Gut microbiota (GM) affects muscle homeostasis, and growing evidence indicates dysbiosis of GM may be a contributing factor in the pathogenesis of dystrophies. Furthermore, GM metabolites can interact with DNA methylation. Facioscapulohumeral muscular dystrophy (FSHD) is the second common dystrophy with hypomethylation of DR1 and 5P regions of D4Z4 repeat on 4qter.

Considering alteration of GM may be a contributing factor, we investigated (i) GM alterations and (ii) the correlation of microbial-derived free fatty acids (FFAs) with methylation of DR1 and 5P regions in FSHD.

Twenty-eight FSHD patients and 28 gender-age-matched controls were included. GM characterisation was performed through 16S-rRNA sequencing. Methylation levels of DR1 and 5P regions were assessed by bisulphite sequencing. Faecal and circulating FFAs including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs) and long-chain fatty acids (LCFAs) were analysed with gas chromatography-mass spectrometry.

Altered GM was observed in patients, along with distinct profiles of faecal and circulating SCFAs, MCFAs and LCFAs. DR1 and 5P regions exhibited significant hypomethylation in FSHD compared to control. Hypomethylation correlated with faecal and circulating FFAs in patients, while no correlation was identified in healthy controls. The severely affected patients exhibited a notable increase in the prevalence of Pasteurellaceae, while the FFA profile was similar among mild and severely affected patients. This is the first study revealing that FSHD patients showed compositional and functional GM dysbiosis. A strong association between proximal D4Z4 hypomethylation with microbial-derived SCFAs was identified.

These findings suggest that GM modulation with its metabolites could be a promising strategy for interventions in FSHD management.

Since cannabis was legalized in Canada in 2018, its use among older adults has increased. Although cannabis may exacerbate cognitive impairment, there are few studies on its use among older adults being evaluated for cognitive disorders.

We analyzed data from 238 patients who attended a cognitive clinic between 2019 and 2023 and provided data on cannabis use. Health professionals collected information using a standardized case report form.

Cannabis use was reported by 23 out of 238 patients (9.7%): 12 took cannabis for recreation, 8 for medicinal purposes and 3 for both purposes. Compared to non-users, cannabis users were younger (mean ± SD 62.0 ± 7.5 vs 68.9 ± 9.5 years; p = 0.001), more likely to have a mood disorder (p < 0.05) and be current or former cigarette smokers (p < 0.05). There were no significant differences in sex, race or education. The proportion with dementia compared with pre-dementia cognitive states did not differ significantly in users compared with non-users. Cognitive test scores were similar in users compared with non-users (Montreal Cognitive Assessment: 20.4 ± 5.0 vs 20.7 ± 4.5, p = 0.81; Folstein Mini-Mental Status Exam: 24.5 ± 5.1 vs 26.0 ± 3.6, p = 0.25). The prevalence of insomnia, obstructive sleep apnea, anxiety disorders, alcohol use or psychotic disorders did not differ significantly.

The prevalence of cannabis use among patients with cognitive concerns in this study was similar to the general Canadian population aged 65 and older. Further research is necessary to investigate patients’ motivations for use and explore the relationship between cannabis use and mood disorders and cognitive decline.

Epilepsy is a relatively common condition that affects approximately 4–5 per 1000 individuals in Ontario, Canada. While genetic testing is now prevalent in diagnostic and therapeutic care plans, optimal test selection and interpretation of results in a patient-specific context can be inconsistent and provider dependent.

The first of its kind, the Ontario Epilepsy Genetic Testing Program (OEGTP) was launched in 2020 to develop clinical testing criteria, curate gene content, standardize the technical testing criteria through a centralized testing laboratory, assess diagnostic yield and clinical utility and increase genetics literacy among providers.

Here we present the results of the first two years of the program, demonstrating the overall 20.8% diagnostic yield including pathogenic sequence and copy number variation detected by next-generation sequencing panels. Routine follow-up testing of family members enabled the resolution of ambiguous findings. Post-test outcomes were collected as reported by the ordering clinicians, highlighting the clinical benefits of genetic testing.

This programmatic approach to genetic testing in epilepsy by OEGTP, together with engagement of clinical and laboratory stakeholders, provided a unique opportunity to gather insight into province-wide implementation of a genetic testing program.

Up-to-date certification of the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) is often required for clinical trials, representing a significant burden on clinical investigators globally.

This systematic review sought to determine if NIHSS or mRS training, re-training, certification or recertification led to improvements in the reliability or accuracy of ratings as well as other relevant user metrics (e.g., user confidence).

Among 4227 studies, 100 passed screening and were assessed for eligibility with full-text review; 23 met inclusion criteria. Among these 23 studies, 22 examined NIHSS training and/or certification, and only a single study included examined the effect of training on mRS performance. Ten of 23 included studies were conference abstracts. The study designs, interventions and outcome measurement of the included studies were heterogeneous. In the case of the NIHSS, two studies found increased accuracy after NIHSS training, and a third study showed statistically significant though clinically trivial decreases in error rate with training. The remaining 19 studies showed no benefit of NIHSS training as it relates to reliability or accuracy outcomes. The single included mRS study did not show the benefit of training.

Although data are sparse with heterogeneous training protocols and outcomes, there is no compelling evidence to suggest benefit of healthcare professionals completing NIHSS or mRS training, certification or recertification. At the very least, recertification/re-training requirements should be reconsidered pending the provision of robust evidence.

Cortical excitability has been proposed as a novel neurophysiological marker of neurodegeneration in Alzheimer’s dementia (AD). However, the link between cortical excitability and structural changes in AD is not well understood.

To assess the relationship between cortical excitability and motor cortex thickness in AD.

In 62 participants with AD (38 females, mean ± SD age = 74.6 ± 8.0) and 47 healthy control (HC) individuals (26 females, mean ± SD age = 71.0 ± 7.9), transcranial magnetic stimulation resting motor threshold (rMT) was determined, and T1-weighted MRI scans were obtained. Skull-to-cortex distance was obtained manually for each participant using MNI coordinates of the motor cortex (x = −40, y = −20, z = 52).

The mean skull-to-cortex distances did not differ significantly between participants with AD (22.9 ± 4.3 mm) and HC (21.7 ± 4.3 mm). Participants with AD had lower motor cortex thickness than healthy individuals (t(92) = −4.4, p = <0.001) and lower rMT (i.e., higher excitability) than HC (t(107) = −2.0, p = 0.045). In the combined sample, rMT was correlated positively with motor cortex thickness (r = 0.2, df = 92, p = 0.036); however, this association did not remain significant after controlling for age, sex and diagnosis.

Patients with AD have decreased cortical thickness in the motor cortex and higher motor cortex excitability. This suggests that cortical excitability may be a marker of neurodegeneration in AD.

The best prehospital transport strategy for patients with suspected stroke due to possible large vessel occlusion varies by jurisdiction and available resources. A foundational problem is the lack of a definitive diagnosis at the scene. Rural stroke presentations provide the most problematic triage destination decision-making. In Alberta, Canada, the implementation and 5-year experience with a rural field consultation approach to provide service to rural patients with acute stroke is described.

The protocols established through the rural field consultation system and the subsequent transport patterns for suspected stroke patients during the first 5 years of implementation are presented. Outcomes are reported using home time and data are summarized using descriptive statistics.

From April 2017 to March 2022, 721 patients met the definition for a rural field consultation, and 601 patients were included in the analysis. Most patients (n = 541, 90%) were transported by ground ambulance. Intravenous thrombolysis was provided for 65 (10.8%) of patients, and 106 (17.6%) underwent endovascular thrombectomy. The median time from first medical contact to arterial access was 3.2 h (range 1.3–7.6) in the direct transfers, compared to 6.5 h (range 4.6–7.9) in patients arriving indirectly to the comprehensive stroke center (CSC). Only a small proportion of patients (n = 5, 0.8%) were routed suboptimally to a primary stroke center and then to a CSC where they underwent endovascular therapy.

The rural field consultation system was associated with shortened delays to recanalization and demonstrated that it is feasible to improve access to acute stroke care for rural patients.

The literature on cortical excitability, inhibitory and facilitatory properties of the brain in patients with primary dystonia is not well elucidated. We aimed to study the changes in these neurophysiological parameters in patients with dystonia using transcranial magnetic stimulation (TMS).

Patients with primary dystonia of presumed genetic etiology (n = 36) and an equal number of healthy controls (HC) (n = 36) were recruited from May 2021 to September 2022. TMS was done using single and paired pulse paradigms. The left motor cortex was stimulated, and responses were recorded from the contralateral first dorsal interosseus muscle. Resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), ipsilateral silent period (iSP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded. All patients underwent whole exome sequencing.

The mean age of patients was 36.6 ± 13.5 years. There was a significant reduction of cSP (79.5 ± 33.8 vs 97.5 ± 25.4, p = 0.02) and iSP (42.3 ± 13.5 vs 53.8 ± 20.8, p = 0.003) in patients compared to HC. SICI was significantly enhanced in patients (0.38 ± 0.23) compared to HC (0.51 ± 0.24, p = 0.006). RMT was higher (42.1 ± 7.9 vs 37.1 ± 6.4%, p = 0.032) with enhanced SICI (0.36 ± 0.21 vs 0.56 ± 0.25, p = 0.004) in patients with generalized dystonia (n = 20) compared to HC. The genetically determined subgroup (n = 13) had significantly enhanced SICI compared to HC (0.23 ± 0.15 vs 0.51 ± 0.23, p = 0.001).

Patients with primary dystonia have altered cortical excitability and inhibition with significantly reduced silent period and enhanced intracortical inhibition suggestive of impaired GABAergic neurotransmission.

Canada’s National Microbiology Laboratory offers diagnostic testing of Creutzfeldt-Jakob disease (CJD) and related prion diseases. Since 2016, the highly sensitive and specific end-point quaking-induced conversion assay (EP-QuIC) of CSF samples has been used for antemortem CJD diagnostic testing alongside tests for surrogate biomarkers 14-3-3 and hTau. To assess EP-QuIC’s utility, we undertook a retrospective study of Canadian CJD diagnostic testing conducted between 2016 and 2024.

Using CJD CSF test results collected between 2016 and 2024, we analyzed the CJD incidence in Canada, estimated based on positive EP-QuIC tests. Multivariate regression models were used to further evaluate CJD CSF testing between CJD subtypes, genders, age groups and codon 129 genotypes.

From 2016 to 2024, the CJD incidence across Canada was estimated at 1.51 cases per million population per year. CJD incidence did not vary significantly across provinces, although a slight increase in CJD incidence was detected in New Brunswick due to increased sampling rates. EP-QuIC offered higher test sensitivity than both surrogate biomarker tests. Analysis of biomarker abundances and test positivity rates across biochemical subtypes revealed significant differences. We also detected variation in CSF test positivity rates across age groups and a trend of increasing biomarker abundance with age within EP-QuIC-negative cases. No significant variation was detected between males and females.

EP-QuIC exhibits exceptional specificity and sensitivity for antemortem diagnosis of CJD, providing a valuable tool for the diagnosis of human prion diseases and for improved surveillance.

The aim of this study is to assess the evolution of respiratory and feeding support in children with spinal muscular atrophy (SMA) type 1 after 24 months of nusinersen treatment.

Data on SMA type 1 children treated with nusinersen between 2017 and 2023 from the Canadian Neuromuscular Disease Registry were extracted. The cohort was divided into two groups based on age at treatment initiation: ≤2 years and >2 years. The primary outcome was the (i) time to death or needing full-time (≥16 hours/day) ventilation and (ii) time to needing feeding tube support. The secondary outcomes were differences in respiratory and feeding support requirements between the two groups at 24-month follow-up.

Thirty-two children were included, and the median age (range) for treatment initiation was 3.2 months (0.8– 13.1) in children who initiated treatment at ≤2 years and 51.2 (28.7–183.8) in those who initiated at >2 years of age. The median age of death or full-time ventilation was 8.6 months (6–22.4) and 10.5 months (4–24) for the two groups, respectively. The median age for initiation of feeding support was 5.1 (1.7–26.4) and 14.5 months (3.9–130.6), respectively. At 24 months (n = 23), there were no significant differences between the need for respiratory or feeding tube support between the two treatment groups.

Most children with SMA type 1 treated with nusinersen across Canada have continued need for respiratory and feeding support over time when initiated after symptom onset.