (HGG) resection compared to using either method alone.

• 5-ALA shows higher sensitivity (84.9%), while ioUS provides higher specificity (84.5%); combined, they reach sensitivity of 91% and specificity of 86%.

• The combined approach is especially valuable for maximizing tumor removal while minimizing neurological damage, particularly near eloquent brain regions.

• A machine learning algorithm (HGGPredictor) was developed to predict tumor presence during surgery based on 5-ALA and ioUS results.

• The study included 72 patients and 301 biopsies, with histological analysis as the reference standard.

• The benefit of combination is greatest for strong fluorescence or hyperechogenicity; ioUS is particularly helpful when 5-ALA fluorescence is weak.

• The combined method is accessible and can be integrated into existing surgical protocols without major additional costs.

• Limitations include single-center design and lack of a control group, but results suggest a new standard for HGG resection.

 

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Safety and therapeutic impact of stereotactic biopsy in very elderly patients with brain tumors

J Neurosurg 143:194–203, 2025

Stereotactic brain biopsy in patients aged ≥80 is safe, with high diagnostic yield (96.2%) and low persistent neurological deficit (1.9%). Prebiopsy Karnofsky Performance Status ≥70% predicts full adjuvant therapy and longer survival. Biopsy findings frequently alter management, supporting its use in very elderly brain tumor patients.

• Stereotactic brain biopsy in patients aged ≥80 years is safe and has a high diagnostic yield (96.2%).

• Symptomatic complication rate was 6.2%, with persistent neurological deficit in 1.9% and a procedure-related mortality of 0.5%.

• The biopsy changed the suspected diagnosis in 11.1% of cases, influencing patient management.

• 80.7% of patients received adjuvant treatment after biopsy; 19.3% received palliative care.

• A Karnofsky Performance Status (KPS) score ≥70% was the only significant predictor for receiving full adjuvant therapy and longer overall survival (OS).

• Median OS after biopsy was 5.6 months; longer in patients with PCNSL or methylated MGMT promoter in glioma.

• No significant increase in complications was seen with deep-seated tumors, anticoagulant use, or advanced age (≥85 or ≥90 years).

• The study supports considering biopsy for very elderly patients when technically feasible and patient condition is good.

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Efficacy and safety of intraoperative MRI in glioma surgery: a systematic review and meta-analysis of prospective randomized controlled trials

J Neurosurg 142:1319–1330, 2025

This meta-analysis of randomized controlled trials found that intraoperative MRI significantly increases gross-total resection rates and progression-free survival in glioma surgery, without increasing neurological deficits or most complications, though it prolongs surgery and may raise infection risk. iMRI is effective and generally safe for maximizing tumor removal.

• Intraoperative MRI (iMRI) significantly increases the rate of gross-total resection (GTR) in glioma surgery compared to conventional neuronavigation.

• Greater extent of resection (EOR) with iMRI leads to improved progression-free survival (PFS), especially in high-grade gliomas.

• No significant difference in overall survival (OS) was observed between iMRI and conventional surgery groups.

• Rates of postoperative neurological deterioration, motor, and language decline are similar between iMRI and control groups.

• iMRI does not increase the risk of postoperative intracranial hemorrhage, but may be associated with higher rates of wound infections in some studies.

• Use of iMRI prolongs surgery time by an average of 42 minutes.

• Only three randomized controlled trials with a total of 384 patients met inclusion criteria for this meta-analysis.

• Combined use of iMRI and 5-ALA may further enhance EOR, but more randomized studies are needed for definitive conclusions.

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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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Predictors of trigeminal neuropathy in patients receiving Gamma Knife stereotactic radiosurgery for vestibular schwannoma

J Neurosurg 142:1134–1140, 2025

The study investigates predictors of trigeminal neuropathy (Tn) in patients receiving Gamma Knife stereotactic radiosurgery for vestibular schwannoma. It identifies the volume of cranial nerve V receiving ≥11 Gy as a significant factor in Tn development, suggesting it be included in dosimetric planning to minimize risk.

• Objective: Validate predictors of trigeminal neuropathy (Tn) in patients receiving stereotactic radiosurgery (SRS) for vestibular schwannoma (VS).

• Methodology: Study included 204 patients treated with SRS, excluding those with pre-existing Tn symptoms or less than 2 years of follow-up.

• Key Finding: The volume of cranial nerve (CN) V receiving ≥ 11 Gy is the only significant predictor of Tn development post-SRS.

• Results: 11.3% of patients developed Tn, with 7.8% experiencing permanent symptoms.

• Statistical Analysis: Maximum dose to CN V was significant in univariate analysis but not in multivariate analysis.

• Tumor Compression: Not significantly correlated with Tn development.

• Clinical Implication: Dosimetric planning should account for CN V volume receiving ≥ 11 Gy to minimize Tn risk.

• Recommendation: Early treatment advised to maintain gap between VS and CN V, reducing Tn risk.

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Long-term survivors in 976 supratentorial glioblastoma, IDH-wildtype patients

J Neurosurg 142:174–186, 2025

Glioblastoma, isocitrate dehydrogenase (IDH)–wildtype is the most aggressive glioma with poor outcomes. The authors explored survival rates and factors associated with long-term survival in patients harboring a glioblastoma, IDH-wildtype.

METHODS In an observational, retrospective, single-center study, the authors examined the medical records of 976 adults newly diagnosed with supratentorial glioblastomas, IDH-wildtype between January 2000 and January 2021. They analyzed clinical-, imaging-, and treatment-related factors associated with 2-year and 5-year survival.

RESULTS The median overall survival was 11.2 months (12.2 months for patients included after 2005 and the introduction of standard combined chemoradiotherapy). The median progression-free survival was 9.4 months (10.0 months for patients included after 2005). Overall, 17.6% of patients reached a 2-year overall survival, while 2.2% of patients reached a 5-year overall survival. Furthermore, 6.6% of patients survived 2 years without progression, while 1.1% of patients survived 5 years without progression. Two factors that were consistently associated with 2-year and 5-year survival were first-line oncological treatment with standard combined chemoradiotherapy and methylated O 6 -methylguanineDNA methyltransferase promoter. Other factors that were significantly associated with 2-year or 5-year survival were age at diagnosis ≤ 60 years, headaches or signs of raised intracranial pressure at diagnosis, cortical contact of contrast enhancement, no contrast enhancement crossing the midline on initial imaging, total or subtotal tumor resection, and a second line of oncological treatment at recurrence. Within 21 cases of 5-year survival, 18 were confirmed to be glioblastomas, IDH-wildtype, and 7 of the 5-year survivors (38.9%) had additional genetic alterations: 3 cases had an FGFR mutation or fusion, 3 cases had a PIK3CA mutation, 1 case had a PTPN11 mutation, and 1 case had a PMS2 mutation in the context of constitutional mismatch repair deficiency syndrome.

CONCLUSIONS Five-year overall survival in patients with glioblastoma, IDH-wildtype is extremely low. Predictors of a longer survival are mostly treatment factors, emphasizing the importance of a complete oncological treatment plan, when achievable. Glioblastoma, IDH-wildtype 5-year survivors could be screened for actionable targets in case of recurrence.

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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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Berberine as a potential enhancer for 5-ALA–mediated fluorescence in glioblastoma

J Neurosurg 141:653–663, 2024

The prognosis of glioblastoma (GBM) correlates with residual tumor volume after surgery. In fluorescenceguided surgery, 5-aminolevulinic acid (ALA) has been used to maximize resection while avoiding neurological morbidity. However, not all tumor cells, particularly glioma stem cells (GSCs), display 5-ALA–mediated protoporphyrin IX (PpIX) fluorescence (5-ALA fluorescence). The authors searched for repositioned drugs that affect mitochondrial functions and energy metabolism, identifying berberine (BBR) as a potential enhancer of 5-ALA fluorescence. In this study, they investigated whether BBR can enhance 5-ALA fluorescence in GSCs and whether BBR can be applied to clinical practice as a 5-ALA fluorescence enhancer.

METHODS The effects of BBR on 5-ALA fluorescence in glioma and GSCs were evaluated by flow cytometry (fluorescence-activated cell sorting [FACS]) analysis. As 5-ALA is metabolized for heme synthesis, the effects of BBR on mRNA expressions of 7 enzymes in the heme-synthesis pathway were analyzed. Enzymes showing significantly higher expression than control in all cells were identified and protein analysis was performed. To examine clinical availability, the detectability and cytotoxicity of BBR in tumor-transplanted mice were analyzed.

RESULTS Fluorescence microscopy revealed much more intense 5-ALA fluorescence in both GSCs and non-stem cells with 5-ALA and BBR than with 5-ALA alone. FACS showed that BBR greatly enhanced 5-ALA fluorescence compared with 5-ALA alone, and enhancement was much higher for GSCs than for glioma cells. Among the 7 enzymes examined, BBR upregulated mRNA expressions of ALA synthetase 1 (ALAS1) more highly in all cells, and activated ALAS1 through deregulating ALAS1 activity inhibited by the negative feedback of heme. An in vivo study showed that 5-ALA fluorescence with 5-ALA and BBR was significantly stronger than with 5-ALA alone, and the sensitivity and specificity of BBR-enhanced fluorescence were both 100%. In addition, BBR did not show any cytotoxicity for normal brain tissue surrounding the tumor mass.

CONCLUSIONS BBR enhanced 5-ALA–mediated PpIX fluorescence by upregulating and activating ALAS1 through deregulation of negative feedback inhibition by heme. BBR is a clinically used drug with no side effects. BBR is expected to significantly augment fluorescence-guided surgery and photodynamic therapy.

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Longitudinal brain volumetrics in glioma survivors

J Neurosurg 141:634–641, 2024

Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT.

METHODS This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models.

RESULTS The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36–18.9 years), and the median number of time points analyzed per patient was 12 (range 2–40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (β = −0.06, p < 0.001) and use of RT (β = −1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (β = −0.08, p < 0.001), midline involvement (β = 1.31, p = 0.006), and use of RT (β = −1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (β = −0.0027, p = 0.001), tumor resection (β = −0.069, p < 0.001), use of chemotherapy (β = −0.0597, p = 0.003), and use of RT (β = −0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model.

CONCLUSIONS This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

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A novel radiological classification of midbrain pilocytic astrocytomas and its implication for surgical management

J Neurosurg 140:1527–1539, 2024

Surgery for midbrain pilocytic astrocytoma (PA) remains a formidable challenge. To facilitate decisionmaking and achieve a better outcome in the management of patients with midbrain PA, the authors have proposed a novel radiological classification of midbrain PAs with long-term follow-up.

METHODS Fifty-seven midbrain PA patients who underwent surgery at Beijing Tiantan Hospital, Capital Medical University, from January 2008 to June 2021, were reviewed. Based on tumor location and the topological anatomical change identified on MRI, midbrain PAs were categorized into four types: crural (12/57, 21.1%), tegmental (25/57, 43.9%), aqueductal (5/57, 8.8%), and tectal (15/57, 26.3%) PAs. The relevant clinical, radiological, and pathological data; surgical procedures and results; and long-term outcomes were collected and analyzed.

RESULTS The 1-, 3-, and 5-year survival rates reached 98%, 96%, and 96%, respectively, with gross-total resection achieved in 66.7% of cases, followed by near-total resection in 17.5% cases. The clinical and radiological features, selection of surgical approaches, and long-term postoperative deficits were distinct among each type. Crural PAs were associated with younger age (median 9 years, IQR 5.0–12.8 years); the largest tumor volume (median 31.9 cm 3 , IQR 17.2–42.6 cm 3 ); the lowest preoperative Karnofsky Performance Scale (KPS) score (median 65, IQR 50–70); the most frequent preoperative motor deficit (91.7%); a mixed solid-cystic component (75%); occupation of the crural cistern; elevation and rotation of the thalamus (medial and/or lateral); displacement of the anterior third ventricle, uncus, and anterior commissure; the most diverse surgical approaches; more frequent use of multimodality image–guided surgery (58.3%); and the most remarkable improvement in KPS score at long-term follow-up. Tegmental PAs were associated with adolescents and young adults (median age 21 years, IQR 8–33 years); tumor volume (median 13.9 cm 3 , IQR 9.5–20.5 cm 3 ); a good preoperative KPS score (median 80, IQR 70–80); a mixed solid-cystic component (72%); occupation of the ambient cistern and cerebellomesencephalic fissure; a close relationship with the dorsal pons, superior cerebellar peduncle, and posterior inferior third ventricle; and a higher probability of permanent postoperative sensory deficits (40%). Aqueductal and tectal PAs were associated with small tumor volume (median 9.14 cm 3 , IQR 5.1–17.4 cm 3 and median 11.84 cm 3 , IQR 5.7–18.3 cm 3 , respectively), a higher percentage of hydrocephalus (80% and 86.7%, respectively), and a straightforward selection of limited surgical approaches.

CONCLUSIONS A novel and comprehensive radiological classification of midbrain PAs was established, which will serve as a valuable tool in patient management and promote uniform communication and comparison across different studies and publications.

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Use of 5-ALA fluorescence–guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study

J Neurosurg 140:987–1000, 2024

Only one phase III prospective randomized study, published in 2006, has assessed the performance of 5-aminolevulinic acid (5-ALA) fluorescence–guided surgery (FGS) for glioblastoma resection. The aim of the RESECT study was to compare the onco-functional results associated with 5-ALA fluorescence and with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care.

METHODS This was a phase III prospective randomized single-blinded study, involving 21 French neurosurgical centers, comparing 5-ALA FGS with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care, including neuronavigation use and postoperative radiochemotherapy. Randomization was performed in a 1:1 ratio stratified by institution. 5-ALA (20 mg/kg) or placebo (ascorbic acid) was administered orally 3–5 hours before the incision. The primary endpoint was the rate of gross-total resection (GTR) blindly assessed by an independent committee. Patients without a confirmed pathological diagnosis of glioblastoma or with unavailable postoperative MRI studies were excluded from the per-protocol analysis.

RESULTS Between March 2013 and August 2016, a total of 171 patients were assigned to the 5-ALA fluorescence group (n = 88) or to the placebo group (n = 83). Twenty-four cases were excluded because the WHO histological criteria of grade 4 glioma were not met. The proportion of GTR was significantly higher in the 5-ALA fluorescence group (53/67, 79.1%) than in the placebo group (33/69, 47.8%; p = 0.0002). After adjustment for age, preoperative Karnofsky Performance Scale score, and tumor location, GTR was still associated with 5-ALA fluorescence (OR 4.13 [95% CI 1.94–8.79]). The mean 7-day postoperative Karnofsky Performance Scale score (≥ 80% in 49/71, 69.0% [5-ALA group]; 50/71, 70.4% [placebo group], p = 0.86) and the proportion of patients with a worsened neurological status 3 months postoperatively (9/68, 13.2% [5-ALA group]; 9/70, 12.9% [placebo group], p = 0.95) were similar between groups. Adverse events related to 5-ALA intake were rare and consisted of photosensitization in 4/87 (4.6%) patients and hepatic cytolysis in 1/87 (1.1%) patients. The 6-month PFS (70.2% [95% CI 57.7%–79.6%] and 68.4% [95% CI 55.7%–78.1%]; p =0.39) and 24-month OS (30.1% [95% CI 18.9%–42.0%] and 37.7% [95% CI 25.8%–49.5%]; p = 0.89) did not significantly differ. In multivariate analysis, GTR was an independent predictor of PFS (hazard ratio 0.56 [95% CI 0.36–0.86], p =0.008) and OS (hazard ratio 0.65 [95% CI 0.42–1.01], p = 0.05). The use of 5-ALA FGS generates a significant extra cost of 2732.36€ (95% CI 1658.40€–3794.11€).

CONCLUSIONS The authors found that 5-ALA FGS is an easy-to-use, cost-effective, and minimally time-consuming technique that safely optimizes the extent of resection in patients harboring glioblastoma amenable to a large resection.

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Intraventricular meningioma resection and visual outcomes

J Neurosurg 140:1001–1007, 2024

Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges because of their deep location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (tumor VFDs) or may develop postoperatively due to the surgical approach (surgical VFDs). This institutional series aimed to review surgical outcomes following resection of IVMs, with a focus on VFDs.

METHODS Patients who received IVM resection at one academic institution between the years 1996 and 2021 were retrospectively reviewed. Diffusion tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative IVM imaging. The VFD course and resolution were documented.

RESULTS Thirty-two adult patients underwent IVM resection, with gross-total resection in 30 patients (93.8%). Preoperatively, tumor VFDs were present in 6 patients, resolving after surgery in 5 patients. Five other patients (without preoperative VFD) had new persistent surgical VFDs postoperatively (5/32, 15.6%) that persisted to the most recent follow-up. Of the 5 patients with persistent surgical VFDs, 4 received a transtemporal approach and 1 received a transparietal approach, and all these deficits occurred prior to regular use of DTI in preoperative imaging.

CONCLUSIONS New surgical VFDs are a common neurological deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical VFDs.

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Subclassification of Koos grade 4 vestibular schwannoma: insights into tumor morphology for predicting postoperative facial nerve function

J Neurosurg 140:127–137, 2024

OBJECTIVE Koos grade 4 vestibular schwannoma (KG4VS) is a large tumor that causes brainstem displacement and is generally considered a candidate for surgery. Few studies have examined the relationship between morphological differences in KG4VS other than tumor size and postoperative facial nerve function. The authors have developed a landmark-based subclassification of KG4VS that provides insights into the morphology of this tumor and can predict the risk of facial nerve injury during microsurgery. The aims of this study were to morphologically verify the validity of this subclassification and to clarify the relationship of the position of the center of the vestibular schwannoma within the cerebellopontine angle (CPA) cistern on preoperative MR images to postoperative facial nerve function in patients who underwent microsurgical resection of a vestibular schwannoma.

METHODS In this paper, the authors classified KG4VSs into two subtypes according to the position of the center of the KG4VS within the CPA cistern relative to the perpendicular bisector of the porus acusticus internus, which was the landmark for the subclassification. KG4VSs with ventral centers to the landmark were classified as type 4V, and those with dorsal centers as type 4D. The clinical impact of this subclassification on short- and long-term postoperative facial nerve function was analyzed.

RESULTS In this study, the authors retrospectively reviewed patients with vestibular schwannoma who were treated surgically via a retrosigmoid approach between January 2010 and March 2020. Of the 107 patients with KG4VS who met the inclusion criteria, 45 (42.1%) were classified as having type 4V (KG4VSs with centers ventral to the perpendicular bisector of the porous acusticus internus) and 62 (57.9%) as having type 4D (those with centers dorsal to the perpendicular bisector). Ventral extension to the perpendicular bisector of the porus acusticus internus was significantly greater in the type 4V group than in the type 4D group (p < 0.001), although there was no significant difference in the maximal ventrodorsal diameter. The rate of preservation of favorable facial nerve function (House-Brackmann grades I and II) was significantly lower in the type 4V group than in the type 4D group in terms of both short-term (46.7% vs 85.5%, p < 0.001) and long-term (82.9% vs 96.7%, p = 0.001) outcomes. Type 4V had a significantly negative impact on short-term (OR 7.67, 95% CI 2.90–20.3; p < 0.001) and long-term (OR 6.05, 95% CI 1.04–35.0; p = 0.045) facial nerve function after surgery when age, tumor size, and presence of a fundal fluid cap were taken into account.

CONCLUSIONS The authors have delineated two different morphological subtypes of KG4VS. This subclassification could predict short- and long-term facial nerve function after microsurgical resection of KG4VS via the retrosigmoid approach. The risk of postoperative facial palsy when attempting total resection is greater for type 4V than for type 4D. This classification into types 4V and 4D could help to predict the risk of facial nerve injury and generate more individualized surgical strategies for KG4VSs with better facial nerve outcomes.

 

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Decoding the clinical effects of low-grade glioma–induced cortical excitability

J Neurosurg 140:18–26, 2024

Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG.

METHODS LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies.

RESULTS A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%–46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale–Fourth Edition [WAIS-IV] Processing Speed Index r = −0.42, p = 0.031; WAIS-IV Coding r = −0.41, p = 0.036; WAIS-IV Symbol Search r = −0.39, p = 0.048), executive function (Trail Making Test Part B r = −0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = −0.50, p = 0.047).

CONCLUSIONS RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

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Microsurgical management of midbrain gliomas: surgical results and long-term outcome in a large, single-surgeon, consecutive series

J Neurosurg 140:104–115, 2024

The authors report on a large, consecutive, single-surgeon series of patients undergoing microsurgical removal of midbrain gliomas. Emphasis is put on surgical indications, technique, and results as well as long-term oncological follow-up.

METHODS A retrospective analysis was performed of prospectively collected data from a consecutive series of patients undergoing microneurosurgery for midbrain gliomas from March 2006 through June 2022 at the authors’ institution. According to the growth pattern and location of the lesion in the midbrain (tegmentum, central mesencephalic structures, and tectum), one of the following approaches was chosen: transsylvian (TS), extreme anterior interhemispheric transcallosal (eAIT), posterior interhemispheric transtentorial subsplenial (PITS), paramedian supracerebellar transtentorial (PST), perimedian supracerebellar (PeS), perimedian contralateral supracerebellar (PeCS), and transuvulotonsillar fissure (TUTF). Clinical and radiological data were gathered according to a standard protocol and reported according to common descriptive statistics. The main outcomes were rate of gross-total resection; extent of resection; occurrence of any complications; variation in Karnofsky Performance Status score at discharge, 3 months, and last follow-up; progression-free survival (PFS); and overall survival (OS).

RESULTS Fifty-four patients (28 of them pediatric) met the inclusion criteria (6 with high-grade and 48 with low-grade gliomas [LGGs]). Twenty-two tumors were in the tegmentum, 7 in the central mesencephalic structures, and 25 in the tectum. In no instance did the glioma originate in the cerebral peduncle. TS was performed in 2 patients, eAIT in 6, PITS in 23, PST in 16, PeS in 4, PeCS in 1, and TUTF in 2 patients. Gross-total resection was achieved in 39 patients (72%). The average extent of resection was 98.0% (median 100%, range 82%–100%). There were no deaths due to surgery. Nine patients experienced transient and 2 patients experienced permanent new neurological deficits. At a mean follow-up of 72 months (median 62, range 3–193 months), 49 of the 54 patients were still alive. All patients with LGGs (48/54) were alive with no decrease in their KPS score, whereas 42 showed improvement compared with their preoperative status.

CONCLUSIONS Microneurosurgical removal of midbrain gliomas is feasible with good surgical results and long-term clinical outcomes, particularly in patients with LGGs. As such, microneurosurgery should be considered as the first therapeutic option. Adequate microsurgical technique and anesthesiological management, along with an accurate preoperative understanding of the tumor’s exact topographic origin and growth pattern, is crucial for a good surgical outcome.

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The influence of tumor topography on the surgical outcome of craniopharyngiomas

J Neurosurg 139:1247–1257, 2023

Various topographical classifications for craniopharyngioma have been proposed based on their relationship with optic chiasm and the third ventricular floor. There is a paucity of literature evaluating the surgical outcome based on tumor topography. This study aims to compare the surgical outcomes of retrochiasmatic craniopharyngiomas (RCPs) and nonretrochiasmatic craniopharyngiomas (non-RCPs).

METHODS This retrospective study includes newly diagnosed patients with craniopharyngioma who underwent surgery between January 2000 and December 2015. Clinical features, the extent of resection (EOR), surgical outcomes, tumor recurrence, and progression-free survival (PFS) of craniopharyngiomas were compared with respect to their relationship to the optic chiasm and third ventricular floor.

RESULTS The authors identified RCPs in 104 and non-RCPs in 33 patients. RCPs were significantly larger and more associated with hydrocephalus than were non-RCPs (p < 0.001) at the time of diagnosis. Puget grade 2 hypothalamic involvement was more frequent with RCPs. EOR and PFS following either subtotal resection (p = 0.07) or gross-total resection (p = 0.7) were comparable between RCPs and non-RCPs. There was no significant difference in the postoperative visual outcome. Resection of RCPs resulted in higher postoperative hypopituitarism (64% vs 42%, p = 0.01) and hypothalamic dysfunction (18% vs 3%, p = 0.02). Location of the tumor, either retrochiasmatic (HR 0.5; 95% CI 0.14–2.2; p = 0.4) or nonretrochiasmatic (HR 1.3; 95% CI 0.3–5.5; p = 0.6), did not show association with recurrence. RCPs with extraand intraventricular components (type 3b) had a higher incidence of postoperative hypothalamic morbidities (p = 0.01) and tumor recurrence (36% vs 19%; p = 0.05) during follow-up than the extraventricular (type 3a) RCP. Between prechiasmatic and infrachiasmatic/intrasellar craniopharyngiomas, EOR (p = 0.7), postoperative diabetes insipidus (p = 0.4), endocrinological outcome (p = 0.7), and recurrence (p = 0.1) were comparable. The patients with complex multicompartmental tumors had a lower rate of gross-total resection (25%, p = 0.02) and a higher incidence of tumor recurrence (75%, p = 0.004) than the rest.

CONCLUSIONS The tumor topography can influence the postoperative outcome. RCPs can be associated with a higher incidence of hypopituitarism and hypothalamic morbidities postoperatively. The influence of topography on EOR and tumor recurrence is controversial. However, this study did not find a significant difference in EOR and tumor recurrence between RCPs and non-RCPs. PFS and overall mortality are also comparable.

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