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.

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.

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.

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.

Noninvasive stimulation techniques are a promising therapy due to the ease of administration and minimal side effects. We investigated the clinical, electrophysiological and side effects of transcranial pulsed current stimulation (tPCS) in patients with Parkinson’s disease (PD).

Ten PD patients were called at monthly intervals in the OFF levodopa state. Patients received active tPCS for 20 minutes in the first visit and sham stimulation for 20 minutes in the second and were assessed for the levodopa response in the third. Clinical and bradykinesia scoring and gait and tremor analysis were done before and after stimulation/sham/levodopa in each visit. Scalp electroencephalography (EEG) was recorded for quantitative analysis during each visit. The interventions were compared between pre- and post-intervention.

A significant improvement with levodopa as compared to active and sham tPCS was seen in clinical scores. Upper limb postural tremor severity (z-score = −2.410, p = 0.016) and the stride velocity variability during post active stimulation improved by 20.7% compared to post sham stimulation though the difference was statistically non-significant. KINARM testing showed a statistically significant difference in the reaction time (p = 0.036) when comparing pre- and post-tPCS active stimulation. EEG recording showed a transitory increase of electrical activity after tPCS, with the most significant increase seen in alpha bandpower (p = 7.95*10-07; z score: −4.93).

tPCS was well tolerated in all patients. With minimal side effects, ease of administration and mild improvement in the electrophysiological parameters assessed, tPCS can be an alternative therapeutic option in patients with PD.

The outcomes of radiosurgery for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) are not as extensively assessed as those for idiopathic or classical TN cases.

Evaluate the safety and efficacy of radiosurgery for TN in MS patients and identify potential predictors of successful outcomes.

A retrospective single-institution cohort study with patients treated between 2009 and 2022 was performed. Fifty patients were included, and a total of 68 radiosurgical interventions were delivered. Outcomes included the maintenance of pain relief assessed using Kaplan–Meier curves and treatment-related complications. Cox regression analyses were used to identify potential predictors of better pain relief.

Following the first radiosurgical treatments, the initial pain relief rate was 86% after a median latency period of 14 days. Adequate pain relief rates at 6, 12, 36 and 60 months were 86%, 52%, 35% and 24%, respectively. Adequate pain relief was sustained for an actuarial median of 12.7 months. After initial relief, pain recurrence occurred in 68% of patients. No statistical difference was seen in the duration of pain relief after initial or repeat radiosurgery (p = 0.368). The most frequent complication was facial hypesthesia (Barrow Neurological Institute facial hypesthesia scale grade II: 10%; III: 6%; IV: 0%). Ipsilateral vascular compression was predictive of better efficacy (p = 0.024).

Radiosurgery for TN in patients with MS appears to be safe and to provide effective pain relief. Notably, radiological identification of vascular compression may predict more sustained pain relief.

A comprehensive understanding of the burden of migraine in Canada is needed to inform clinicians, clinical care and policymakers. This study assessed real-world healthcare resource utilization (HCRU) and costs of patients with episodic migraine (EM) and chronic migraine (CM) in Ontario, Canada.

This study utilized administrative databases from the Institute for Clinical Evaluative Sciences (ICES) containing publicly funded health services records for the covered population of Ontario. Patients ≥26 years old with a migraine diagnosis between January 2013 and December 2017 were selected. EM and CM were inferred in eligible patients based on previously studied predictors. Cases were matched with non-migraine controls and followed for two years.

452,431 patients with migraine, 117,655 patients inferred with EM and 24,763 patients inferred with CM were selected and matched to controls. 39.4% of the inferred EM and 69.3% of the inferred CM subpopulations had ≥1 claims of preventive medications. Migraine-specific acute medications were underutilized (EM: 1.0%, CM: 3.3%), and high proportions of patients utilized opioids (EM: 38.8%, CM: 64.9%). Mean all-cause two-year costs per patient for the overall migraine population and inferred EM and CM subpopulations were $7,486 (CAD), $11,908 (CAD) and $24,716 (CAD), respectively. The two-year incremental all-cause cost of migraine to the Ontario public payer was $1.1 billion (CAD).

Migraine poses a significant unmet need and burden on the Canadian healthcare system. These results demonstrate a gap between real-world care and recommendations from treatment guidelines, emphasizing the need for improved awareness and expanded access to more effective treatment options.

During the COVID-19 pandemic, virtual physician visits rapidly increased among community-dwelling older persons living with dementia (PLWD) in Ontario. Rural residents often have less access to medical care compared to their urban counterparts, and it is unclear whether access to virtual care was equitable between PLWD in urban versus rural locations.

Using population-based health administrative data and a repeated cross-sectional study design, we identified and described community-dwelling PLWD between March 2020 and August 2022 in Ontario, Canada. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals comparing rates of virtual visits between rural and urban PLWD by key physician specialties: family physicians, neurologists and psychiatrists/geriatricians.

Of 122,751 PLWD in our cohort, 9.2% (n = 11,304) resided in rural areas. Rural PLWD were slightly younger compared to their urban counterparts (mean age = 81 vs. 82 years; standardized difference = 0.16). There were no differences across areas by sex or income quintile. In adjusted models, rates of virtual visits were significantly lower for rural compared to urban PLWD across all specialties: family physicians (RR = 0.71 [0.69–0.73]), neurologists (RR = 0.79 [0.75–0.83]) and psychiatrists/geriatricians (RR = 0.72 [0.68–0.76]).

PLWD in rural areas had significantly lower rates of virtual family physician, neurologist and psychiatrist/geriatrician visits compared to urban dwellers during the study period. This finding raises important issues regarding access to primary and specialist healthcare services for rural PLWD. Future work should explore barriers to care to improve health care access among PLWD in rural communities.

The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial demonstrated that minimally invasive surgery to treat spontaneous lobar intracerebral hemorrhage (ICH) improved functional outcomes. We aimed to explore current management trends for spontaneous lobar ICH in Canada to assess practice patterns and determine whether further randomized controlled trials are needed to clarify the role of surgical intervention.

Neurologists, neurosurgeons, physiatrists and trainees in these specialties were invited to complete a 16-question survey exploring three areas: (1) current management for spontaneous lobar ICH at their institution, (2) perceived influence of ENRICH on their practice and (3) perceived need for additional clinical trial data. Standard descriptive statistics were used to report categorical variables. The χ2 test was used to compare responses across specialties and career stages.

The survey was sent to 433 physicians, and 101 (23.3%) responded. Sixty-eight percent of participants reported that prior to publication of the ENRICH trial, spontaneous lobar ICH was primarily managed conservatively, with surgery reserved for life-threatening situations. Forty-three percent of participants did not foresee a significant increase in surgical intervention at their institution. Of neurosurgical respondents, 33% remained hesitant to offer surgical intervention beyond lifesaving operations. Only 5% reported routinely using specifically designed technologies to evacuate ICH. Seventy percent reported that another randomized controlled trial comparing nonsurgical to surgical management for spontaneous lobar ICH is needed.

There is significant practice variability in the management of spontaneous lobar ICH across Canadian institutions, stressing the need for additional clinical trial data to determine the role of surgical intervention.

Endovascular thrombectomy (EVT) is the gold standard treatment for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Multiple factors can influence EVT outcomes, including procedural and patient-related variables. This meta-analysis investigated the impact of periprocedural hemoglobin (Hb) levels on EVT outcomes.

We performed a comprehensive literature search across PubMed, Scopus, Web of Science and Cochrane CENTRAL. We analyzed the mean difference (MD) in Hb levels between good (modified Rankin Scale [mRS] 0–2) and poor (mRS 3–6) prognosis groups. We calculated pooled odds ratios (OR) for Hb levels as a predictor of prognosis and compared mortality and symptomatic intracranial hemorrhage (sICH) across different Hb levels.

The analysis included 921 patients from four studies. Patients in the good prognosis group had significantly higher Hb levels (MD: 0.48 g/dL, 95% CI: [0.2, 0.75], P = 0.0007). Each 1 g/dL increase in Hb was associated with a 22% increase in the odds of achieving a good three-month prognosis (OR: 1.22, 95% CI: [1.13, 1.33], P < 0.00001). Patients with Hb levels ≤13 g/dL in males and ≤12 g/dL in females were 1.69 times more likely to experience mortality (OR: 1.69, 95% CI: [1.1, 2.59], P = 0.02). No significant difference was observed in sICH occurrence between anemic and non-anemic patients.

Higher Hb levels may be associated with improved prognosis, and lower Hb levels might increase mortality risk in AIS-LVO patients undergoing EVT. Further research is needed to validate these findings.

The determinants of door-in-door-out metrics (DIDO) at centers referring acute ischemic stroke patients for endovascular thrombectomy (EVT) and the impact of DIDO on functional outcomes are unclear. Our primary objective was to study the association between DIDO and 90-day functional outcomes. Our secondary objective was to investigate the associations between patient clinical and workflow characteristics and DIDO.

We conducted a province-wide multicentric retrospective cohort study in Québec, Canada, of adults with acute ischemic stroke who were transferred from a primary stroke center (PSC) to a comprehensive stroke center for EVT between 2017 and 2020. DIDO was calculated as the time spent in the PSC emergency department. Our co-primary outcomes, assessed 90 days after stroke, were a favorable functional outcome (modified Rankin score of 0–2) and death. We estimated associations between DIDO and co-primary outcomes and between patient characteristics and DIDO using logistic mixed models.

Among 790 included patients, the mean age was 69 (+/–14) years, and 400 (51%) were female. The median DIDO was 102 (80–135) minutes. DIDO was not associated with 90-day favorable functional outcome (aOR: 1.00, 95% CI [0.99–1.00], p = 0.54) or death (aOR: 1.00, 95% CI [0.99–1.01], p = 0.69). Arrival at the PSC outside daytime hours (aOR: 3.28, 95% CI [1.26–8.51], p = 0.01) was significantly associated with DIDO ≥ 60 minutes.

Although DIDO are long in Québec, they are not associated with 90-day functional outcomes or mortality among patients transferred for EVT. Further research is required to develop strategies to improve modifiable determinants of DIDO, including workflow outside of daytime hours.