Background: While the endoscopic endonasal approach has revolutionized pituitary surgery, postoperative complications contribute to significant morbidity. Tobacco smoking is a well-established risk factor for poor wound healing and adverse outcomes in other skull base procedures, yet its direct influence following transsphenoidal resection is largely unaddressed. This study seeks to define the association between smoking history and adverse outcomes in this population. Methods: This is a retrospective cohort study utilizing the TriNetX global federated research network (2011–2024) to identify adults undergoing primary endoscopic transsphenoidal resection for benign pituitary tumors. Patients were stratified by tobacco use or nicotine dependence. To control for confounding, cohorts were matched via 1:1 propensity score matching (PSM). A panel of outcomes, defined by the PitCOP Delphi consensus, was analyzed. Time-to-event analysis for reoperation was performed, and survival distributions were compared between cohorts. Results: The study population included 11,376 patients: 3,597 smokers and 7,779 non-smokers. Following PSM, 3,219 well-balanced pairs were established. In the matched cohorts, smoking was associated with significantly higher odds of postoperative cerebrospinal fluid leak (OR 1.30; p=0.006), 30-day hospital readmission (OR 1.33; p<.001), and new postoperative hypopituitarism (OR 1.23; p=.0086). Rates of infection and in-hospital mortality were similar. The time-to-event analysis for reoperation showed a higher cumulative incidence in the smoking cohort at 2-year follow-up; however, this difference in survival distributions was not significant after PSM. Conclusions: This large, population-based study suggests that smoking may be associated with adverse outcomes following endoscopic pituitary surgery. Our findings indicate a significant correlation between tobacco use and a triad of major complications: impaired healing of CSF leak repairs, increased morbidity requiring early hospital readmission, and a risk of new-onset hypopituitarism. This evidence reinforces the importance of smoking as a critical, modifiable risk factor and warrants greater emphasis on cessation during preoperative counseling and patient optimization.

BACKGROUND:Glioblastoma (GBM) is a lethal brain tumor with limited treatment options, largely due to profound immune suppression within the tumor microenvironment (TME), the failure of current immunotherapies to restore CD8+ T cell function, and persistence of glioma stem cells (GSCs) after treatment. Oncolytic Zika virus (ZIKV) is a promising therapeutic that selectively targets GSCs and remodels the TME to enhance anti-tumor CD8+ T cell responses. In this study we investigated how ZIKV efficacy in GBM is driven through monocytes. METHODS:We performed single-cell RNA sequencing and T cell receptor (TCR) sequencing to evaluate CD8+ T cell responses following ZIKV treatment. We used CellChat to define signaling networks between ZIKV-activated CCR2+ monocytes and CD8+ T cells in the TME. We used syngeneic, immunocompetent murine GBM models to validate mechanisms in vivo, applying genetic and antibody-based approaches to impair CCR2+ monocyte trafficking and function. RESULTS:ZIKV-induced clonal expansion of tumor-infiltrating CD8+ T cells enriched in granzyme B and perforin-1, with reduced expression of exhaustion markers. CCR2+ monocytes were essential for the recruitment, proliferation, and effector functions of anti-tumor CD8+ T cells in the TME. Disruption of monocyte trafficking or function impaired these responses, diminishing cytotoxic activity and T cell recruitment. CONCLUSIONS:ZIKV-driven activation and recruitment of CCR2+ monocytes supports robust anti-tumor CD8+ T cell responses by enhancing cytotoxicity and limiting exhaustion. These findings highlight the previously unappreciated therapeutic potential of modulating monocyte-T cell crosstalk to overcome immune suppression in GBM.

BACKGROUND AND OBJECTIVES:Intraventricular hemorrhage (IVH) occurs in 30% to 50% of intracerebral hemorrhage (ICH) cases and frequently requires permanent cerebrospinal fluid (CSF) shunting. This study aims to identify factors associated with permanent CSF shunt and its related outcomes. METHODS:A retrospective analysis of prospectively collected data from the Ethnic/Racial Variations of Intracerebral Hemorrhage study was conducted. Factors associated with permanent CSF shunting were assessed using univariable and bidirectional stepwise logistic regression models. Patients were dichotomized based on permanent CSF shunting and propensity score-matched 1:1. The primary outcome was 3-month mortality. Secondary outcomes included in-hospital mortality; 3-, 6-, and 12-month modified Rankin Scale; EuroQoL Group 5-dimension self-report questionnaire; and Barthel Index. RESULTS:Among 2995 patients with ICH (median age 61 years, IQR 51-73), 141 (4.7%) underwent permanent CSF shunting. Factors independently associated with permanent shunting included younger age (odds ratio [OR] = 0.96 [0.95-0.98]), previous antiplatelet (OR = 1.61 [1.08-2.42]) or anticoagulant use (OR = 2.41 [1.28-4.53]), lower admission Glasgow Coma Scale (OR = 0.90 [0.86-0.94]), thalamic hemorrhage (OR = 1.59 [1.06-2.39]), and concomitant IVH (OR = 5.64 [3.38-9.39]). After 1:1 propensity matching (n = 124 per group), 3-month mortality was lower in the permanent CSF shunt group (OR = 0.32 [0.17-0.59]). Ambulatory independence and Barthel Index scores were significantly worse at 3 and 6 months after shunt placement. The odds of incontinence at 3 months were higher among this group (OR = 3.30 [1.58-6.87]). By 12 months, functional outcomes were comparable between groups. CONCLUSION:Younger age, antiplatelet or anticoagulant use, lower admission Glasgow Coma Scale, thalamic hemorrhage, and concomitant IVH are independently associated with shunt dependency in patients with ICH. Permanent CSF shunting was associated with a 60% reduction in 3-month mortality. Although early functional outcomes were worse among shunted patients, overall functional status was comparable by 12 months. Permanent CSF shunting may offer survival benefits, highlighting the need to determine the optimal timing for placement and rehabilitation programs following the procedure.

Genetic, epigenetic, and transcriptomic analyses have stratified medulloblastoma (MB) into four canonical subgroups of Wingless Type (WNT), Sonic Hedgehog (SHH), and Group 3 and Group 4, with distinct patient profiles and prognoses. Recent classification strategies have also considered combining Group 3 and Group 4 tumors into a Non-WNT/Non-SHH subgroup to account for biological overlap and heterogeneity. Using high-dimensional gene expression data from 487 pediatric and young adult patients and over twenty-one thousand transcripts, this study explores which genes can improve prognostic accuracy for survival while accounting for molecular stratification, histological subtype, key oncogenic drivers (MYC and MYCN amplification), and established clinical covariates, including age group (< 3 vs. 3–21 years) and metastatic status. We then develop a multi-stage framework for identifying prognostic genes and evaluating modern survival modeling strategies. In the first stage, gene screening was performed using Benjamini–Hochberg adjusted Cox regression across false discovery rate (FDR) thresholds from 1

OBJECTIVE:The aim of this study was to develop and validate a machine learning (ML) algorithm to predict the delayed need for syrinx shunt placement following posterior fossa decompression (PFD) for Chiari malformation type I (CM-I) with concurrent syringomyelia. METHODS:This multicenter retrospective cohort study utilized the TriNetX network to identify patients undergoing index PFD for CM-I and syringomyelia (2010-2020) with at least 2 years of continuous follow-up. The primary outcome was unplanned syringosubarachnoid, syringopleural, or syringoperitoneal shunt placement. Five supervised ML classifiers were trained on 30 preoperative clinical and demographic variables using the Synthetic Minority Over-Sampling Technique to address class imbalance. RESULTS:Of 3112 patients (62.3% female, median age 28.4 years) with a median follow-up of 5.1 years, 271 (8.7%) experienced refractory syringomyelia requiring a shunt. The CatBoost classifier achieved the highest discriminative performance on the independent validation set, yielding an area under the curve of 0.87, accuracy of 83%, sensitivity of 0.78, and specificity of 0.82. Shapley Additive Explanations analysis identified adolescent idiopathic scoliosis, prolonged symptom duration, age > 40 years, and preoperative opioid dependency as the strongest predictors of delayed shunt placement. Notably, partial dependence analysis revealed that every 1-month delay in surgical intervention increased the absolute probability of shunting by approximately 0.8%-1.0%. CONCLUSIONS:The CatBoost ML algorithm accurately predicted the delayed need for syrinx shunting after PFD. The prominent risk associated with concomitant scoliotic deformity and surgical delay provides actionable intelligence, strongly supporting early operative intervention and guiding highly individualized long-term postoperative surveillance.

Purpose High-grade gliomas are among the most treatment-resistant cancers, with few therapies improving survival despite hundreds of clinical trials. The biostatistical parameters used to design these trials are critical but uncharacterized in aggregate. Currently, no data-driven benchmarks exist to inform these parameters, including the target effect size. This study therefore aimed to analyze trends in their use across neuro-oncology trials. Methods We systematically searched PubMed for publications of phase 2 and 3 high-grade glioma or medulloblastoma trials comparing two or more arms with a time-to-event primary endpoint. Key biostatistical parameters were extracted from each study, including trial phase, endpoints, effect size, control arm survival assumptions, Type I error, power, sample size, and accrual time. Results We analyzed 210 trials published between 1976 and 2025, evaluating 254 primary time-to-event endpoints (overall, OS, or progression-free survival or similar). Survival assumptions and target effect sizes (ie, hazard ratios, HRs) used for trial powering varied substantially. Assumed control arm OS was often lower than observed OS, and the application of type I error rates did not consistently reflect the stated hypothesis directionality. Trials with planned sample sizes below 500 and lower HR targets were less likely to meet accrual goals. Trials generally aimed to complete accrual by 36 months with a median follow up of 24 months. Conclusion This study provides historical benchmarks for sample size assumptions to support more transparent, data-driven, and context-aware trial design. They may also serve as a resource for feasibility planning, protocol development, and statistical justification in future trials.

BACKGROUND:While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps. METHODS:We compiled and harmonized raw transcriptomic and clinical data for neoplastic (n = 5,402) and nonneoplastic (n = 1,973) nervous system samples from publicly available sources, all profiled on the same microarray platform. After adjusting for surrogate variable effects ("batch effects"), machine learning methods were used to visualize, cluster, and reclassify samples with uncertain diagnoses (n = 2,225). RESULTS:We generated the largest clinically annotated transcriptomic atlas of nervous system tumors to date. Sample clustering was primarily driven by diagnosis. We show the utility of the atlas by refining the transcriptional subtypes of pheochromocytoma and paraganglioma (PH/PG), revealing 6 robust subtypes (Neuronal, Vascular, Metabolic, Steroidal, Developmental, Indeterminate), which were independently validated using TCGA RNA-seq data and that correlated with specific mutational signatures and clinical behaviors of these tumors. CONCLUSIONS:Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas' broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH/PG analyses. For access, visit http://kdph.shinyapps.io/atlas/ or https://github.com/axitamm/BrainTumorAtlas.

Intraventricular hemorrhage (IVH) occurs in 30-50% of patients with intracerebral hemorrhage (ICH) and may be associated with acute hydrocephalus. A subset of patients require external ventricular drainage of cerebrospinal fluid (CSF) and subsequent permanent shunting. Prospectively collected data from the Ethnic/Racial Variations of Intracerebral Hemorrhage study was analyzed. Predictors of permanent CSF shunting were assessed using univariable and stepwise backward logistic regression models. Patients were dichotomized based on permanent CSF shunting and then propensity score matched in a 1:1 ratio. Outcomes of interest were mortality at discharge, modified Rankin Scale (mRS), EuroQoL Group 5-Dimension self-report questionnaire (EQ-5D), and Barthel Index scores at 3, 6, and 12 months. 2995 ICH patients were included. Median age at presentation was 61 years (IQR 51-73). A permanent CSF shunt was placed in 141 patients (4.7%). Independent predictors of permanent shunting were past ICH (OR=3.81 [1.14-12.75], antiplatelet medication before ICH (OR=2.31 [1.13-4.74]), lower GCS at admission (OR=0.84 [0.78-0.91]), thalamic location (OR=2.06 [1.03-4.12]), and concomitant IVH (OR=7.15 [2.84-17.97]). Overall discharge mortality was 11.1%, with a comparable risk between groups (OR=0.87 [0.49-1.53]). Patients with a permanent CSF shunt were more likely to have worse mRS, EQ-5D, and Barthel Index scores at 3, 6, and 12 months. Matched cohorts comprised 138 patients each. Mortality at discharge was significantly lower for those undergoing permanent shunting (OR=0.40 [0.20-0.80]), and like the unmatched cohorts, their EQ-5D and Barthel Index scores were significantly worse. Past ICH, use of antiplatelets, low GCS at admission, thalamic location, and concomitant IVH significantly predict shunt dependency among ICH patients. The significantly increased morbidity among ICH survivors requiring permanent CSF shunting highlights the need to improve current treatments and recognize all the components involved in acute ICH inpatient care.

Meningiomas, the most prevalent tumors of the central nervous system, can have overlapping histopathological features with solitary fibrous tumors (SFT), presenting a significant diagnostic challenge. Accurate differentiation between these two diagnoses is crucial for optimal medical management. Currently, immunohistochemistry and molecular techniques are the methods of choice for distinguishing between them; however, these techniques are expensive and not universally available. In this article, we propose a rotational and scale-invariant deep learning framework to enable accurate discrimination between these two tumor types. The proposed framework employs a novel architecture of conical transformers to capture both global and local imaging markers from whole-slide images, accommodating variations across different magnification scales. A weighted majority voting schema is utilized to combine individual scale decisions, ultimately producing a complementary and more accurate diagnostic outcome. A dataset comprising 92 patients (46 with meningioma and 46 with SFT) was used for evaluation. The experimental results demonstrate robust performance across different validation methods. In train-test evaluation, the model achieved 92.27% accuracy, 87.77% sensitivity, 97.55% specificity, and 92.46% F1-score. Performance further improved in 4-fold cross-validation, achieving 94.68% accuracy, 96.05% sensitivity, 93.11% specificity, and 95.07% F1-score. These findings highlight the potential of AI-based diagnostic approaches for precise differentiation between meningioma and SFT, paving the way for innovative diagnostic tools in pathology.

Intraoperative rupture (IOR) is the most common adverse event encountered during surgical clip obliteration of ruptured intracranial aneurysms. Besides increasing surgeon experience and early proximal control, no methods exist to decrease IOR risk. Thus, our objective was to assess if partial endovascular coil embolization to protect the aneurysm before clipping decreases IOR. We conducted a retrospective analysis of patients with ruptured intracranial aneurysms that were treated with surgical clipping at two tertiary academic centers. We compared patient characteristics and outcomes of those who underwent partial endovascular coil embolization to protect the aneurysm before clipping to those who did not. The primary outcome was IOR. Secondary outcomes were inpatient mortality and discharge destination. We analyzed 100 patients. Partial endovascular aneurysm protection was performed in 27 patients. Age, sex, subarachnoid hemorrhage severity, and aneurysm location were similar between the partially-embolized and non-embolized groups. The median size of the partially-embolized aneurysms was larger (7.0 mm [interquartile range 5.95–8.7] vs. 4.6 mm [3.3–6.0]; P < 0.001). During surgical clipping, IOR occurred less frequently in the partially-embolized aneurysms than non-embolized aneurysms (2/27, 7.4

Rigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons grade) on the outcome most used in pivotal stroke randomized controlled trials (modified Rankin Scale) and, consequently, on the sample size. Furthermore, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of the World Federation of Neurological Surgeons grades in addition to showing their effects on the sample size. Finally, we offer methods that investigators can adapt to more precisely understand the effect of common modified Rankin Scale analysis methods and trial eligibility pertaining to the World Federation of Neurological Surgeons grade in designing their large-scale SAH randomized controlled trials.

Integration of Vision Transformer models with texture analysis presents a novel dual-stage approach for histopathology diagnosis. The proposed approach is mainly focused on discriminating between Meningioma (MEN) and Solitary Fibrous Tumor (SFT), two tumors known for their similar morphological characteristics. This approach leverages the inherent power of ViT models to capture global and local features from whole-slide images (WSIs), complementing this capability by integrating texture analysis techniques aimed at improving classification accuracy. Initially, ViT models are applied across three levels of WSI magnification, using rotationally and multi-scaled tiles to handle diverse scales and orientations inherent in histopathological imagery. ViT’s attention mechanisms capture intricate details and spatial correlations within WSIs, offering a comprehensive view of histological structures. Concurrently, texture analysis methods including 3D-CLBP, 3D-GLCM, and 3D-GLRLM are used to extract the inherent patterns of the WSIs, such as homogeneity/inhomogeneity, morphology, and connectivity alongside the three RGB channels to capture the influence of color features. The scores obtained at the output of both stages are then fused and passed to a deep neural network, enabling a more reliable diagnosis. The experimental results show an accuracy of 93.42

Abstract Adult IDH-wildtype glioblastoma (GBM) is an aggressive brain tumor with no established immunotherapy. Glioblastoma tumors that contact the ventricular-subventricular zone (V-SVZ) stem cell niche have especially poor clinical outcomes (PMC5771712, PMC5262526) and abnormal immune microenvironments filled with CD32+ HLA-DRhi macrophages that have displaced resident microglia (PMC10371245). Identifying the origin and role of these CD32+ macrophages is likely critical to developing successful GBM immunotherapies. Here, we present a mechanistic origin for these CD32+ cells as M_IL-8 macrophages. In ex vivo experiments with conditioned medium from primary human tumor cells, IL-8 was sufficient and necessary for tumor cells to instruct healthy macrophages, and inhibitory antibodies to IL-8 blocked the generation of CD32+ CD163+ M_IL-8 cells. Additionally, IL-8 protein was present in GBM tumor cells in vivo and especially common in tumors contacting the V-SVZ (p<0.0001, N=192 cores from 73 patients). Surface proteins CXCR1 and CXCR2, the primary receptors for IL-8, were detected on cells that were spatially separated from IL-8+ glioblastoma cells in tumors contacting the V-SVZ. These results suggest the hypothesis that glioblastoma-cell IL-8 instructs incoming CXCR1+ hematopoietic macrophages to adopt a suppressive M_IL-8 identity in V-SVZ-contacting GBM. Abundant HLA-DR (MHC II) observed on the CD32+ M_IL-8 cells closely matched the signature phenotype of cells in human tumors (PMC10371245) and contrasted with lower surface MHC II expression typically observed on human myeloid derived suppressor cells (PMC6608074). M_IL-8 cells might especially target CD4+ helper T cells required for effective cancer immunotherapy (PMC5312823). IL-8 and CD32+ macrophages should now be explored as targets in combination with GBM immunotherapies, especially for patients whose tumors present with radiographic contact with the V-SVZ stem cell niche. Some results here have been shared in a bioRxiv preprint by the these authors (PMC10996638).

Background: There is considerable debate regarding the efficacy of preoperative embolization in decreasing operative estimated blood loss (EBL) during resection.

Meningioma (MEN) and Solitary Fibrous Tumor (SFT) pose challenges in diagnosis due to their similar histological characteristics. Common diagnostic methods like immunohistochemistry (IHC) have drawbacks in terms of time, cost, and accessibility. This paper introduces a new approach using Vision Transformer (ViT) on whole-slide images (WSI) for MEN and SFT classification, addressing these challenges. The proposed model employs a rotational and scale invariance approach with a ViT architecture, capturing global and local features at various optical scales in WSIs. To comprehensively an-alyze, pre-trained ViT models (ViT B/16, B/32, L/16, L/32) were applied to different WSI magnification levels. Diagnosis was determined by combining WSI scales using a weighted majority voting scheme. Evaluation on a 92-patient cohort (46 MEN, 46 SFT) showed ViT L/16 model’s robust performance with 90.45% accuracy, 93.03% sensitivity, 87.94% specificity, 88.21% precision, 90.48% balanced accuracy, 90.62% ROC, and 90.56% F1-score. These results affirm the effectiveness of the proposed model, promising innovative tools in histopathology diagnostics.

Background: The usage rates of mineralocorticoids (fludrocortisone) to treat hyponatremia and isotonic crys-talloids (saline and balanced crystalloids) to maintain intravascular volume in patients with aneurysmal sub-arachnoid hemorrhage (aSAH) patients across the United States are unknown.Methods: We surveyed National Institute of Neurologic Disorders and Stroke (NINDS) StrokeNet sites in 2023, which are mostly large, tertiary, academic centers, and analyzed subarachnoid hemorrhage encounters from 2010 to 2020 in the Premier Healthcare Database that is representative of all types of hospitals and captures about 20 % of all acute inpatient care in the United States.Results: Although mineralocorticoids are used by 70 % of the NINDS StrokeNet sites, it is used in less than 20 % of the aSAH encounters in the Premier Database. Although saline is ubiquitously used, balanced crystalloids are increasingly used for fluid therapy in aSAH patients. Its use in the NINDS StrokeNet sites and the Premier Healthcare Database is 41 and 45 %, respectively.Conclusions: The use of mineralocorticoids remains low, and balanced crystalloids are increasingly used as fluid therapy in aSAH patients. The effectiveness of mineralocorticoids and balanced crystalloids in improving out-comes for aSAH patients must be rigorously tested in randomized clinical trials.