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: 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: There is no guideline for imaging post endovascular therapy (EVT). MRI is considered superior to noncontrast CT for assessment of final infarct volume and to distinguish contrast from hemorrhage. We sought to align the post EVT imaging practices with those after intravenous thrombolysis Methods: We reviewed the EMR records for all EVT patients from Jan 1, 2019 to Dec 31, 2021. We assessed quantity of CT within 24h of EVT, quantity of MRIs performed, and indications listed. We then undertook an educational program targeting stakeholders. The objective was to transition to MRI at 24h for imaging post EVT. Exceptions included neurologic change, need for antiplatelet infusion, or intraoperative complications. Results: Post intervention, a significant reduction in CT within 24h (-28%, P=0.01) and increase in MRIs (+42%, P<0.00). CT within 24h per patient dropped by 50% (1.12 pre vs 0.57 post). Radiation dose per patient dropped by 49%. Average imaging costs increased by 17%, and the number of transfers off unit for imaging increased by 11%. Good functional outcome dropped from 44% preintervention to 34% postintervention (P=0.06). Conclusions: This represents the first systematic evaluation of post EVT imaging in a single center. We demonstrate successful behavior changes for post EVT imaging.

Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.

Background: Zilucoplan, a macrocyclic peptide complement component 5 inhibitor, sustained efficacy for up to 60 weeks of treatment, with a favourable safety profile in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis in an interim analysis of RAISE-XT (NCT04225871). We evaluate the safety and efficacy of zilucoplan up to 96 weeks. Methods: RAISE-XT, a Phase 3, multicentre, open-label extension study, included patients who participated in the double-blind Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg injections. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: At data cut-off (11 May 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years (N=200). TEAEs occurred in 191 (95.5%) patients; the most common TEAE was COVID-19 (n=64; 32.0%). At Week 96, mean (standard error) change in MG-ADL score from double-blind study baseline was –6.33 (0.49) and –7.83 (0.60) for patients who received zilucoplan 0.3mg/kg and placebo in the double-blind studies, respectively. Conclusions: Zilucoplan demonstrated a favourable long-term safety profile. Efficacy was sustained for 96 weeks in patients who had previously received zilucoplan and who switched from placebo.

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: Vertebral compression fractures (VCF) lead to both considerable morbidity and increased mortality. Kyphoplasty, a minimally invasive surgery, treats VCFs providing significant pain relief, preserving vertebral height, and reducing spinal deformity. Methods: A retrospective cohort study at Hamilton Health Sciences (HHS) was conducted on elderly patients (60 years or older) who underwent kyphoplasty at between 2012 and 2022. The patients had prior hospital admissions under non-spine-related specialties at HHS within two years before their surgery. Primary outcomes were the progression of vertebral height loss and focal kyphotic deformity. Results: The study included 119 patients (52.1% female, mean age 70.71 years). A significant increase in vertebral height loss was observed from diagnosis to pre-kyphoplasty (0.32% change, p < 0.0001) and from diagnosis to post-kyphoplasty (0.24% change, p = 0.015). However, there were no significant correlations between delay times and changes in vertebral height or focal kyphotic deformity. Conclusions: Delays in neurosurgical consultation and kyphoplasty did not significantly affect radiographic outcomes in elderly patients with VCF despite the progression of vertebral height loss. This suggests that while timely patient care is essential, delayed treatment may not adversely affect key radiographic metrics in elderly VCF patients.

Background: Neurosurgical conditions impose a significant burden on the Canadian healthcare system. This study quantifies the economic impact and explores predictive models for postoperative length of stay. Methods: We analyzed data from the Canadian Institute for Health Information National Health Expenditure Trends database for 2015-2019, focusing on case volumes, healthcare costs, and lengths of stay (LOS) across age groups and conditions. Decision tree models were created to predict total LOS from patient age and average acute LOS. Results: There was a modest increase in case volumes from 6,220 ± 3,103 in 2015 to 6,492 ± 3,240 in 2018, with a slight decrease in 2019. The total estimated hospital costs ranged from 2.27 ± 0.38 million CAD in 2015 to 2.23 ± 0.44 million CAD in 2019. The highest costs were seen in the 18-59 age group, at 2.53 ± 0.43 million CAD. Decision tree models showed high accuracy for predicting LOS in cases like spinal injury (F1-score: 0.98) but were less accurate for interventions with trauma or complications (F1-scores from 0.66 to 0.97). Conclusions: The study delineates the financial demands of neurosurgery in Canada and suggests decision tree models as useful tools for predicting hospital stay, with variable accuracy depending on the case complexity.

Background: The primary aim was to determine if functional outcomes among young adults with stroke differed based on sex. The secondary aim was to identify differences in stroke risk factors and etiologies between females and males. Methods: Retrospective analysis of acute ischemic stroke patients aged 18 to 55 years from a stroke registry between 2018 to 2022. Multivariable logistic regression to analyse if modified Rankin Scale at 3-6 months (mRS, 0-2 versus 3-6) was associated with sex. Results: 315 patients (127 female), median age 48 years (IQR 42-52), median NIHSS 10 (IQR 4-19, median mRS (3-6 months) 2 (IQR 1-3). Following adjustment for vascular risk factors, clinical stroke characteristics, baseline mRS and stroke time metrics no significant difference in mRS (3-6 months) based on sex (p=0.40). Females more frequently had an unknown time of stroke onset (p=0.03). Large-artery atherosclerosis as a stroke etiology (p=0.01), known atrial fibrillation (p=0.03) and drug use (p=0.003) were more frequent in males. Conclusions: Patient-oriented outcomes maybe of interest in future studies as functional mRS outcomes do not differ between young male and female stroke patients. Males had a higher prevalence of large-artery atherosclerosis and risk factors including drug use and atrial fibrillation. These findings could help develop targeted stroke prevention strategies.

Background: Degenerative Cervical Myelopathy (DCM) is the functional derangement of the spinal cord because of compression from degenerate tissues. Typical neurological symptoms of DCM include gait imbalance and upper extremity paresthesia. While it is thought that greater spinal cord compression leads to increased neurological deterioration, our clinical experience suggests a more complex mechanism involving spinal canal diameter (SCD). Methods: 124 MRI scans from 59 non-operative DCM patients underwent manual scoring of cord compression and SCD measurements. Unsupervised machine learning dimensionality reduction techniques and k-means clustering were used to establish patient groups. These patient groups underwent manual inspection of common compression patterns and SCD similarities to define their unique risk criteria. Results: We found that compression pattern is unimportant at SCD extremes (≤14.5 mm or >15.75 mm). Otherwise, stenosis with clear signs of cord compression at two disc levels and stenosis without clear signs of cord compression at two disc levels result in a relatively higher and lower likelihood of deterioration, respectively. We elucidated five patient groups with unique associated risks for neurological deterioration, according to both SCD range and their cord compression pattern. Conclusions: The specific combination of narrow SCD with focal cord compression increases the likelihood of neurological deterioration in non-operative patients with DCM.

Background: Historical literature suggests the risk of neurologic injury in children supported by extracorporeal life support (ECLS) is between 10-20%, however recent studies suggest the incidence may be much higher. Methods: The Alberta Children’s Hospital (ACH) Rescue ECLS program cannulates patients who are then transferred to the partner program at Stollery Children’s Hospital. Data was systematically collected from all patients cannulated for Rescue ECLS at ACH October 2011 and May 2023. Neuroimaging (CT, MR) performed after cannulation was reviewed for evidence of ischemic and hemorrhagic strokes and hypoxic-ischemic brain injury. Results: Seventy-one patients were included in the Rescue ECLS cohort. Median age at cannulation was 1.74 years (range 0-17.6 years, 51% female). Survival to hospital discharge was 65%. Primary indication for ECLS included cardiac (42%), respiratory (33.3%), extracorporeal cardiopulmonary resuscitation (ECPR; 23.2%) and trauma (1.4%). Seventy four percent of the cohort underwent neuroimaging, of whom 67% had evidence of neurologic injury including stroke (ischemic 67%; hemorrhagic 50%) or hypoxic-ischemic injury (33%). Risk of neurologic injury did not differ by indication for ECLS. Conclusions: Neuroimaging abnormalities are present in most pediatric patients imaged post-cannulation for Rescue ECLS. Further research into modifiable risk factors for specific ECLS-related brain injuries may help to improve outcomes for survivors.

Background: Limited data exists on neurological care and outcomes of Canadian pregnant patients with epilepsy (PPWE). This study provides Canadian data to inform practice patterns and observed outcomes for PPWE at a tertiary care center. Methods: PPWE receiving care at the University Health Network (Toronto, Canada) epilepsy clinic from January 1, 2014 to November 20 2020 were retrospectively identified with demographics and neurological data and outcomes collected. Results: A total of 195 cases were identified, with a median maternal age of 32 years (SD 4.58), a median age at first seizure of 17 years (range 1 month – 36 years old), 52% were diagnosed with genetic generalized epilepsy and 50% endorsed 6 months of seizure freedom prior to conception. In pregnancy, 93% took ASM(s) with 77% receiving therapeutic drug monitoring (TDM) and drug dose adjustments reported in 69%. Most cases (73%) maintained a stable seizure frequency. Conclusions: This study provides new Canadian data on PPWE at a tertiary care center. PPWE are overall well controlled, more likely to have young adult onset, genetic generalized epilepsy with nearly all taking ASM(s) during pregnancy. While high rates of TDM and drug dose adjustments were observed, most experienced seizure stability in pregnancy.

Background: Carotid body tumours (CBT) are rare neoplasms of the paraganglia at the carotid bifurcation. Histopathologic analysis alone is insufficient to confirm malignancy, requiring metastases to non-neuroendocrine tissue including cervical lymph nodes for definitive diagnosis. The role of selective neck dissection (SND) during CBT surgeries in detecting malignancy and guiding subsequent management remains uncertain. Methods: A retrospective case series was performed on all patients undergoing CBT surgeries with SND between 2002 and 2022. Data collection included demographics, genetic and laboratory testing, imaging, intra- and post-operative complications, follow-up and histopathology. Results: Twenty-one patients underwent CBT resection with SND. Of these, 3 had carotid artery injuries, and 5 had nerve injuries. One patient experienced peri-operative embolic strokes, presumed related to tumour embolization. Three patients were found to have lymph node involvement, confirming malignancy. Malignancy was significantly associated with the risk of carotid injury (p = 0.04.) Conclusions: SND is a useful adjunct in detecting malignancy during CBT resection. The incidence of malignancy in CBT is low but not negligible and SND should be considered in patients with suspected malignancy or high-risk factors. This study’s 14% incidence of malignancy suggests there may be a rationale for considering universal implementation of SND during CBT resection.

Background: Long-term efficacy of inebilizumab (INEB), an anti-CD19+ B cell-depleting antibody approved for the treatment of seropositive-aquaporin-4-antibody (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) was evaluated over N-MOmentum (NCT02200770) open-label period (OLP) vs azathioprine and other immunosuppressants (AZA/IST) and vs PBO. Methods: Two historical comparator groups (HCGs), AZA/IST (N=132) and PBO (N=106), derived from published NMOSD studies, were used to compare efficacy of INEB (N=208) over the OLP. Hazard ratios (HR) for INEB vs HCGs were estimated using Cox proportional hazards (PH) regression. Time to NMOSD attack was analysed using parametric and flexible survival (spline) models. Results: Time to NMOSD attack for N-MOmentum PBO compared to PBO was HR 1.15;(95% CI:0.67–1.91; P=0.58). The HRs for time to NMOSD attack for INEB vs AZA/IST and PBO groups were 0.29(95% CI:0.17, 0.42; P<0.001) and 0.15 (95% CI:0.10, 0.21; P<0.001). At 4 years, estimated attack-free survival was 77% (95% CI:71, 83) for INEB, 36% (95% CI:27, 46) for AZA/IST, and 12% (95% CI:7, 20) for PBO. Conclusions: INEB was associated with a statistically significant reduction in risk of an NMOSD attack and provided a long-term attack-free probability over the OLP compared to the relative short-term benefit observed with AZA/IST.

Background: More than 1 in 4 children admitted to the pediatric ICU (PICU) have suspected neuroinflammation for a variety of reasons. While often beneficial, uncontrolled inflammation can lead to secondary neurologic injuries and interfere with repair mechanisms. Methods: A prospective cohort study was initiated at Alberta Children’s Hospital to evaluate neuroinflammation in children admitted to the PICU. Forty-eight cytokines, chemokines and growth factors collected at multiple pre-determined timepoints were analyzed along with data on clinical trajectory. Preliminary exploratory analyses of patients enrolled January 2022-July 2023 were completed. Results: Fifty-three patients were included in the initial analysis. Encephalopathy (18.9%), hypoxia (17%) and TBI (15.1%) were the most common reasons for enrollment. All groups had temporal alterations in serum cytokines, with primary inflammatory brain diseases having the highest levels of innate inflammation (cytokine storm) on admission and day one compared to other subgroups. There was a trend towards normalization of cytokine levels over time. Conclusions: Temporal profiling of cytokine levels can inform on neuroinflammatory pathways contributing to the clinical course in critically ill children. Further analysis is ongoing with the entire cohort to evaluate longitudinal and between-group differences. Improved understanding of altered neuroinflammatory pathways in this population may assist with rationalizing targeted immunotherapies to improve outcomes.

Background: Pediatric arteriovenous malformations (AVMs) are rare, but represent the leading cause of intracranial hemorrhage in children. These are traditionally understood to be congenital lesions, however AVMs recurrence within previously unaffected tissue challenges this understanding. Recurrence after microsurgery and endovascular treatment have been studied in greater detail, but little literature exists surrounding recurrence after Gamma Knife Radiosurgery (GKRS). Methods: We performed a retrospective chart review of all pediatric AVMs treated with GKRS at our centre. Charts were assessed by two reviewers to identify cases of AVM recurrence after angiographically confirmed obliteration. To contextualize our institutional patterns, we also performed a structured literature review of published data reporting pediatric AVM recurrence after GKRS. Results: Our institutional review revealed two cases of AVM recurrence after angiographically proven cure, and our review of literature identified nine retrospective reviews and three case reports, which in total reported 22 individual cases of recurrence. The recurrence rate in the retrospective reviews ranged from 0 to 18%. Conclusions: The current work illustrates that while AVM recurrence is rare, it is a possible complication of GKRS. There was also a qualitative suggestion that embolization prior to CT increased risk of recurrence. Both these facts should be included in decision-making and patient counselling.

Background: Primary central nervous system lymphoma (PCNSL) is highly sensitive to corticosteroid induced cell arrest, apoptosis and shrinkage. However, the precise impact of preoperative corticosteroid on accuracy of PCNSL diagnosis using tissue obtained from open or stereotactic biopsies remains debated. Methods: We conducted a systematic review and meta-analysis to determine the effect of preoperative corticosteroids on non-diagnostic biopsy rates for PCNSL in immunocompetent adults. Subgroup analyses explored whether non-diagnostic rates varied based on biopsy type. Results: Nineteen studies, comprising 1226 patients (55% male; mean age: 60.3 years), of which 679 (55.4%) received corticosteroids prior to biopsy were included. Overall, patients pretreated with corticosteroids were two times more likely to have a non-diagnostic biopsy compared to patients that were corticosteroid-naïve prior to biopsy (RR = 2.1 [95% CI: 1.1-4.1]). In the subgroup analysis limited to stereotactic biopsies, patient pretreated with corticosteroids were three times more likely to have a non-diagnostic biopsy (RR = 3.0 [95% CI: 1.2-7.5]). Whereas, in the open biopsy subgroup, there was no significant difference in non-diagnostic rates. Conclusions: Corticosteroids should be withheld, if clinically safe, prior to stereotactic biopsies in cases of suspected PCNSL. If corticosteroids are administered preoperatively, an open biopsy should be considered instead of stereotactic biopsy.

The business and human rights (BHR) framework has regularly been considered the superior legal regime of corporate accountability for business-related human rights abuses, which must be both protected from and incorporated into investment treaties. However, investment treaties have surpassed the BHR framework in an important respect: certain investment treaties impose strict international legal obligations, including human rights-related obligations, directly on investors, thereby going beyond the normatively ambiguous corporate responsibility to respect. Investment treaty reform initiatives, including those seeking to align investment treaties with the BHR agenda, should, therefore, take care to avoid inadvertently undoing this advance towards investors’ legal accountability.

Background: Care for patients with compression neuropathies (carpal tunnel syndrome, ulnar neuropathy) is often fragmented, uncoordinated, and slow. Patients go through multiple steps (neurology consultation, nerve testing, ultrasound, splints, injection, surgical opinion, surgery) with waits between each step. We used a Value-Based Health Care (VBHC) model to develop a multidisciplinary clinic with a novel care pathway. Methods: A Shared Care initiative supported the development of an Integrated Practice Unit (IPU). Key multidisciplinary team members were identified. Participants attended a curated three part VBHC workshop. Process mapping enabled identification of efficiencies. Results: 14 team members participated in the workshops. Condition specific outcome measures were identified (Boston CTS measure, 10-point touch, MRC strength and pain scale) and will be collected longitudinally. Criteria and clinical pathways were developed for mild, moderate, and severe carpal tunnel syndrome. Resource materials for patients and providers were developed. Conclusions: A VBHC framework supported development of a novel clinic for compression neuropathy. Responsibility for the full cycle of care rests with the IPU. Systematically tracking functional outcome measures enables quality improvement. By streamlining the patient journey and substantially reducing wait times between steps, the new care pathway reduces complexity and improve outcomes. Evaluation of impact if this new clinical model is ongoing.