Background: Medulloblastoma (MB), the most common malignant pediatric brain tumor, is often incurable upon recurrence, largely driven by treatment-resistant quiescent cells. While quiescent SHH MB populations have been identified, the mechanisms driving their chemoresistance remain unclear. Here, we investigate the role of the cell cycle inhibitor p57 in inducing quiescence and show that dexamethasone, widely used in MB management, promotes p57-mediated quiescence, potentially reducing treatment efficacy. Methods: To assess p57’s role, we introduced a TMP-inducible p57 construct into Ptch1+/- SHH MB cells and treated them with vincristine. We also treated Ptch1+/- SHH MB cells with dexamethasone and quantified p57 levels and cell cycle states using high-throughput immunofluorescence imaging. Results: In culture, nuclear p57 was enriched in Sox2+ and Nestin+ stem-like SHH MB cells relative to rapidly-cycling Atoh1+ cells. Stabilizing p57 with TMP increased G0-phase cells six-fold, exhibiting survival to vincristine doses that caused complete cell death in controls. Dexamethasone treatment increased nuclear p57 by 40% and G0-phase cells by 15% in Ptch1+/- cells, while doubling G0-phase cells in Ptch1+/-;Trp53-/- cells. Conclusions: These findings suggest dexamethasone promotes p57-mediated quiescence, potentially contributing to chemoresistance in SHH MB. This raises critical concerns about the use of dexamethasone in MB treatment, as it may inadvertently enhance tumor recurrence.

Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.

Background: Increased availability of genetic testing has led to increased burden of follow up of variants of uncertain significance (VUS). As of January 2025, 327 VUS were identified patients at BC Children’s Hospital. We propose a pipeline to triage and follow up of patients with identified VUS to clarify diagnosis through paternal testing. Methods: Of the 327 patients with VUS, 13 patients with high clinical suspicion for a genetic disorder were identified by their neurologist. Initial chart review for each patient was performed. Clinical phenotype data and the patient’s variant were inputted into the online tool Franklin. This program generates a variant interpretation based on 17/ 28 criteria in ACMG scoring. For each patient the variant would be assumed to be de novo in order to determine if parental testing could change variant classification. Results: 5/13 of the patients had suggested reclassification of variants. 6/13 of the patients would have reclassification of variant to likely pathogenic/pathogenic if the variant was found to be de novo, suggesting a need for paternal testing. Conclusions: This highlights a novel clinical pipeline to improve expediency and triaging of VUS reclassification for paternal testing in epilepsy genomics.

Background: While efgartigimod usage is expected to reduce immunoglobulin (IG) utilization, evidence in clinical practice is limited. Methods: In this retrospective cohort study, patients with gMG treated with efgartigimod for ≥1-year were identified from US medical/pharmacy claims data (April 2016-January 2024) and data from the My VYVGART Path patient support program (PSP). The number of IG courses during 1-year before and after efgartigimod initiation (index date) were evaluated. Patients with ≥6 annual IG courses were considered chronic IG users. Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before and after index were obtained from the PSP where available. Descriptive statistics were used without adjustment for covariates. Results: 167 patients with ≥1 IG claim before index were included. Prior to efgartigimod initiation, the majority of patients (62%) received IG chronically. During the 1-year after index, the number of IG courses fell by 95% (pre: 1531, post: 75). 89% (n=149/167) of patients fully discontinued IG usage. Mean (SD) best-follow up MG-ADL scores were significantly reduced after index (8.0 [4.1] to 2.8 [2.1], P<0.05, n=73/167, 44%). Conclusions: Based on US claims, IG utilization was substantially reduced among patients who continued efgartigimod for ≥1-year, with patients demonstrating a favorable MG-ADL response.

Background: Computed tomography (CT) is common imaging modality, though its utilization of iodinated contrast media (ICM) has been historically associated with adverse effects on the kidneys including nephropathy. This study aims to investigate whether administration of ICM in critically ill patients is associated with reduced kidney function and acute kidney injury (AKI). Methods: Data was used from two prospective cohort studies- ACT-TBI and CANCCAP, where patients underwent a whole head CT perfusion with additional CT scans. Serum creatinine (CR) and glomerular filtration rate (eGFR) were sequentially collected for five days of their ICU stay. AKI was evaluated following the KDIGO criteria. Results: Of the 291 patients enrolled, a stratified trend analysis for eGFR could be conducted in 158 patients. No AKI was identified in any of these patients in our study. A significant upward trend in eGFR was observed in those older than 40 years (p=0.027), those with hypertension (p=0.027), diabetes (p=0.027) and history of smoking (p=0.027), The volume of ICM received was not significantly associated with patients’ eGFR. Conclusions: AKI was not identified in critically ill patients who received ICM but significant upward trend of eGFR was seen in older individuals and those with diabetes, hypertension, and a history of smoking.

Rodney M. Feldmann (1939–2024) had a remarkable scientific career. Publishing primarily in paleontology and geology during seven decades, his legacy includes more than 500 journal articles, conference proceedings, books, book chapters, field guides, and laboratory manuals, in addition to many abstracts of talks presented at conferences. His published work has considerable breadth, but much of it concerns the paleobiology of decapods and other crustaceans. He supervised 47 M.S. theses and 14 Ph.D. dissertations and served in multiple societies and organizations and on editorial boards. Prof. Feldmann was an inspiration to his many students and colleagues around the globe and has left a lasting impact on science.

Background: Although the history of the ketogenic diet dates back centuries, with the advancement of anti-seizure medications, the use of the diet for epilepsy declined. It was not until the early 1990s that there was a resurgence of the diet as an adjunct therapy to anti-seizure medication. In 1998, the Montreal Children’s Hospital introduced the ketogenic diet to a child with drug resistant epilepsy. Shortly after, a presentation of the ketogenic diet at hospital Grand Rounds met much skepticism. However, over time the diet has developed into a well-established treatment option for children with drug resistant epilepsy. Two hundred children have since utilized the diet at the Montreal Children’s Hospital. Methods: A review of patient files since the initiation of the program was undertaken. Data was extracted regarding adverse effects, common errors in both hospital and home setting, risks for unfavorable outcomes and parental concerns Results: The development of a rigorous protocol has reduced potential adverse effects, inadvertent complications from errors have improved and parent satisfaction enhanced. Conclusions: This poster will demonstrate how an interdisciplinary approach for a ketogenic diet protocol, involving an advanced Practice Nurse, nutritionist, neurologist and parent, resulted in improved care.

Background: Schizencephaly is a congenital brain malformation involving a cleft in the cerebral hemisphere lined with abnormal gray matter with an estimated incidence of 1.5 per 100,000 live births. Methods: This study aims to characterize the radiological, etiological, and clinical features of schizencephaly, identifying factors predictive of patient outcomes. A retrospective cohort of 94 individuals, both adult and pediatric, was analyzed across four tertiary care centers. A neuroradiologist systematically reviewed imaging, while charts were reviewed for clinical features. Results: Several perinatal risk factors were identified, including young maternal age and prenatal infections. However, genetic testing yielded only one pathogenic COL4A1 mutation. MRI findings showed frequent additional malformations, including those in the pituitary, corpus callosum, and fornix. Clinical characteristics included neurodevelopmental delay (71.6%), seizures (50.0%), and motor impairments (53.3%). Outcomes were heterogeneous, with bilateral and open-lip clefts associated with more severe developmental delays, while seizure rates were comparable across subtypes. Conclusions: The complexity of schizencephaly is highlighted in the largest cohort reported with high rates of seizures, neurodevelopmental delays, and motor impairments, but outcomes varied widely based on imaging features, underscoring the importance of individualized management. The low yield of genetic findings emphasizes prenatal environmental risk factors as etiological contributors.

Background: The brachial plexus provides motor and somatosensory innervation to the upper limb and upper chest. Evaluation of brachial plexus disease is based on history, physical examination etc but imaging plays an important role for lesion localization, characterization and its classification. Effective reporting of imaging findings requires that neuroradiologist should be familiar with the brachial plexus anatomy, relevant landmarks, the spectrum and categories of brachial plexopathies. All above objectives will be discussed in this oral presentation. Methods: Normal brachial plexus anatomy is assumed for five anatomic landmarks: neural foramen, interscalene triangle, lateral border of the first rib, medial border of the coracoid process, and lateral border of the pectoralis minor corresponding to level of roots, trunks, divisions, cords and terminal branches. Conventional radiography has role in evaluating bony injuries. CT has limited role. MR used for comprehensive evaluation of the brachial plexus. Causes of brachial plexopathy are divided into traumatic and nontraumatic with specific features of each. Results: Imaging of brachial plexus is important part of treatment planning and rehabilitation of brachial plexopathies. Confident reporting can be done by knowing basics and injury patterns. Conclusions: Neuroradiologist should have sound knowledge of brachial plexus imaging in order to better contribute to pateint care.

Background: Hybrid Nerve Sheath Tumours (HNST) were introduced in the WHO Blue Book in the 2016 edition. Since that time, extracranial HNST are commonly identified but intracranial lesions are rare. Methods: A systematic review of the literature was completed. Additionally, chart reviews were completed on two cases of HNST identified at our academic center. Results: 3 reports of intracranial HNST located on a cranial nerve have been published to date. 2 cases of cranial nerve associated HNST have been identified at our academic centre. Conclusions: HNSTs may be underreported in the cranial region.

Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Background: Artery of Percheron (AOP) infarct is a rare but devastating complication following endoscopic transnasal transsphenoidal surgery (ETTS) for pituitary adenoma resection, characterized by decreased level of consciousness, mydriasis, and cognitive impairment. We reported two new and one remote case in a single institution. Methods: A retrospective case analysis and literature review was conducted. All patients had MRI-confirmed bilateral paramedian thalamic and/or midbrain infarcts following primary or redo ETTS for pituitary adenomas. Results: 8 total cases were identified, with a mean age of 45.8 years (SD: 6.06), including 6 females (75%) and 2 males (25%), undergoing initial (6/8, 75%) or repeat (2/8, 25%) ETTS for pituitary macroadenomas. Tumour consistency was solid in 6/8 (75%), hemorrhagic in 1/8 (12.5%) and cystic in 1/8 (12.5%). MRI showed bilateral paramedian thalamic infarcts (8/8 100%), with midbrain extension in 5/8 (62.5%). Intraoperative CSF leaks occurred in 6 of 8 (75%). The mean Glasgow Outcome Scale (GOS) score was 3 (range 2-4, SD: 0.37) at a mean follow-up of 8.6 (SD: 5.5) months. Conclusions: AOP infarcts are rare following ETTS for pituitary adenomas. Possible associations include large tumour size, firm consistency, and intraoperative CSF leak. Clinical outcomes are typically poor and characterized by severe long-term disability.

The Corn Belt is famously responsible for the bulk of U.S. corn production, and over half of its production comes from counties that rely on artificial drainage. We trace the history of this extensive investment in farmland and document the importance of a key institutional innovation, the drainage management district, which increased the land value of naturally wet eastern U.S. counties by 20–37 percent ($16.8–18.7 billion in 2020 dollars). While dramatically increasing agricultural productivity, drainage converted more than half of the 215 million acres of wetlands estimated to have existed in the United States at the time of colonization to agriculture.

Background: Lecanemab is the first anti-amyloid monoclonal antibody to receive full approval in the US for early Alzheimer’s Disease (AD). Methods: Using open administrative claims from the PurpleLab (6Jan2023–1Aug2024) database, patients receiving ≥1 lecanemab and with continuous clinical activity ≥6 months prior to the first lecanemab infusion were included. The follow-up period ran from the first lecanemab administration to the latest clinical activity. Treatment gap was calculated as the number of days without lecanemab supply between consecutive infusions. Results: A total of 2,840 patients were included. Mean observation period was 130.7 days. Mean age was 75.4 (SD 6.2) years, and 54.8% were female. Most prescribers were neurologists (82.0%). Within 30 days before lecanemab initiation, 77.0% of patients had AD diagnosis, and 32.1% had mild cognitive impairment diagnosis. During lecanemab treatment, 27.2% of patients received cholinesterase inhibitors and 15.5% memantine. Among patients with ≥2 lecanemab infusions, average number of administrations per month was 1.9 (SD 0.4), 17.2 (SD 7.9) days apart; 9.9% had a treatment gap of ≥90 days, including those who discontinued or continuing beyond the gap, and 2.5% of patients experienced a treatment interruption with ≥90 days gap. Conclusions: Real-world use of lecanemab appears to follow FDA-approved prescribing information with high adherence.

Background: Functional movement disorder (FMD), a subtype of functional neurological disorder, is a complex neuropsychiatric syndrome characterized by inconsistent and incongruent motor symptoms, such as tremor and gait disorder. Despite its prevalence and associated disability, FMD remains understudied. The multidisciplinary FMD Clinic in Calgary, Alberta offers an opportunity to describe characteristics of FMD, focusing on sex and gender differences, neuropsychiatric risk factors, healthcare utilization and motor phenotypes. Methods: This ongoing registry study evaluates adult FMD patients seen in the Calgary FMD Clinic by a movement disorders neurologist and neuropsychiatrist. Patients undergo detailed movement disorders and neuropsychiatric assessments, including identifying motor phenotypes, psychiatric comorbidities, and relevant psychological traits. Standardized scales evaluate symptom severity and impact. Descriptive statistics and measure of variance will be calculated for variables of interest. Results: The Calgary FMD Registry was approved in March 2024, with 53 participants currently enrolled. Data collection for this study is projected to conclude in March 2025. Conclusions: The Calgary FMD Registry is the first of its kind to systematically characterize FMD based on both movement disorders and neuropsychiatric variables. This study aims to improve our understanding of neuropsychiatric factors related to FMD. Future studies from this registry will examine short- and long-term outcomes.

Background: Efgartigimod, a human immunoglobulin G1 (IgG1) antibody Fc fragment, reduces IgG levels through neonatal Fc receptor blockade. Efgartigimod PH20 SC (1000-mg fixed dose, coformulated with recombinant human hyaluronidase PH20) is provided in a vial administered via a separate syringe (V+S). Here, we investigate bioequivalence, safety, and tolerability of efgartigimod PH20 SC administered via prefilled syringe (PFS) vs V+S in healthy participants. Methods: Bioequivalence was assessed in a phase 1, open-label study. Healthy participants (n=72) were randomized to receive one injection of efgartigimod PH20 SC via PFS or V+S in a crossover design. Separate studies evaluated feasibility of different injection speeds and usability of the PFS. Results: Bioequivalence between efgartigimod PH20 SC via PFS or V+S was established, as the 90% CI around the geometric least-squares mean ratio of Cmax and AUC0-inf was within predefined criteria (80.00%-125.00%). Most adverse events were mild to moderate. No observed differences in incidence of reported injection site reactions emerged. No serious adverse events or deaths occurred. Rapid (20-second) administration was feasible and the PFS could be safely prepared and administered by participants/caregivers. Conclusions: Efgartigimod PH20 SC administered via PFS is bioequivalent to efgartigimod PH20 SC administered via V+S, which may provide an additional convenient treatment option.

Background: RAISE-XT (NCT04225871; Phase 3 study) showed clinically meaningful and sustained improvements in myasthenia gravis (MG)-specific outcomes with zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with acetylcholine receptor autoantibody-positive generalised MG. Methods: Adults self-administered once-daily subcutaneous zilucoplan 0.3mg/kg. This post hoc analysis assessed durability of response to Week 120 in MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) responders at Week 1 of two double-blind studies (NCT03315130, NCT04115293). Responder definitions: improvements of ≥3-points (MG-ADL) or ≥5-points (QMG) (interim data cut: 11 November 2023). Results: 93 patients were randomised to zilucoplan 0.3mg/kg in the double-blind studies; 43.0% (n=40/93) and 33.3% (n=31/93) were MG-ADL and QMG responders, respectively, at Week 1. Week 1 responders spent a median #of 98.9% (5.8–99.2) and 99.0% (2.5–99.2) time in response up to Week 120 for MG-ADL and QMG. Week 1 non-responders spent# a median #of 84.6% (0.0–98.3) and 66.7% (0.0–98.9) time in response up to Week 120 for MG-ADL and QMG, with most responding later in the study. Conclusions: Among early (Week 1) zilucoplan responders, time in response remained high (99%) up to Week 120. These data demonstrate rapid and sustained efficacy with long-term zilucoplan treatment.#

Background: This local study aims to address gaps in understanding factors influencing local control in patients with brain metastases treated with adjuvant Gamma Knife Radiosurgery Methods: A retrospective analysis used a local, prospectively kept Gamma Knife database. Sixty-three patients treated with GK SRS were included. Variables included demographics, tumor characteristics, SRS parameters, and outcomes such as local control, recurrence, survival, and adverse effects. Results: At 12 months, local control was 66.7%, decreasing to 57.1% at 24 months. Distant progression occurred in 58.7%, leptomeningeal disease in 15.9%, and adverse radiation effects in 20.6%. The 12-month survival rate was 63.5%, dropping to 38.1% at 24 months. None of the examined factors significantly influenced local control. Local progression within the first year of treatment was associated with a 5.0-fold increased risk of death at 24 months, while distant intracranial progression showed a 6.0-fold increased risk at 12 months and an 8.2-fold increased risk at 24 months. Conclusions: While the parameters we examined were not linked to local control, intracranial progression significantly impacted survival. This real-world cohort provides valuable insights into the challenges of managing brain metastases. Further work is needed to refine the current treatment strategies for intracranial progression and ultimately improve survival outcomes.

Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.