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: Biochemical cure in functional pituitary adenomas (FPA) is crucial for reducing patient morbidity and improving quality of life following endoscopic endonasal procedures (EEA). The extent of resection plays a key role in achieving these outcomes. However, even with the aid of intraoperative navigation, complete resection of tumor components can be challenging due to the difficulty in distinguishing them from normal pituitary tissue. Indocyanine green (ICG) fluorescence has been used effectively in various cranial and spinal procedures, but its role in endoscopic skull base surgery has not yet been routinely established Methods: In this study, we describe our experience using ICG during EEA for the resection of FPA. Results: We discuss the fluorescence profiles of both adenomas and normal gland tissue. ICG helped identify additional tumor tissue that was not initially detected after macroscopic adenoma resection. It also allowed for perfusion assessment of the pituitary gland and nasoseptal flaps. No complications were observed following the ICG injection, and biochemical cure was achieved in more than 90% of cases. Conclusions: Our experience suggests that ICG is a safe and promising tool, improving both the extent of resection and endocrinologic outcomes in patients undergoing EEA for FPA.

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: Attitudes toward aging influence many health outcomes, yet their relationship with cognition and Alzheimer’s disease (AD) remains unknown. To better understand their impact on cognition and AD risk, we examined whether positive attitudes predict better cognition and diminished risk on AD biomarkers. Methods: A subsample of older adults with a family history of AD (n=54; women=39) from the McGill PREVENT-AD cohort participated in this study. Participants completed the Attitudes to Ageing Questionnaire (AAQ-24), providing three scores: psychosocial loss, psychological growth and physical change. Participants underwent cognitive testing (Rey Auditory Verbal Learning Test, RAVLT; Delis-Kaplan Executive Function System-Color Word Interference Test, D-KEFS-CWIT), and AD blood-based biomarker assessments (p-tau217, Aβ42/40). Regression models tested associations, adjusting for covariates (age, sex, education, depression, APOE4), and were Bonferroni corrected. Results: Positive attitudes were associated with better recall and recognition (RAVLT) and improved word reading, colour naming, switching, and inhibition (D-KEFS-CWIT) (p<0.00077), while negative attitudes showed the opposite pattern. Negative attitudes were correlated with lower Aβ42/40 ratios, while positive attitudes were linked to lower p-tau217 (p<0.0167). Conclusions: These findings demonstrate that positive attitudes predict better cognition and a lower risk profile for AD biomarkers, suggesting that life outlook may be an early disease feature or a risk factor.

Background: Reversible cerebral vasoconstriction syndrome (RCVS) is defined clinically by headaches associated sometimes with seizures and neurological deficits, and radiologically with intermittent spasms in cerebral arteries that would resolve in 3 months. It can present with multiple bleeding patterns. Intraventricular hemorrhage (IVH) is a rare presentation for RCVS as there are 4 reported cases. Methods: This is a case report and review of literature. Results: A 36-year-old patient sought medical attention due to the acute onset of thunderclap headache. A computed tomography (CT), and CT angiogram (CTA) of his head and neck were done. It showed large IVH associated with hydrocephalus and no underlying vascular abnormalities. An external ventricular drain was placed and he was on nimodipine. A CTA was done on day 17 because he had acute global aphasia, right hemibody weakness, and right homonomous hemianopia, which showed severe diffuse intracranial stenosis involving the circle of Willis. He was taken to the angiography suite for chemical spasmolysis with verapamil. There was radiographic improvement and clinical resolution. Conclusions: This case highlights the rarity of RCVS presentations and further signifies the utility of intraarterial spasmolytics as an adjunct in the diagnosis of difficult cases. Further retrospective and prospective data are needed.

Background: The increasing use of anti-B cell therapies in managing multiple sclerosis(MS) around the time of conception has raised important considerations for neonates exposed in utero. International recommendations suggest assessing neonatal B cell count in potentially exposed neonates. Practical implementation of cord blood collection at birth requires coordinated care across specialties, including paediatric haematology, neurology and obstetrics. Methods: This workshop, scheduled for 01/30/2025, will address clinical and logistical challenges of neonatal B cell assessments following in utero exposure to anti-B cell therapies. Presentations by MS pregnancy specialists from Toronto,Ontario, will be complemented by collaborative problem-solving among participants, including a paediatric haematologist, MS neurologists, obstetricians, paediatricians, and a quality specialist. A patient with lived experience will contribute to discussions. Results: The workshop will develop a care pathway for cord blood B cell testing, optimizing vaccine scheduling at London Health Sciences Center (LHSC) in London Ontario. Outcomes will include enhanced multidisciplinary collaboration, participant feedback, development of a practical clinical care plan for B cell collection and interpretation and measures of the pathway’s impact on patient satisfaction and clinical decisions. Conclusions: This initiative will improve care for mothers and neonates exposed to anti-B cell therapies, addressing critical gaps in clinical practice through collaboration and a standardized approach.

Previous studies on the association between fruit juice consumption and type 2 diabetes remain controversial, which might be due to heterogeneity in the polygenic risk score (PRS) for type 2 diabetes. We examined the association between fruit juice and type 2 diabetes by PRS for type 2 diabetes. We investigated whether fruit juice influences type 2 diabetes risk differently among individuals with varying genetic risks. Data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, a cross-sectional study of 13 769 Japanese individuals was used for our analysis. The primary exposure was the frequency of fruit juice, categorised as do not drink, less than 1 cup per day or more than 1 cup per day. We selected PGS002379, a PRS for type 2 diabetes developed using East Asian populations. The primary outcome was physician-diagnosed type 2 diabetes, reported by participants. The consumption of fruit juice was significantly inversely associated with type 2 diabetes in the group with a high PRS for type 2 diabetes (OR: 0·78, 95 % CI: 0·65, 0·93 for < 1 cup/d and OR: 0·54, 95 % CI: 0·30, 0·96 for > 1/d), but this association was not observed in the low PRS group. Fruit juice consumption was inversely associated with type 2 diabetes, especially in genetically high-risk populations for type 2 diabetes.

This paper considers two commuting smooth transformations on a Banach space and proves the sub-additivity of the measure theoretic entropies under mild conditions. Furthermore, some additional conditions are given for the equality of the entropies. This extends Hu’s work [Some ergodic properties of commuting diffeomorphisms. Ergod. Th. & Dynam. Sys. 13(1) (1993), 73–100] about commuting diffeomorphisms in a finite dimensional space to the case of systems on an infinite dimensional Banach space.

Background: In Canada, individuals with intellectual disabilities (ID) make up approximately 25% of the epilepsy population. Despite making up only a small portion, adult hospitalization data in Canada shows that individuals with ID are significantly more likely to be seen in the ED, be hospitalized, and to die as a result of epilepsy and epilepsy complications, than individuals with typical cognitive development. Data looking at ED visits in adolescents with epilepsy and varying cognitive abilities is extremely limited. Methods: To address this, a retrospective chart review of 122 adolescents (42 MID and 80 typical cognitive development) with epilepsy between the ages of 14 and 18 was done. Results: Results showed that adolescents with typical cognitive development had significantly more ED visits (p=.006), and seizure related ED visits (p= .008) than adolescents with MID. Despite the reasons for ED visits not significantly differing between the two groups, adolescents with MID had significantly longer ED visits (p=.023). Finally, when looking exclusively at the MID group, results showed that females were significantly more likely to be seen at the ED than males (p=.001). Conclusions: Results suggest that ED visit frequencies differ among adults and adolescents with ID, potentially suggesting the presence of unique protective factors for adolescents.

Background: Advanced parkinsonian syndromes represent a growing challenge for healthcare systems as their care needs are complex and costly. Current care models often lack integration of specialized neurology and palliative care, leading to suboptimal outcomes. The Advanced Care Team for Parkinson’s program (ACT-PD) addresses this gap by enhancing care quality and reducing costs. This study evaluates the cost-effectiveness of ACT-PD interventions compared to standard care (SC). Methods: A retrospective analysis compared 27 deceased ACT-PD patients (2022–2024) with 1,439 deceased SC patients (2011–2017). It assessed healthcare utilization, place of death, and patient Quality-Adjusted Life Years (QALYs). Healthcare utilization measures included hospitalizations, Intensive Care Unit (ICU) admissions, emergency department (ED) visits, and palliative care consultations. The analysis incorporated the incremental cost-effectiveness ratio (ICER) using Calgary Zone cost data from 2021–2022. Results: ACT-PD patients experienced fewer hospital deaths (33.33% vs. 45.90%) and more deaths at home (22.22% vs. 7.90%). They also had greater neurology (48.00% vs. 37.20%) and palliative care engagement (36.00% vs. 17.40%). ACT-PD avoided ICU admissions, saving $2.56 million annually, with total cost savings of $2.66 million. The ICER was $1,459 per QALY gained. Conclusions: Multidisciplinary palliative care interventions provided by ACT-PD are highly cost-effective, improving care quality while reducing healthcare costs.

The frequency responses of circulation control and separation control using mini-spoilers for loads attenuation on plunging swept and unswept wings were compared in a water tunnel study. At the pre-stall angle-of-attack, the effectiveness of the spoilers significantly diminishes with increasing reduced frequency of the plunging motion. For the leading-edge spoiler, this happens because the roll-up of the vorticity promotes flow reattachment and reduces the effectiveness of loads attenuation. For the trailing-edge spoiler, the effectiveness of lift attenuation also decreases with increasing reduced frequency, due to the shedding of leading-edge vortices and immersion of the trailing-edge spoiler in the separated flow. The decay of the frequency response for both types of spoilers is similar, implying that it is dictated by the flow separation near the leading edge of the wing in both cases. With increasing sweep angle of the wings, the spoilers’ effectiveness decreases significantly in comparison to the unswept wing. Strong spanwise flow develops for the leading-edge spoiler, which sheds a streamwise vortex, with the same direction of rotation as the wing-tip trailing vortex. This causes partial reattachment of the flow and reduction of the separation area behind the spoiler. With increasing reduced frequency, strong leading-edge vortices dominate the flow over the wing. The leading-edge vortices generate additional vortex lift and also cause the trailing-edge spoiler to be immersed in the massively separated flows. Both factors reduce the effectiveness of the spoilers.

Background: Tuberous Sclerosis Complex (TSC) is a genetic condition marked by multisystem benign tumours. mTOR inhibitor (mTORi) therapy is indicated for subependymal giant cell astrocytomas (SEGA), renal angiomyolipomas (AML), and drug-resistant epilepsy. This study aimed to evaluate the efficacy and safety of mTORi in our paediatric TSC cohort. Methods: Data on patient demographics, clinical outcomes, and adverse events (AEs) were obtained from SickKids’ prospective observational TSC Database (n=107). Results: 19 children (median age at diagnosis 0.6 years, range 0-8.3; F:M 10:9) received mTORi. Indications were SEGA (n=6), AML (n=4), seizures (n=4), prophylactic (n=2), AML/SEGA (n=1), seizures/AML (n=1), and seizures/SEGA (n=1). Median age at mTORi initiation was 8.4 years (range 2.1-15.4). 68.4% (n=13/19) received sirolimus and 31.6% (n=6/19) received everolimus. 24 months post-mTORi initiation, 50% showed stable SEGA (n=4/8), 50% reduced SEGA (n=4/8), 66.7% stable AML (n=8/12), 25% reduced AML (n=3/12), and 8.3% larger AML (n=1/12). Variability in reporting seizure frequency rendered mTORi effects on epilepsy inconclusive. mTORi was overall well tolerated, yet 100% (n=19/19) reported AEs, majority Grade 1-2. Conclusions: This study describes the efficacy and tolerability of mTORi in a Canadian paediatric TSC cohort, which demonstrates beneficial effects on SEGA and AML, with mild to moderate AEs reported.

Background: Mesial temporal lobe epilepsy (mTLE) is a heterogenous condition with variable post-surgical outcomes. Combining high resolution magnetic resonance imaging (MRI), stereoelectroencephalography (SEEG) and histology may establish different subtypes of mTLE. Methods: Retrospective analysis of patients with mTLE with 1) SEEG Patterns 2) MRI 3) Post temporal lobectomy tissue analysis 4) Engel Classification. HippUnfold method was used to segment hippocampus on MRI. Results: Of 109 patients investigated with SEEG, 11 patients were analyzed so far. Low voltage fast activity was seen in 215 seizures, low-frequency periodic spikes in 21, sharp activity at <13 Hz in 58, rhythmic spike sharp wave activity in 86, and other types were less frequent. MRI revealed unilateral mesial temporal sclerosis (MTS) in 6 (54.55%), bilateral MTS in 2 (18.18%), and was normal in 3 (27.27%) patients. Histopathology showed ILAE grade I in 3 (37.5 %), II in 4 (50 %), IV in 1 (12.5%) patient. 63.63% had Engel Class I at 6 months. HippUnfold analysis and SEEG electrode coregistration was done in one patient and will be attempted in the rest. Conclusions: Our study highlights a strong correlation between SEEG findings and histological analysis in mTLE. A multidimensional classification will help predict long term outcomes.

Background: We’ve adopted a novel approach that combines cellular barcoding with CRISPR/Cas-9 technology and single-cell RNA sequencing known as continuous lineage tracing to track the development, treatment and inevitable recurrence of glioblastoma. Methods: Patient derived glioma initiating cell lines were engineered with expressed DNA barcodes with CRISPR/Cas-9 targets and engrafted into NOD scid-mice. Clonal and relationships are surmised through identification of expressed barcodes, and cells were characterized by their transcriptional profiles. Phylogenetic lineage trees are created using lineage reconstructive algorithms to define cell fitness and expansion. Results: Our work has revealed a significant amount of intra-clonal cell state heterogeneity, suggesting that tumour cells engage in phenotype switching prior to therapeutic intervention. Phylogenetic lineage trees allowed us to define a gene signature of cell fitness. GBMs exist along a transcriptional gradient between undifferentiated but “high-fit” cells and terminally differentiated, “low-fit” cells, lending further evidence that these tumours consist of pools of cells that are capable of recapitulating the tumour microenvironment after treatment. Conclusions: We have successfully engineered a set of glioma initiating tumours with a novel lineage tracing technique, creating a powerful tool for real-time tracing of tumour growth through the analysis of highly detailed singe-cell RNA sequencing data with associated clonal and phylogenetic relationships.

Background: Ontario and other Canadian provinces fund multi-gene sequencing panels as the initial testing approach for patients with epilepsy. However, genetic testing guidelines issued by the US-based National Society for Genetic Counselors and endorsed by the American Epilepsy Society recommend exome as a first-line test. We explored the theoretical improvements in diagnostic yield when selecting exome over provincially-funded panels (PFPs). Methods: Our comparative analysis used a list of 768 diagnostic genes and 4474 diagnostic variants identified in diagnostic exome cases involving clinical indications of seizure. We compared these lists to the genes included in two PFPs (190 genes and 474 genes) to see which exome-identified genes and variants would have been captured by the PFPs. Results: Most exome-identified diagnostic genes may have been missed by the PFPs (82% and 65% for the 190 and 474-gene PFPs), and close to half of the exome-identified diagnostic variants (62% and 43% for the 190 and 474-gene PFPs) may have been missed. Conclusions: Exome-based testing captures a broader range of diagnostic genes and more diagnostic variants than PFPs. The adoption of exome over panels as a first-line test may lead to improved diagnostic rates and permit earlier treatment for individuals with seizures.

Background: We aim to assess the resting state functional connectivity (RSFC) and reactivity with functional near-infrared spectroscopy (fNIRS) in patients with acute stroke compared to age, sex and comorbidity-matched subjects. Methods: Patients with acute anterior circulation stroke syndrome localizing to the right (RH) or left hemisphere (LH) were enrolled. RSFC was assessed using group-level seed-based (Primary Motor cortex,PMC) correlation analysis. Finger-tapping-associated relative oxygen Hemoglobin (ΔHbO) changes were analyzed with generalized linear model regression. Results: 127 participants (RH stroke, 51; LH stroke, 43; control, 33) enrolled at a median of 21 (15,29) hours after symptom onset. Compared to the control group, the RSFC with the affected PMC (LH stroke) was reduced over the affected somatosensory cortex (SSC) in the minor ischemic stroke (IS) (r = -0.14 (-0.3,-0.01)), minor intracerebral hemorrhage (ICH) (-0.48 (-0.78,-0.18)) and major ICH groups (-0.2 (-0.4,-0.01). In the FT task compared to the control groups in LH stroke, ΔHbO was increased over the affected SSC in minor IS (β11.2(1.9,20.5)) and major ICH group (β11.7 (1.4,22.1)). In the FT task in RH stroke, ΔHbO was increased over the unaffected PMC in minor IS (β12.1(2.3,21.8)), major IS (β14.9 (0.3,29.5)), minor ICH (β25.7 (10.1,41.2)) and major ICH (β13.4 (1.1,25.6). Conclusions: Motor cortex dysconnectivity may be worse over the LH stroke. In RH stroke, there is early compensatory increased neuronal activity over the unaffected PMC. These results suggest differential acute remodelling in RH and LH strokes.

Background: Routine electroencephalography (EEG) provides excellent temporal resolution for evaluation of focal epilepsy, but lacks spatial resolution. High-density-EEG (HDEEG)-based source-localization significantly enhances spatial resolution, but requires greater standardization. We systematically review HDEEG systems, methods, and metrics utilized for evaluating focal epilepsy. Methods: A systematic search was conducted in PubMed using PRISMA guidelines with keywords “HDEEG” or “high-density EEG”, “source localization and “focal epilepsy”. Inclusion criteria: studies from the last 20 years, human subjects with focal epilepsy, sample size ≥ 10 and HDEEG with source localization methods clearly described. Results: 37 of 65 studies fulfilled inclusion criteria, with most reporting N<50. Most studies (14) used a 256-electrode HDEEG setup; 10 used 128-electrode configurations, and 6 used 76–83 electrodes. EEG source localization most commonly used Cartool (N=12) and Curry (N=5) softwares. Standard MRIs were used in 25 studies, and customized MRIs in 12. Metrics like clustering coefficient were reported to represent dipole distribution (10 studies); while functional connectivity analysis was reported in 7 studies. Conclusions: Variations in software choice, metrics for dipole distribution assessment, and MRI integration are evident from the current literature. Clustering methods and functional connectivity metrics are most commonly employed to represent dipole distribution, reflecting their increasing utility in understanding brain networks.