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: The long-term outcomes of inebilizumab in participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without was evaluated. Methods: N-MOmentum (NCT02200770) was a 28-week randomized phase 2/3 trial of inebilizumab vs placebo, with an optional Open-Label Period (OLP) (>2 years). In this post hoc analysis, AQP4+ participants who received inebilizumab (through the OLP) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Results: Among participants who received inebilizumab during the study, 94 received prior AZA/MMF and 103 were immunosuppressant naïve. Annualized relapse rate (95%CI) for participants with prior AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. Participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior AZA/MMF and 46.6% (48/103) of naïve. Most adverse events were infection-related for both groups; 72.3% (68/94) for prior AZA/MMF and 77.7% (80/94) for naïve. Conclusions: This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.

Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.

Background: The complement component 5 inhibitor therapies (C5ITs) eculizumab and ravulizumab have been approved or submitted for regulatory approval in several regions for AQP4+ NMOSD. Methods: This global, long-term, prospective, multicenter, observational registry will enroll adult patients with AQP4+ NMOSD being treated with eculizumab or ravulizumab and who have received ≥1 dose of eculizumab or ravulizumab within 4 or 12 weeks prior to enrollment, respectively. Inclusion criteria include available historical data on C5IT dosing since initiation and the number and types of relapses from 1 year prior to C5IT initiation through enrollment. The primary outcome is annualized relapse rate. Safety outcomes will include serious adverse events, meningococcal infections, and pregnancy, breastfeeding, and neonatal outcomes. Data will be collected prospectively for up to 5 years. Approximately 130 patients will be enrolled, with a maximum of around 200 patients in up to 10 countries globally. Results: N/A Conclusions: This registry will collect data to characterize the long-term effectiveness and safety of the C5ITs eculizumab and ravulizumab in patients with AQP4+ NMOSD to provide evidence on the real-world impact of C5ITs in this patient population.

Background: Virtual neurological assessments were increasingly used and an important viable option during the COVID-19 pandemic. However, the accuracy of such assessments is unknown. Methods: Clinical records were reviewed in a predominant multiple sclerosis outpatient clinic at an academic teaching hospital from March 23rd 2020 to March 23rd 2021 during the COVID-19 pandemic. Patients assessed during this period were analyzed with an initial virtual assessment compared to subsequent in person evaluations. Results: 1036 patients were included. 27.8% (n=288) of consultations were video and 72.2% (n=748) telephone. A total of 13.8% (n=143) of virtual consultations revealed clinical disparities, specifically 13.5% (n=39) video and 13.9% (n=104) telephone consultations. Of all the 1036 cases, 2.32% (n=24) patients stated they were stable but significant changes were seen on the exam, changing the clinical impression. 11.5% (n=119) stated they were deteriorating virtually but not confirmed when examined in person, with an alternative explanation found. Conclusions: Virtual assessments were accurate in over 85% of the outpatient neurological cases during the pandemic. However, it should be noted that the in person neurological exam led to a change in clinical opinion in 13.8% of assessments. 2.32% patients described clinical stability, but different clinical management plans resulted when significant exam findings were identified.

Background: Intravenous Immunoglobulin (IVIg) use for Central Nervous System (CNS) conditions has increased over the last decade. In many CNS disorders, robust evidence for IVIg efficacy is still lacking. Building on the success of the British Columbia (BC) Neuromuscular IVIg utilization initiative, Guidelines for IVIg use in CNS conditions were developed. A provincial screening program was launched in 2023. Methods: For CNS IVIg, requests, diagnosis, dosing, consultation letters and treatment questionnaires were reviewed. Patient management was compared to provincial guidelines. A letter was sent to the ordering physician with the results of the review and treatment recommendations when management differed significantly from guidelines. Review of the first year’s cases was conducted. Results: Over the first 11 months of the program, 79 IVIg renewal requests were reviewed. The most common diagnoses were antibody mediated autoimmune encephalitis, severe drug resistant non-surgical epilepsy and Susac’s syndrome. Recommendations included dose reduction, discontinuation of IVIg, or initiation of alternative therapies for many of the requests. Conclusions: IVIg may be effective in the management of some CNS inflammatory conditions. A physician-led utilization program in BC with targeted education to ordering physicians promotes best practice. Review of year one data will inform a quality improvement cycle to optimize the guidelines.

Background: Vestibular schwannomas are the most common tumour of the CPA with an annual incidence of 17.4/1 million. Approximately 5-10% of these tumours demonstrate spontaneous regression without intervention while under observation. Previous research studies have assessed patient factors and imaging characteristics through chart review to attempt to identify predictive factors of spontaneous regression. There have not been any studies where patient questionnaires are used to assess patient lifestyle factors or characteristics which may predict spontaneous regression. Methods: Using a clinical database of acoustic schwannomas treated by one team at our institution, we have identified approximately 40 patients, of a database of 900 patients, who have demonstrated significant spontaneous regression (>5mm in size reduction in one dimension) or complete resolution of their acoustic schwannoma. Clinical, radiological, and lifestyle factors are reviewed though clinical records and patient questionnaire. Regression analysis is performed. Results: Using patients who have tumors with significant spontaneous regression, we attempt to create a model that predicts regression of these tumours. Conclusions: In conclusion, this is the first study to consider patient lifestyle factors obtained through patient survey in addition to clinical and radiographic factors to attempt to create a predictive model of spontaneous regression of acoustic schwannoma.

Background: Medical curricula are often created with limited patient and student input and underrepresent certain body types. Traditional medical education often prepares learners to perform procedures, such as lumbar punctures (LPs), on a young white able-bodied 70kg male. When approaching diverse patients, this educational gap can lead to medical learners’ lack of confidence, skill, and knowledge, resulting in poor patient experiences. Methods: This co-design project involves patient and student input. We interviewed five patients who underwent LPs and explored their experience through a trauma-informed approach. To visualize landmarking across body types, we recruited nine volunteers of diverse body sizes, ages, tattoos, and skin colour (Fitzpatrick Scale). Incorporating patient narratives, as well as videos and photographs showing landmarking on diverse bodies, we crafted an online LP instructional module. Focus groups of 6-10 students will be held to collect student perception of the effectiveness of the module. Results: Our learning module and related media will be built into Western University’s Undergraduate Medical Education curriculum, available under a Creative Commons license through the Western Health Education Media Library. Conclusions: Integrating patient experience and student feedback, we are developing a comprehensive educational tool to better equip medical learners to deliver patient-centered LPs across diverse body types.

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: Shared decision-making (SDM) is a dynamic, patient-engaged approach to collaborative medical care. Limited SDM tools exist in pregnancy. We aimed to examine the need and usability of a novel SDM tool for pharmaco-therapeutic treatment of neurological conditions in pregnancy. Methods: This is an exploratory mixed-methods study. Non-pregnant women of any age were recruited using convenience, purposive sampling from an academic neurology clinic in Toronto. Participants reported the user friendliness of the SDM by completing the systems usability (SUS) questionnaire and participated in a focus group to further elaborate on their experience. Results: Eleven participants completed the survey 45% each between age 31-40, and 51-60. Median time spent on the tool was 17.2 minutes, and median SUS score 70 (<68 being not usable). Thematic data analysis from 2 focus groups, identified technical and content improvements: use of inclusive language, simplified design, and importance of patient engagement in SDM. Conclusions: Based on our preliminary results, a SDM web-tool for medication-related concerns of pregnant patients with neurological conditions is needed and usable. With integration of patients’ lived experiences, this novel tool may serve as an anchor point for future work in this field.

Background: Improvements in daytime functioning ideally accompany improvements in insomnia. Scores on the Insomnia Severity Index (ISI) daytime-related items were analyzed following treatment with lemborexant (LEM), a dual orexin receptor antagonist, or placebo (PBO), based on baseline severity. Methods: Participants (≥18 y) with insomnia disorder in E2006-G000-303, a 12-month, randomized, double-blind, PBO-controlled study (first 6 months: Treatment Period 1 [TP1]), were randomized to PBO or LEM 5 mg (LEM5) or 10 mg (LEM10) for 6 months. ISI items are rated 0 (no problem) to 4 (very severe problem); daytime-related ISI items have a maximum score of 16. Results: Of 949 participants, 749 (78.9%) completed the ISI at baseline and end of TP1. Baseline daytime ISI total score distributions were similar between groups. More participants with baseline scores of 9-12 and 13-16 shifted to 0-4 with LEM5 (49.7% and 39.1%, respectively) and LEM10 (46.2% and 46.3%) versus PBO (26.6% and 29.6%). Overall shift distributions were significantly different, favoring both LEM groups (P<0.01). LEM was well tolerated. Conclusions: More LEM-treated participants had improved daytime functioning, evidenced by the significantly larger number of participants whose scores moved into lower categories (ie, better sleep) versus PBO-treated participants, demonstrating additional value beyond improved sleep parameters.

Background: Traditional insomnia drugs enhance gamma-aminobutyric acid and are associated with abuse/dependence. Dual orexin-receptor antagonists (DORAs) represent an alternate mechanism promoting wakefulness, rather than inhibition. Nonclinical studies indicate DORAs do not demonstrate abuse potential. Nonetheless, based on human abuse potential (HAP) studies and lack of postmarketing data at approval, DORAs are Schedule 4 controlled substances. However, HAP studies may not predict real-world abuse-potential risk. Methods: Adverse events with preferred terms (PTs) of drug-withdrawal-syndrome, drug-abuse, and drug-dependence were evaluated from Eisai’s ongoing global postmarketing safety surveillance system in the US, Canada, and Japan (20/Dec/2019–30/Sep/2023) and the FDA Adverse Event Reporting System (FAERS; 01/Jan/2015–30/Jun/2023). In FAERS, reports of those PTs from DORAs (lemborexant/suvorexant/daridorexant) were compared with zolpidem and with benzodiazepines approved for patients with insomnia (estazolam/temazepam/triazolam). Results: Since lemborexant’s approval, few of the 3 PTs were reported in Eisai’s surveillance system (~0.15 cases per million patient-days of global exposure). Reports in FAERS for PTs of drug-withdrawal-syndrome, drug-abuse, and drug-dependence for DORAs (10,202 reports) were <0.1%/<0.1%/0.1%, respectively. Reports for benzodiazepines (5534 reports) were 0.8%/12.9%/3.7%, respectively, and 1.0%/9.1%/5.3% for zolpidem (18,330 reports), respectively. Conclusions: Abuse potential may be better represented by nonclinical studies and national surveillance systems, suggesting DORAs may not pose meaningful abuse potential and related risks.

Background: Despite efforts to advance equity, women face gender-based barriers in research, including fewer senior authorship and grant opportunities. We examined gender disparities in Canadian Institutes of Health Research (CIHR) funding for Canadian neurology divisions and departments. Methods: Data on CIHR grant recipients and metrics (duration, quantity, and contribution) within Canadian neurology divisions and departments (2008-2022) were acquired from the CIHR Funding Decisions Database. Gender-based differences in grant prevalence, duration, and contribution amount within neurology were calculated with subgroup analysis for Canadian neurologists and Project Grant awards. Results: 1604 grants were awarded to Canadian neurology divisions and departments between 2008-2022. Women received fewer grants (41.46%), less funding (p<0.0001), and shorter grant durations (p<0.0001) than men annually. Women comprised the minority of recipients (45.47%) and were less likely to be awarded grants (p<0.001) annually relative to men. Differences were consistent in subgroup analyses, except grant durations were equal across genders in Project Grant awards. Conclusions: Gender disparities persist in CIHR grant funding to Canadian neurology divisions and departments. Women receive fewer grants, lower contribution amounts, and are less likely to be recipients compared to men. Future work includes addressing gender differences and continuing to evaluate CIHR funding to provide equitable opportunities for women.

Background: Cancer survival rates in Canada have been improving, leading to a steady increase in the number of survivors entering the typical ages of dementia onset. Yet, some cancer treatments (e.g. chemotherapy) are neurotoxic and adversely affect normal brain functioning. We conducted a review to examine changes observed in brain imaging and cognitive measures in survivorship, and long-term risk of dementia among cancer survivors. Methods: 91 Primary studies were selected from PubMed. Inclusion criteria were studies investigating the changes in brain imaging, cognition, and future dementia risk among adult survivors who received chemotherapy. Study quality was assessed based on 1) prospective, controlled design, 2) sample size, and 3) validated imaging and cognitive metrics. Results: Imaging studies identified MRI-based structural grey and white matter changes and functional network changes among survivors. Cognitive studies reported heterogeneous impairments in attention, memory, and executive function. In studies that examined dementia risk among cancer survivors, 67% reported lower risk of dementia, while 33% reported no association or a higher risk. Conclusions: While short-term cognitive impairment with associated changes on brain imaging is widely reported, findings concerning future or long-term cognitive impairment are mixed. Studies are warranted to identify potential connections between short-term and long-term cognitive function after cancer treatment.

Background: Sex and gender are related but distinct determinants of disease, treatment response, and research reproducibility whose consideration is increasingly required for research funding. Nevertheless, the quality of sex and gender reporting in neurological randomized controlled trials (RCTs) remains unknown. Methods: This ongoing study of RCTs associated with Food and Drug Administration neurological drug approvals aims to determine the frequency of accurate reporting of RCT participants’ sex and gender. Secondary outcomes include changes in reporting over time and RCT design characteristics. Results: Preliminary analysis included 145 RCTs (153,410 participants) associated with 77 medications approved in 1985-2023, most commonly for epilepsy (19%), migraine (16%), and multiple sclerosis (16%). Sixty-six RCTs (45.5%) used sex-related terms appropriately. Nine RCTs (6.2%) reported gender accurately. Fifty-three RCTs (37%) used sex- or gender-related terms interchangeably. There are no statistically significant differences in the proportions of studies reporting sex and/or gender accurately when comparing those published until versus after 2017. No RCT reported sex or gender collection methods, definitions of sex or gender, or including sex or gender minority participants. Conclusions: Preliminary results suggest shortcomings in reporting sex and, especially, gender accurately and inclusively among neurological drug RCTs and no significant improvement thereof in recent years.

Background: We evaluated the accuracy of code strokes activations at two comprehensive stroke centres in Toronto, Canada. Methods: We conducted a multi-centre, retrospective cohort study of all adult patients seen as code stroke in emergency rooms (ER) of two comprehensive stroke centres (CSC) in Toronto, Canada between January 1, 2022 and Dec 31, 2022. We included cases where the code stroke was activated in the field by paramedics and where it was activated in the ER by a physician. We reported off-criteria code stroke activations as the proportion of code stroke activations that did not meet all criteria for activation, and described the criteria that were not met. Results: A total of 677 (61.9% paramedic) code strokes were seen at CSC1 and 439 (80.6% paramedic) at CSC2. At CSC1, 21.2% paramedic-activated and 38.6% ER-activated were off-criteria, and at CSC2, 14.2% paramedic-activated and 48.1% ER-activated code stroke were off-criteria. Most of these were due to incorrect assessment of the last seen normal time. Conclusions: One in five code strokes did not meet criteria for activation. Improving the accuracy of paramedic and ER assessment of last seen normal time may be an avenue to reduce off-criteria code stroke activations.

Background: Previous research demonstrates that for acute ischemic stroke (AIS) cases, rapid endovascular therapy (EVT) performance improves outcomes. This study provides updated metrics summarizing estimates for modified Rankin Scale (mRS) gains accrued by streamlining time to EVT. Methods: A systematic review and meta-analysis (MA) was conducted using electronic databases. Eligible studies reported time-benefit slope with times from AIS onset (or time last-seen-normal) to EVT commencement; the predictor was onset-to-groin (OTG) time. Primary and secondary outcomes were 90-day functional independence (mRS 0-2) and 90-day excellent function (mRS 0-1), respectively. Results: The five included studies showed increased chance of good outcome with each hour of pre-EVT time savings for mRS 0-2 for 0-270’ (OR 1.25, 95% CI 1.16-1.35, I2 40%) and 271-360’ time frame (1.22, 95% CI 1.12-1.33, I2 58%). For studies assessing mRS 0-1, pooled effect estimates were appropriate for the 0-270’ time frame (OR 1.34, 95% CI 1.19-1.51, I2 27%) and the 271-360’ time frame (OR 1.20, 95% CI 1.03-1.38, I2 60%). Conclusions: Each hour saved from AIS onset to EVT start is associated with a 22-25% increased odds of functional independence, a useful metric to inform patient-specific and systems planning decisions.

Background: Stroke incidence is rising among younger adults (≤65yrs). Modifiable and behavioural risk factors are linked to stroke; however, limited understanding of knowledge and behaviour exists around preventative/lifestyle medicine (LSM) among this patient population. Study aim was to assess younger adult stroke patients’ lifestyle knowledge, habits, and barriers. Methods: A cross-sectional design was employed. Data were collected through an online, self-reported survey following a routine stroke prevention clinic visit and analyzed using descriptive and inferential statistics. Results: Sample included 103 participants (56.3% women, 60% white, mean age 47.6, 54.5% prior stroke). Majority (63%) understood current healthy lifestyle recommendations around blood pressure, sleep, and alcohol use, but fewer (<24.3%) around exercise and diet. Almost 70% ate processed food weekly, with emotions and social/family situations influencing eating habits. Interestingly, despite not understanding the current recommendations, >80% exercised moderately (3.5d/wk) with work and family responsibilities as main barriers. Over 50% slept <7hrs/night, had moderate to high stress levels, and implemented different coping strategies (food, TV, video games, and exercise). Majority (82.4%) reported willingness to change habits. Conclusions: Our findings provide valuable insight on young adult stroke patients’ preventative/LSM-related knowledge, habits, and barriers and provide new opportunities for the development of brain care-related initiatives.

Background: Over the past decade, worldwide stroke incidence has been increasing among young adults (≤65years), which has implications during the most dynamic period of their life. There is a dearth of research exploring young adults stroke patients’ experiences, healthy lifestyle habits, preferences, and recommendations for brain care-related initiatives. The study aimed to gain knowledge and a deeper understanding of young adult stroke patients’ experiences, lifestyle habits, and support needs for brain care-related education and interventions. Methods: A descriptive qualitative study was used. Participants who took part in the quantitative phase of a larger mixed methods study (n=103 that expressed an interest in the qualitative phase, were invited to take part in semi-structured focus groups. Simultaneous data collection and analysis are being conducted. Data are being analyzed using inductive thematic analysis outlined by Braun and Clarke (2006). Results: Findings will be available by May 20, 2024. Conclusions: Study findings will be essential to 1) mobilize an understanding of young adult stroke patients’ lived experience; 2) reconceptualize the current model of stroke care and services that is traditionally geared towards older adults; and 3) inform the development of brain care-related education and interventions to meet the unique needs, priorities, and preferences of young adult stroke patients.

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.