Background: Stereotactic laser amygdalohippocampotomy (SLAH) has recently been shown to be comparable to traditional temporal lobectomy procedures. The ideal extent and volume of laser ablations remains an area of investigation Methods: 65 patients treated with SLAH for MTS were considered in this retrospective study. Manual segmentations of ablations were created using post-procedure T1-MRI scans. Ablations were assessed in relation to whether they crossed the coronal plane of the superior lateral mesencephalic sulcus (LMS), the extent to which ablation crossed this landmark, and extent of ablation of the uncus. Analysis of was done with binary categorization of 12-month Engel classification score. Results: Distance of ablation posterior to the coronal plane of the LMS was not associated with better surgical outcome (Engel class 1: 6.32 ± 4.16 mm; Engel class 2-4: 7.93 ± 3.75mm; (p = 0.099)). Ratio of ablations extending posterior to the LMS was 0.82 (SD = .39) in Engel 1 patients, and 0.90 (SD = 0.3) in Engel 2-4 patients; (p = 0.370). Volume of ablation showed little correlation with outcome (Engel class 1: 6064 ± 2128 mm3; Engel class 2-4: 5828 ± 3031 mm3; (p=0.239)). Ablation of the uncus showed a strong association with better surgical outcome (Engel class 1: 0.71(SD = 0.31); Engel 2-4: 0.37 (SD = 0.36); p <0.001). Conclusions: Contrary to current practice, extension of ablation posterior to the LMS did not demonstrate improved outcome.

Background: Trofinetide significantly improved core symptoms of Rett syndrome (RTT) with an acceptable safety profile in LAVENDER. Here, we report the safety and efficacy results of LILAC and LILAC-2, open-label extension studies of LAVENDER. Methods: Females with RTT, aged 5–21 years, received twice-daily, oral trofinetide in LILAC for 40 weeks. Participants who completed LAVENDER and LILAC continued trofinetide in LILAC-2, a 32-month extension study. Safety assessments included the incidence of adverse events (AEs). Efficacy endpoints included the Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression–Improvement (CGI-I) scale. Results: Overall, 154 patients were enrolled in LILAC. The most common AEs were diarrhea (74.7%) and vomiting (28.6%). The mean (standard error [SE]) change from the LAVENDER baseline to Week 40 in the LILAC study in RSBQ was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean (SE) CGI-I scores compared with the LILAC baseline at Week 40 were 3.1 (0.11) and 3.2 (0.14) for patients treated with trofinetide and placebo in LAVENDER, respectively. Similar safety and efficacy trends were observed in LILAC-2. Conclusions: Trofinetide continued to improve symptoms of RTT in LILAC and LILAC-2 with a safety profile consistent with LAVENDER.

Background: The diagnosis of leptomeningeal metastatic disease has major prognostic implications. We report 13 patients with a radiologically distinct, focal, enhancing leptomeningeal lesion on brain MRI mimicking leptomeningeal metastatic disease. Methods: These patients were assessed at University Health Network between January 2001 and December 2023. Results: Median age was 68 years and 10 patients were women. All patients had brain MRI including contrast-enhanced T2-weighted FLAIR and T1-weighted spin echo sequences. MRI in all patients showed a focal enhancing lesion along the leptomeningeal surface of the brain. The MRI exams were reported as possible metastatic disease for the majority (9/13) of patients. Each lesion was curvilinear rather than sheet-like, and some consisted of multiple connected/branching curvilinear structures with the appearance of abnormal vessels. Some lesions had visible connection with a nearby cortical vein. The lesions were distinct from normal blood vessels. Follow-up contrast-enhanced brain MRI for 8/13 patients at a median of 3.9 years showed all lesions were unchanged over time. Conclusions: We describe a distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics metastatic disease. These lesions are likely a type of low-flow vascular anomaly. Their curvilinear/branching shape and intense enhancement particularly on T2-weighted FLAIR images distinguishes these lesions from tumor.

Background: Aromatic l-amino acid decarboxylase (AADC) deficiency is a metabolic disorder that causes deficient serotonin, dopamine, and catecholamine synthesis. How children respond to neurological insult post intracranial gene therapy remains underreported. We present a 10 year old girl with profound neurological injury after a brief in-hospital cardiac arrest, secondary to viral infection-induced respiratory failure, 4 years after gene therapy. Methods: Patient’s chart review included brain imaging, clinical notes, laboratory results, and treatment. Results: MRI showed symmetric abnormalities in the basal ganglia, thalami, cortex, and cerebellar hemispheres. CSF analysis showed homovanillic acid 27 nmol/L (reference range 167-563) and 5-hydroxyindoleacetic acid 7 nmol/L (reference range 67-189). She developed generalized dystonia and oculogyric crises which were not seen since before gene therapy. There was poor catecholamine production causing refractory hypotension. She required a one-month stay in ICU for hypotension and status dystonicus. Dystonia was controlled with high doses of 6 agents. Conclusions: We describe a patient with AADC deficiency post gene therapy who experienced disproportionately severe neurological injury and decreased AADC activity after hypoxic neurological insult. There may be unique considerations of dopaminergic neuron integrity, AADC gene promoter sensitivity, and cerebrovascular autoregulation in children with AADC deficiency post gene therapy.

Background: Degenerative cervical myelopathy (DCM) is the most common form of atraumatic spinal cord injury globally, yet clinical guidelines remain unclear on surgical recommendations for patients with mild forms of DCM. This is in part due to limitations in current MR imaging interpretation and complex mechanisms of neurological deterioration. Supervised machine learning (ML) models can help to identify clinical and imaging indicators of deterioration within mild DCM patients. Methods: 127 MRI scans (T2w, Diffusion Tensor Imaging, and Magnetization transfer scans) accompanied by a series of clinical tests underwent a semi-automated analysis to derive quantitative metrics. Random forest classifier, Support Vector Machine, and Logistic Regression models were trained and tested to predict 6-month neurological deterioration within patients. Results: The ML models performed, on average, better than previous studies with a balanced accuracy ranging between 70-75%. “Advanced” imaging metrics such as diffusion tensor imaging and magnetization transfer scans played an important role in improving model accuracy but only when used near the maximally compressed disc level, suggesting that limited yet targetted imaging metrics support ML model performance. Conclusions: The inclusion of specific, targeted imaging and clinical metrics support ML model performance in predicting neurological deterioration within mild DCM patients.

Background: A key efficacy indicator in generalized myasthenia gravis (gMG) treatment is improvement in MG-ADL score. Minimal symptom expression (MSE, MG-ADL total score of 0 or 1) is explored as a novel proposed treatment target in gMG in the phase 3 study of intravenous efgartigimod, ADAPT, and its open-label extension, ADAPT+. Methods: Post hoc analyses of acetylcholine receptor antibody positive participants in ADAPT (n=129) and ADAPT+ (n=111) were performed. Results: In ADAPT, 44.6% receiving efgartigimod achieved MSE vs 10.9% of participants given placebo. Despite less frequent assessment during ADAPT+, 40.5% of participants achieved MSE. Eighty-one percent of participants treated with efgartigimod who achieved MSE in ADAPT also achieved MSE during ADAPT+; 23% who had not achieved MSE in ADAPT did in ADAPT+. Achieving MSE was associated with substantial improvements in QMG, MGC, MG-QoL15r, and EQ-5D-5L mean scores of 11.4, 16.0, 12.4, and 0.3 points, respectively, from baseline to best score (across all visits). These drastic improvements resulted in quality of life (QoL) comparable to that of healthy populations. MSE achievement also resulted in sustained improvements in these disease-specific and QoL measures. Conclusions: Participants who achieved MSE showed substantial and consistent improvements across multiple disease measures and experienced QoL comparable to that of healthy populations.

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: Duchenne muscular dystrophy (DMD) causes progressive muscle wasting. The Canadian Neuromuscular Disease Registry (CNDR) previously developed a comprehensive DMD dataset in accordance with the International Classification of Functioning, Disability, and Health (ICF). Our objective was to develop a brief ICF core set that best aligns with the priorities of individuals and families affected by DMD. Methods: A literature review of best practices was prepared and reviewed by a multidisciplinary team at the CNDR. The entire process involved patient and parent input and participation and was compliant with the World Health Organization guideline to develop brief ICF core sets. Results: An eight step process was developed. In brief, these included multi-stakeholder consensus meetings, ranking surveys, mapping to international standards, further consensus meeting, evaluation of clinical feasibility in multidisciplinary clinics across Canada, an integrated literature review, and development of a finalized brief ICF core set for DMD. Conclusions: The process of identifying the priorities of those living with DMD using the brief ICF core set will support post-marketing surveillance of novel therapies. The next step in this project will be to identify the specific outcome measures that best align with the brief ICF core set for DMD, for their eventual inclusion in the CNDR registry.

Background: Children with neurological injuries/insults carry the highest risk of death and disability in Pediatric and Neonatal ICUs. These patients comprise 25-30% of admissions and have a myriad of diagnoses. Longitudinal outcome data is required to inform treatment effects and innovation strategies. NCC at the Alberta Children’s Hospital (ACH) participates in acute, subacute, and long-term/outpatient management with an aim to use comprehensive clinical data to improve outcomes. Methods: A prospective, longitudinal, population-based observational cohort study of NCC patients from local NICUs, PICU, and a NCC follow-up program, with comprehensive data from clinical records, development scores and QoL assessments. Results: Since 2019, 929 patients have been enrolled including: 407 neonates, 167 infants, 106 preschool-age and 100 school-age children, and 152 adolescents. The most common reasons for NCC consult were paroxysmal events (36%), encephalopathy (27%) and neonatal HIE (20%). Conclusions: Our database encapsulates the diverse nature of NCC patients and has enabled cohort-specific studies (e.g., neonatal HIE and ECLS outcomes). Program evolution will further facilitate higher powered research studies through large enrollment, comprehensive data capture (with a provincial EHR), and longitudinal outcomes. Engagement with staff and families will also inform treatment and afford evidence-based counseling to families.

Background: Chordomas are rare, malignant bone tumors that present significant challenges in management and treatment due to their complex anatomical locations and propensity for recurrence. Advancements in artificial intelligence (AI) and machine learning (ML) show promise in improving chordoma management. Methods: A comprehensive literature search was conducted following PRISMA guidelines across multiple databases, including MEDLINE, Cochrane, Embase, Scopus, and Web of Science. The search targeted articles related to AI and ML applications in clinical tasks associated with chordoma management. The selection process involved systematic screening, data extraction, and assessment of inter-rater variability. Results: The search yielded 1,006 records, with 18 included for analysis. Convolutional neural networks (CNNs) excelled in tumor volume estimation, with the state-of-the-art model achieving a Dice similarity score of 74.2%, sensitivity of 79.4%, and positive predictive value of 74.3%. Clustering algorithms were effective in prognostic evaluations. Bayesian models and logistic regression demonstrated robustness in diagnostics. Support vector machines (SVMs) were noted for their diagnostic precision. Conclusions: AI and ML algorithms, particularly CNNs, clustering algorithms, Bayesian models, logistic regression, and SVMs, show promise in improving chordoma management through enhanced imaging, diagnostics, and prognostics. Future research should focus on larger, externally validated datasets and explore underutilized techniques like multi-modal data integration.

Background: Stroke simulation-based training has been associated with improved stroke quality metrics. The purpose of this study was to assess whether high-fidelity acute stroke simulation participation led to better knowledge retention one month post simulation in off-service residents. Methods: Off-service residents were provided with non-mandatory pre-simulation pre-reading on stroke. Immediately before stroke simulation, they completed a questionnaire to test their knowledge on a set of 8 questions related to stroke. Immediately post-stroke simulation, they were provided with a debrief including teaching on stroke. After the debrief and one month later, they completed the same questionnaire again. Results: There were a total of 16 off-service resident participants. Wilcoxon signed ranks test was performed. There was a significant difference between pre-simulation and immediate post-simulation scores on the knowledge retention questionnaire (p = 0.008). There was a significant difference between pre-simulation and one-month post-simulation on the knowledge retention questionnaire (p = 0.007). There was no difference between immediate post-simulation and one-month post-simulation on the knowledge retention questionnaire (p = 0.77). Conclusions: Participants performed better on the questionnaire after the simulation, and this improved performance was retained at one month. This is the first study to demonstrate delayed knowledge retention in stroke simulation literature.

Background: Reliable real-world data on the burden of MG is needed to inform Canadian clinical and policy decisions in the era of new MG therapeutics, including FcRn inhibitors. Given the lack of recent Canadian data on MG disease burden, the MG-REST Study aims to estimate the clinical burden of MG in Ontario. Methods: Ontario administrative data from ICES were utilized for a retrospective population-based cohort study of adults with MG identified through a validated algorithm (April 2013-March 2019) and followed for up to seven years (March 2020) to determine myasthenic crisis characteristics and overall survival (OS). Results: The MG cohort (n=2,601) had an average age of 65.7 years and 53.3% were males. Incidence of first myasthenic crisis was 9%, with 87% of events occurring at/after diagnosis. MG OS was 89%, 85% and 75% at 1-year, 2-years and 5-years, respectively, while OS after first crisis was 60%, 52%, and 39% for the same years. Conclusions: Despite the availability of conventional therapies throughout the study, MG crisis remains a serious, common complication of MG, with decreased survival at 1-year post-crisis (29% difference versus 1-year OS following MG diagnosis). Study highlights MG burden and unmet need for new effective therapies for MG treatment.

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal symptoms of Parkinson’s disease (PD). However, the therapeutic mechanisms are incompletely understood. By leveraging patient-specific brain responses to DBS using functional magnetic resonance imaging (fMRI) acquired during stimulation, we identify and validate symptom-specific networks associated with clinical improvement. Methods: Forty PD patients with STN-DBS were enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. The four cardinal motor outcomes of PD were chosen a priori and measured using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRSIII): axial instability, tremor, rigidity, bradykinesia. Stimulation-dependent changes in blood oxygen level-dependent (BOLD) signal were correlated with each symptom. Results: The relationship between BOLD response and outcomes revealed significant networks of clinical response (p<0.001). Using BOLD responses from the network hubs, each symptom-specific model was significantly predictive of actual improvement: axial instability (R2=0.38, p=0.000026), bradykinesia (R2=0.29, p=0.00033), rigidity (R2=0.40, p=0.000013), tremor (R2=0.26, p=0.00073). Conclusions: Using patient-specific imaging, we provide evidence of an association between DBS-evoked fMRI response and individual symptom improvement. Brain networks associated with clinical improvement were different depending on the PD symptom examined, suggesting the presence of symptom-specific networks of efficacy which may allow personalization of DBS therapy.

Background: Climate change, and fossil fuel combustion threaten the health of children globally through direct and indirect mechanisms,1 such as the exacerbation of ambient air pollution.1,2 Increased ambient air pollutant concentrations are associated with emergency department (ED) visits for episodic and paroxysmal neurologic conditions in adults in the Toronto region of Canada.4,5 We hypothesize that, in Calgary, Alberta, increased ambient air pollutants will be positively associated with the daily burden of pediatric ED presentations for migraine and seizures, and that a greater effect size may be present due to increased regional variability in ambient PM2.5 concentrations.3,4 Methods: Emergency records from the National Ambulatory Care Reporting System, comprising 17552 primary seizure and headache cases between 0-18 years of age and presenting to Calgary-region emergency departments between January 2012-December 2021, will be included. Quasi-Poisson regression modeling incorporating ambient air pollutants, seasonality and meteorological covariates will estimate relative risk and 95% confidence intervals of ED visit counts relative to increases in air pollutants. Results: Results currently pending and will be available for presentation. Conclusions: Significant results may inform further inquiry into the impact of air pollutants on children with neurological conditions and identify potential contributions of air quality to healthcare service demand in the Calgary region.

Background: Intracranial epidermoid cysts (IEC) are benign congenital intracranial lesions that rarely undergo malignant transformation. We report a case of IEC evolving into squamous cell carcinoma (SCC) 1-year post-resection. Further, we conducted a systematic review on cases of early malignant transformations of IECs. Methods: MEDLINE, EMBASE, and Scopus were searched from inception until December 2023 for studies reporting malignant transformations of IECs within 2 years of diagnosis. Results: A 48-year-old female underwent surgical resection of a cerebellopontine angle (CPA) IEC in May 2022. She re-presented in July 2023 with headaches, nausea, vomiting, right facial weakness, and rapid cyst progression. Repeat surgical resection revealed a high-grade SCC. Our systematic review identified 19 (10 females, 9 males) additional IEC cases undergoing malignant transformation within 2 years. The mean age at presentation was 57.6 years, most common location was CPA (n=13, 68.4%) and mean time between IEC to malignant transformation was 10.6 months. Eighteen (94.7%) cases transformed to SCC, of which 2 had leptomeningeal carcinomatosis, and 1 transformed to glioblastoma. Conclusions: While malignant transformations of IECs are rare, regular postoperative follow-up is crucial for early malignancy detection and treatment initiation. Further study is warranted to evaluate factors contributing to accelerated malignant progression of IECs.

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.