Background:Glioblastoma (GB) exhibits marked tumor microenvironmental heterogeneity, contributing to both therapy resistance and poor survival outcomes. Intercellular adhesion molecule 1 (ICAM1) is an inflammation-associated adhesion molecule implicated in immune-stromal interactions, but its clinical and biological significance in GB remains incompletely defined. Methods:We performed ICAM1 immunohistochemistry, bulk RNA sequencing, DNA methylation analysis, single-nucleus RNA sequencing, and preoperative MRI-derived morphologic feature analysis across multi-institutional cohorts of treatment-naïve IDH-wildtype GB. Results:High ICAM1 expression at both transcript and protein levels is associated with shorter overall survival, particularly within the mesenchymal transcriptional subtype. ICAM1 expression is inversely associated with promoter methylation. Single-nucleus RNA-sequencing analysis shows that ICAM1-high tumors are enriched for mesenchymal, hypoxia, stress-associated, and immunosuppressive myeloid programs, suggesting that ICAM1 reflects a multicompartment inflammatory tumor ecosystem. ICAM1 expression, tumor surface irregularity, and patient age are independently prognostic and minimally correlated, capturing complementary clinical, imaging, and molecular features of GB biology. When combined, our Clinical-Imaging-Molecular (CIM) framework refines outcome prediction across independent GB cohorts using routinely available clinical data, conventional imaging, and standard immunohistochemistry. Conclusions:ICAM1 characterizes an immune-remodeled, stress-adapted GB ecosystem associated with poor clinical outcomes. Integrating patient age, surface irregularity, and ICAM1 expression yields a scalable and clinically accessible prognostic framework for GB, supporting tailored outcome prediction, particularly in low- and middle-resource settings without routine access to advanced molecular profiling.

Whether speech perception is implemented through a sequential cortical hierarchy or distributed parallel processing remains a central question in systems neuroscience. To determine how auditory inputs with and without linguistic content are represented at fine temporal and spatial scales, we recorded electrocorticography (ECoG) from the language-dominant hemisphere during awake neurosurgery while participants listened to isolated words and duration-matched tones with comparable spectral characteristics. Both stimuli elicited gamma-band (50–110 Hz) responses but differed markedly in their spatial and temporal organization. Early gamma activity originated in the posterior superior temporal gyrus and inferior parietal lobule for both stimulus classes, consistent with shared acoustic-feature processing. In contrast, words engaged a broader cortical network extending anteriorly into superior and middle temporal gyri, sensorimotor cortex, and inferior frontal regions, accompanied by stronger and more sustained gamma activity. Analysis of temporal response dynamics revealed that word processing was supported by two complementary mechanisms. First, cortical sites exhibiting brief onset responses to tones frequently transitioned to sustained response profiles during word processing, demonstrating functional temporal reconfiguration within the shared auditory cortex. Second, numerous cortical sites that were inactive during tone processing became selectively engaged by words, predominantly exhibiting sustained response dynamics within anterior extent of the superior and middle temporal gyri and frontal language regions. Together, these findings indicate that linguistic processing is supported by both adaptive modulation of shared auditory representations and selective recruitment of additional language responsive cortex. These results demonstrate that speech perception emerges from a distributed and temporally adaptive cortical network rather than a strictly serial processing hierarchy. By revealing how temporal reconfiguration and selective cortical recruitment jointly transform acoustic representations into linguistic processing, this work provides a neurophysiological framework that reconciles classical hierarchical and distributed models of human speech perception.

BACKGROUND:Current literature suggestsisocitrate dehydrogenase (IDH)-mutant astrocytoma contains several molecular subgroups. In this study, we are interested in determining the connection between different molecular subgroups with grade and/or survival. METHODS:A cohort of 470 Mayo Clinic adult patients (≥18 years, 56.2% male) with primary IDH-mutant astrocytoma diagnosed by World Health Organization (WHO) 2021 criteria were examined. Results were validated in an independent cohort of 614 Mayo Clinic Neuropathology consult patients and 235 The Cancer Genome Atlas (TCGA) patients. RESULTS:The Mayo Clinic Practice cohort confirmed the association of CDKN2A/B deletion with overall survival (OS, homozygous vs hemizygous vs intact, 2.7 vs 9.6 vs 17.2 years, P < .001). Phosphatase and tensin homolog (PTEN) deletion was also associated with poor OS (7.3 vs 17.4 years, P < .001). Increased number of copy number alterations was associated with OS (continuous variable, HR = 1.027, P < .001). Carrying one or more copies of the germline risk allele at rs55705857 was associated with earlier age of onset (median age 33 vs 35 years, P = .01), and a shorter OS after adjusting for age, grade, sex and treatment (HR = 1.81, P = .007). The Mayo Clinic Neuropathology Consult cohort and TCGA were utilized to validate age of onset and survival, respectively. Unsupervised clustering of the copy number alterations identified several clinically significant groups that may define pathways to disease progression. Losses of chromosomes 11p, 13q, 1p, and 10q were all associated with reduced overall survival in the Mayo Clinic cohort. CONCLUSIONS:Patients with hemizygous loss of CDKN2A/B, loss of PTEN, increased number of copy number alterations, specific chromosomal arm losses or rs55705857 germline risk allele have reduced overall survival.

OBJECTIVE:Maximal safe resection of intra-axial brain tumors near the motor cortex is aided by intraoperative motor mapping. Here, the authors compared outcomes in patients undergoing either low-frequency bipolar stimulation (LFBS) or high-frequency monopolar stimulation (HFMS) for cortical and/or subcortical motor mapping during brain tumor resection. METHODS:A retrospective analysis of patients undergoing an asleep craniotomy with motor mapping or an awake craniotomy with motor and speech mapping with a single surgeon was performed. Three cohorts were compared: 1) asleep LFBS (AsLFBS), 2) awake LFBS (AwLFBS; motor + speech mapping), and 3) asleep HFMS. HFMS mapping was not used for awake craniotomies. RESULTS:A total of 284 patients who underwent 300 craniotomies with motor mapping were identified. No significant differences in permanent neurological deficits (p = 0.377) or extent of resection (EOR) of nonenhancing tumors (p = 0.453) were identified between LFBS or HFMS motor mapping cases. Both EOR (92.7% vs 83.5%, p = 0.035) and permanent neurological deficits (7.6% vs 3.3%) occurred more frequently in enhancing tumors with LFBS, although the latter was not statistically significant. HFMS was associated with higher rates of subcortical motor pathway identification (p = 0.001) and fewer total intraoperative seizures (p = 0.003) compared with LFBS. Previous resection (HR 0.46, p = 0.003) and a higher cortical threshold (HR 0.95, p = 0.023) were significantly associated with longer survival, while preoperative aphasia (HR 2.24, p = 0.022), hospital length of stay (HR 1.1, p = 0.005), an insular-based tumor (HR 3.5, p = 0.021), and a histological diagnosis of glioblastoma (HR 2.9, p = 0.001) were negative predictors. Interestingly, overall FLAIR EOR was significantly associated with a marginally decreased overall survival (HR 1.01, p = 0.011). CONCLUSIONS:No significant differences in postoperative neurological deficits were found between LFBS and HFMS paradigms. HFMS may identify subcortical motor fibers more reliably while resulting in significantly fewer intraoperative seizures. Although LFBS was associated with greater EOR of contrast-enhancing tumors, it may also be associated with higher rates of postoperative deficits, perhaps reflecting less reliable identification of subcortical motor fibers.

BACKGROUND:Immunotherapy has yet to make significant gains in glioblastoma (GBM) treatment, due in part to GBM-mediated immune suppression. Increasing evidence points to critical roles for tumor-derived extracellular vesicles (EVs) and immunosuppressive myeloid cells as key factors in this process. METHODS:Immunophenotyping of the tumor-immune microenvironment was performed using ultrasonic aspirate collected during GBM resection by high-dimensional flow cytometry. EVs collected from patient-derived GBM cell lines were used to condition myeloid cells collected from healthy donors to generate immunosuppressive myeloid cells. siRNA was used to knockdown TIGIT and/or NLRP3 expression prior to EV conditioning. T cell co-culture studies were performed with donor-matched T cells. RESULTS:Immune phenotyping of the tumor microenvironment and EV-conditioned myeloid cells revealed similar immunomodulatory protein expression across myeloid cell populations, with particularly elevated TIGIT expression. Knockdown of TIGIT reduced the immunosuppressive polarization of myeloid cells, resulting in improved T cell function. This finding proceeded in an NLRP3-dependent manner, with substantial co-expression of TIGIT and NLRP3 expression prior to knockdown, and concomitant knockdown of NLRP3 abrogating the effect of TIGIT knockdown. TIGIT expression correlated with increased IL-13 expression, and IL-13 blockade unmasked a pro-inflammatory myeloid cell phenotype. CONCLUSION:TIGIT expression in myeloid cells in the GBM microenvironment is a functional marker of immunosuppressive activity, with TIGIT knockdown reducing IL-13 expression and unmasking the pro-inflammatory activity of NLRP3. This study bolsters our understanding of the immunosuppressive complexities of the GBM microenvironment and supports attenuation of immunosuppressive myeloid cell activity as a strategy to restore immune function in GBM.

Background Isocitrate dehydrogenase (IDH)-mutant gliomas are infiltrative tumors with limited treatment options at recurrence. Early studies suggest IDH inhibition has therapeutic activity. We evaluated clinical outcomes associated with IDH-1 inhibitor ivosidenib in recurrent IDH-1-mutant gliomas and molecular predictors of response.Methods We retrospectively analyzed adults treated with ivosidenib from January 2021 to August 2025 with predominantly recurrent, pretreated CNS WHO grade 2-4 astrocytoma IDH-mutant or grade 2-3 oligodendroglioma, IDH-mutant and 1p/19q codeleted. Prior anticancer treatments, toxicities, enhancement status at ivosidenib initiation, and genomic alterations were collected. The primary endpoint was progression-free survival (PFS); secondary analyses evaluated associations between PFS, genomic complexity, and CDKN2A/B homozygous deletion.Results Ninety-two adults, median age 43, were included: 61 astrocytomas and 31 oligodendrogliomas, mostly grade 2. Before ivosidenib, 69 had surgery, 64 chemotherapy, and 64 radiation. Median time from diagnosis to ivosidenib was 4.8 years, with median of two prior progressions. Median treatment duration was 5.8 months. Median PFS was 15.2, 4.6, and 2.1 months for astrocytoma grades 2-4, 14.0 and 6.9 months for oligodendroglioma grades 2-3. Increasing genomic complexity was associated with shorter PFS in univariate analysis. Patients without CDKN2A/B homozygous deletion had median PFS of 19.2 months. Two patients with homozygous deletion had median PFS of 0.6 months.Conclusions In this retrospective analysis of predominantly recurrent IDH-1-mutant glioma, ivosidenib was associated with longer PFS in lower-grade, non-enhancing tumors that received little or no prior anticancer treatment and less complex genomic profiles. These findings support a context-dependent benefit of IDH inhibition in recurrent disease. Gliomas with mutations in the gene called isocitrate dehydrogenase (IDH) typically occur in younger adults and can be treated with a combination of surgery, radiation therapy, chemotherapy, and with IDH inhibitors such as vorasidenib or ivosidenib. In this study, we evaluated patients with recurrent IDH-mutant gliomas treated with ivosidenib at our institution. Ninety-two patients with IDH-mutant astrocytomas or oligodendrogliomas were studied. Individuals with lower-grade tumors that had less genetic complexity and fewer prior tumor-directed treatment experienced longer progression-free survival with ivosidenib treatment. Treatment was generally well-tolerated. Ivosidenib can be considered as a treatment option for individuals with recurrent IDH-mutant gliomas.

OBJECTIVE:Brain metastases significantly impact neurocognitive function and overall survival. Stereotactic radiosurgery (SRS) is a cornerstone of treatment for patients with limited metastases and expected survival beyond 3 months. Despite current guidelines, up to 20% of patients with brain metastases undergoing SRS have been reported to die within 90 days. This study retrospectively evaluated prognostic factors associated with 90-day survival after SRS, aiming to improve patient selection. METHODS:The authors retrospectively analyzed a cohort of 1546 patients who underwent Gamma Knife SRS for brain metastases at their institution between 2015 and 2023. One hundred seventy patients who survived less than 90 days after SRS were identified and case matched to 170 patients who survived over 90 days. Measured variables included patient demographic characteristics, tumor characteristics, treatment history, functional status, and control of the primary cancer. The authors modeled post-SRS 90-day survival using binomial and multivariate logistic regression. RESULTS:Multivariate analysis highlighted Karnofsky Performance Score (KPS) < 70 (OR 17.4, p < 0.001), prior whole-brain radiation (OR 6, p = 0.004), and focal neurological deficits (OR 3.02, p = 0.003) as significant predictors of poor survival, whereas CNS progression before SRS (OR 0.22, p < 0.001) and control of systemic cancer (OR 0.556, p = 0.002) were associated with survival < 90 days. The predictive model demonstrated acceptable performance with an area under the curve (AUC) of 0.85, accuracy of 80%, sensitivity of 87%, and specificity of 71%. CONCLUSIONS:Key predictors of 90-day survival after SRS for brain metastases include functional status (KPS), control of systemic cancer, CNS progression status, and focal neurological deficits. These findings are complementary factors that can assist in making decisions and SRS patient selection.

BACKGROUND:Disruption of the blood-brain barrier (BBB) in high-grade brain tumors is characterized by contrast accumulation on diagnostic imaging. This window of opportunity study correlates contrast imaging features with the tumor distribution of BBB-permeable (levetiracetam) and -impermeable (cefazolin) drugs. METHODS:Patients with a clinical diagnosis of a high-grade brain tumor underwent MRI for surgical planning. Cefazolin and levetiracetam were administered prior to skin incision, and serial plasma and image-registered tumor samples were collected during the operation. Drug levels were measured by LC-MS/MS, tissue drug levels were corrected for residual blood, and tumor-to-plasma concentration ratios were calculated. Intraoperative microdialysis was performed in a subset of patients to measure the same two drugs. RESULTS:Tumor (n = 125) and plasma (n = 261) samples were available for analysis from 42 operative cases. Across all samples, the tumor-to-plasma ratio was significantly lower for cefazolin (marginal mean [MM]: 0.15, 95% CI: 0.11-0.19) as compared to levetiracetam (MM: 0.70, 95% CI: 0.64-0.75; P < .001). When compared between contrast-enhancing and non-enhancing regions, tumor-to-plasma ratios for cefazolin varied by 4.4-fold (0.27, 95% CI: 0.20-0.35 vs. 0.06, 95% CI: 0.04-0.08, respectively; P < .001), and varied for levetiracetam by 1.4-fold (0.88, 95% CI: 0.78-0.97 vs. 0.61, 95% CI: 0.55-0.66, respectively; P < .001). These results were confirmed with the intra-operative microdialysis and a population pharmacokinetic analysis. CONCLUSIONS:This study demonstrates significant inter- and intra-tumoral heterogeneity in drug delivery for both levetiracetam and cefazolin within high-grade brain tumors that is not necessarily predicted by clinical MR imaging and may reflect tumor-induced changes in both perfusion and BBB integrity.

Glioma diagnosed during pregnancy and pregnancy following glioma treatment present complex management challenges. Safety of glioma treatment during pregnancy is not well established. The ability to counsel patients on timing of conception after treatment remains limited. The aim of this study was to describe our institution’s experience with pregnancy during and/or after treatment for glioma. In this single-institution study, we retrospectively identified patients diagnosed with glioma during or prior to pregnancy and described treatment courses and maternal and neonatal outcomes. Twenty-one female patients were included. Glioma diagnoses included 12 high-grade tumors and 9 low-grade tumors. Cohort A consisted of 8 patients who presented with glioma during pregnancy, of which, 7 underwent glioma treatment during pregnancy. All pregnancies in cohort A were without significant maternal complications and resulted in delivery of a healthy neonate. Cohort B consisted of 13 patients who experienced pregnancy after a prior diagnosis of glioma, totaling 18 pregnancies that resulted in delivery of a neonate. Antepartum course was complicated by seizure in 3/18 pregnancies. Functionally inconsequential anatomic abnormalities in childhood offspring of cohort B occurred in 5/18 pregnancies. Anatomic abnormalities occurred in 4/13 (31

OBJECTIVE:Neurosurgical oncology outcomes are influenced by histological factors not available before surgery, complicating preoperative counseling regarding surgical risks. Anatomically tailored outcome data have demonstrated potential predictive value. This study aims to compare the incidence of supplementary motor area (SMA) syndrome and other postoperative outcomes for tumors in the middle and superior frontal gyri undergoing resection. METHODS:A retrospective single-center cohort study of patients undergoing resection of the middle frontal gyrus (MFG), superior frontal gyrus (SFG), or both (SMFG) from 2008 to 2020. The study followed STROBE guidelines. RESULTS:A total of 124 patients underwent 144 craniotomies. Seizures were the most common preoperative symptom, particularly in patients with MFG tumors, who also had higher rates of preoperative aphasia. Pathology varied significantly (P < 0.05) between groups, with glioblastoma multiforme more prevalent in SMFG tumors and metastases more common in MFG tumors. Supplementary motor area (SMA) syndrome occurred in 43%, more frequently in SFG tumors (47%) compared to MFG (40%) and SMFG (27%), although these differences were not statistically significant. SMA syndrome duration varied significantly (P < 0.05) across groups, with SMFG cases being the most persistent. Early postoperative aphasia was more common (P < 0.001) in MFG cases (55%), but there were no permanent deficits in the MFG group. The SMFG group had more permanent neurological deficits and higher rates of early complications (P < 0.05). Survival was significantly lower in SMFG tumors (P < 0.05) on univariate analysis but not on multivariate analysis. CONCLUSIONS:The study found no significant difference in SMA syndrome frequency by location, although the duration of SMA syndrome was significantly longer in SMFG cases. Postoperative aphasia was more common in MFG tumors but was temporary. Permanent deficits were rare across all regions. These anatomically tailored findings provide valuable information for surgical planning and patient counseling.

Despite advances in therapy and improved survival for patients with primary central nervous system lymphoma (PCNSL), optimal management of suspected recurrent or refractory PCNSL (r/r PCNSL) remains unclear. Repeat brain biopsy is often performed to confirm recurrence, though its diagnostic and therapeutic utility is uncertain. This study evaluates whether repeat biopsy provides new insights that influence treatment. A retrospective analysis was conducted on patients with confirmed PCNSL who underwent repeat biopsy for suspected r/r PCNSL between 2005 and 2023. Patients with other CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. Data analysis used R version 4.4. Twenty patients met the inclusion criteria (55

Glioblastoma (GBM) is a deadly brain cancer with near-universal recurrence despite maximal treatment for which new innovations are sorely needed. Immunotherapy has yet to make significant gains in GBM treatment despite revolutionizing other cancer therapies, due in part to GBM-mediated immune suppression. This immune derangement proceeds through several mechanisms, but increasing evidence points to critical roles for tumor-derived extracellular vesicles (EVs) and immunosuppressive myeloid cells as key factors in this process. In the present study, we demonstrate broad expression of TIGIT across myeloid cell populations in the GBM microenvironment, a finding recapitulated by conditioning healthy monocytes with GBM-derived EVs. Further, knockdown of TIGIT expression reduced the immunosuppressive polarization of monocytes, resulting in improvement in T cell function. This finding proceeded in an NLRP3-dependent manner, with substantial co-localization of TIGIT and NLRP3 expression prior to knockdown. These findings point to a novel role for TIGIT expression in diverse myeloid cells in the GBM microenvironment as a marker of immunosuppressive activity and further indicate a hierarchy of immunomodulatory protein activity in these myeloid cells, with TIGIT knockdown unmasking the pro-inflammatory activity of NLRP3. This study bolsters understanding of the immunosuppressive complexities of myeloid cells in the GBM microenvironment, while lending further support to prevention or attenuation of immunosuppressive myeloid cell activity as a means of restoring immune function in GBM.

INTRODUCTION: Quality Improvement (QI) initiatives have improved patient outcomes and streamlined hospital processes, so the Accreditation Council for Graduate Medical Education requires residents to participate in QI. However, neurosurgeons and residents at our institution reported barriers to commencing QI projects. METHODS: A multidisciplinary team with representatives from all stakeholder groups conducted the project at the Mayo Clinic from Oct 2019-Jan 2024 following Define-Measure-Analyze-Improve-Control QI methodology, Awareness-Desire-Knowledge-Ability-Reinforcement change management framework, and Standards for QI Reporting Excellence guidelines. This initiative did not require institutional review board approval. RESULTS: The team used a charter and a Suppliers-Inputs-Processes-Outputs-Customers+Requirements tool to diagram the baseline process. Electronic databases quantified baseline metrics. An Ishikawa diagram categorized gaps in quality and Failure Modes and Effects Analysis determined that the primary barriers were suboptimal education and mentorship. The team brainstormed solutions during a Kaizen burst and evaluated proposals via an Impact/Effort grid. To improve education, residents attended a day-long QI fundamentals course and passed an examination. The team conducted three Plan-Design-Study-Act cycles to optimize mentorship. The percentage of residents who completed a project increased from 9% to 87%. Twenty-one residents, 11 neurosurgeons, 14 nurses, 9 staff, and 7 APPs participated on projects. Eleven QI projects commenced, nine were completed, eight resulted in practice changes, and two are ongoing. Interventions included a cart to streamline procedures, a reorganization of personnel to increase efficiency, protocols, and electronic medical record tools. Rigorous stakeholder analysis and sequential completion of QI phases was associated with achievement of initial aims and sustained initiatives over time. CONCLUSIONS: Using QI and change management frameworks, a team developed a novel program comprised of education and mentorship for residents to complete QI projects. We recommend that residents receive formal training and coaching from experienced mentors.

Brain metastases significantly impact neurocognitive function and overall survival. Stereotactic radiosurgery (SRS) is a cornerstone of treatment for patients with limited metastases and expected survival beyond three months. Despite current guidelines, up to 20% of patients with brain metastases undergoing SRS have been reported to die within 90 days. This study retrospectively evaluates prognostic factors associated with 90-day survival after SRS, aiming to improve patient selection. We retrospectively analyzed a cohort of 1,546 patients who underwent Gamma Knife SRS for brain metastases at our institution between 2015 and 2023. One hundred seventy patients who survived fewer than 90 days post-SRS were identified and case-matched to 170 patients who survived over 90 days. Measured variables included patient demographics, tumor characteristics, treatment history, functional status, and control of the primary cancer. We modeled post-SRS 90-day survival using binomial and multivariate logistic regression. Multivariate analysis highlighted Karnofsky Performance Status (KPS) < 70 (OR: 17.4, p < 0.001), prior whole brain radiation (OR: 6, p = 0.004), and focal neurological deficits (OR: 3.02, p = 0.003) as significant predictors of early deaths, while CNS progression before SRS (OR: 0.22, p < 0.001) and control of systemic cancer (OR: 0.556, p = 0.002) were associated with a less than 90-day survival. The predictive model demonstrated acceptable performance with an area under the curve (AUC) of 0.85, accuracy of 80%, sensitivity of 87%, and specificity of 71%. Key predictors of 90-day survival following SRS for brain metastases include functional status (KPS), control of systemic cancer, CNS progression status, and focal neurologic deficits. These findings are complementary factors that can assist in making decisions and SRS patient selection.

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, has a median survival of 14-15 months despite aggressive treatment. Monitoring relies on MRI, but differentiating tumor progression from pseudo-progression or radiation necrosis remains difficult. Plasma extracellular vesicles (EVs) are emerging as promising non-invasive biomarkers due to their molecular cargos and accessibility. This review evaluates studies that specifically isolated plasma EVs for molecular profiling in GBM diagnosis and monitoring. Biomarkers (miRNA, RNA, DNA, proteins), EV characterization methods, and advancements in enriching tumor-derived EV subpopulations and assessing their diagnostic and prognostic potential are highlighted. Plasma EVs carry diverse cargos, including miRNAs (e.g., miR-21, miR-15b-3p), mRNAs (e.g., EGFRvIII), circRNAs, and proteins (e.g., CD44, GFAP). Composite molecular signatures have achieved sensitivities of 87-100% and specificities of 73-100% for GBM diagnosis. Tumor-derived EVs, enriched using techniques like SEC-CD44 immunoprecipitation, microfluidic platforms, or 5-ALA-induced PpIX fluorescence, enhance biomarker detection. Non-tumor-derived EVs may also reflect GBM's systemic effects. Challenges include EV heterogeneity, non-EV contamination, and variable biomarker expression across studies. Plasma-EV-based liquid biopsies offer significant potential for GBM monitoring, with advanced enrichment methods improving tumor-specific biomarker detection. Standardizing isolation protocols and validating biomarkers in larger cohorts are critical for clinical translation.

Primary gliomas arising within midline structures of the central nervous system are associated with a worse prognosis compared with hemispheric gliomas. In adults, compared to their pediatric counterparts, adult midline gliomas are not as clearly characterized on the clinical behavior, prognostic factors, and treatment approaches for these diseases. This retrospective cohort assessed all adult (≥ 18 years) patients from our institution with diffuse gliomas arising from midline structures at time of diagnosis (2014–2020). Molecular features characterized using immunohistochemistry, targeted next-generation sequencing, and chromosomal microarray analysis were collected. Patient characteristics were compared across groups using analysis of variance, Kruskal–Wallis, and the chi-square test as appropriate. Cumulative progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan–Meier method. Comparisons across groups were made using the log rank test. 79 patients were included in analysis, with a median follow-up of 22.5 months (range, 0.6–123). The mean age at diagnosis was 44.5 years (range, 19.4–76.4), and 51

While clinical outcomes of glioblastoma (GBM) are well-documented, its socio-economic impact, particularly on return to work (RTW) remains unexplored. In this study we aimed to identify the predictors of RTW at 6 months postoperatively in patients undergoing GBM treatment and to assess its association with post-operative neurological deficits and median overall survival (mOS). We retrospectively studied 106 adults with pre-operative employment, undergoing primary GBM resection or biopsy at three tertiary centers. RTW at 3 and 6 months postoperatively were assessed using univariate and multivariate analyses. After 6 months 33 patients (33.1

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection. Moreover, radiographic features, such as tumor-CSF contact and blood-brain barrier disruption, are critical covariates that may affect biomarker detection and the abundance of plasma-derived analytes in CSF, respectively. Longitudinal intracranial CSF sampling, enabled by access devices like Ommaya reservoirs, may offer a window into treatment response and disease progression, though variability in analyte yield, sample volumes, and the dynamic effects of surgical resection pose challenges. This review critically evaluates the anatomic, radiographic, and longitudinal factors, or "time-space continuum," that impact glioma CSF biomarker abundance. Practical considerations for longitudinal CSF biobanking, including access device placement and collection, are also reviewed. Key takeaways and recommendations for CSF glioma biomarker discovery and validation are provided as a "hitchhiker's guide" based on our collective experience, along with resources for investigators aiming to develop CSF biobanking at their institutions.

Glioblastoma is an aggressive brain tumor characterized by its complex Microenvironment and profound immune suppression. Recent studies have highlighted the involvement of primary cilia in various cellular processes, including the modulation of the tumor microenvironment. In this study, we aimed to investigate the role of primary cilia-derived extracellular vesicles (EVs) in promoting myeloid-derived suppressor cell (MDSC) induction and its subsequent impact on T cell proliferation in glioblastoma. We established an in vivo glioblastoma model by implanting glioblastoma cells with knockdown of primary cilium components and control cells into the brains of immunocompetent mice. We analyzed the brain tissue to assess the levels of MDSCs and T cells within the tumor microenvironment. Our results showed that primary cilia knockdown significantly reduced MDSC infiltration in the tumor, while concomitantly increasing T cell proliferation and activity.These findings suggest that primary cilium-derived extracellular vesicles contribute to the immunosuppressive microenvironment of glioblastoma by promoting MDSC expansion, which inhibits T cell proliferation. Targeting primary cilia signaling may represent a novel therapeutic strategy to enhance anti-tumor immunity in glioblastoma by reducing immune suppression.