Background: The drivers that activate endogenous ependymal-derived neural stem/progenitor cells (epNSPCs) remain unknown. Understanding the mechanisms that govern the biology of these cells is critical in developing a therapeutic strategy to harness their regenerative potential after injury. Methods: FoxJ1-CreER-tdTomato reporter mice were used for epNSPC lineage tracing. A conditional genetic knock-out mouse line of glutamate-subtype AMPA receptor (AMPAR) subunits in epNSPCs was generated. Electrophysiological properties were assessed using single cell patch clamp and slice culture recordings. For in vivo studies, mice underwent cervical SCI. To examine the effect of positive modulation of AMPARs, mice received the ampakine CX546 or vehicle and underwent electrophysiological testing, behavioural assessment and spinal cord extraction. Results: Glutamate excitotoxicity, a hallmark in the pathogenesis of acute SCI, drives epNSPCs activation via AMPARs. Genetic knock-out of AMPARs in epNSPCs inhibits their activation following SCI. Positive pharmacological modulation of AMPARs after SCI enhances the migration and differentiation of epNSPCs, increases neuronal sparing and improves long-term locomotor/forelimb function. SCI decreases the excitability of corticospinal tract projections, which is improved with positive AMPAR modulation. Conclusions: Glutamatergic signaling via AMPARs is an important mediator of epNSPC activation after injury. Pharmacological targeting of this mechanism can be used to enhance endogenous regeneration and improve recovery post-SCI.

Background: Canadian Emergency Departments (EDs) are overburdened. Understanding the drivers for postoperative patients to attend the ED allows for targeted interventions thereby reducing demand. We sought to identify “bounce back” patterns for subsequent QI initiatives. Methods: From April 1, 2016 to March 31, 2022, all provincial ED datasets (EDIS, STAR, Meditech) identified patients presenting within 90 days post-spine surgery. Using Canadian Classification of Health Interventions codes, laminectomies (1SC80) and discectomies (1SE87) demonstrated the highest ED visit rates. Comprehensive chart reviews were conducted identifying surgical and medical reasons for presentation within this timeframe. Results: Reviewing a cohort of 2165 post-decompression patients, 42.1% presented to the ED (n=912) with 62.8% of these directly related to surgery. Primary reasons included wound care (31.6%), pain management (31.6%), and bladder issues (retention or UTI, 11.0%). Simple wound evaluation constituted 49.7% of wound-related visits, with surgical site infection 37.6% and dehiscence 6.6% accounting for the remainder. Pain-related presentations resulted in 72.3% discharge with additional medications, and 27.7% necessitating hospital admission. New or worsening neurologic deficits were reported in 8.9% of ED visits. Conclusions: These findings illuminate crucial aspects of postoperative care and ED utilization patterns. Prioritizing patient education, pain management, and wound care could help alleviate the national ED crisis.

Background: This study aimed to investigate the effect of impulsivity on the planning & decision-making of individuals with OCD compared to a control group, focusing on amplitude and latency during the Tower of London (TOL) task. Methods: A sample of a total of 76 (dominantly right-handed & aged between 18-30 yrs) participated. Participants with OCD were assessed with the Y-BOCS & symptom checklist, BIS-11, and the HCs were screened with the GHQ-12. ERP components were measured by using TOL on E-prime 3.0. The amplitude and latency along with the spectral power for each problem-solving task were measured and analyzed. Results: Statistically significant differences were found in the Latency variable in the left frontal area of the brain, indicating distinctive latency patterns in individuals with OCD compared to controls. No statistically significant differences were observed in amplitude or latency for other move sequences. High spectral activity was detected in individuals with OCD for an extended period. Conclusions: Individuals with OCD exhibit higher activity indicative of ambivalence during decision-making which indicates that to overcome impulsive urges, thus they need to put more cognitive effort to maintain the same outcomes. To maintain error-free results obsessive & compulsive behaviors are a necessary evil.

Background: Frontotemporal dementia (FTD) often presents with varying neuropsychiatric symptoms (NPS), which may differ based on genetic mutations. We hypothesized distinct NPS trajectories in FTD progression among carriers of chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), and microtubule-associated protein tau (MAPT) mutations. Methods: We analyzed 1662 participants from ALLFTD, including 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers. We categorized participants into four stages based on CDR plus NACC FTLD global scores: 1) Presymptomatic (consistent CDR=0), 2) Early conversion (CDR increasing from 0 to 0.5), 3) Advanced conversion (CDR increasing from 0.5 to ≥1.0), and 4) Symptomatic (CDR>1.0). The Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed NPS changes, analyzed using a mixed-effects model, accounting for age and baseline scores. Results: Our results indicated similar NPS trajectories in the presymptomatic stage for all groups. Notably, during early conversion, C9orf72 and GRN carriers exhibited significantly higher NPI-Q score increases than MAPT carriers, primarily in psychosis and hyperactivity domains. In later stages, increases in NPS were similar across groups. Conclusions: This study suggests familial FTD progression, particularly in TDP-43 pathology, may involve more severe NPS like psychosis or hyperactivity, differing from tau pathology or sporadic FTD. Further research is needed to explore these distinct trajectories.

Background: study patients with PNES’ outcome after their diagnosis in the EMU. Methods: Comparative analyses were carried out on several variables before and after diagnosis: number of participants with daily PNES, number of visits to the emergency department, number of participants who took ASMs or psychotropic drugs, and employment status. Results: 61/103 patients (79% female) participated. The median age at PNES onset was 35 years. 62% were receiving ASMs and 40% psychotropic drugs. The mean stay at the EMU was five days. PNES diagnosis was explained to almost all patients (97%) by the end of their EMU stay and was well accepted by most (89%). When contacted, 46% of participants no longer had PNES; 32% mentioned that their PNES had ceased immediately upon communication of the diagnosis. Fewer patients had daily seizures after the diagnosis. Similarly, the median number of emergency department visits was significantly lower. Only 17 patients consulted their general practitioner and 20 a neurologist after a PNES attack. The use of ASMs was also significantly reduced from 70% to 33%, with only one still taking an ASM for its antiseizure properties. Conclusions: significant reductions in PNES frequency, health care utilization and ASM use.

Background: Since 2018, several CGRP-targeted therapies have entered the migraine market, including eptinezumab. Minimal evidence exists evaluating the real-world effectiveness of switching from a subcutaneous to an intravenous anti-CGRP mAb. Methods: An observational, multi-site (n=4), US-based study, REVIEW evaluated real-world experiences of patients with chronic migraine (CM) treated with eptinezumab using a chart review, patient survey, and physician interviews. Adults (≥18 years) with a diagnosis of CM who had completed ≥2 consecutive eptinezumab infusion cycles were eligible. Results: Enrolled patients were primarily female (83%, 78/94), had a mean age of 49 years and a mean migraine diagnosis duration of 15.4 years. All patients (94/94) self-reported prior preventive therapy with 89% (84/94) reporting prior subcutaneous anti-CGRP mAb use (i.e., fremanezumab, galcanezumab, or erenumab). Regardless of prior exposure to a CGRP ligand or receptor blocker, the number of “good” days/month more than doubled following eptinezumab. Patients experienced a similar mean change in the number of “good” days/month regardless of the number and type of previous subcutaneous anti-CGRP mAb used. Conclusions: This real-world, patient survey showed that patients with prior exposure to subcutaneous anti-CGRP mAbs had high overall satisfaction with the effectiveness of eptinezumab treatment regardless of the number and type of previous therapies used.

Background: This post hoc analysis evaluated the efficacy of eptinezumab vs placebo across 24 weeks of treatment in the placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure. Methods: DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo intravenous infusion every 12 weeks. Eligible patients needed documented evidence of 2–4 prior preventive treatment failures within the past 10 years. This post hoc analysis focused on subgroups of patients with prior treatment failure on topiramate, beta blockers, amitriptyline, and/or flunarizine. Results: The full analysis set included 890 patients: 633 previously failed topiramate, 538 failed beta blockers, 508 failed amitriptyline, and 333 failed flunarizine; within each subgroup, most patients had 2 prior treatment failures (51–56%). Across Weeks 1–12 in all subgroups, patients treated with eptinezumab experienced greater reductions from baseline in MMDs than those receiving placebo, with larger reductions observed over Weeks 13–24. Similarly, ≥50% MRRs were higher with eptinezumab than with placebo and increased following a second infusion. Conclusions: Eptinezumab demonstrated greater reductions in MMDs compared with placebo across all subgroups of prior preventive treatment failure, with evidence to suggest that a second dose provides additional benefit.

Background: Migraine affects more than 1 billion people, with attacks triggered by a variety of factors. Knowledge of environmental triggers for migraine attacks is limited, and has mostly been studied via emergency room (ER) visits. There are significant barriers and delays for attending ER for migraine treatment, which create challenges for estimating causal links to environmental exposures. We assessed whether smartphone app records may have fewer barriers and reduced lags. Methods: American and Canadian participants completed an online survey about their migraine attacks, smartphone app use, and ER visits. Results: Among 308 participants, barriers to visiting ER were similar in both countries, except for financial concerns in the US. About half of participants who attended ER also recorded the attack in a diary or app. Whereas migraine patients often present to ER 7+ days after onset, records in a smartphone app dataset were created within 2 days of onset. Conclusions: Although not all severe migraine attacks are recorded by smartphone users, smartphone app records may have fewer barriers to creation and shorter time lags compared to ER visit records, making them a rich source of data for research on transient neurologic health outcomes and environmental exposures.

Background: Healthcare systems incur a significant financial burden through unnecessary neuroimaging, which globally, is in the order of the billions of dollars. Current recommendations suggest avoiding neuroimaging in patients with stable headaches, particularly those meeting the criteria for migraine. Methods: We conducted a retrospective chart review of 100 headache patients in an outpatient neurology clinic. We evaluated the use of CT and MRI imaging and the impact of neuroimaging on clinical management. Results: 55% of patients had a history of migraine. Overall, 74 of 100 patients had either CT or MRI imaging. Imaging was largely normal or identified non-specific, clinically irrelevant findings. There was 1 case of a cerebellopontine angle epidermoid tumor and another of suspected MS. Neuroimaging did not alter headache management. Conclusions: The data is consistent with current guidelines suggesting that neuroimaging is not necessary in patients with stable headaches, particularly migraine. Neuroimaging overuse might reflect lack of awareness of guideline recommendations, insecurity over diagnoses, medicolegal concerns, as well as patients and primary practitioners’ expectations. Resources to help improve public and physician awareness regarding neuroimaging use in patients with stable headache may help reduce unwarranted imaging studies and could have significant financial savings for healthcare systems.

Background: Postural instability is a common symptom of progressive supranuclear palsy (PSP). Retropulsion is one form of postural instability. Spontaneous retropulsion involves loss of balance without external provocation. Others have reported on retropulsion in the clinical setting while testing for postural instability but rates of spontaneous retropulsion in the community have not been described. This study examines the prevalence of spontaneous retropulsion in PSP. Methods: A retrospective chart review examined 60 patients from the Saskatchewan Movement Disorders Program with clinical and pathology-confirmed diagnosis of PSP. We identified patients who endorsed spontaneous retropulsion. The data was analysed with univariate logistic regression. Results: The study included 43 males and 17 females. Spontaneous retropulsion was reported in 18 (30%) patients. Among the variables, only sex showed a statistical significance (p = 0.0184) with females more likely to report spontaneous retropulsion (OR = 4.25). Other variables (PSP onset age, onset age of balance impairment, gait impairment, and disease duration) were not statistically significant. Conclusions: Our data suggest that spontaneous retropulsion is common in PSP, with females being at a significantly higher risk than males. This is useful information when counselling patients on risk-avoidance behaviour to prevent falls.

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.