Background: High-grade gliomas (HGG) present challenges with short post-surgery survival and high progression rates. Extracellular vesicles (EVs) in the tumor microenvironment (TME) contribute to a pro-tumorigenic setting. Investigating Transfer RNA fragments (TfRNA) in HGG patient plasma EVs reveals potential biomarkers and therapeutic targets, shedding light on the molecular landscape for enhanced diagnostic and therapeutic strategies. This study examines TfRNA in 10 HGG patients at diagnosis, offering insights into the molecular landscape for improved management strategies. Methods: The study involved the collection of plasma samples from HGG patients and controls. EVs were isolated from these samples and subsequently analyzed for tfRNA. Results: Analysis of plasma EVs highlighted distinct differences in TfRNA fragments between High-Grade Glioma (HGG) and control samples. HGG EVs showed a global reduction in tRNA content, higher 5’ tfRNA proportions, and increased nuclear tfrna compared to controls. A notable biological marker, elevated in HGG, holds potential as a diagnostic indicator. Conclusions: Our study concludes that High-Grade Gliomas (HGG) demonstrate a global reduction in tfRNA content in plasma extracellular vesicles compared to non-cancer controls, echoing findings in other cancers. Despite this, specific tfRNA molecules in HGG show significant differential expression or sorting into EVs, indicating their potential as future biomarkers or therapeutic targets.

Background: High grade gliomas (HGGs) and cells of the tumour microenvironment secrete extracellular vesicles (EVs) into the plasma that contain genetic and protein cargo which function in paracrine signalling. Isolation of these EVs and their cargo could lead to an important tool that can inform on diagnosis and disease-course of HGGs. Methods: EVs were isolated using Vn96 capture from plasma obtained longitudinally from HGG patients. sRNA was enriched from the EVs, followed by next-generation sequencing, multidimensional scaling, differential expression, and in silico functional enrichment analyses. Results: Over 750 differentially expressed sRNA were identified between HGG and controls. Pathway analysis revealed miRNA highly enriched in both EV and HGG pathways demonstrating the validity of results in capturing a signal from HGG. Other sRNA included several novel HGG plasma-EV biomarkers including lncRNA RPPH1, RNY4, and RNY5. Furthermore, in paired longitudinal patient sampling, RPPH1 informed on surgical resection (decreased on resection) and importantly increased again with clinically defined progression. TCGA analysis demonstrated increased expression of RPPH1 in HGG tissue and additionally, higher expression of RPPH1 was associated with a worse disease-specific prognosis. Conclusions: The present study supports the role of plasma-EV sRNA sampling (and particularly RPPH1) as part of a multi-pronged approach to HGG disease course surveillance.

Background: Gliomas are highly aggressive brain tumors with nearly universal recurrence rate. Despite this, the ability to accurately predict tumor recurrence relies solely on serial MRI imaging, highlighting the need for prognostic biomarkers. Due to the low accuracies of individual serum markers, we have proposed the use of an integrated, multi-platform approach to biomarker discovery. Methods: A cohort of 107 glioma plasma samples, including 30 pairs, underwent plasma proteomic, consisting of a panel of serum proteins (FABP4, GFAP, NFL, Tau and MMP3,4 &7) quantified through ultrasensitive electrochemiluminescence multiplexed immunoassays, and plasma DNA methylation analysis, captured through cell-free methylated DNA immunoprecipitation and high-throughput sequencing. Results: Unsupervised hierarchal clustering revealed robust separation of primary and recurrent tumors through plasma proteomics, associated with a distinct plasma methylation signature. NFL, Tau and MMP3 levels differed between primary and recurrent samples; pair-wise analysis revealed increased in NFL and Tau concentrations upon recurrence. Tau levels predicted outcome independent of WHO Grade and IDH status. A predictive model created through the integration of the proteomic and methylation signatures revealed an AUC of 0.83. Conclusions: The combination of DNA methylation and plasma proteomics showcases that an integrative approach may improve the ability of these techniques for the serial monitoring of gliomas patients.

Background: Pituitary adenomas are treated with endoscopic surgery, while stereotactic radiosurgery addresses complex cases. Our study highlights AI’s role in accurate segmentation, improving treatment planning workflow efficiency Methods: In a retrospective study at Na Homolce Hospital (January 2010 to October 2022), SRS for pituitary adenomas was analyzed. Data were split 80:20 for training and validation. Using nnU-net, a medical image segmentation tool, a model predicted precise tumor, optic nerve, and pituitary gland segmentation. Accuracy was evaluated quantitatively with Dice similarity coefficient and qualitatively by human experts. The study explored the impact of tumor volume and hormonal activity status on segmentation accuracy. Results: The study comprised 582 and 146 patients in training and validation sets, respectively. The model achieved Dice similarity coefficients of 83.1% (tumor), 62.9% (normal gland), and 78.0% (optic nerve). Expert assessments deemed 41% directly applicable, 31.5% needing minor adjustments, and 27.4% unsuitable for clinical use. Larger tumor volume and non-functioning adenomas correlated with higher accuracy. Including T2 weighted scans improved DSC for optic nerve and normal gland. Conclusions: The study showcases deep learning’s potential in automating pituitary adenoma segmentation from MRI data, particularly excelling in large, hormonally inactive macroadenomas. Encourages collaborative use with clinicians for improved neurosurgical patient care.

Background: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR). This study aimed to identify threshold values of rSO2 and rSO2 based CVR at which outcomes worsened following traumatic brain injury (TBI). Methods: A retrospective multi-institutional cohort study was performed. The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. 2x2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated to identify the most discriminative significant threshold. Results: In the cohort of 129 patients rSO2 did not have any statistically significant threshold value. For COx and COx_a, an optimal threshold value of 0.2 was identified for both survival and favorable outcomes with values above this associated with worse outcomes. Conclusions: In this study, raw rSO2was found to contain no significant prognostic information. However, rSO2 based indices of CVR, were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

Background: Infantile hydrocephalus is characterized by an atypical accumulation of cerebrospinal fluid in the brain, diagnosed and treated before the age of 2 years. Hydrocephalus development is linked to thinning of the corpus callosum (CC), mainly due to the expansion of lateral ventricles, causing upward elevation and compression of periventricular and subcortical white matter. Methods: This study investigates structural alterations in the CC in children diagnosed with infantile hydrocephalus. We examined both macrostructural and microstructural facets of the CC, providing insights into the nature and extent of alterations associated with this condition. 18 patients with infantile hydrocephalus (mean age = 9 years), and 18 age and sex matched typically-developing healthy children, participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were utilized to assess CC volume and microstructure, respectively. Results: Our findings reveal reductions in CC volume, particularly in posterior area, and distinct microstructural disparities, notably pronounced in these same segments. Conclusions: Investigating these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on CC integrity, given its role as a neural bridge. This knowledge offers a more nuanced perspective on neurological disorders and underscores the significance of investigating the CC’s health in such contexts.

Background: Pineal region tumors are a heterogenous group of pathologies often symptomatic due to occlusive hydrocephalus leading to elevated intracranial pressure (ICP). High ICP may not always be associated with clinical signs. A non-invasive technique for assessment of ICP is measuring the optic nerve sheath diameter (ONSD). The goal of this study was to determine the utility of preoperative and postoperative ONSD measurements for assessment of elevated ICP in children with pineal region tumors. Methods: Retrospective data analysis was performed in patients operated for pineal region tumors at our tertiary care center between 2003 and 2022. Preoperative and postoperative MRI scans were reviewed. Clinical data and ONSD at multiple time points were analyzed and correlated. Results: Thirty-four patients with forty operative cases met the inclusion criteria. Hydrocephalus was seen in 80% of patients preoperatively (n=32/40). Presence of hydrocephalus was associated with significantly elevated ONSD preoperatively (p=0.006) and postoperatively (p=0.017). There was significant decrease in ONSD immediately postoperatively (p<0.001), at 3 months (p<0.001) and 12 months (p<0.001). In patients without hydrocephalus, no significant changes in ONSD were observed (p=0.369). Conclusions: ONSD is a useful adjunct for the identification of high ICP preoperatively and evaluation of treatment response postoperatively in patients presenting with pineal region tumors.

Background: Subarachnoid hemorrhages (SAH) are emergencies that require expedient workup. While Aneurysms and vascular malformations are a common cause, a subset of cases may lack detectable structural causes. If a CT angiogram (CTA) is negative, the more invasive Digital Subtraction Angiogram (DSA) is used for diagnosis. It is unclear how often DSA alters treatment for CTA negative SAHs. Methods: A retrospective review of SAH patients from our institution (Vancouver General Hospital) with a negative CTA with subsequent DSA in the past 25 years. Results: Our preliminary analysis included 233 patients. The median age was 55. 105 (45%) were female, and 128 (55%) were male. The average length of hospitalization was 9.6 days, and 226 (97%) were discharged alive. The median number of CTAs and DSAs administered were 2 and 1 respectively. In 12 (5%) cases, DSA detected an abnormality not seen on CTA, which led to endovascular or open surgery treatment in 5 (2%) cases. 5 DSA procedures led to complications including transient neurologic changes and ischemia. Conclusions: In SAH patients with CTA negative scans, additional DSA testing identified actionable pathology in only a small minority of cases. Clinicians must weigh the benefit of DSAs in these cases.

Background: Postoperative cranial neurosurgical imaging practices are highly variable. We evaluated the rate and utility of early postoperative computed tomography (EPCT, defined as a CT head scan within 24h of surgery) in consecutive adult craniotomies. Methods: We retrospectively reviewed consecutive adult craniotomies at the University of Alberta Hospital over a 45-day period (17/09/2022 to 01/11/2022). Electronic medical records were reviewed to extract data on the rate, timing, and utility of EPCT as well as the rate of neurologic deterioration and repeat surgical intervention. Results: A total of 56 patients (27 female; 55.5 ± 2.1 yrs, range: 19-84 years) were identified. All patients underwent EPCT, including 10/56 (17.9%) on POD0 and 46/56 (82.1%) on POD1. Surgical complications (bleeding, extensive pneumocephalus, edema, ischemia) were identified in 8/56 (14.3%) of the EPCT, of which 6 (10.7%) were reported to have neurologic deterioration and 2 (3.6%) underwent further surgical intervention (hematoma evacuation). Clinical and radiological postoperative changes were highly related (p=5.16e-06), and the rate of EPCT being adverse without neurologic deficit, managed surgically, was 1/56 (1.8%). Conclusions: EPCT is routine practice. Given the low rate (1.8%) of repeat surgical intervention in the absence of neurologic deficit despite abnormal EPCT, omitting EPCT in neurologically intact patients may be warranted.

Background: Degenerative cervical myelopathy (DCM) is the most common form of atraumatic spinal cord injury globally, yet clinical guidelines remain unclear on surgical recommendations for patients with mild forms of DCM. This is in part due to limitations in current MR imaging interpretation and complex mechanisms of neurological deterioration. Supervised machine learning (ML) models can help to identify clinical and imaging indicators of deterioration within mild DCM patients. Methods: 127 MRI scans (T2w, Diffusion Tensor Imaging, and Magnetization transfer scans) accompanied by a series of clinical tests underwent a semi-automated analysis to derive quantitative metrics. Random forest classifier, Support Vector Machine, and Logistic Regression models were trained and tested to predict 6-month neurological deterioration within patients. Results: The ML models performed, on average, better than previous studies with a balanced accuracy ranging between 70-75%. “Advanced” imaging metrics such as diffusion tensor imaging and magnetization transfer scans played an important role in improving model accuracy but only when used near the maximally compressed disc level, suggesting that limited yet targetted imaging metrics support ML model performance. Conclusions: The inclusion of specific, targeted imaging and clinical metrics support ML model performance in predicting neurological deterioration within mild DCM patients.

Background: The integration of Artificial Intelligence (AI) in medical education is an area of growing importance. While AI models have been evaluated extensively in multiple-choice question formats, their proficiency in written exams remains to be explored. Methods: Four AI models—GPT-4 (OpenAI), Claude-2.1 (Anthropic), Gemini Pro (Google), and Perplexity 70B (Perplexity)—were tested using the Canadian Royal College Sample Neurosurgery Exam. The written exam covered diagnostic reasoning, knowledge of neurosurgical conditions, and understanding of radiographic imaging techniques. Results: GPT-4 and Perplexity 70B both achieved a score of 68.42%, followed by Claude-2.1 with 60.53%, and Gemini Pro with 57.89%. The models showed proficiency in answering questions that required factual knowledge, such as identifying pathogens in spinal epidural abscess. However, they struggled with more complex diagnostic reasoning tasks, particularly in explaining the pathophysiology behind a sudden rise in blood pressure during surgery and interpreting radiographic characteristics of intracranial abscesses on MRI. Conclusions: The findings indicate that while AI models like GPT-4 and Perplexity 70B are adept at handling factual neurosurgical questions, their performance in complex diagnostic reasoning in a written format is less consistent. This underscores the need for more advanced and specialized AI training, particularly in the nuances of medical diagnostics and decision-making.

Background: Cognitive flow has been linked with enhanced performance, career satisfaction, and decreased burnout. However, while elite sport has long trained athletes to enter flow states, the concept has not been adopted strongly in healthcare. Flow has primarily been explored from a unidimensional (cognitive) perspective. The present study sought to understand the experience of flow among surgeons through a multidimensional lens. Methods: Using a constructivist grounded theory methodology, semi-structured interviews were conducted with 19 staff surgeons at the University of Toronto, purposively sampled. Data were coded and analyzed iteratively by three researchers until theoretical saturation was achieved. Results: Although many surgeons had not previously heard of cognitive flow, the phenomenon deeply resonated with most. Participants described different physical, cognitive, emotional, sociocultural, and environmental components that interacted to shape the subjective experience of flow: “I think that there are many different facets of [flow] that don’t always come together all at the same time, you may feel different parts of it… depending on what the kind of case is, who your help is, if you recently had a complication.” (P4) Conclusions: Understanding flow in clinical practice may lead to new avenues for enhancing career satisfaction and promoting physician wellness.

Background: Gender disparities persist in neurosurgery, unfortunately impacting career progression for women. Understanding these challenges is vital for fostering inclusivity. Methods: An international survey designed using a physician wellness framework was sent to neurosurgeons between June 2021 and November 2021. Univariate analysis (Kruskal-Wallis Test) was performed to assess various aspects of perceived career progression as a function of gender. Results: Of the total 537 respondents (64% neurosurgeons, 6% fellows, and 30% residents), 69% identified as male, 29% as female, and 2% as other. Compared to their male colleagues, female neurosurgeons expressed greater desire to advance in their career (p<0.05) and to leave their home country in the interest of job prospects (p<0.05). Despite these aspirations, female neurosurgeons reported that they did not have available career advancement opportunities (p<0.05), that the culture in their country inhibited their career advancement (p<0.05), and that they felt subject to harassment at their workplace (p<0.05). Conclusions: Our survey highlights significant gender-related obstacles in neurosurgical career advancement. Female neurosurgeons express strong career aspirations but face barriers such as limited opportunities, cultural impediments, and harassment. Addressing these challenges is crucial for achieving gender equity in neurosurgery.

Background: Gender disparities endure in neurosurgery, impacting the experiences of female practitioners. Unveiling these challenges is crucial for promoting inclusivity and addressing the unique obstacles faced by women in the field. Methods: An international survey designed using a physician wellness framework was sent to neurosurgeons between June 2021 and November 2021. Univariate analysis (Kruskal-Wallis Test) was performed to assess feelings of inclusion and diversity as a function of gender. Results: Of the total 384 respondents (65% neurosurgeons, 6% fellows, and 29% residents), 71% identified as male, 27% as female, and 2% as other. Compared to their male colleagues, female neurosurgeons more strongly endorsed feeling that their career progression has been limited by their gender (p<0.05) and were less likely to feel entrusted in their surgical ability (p<0.05) or to have equal access to surgical resources (p<0.05). Furthermore, they were less likely to endorse feelings that leaders in their department were committed to creating an inclusive environment (p<0.05). Conclusions: Our survey sheds light on significant gender-related disparities in neurosurgery. Female neurosurgeons express heightened concerns about gender-limiting career progression, reduced trust in their surgical abilities, and disparities in resource access. These findings underscore the imperative to foster a more inclusive and supportive environment within the field.

Background: An estimated 27-69 million individuals worldwide sustain a mild Traumatic Brain Injury (mTBI) each year, making it an important public health concern. Many victims experience post-injury neuropsychological issues such as anxiety and depression, which are associated with more post-concussive symptoms and worse functional outcomes. We sought to determine a systematic process to document the presence of anxiety and depression symptoms in mTBI patients to prevent negative impacts on their recovery. Methods: We administered the Generalized Anxiety Disorder-7 (GAD-7) and Center for Epidemiologic Studies Depression Scale Revised (CESDR-10) questionnaires, no more than three months after injury, to screen for these symptoms. A retrospective chart review was performed for 328 patients from the Montreal General Hospital mTBI Clinic who either received these questionnaires (N=143, Mage=40.36, SDage=15.557, Nfemale=90, Nmale=53) or did not (N=185, Mage=41.17, SDage=16.449, Nfemale=114, Nmale=71). The number of interventions received between groups were compared using ANOVA. Results: Patients who received the questionnaires (M=1.34, SD=0.978) were referred to significantly more interventions than those who did not (M=0.90, SD=0.876, p<0.001) and the rate of referral positively correlated with GAD-7 and CESDR-10 scores. Conclusions: Screening for symptoms of anxiety and depression post mTBI helps clinicians refer patients to the appropriate resources, which in turn should improve outcome.

Background: Employment and personal income loss after traumatic brain injury (TBI) is a major source of post-injury stress and barrier to societal reintegration for affected patients. We sought to quantify the labor market implications for tax-filing adult TBI survivors. Methods: We performed a matched difference-in-difference analysis using a national retrospective cohort of working adult TBI survivors injured between 2007-2017. Linear and logistic mixed effects regressions were used to estimate the magnitude of personal income loss and proportion of patients displaced from the workforce in the three post-injury years (Y+1 to Y+3). Results: Among 18,050 patients identified with TBI, the adjusted average loss of personal annual income was $-7,635 dollars in Y+1 and $-5,000 in Y+3. An additional -7.8% individuals were newly unemployed compared to the pre-injury baseline. For mild, moderate, and severe TBI subgroups, income loss was $-3354, $-6750, and $-17375 respectively in Y+3; the proportion of newly unemployed individuals in Y+3 was 5.8%, 9.2%, and 20% lower than baseline. We estimated 500 million dollars of incurred labor markets losses related to TBI in Canada. Conclusions: This work represents the first national cohort data quantifying the labor market implications of TBI. These results may be used to inform post-injury care pathways and vocational rehabilitation.

Background: Despite the utility of administrative health data, there remains a lack of patient-centered outcome measures to meaningfully capture morbidity after traumatic brain injury (TBI). We sought to characterize and validate days at home (DAH) as a feasible measure to assess population-level moderate to severe TBI (msTBI) outcomes and health resource utilization. Methods: We utilized linked health administrative data sources to identify adults with msTBI patients presenting to trauma centers in Ontario injured between 2009-2021. DAH at 180 days reflects the total number of days spent alive and at home excluding the days spent institutionalized in acute care, rehabilitation, inpatient mental health settings or post-acute readmissions. Construct and predictive validity were determined; we additionally estimated minimally important difference (MID) in DAH180days. Results: There were 6340 patients that met inclusion criteria. Median DAH180days were 70 days (interquartile range 0-144). Increased health resource utilization at baseline, older age, increasing cranial injury severity and major extracranial injuries were significantly associated with fewer DAH180days. DAH180days was correlated to DAH counts at 1-3 years. The average MID estimate from anchor-based and distribution-based methods was 18 days. Conclusions: We introduce DAH180days as a feasible and sufficiently responsive patient-centered outcome measure with construct, predictive and face validity in an msTBI population.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical condition which can be treated with surgical evacuation. A significant percentage of CSDH patients are on antiplatelet or anticoagulation therapy at baseline which may influence risk of recurrence and postoperative thromboembolic events Methods: A search was conducted in MEDLINE (1946 to April 6, 2023), Embase (1974 to April 6, 2023), and PubMed (up to April 6, 2023) on preoperative use of antiplatelet or anticoagulation therapy and outcomes following surgical evacuation of CSDH. Results: Our literature includes 14,410 patients ifrom 42 studies, with 3218 (22%) in the antiplatelet (AP) group, 1731(12%) in the anticoagulation (AC) group, and 9537 (66%) in the no antithrombotics (NA) group. The AP group had significantly higher recurrence compared to NA (OR = 1.21, 95% CI = 1.04 to 1.40, p = 0.01). The AC group also had significantly high recurrence compared to NA (OR = 1.39. 95% CI = 1.15 to 1.68, p = 0.0007). However, being on any antithrombotic therapy is also associated with significantly higher thromboembolic events (OR 5.41, 95% CI 3.16 to 9.26, p < 0.00001). Conclusions: Patients on antithrombotic therapy have both higher recurrence and higher thromboembolic risk compared to patients not on antithrombotic therapy.

Background: Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) based cerebrovascular reactivity (CVR) indicies have enable the entirely non-invasive continuous monitoring. This study aims to compare CVR in those recovering from moderate/severe TBI to a health control group. Methods: In this prospective cohort study the cerebral oxygen CVR index, COx_a (using rSO2 and arterial blood pressure), was measured in subjects with moderate/severe TBI at follow-up. COx_a was also measured in a group of healthy controls. CVR was compared within and between these groups using conventional statistics. Results: A total of 101 heathy subject were recruited for this study along with 29 TBI patients. In the health cohort COx_a was not statistically different between males and females or in the dominate and non-dominate hemisphere. The TBI cohort, COx_a was not statistically different between first and last available follow up. Surprisingly, CVR as measured by COx_a was statistically better in those recovering from TBI than in the healthy cohort. Conclusions: In the prospective cohort study, CVR as measured by NIRS based methods, was found to be more active in those recovering from TBI than in a healthy cohort. This study may indicate that, in those that survive TBI, CVR may be enhanced as a neuroprotective measure.

Background: Subdural and subgaleal drains are equally effective after burrhole craniostomy for chronic subdural haematoma, however the optimal location of drains after minicraniotomy is not clear. As such we present the first study to assess this. Methods: Consecutive patients undergoing minicraniotomy for cSDH between 2019 and 2023 at a single institution were included. Subgaleal drains were placed exclusively by a single surgeon with the rest of the department utilising standard subdural drains. Cases were stratified by drain location. Primary outcomes included changes in functional status (Modified Rankin Score, mRS) at 3 months from preoperative baseline. Results: A total of 137 patients were included, of which 24.6% received subgaleal drains. Discharge home was higher in the subgaleal group compared to subdural group (79.4% vs 57.3%, p=0.02). Subgaleal drain location (p<0.0001) and better preoperative GCS (p=0.01) were predictors of improved 3 month mRS. Worse premorbid mRS (p=0.002), subdural drain (p=0.004), and decreased consciousness at presentation (p<0.002) were predictors of not being discharged home. Surgical recurrence was lower in the subgaleal group than the subdural group (2.9% vs 13.6%, p=0.12), but not statistically significant. Conclusions: Subgaleal drains are associated with shorter hospitalisation, greater chance of discharge home, and better functional outcomes than subdural drains.