Background: Around 10% of ischemic stroke patients have pre-existing dementia and are excluded from stroke trials and routine care. Little is known about physician practices in the stroke care of people living with dementia (PLWD) leading to limited understanding of their experiences, priorities, and outcomes. This study aims to better understand PLWD through in-depth interviews. Methods: This study employs a qualitative descriptive methodology with two sets of 20 semi-structured interviews with PLWD and their primary caregivers (dyads), and with stroke physicians. Interviews with dyads investigate their experiences, priorities, and attitudes towards stroke care. Participants will be recruited through snowball sampling and interviews will be analyzed through qualitative data analysis software. Results: Initial analyses of the PLWD-caregiver dyad interviews have been completed, revealing themes of independence, uncertainty about the future, and fears of another stroke. Conclusions: As the population ages, stroke teams will likely encounter more PLWD. Engaging PLWD and their caregivers is crucial to better understand their experiences and priorities, which will inform future studies and improve their care. The findings from the dyad and physician interviews will be relevant to a broad audience, including patients, caregivers, physicians, researchers, and policymakers.

Background: The presence of intraluminal thrombi (ILT) in acutely symptomatic carotid stenosis (“hot carotid”) represents a therapeutic dilemma for physicians. With little evidence to guide treatment, current ILT management approaches rely on individual or institutional preferences. Methods: This mixed methods study analyzed themes from semi-structured interviews with 22 stroke physicians from 16 centers, paired with a worldwide case-based survey of 628 stroke physicians conducted through the “Practice Current” section of Neurology: Clinical Practice. Results: In the thematic analysis of the interviews and quantitative analysis of the survey, participants favoured using anticoagulation with or without antiplatelet agents in patients with ILT (463/628, 74%). Despite a preference for anticoagulation, uncertainty regarding optimal antithrombotic management was noted in the thematic analysis. Additional themes identified included a preference for re-imaging patients in 3-5 days after initiating treatment to look for complete or partial clot resolution, at which point most experts would then be comfortable proceeding with revascularization if indicated, though uncertainty regarding the optimal timing of revascularization was noted. Conclusions: In cases of ILT in the “hot carotid” practice patterns of global experts show a preference for using anticoagulation and reimaging patients in 3-5 days, though there is considerable equipoise regarding the most appropriate management of these patients.

Background: Edaravone (EDV) is an antioxidant that scavengs ROS, which is known to associate with pathophysiology of ischemic stroke. Low stability and bioavailability are major EDV drawbacks. Decorating nanogel surface with glutathione to target brain tissue was performed to optimize drug delivery. Methods: Nano vehicle characterization was assessed with FT-IR and HNMR. Images from the surface of nano vehicle was captured by AFM and TEM instruments. After development of mPEG-b-PLGA EDV nano particles, their effect on biochemical factors including malondialdehyde and protein carbonyl level was measured on Wistar rats under global ischemia. The level of GSH and FRAP were also measured. Results: The Size (199 nm, hydrodynamic diameter) and zeta potential (-25 mV) of optimum formulation was assessed and the calibration curve in deionized water was created at 244 nm. In-vitro drug release profile depicted a sustained release process. EDV and glutathione presence in one vehicle simultaneously, resulted in elevated spatial memory and learning along with cognitive function. In addition, significantly lower MDA and PCO, and higher level of neural GSH and FRAP were observed. Conclusions: The developed mPEG-b-PLGA EDV nanogel can be a suited vehicle for brain drug delivery of EDV, while managing to minimize the biochemical and pathophysiological alterations in ischemic-like disorder.

Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.

Background: Little evidence exists to guide the management of symptomatic non-stenotic carotid disease (SyNC). SyNC, which refers to carotid lesions with less than 50% artery stenosis, has been increasingly implicated as a cause of stroke and TIA. Methods: Semi-structured interviews with 22 stroke physicians from 16 centers were conducted as part of the Hot Carotid Qualitative Study. This study explored decision-making approaches, opinions and attitudes regarding the management of symptomatic carotid disease. Presented here are a subset of results related to the decision to revascularize patients with SyNC. Results: Thematic analysis revealed equipoise in the decision to revascularize patients with SyNC. Participants discussed a desire to use imaging features (e.g plaque rupture and plaque morphology) to inform the decision to revascularize, though significant uncertainty remains in appraising the risk conferred by certain features. Experts support further study to better understand the use of these features in risk appraisal for patients with SyNC. Conclusions: The decision to revascularize patients with SyNC is an area with significant equipoise. Experts identify the use of imaging features as an important tool in informing the decision to pursue revascularization in patients with SyNC though more study is required in this area to better inform practice.

Background: Infantile Spasms (IS) is a rare epilepsy syndrome with characteristic features, and a strong consensus regarding treatment strategies. Clinical care pathways provide standardized and evidence-based patient care, support care quality and improve patient outcomes. Standardized electronic notes may support data collection and quality. After the concurrent implementation of an IS pathway and standardized electronic note at the Alberta Children’s Hospital in 2015, improvements in patient outcomes and quality of care were anticipated. Methods: A single-centre, retrospective chart review of patients diagnosed with Infantile spasms in Alberta, Canada from 2011-2019 was completed. Patient characteristics and outcomes were analyzed by pre-pathway and post-pathway implementation status. Results: Rates of 3-month spasm remission, and of remission without relapse did not significantly differ between pre- and post-pathway cohorts. Rates of 2-week spasm remission were not obtainable from a significant proportion of pre-pathway patient records when compared to the post-pathway group, indicating patient record quality improved following the electronic note implementation. A significant proportion of patients received Prednisolone as their first treatment for IS post-pathway implementation compared to pre-pathway (p<0.001). Conclusions: A single-centre experience with concurrent implementation of an IS pathway and standardized electronic note demonstrated no significant changes in patient outcomes. Potential improvements for patient care are identified.

Background: The Epilepsy Monitoring Unit (EMU) plays a crucial role in a patient’s diagnosis and management for seizures and epilepsy. The duration of stay required to obtain adequate information is not clear, especially in the pediatric population. In this study, we examine whether a one to four day length of stay in the EMU is sufficient to obtain the necessary information. Methods: Retrospective review of 522 admissions (2014-2021). Included any patient admitted to CHEO’s EMU for any length of time. Results: The average admission was 1.75 days with 35.7% of patients requiring repeat EMU visits. Through a binary logistic regression, we show that a previous diagnosis of refractory seizures increases the chance of readmission to the EMU. However, a diagnosis of refractory seizures is also associated with a higher chance of achieving admission goals. While other factors including seizure type, weaning of meds, goals of admission, age, and gender have no influence on likelihood of readmission or achieving admission goals. Conclusions: This study indicates that having a short admission for EMU monitoring is sufficient to capture enough data to achieve admission goals in the pediatric population.

Background: Glasgow Coma Scale (GCS) is the gold standard for neurological assessment in traumatic head injury. Limitations to GCS include variations in rater reliability, test setting and sedation/intubation. Serial Neurological Assessments in Pediatrics (SNAP) was designed to standardize neurological assessment. We examined the efficacy of SNAP for earlier detection of acute neurological decompensation. Methods: Retrospective analysis identified patients with acute neurological decline (drop in GCS of >2 in 1 hour). We reviewed GCS and SNAP (calculated using neurological consultant notes) scores 48 hours prior to decline. Slopes were calculated for each score over time. Results: Four patients were eligible, with > 2 GCS and SNAP scores available for calculation. Average slopes for GCS were 1.3, -0.8, 1.6 and 2.1 for eyes, voice, motor, and total GCS, respectively, and -2.6, 0, -2.3, -2.4, -2.4, -2.0, -2.8 and -11.9 for mental status, cranial nerve, communication, left and right upper extremities, left and right lower extremities, and total SNAP score, respectively. Conclusions: All aspects of the SNAP score had negative and steeper slopes prior to neurological decline, whereas only ‘voice’ in GCS had a negative trend. These findings suggest that the SNAP tool may be useful in earlier identification of acute decline. Ongoing prospective studies are underway.

Background: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by biallelic mutations of the survival motor neuron 1 (SMN1) gene. Early diagnosis via newborn screening and presymptomatic treatment are essential to optimize health outcomes for affected individuals. Methods: We developed a multiplex real-time polymerase chain reaction assay using dried blood spot samples for the detection of homozygous deletion of exon 7 of the SMN1 gene. Newborns who were screened positive were seen urgently for clinical evaluations. Copy numbers of SMN1 and SMN2 genes were determined by multiplex ligation-dependent probe amplication for confirmatory testing. Results: From February 28, 2022 to December 31, 2022, 42,450 newborns were screened in Alberta. Four infants had abnormal screen results and were subsequently confirmed to have SMA. No false positive newborns were detected. Three infants received adeno-associated virus serotype 9 (AAV9)-mediated SMN1 gene replacement therapy <31 days of age. One infant received SMN2-splicing modulator treatment due to maternally-transferred AAV9 neutralizing antibodies prior to gene therapy at 3 months of age. Conclusions: The estimated incidence of SMA in Alberta is 9.4 (95% CI: 2.5 – 24.1) per 100,000 live-births. During the first year of the SMA-NBS program, 4 asymptomatic infants received treatment and demonstrated excellent developmental progress to date.

Background: Duchenne muscular dystrophy (DMD) is an X-linked disease that causes progressive muscle wasting. The Canadian Neuromuscular Disease Registry (CNDR) DMD subset collects data focused on body structure and function. Our objective is to develop a broader dataset including the priorities of those living with DMD in accordance with the International Classification of Functioning, Disability, and Health (ICF) – a framework for describing disease and health functions developed by the World Health Organization. Methods: Clinically relevant ICF categories for DMD were identified and reviewed by two independent committees including two patients and six parent representatives. The Delphi approach was used to narrow ICF categories to a core set representative of DMD, which will be mapped to the CNDR-DMD subset. Results: With full result expected by the conference, the mapping of the ICF to the CNDR-DMD subset will identify data collection priorities in the four domains of functioning and disability: body functions and structures, activities at the level of the individual, participation in all areas of life, and environmental factors. Conclusions: The ICF can be used to identify data collection priorities. Broadening the CNDR-DMD subset will foster future research to include outcome measures important to patients and families affected by DMD.

Background: Perinatal arterial ischemic stroke (PAIS) is a leading cause of hemiparetic cerebral palsy. Multiple risk factors are associated with PAIS but studies are limited by small sample sizes and complex interactions. Unbiased machine learning applied to larger datasets may enable the development of robust predictive models. We aimed to use machine learning to identify risk factors predictive of PAIS and compare these to the existing literature. Methods: Common data elements of maternal, delivery, and neonatal factors were collected from three perinatal stroke registries and one control sample over a 7-year period. Inclusion criteria were MRI-confirmed PAIS, term birth, and idiopathic etiology. Random forest machine learning in combination with feature selection was used to develop a predictive model of PAIS. Results: Total of 2571 neonates were included (527 cases, 2044 controls). Risk factors uniquely identified through machine learning were infertility, miscarriage, primigravida, and meconium. When compared, factors identified through both literature-based selection and machine learning included maternal age, fetal tobacco exposure, intrapartum fever, and low 5-minute APGAR. Conclusions: Machine learning offers a novel, less biased method to identify PAIS predictors and complex pathophysiology. Our findings support known associations with concepts of placental disease and difficult fetal transition and may support early screening for PAIS.

Background: Tuberculosis is an airborne disease caused by Mycobacterium Tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to hematogenous spread to subpial and subependymal regions. Intracranial tuberculoma can occur with or without meningitis. Methods: A 3-year-old male who recently emigrated from Sudan presented to the emergency department with right-sided seizures lasting 30 minutes which were aborted with levetiracetam and midazolam. CT head revealed a multilobulated left supratentorial mass, with solid and cystic components measuring 8.0 x 4.8 x 6.5 cm. The patient had successful surgical resection of the mass which was positive for Mycobacterium Tuberculosis. He was started on rifampin, isoniazid, pyrazinamide, ethambutol, and fluoroquinolone and discharged home in stable condition. Results: Literature review on pediatric intracranial tuberculoma was performed which included 48 studies (n=49). The mean age was 8.8 ± 5.4 years with slight female predilection (59%). Predominant solitary tuberculomas (63%) were preferentially managed with both surgical resection and antitubercular therapy (ATT) compared to multifocal tuberculomas that were preferentially managed with ATT. Conclusions: Intracranial tuberculoma is a rare but treatable cause of space-occupying lesions in children. Clinicians should maintain high-level of suspicion in patients from endemic regions and involve infectious disease service early in patient’s care.

Background: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of patients with hypertonia across Canada. Methods: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative rehabilitation sites in each province. All statistical analyses were performed using the R statistical software version 4.0. Results: CP was found to be the most common diagnosis for tone dysfunction, with 58% (7/12) of sites diagnosing greater than 20 new patients per year. All 12 sites offered oral baclofen and gabapentin, and 92% of sites offered trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity procedures were offered in 83% of the sites. In 8 of 12 sites (67%), patients were seen within a formal multidisciplinary clinic to manage hypertonia. Conclusions: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Background: Prior to the pandemic, telemedicine use was limited and sparsely funded within Ontario. During the pandemic, a shift in clinical recommendations and government funding models promoted telemedicine. We aim to highlight both quantitative and qualitative aspects of the patient and provider experience over 2.5 years within a Canadian Pediatric Neurology clinic. Main objectives of the study are to assess the safety, efficiency and convenience of telemedicine. Methods: A REDCap survey was sent to all patients with a telemedicine appointment from March 2020 –September 2022 and all Pediatric Neurology providers. Survey included a 5-point Likert scale questions, open questions, and patient characteristics. Results: Responses received from 272 patients and 7 providers. 91% of patients and all providers were satisfied with telemedicine. 95% of patients and all providers felt they received or were able to provide safe/adequate care. 90% of patients and all providers reported that telemedicine was more convenient. 87% of patients and all providers were interested in future appointments via telemedicine. Conclusions: Our survey shows patients and providers had highly positive experiences with telemedicine – reporting care was adequate, safe, and more convenient. This data supports incorporating telemedicine into future care and advocates that Canadian regulations/billing codes to continue to support telemedicine.

Background: Recently, we showed cathodal high-definition transcranial direct current stimulation (HD-tDCS) inhibits spikes in refractory status epilepticus (RSE) patients. We sought to characterize relative power changes within regional frequency bands to explore connectivity throughout stimulation. Methods: 28 ICU-EEGs from 10 patients were filtered with 1Hz-lower/127Hz-upper/60Hz-notch. Power spectral density was computed for each individual bipolar-longitudinal (excluding midline) electrode chain in delta/theta/alpha/beta/gamma frequency bands. Relative power was extracted throughout recordings by Welch’s method with 2.5-second Hanning window size with 50% overlap every 10 seconds. The average of relative powers from ≤20-minute pre/during/post stimulation windows were calculated per session/chain/band. Absolute maximal relative power change between pre-during and during-post were computed. ANOVA statistically tested for differences. Results: Change in pre-during for delta/theta/alpha/beta/gamma were respectively -0.7%/-3.1%/-2.8%/-2.1%/8.2%, and during-post were 1.3%/2.8%/2.3%/1.7%/-7%. Positive average changes are increases in average relative power where negative changes show decreases. Changes in absolute maximal average relative power between pre-during and during-post stimulation between frequency bands were significant respectively (p=0.0011, p=0.0139). Conclusions: Relative power in all bands drop pre-during and increase during-post except gamma which correlates with desynchronization being a mechanism for HD-tDCS efficacy in RSE. These frequency band power changes may imply brain connectivity changes that need to be further explored.

Background: We report a case of distal right radial cutaneous sensory neuropathy secondary to participation in Pickle Ball. Methods: Case Report & Review of the LiteratureResults: Our 67yoF patient developed acute onset persistent numbness and dysesthesia in the distal right radial sensory distribution while participating in Pickle Ball, a sport undergoing rapid growth of popularity over the past decade. Nerve conduction studies (NCS) were performed in our lab following symptom onset, and the patient had previous NCS that allowed for comparison. NCS in our lab demonstrated asymmetrically reduced amplitude of right distal radial sensory responses (14.5 uV), in comparison to normal (42 uV) radial sensory responses from her previous NCS using the same protocol. All remaining NCS were normal in both studies. Conclusions: This study represents the first reported case within the literature of a Pickle Ball induced distal radial cutaneous sensory neuropathy demonstrated objectively using comparative nerve conduction studies. It is important that clinicians be aware of this entity and the possibility that it can manifest in the context of activities involving repetitive extension of the wrist. We present this case along with a review of the current literature of focal neuropathies involving the upper & lower extremities.

Background: Wolfram syndrome (WFS) is a genetic disorder clinically characterized by optic atrophy (OA), diabetes mellitus, sensorineural deafness, and diabetes insipidus. It is caused by mutations in WFS1 (mono- or biallelic) or CISD2 (biallelic) genes. Neuroradiological features include cerebellar and/or brainstem atrophy with visual pathway and white matter involvement. We report two subjects with WFS in which multifocal, progressive, and contrast-enhancing white matter abnormalities (WMA) led to the consideration of multiple sclerosis (MS). Methods: We retrospectively analyzed the clinical, genetic, and radiological data from two unrelated subjects with genetically confirmed WFS and multifocal WMA. Results: Subject I: a 43-year-old woman, heterozygous for a known WFS1 variant, had a history of congenital deafness and OA. The brain MRI documented progressive multifocal WMA including pericallosal lesions. Subject II: a 28-year-old woman, compound heterozygous for two WFS1 variants, was known for OA and diabetes mellitus. The brain MRI revealed multifocal periventricular, callosal, subcortical, and juxtacortical WMA, with some enhancing after gadolinium injection. Conclusions: Our report expands the WFS spectrum of white matter involvement to include progressive, seemingly inflammatory lesions. Although we cannot exclude a dual diagnosis, the roles of WFS1 and CISD2 in myelination suggest a selective white matter vulnerability in WFS.

Background: Circulating cell-free DNA (cfDNA) is a novel type of biomarker with a broad utility in diagnostic medicine, based on the release of DNA fragments from dying cells to the circulation. We developed an approach for identifying the tissue origins of cfDNA, using cell-type-specific DNA methylation patterns, based on a massive reference atlas of the genome-wide methylomes of multiple human tissues and cell types. Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. We demonstrated that brain cell death in CNS cancer can be detected by tissue-specific methylation patterns of circulating cfDNA. Methods: We developed a cocktail of brain-specific DNA methylation markers, and used it to assess the presence of brain-derived-cfDNA in the plasma of patients with brain metastasis. Results: We identified significantly elevated neuron-, oligodendrocyte-, and astrocyte-derived cfDNA (p<0.0001) in patients with brain metastases (n=29) compared with cancer patients without brain metastasis (n=113). Conclusions: We show a new set of biomarkers to identify brain damage with high specificity and resolution. We detected brain (neurons, oligodendrocytes, astrocytes) cfDNA in the plasma of patients with brain metastasis. Cell-type-specific cfDNA methylation markers allow the identification of collateral tissue damage, reveals the presence of metastases, and potentially assist in early cancer detection.

Background: Patient registries are an effective tool in tracking the natural history of rare diseases as well as post-marketing surveillance of novel therapies. The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects Spinal Muscular Atrophy (SMA)-specific data in 28 clinics across Canada. The objective of this study is to describe real-world data from the CNDR-SMA patient population. Methods: We report cross-sectional data from Canadian SMA patients. Patients were included in analysis if they were active (alive and with follow-up within 24 months). Results: Of 171 SMA patients included in analyses, 37% currently use non-invasive ventilation, 2% invasive ventilation, and 61% no ventilation support. Feeding tubes are used by 27% of patients. and 28% of patients have a history of scoliosis surgery. Of the 171 patients, 137 have had disease-modifying therapy: 96 on nusinersen, 22 on risdiplam, and 19 on onasemnogene abeparvovec (OA). Median (min,max) years of age at therapy initiation was 7 (0,54), 20.5 (5,53), and 1 (0,6), respectively. At therapy initiation, functional status was 32% non-sitters, 38% sitters, and 30% walkers. Conclusions: The CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada.

Background: The effect of remote ischemic conditioning on cognitive and radiological outcomes in patients with cerebrovascular disease is uncertain. We performed a systematic review to evaluate the effects of remote ischemic conditioning on cognitive and radiological outcomes in patients with cerebrovascular diseases. Methods: A systematic search using relevant keywords and database specific terms was conducted in MEDLINE, Embase, and Web of Science from inception to October 27 2022. Results: A total of 4269 articles were screened, of which 20 were included. Ten papers assessing cognitive outcomes were included, with 5/10 reporting improvements in cognitive scores relative to a control group. Sixteen papers reporting on radiologic outcomes were included, three reporting on changes in infarct volume, and four on lesion volume. Improvement in infarct and lesion volume was reported in 1/3 studies and 4/4 studies respectively, however there was considerable variation in the time between assessments (range 1-365 days). Nine papers assessing blood flow changes were found, of which 3/8 using transcranial doppler reported improved blood flow velocity post intervention. Conclusions: The articles identified suggest that remote ischemic conditioning may provide improvement for both cognitive and radiological outcomes in patients with cerebrovascular diseases, however future well-designed studies are needed to determine degree of benefit.