Foslevodopa-foscarbidopa (LDp/CDp) is a soluble formulation of levodopa/carbidopa delivered as a continuous subcutaneous infusion for the treatment of motor fluctuations in people with Parkinson’s disease. No real-world use data exist regarding its efficacy and safety from a high-volume Canadian center.

This is an ambispective longitudinal study (with the second visit at 1 month of enrollment) in patients with advanced Parkinson’s disease from a tertiary care movement disorder center in Canada.

The primary objective of the study was to examine the efficacy of LDp/CDp in improving MDS UPDRS III scores, EURO-Q Index, EURO Q VAS score and ON time while reducing OFF time. Secondary objectives focused on safety.

The study was conducted from April 2024 to August 2025, with the prospective part comprising 11 patients and the retrospective part 53 patients. There was a significant (p < 0.05) improvement in clinical efficacy parameters like the MDS UPDRS III (−11.37), OFF hours (−2.77), ON time without dyskinesias (+2.07), ON time with troublesome dyskinesias (−0.74 hours) and quality of life-related parameters like EURO Q Index (+0.10) and PDQ-39 (−10.78). One-fourth (26.5%) of the patients discontinued treatment, mostly due to infusion-site reactions or infections.

LDp/CDp can be an effective treatment option for carefully selected patients with advanced Parkinson’s disease and disabling motor complications. Appropriate hygiene measures may reduce the proportion of infusion site reactions, thereby improving patient retention on LDp/CDp infusion.

Early detection of respiratory decline is crucial in amyotrophic lateral sclerosis (ALS). We tested if nocturnal polysomnography (PSG) predicts dyspnea onset in mild ALS patients with preserved daytime function.

In this study, 41 mild ALS patients (ALS Functional Rating Scale-Revised [ALSFRS-R] ≥ 37, sitting forced vital capacity [FVC] ≥80% predicted, no dyspnea) and 41 matched controls underwent baseline assessment, including ALSFRS-R scoring, pulmonary function tests, and overnight PSG. ALS patients were followed for 12 months. Baseline apnea–hypopnea index (AHI) and oxygen saturation (mean SpO2, minimum SpO2) were analyzed as continuous predictors and using exploratory thresholds (AHI ≥ 5 events/h, min SpO2 ≤ 88%, mean SpO2 ≤ 95%) for dyspnea onset (Dyspnea-ALS-15 [DALS-15] > 0).

Compared to controls, ALS patients had significantly higher AHI (p = 0.004) and lower minimum SpO2 (p = 0.018). The ALSFRS-R orthopnea subscore showed a significant positive correlation with mean and minimum SpO2 (P < 0.05). Cox regression identified baseline AHI (HR 1.08 per event/h; 95% CI 1.01–1.15, p = 0.028) and minimum SpO2 (HR 0.94 per %; 95% CI 0.88–0.99, p = 0.033) as independent predictors of dyspnea onset within 12 months. Thresholds AHI ≥ 5 (HR 2.28, p = 0.031) and min SpO2 ≤ 88% (HR 2.42, p = 0.027) also predicted increased risk. Patients meeting ≥1 threshold (n = 25/37) showed trends toward greater FVC and ALSFRS-R decline.

In patients with mild ALS and normal daytime function, specific nocturnal PSG parameters (AHI, minimum SpO2) predicted the risk of dyspnea within 12 months. This longitudinal study provides novel evidence that PSG could identify early respiratory vulnerability in the incipient stage, earlier than conventional FVC-based monitoring, supporting its potential utility in refining early intervention strategies. Validation in larger cohorts is warranted.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and disabling neuroinflammatory disorder. Previous studies of aquaporin-4 IgG-positive (AQP4+) NMOSD in Canada have been limited by small sample sizes and regional focus. This study aimed to characterize the sociodemographic and clinical profile of individuals living with AQP4+ NMOSD and the treatment landscape in a multicenter study.

Data were collected from the CAnadian Neuromyelitis OPTIca Spectrum Disorder and other atypical demyelinating diseases Cohort Study (CANOPTICS), a prospective longitudinal study involving seven Canadian centers. Participants were diagnosed with AQP4+ NMOSD using the 2015 International Panel for NMO Diagnostic criteria. We analyzed sociodemographic and clinical characteristics in addition to treatment utilization over time.

133 participants with AQP4+ NMOSD were included, with a mean (SD) age of 52.0 (15.0) years at enrollment and 45.9 (15.5) years at index attack. Most were female (84.9%), ethnically and racially varied (33.3% North American or European White, 25.2% African/Caribbean Black, 22.7% East/Southeast Asian) and born abroad (63.3%). Two-thirds had moderate or mild disability, as measured by an Expanded Disability Status Scale of 3.5 or less. Azathioprine was the most used first-line therapy (59.3%), followed by mycophenolate mofetil (12.5%) and rituximab (10.5%). Use of novel monoclonal antibodies (MAbs) was least common (6.3%); however, first-line use of rituximab and novel MAbs increased in recent years (2018–2023).

Canadians with AQP4+ NMOSD are predominantly female and ethnically and racially varied, with more favorable outcomes than in previous reports. Despite a trend toward increasing use of rituximab and novel MAbs, these higher-efficacy treatments remain underutilized for NMOSD in Canada.

Highly purified cannabidiol (CBD) represents a novel anti-seizure medication (ASM) with established efficacy in specific epilepsy syndromes; however, real-world evidence across diverse etiologies remains limited. Following Health Canada approval in November 2023, CBD provides an additional option for treatment-resistant seizures. This study describes early real-world experience with CBD within a Provincial Comprehensive Epilepsy Program during its inaugural year of availability in Canada.

A retrospective chart review examined all pediatric patients prescribed CBD between June 2024 and April 2025.

Sixty-one patients (median age 10.5 years) were included. Prior to CBD initiation, patients had trialed a median of eight ASMs and were receiving a median of three concomitant ASMs. Fifteen patients had prior CBD exposure, including nine who transitioned directly to the highly purified formulation. Diagnoses comprised Lennox–Gastaut syndrome (38%), Dravet syndrome (11%), other developmental and epileptic encephalopathies (39%) and focal/multifocal epilepsy (11%). After a median treatment duration of 172 days, 22% of patients achieved ≥50% seizure reduction, including 7% who became seizure-free, while 30% experienced a 25%–49% reduction. Forty-eight percent demonstrated ≤25% seizure reduction, and 11% experienced seizure exacerbation. Despite variable seizure outcomes, 70% continued CBD therapy, frequently attributable to benefits transcending seizure frequency, including diminished seizure severity, increased seizure-free intervals, improved behavior and enhanced sleep quality. Adverse effects occurred in 30% of patients, prompting treatment discontinuation in 6.5%.

This real-world analysis suggests that CBD may be effective and well tolerated in children with highly refractory epilepsy across heterogeneous etiologies, with potential benefits beyond seizure control.

The impact of inter-hospital transfer before endovascular thrombectomy (EVT) on short-term outcomes has been reported, but its effect on long-term outcomes remains unclear. We examined long-term clinical outcomes after EVT, stratified by whether patients underwent inter-hospital transfer.

We conducted a population-based cohort study using linked administrative data from Ontario, Canada (2017–2023). We included all community-dwelling residents hospitalized with acute ischemic stroke who received EVT. Inter-hospital transfer was defined as any transfer from a non-comprehensive stroke center (CSC) to a CSC before EVT. The primary outcome was all-cause mortality at maximum follow-up, assessed using propensity score-weighted hazard ratios.

Of 68523 ischemic stroke patients, 5394 (7.9%) underwent EVT, with 42.9% transferred before EVT. Direct-to-CSC patients were older, had higher rates of atrial fibrillation and dyslipidemia and were more likely to reside in urban areas. Propensity score-weighted analysis comparing transferred versus direct-to-CSC patients showed no difference in all-cause mortality, but the hazard ratio varied over time, violating the proportional hazards assumption. Transfer was associated with higher early mortality than direct-to-CSC, which declined over time, with mortality lower after 6.3 months, remaining below 1 over prolonged follow-up out to 34.6 months. Transferred patients were more likely to be admitted to long-term care (aHR 1.17, 95% CI: 1.03–1.33), but there was no significant difference in recurrent stroke.

Nearly half of EVT patients underwent inter-hospital transfer, which showed a time-varying association with all-cause mortality, with early risk that attenuated after 6.3 months and reversed over time.

Caregivers of older individuals with dementia experience substantial and enduring burden, often exacerbated by patient neuropsychiatric symptoms (NPS). Few longitudinal studies have examined how specific NPS contribute to prolonged caregiver burden.

We conducted a 6-month prospective cohort study of 100 dyads of caregivers and older adults with Alzheimer’s disease, frontotemporal dementia and Lewy body dementia recruited from specialized neurology and geriatric clinics. Caregiver burden was assessed using the Zarit Burden Interview (ZBI), and NPS were measured with the neuropsychiatric inventory (NPI) and associated distress scale (NPI-D). Correlation analyses examined associations between baseline NPS and both concurrent and prolonged high caregiver burden.

At baseline, nearly one-third of caregivers reported moderate-to-severe burden (mean ZBI 31.4 ± 15.4), a prevalence that persisted at 6 months. Higher burden was strongly correlated with total NPI and NPI-D scores (p < 0.001). Specific symptoms – including delusions, hallucinations, agitation, anxiety, disinhibition, depression, sleep disorders and irritability – were consistently associated with greater burden. Depression, anxiety, disinhibition and sleep disturbances predicted prolonged high burden over 6 months. Sex-specific patterns emerged: psychotic symptoms and sleep disorders were more strongly associated with burden in female caregivers, whereas depression and irritability were key drivers for male caregivers.

Caregiver burden in dementia is both prevalent and persistent, with NPS emerging as major correlates and predictors. Recognition of sex-related patterns may enable earlier identification of at-risk caregivers. Interventions addressing both patient NPS and caregiver coping resources could help reduce long-term distress and improve outcomes for both caregivers and patients.

To describe neuropathological findings in autopsies of patients with isolated, partial or all classic features of the septo-optic-pituitary dysplasia (SOD) triad, speculate on SOD etiology and ascertain the causes of death.

Retrospective review of autopsy reports of patients with one or more features of the SOD triad.

Twenty-one (14 females) cases were identified. Median age at death was 2.3 years. Two fetuses died soon after birth, and the rest died at postnatal ages of 3 weeks to 50 years. Ten cases had optic nerve hypoplasia (ONH) with either (i) small pituitary gland/hypopituitarism (five cases) or (ii) absent septum pellucidum (SP)/abnormal corpus callosum (CC) (two cases) or (iii) both (three cases). Eleven cases had one or two features of the SOD triad. A wide spectrum of neuropathological findings was evident, with 12 cases resulting from in utero/perinatal vascular lesions in brain regions that led to ONH/chiasm hypoplasia, hypothalamus/pituitary gland anomalies and agenesis or abnormalities in the SP, CC and olfactory bulbs and tracts. Other suspected causes included three genetic (one with holoprosencephaly), two in utero infection and one arachnoid cyst with hydrocephalus. The most common cause of death was a respiratory illness.

The autopsy findings appear to be the result of destructive or less commonly impaired developmental processes. Our findings suggest that SOD is not a single disease entity but represents a syndrome with ONH and one or more of: hypothalamic-pituitary dysfunction and absent SP or abnormal CC. We consider ONH an essential part of SOD.

Kinesiophobia is defined as an excessive and irrational fear of movement and physical activity. Individuals living with Parkinson’s disease (PD) can be at risk of developing this phobia, due to the debilitating nature of the disease’s motor symptoms such as impaired balance, bradykinesia, rigidity and tremor. This is particularly problematic, as exercise is crucial for people with PD, especially considering its potential to slow down disease progression. The Tampa Scale of Kinesiophobia for Parkinson’s disease (TSK-PD) is a valid and reliable instrument for measuring kinesiophobia in PD. However, no French translation of this scale existed prior to this study.

The English TSK-PD was translated, cross-culturally adapted into Canadian French, and administered to 102 ambulatory French-speaking Canadians living with PD, aged 46–83. Statistical analyses were then conducted to examine the psychometric properties of the translated scale.

Results confirmed the construct validity of the translated version and revealed high internal consistency (Cronbach’s alpha = 0.90), good test-retest reliability (ICC = 0.84), with no evidence of floor or ceiling effects. Exploratory and confirmatory factor analyses supported a two-factor structure consisting of “Activity Avoidance” and “Harm.”

The French-Canadian TSK-PD can be recommended for use in research and in clinical settings to better identify fear of movement in French-speaking PD patients and promote physical activity.

Emerging evidence suggests that metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) may increase vulnerability to neurodegenerative disorders. However, the link between PCOS and Alzheimer’s disease (AD)-related pathology remains unclear.

In this cross-sectional study, plasma levels of β-amyloid (Aβ40, Aβ42), phosphorylated tau (p-tau181), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified in women with PCOS and age-matched controls. Homeostasis model assessment of insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, TNF-α) and hormonal parameters were assessed. Mediation and moderation analyses were conducted to explore metabolic and hormonal pathways underlying biomarker alterations.

Among 400 women (200 PCOS, 200 controls), age and BMI were comparable (P > 0.05). Compared with controls, PCOS participants had increased Aβ40, p-tau181, NfL and GFAP, a slightly higher Aβ42, and a lower Aβ42/40 ratio (all P < 0.05). p-tau181 correlated positively with HOMA-IR (r = 0.41) and IL-6 (r = 0.36), while Aβ42/40 ratio correlated negatively with HOMA-IR (r = –0.27). In multivariable analysis, p-tau181 (aOR = 1.34, 95% CI 1.05–1.71), IL-6 (aOR = 1.19) and TNF-α (aOR = 1.14) were independent predictors of insulin resistance. Mediation analysis indicated that HOMA-IR, IL-6 and TNF-α jointly mediated ∼ 71% of the PCOS–p-tau181 association, suggesting a metabolic–inflammatory pathway linking PCOS to AD-related tau pathology.

PCOS is linked to peripheral markers of early Alzheimer’s pathology, largely mediated by insulin resistance and inflammation. PCOS may provide a clinical context to explore metabolic–inflammatory contributors to early neurodegenerative changes.

Timely access to endovascular treatment (EVT) for ischaemic stroke patients is critical for optimal outcomes, but Canada’s size and population distribution create barriers to access. EVT is mostly available in tertiary centres located in large urban cities, and patients that arrive at intravenous thrombolysis (IVT)-only stroke centres need to be transferred for EVT.

Geographic modelling of access to an IVT-only centre and an EVT-capable centre was conducted for Canada. Canada was divided into small grid sections. Drive times from the centre of each grid section to the closest stroke centres and the population of each grid section were obtained. The onset to paramedic arrival time and on-scene time were assumed to be 30 and 30 minutes, respectively. In the suboptimal and optimal scenarios, the door-in-door-out (DIDO) times were 150 minutes and 45 minutes, respectively. The poor access regions and population were calculated for onset to thrombolysis at 4.5 hours and to EVT-capable centre arrival for EVT within 6 and 3 hours.

The results show 99.37% of the population having access to thrombolysis within 4.5 hours. However, with a suboptimal DIDO time, 13.6% (5.2 million people) and 42.7% (16.2 million people) do not have access to EVT within 6 and 3 hours, respectively. With an efficient DIDO time, an additional 5.6% (2.1 million people) and 15.7% (6.0 million people) have access to EVT within 6 and 3 hours, respectively.

There is an imperative to reduce DIDO times to an ambitious median of 45 minutes to ensure optimal access to EVT across Canada.

A critical step toward determining eligibility for experimental and clinical treatment with anti-amyloid therapies in Alzheimer’s disease (AD) is to select appropriate subjects having a high likelihood of being Aβ+. We propose a clinical biomarker composite score, named Clinical β-Amyloid Positivity Prediction Score Plus (CAPS Plus), for Aβ+ prediction in people presenting with clinical Alzheimer’s syndrome including both prodromal and mild AD.

The original CAPS incorporated scores from the neuropsychiatry inventory questionnaire, mini-mental state examination score loss per year and Fazekas score. Plasma p-tau-217, a novel addition to CAPS, was measured using the Simoa HD-X with the AlzPATH p-tau217 Advantage Plus assay. To incorporate p-tau-217 into CAPS Plus, an intra-cohort cut-off (>0.698 pg/ml) for p-tau217 was generated using logistic regression and Yoden’s index. CAPS Plus had a maximum score of 5, with those ≥4 indicating a high probability of being Aβ+. The accuracy of CAPS Plus was computed through logistic regression and area under the receiver operating characteristic curve (AUROC) analysis.

Of n = 44 patients, n = 25 (57%) were Aβ+. Plasma p-tau-217 was significantly higher in the Aβ+ subgroup (1.36 vs 0.46 pg/mL, p < 0.0001). The AUROC was 0.89 for a CAPS Plus score of 4 or more, suggesting excellent discrimination and improving the accuracy of the original CAPS (0.86). CAPS Plus has a notably better specificity (89%) than the original CAPS (80%) and p-tau-217 alone (74%).

CAPS Plus is potentially a useful screening tool for enrollment in anti-Aβ therapy and clinical trials for AD, specifically addressing people with prodromal and mild AD.

This study aims to evaluate differences in healthcare utilization among patients with ischemic stroke in metropolitan versus non-metropolitan Manitoba.

This study is a population-level analysis using the Discharge Abstract Database from Manitoba. The database includes all patients who received care in a Manitoba facility for ischemic stroke between April 2019 and March 2023. Data were collected on patient demographics, comorbidities and geographical location of stroke presentation (metropolitan Winnipeg vs non-metropolitan). Outcomes included length of stay (LOS), treatment, discharge disposition and mortality. Regression analysis was performed to analyze outcomes, adjusting for age, sex and comorbidities.

3704 (71.6%) patients were admitted in Winnipeg, and 1471 (28.4%) patients were admitted in non-metropolitan Manitoba. Patients presenting to Winnipeg were younger (mean age 72.3 vs 74.3 years) and had higher rates of atrial fibrillation, hypertension, diabetes, chronic kidney disease and heart failure. Patients presenting to Winnipeg had a shorter LOS (16.1 days vs 18.4 days, coefficient 0.05, 95% CI −4.54 to −1.27), had higher rates of intravenous thrombolysis (adjOR 5.13, 95% CI 3.85–6.84), were less likely to be discharged home (39.8% vs 57.5%, adjOR 0.47, 95% CI 0.41–0.53) and were more likely to be transferred for inpatient stroke rehabilitation (adjOR 3.46, 95% CI 2.64–4.54). There were no differences in in-hospital mortality. There was a higher incidence of stroke in Winnipeg compared to non-metropolitan Manitoba (F-statistic 23.84, p = 0.0028).

This study illustrates differences in healthcare utilization outcomes between patients living in metropolitan Winnipeg versus non-metropolitan Manitoba presenting with ischemic stroke.

Cognitive fatigability (CF), which refers to a decline in performance during sustained cognitive effort, can significantly impact people with multiple sclerosis (PwMS). This study examined the unmet needs related to perceived CF in PwMS.

One hundred PwMS completed a survey assessing factors known to contribute to CF. Participants indicated whether each factor, including CF itself, was disruptive and whether adequate support was available to address these concerns. A factor identified as disruptive and insufficiently addressed was considered an unmet need (Need Index [NI] ≥50%).

Group-level analysis revealed no significant unmet needs, although fatigue (NI = 30.23), CF (NI = 22.96) and physical activity (NI = 19.55) were more frequently reported. Individual-level analyses revealed that unmet needs varied by community setting (rural vs urban) and socioeconomic status (SES) (lower vs higher SES), with rural participants and those with lower SES reporting higher rates of unmet needs. In addition, PwMS who indicated CF was an unmet need reported more difficulties across most contributory factors, including sleep quality, fatigue, cognitive impairment, depression and contextual factors. The presence of fatigue and CF combined contributed to greater unmet needs across various domains, especially fatigue, CF and cognitive impairment, compared to fatigue alone.

Participants from rural and low socioeconomic backgrounds were more likely to have unmet needs. Notably, 36% of participants (N = 33) reported unmet needs related to perceived CF. The findings highlight the importance of tailoring future interventions to address identified needs more adequately.