Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.

Background: While developing a differentiation therapy for Sonic Hedgehog Medulloblastoma (MB), we discovered a potential paradoxical feedback cycle between Ezh2, a protein that temporarily keeps differentiation genes silenced via trimethylating H3K27, and Cyclin D1, a protein that regulates cell cycle entry. Methods: We quantified H3K27me3 in P7 purified cerebral GNPs using chromatin immunoprecipitation sequencing and correlated it with gene expression via RNA sequencing (RNAseq). To assess transcriptional effects of Ezh2 loss, we purified P7 GNPs from Math1-Cre, Ezh2-flox knockout mice. MB cells were cultured in suspension spheres and imaged using the ImageXpress Micro XLS system, with nuclei segmented based on DAPI staining. Results: Cyclin D1 ranked among the top 7.37% of expressed genes but was heavily marked by the repressive histone mark H3K27me3 (top 5.5%) in GNPs. Ezh2 overexpression increased G0-arrested MB cells 2.7-fold, while, in GNPs, RNAseq showed significant Cyclin D1 upregulation in Ezh2 knockout mice (Log2FC: 1.301). Cyclin D1 regulates the pRb/E2F1 complex, and we observe that Ezh2 expression depends on pRb/E2F1 complex abundance, forming a feedback loop. Notably, combining the Hedgehog inhibitor Vismodegib with an Ezh2 inhibitor rescued MB cells from Vismodegib-induced death. Conclusions: Our study introduces a model that promotes GNP differentiation, leading tumor cells to differentiate into neurons.

Background: Dermoid cysts are rare benign intracranial lesions arising from abnormal neuroectodermal folding during embryogenesis. While typically midline, near the sella or posterior fossa, we report an unusual case of a convexity dermoid cyst extending into the sylvian fissure. Methods: A 33-year-old female with a left convexity mass underwent resection, confirming a dermoid cyst. A literature review was also conducted. Results: The patient presented with progressive, intermittent right-sided hand and face paresthesias. CT showed a 4.3 × 4.7 cm hypodense lesion with peripheral calcification contiguous with the calvarium. MRI revealed an extra-axial, T2-hyperintense, T1-hypointense lesion with internal septations extending from the calvarium into the sylvian fissure. Craniotomy achieved gross total resection, revealing a soft lesion with interwoven hair, suggestive of a dermoid cyst. Pathology confirmed a cystic lesion with mature squamous epithelium, keratin, skin appendages, and chronic inflammation. Conclusions: Dermoid cysts are rare intracranial lesions that most commonly occur in the midline. This case highlights a rare convexity dermoid cyst, expanding our understanding of its atypical locations.

Background: Postoperative visual deterioration following endoscopic endonasal surgery for pituitary adenoma is very rare yet significant morbidity. Visual deficit can arise from iatrogenic injury, compression or ischemic insults. The specific predictors of visual decline and their correlation with the effectiveness of various interventions remain poorly understood. Methods: We retrospectively reviewed data from790 patients who underwent endoscopic endonasal surgery for pituitary adenoma between 2014-2024. We included all the patients who had New Postoperative visual deterioration. Demographic, preoperative, intraoperative, postoperative data were collected and analyzed. Results: Nine patients (1.13%) experienced early postoperative visual deterioration. None of the patient has intraoperative report of direct injury to the optic apparatus, ischemic etiology was seen in five patients. Four patients underwent early reoperation to explore and decompress the optic apparatus. Vision was restored to baseline after reoperation in all 4 compressive cases. In the ischemic group (n=5), three patients improved with supplemental oxygen and hypervolemic-hypertensive therapy (p=0.03). Conclusions: Prognosis and outcome of Postoperative visual deterioration depends on the underlying cause and the effectiveness of intervention. Compressive etiology has a favorable prognosis when identified and managed with reoperation and decompression. Ischemic etiology potentially treatable with supplemental oxygen hypervolemic-hypertensive and high mean arterial pressure in more than half of cases.

Background: Giant olfactory groove meningiomas (OGMs), though rare, pose challenges due to their size. These slow-growing tumors often remain asymptomatic until exceeding 6 cm in diameter. While surgery has advanced, understanding long-term outcomes remains crucial. Methods: This retrospective study at a major medical center included all patients with giant OGMs (>6 cm) undergoing resection from 2000-2022.Data on visual status, recurrence, and functional status were collected. Multivariable logistic regression identified predictors of recurrence and functional outcome. Results: Thirty-two patients met the inclusion criteria for this study, with a mean age of 55.8years.The mean follow-up period was 62months. The majority of giant OGMs were classified as WHO grade 1(84.4%).Postoperatively, 19patients demonstrated improvement in visual acuity and visual field deficits.Radiological recurrence was observed in nine patients(28.1%) at a mean follow-up of 56months, with only three requiring reoperations for tumor resection.One patient developed a brain abscess, necessitating reoperation.Multivariable analysis identified patient age, Simpson grade of excision, and WHO grade as significant predictors of recurrence rate. Conclusions: This study demonstrates that surgery can improve visual deficits and functional outcomes. Postoperative outcomes were strongly predicted by age, resection extent, and histological grade. Developing a new predictive scale based on these parameters appears to strongly predict the Giant OGMs Long-Term outcome.

Background: Patients with severe traumatic brain injury (TBI) are at uniquely high risk of venous thromboembolism (VTE), but the benefits of VTE prophylaxis must be weighed against the risk of intracranial hemorrhage expansion. Current guidelines are heterogenous in their recommendations for chemical VTE prophylaxis (cVTEp) in this high-risk cohort. We conducted a systematic review to identify the optimal timing of cVTEp in severe TBI patients. Methods: We executed a systematic search of the literature to identify adult severe TBI patients treated with cVTEp. Results were pooled, analyzed using random-effects models, and presented as Forest plots and odds ratios. Results: We included 21 studies representing 322,735 patients. The odds of VTE were 0.47 (95% CI: 0.37,0.60) when using the authors’ own criteria for early initiation, and the odds of VTE remained significantly decreased in subgroup analysis (<24h, <48 and <72h). Early VTEp both as defined by authors and in subgroup analysis did not significantly impact the odds of hemorrhage progression or mortality; except for initiation <48h which showed a positive impact on mortality (OR: 0.74, 95% CI: 0.63-0.87). Conclusions: This study supports early initiation of cVTEp in reducing the odds of VTE events without significantly increasing the risk of adverse events.

Background: Diffusion tensor imaging (DTI) tractography enables detailed visualization of white matter tracts (WMT) relevant to surgical planning. Head-to-head performance of clinically available DTI software has not been assessed. We retrospectively compared Synaptive’s Modus Plan™(vers. 2.0.1.1743) and Medtronic’s StealthViz™(vers. 1.4) software, focusing on workflow, usability, stability, and capacity to generate WMT reconstructions. Methods: Retrospective evaluation of patients (n=13) with intrinsic brain lesions (01/2021-12/2023) with MP and SV software. Corticospinal and optic radiation WMT reconstruction was attempted according to the manufacturers specifications and was rated as clinically useful or not, based on anatomic plausibility. Duration of each analysis step (image importing, post-processing, segmentation, fine-tuning and tract export) was recorded. Ease of use, degree of clinician input, program stability, and tract output type were also assessed. Results: 13 patients (31±;19 yrs; 6F) were included. Mean workflow duration was significantly longer for MP (22:51 min) versus SV (7:35 min) (p<0.0001). Successful WMT reconstruction occurred in 9/13 (69.2%) with MP, versus 5/13 (38.5%) for SV. MP was rated to have superior usability, stability and required less clinician input but technical parameters (e.g. FA) or export object type was inflexible. Conclusions: Synaptive’s MP permitted more robust WMT reconstruction with enhanced usability and stability but with significantly longer workflow.

Background: Routine early postoperative CT (EPCT) in neurologically intact patients is unsupported but still common. Recent studies suggest 135 scans are needed to detect one clinically silent abnormality (Blumrich, 2021). This study assessed the rate and utility of EPCT, defined as a CT head scan within 24 hours of adult craniotomy. Methods: Retrospective review of adult craniotomy cases at the University of Alberta Hospital was conducted over a 10-month period. Data on EPCT rates, timing, adverse findings (complication or unfavourable outcome, e.g., bleeding, extensive pneumocephalus, edema, ischemia), as well as clinical data on neurologic deterioration (e.g., weakness, aphasia, visual impairment, decreased LOC), and repeat surgical interventions were extracted. Results: Of 405 patients (200 female, 54.6 ± 0.8 years, range: 19-89), 96.5% (391/405) underwent EPCT. Adverse EPCTs occurred in 9.2% (36/391), with neurologic deterioration in 7.7% (30/391) and repeat surgery in 2.8% (11/391). Adverse scans and neurologic deterioration were strongly correlated (X2=141.1, p=1.54e-32). Only 0.5% (2/405) of EPCT findings prompting surgery lacked prior neurologic deterioration. Conclusions: EPCT in the absence of neurologic deterioration has a low yield for surgical intervention and may be safely omitted.

Background: Hemifacial spasm (HFS) is a disorder of unilateral facial myoclonus that can be psychosocially debilitating. It is generally caused by microvascular compression of the facial nerve and is amenable to potentially curative surgery. Unfortunately, many patients receive delayed surgical referrals and are instead managed with injections of botulinum toxin to varying benefit. The reason behind late referrals is unclear, but one factor may be misleading diagnostic information; specifically, MRI reports that indicate incorrect or absent neurovascular conflict. The goal of this study was to explore the association between MRI reports and operative findings in HFS patients, with the hopes of identifying opportunities for improved diagnosis and treatment. Methods: We performed a single-center, retrospective chart review of 30 consecutive patients who underwent surgery for HFS between January 2019 and January 2020. Descriptive data were extracted from pre-operative MRI reports and operative notes, then coded for statistical analysis. Results: Pre-operative MRIs were reported by radiologists from 6 provinces. Across all MRIs (n = 45), a positive finding was only identified in 51.1%. All 30 patients had clear neurovascular conflict noted in surgery. Conclusions: There is a need for improved diagnostic accuracy in HFS, with the goal of expediting surgical referrals and possible cure.

Background: This retrospective cohort study investigates radiographic factors linked to the success of Endoscopic Third Ventriculostomy (ETV) for hydrocephalus. Methods: We examined 48 patients who underwent ETV between August 2011 and March 2023. Radiographic factors analyzed included the basal skull angle, modified basal skull angle, interpeduncular cistern diameter, prepontine diameter, and approach angle to the third ventricle floor. Statistical analysis was performed using R studio. Results: The cohort had a median age of 41 years, with 22 females. Pathologies included aqueductal stenosis (21 cases), tectal tumors (7), and IVH (5). The mean ETV Success Score (ETVSS) was 76.7. Of the 21 failures, 16 required a shunt. A strong correlation was found between ETVSS and procedure success (p<0.001). Modified basal skull angle (p=0.028), interpeduncular cistern diameter (p<0.001), and approach angle (p<0.001) were all associated with ETV success. Decision tree analysis showed that the inclusion of approach angle to ETVSS improved sensitivity and specificity, reaching 1.0 for both. Conclusions: In conclusion, the study highlights that radiographic factors, particularly the modified basal skull angle, interpeduncular cistern diameter, and approach angle, are key predictors of ETV success. This information can assist neurosurgeons in planning cases more effectively.

Background: Canadian neurosurgery residency programs have an alarming 28.4% attrition rate—seven times higher than the average for most other specialties (1–4%) and double that of US neurosurgery programs. Canadian data for this issue is over 30 years old, highlighting the need for updated research. This study identifies factors contributing to Canadian neurosurgery attrition rates. Methods: Using critical constructivist theory, virtual interviews were conducted with current program directors (PDs) from Canada’s 14 neurosurgery programs and neurosurgery residents who left training between 2013–2023. Interviews were recorded, transcribed, anonymized, and iteratively coded through descriptive thematic analysis to construct an analytical framework. Results: We conducted interviews with 7 PDs and 7 former neurosurgery residents, representing 7 neurosurgery programs across Canada. The average attrition rate was 14.11% (0%–28.6%) from 2013–2023. Contributing factors include poor job prospects in Canada, resource constraints leading to high workloads, poor work-life balance, moral distress due to high levels of patient mortality, and a lack of teaching and support from staff and senior residents. Conclusions: Neurosurgery residents are the future of neurosurgery. Our study uncovers factors contributing to high attrition rates in neurosurgery training, indicating that change must come from provincial governments and within training programs to retain residents.

Background: Neurosurgery is a long and arduous training program, and the demands of neurosurgical training have led to resident burnout prevalence ranging from 11-67%, attrition, and suicide. We aimed to assess whether implementation of a weekly self-assessment tool with optional psychological counselling improves neurosurgical resident quality of life. Methods: We performed a one year prospective cohort study including 14 Calgary (intervention group) and 12 Toronto/Winnipeg residents (control group). Calgary residents utilized a mobile application (“HONE”) weekly, and all residents responded to questionnaires at baseline, midpoint and endpoint: EQ-5D-5L, Maslach Burnout Inventory (MBI), and Mayo Clinic Well-being Index (WBI). Between and within group results were compared using two-tailed t-tests. Results: Pooled baseline scores were comparable to population norms, with increased mean MBI depersonalization scores (10.28 versus 7.12, p=0.033), and more WBI “at risk” scores compared to normative data. There were no baseline differences between cohorts. EQ-5D-5L, MBI, and WBI scores were comparable between and within cohorts at all three time points. Three intervention group residents accessed psychological counselling, totalling ten sessions. Conclusions: Weekly use of the HONE application did not impact resident quality of life, although multiple residents displayed help-seeking behaviours. HONE provided tangible data for the program director to track trends in team well-being.

Background: Traumatic brain injury (TBI) patients exhibit variable post-injury recovery trajectories. Days at Home (DAH) is a patient-centered measure that captures healthcare transitions and offers a more nuanced understanding of recovery. Here, we use DAH to characterize longterm recovery trajectories for moderate to severe TBI (msTBI) survivors. Methods: This multicenter retrospective cohort study utilized population health data from Ontario to identify adults sustaining isolated msTBI hospitalized between 2009-2021. DAH were calculated in distinct 30-day intervals from index admission to 3 years post-injury; latent class mixed modeling identified unique recovery trajectories and trajectory attributes were quantified. Results: There were 2,510 patients eligible for latent class analysis. Four DAH trajectories were identified: early recovery (69.9%), intermediate recovery (11.4%), late recovery (2.9%), and poor recovery (15.8%). Patients in the poor recovery group were older, more frail, and had lower admission GCS scores, while those in early recovery exhibited lower acute care needs. Intermediate and late recovery groups exhibited protracted transitions home, with near-complete reintegration by 24 months. A prediction model distinguished unfavorable trajectories with good accuracy (C-index=0.824). Conclusions: Despite high initial institutional care requirements, 85% of patients reintegrated into the community within three years of msTBI. These findings shed light on post-injury care requirements for brain-injured patients.

Background: Artificial intelligence (AI) holds promise to predict outcomes for patients sustaining moderate to severe traumatic brain injury (msTBI). This systematic review sought to identify studies utilizing AI-based methods to predict mortality and functional outcomes after msTBI, where prognostic uncertainty is highest. Methods: The APPRAISE-AI quantitative evidence appraisal tool was used to evaluate methodological quality of included studies by determining overall scores and domain-specific scores. We constructed a multivariable linear regression model using study sample size, country of data collection, publication year and journal impact factor to quantify associations with overall APPRAISE-AI scores. Results: We identified 38 studies comprising 591,234 patients with msTBI. Median APPRAISE-AI score was 45.5 (/100 points), corresponding to moderate study quality. There were 13 low-quality studies (34%) and only 5 high-quality studies (13%). Weakest domains were methodological conduct, robustness of results and reproducibility. Multivariable linear regression highlighted that higher journal impact factor, larger sample size, more recent publication year and use of data that were collected in a high-income country were associated with higher APPRAISE-AI overall scores. Conclusions: We identified several study weaknesses of existing AI-based prediction models for msTBI; this work highlights methodological domains that require quality improvement to ultimately ensure safety and effiicacy of clinical AI models.

Background: Treatment of aneurysmal subarachnoid hemorrhage (aSAH) in a high-volume center by experienced cerebrovascular and neuroendovascular surgeons improves outcomes. We studied whether rural aSAH patients experience treatment delays in British Columbia. Methods: Vancouver Ruptured Aneurysm Database (VRAD) started in 2023 to prospectively capture consecutive aSAH patients at Vancouver General Hospital (VGH), an academic neurosurgical hospital with comprehensive stroke center capabilities. We included patients ≥18 years-old, presenting ≤72h post-ictus and excluded untreated aneurysms and patients not residing in British Columbia. Patients were classified as rural or urban using the provincial government categorization of rurality. Results: We included 84 patients, 65.5% urban and 34.5% rural, with mean age 57.7 years (SD: 15.6) and 64.3% female. Aneurysm treatment consisted of 75% microsurgical clipping and 25% endovascular techniques. Median time from ictus to VGH was 5.9h [IQR: 2.6-16.6] urban and 13.2h [IQR: 8.3-27.8] rural, p=0.001. Median transfer time was 4.7h [IQR: 2.5-8.8] urban and 11.9h [IQR: 6.7-13.5] rural, p=0.006. Ictus to treatment time was 5.9h longer for rural patients, p=0.077. Conclusions: Rural aSAH patients in British Columbia take 7.3 hours longer to reach a neurosurgical center capable of comprehensive aneurysm treatment compared to urban patients. Improved inter-hospital transfer systems may reduce geographic disparities for aSAH in British Columbia.

Background: Advancements in AVM surgical techniques for cerebral arteriovenous malformation (AVM) underscore its efficacy. Our research aims to showcase the positive outcomes of treating low-grade AVMs surgically, focusing on safety and effectiveness. Methods: We retrospectively reviewed 55 patients with Spetzler-Martin (S-M) grade 1 and 2 AVMs who underwent surgical resection between January 2009 and December 2024. Results: In our study, 55 patients with S-M grade 1 and 2 AVMs underwent surgical resection, evenly divided between grades 1 (50.9%) and 2 (49.1%). Intracranial hemorrhage was the primary symptom in 74.5% of cases. Pre-operative Glasgow coma scale (GCS) scores revealed 69.1% of patients scored above 13, with 18% below 8. Successful resection was achieved in 87.3%. Postoperatively, 95.5% of ruptured and 90.9% of unruptured AVM patients showed lower or same modified Rankin scale scores. Poorer outcomes were significantly linked to lower GCS scores and intranidal/flow-related aneurysms. Conclusions: Our findings indicate surgical resection as a beneficial treatment for low-grade AVMs, yielding high cure rates and positive functional outcomes in both ruptured and unruptured cases. Preoperative GCS scores and the presence of associated aneurysms are predictive of postoperative functional status. Additionally, managing postoperative seizures effectively is key to enhancing prognosis

Background: This study aimed to describe the technical characteristics and clinical efficacy of intracranial-to-intracranial (IC-IC) bypass for the treatment of complex intracranial aneurysms. Methods: We retrospectively reviewed all patients with aneurysms who underwent a preplanned combination of surgical or endovascular treatment and IC-IC bypass at our institution between January 2006 and September 2023. IC-IC bypass techniques included four strategies: type A (end-to-end reanastomosis), type B (end-to-side reimplantation), type C (in situ side-to-side anastomosis), and type D (IC-IC bypass with a graft vessel). Results: We performed the type A strategy on five patients (50.0%), type B on one (10.0%), type C on one (10.0%), and type D on three (30.0%). During a mean period of 68.3 months, good clinical outcomes (modified Rankin Scale score, 0-2) were observed in all patients. Follow-up angiography demonstrated complete aneurysmal obliteration in all patients and good bypass patency in nine of ten patients (90.0%). Conclusions: The treatment of complex aneurysms remains a challenge with conventional surgical or endovascular treatments. IC-IC bypass surgery is a useful technique, associated with favorable clinical outcomes, for treating complex aneurysms.

Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

Background: Use of neurosurgical data for research and machine learning model development is often constrained by privacy regulations, small sample sizes, and resource-intensive data preprocessing. We explored the feasibility of using the large language model (LLM) GPT-4o to generate synthetic neurosurgical data. Methods: A plain-language prompt instructed GPT-4o to generate synthetic data based on univariate and bivariate statistical properties of 12 perioperative parameters from a real-world open-access neurosurgical dataset (n = 139). The prompt was input over independent trials to generate 10 datasets matching the reference size (n = 139), followed by an additional dataset representing a ten-fold amplification (n = 1390). Fidelity was assessed using t-tests, two-sample proportion tests, Jensen-Shannon divergence, two-sample Kolmogorov-Smirnov, and Pearson’s product-moment correlation. Results: Generated data preserved distributional characteristics and relationships between desired parameters. In all generations, at least 11/12 (91.67%) parameters showed no statistically significant differences in means and proportions from real data, including the amplified dataset. Five of the synthetic datasets showed no significant differences in all 12 parameters. Conclusions: The findings demonstrate that a zero-shot prompting approach can generate synthetic neurosurgical data and amplify sample sizes with consistent high fidelity compared to real-world data. This underscores LLMs’ potential in addressing data availability challenges for neurosurgical research.

Background: Aplasia Cutis Congenita is a rare congenital abnormality characterized by varying absence of skin and mesodermal tissues. Management remains controversial, with significant inconsistency across specialties and over time. This review evaluates trends in management based on journal specialty and publication epoch. Methods: A review of pediatric scalp Aplasia Cutis Congenita management was conducted. Articles were categorized by journal type (neurosurgery, plastic surgery, dermatology, other medical, and other surgical) and management approach (surgical, conservative, or combined). Descriptive statistics were used to summarize trends in recommendations, and assess associations between journal type and treatment. Trends over time were analyzed based on publication year. Results: A total of 171 studies were included. Among surgical journals, 33.7% recommended surgical management, while medical journals favored conservative (14.1%) or combined approaches (84.5%) (p < 0.001). Recommendations for surgical management decreased from 80% in the 1970s to 30% in the 2020s. Notably, among 119 studies advocating for a combined approach, only 27 provided criteria for surgical indications, with lesion thresholds ranging from >1cm to >15 cm. Conclusions: This study highlights the lack of guidelines for ACC management and reveals specialty and time epoch of publication-dependent biases in treatment. These findings emphasize the need for multidisciplinary guidelines for consistent, patient-centered care.