Background: Recent research has identified the coexistence of normal pressure hydrocephalus (NPH) with neurodegenerative disorders, such as progressive supranuclear palsy (PSP). We present a patient with shunt-responsive NPH that was diagnosed with PSP at autopsy, in the absence of the typical clinical features of PSP antemortem. Methods: Medical records were reviewed, including diagnostic imaging and neuropathology. A literature review was conducted. Results: A 78-year-old female presented with a 4-year history of progressive gait dysfunction and cognitive impairment. MRI imaging was consistent with NPH. The patient’s clinical status improved significantly following high-volume lumbar puncture, with TUG test results decreasing to 25.19 sec from 58.73 sec. A lumboperitoneal shunt was inserted. Subsequent clinical improvement was impermanent, despite the absence of shunt malfunction. Autopsy revealed neuropathological findings consistent with PSP. We have identified 7 similar cases of NPH patients found to have concomitant PSP at autopsy in the literature. Like the case we present, these shunted patients experienced an initial, but unsustained, improvement in clinical status. Conclusions: We recommend the clinical management of NPH patients includesurveillance for neurodegenerative disorders. CSF diversion in NPH patients who develop concomitant PSP benefit from CSF diversion, offering them an interval of significantly improved quality of life.

Background: Spinal muscular atrophy (SMA) is caused by biallelic mutations in the SMN1 gene. Early diagnosis through newborn screening (NBS) and presymptomatic treatment optimize health outcomes. Methods: SMA-NBS began in Alberta on 28February2022. A multiplex quantitative PCR assay detected homozygous deletions of exon 7 in dried blood spot samples. Screen-positive infants underwent genetic confirmation by multiplex ligation-dependent probe amplification to determine SMN1/SMN2 copy numbers. We report clinical outcomes of SMA diagnoses through Alberta NBS over 3 years. Results: From 28February2022-31December2024, twelve infants were confirmed SMA positive, including two with 2 SMN2 copies and six with 3 SMN2 copies. Median age at initial positive screen was 6 days (range=3-9), and at diagnosis, 15 days (range=11-27). Seven infants (median age=29 days, range=18-142) received onasemnogene abeparvovec-xioi. Two received nusinersen (Day 22) or risdiplam (Day 72), followed by onasemnogene abeparvovec-xioi (Day 48 and 111, respectively). Two infants received risdiplam after 3 months of age. One infant was symptomatic at treatment initiation. Post-treatment evaluations showed ongoing motor milestone achievements. Conclusions: SMA incidence in Alberta during 2022-2024 was 8.2 (95%CI: 3.5-12.8) cases per 100,000 live births. Efforts continue to shorten age at treatment initiation, especially for those with two SMN2 copies, and to promote uniform coverage for 4-copy cases.

Background: Over 28% of people with epilepsy (PwE) experience anxiety related to their seizures, yet research on interventions for epilepsy-specific (ES) interictal anxiety remains limited. The community-based pilot, ’AnxEpi-VR,’ tested virtual reality exposure therapy (VR-ET), showing potential effectiveness and laying the groundwork for evaluating its impact on ES-anxiety in the present randomized controlled trial. Methods: Fourteen PwE admitted to the Epilepsy Monitoring Unit at Toronto Western Hospital used a 360-degree VR-intervention twice daily for five minutes up to ten days. The control group (n=7) viewed neutral VR environments (e.g., beach, forest scenes), while the experimental group (n=7) experienced VR-ET targeting ES anxiety (e.g., subway seizure scenarios). Data was collected at baseline, pre and post-VR exposure, post-intervention, and one-month follow-up using self-report questionnaires, semi-structured interviews, and VR-usage metrics. Clinicaltrials.gov NCT06028945. Results: At baseline, 71% of the control group and 83% of the exposure group had a brEASI score ≥7, indicative of an anxiety disorder. Post-intervention, this decreased to 57% and 50%, respectively. The average Fast Motion Sickness rating was 1.29, indicating minimal motion sickness. Of the exposure participants, 71% felt the scenarios simulated their real-world anxiety triggers. Conclusions: VR-ET was well-tolerated in PwE. Future recommendations include diversifying scenarios, adding interactive features, and improving software connectivity.

Background: Dermoid cysts are rare benign intracranial lesions arising from abnormal neuroectodermal folding during embryogenesis. While typically midline, near the sella or posterior fossa, we report an unusual case of a convexity dermoid cyst extending into the sylvian fissure. Methods: A 33-year-old female with a left convexity mass underwent resection, confirming a dermoid cyst. A literature review was also conducted. Results: The patient presented with progressive, intermittent right-sided hand and face paresthesias. CT showed a 4.3 × 4.7 cm hypodense lesion with peripheral calcification contiguous with the calvarium. MRI revealed an extra-axial, T2-hyperintense, T1-hypointense lesion with internal septations extending from the calvarium into the sylvian fissure. Craniotomy achieved gross total resection, revealing a soft lesion with interwoven hair, suggestive of a dermoid cyst. Pathology confirmed a cystic lesion with mature squamous epithelium, keratin, skin appendages, and chronic inflammation. Conclusions: Dermoid cysts are rare intracranial lesions that most commonly occur in the midline. This case highlights a rare convexity dermoid cyst, expanding our understanding of its atypical locations.

Pieris brassicae (Linnaeus, 1758) (Lepidoptera: Pieridae), commonly known as the cabbage butterfly, is a major herbivorous pest causing significant damage to Brassica crops, which are widely cultivated for edible parts and economic uses such as oilseed production. Conventional chemical-based pest control methods pose risks to environmental and human health, prompting interest in sustainable alternatives like biological control using parasitoids. This study evaluated crop damage by P. brassicae larvae and the potential of the larval parasitoid Cotesia vestalis (Haliday, 1834) (Hymenoptera: Braconidae) in managing pest populations. Larvae and fertilized eggs of P. brassicae were collected and reared on four host diets (cabbage, cauliflower, turnip, and generic brassica) under controlled laboratory conditions. Larval growth, feeding behavior, and development were assessed, along with a feeding index for dietary efficiency. Parasitisation was introduced by exposing larvae to adult C. vestalis, and host-parasitoid interactions were statistically analyzed using one-way ANOVA and regression models. Results revealed that larvae had the highest feeding preference and weight gain on brassica, while turnip-fed larvae consumed the least. Parasitisation by C. vestalis significantly suppressed larval development, with a strong correlation between parasitisation rates and reduced host fitness. These findings highlight C. vestalis as a promising biological control agent for P. brassicae, offering an effective and eco-friendly alternative to chemical pesticides. Further research should focus on optimizing C. vestalis mass-rearing protocols and release strategies tailored to diverse Brassica cropping systems to promote sustainable pest management.

Background: Protein phosphorylation is critical in development and tumor progression, but kinase promiscuity limits selective regulation. Alternative transcription start sites (ATSS) and alternative splicing (AS) may generate isoforms with or without the phosphorylation sites, offering a mechanism of precise control. Sonic Hedgehog (Shh) medulloblastoma (MB), the most common pediatric cerebellar tumor, arises from granule neuron precursors (GNPs) via aberrant Shh signaling. Highly proliferative postnatal day 7 (P7) GNPs and MB share transcriptomic and molecular characteristics, acting as a model for further investigation. Here, we examined the regulation of phosphorylation sites in the mRNA level in P7 GNP and MB. Methods: Integrated phosphoproteomics, proteomics, and RNA-Seq datasets were analyzed to identify candidates producing alternative transcripts with phosphorylation changes in murine P7 GNPs and Ptch1+/- MB. Differential isoform expression was validated via RT-qPCR and RNA-FISH. Results: Rnf220 and Septin9 were identified as candidates that utilize ATSS to produce differential isoforms with or without the phosphorylation sites. RT-qPCR and RNA-FISH showed significant upregulation of their long isoforms in Shh MB compared to GNPs. Conclusions: Alternative transcript generation may act as a novel mechanism for regulating phosphorylation in Shh MB. Differential expression of Rnf220 and Septin9 phosphorylated isoforms suggests their involvement in MB development, warranting further functional investigations.

Background: Vasospasm is an important complication of subarachnoid hemorrhage (SAH). Attempts to identify patients at highest risk of vasospasm have not led to practice change. We sought to identify patients at lowest risk of vasospasm by testing the prognostic utility of novel low risk criteria: mean MCA velocities on TCD that peaked and remained below 120 cm/s by the 7th day. Methods: Retrospective observational study of TCD values in patients admitted to The Ottawa Hospital with SAH 2018-2023. The primary outcome was presence of moderate to severe vasospasm (MCA mean velocity >160 cm/s) by day 21. Results: Data were collected on 211 patients, of whom 197 fulfilled inclusion criteria. Only 2 of 104 patients (2%) meeting our low-risk criteria developed the primary outcome, compared to 48 of 93 patients (52%) who did not meet criteria (RR 27). The Negative Predictive Value (NPV) for vasospasm in our low-risk group was 98%. Conclusions: Our low-risk criteria based on TCD patterns in the first 7 days after SAH can identify patients at very low risk of vasospasm with great accuracy. This could inform a future prospective study.

Background: Under Competence by Design (CBD), there are required training experiences (TEs) and entrustable professional activities (EPAs) in the Transition to Practice (TTP) stage. Limited literature exists to support an evidence-based approach to its implementation and evaluation. We created a novel outpatient rotation for PGY5 neurology residents, simulating independent practice and addressing the TTP TEs. Methods: We conducted a needs assessment with informal interviews of senior residents, the program director, and program administrator of our neurology residency program. Guided by Royal College requirements, and available TTP-focused literature, we designed a general neurology clinic run by PGY5 neurology residents. Focuses included increased independence and efficiency, longitudinal follow-up, and applied principles of practice management. Results: Go-live was August 1, 2024. Eight PGY5 residents completed one block, with a second scheduled later in the academic year. Eleven supervisors participated across two sites. Surveys and structured interviews will be used for both groups to evaluate the program, based on the Kirkpatrick Model. Conclusions: Development of a dedicated clinic addressing the TTP TEs in CBD is feasible. Iterative evaluation of the structure, delivery and outcomes of this required TE is critical to ensure that objectives are met and value is added to the residency curriculum.

Background: Residency training is well-known to be an arduous life event - especially in neurosurgery. The Maslach Burnout Index (MBI) is the gold standard for assessing burnout while the Perceived Stress Scale (PSS) identifies the relative importance of stressors. The purpose of this study is to quantify resident wellness using two validated instruments (MBI and PSS). Methods: The MBI and PSS were anonymously administered to all residents. Scores were compiled and analyzed. Freeform data was collected to identify areas for intervention. Results: Completion rate was 8/9 residents. Baseline scores showed 71% had at least moderately low personal accomplishment, 86% at least moderate emotional exhaustion, and 71% at least moderate depersonalization. 86% had above average perceived stress. Areas for improvement included call room conditions, increased social events, and study resource funding. Conclusions: Most residents are objectively experiencing low personal accomplishment, above average emotional exhaustion and depersonalization, and above average perceived stress. Assessments will characterize temporal trends, identify avenues for wellness improvement, and be correlated with interventions.

Background: Vestibular schwannoma (VS) are the most common tumour of the CPA with an annual incidence of 17.4/1 million. They typically demonstrate slow growth over time and as such, observation is a reasonable approach to management. A portion of these tumour remain static and approximately 5-10% of these tumours will demonstrate spontaneous regression while under observation, including those associated with neurofibromatosis type-2.

Previous case series (N= 13-14) have attempted to identify predictive factors for tumour growth and regression, but few have reached significance or demonstrated reproducible findings. Methods: Using a clinical database of VS treated by one team at our institution, we identified 40 patients who have demonstrated significant spontaneous regression or complete resolution of their VS. All patients received a survey by mail and telephone. Results: Radiographic descriptions were collected on 40 patients. Surveys were completed by 18 participants and an additional 18 control patients who demonstrated growth and underwent surgical resection. Conclusions: This is the largest case series we know of to date describing radiographic and clinical presentations of patients shrinking vestibular schwannoma. It is also the only study known to date to consider patient factors by survey in an attempt to identify protective factors.

Background: Arachnoid cysts are fluid collections within the arachnoid membrane. Although rare, ruptured or hemorrhagic arachnoid cysts pose significant clinical challenges and management controversies. The present study analyzes factors influencing their treatment decision using Bayesian network models. Methods: PubMed and EMBASE databases were searched to identify reports of ruptured arachnoid cysts with patient-level data. Demographic, clinical, imaging and treatment data were extracted to develop Tree-augmented naïve Bayes (TAN) classifiers for analyzing the factors influencing decision of surgery and type of surgery. A web application was developed to explore the networks. Results: Middle cranial fossa cysts were most common (95%) along with a male predominance (M:F ratio 4.29:1). Headache and vision changes were the most common symptoms and >50% had a history of head injury. Surgery was performed in 89.8% of cases with craniotomy being the most common surgical procedure. Key factors influencing the decision of surgery were cyst location, hemorrhage type, age group, and Galassi classification, while type of surgery was also influenced by head trauma, seizures, and macrocrania. Conclusions: Bayesian network analysis demonstrates that decision of surgical treatment of a ruptured arachnoid cyst is dependent on multiple interdependent factors and should be individualized to match the presentation with the surgical modality.

Background: The efficacy and safety of lecanemab have previously been evaluated in the Phase 3 randomized clinical trial, Clarity AD (NCT03887455). Methods: A Markov cohort model was developed to estimate the cost-effectiveness of lecanemab versus standard of care (SoC) in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD), with confirmed beta-amyloid (Aβ) pathology, from a Canadian societal perspective. Health states were determined by Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Transitions between health states during month 0-18 were estimated from Clarity AD. Beyond month 18, relative efficacy for lecanemab in the form of the hazard ratio for time-to-worsening of CDR-SB was applied to literature-based transition probabilities. The model included the effects of lost productivity and impact on carer health-related quality of life. Results: The incremental cost-effectiveness ratio (ICER) for lecanemab vs SoC was estimated to be CAD 62,751 per QALY gained. The probability that lecanemab was cost-effective at a threshold of CAD 100,000 was estimated to be 88.5%. Conclusions: Lecanemab represents a cost-effective option for the treatment for early AD from the Canadian societal perspective. The results of this analysis can be used to inform clinical and economic decision making.

Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

Background: Axonal degeneration has been recognized as a key early contributor to the clinical presentation and pathogenesis of amyotrophic lateral sclerosis (ALS). Activation of the calcium-dependent cysteine protease calpain-2 is considered a critical effector of axonal degeneration. Based on evidence supporting a potential benefit of calpain-2 modulation in ALS and other neurodegenerative diseases, Amylyx developed AMX0114, an antisense oligonucleotide (ASO) inhibitor of calpain-2. This phase 1 study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMX0114 in people with ALS. Methods: LUMINA is planned to be conducted at ~15 sites in North America enrolling approximately 48 participants randomized 3:1 to receive AMX0114 or placebo. After study completion, an open-label extension study of AMX0114 will be implemented if data supports a positive benefit-risk profile. Results: The primary endpoints of the study include the incidence of adverse events (AEs), serious AEs, and dose-limiting toxicities. Secondary and tertiary endpoints include PK measurements (plasma and cerebrospinal fluid [CSF] levels of AMX0114), PD biomarkers, and functional measures of ALS progression. Conclusions: LUMINA is a first-in-human study evaluating the safety, tolerability, PK, and PD of AMX0114, the first ASO targeting calpain-2 in adult participants with ALS. Enrollment is planned to begin in Canada in early 2025.

Background: Polymicrobial brain abscess (PBA) is a complex infection caused by two or more pathogens and a life-threatening condition with diagnostic and therapeutic challenges. Methods: We retrospectively identified PBAs in 31 patients (a median of 58 years; 24 male, and 7 female) then examined their clinical, radiological and pathological characteristics. These characteristics of PBAs were compared with those of monomicrobial BAs (MBAs) in the previously reported 113 patients. Results: PBAs and MBAs had a few similarities such as nonspecific clinical presentations and overall similar prognosis following surgical intervention with broad-spectrum antimicrobial therapy. However, PBAs were highly heterogeneous with more complexity on MRI/CT imaging and histopathology. While PBAs were typically rim-enhancing lesions at late-stages, 30/31 (97%) of PBAs showed the lobulation of enhancing rims/walls; on MRI, 14/26 (54%) of cases demonstrated marked difference in the thickness of enhancing rim, marked difference in the degree of DWI signal, and/or marked variation in intra-lesional MRI signal. PBA histopathology was characterized by alternating early-stage and late-stage features with a combinations of 2-4 pathogens. Conclusions: BPAs share some features with MBAs, but they are more heterogeneous with greater complexity on imaging and histopathology. Their diagnosis and disease staging require a clinico-radiologico-pathological approach.

Background: Facial diplegia with paresthesias (FDP) is a rare Guillain-Barré Syndrome (GBS) variant, characterized by subacute onset of bilateral facial palsy with no other motor weakness, absent reflexes and distal paresthesias, that may be associated with anti-ganglioside autoantibodies. Methods: Patient chart, including medical notes, radiologic, electrophysiological and laboratory testing during the patient’s hospitalization in December 2024 were reviewed. Results: We report the case of a 24-year-old woman, who presented one-week post-partum with a history of tongue and progressive distal extremity paresthesias, headache and gait instability. During hospitalization patient progressively developed bilateral lower limbs areflexia and facial diplegia. Imaging was negative for a central cause but lumbar puncture and clinical examination guided the diagnosis of FDP. Patient responded to a course of intravenous immunoglobulins (IVIg) and was discharged home without any weakness. Conclusions: This case illustrates the rarer FDP presentation of GBS, which can be more frequent in the postpartum period, and explores the differential diagnosis of subacute facial diplegia.

This paper investigates public attitudes towards education spending based on a survey experiment. It enquires whether a trade-off between education and other welfare domains, namely healthcare, unemployment benefits and pensions, diminishes support for higher public spending on education. Drawing on five Organisation for Economic Co-operation and Development (OECD) countries (Italy, Spain, Greece, Mexico and Turkey), the paper demonstrates that education spending preferences are contingent on the nature of trade-offs and the priorities of the stakeholder groups. Testing the predictive power of age, income, ideology, labour market positioning and gender, our research finds robust support for public spending on education across all countries. Nonetheless, this support diminishes significantly when trade-offs that are linked to cuts in other welfare domains are introduced.

Background: TeleStroke can improve access to stroke care in rural areas. We aim to evaluate the safety and effectiveness of intravenous thrombolysis in our TeleStroke system. Methods: The Manitoba TeleStroke program was rolled out across 7 sites between November 2014 and January 2019. We retrospectively analyzed prospectively collected consecutive acute stroke patients’ data in this duration. The primary outcome was safety and effectiveness measured in terms of 90-day modified Rankin score (mRs). The number of acute ischemic stroke (AIS) patients receiving thrombolysis and endovascular thrombectomy [EVT] and process metrics were also analyzed. R/RStudio version-4.3.2 was used (p<0.05). Results: Of the 1,748 TeleStroke patients (age 71 years [IQR 58-81], female 810[46.3%]), 696 were identified as AIS. Of these, 265(38.1%) received thrombolysis and 48(6.9%) EVT. Ninety-day mortality was 53(20.0%) among those receiving thrombolysis and 117(44.2%) had a favorable outcome (mRs ≤2). Of those who received intravenous thrombolysis, 9 patients (4.2%) were found to have symptomatic intracranial hemorrhage. The median last-seen-normal (LSN)-to-door was121 minutes and the median door-to-needle, 55 minutes. Conclusions: Intravenous thrombolysis was found to be effective with acceptable safety. TeleStroke improved overall access to stroke care and played an important role in identifying AIS patients eligible for thrombolysis and EVT.