Background: The complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.

Background: Neurointerventional radiology (NIR) is a growing field, offering minimally invasive treatments for cerebrovascular conditions like ischemic stroke. However, no comprehensive analysis of the current NIR landscape in Canada exists. This study aims to evaluate the NIR landscape through analysis of hospital-based services and training programs. Methods: Publicly available hospital data, fellowship programs, and national workforce statistics were analyzed to assess the expansion of NIR centers, practitioners, and services in Canada. The analysis focused on temporal trends in geographic distributions, specialists, and training programs. Results: From 2022 to 2024, the number of NIR centers increased by 20% (from 25 to 30), with new sites established in British Columbia, Quebec, and Newfoundland. Seven accredited RCPSC NIR training programs were identified, with 2 new programs expected to begin training fellows by 2030. Annual trainee enrollment also increased by about 10% per year, with over 50% being from radiology backgrounds. Endovascular thrombectomy, the most common NIR procedure, has seen an annual volume increase of approximately 13% since 2019. Conclusions: NIR is experiencing substantial growth in Canada across centers and training sites, aligning with public health goals. However, continued investment in infrastructure and workforce development is required to ensure equitable access to life-saving neurointerventional therapies nationally.

Percutaneous closure of patent ductus arteriosus has become increasingly common with advancements in interventional cardiology, especially in preterm infants. However, complications related to vascular access remain a significant concern, particularly in neonates with low birth weight. We reported a case of a 12-day-old preterm infant born at 33 weeks of gestation, who developed a right external iliac artery injury during catheter-based patent ductus arteriosus closure, necessitating emergent surgical intervention. Postoperatively, the patient recovered without signs of ischaemia or neurologic deficit. This case underscores the importance of careful vascular access planning and highlights the potential for serious complications even in technically successful patent ductus arteriosus closures in neonates.

Background: Endovascular coiling is a minimally invasive technique for managing carotid blowout in head and neck malignancies. Internal carotid artery (ICA) coil extrusion is a rare complication of this procedure, with an increased risk in post radiated neck. Methods: We present a case of advanced nasopharyngeal carcinoma with cervical nodal metastasis treated with chemoradiation and complicated with left ICA blowout which was successfully coiled and embolized endovascularly. Results: He was subsequently presented with left-sided nosebleed. Imaging demonstrated patent occluded left ICA, however with extrusion of coil material into the nasopharynx which was most likely attributed by the soft tissue necrosis in the left parapharyngeal space. He was managed conservatively as his symptoms was mild and self-limiting. Subsequent follow-up imaging confirmed stable coil extrusion. Conclusions: This case highlights the importance of identifying and assessing coil extrusion on imaging, which includes assessment of the location of extrusion, vessel occlusion patency, and potential causes of extrusion. Goals of management for symptomatic patients aims to remove extruded foreign bodies and stabilize the wound to prevent massive bleeding or further coil migration.

Macro- and microbotanical remains recovered from post-Teotihuacan occupations in quarry tunnels east of the Sun Pyramid, Teotihuacan, contribute to understanding lifeways in the surrounding valley after the partial abandonment of the city. Plant remains associated with domestic and ritual contexts from the excavations directed by Linda Manzanilla (1993–1996) are relevant to subsistence questions, aspects of surrounding vegetation, landscape exploitation, and the possibility of less-intensive agricultural production during the Epiclassic and Early Postclassic occupations.

Background: Dural tears (DT) are relatively common spine surgery complications, increasing risks of cerebrospinal fluid leaks, adverse events, and prolonged hospitalization. This study sought to identify DT predictors and compare postoperative outcomes including adverse events, revision, emergency room (ER) care, and length of stay between DT and non-DT cohorts. Methods: Retrospective analysis of elective spine surgery patients at a single tertiary centre. Variables included demographics, DT repair techniques, risk factors, post-operative adverse events, ER care within 30 days post-op, and revision. Binary logistic regression was used to analyze risk factors while hierarchical logistic and linear regressions analyzed postoperative events. Results: 6.6% of patients experienced DTs, with patches used in 40% of repairs. Age was a risk factor for DT (EXP(B)=1.039, CI [1.016, 1.063]), while minimally invasive surgery (MIS) (EXP(B)=0.521, CI [.297, .912]) reduced risk. DTs were associated with increased rates of cardiac arrest (EXP(B) = 3.966, CI [1.046, 15.033]), urinary retention (EXP(B)=2.408, CI [1.218, 4.759]), revision (EXP(B)=4.574, CI [1.941, 10.779]), ER visits (EXP(B)=1.975, CI [1.020, 3.826]), and length of stay (B=3.42, p<0.001). Conclusions: MIS seems to be associated with decreased DT risk. DTs are also associated with post-operative cardiac arrest, urinary retention, required revision surgery, and visits to the ER within 30 days post-op.

Homophonous morphs have been reported to show differences in acoustic duration in languages such as English and German. How common these differences are across languages, and what factors influence the extent of temporal differences, is still an open question, however. This paper investigates the role of morphological disambiguation in predicting the acoustic duration of homophones using data from a diverse sample of 37 languages. Results indicate a low overall contribution of morphological affiliation compared to other well-studied effects on duration such as speech rate and Final Lengthening. It is proposed that two factors increase the importance of homophony avoidance for the acoustic shape of morphs: crowdedness (i.e. the number of competing homophones) and segmental make-up, in particular the presence of an alveolar fricative. These findings offer an empirically broad perspective on the interplay between morphology and phonetics and align with the view of language as an adaptive and efficient system.

Background: Autonomic nervous system (ANS) dysfunction in people with epilepsy (PwE) is a likely contributor to sudden unexpected death in epilepsy (SUDEP). However, the nature of autonomic dysfunction among PwE remains poorly understood. We aimed to delineate self-reported ANS functioning among people with drug-resistant epilepsy, a patient group at increased risk for SUDEP. Methods: People with focal drug-resistant epilepsy undergoing stereoelectroencephalography at the Epilepsy Monitoring Unit in London, Ontario completed the Composite Autonomic Symptom Score (COMPASS-31), a widely used questionnaire for ANS function. Results: The mean total COMPASS-31 score (N=34; 13 females) was 27.36 (SD=13.77). There was no significant correlation between total COMPASS-31 score and current age (mean=32.71 years, SD=10.58; r(32)= -0.04) or age of epilepsy onset (mean=17.31 years, SD=8.26; r(30)=0). Females scored higher than males (t(32)=3.41, p<.05), but scores did not differ between participants with an epileptogenic zone in the temporal lobe(s) (N=20) and participants with multi-focal, extra-temporal or unknown epileptogenic zones (t(32)=0.18). Participants prescribed 2-3 sodium channel blocking anti-seizure medications (cardiotoxic; N=17), scored worse than participants on 0-1 sodium channel blockers (N=17) (t(32)= -2.15, p<.05). Conclusions: Autonomic testing should be a standard component of clinical care for people with drug-resistant epilepsy, especially for females and for those on sodium channel blockers.

Background: Ventricular shunt infections lead to significant morbidity and mortality. This study aimed to identify risk factors for 30-day postoperative infection outcomes of ventricular shunts for pediatric hydrocephalus. Methods: A retrospective cohort study using the National Surgical Quality Improvement Program (NSQIP) Pediatric database for years 2016-2021 was conducted. Patients under 18 years undergoing ventricular shunt surgery were included. The primary outcome was 30-day postoperative shunt infection. A multivariable logistic regression analysis of fourteen prognostic variables was performed. Results: A total of 10,878 patients (mean age 3.1 years, 44.2% female) were included. The 30-day postoperative shunt infection rate was 3.7%. Infection risk increased with nutritional support, longer operating room duration, and congenital hydrocephalus. Risk decreased with increasing age, intraoperative intraventricular antibiotics, and first-time shunt placement. Variables not significantly affecting infection risk included sex, BMI, ostomy, tracheostomy, neuromuscular disease, structural pulmonary/airway abnormality, steroid use, antibiotic-impregnated shunts, and endoscopic catheter placement. Conclusions: Postoperative shunt infections in pediatric patients are influenced by both modifiable and non-modifiable factors. Identifying and addressing modifiable risks can significantly reduce infection rates, minimize the need for surgical revisions, and enhance therapeutic outcomes and overall quality of life.

Background: Primary melanocytic neoplasms of the central nervous system (PMN-CNS) are rare lesions of variable aggressiveness originating from leptomeningeal melanocytes. They present as either circumscribed or diffuse lesions within the CNS. Given the limited number of reported cases, survival and recurrence outcomes are poorly understood. Methods: A retrospective chart review of all local adult (≥18 years) cases of PMN-CNS in British Columbia, Canada (1993-present). Results: We identified 11 cases, median age at diagnosis was 60 years (IQR: 45-64), 72% female. Tumor location included cerebrum (54.5%), spine (36.4%) and multifocal (9.1%). Four cases (36%) had confirmed GNAQ/GNA11 mutations and six cases (54.5%) were negative for BRAF V600E mutations. Operative outcomes were: gross total resection (27.3%), subtotal resection (63.6%) and biopsy-only (9.1%). Surgery was followed by adjuvant fractionated radiotherapy in 10 (91%) cases. Seven cases (63.6%) received adjuvant chemotherapy and/or immunotherapy, specifically ipilimumab and nivolumab (n=6) and temozolomide (n=1). Radiographic recurrence was observed in 7 (63.6%) cases at a median 11 (IQR: 3.5-14) months postoperatively. Median survival was 24 months (IQR: 4-103). Conclusions: Findins from this case series will assist in prognostication for PMN-CNS. Further multicenter international case series are needed to better understand these very rare neoplasms.

Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.

In the past decade, researchers have been increasingly interested in understanding the process of language learning, in addition to the effect of instructional interventions on L2 performance gains (i.e., learning products). One goal of such investigations is to reveal the interplay between learning conditions, processes, and outcomes where, for example, certain conditions can promote attention to the learning targets, which in turn facilitates learning. However, the statistical modeling approach taken often does not align with the conceptualization of the complex relationships between these variables. Thus, in this paper, we introduce mediation analysis to SLA research. We offer a step-by-step, contextualized tutorial on the practical application of mediation analysis in three different research scenarios, each addressing a different research design using either simulated or open-source datasets. Our overall goal is to promote the use of statistical techniques that are consistent with the theorization of language learning processes as mediators.

Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.

Background: Recent research has demonstrated that DBS sites in Alzheimer’s (AD) and Parkinson’s (PD) influencing cognition are functionally connected to the subiculum. However, the results are mixed, and it is unclear how or if DBS site-subiculum connectivity can be optimized to improve patient cognition. Methods: We studied how subiculum connectivity influenced cognitive outcomes in both PD (subthalamic nucleus) and AD (fornix) DBS patients (total n = 110). We first confirmed DBS site-subiculum connectivity had opposite cognitive effects in each disease. We next investigated patient factors underlying these opposing effects. Lastly, we related our findings back to clinical practice to guide DBS programming in PD and AD. Results: DBS site-subiculum connectivity correlated with cognitive improvement in AD but decline in PD. This was dependent upon hippocampal atrophy; such that higher subiculum connectivity was beneficial when the hippocampus was atrophic but deleterious when it was intact. Finally, we related our findings back to anatomy with cadaveric dissections and present how DBS stimulation can be optimized to improve patient cognition. Conclusions: DBS site-subiculum connectivity influences cognition but depends on patient factors. Thus, to optimize cognition based on patient factors, DBS electrodes can be programmed to stimulate subregions with higher or lower subiculum connectivity.

Background: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) is a rare, acquired polyneuropathy, especially in children, affecting the peripheral nervous system. It most commonly presents in a symmetric, proximal and distal, sensorimotor fashion. Immunosuppression and immunomanipulation are treatment modalities. This is an update of the 14-year-old male presented, at the 2024 CNSF meeting, with severe progressive CIDP who became refractory to steroid and IVIg but responded to Rituximab. Methods: At the age of 16, at a stage of recovery where he had regained MRC grade 5 strength diffusely, all therapies were sequentially tapered (prednisone & IVIg) or withdrawn (rituximab). He did well for approximately 6 months at which point he relapsed severely to the point of needing a walker. Repeat electrodiagnostics confirmed latency, amplitude, and conduction velocity deteriorations as compared to previous. As a result, prednisone, IVIg, and rituximab were reinstated. Results: As per the first exposure to rituximab, the patient began to respond roughly 3 months after the retreatment with targeted anti-CD20 therapy. He has again made a complete recovery physically but not electrophysiologically. This is the same pattern of response that was originally manifested. Conclusions: Rituximab appears to be an effective treatment for severe IVIg-refractory pediatric CIDP.

Background: MLASA (myopathy, lactate acidosis and sideroblastic anemia) is a rare autosomal recessive mitochondrial disorder, which affects oxidative phosphorylation and iron metabolism in skeletal muscle and bone marrow. Three genes have been identified so far, PUS1 is the most common, followed by YARS2 and MT-ATP6. We present a patient with a novel variant in YARS2 and a literature review. Methods: We report a 20-months-old girl with ptosis and low birth weight. She presented with delayed motor milestones and bulbar weakness with feeding difficulties. She had mild anemia and elevated lactate, echocardiogram revealed a mild to moderate left ventricular hypertrophy without LVOT obstruction. Results: Genetic testing showed two heterozygous variants in YARS2. The maternal one (c.948G>T, p. Arg316Ser) has been reported previously in a compound heterozygous state, while the paternal one (c.917T>C, p.Phe306Ser) has not been previously described. Genetic findings were supported by enzyme activities, which showed reduced complex I+III and complex IV activities and reduced cytochrome oxidase (COX). Conclusions: In this case report we describe a 20-months-old girl with clinical features of MLASA. A novel variant in the YARS2 gene was found, pathogenicity could be proven with clinical phenotype and enzyme activity testing.