Predicting isocitrate dehydrogenase (IDH) mutations in gliomas using magnetic resonance imaging (MRI) is clinically important for treatment planning. This study compared two artificial intelligence (AI) models, GliomaDepth-IDH (ResNet34-based) and GliomaVista-IDH (Vision Transformer-based), with 18 physicians (eight neuroradiologists, five neurosurgeons, and five neurosurgery residents) in predicting IDH mutation status. On the Brain Tumor Segmentation Challenge dataset, the GliomaVista-IDH AI model achieved an area under the curve (AUC) value of 0.97, significantly outperforming all physician groups. However, external validation on a Japanese cohort revealed performance degradation: GliomaDepth-IDH declined to an AUC of 0.75 and GliomaVista-IDH to 0.82, with GliomaVista-IDH showing significant calibration issues (Brier score = 0.32). High-performing physicians achieved comparable results (AUC = 0.88) with superior calibration (Brier score = 0.19). Inter-rater reliability analysis revealed substantial variability across physician groups. These findings suggest that AI models can assist many physicians, while experienced practitioners remain competitive with better-calibrated predictions in challenging domains.

Long-term functional independence after shunt surgery for idiopathic normal pressure hydrocephalus varies widely, particularly in older patients with multiple comorbidities. We aimed to develop and prospectively validate a frailty-integrated prognostic prediction tool to support patient selection and preoperative decision-making. A retrospective cohort of 82 patients with idiopathic normal pressure hydrocephalus who underwent shunt surgery between 2005 and 2014 was used to develop a weighted idiopathic normal pressure hydrocephalus-specific frailty index based on multivariable logistic regression. The index incorporated neurological and non-neurological comorbidities, including dementia, cancer, depression, and movement disorders. The weighted idiopathic normal pressure hydrocephalus-specific frailty index was combined with preoperative modified Rankin Scale scores to estimate the probability of achieving functional independence (modified Rankin Scale ≤2) at 1, 2, and mid- to long-term follow-up (up to 4 years). Prospective validation was performed in an independent cohort of 30 patients treated between 2018 and 2023. The weighted idiopathic normal pressure hydrocephalus-specific frailty index demonstrated improved predictive performance, particularly for mid- to long-term outcomes (2-4 years), compared with conventional frailty indices, with higher correlation coefficients and lower Akaike Information Criterion values. Predicted probabilities of long-term independence declined stepwise with increasing frailty burden. In the validation cohort, predicted and observed outcomes showed good agreement, with adequate calibration confirmed by the Hosmer-Lemeshow test. This frailty-integrated prognostic prediction tool provides individualized estimates of long-term postoperative independence, particularly in the context of frailty and comorbidity burden. By incorporating comorbidity burden into preoperative assessment, the tool supports patient selection and shared decision-making and may facilitate realistic counseling and long-term care planning in older patients.

Background:Preoperative survival prediction in newly diagnosed glioblastoma (nGBM) remains challenging due to limited robustness and standardization across radiomic approaches. We aimed to validate a machine learning-based prognostic model using preoperative MR images and assess its generalizability. Methods:Two independent cohorts were analyzed: the Kansai Molecular Diagnosis Network for CNS Tumors (KNBTG) and The Cancer Genome Atlas (TCGA). All cases with available preoperative MR images (T1WI, T2WI, and Gd-T1WI) were included. The KNBTG cohort was divided into a training dataset (TD, n = 137) and an internal test dataset (ITD, n = 141), while the TCGA cohort served as the external test dataset (ETD, n = 105). A total of 489 texture features were extracted. Overall survival (OS) was dichotomized at the median, and predictive modeling was performed using least absolute shrinkage and selection operator regularization. The trained model was validated on ITD and ETD. Results:Radiomic high-risk status was associated with significantly shorter OS in both ITD and ETD (log-rank P < .05) and remained independently prognostic in multivariate Cox analysis. Time-dependent area under the receiver operating characteristic curves was consistently higher in models incorporating radiomic-based risk. Of the 13 selected features, "T2_core_GLCMhomogeniety_3_SD" was the only consistent predictor across cohorts and showed strong prognostic stratification, particularly between low- and high-risk groups (cutoff range: 0.0145-0.0180). Conclusions:Radiomics-based modeling provides reproducible prognostic value in nGBM. The feature "T2_core_GLCMhomogeniety_3_SD" may serve as a reliable imaging biomarker for preoperative risk stratification and individualized treatment planning.

Background:The aim of this study was to identify and validate clinically meaningful predictors of local treatment failure (LTF) after stereotactic radiotherapy (SRT) for brain metastases by integrating machine learning (ML)-based feature selection with generalized linear mixed-effects modeling (GLMM). Method:The retrospective study included 211 brain metastases from 63 patients treated with SRT. Each lesion was investigated independently, considering the within-patient clustering. Random forest classifiers were trained using a 3-fold cross-validation repeated 100 times to assess predictive performance and feature importance. The predictors included age, lesion length, biological effective dose (BED), sex, post-SRT systemic therapy, Karnofsky Performance Status (KPS), type of primary tumor, and lesion location. Features with high importance were further evaluated using GLMM to determine statistical significance. Receiver operating characteristic (ROC) analysis was performed to determine optimal thresholds and diagnostic accuracy. Results:The median duration of follow-up was 232 days, and 31 lesions (14.7%) developed LTF following SRT. The ML model achieved a mean area under the ROC curve (AUC) of 0.88 and an accuracy of 0.84. Variable importance rankings identified age, primary tumor, BED, length, and KPS. The GLMM confirmed associations of lower BED (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.80-0.98; P = .023) and greater lesion length (OR = 1.16, 95% CI = 1.08-1.24; P < .001) with LTF. The ROC analysis identified BED ≤60.0 Gy (AUC = 0.72; sensitivity = 0.81; specificity = 0.71) and lesion length ≥19.3 mm (AUC = 0.78; sensitivity = 0.58; specificity = 0.88) as thresholds. Conclusion:Lesion length was the most robust predictor of LTF after SRT, with a length ≥19.3 mm indicating increased risk.

Neuroinflammation driven by activated glial cells contribute to neuronal death in a spectrum of neurodegenerative disorders. However, the precise mechanisms underlying activated astrocytes promote neuronal death in a neuroinflammatory microenvironment remain unclear. In this study, we investigated whether interferon (IFN)gamma-activated human astrocytes induce pyroptosis, an inflammatory form of programmed cell death, in human neuroblastoma cells. Human astrocytoma U-251MG cells and adult human astrocytes isolated from surgical brain tissues were treated with IFN-gamma. The astrocyte-conditioned medium (ACM) was then transferred to SH-SY5Y cell cultures. Significant SH-SY5Y cell death was observed when incubated in the ACM of IFN-gamma-activated U-251MG, as characterized by reduced cell viability in the MTT and LDH assays, condensed nuclei stained with ethidium homodimer-1, and DNA fragmentation. Immunoblot analysis revealed significant increases in the expression levels of pro-caspase-1, cleaved caspase-1, cleaved caspase-3, gasdermin D (GSDMD), the N-terminal fragment of GSDMD, and the N-terminal fragment of gasdermin E (GSDME) in SH-SY5Y cells incubated in the ACM of either IFN-gamma-activated U-251MG or adult human astrocytes compared to those in non-stimulated control ACM. These findings demonstrate that IFN-gamma-activated adult human astrocytes induce pyroptosis in SH-SY5Y cells through the cleavage of caspase-1, caspase-3, GSDMD, and GSDME, highlighting astrocytic activation as a potent driver of neuronal pyroptosis in neurodegeneration.

Glioblastoma is an aggressive primary brain tumor that invariably recurs despite maximal resection and chemoradiotherapy. Understanding the spatial and directional dynamics of recurrence is crucial for informing treatment strategies, yet prior studies have relied mainly on qualitative classification schemes. We conducted a quantitative analysis of glioblastoma recurrence patterns using a two-pronged approach: voxel-based lesion mapping and vector analysis. Lesion distribution shifts between initial and recurrent tumors were statistically evaluated using anatomical labeling based on the AAL atlas. For directionality, we computed vectors from initial to recurrent lesion centroids and assessed their alignment with normative white matter fiber orientations derived from the Human Connectome Project. Lesion mapping revealed a significant posterior shift of distribution in recurrence, particularly involving the parietal lobe. Vector analysis demonstrated that the recurrence vectors exhibited significant directional concordance with local white matter trajectories, as indicated by high mean absolute correlation coefficients (0.60 ± 0.23). These findings suggest that white matter pathways may guide tumor cell migration during recurrence. This study introduces a novel quantitative framework for assessing the spatial and directional features of glioblastoma recurrence. Our integrative analysis highlights the influence of structural brain connectivity on tumor spread and may ultimately contribute to refining initial treatment planning strategies.

BACKGROUND:T2- and FLAIR-weighted MRI are standard modalities for visualizing brain parenchyma in neurosurgical practice but often fail to adequately depict critical structures such as sulci, ventricles, and vessels. We aimed to address this limitation by applying maximal intensity projection (MIP) and minimal intensity projection (MinIP) techniques to conventional T2-weighted MRI (T2-MIP and T2-MinIP, respectively) to improve anatomical understanding. METHODS:We retrospectively reviewed patients with gliomas imaged between 2023 and 2024 who underwent three-dimensional T2-weighted imaging (T2WI) together with angiographic studies, including CT angiography (CTA) or 3-tesla time-of-flight (TOF) MRI. MIP and MinIP reconstructions with projection thickness of 2-10 mm were applied to enhance visualization of cerebrospinal fluid (CSF)-filled structures and parenchymal vascular flow voids. Visualization was qualitatively compared with conventional T2WI and angiographic images, and the number of lenticulostriate arteries (LSAs) was quantified. RESULTS:In all glioma cases, T2-MIP highlighted CSF-filled structures while preserving visualization of the surrounding brain parenchyma, facilitating recognition of sulcal and ventricular anatomy. T2-MinIP enhanced visualization and spatial localization of vascular structures embedded within the brain parenchyma, including perforating arteries, corresponding to CTA and DSA findings. The mean numbers of LSAs visualized by TOF, conventional T2WI, CTA, and T2-MinIP were 4.9, 0.9, 3.5, and 2.4, respectively; LSA counts were significantly higher on T2-MinIP than on conventional T2WI (P = 0.0032). CONCLUSIONS:Applying MIP and MinIP to conventional T2WI enables simultaneous visualization of CSF-filled and vascular structures without obscuring brain parenchyma. T2-MinIP facilitates anatomical localization of vessels embedded within the brain parenchyma, which is particularly relevant in glioma surgery. This simple post-processing approach may enhance anatomical interpretation and preoperative planning in neurosurgical practice.

2001 Background: Three randomized phase III trials evaluated carmustine wafers (CWs) before temozolomide (TMZ) became standard therapy. To date, no randomized study has assessed CWs with standard TMZ chemoradiotherapy in newly diagnosed glioblastoma (GB). A post hoc analysis of Westphal’s phase III trial, which evaluated CWs versus placebo, suggested a survival benefit with CWs in GB patients with ≥90% resection. We conducted a randomized phase III trial to determine whether adding CWs to standard chemoradiotherapy improves overall survival (OS) in newly diagnosed GB with ≥ 90% resection. Methods: This multicenter trial (38 institutions; JCOG1703) enrolled patients with newly diagnosed GB considered resectable at ≥90%. After intraoperative pathological confirmation of malignant glioma and ≥90% removal, patients were randomized (1:1) to CW implantation (Arm B) or no implantation (Arm A). Arm B received intraoperative placement of up to 8 CWs. All patients received 60 Gy radiotherapy with concomitant daily TMZ followed by 12 cycles of maintenance TMZ. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), loco-regional PFS (LPFS), and adverse events. DNA methylation array analysis and molecular testing included MGMT promoter methylation and copy number profiling. Results: Among 234 registered patients, 221 (Arm A, n=110; Arm B, n=111) were randomized between June 2019 and November 2022. Baseline characteristics were well balanced. Median OS for all randomized patients was 26.5 months (1-year 86.4%, 2-year 54.3%, 5-year 16.6%), with no significant difference between Arm A and B (21.7 vs 27.7 months; hazard ratios (HR) 0.907, 91.5% confidence interval (CI) 0.691–1.192; one-sided p=0.269 by the stratified log-rank test). Median PFS was 9.8 months (1-year 43.4%, 2-year 16.3%), also without significant difference (9.5 vs 10.4 months; HR 0.867, 95% CI 0.658–1.141). Median LPFS was 11.6 months (1-year 48.4%, 2-year 25.1%), with no difference between arms (10.6 vs 12.7 months; HR 0.886, 95% CI 0.669–1.173). MGMT promoter methylation was a significant favorable factor for OS, PFS, and LPFS. Early postoperative complications and adverse events were comparable between groups, and no treatment-related deaths occurred. Conclusions: CW implantation added to standard TMZ chemoradiotherapy did not significantly improve OS in newly diagnosed GB after ≥90% resection. Based on these findings, CW implantation does not provide significant therapeutic or survival benefit when standard TMZ chemoradiotherapy is feasible in this population. Clinical trial information: jRCT1031190035.

In the era of advanced three-dimensional imaging technologies, cerebral angiography remains a fundamental modality for understanding dynamic cerebral hemodynamics. Although computed tomography angiography (CTA), magnetic resonance angiography (MRA), and 3D reconstruction techniques have markedly improved anatomical visualization, the ability to interpret two-dimensional angiographic images and mentally reconstruct vascular structures is increasingly important. This article revisits the core principles of diagnostic cerebral angiography, with an emphasis on practical insights that are often under-recognized in routine training. Key topics include preprocedural risk assessment, evaluation of vascular access route, radiation safety, optimal imaging angles for aneurysms visualization and mechanical thrombectomy planning, assessment of dural arteriovenous fistulas, and dynamic assessment of collateral circulation. By reorganizing these fundamental concepts, we highlight practical "Kandokoro" that bridge basic angiographic technique with therapeutic decision-making. This review aims to support the development of clinical judgment and angiographic interpretation skills in the era of advanced 3D imaging.

Advances in systemic therapy for cancer are expected to influence post-surgical outcomes in patients with brain metastases. This study aimed to assess the prognostic impact of multimodal treatment strategies following brain metastasis surgery by analyzing an original recent cohort. We retrospectively analyzed patients who underwent initial surgery for brain metastases at single center between April 2017 and March 2025. Of 122 cases, 106 were included after excluding emergent hematoma evacuation, biopsy, cyst fenestration, dural metastases, and preoperative radiotherapy. Kaplan-Meier method and log-rank tests were used for survival analysis, including overall survival (OS), local progression-free survival (LPFS), and time to leptomeningeal metastasis (LM). The median age was 65 years (range: 27 to 88). The most common primary site was non-small cell lung cancer (n = 30). At analysis, 55 patients had died. Median OS was 19. 4 months, LPFS was 9. 0 months, and LM occurred in 32 patients. Poor prognostic factors included infratentorial lesions, Karnofsky Performance Status (KPS) under 70, and uncontrolled extracranial disease. Non-gross total resection and absence of postoperative chemotherapy were also associated with worse prognosis. Cavity-directed radiotherapy reduced local recurrence but did not improve OS, LPFS, or delay LM. In contrast, postoperative systemic therapy significantly improved OS, LPFS, and delayed LM onset. Among 52 cases with known causes of death, systemic progression accounted for 28, LM for 17, uncontrolled brain metastasis for 6. While postoperative radiotherapy contributes to local control, it does not prolong survival or prevent LM. Postoperative systemic therapy plays a critical role in improving not only survival but also reducing LM incidence. These findings highlight the growing importance of systemic therapy in the multidisciplinary management of brain metastases.

Management of intracranial epidural abscess (ICEA) typically requires a combination of surgical drainage and antibiotic therapy. However, the indications for neurosurgical drainage of ICEA have not been well established by evidence-based data and remain controversial. This article describes a case of ICEA that enlarged during antibiotic therapy but was managed successfully without neurosurgical drainage. A 13-year-old boy was admitted to the authors' hospital with a 6-day history of high fever, fatigue, and headache. Computed tomography and magnetic resonance imaging (MRI) revealed an ICEA in the right middle fossa with right-sided sinusitis. Initial empiric intravenous antibiotic therapy resulted in rapid improvement in clinical course. Despite clinical improvement, the abscess progressively enlarged by 158% after 2 weeks. Based on the patient's symptoms, age, and location of the lesion and considering the invasive surgical risks, neurosurgical drainage was not performed. Subsequently, the abscess began to decrease in size, and the patient was discharged after 5 weeks of hospitalization. Follow-up MRI at 6 months confirmed complete resolution of the abscess. Despite abscess enlargement, conservative management might be feasible when the patient demonstrates symptomatic improvement; thus, a tailored approach combining close monitoring with serial imaging is recommended. https://thejns.org/doi/10.3171/CASE24702.

The exoscope, proposed by Gildenberg et al. in 1994, was developed as a new surgical assistive technology that differed from conventional microscopic surgeries. However, no significant progress has been made in this regard over the past decade. In 2008, a high-definition exoscope (HDXO-SCOPE) system developed by Mamelak et al. achieved a focal length of approximately 200 mm with an accuracy comparable to that of an operating microscope. This camera, commercialized as VITOM® (Karl Storz) was smaller than an operating microscope but had a wider field of view. Furthermore, the VITOM® was later adapted to three-dimensional imaging, providing an experience similar to microsurgery. The ORBEYE® (Olympus), on the other hand, was developed as an alternative to the operating microscope and provided a three-dimensional field of view with a focal length of 220 to 550 mm. The most significant advantage of the exoscope is the increased freedom of surgical positioning. Conventional microscopes restrict the surgical approach and surgeons' physical position when conducting surgery, which can be problematic. On the other hand, the exoscope reduces burden on the arms and body and allows for more precise surgery. The exoscope is especially useful in surgeries of posterior cranial fossa, and surgeries on elderly patients. The use of an exoscope also allows greater flexibility when conducting surgery of midbrain lesions. In general, exoscopes are good alternatives to microscopes for brain tumor surgery; however, the current technology should be further improved. Exoscopes are expected to ultimately surpass surgical microscopes in the future leading to their adoption in an increasing number of surgeries.

Background:11C-methionine positron emission tomography is one of the most reliable imaging modalities for -glioblastoma visualization. This investigation aimed to generate an 11C-methionine positron emission tomography-like image, "Gliomap," from contrast-enhanced magnetic resonance imaging via a conditional Generative Adversarial Network (Gliomap-GAN). Methods:Eighty-one newly diagnosed glioblastoma patients with preoperative contrast-enhanced magnetic resonance imaging and 11C-methionine positron emission tomography were retrospectively collected. T1-weighted, T2-weighted, and Gd-enhanced T1-weighted images were co-registered and intensity normalized, followed by the creation of a contrast-enhancement subtraction map. They were used as source data to train Gliomap-GAN, targeting the corresponding 11C-methionine positron emission tomography image. The training dataset comprised 2459 images augmented to 4918 pairs by mirroring. The test dataset consisted of 593 pairs. Furthermore, an additional five patients with 16 image-guided sampled tissues were used for histological validation of the generated Gliomap. Results:Gliomaps visually resembled the original 11C-methionine positron emission tomography images. The residual error between Gliomaps and the original images from test datasets was 0.07 ± 0.04 (mean ± SD) in tumor-to-normal tissue ratio. The Sørensen-Dice coefficient between the lesions predicted by Gliomap and 11C-methionine positron emission tomography reached 0.88 ± 0.07 (mean ± SD) at a threshold of tumor-to-normal tissue ratio of 1.5. The absolute values of Gliomap showed a significant positive correlation with tumor cell density (P = .02). Conclusion:The present research demonstrates that the Gliomap, generated from contrast-enhanced magnetic resonance imaging using generative artificial intelligence, is a promising imaging surrogate for visualizing tumor cell density in newly diagnosed glioblastoma.

Astrocytoma, isocitrate dehydrogenase (IDH)-mutant, is one of the intraparenchymal brain tumors, strictly defined by its molecular characteristics. This tumor type is typically found in the frontal, insular, and temporal lobes. Patients harboring this type of tumor benefit the most from aggressive tumor removal compared to other low-grade appearing gliomas. Thus, accurate preoperative diagnosis is crucial in providing these patients with the most efficient and effective treatment strategy. This case study presents a 40-year-old male with an IDH-mutant astrocytoma in the subcallosal gyrus, an unusual location. The diagnosis was aided by the presence of the "T2-FLAIR (fluid-attenuated inversion recovery) mismatch sign," a key radiological feature of IDH-mutant astrocytomas, accompanied by magnetic resonance (MR) relaxometry that allows quantitative tissue characterization. This case highlights the importance of combining qualitative imaging features, such as the T2-FLAIR mismatch sign, with quantitative data, such as MR relaxometry, for accurate diagnosis, especially in cases with unusual tumor locations.

Diffuse intrinsic pontine glioma (DIPG) is a very challenging-to-treat pediatric malignant tumor, with a median survival time less than 12 months. Convection-enhanced delivery (CED) allows for direct drug administration into the tumor site, showing potential as a novel therapeutic approach. Recently, we reported the result of our study that evaluated the efficacy of CED of nimustine hydrochloride (ACNU) in children with DIPG (Saito R, et al. Cancer Sci 2025; jRCT2021190003). This phase 2, single-arm, multicenter study enrolled patients aged 3–21 years and diagnosed with DIPG. As a result, the 1-year survival rate from the start of radiotherapy was 60%, and the median survival time was 15 months. The response rate analyzed in 20 patients resulted in a response rate of 35% (CR+PR). In this study, we compared the results with Japanese historical controls as well as international registries. Reported median overall survival in Japanese historical control was 11 months, and in two international registries were 11.2 months and 11 months. In addition, in this study, we examined the previously reported prognostic factors for brainstem gliomas including symptomatic period before diagnosis, presence of cranial nerve palsy, infiltration outside the pons, and enhancement on MRI. There was no obvious bias in this study group in terms of prognostic factors, confirming that although this is a single-arm study, the groups are sufficiently comparable to the historical control data. Therefore, we concluded that the CED of ACNU in the brainstem of children with DIPG after radiotherapy appears to be an effective therapeutic strategy.