The depression, obstructive sleep apnea and cognitive impairment (DOC) screen assesses three post-stroke comorbidities, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure.

To assess DOC screen completion time as a predictor of cognitive impairment in stroke/transient ischemic attack clinics.

Consecutive English-speaking stroke prevention clinic patients consented to undergo screening and neuropsychological testing (n = 437). DOC screen scores and times were compared to scores on the NINDS-CSC battery using multiple linear regression (controlling for age, sex, education and stroke severity) and receiver operating characteristic (ROC) curve analysis.

Completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for covariates, the completion time was a significant predictor of the speed of processing (p = 0.002, 95% CI: −0.016 to −0.004), verbal fluency (p < 0.001, CI: −0.012 to −0.006) and executive function (p = 0.004, CI: −0.006 to −0.001), but not memory. Completion time above 5.5 minutes was associated with a high likelihood of impairment on executive and speed of processing tasks (likelihood ratios 3.9–5.2).

DOC screen completion time is easy to collect in routine care. People needing over 5.5 minutes to be screened likely have deficits in executive functioning and speed of processing – areas commonly impaired, but challenging to screen for, after stroke. DOC screen time provides a simple, feasible approach to assess these under-identified cognitive impairments.

Autoimmune encephalidities (AIE) are becoming an increasingly recognized cause of encephalitis. While diagnosis and acute management are well described, information on long-term management and outcomes is limited. Given this, we reviewed 5 years of AIE patients, reporting on chronic management, relapse incidence and possible relapse predictors.

We performed a chart review of all patients with non-paraneoplastic AIE presenting to Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Severity of relapse was determined using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Variables were assessed with descriptive analysis and/or t-test.

Patients were followed for a mean of 38.2 months. Outcome data were assessable in 37/38 patients. Relapse rate ranged from 0% (GFAP) to 67% (NMDA), with a mean of 46%. Most relapses (76%) occurred within 3 years. Time to treatment initiation at relapse was significantly shorter than initial presentation (p = 0.0015), and patients had less severe relapses compared to initial presentation (CASE score 5.18 vs 6.53; p = 0.040).

Use of chronic immunotherapy did not appear to impact overall relapse risk, although patients on any immunotherapy at relapse had milder relapses based on ΔCASE (p = 0.0035).

Relapse was not uncommon (46%) for various AIE subtypes in our cohort, particularly within the first 3 years. Our data enforce the importance of long-term follow-up, which in our study allowed for earlier treatment and less severe relapses compared to initial presentation, as well as the need to further explore which patients would benefit from chronic immunotherapy.

Vanishing white matter syndrome is one of the leukoencephalopathies caused by recessive mutations in gene EIF2B1–5. Adult-onset EIF2B-pathies (clinical onset after age 16 years) have been reported to be less common.

Description of the clinical, imaging and genetic profile of adult-onset EIF2B-pathies and comparison of Indian cohort with Asian and European cohorts.

Report of two cases of adult-onset EIF2B-pathies and a comprehensive review of genetically confirmed adult-onset EIF2B-pathies since 2001 from Indian, Asian and European cohorts.

Two patients were females, with median age at presentation of 25.5 years (24–27 years) and onset at 19 years (18–20 years). The median duration of symptoms was 6.5 years (6–7 years). Both had cerebellar ataxia, spasticity, cognitive impairment and bladder involvement. Brain magnetic resonance imaging (MRI) showed leukoencephalopathy with rarefaction in both patients and corpus callosum involvement in one patient. Genetics showed homozygous missense variant in the EIF2B3 gene in both patients. The Indian cohort of seven patients had similar clinical and radiological features and common variants in EIF2B3 (n = 4). The Asian cohort had 24 cases, and the European cohort had 61 cases with similar clinical features, radiological features and common variants in EIF2B5.

Adult-onset EIF2B-pathies have a distinct clinical profile of female predominance with cerebellar ataxia, spasticity and cognitive decline as the commonest triad of clinical manifestations and leukoencephalopathy with rarefaction on brain MRI. Variants in EIF2B5 were common in the Asian and European cohorts and EIF2B3 in the Indian cohort.

Bibliometrics methods have allowed researchers to assess the popularity of brain research through the ever-growing number of brain-related research papers. While many topics of brain research have been covered by previous studies, there is no comprehensive overview of the evolution of brain research and its various specialties and funding practices over a long period of time.

This paper aims to (1) determine how brain research has evolved over time in terms of number of papers, (2) countries' relative and absolute positioning in terms of papers and impact, and (3) how those various trends vary by area.

Using a list of validated keywords, we extracted brain-related articles and journals indexed in the Web of Science over the 1991–2020 period, for a total of 2,467,708 papers. We used three indicators to perform: number of papers, specialization, and research impact.

Our results show that over the past 30 years, the number of brain-related papers has grown at a faster pace than science in general, with China being at the forefront of this growth. Different patterns of specialization among countries and funders were also underlined. Finally, the NIH, the European Commission, the National Natural Science Foundation of China, the UK Medical Research Council, and the German Research Foundation were found to be among the top funders.

Despite data-related limitations, our findings provide a large-scope snapshot of the evolution of brain research and its funding, which may be used as a baseline for future studies on these topics.

Epidemiological studies on the association between migraine and Alzheimer’s disease (AD) risk have yielded inconsistent conclusions. We aimed to characterize the phenotypic and genetic relationships between migraine and AD.

To investigate the association between migraine and the risk of AD by analyzing data from a large sample of 404,318 individuals who were initially free from all-cause dementia or cognitive impairment, utilizing the UK Biobank dataset. We employed Cox regression modeling and propensity score matching techniques to examine the relationship between migraine and subsequent occurrences of AD. Additionally, the study utilized Mendelian randomization (MR) analysis to identify the genetic relationship between migraine and the risk of AD.

Migraine patients had a significantly increased risk of developing AD, compared to non-migraine patients (adjusted hazard ratio (HR) = 2.34, 95% confidence interval (CI) = 2.01–0.74, P < 0.001). Moreover, the propensity scores matching analyses found that migraine patients had a significantly higher risk of developing AD compared to non-migraine patients (HR = 1.85, 95%CI = 1,68–2.05, P < 0.001). Additionally, the MR suggested that significant causal effects of migraine on AD risks were observed [odds ratio (OR) = 2.315; 95% confidence interval (CI) = 1.029–5.234; P = 0.002]. Moreover, no evidence supported the causal effects of AD on migraine (OR = 1.000; 95%CI = 0.999–1.006; P = 0.971).

The present study concludes that migraine patients, compared to a matched control group, exhibit an increased risk of developing AD. Moreover, migraine patients exhibit an increased predisposition of genetic susceptibility to AD. These findings hold significant clinical value for early intervention and treatment of migraines to reduce the risk of AD.

Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada.

We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV.

We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable.

PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Unlike other causes of stroke, symptoms in cerebral venous thrombosis (CVT) can be nonspecific at onset with gradual worsening over time. To explore potential opportunities for earlier diagnosis, we analyzed healthcare interactions in the week prior to hospitalization for patients admitted with incident CVT in British Columbia (BC).

We constructed a population-based cohort (2000–2017) using linked patient-level administrative data to identify patients aged ≥18 diagnosed with CVT in BC. We used descriptive analysis to describe the frequency and types of healthcare encounters within the 7 and 3 days prior to hospitalization. Multivariable logistic regression modeling was performed to examine risk factors associated with prior encounters.

The cohort included 554 patients (mean age 50.9 years, 55.4% female). Within the 7 days prior to CVT hospitalization, 57.9% of patients had ≥1 outpatient encounter and 5.6% had ≥1 inpatient encounter. In the 3 days prior to hospitalization, 46.8% of patients had ≥1 outpatient encounter and 2.0% had ≥1 inpatient encounter. Women more frequently had outpatient interactions within 7 days (64.8% women vs. 35.2% men, p < 0.001) and 3 days (51.8% vs. 48.2%, p = 0.01) before admission. Common provider specialties for outpatient encounters were general practice (58.0%), emergency (8.3%) and neurology (5.7%). Females had higher odds (OR = 1.79) of having ≥1 outpatient encounter after adjusting for confounding.

Within our Canadian cohort, over half of patients had a healthcare encounter within 7 days before their hospitalization with incident CVT. Women more commonly had an outpatient encounter preceding hospital admission.

We aimed to (1) report updated estimates of direct healthcare costs for people living with MS (pwMS), (2) contrast costs to a control population and (3) explore differences between disability levels among pwMS.

Administrative data were used to identify adult pwMS (MS cohort) and without (control cohort) in Alberta, Canada; disability level (based on the Expanded Disability Status Scale) among pwMS was estimated. One- and two-part generalized linear models with gamma distribution were used to estimate the incremental direct healthcare cost (2021 $CDN) of MS during a 1-year observation period.

Adjusting for confounders, the total healthcare cost ratio was higher in the MS cohort (n = 13,089) versus control (n = 150,080) (5.24 [95% CI: 5.08, 5.41]) with a predicted incremental cost of $15,016 (95% CI: $14,497, $15,535) per person-year. Among the MS cohort, total predicted direct healthcare costs were higher with greater disability, $14,430 (95% CI: $13,980, $14,880) to $58,697 ($51,514, $65,879) per person-year in mild and severe disability, respectively. The primary health resource cost component shifted from disease-modifying therapies in mild disability to supportive care in moderate and severe disability.

Adult pwMS had greater direct healthcare costs than those without. Extrapolating to the population level (where 14,485 adult pwMS were identified in the study), it is estimated that $218 million per year in healthcare costs may be attributable to MS in Alberta. The significantly larger economic impact associated with greater disability underscores the importance of preventing or delaying disease progression and functional impairment in MS.

There is limited information on rare spinocerebellar ataxia (SCA) variants, particularly in the Canadian population. This study aimed to describe the demographic and clinical features of uncommon SCA subtypes in Canada and compare them with international data.

We conducted a case series and literature review of adult patients with rare SCA subtypes, including SCA5, SCA7, SCA12, SCA14, SCA15, SCA28, SCA34, SCA35 and SCA36. Data were collected from medical centers in Ontario, Alberta and Quebec between January 2000 and February 2021.

We analyzed 25 patients with rare SCA subtypes, with onset ages ranging from birth to 67 years. Infantile and juvenile-onset cases were observed in SCA5, SCA7, SCA14 and SCA34. Most patients presented with gait ataxia, with no significant differences across groups. Additional common features included saccadic abnormalities (22 of 25), dysarthria (19 of 25) and nystagmus (12 of 22, except in SCA7). Less common findings included dystonia (8 of 25), cognitive impairment (7 of 25), tremor (9 of 25) and parkinsonism (3 of 25).

Our study highlights the heterogeneity of rare SCA subtypes in Canada. Ongoing longitudinal analysis will improve the understanding, management and screening of these disorders.

Parkinson’s disease (PD) is characterized by the inability of dopamine production from amino acids. Therefore, changes in amino acid profile in PD patients are very critical for understanding disease development. Determination of amino acid levels in PD patients with a cumulative approach may enlighten the disease pathophysiology.

A systematic search was performed until February 2023, resulting in 733 articles in PubMed, Web of Science and Scopus databases to evaluate the serum amino acid profile of PD patients. Relevant articles in English with mean/standard deviation values of serum amino acid levels of patients and their healthy controls were included in the meta-analysis.

Our results suggest that valine, proline, ornithine and homocysteine levels were increased, while aspartate, citrulline, lysine and serine levels were significantly decreased in PD patients compared to healthy controls. Homocysteine showed positive correlations with glutamate and ornithine levels. We also analyzed the disease stage parameters: Unified Parkinson’s Disease Rating Scale III (UPDRS III) score, Hoehn–Yahr Stage Score, disease duration and levodopa equivalent daily dose (LEDD) of patients. It was observed that LEDD has a negative correlation with arginine levels in patients. UPDRS III score is negatively correlated with phenylalanine levels, and it also tends to show a negative correlation with tyrosine levels. Disease duration tends to be negatively correlated with citrulline levels in PD patients.

This cumulative analysis shows evidence of the relation between the mechanisms underlying amino acid metabolism in PD, which may have a great impact on disease development and new therapeutic strategies.

To examine the association of co-morbidity with home-time after acute stroke and whether the association is influenced by age.

We conducted a province-wide study using linked administrative databases to identify all admissions for first acute ischemic stroke or intracerebral hemorrhage between 2007 and 2018 in Alberta, Canada. We used ischemic stroke-weighted Charlson Co-morbidity Index of 3 or more to identify those with severe co-morbidity. We used zero-inflated negative binomial models to determine the association of severe co-morbidity with 90-day and 1-year home-time, and logistic models for achieving ≥ 80 out of 90 days of home-time, assessing for effect modification by age and adjusting for sex, stroke type, comprehensive stroke center care, hypertension, atrial fibrillation, year of study, and separately adjusting for estimated stroke severity. We also evaluated individual co-morbidities.

Among 28,672 patients in our final cohort, severe co-morbidity was present in 27.7% and was associated with lower home-time, with a greater number of days lost at younger age (−13 days at age < 60 compared to −7 days at age 80+ years for 90-day home-time; −69 days at age < 60 compared to −51 days at age 80+ years for 1-year home-time). The reduction in probability of achieving ≥ 80 days of home-time was also greater at younger age (−22.7% at age < 60 years compared to −9.0% at age 80+ years). Results were attenuated but remained significant after adjusting for estimated stroke severity and excluding those who died. Myocardial infarction, diabetes, and cancer/metastases had a greater association with lower home-time at younger age, and those with dementia had the greatest reduction in home time.

Severe co-morbidity in acute stroke is associated with lower home-time, more strongly at younger age.

Understanding sex differences among persons with moderate-to-severe traumatic brain injury (TBI) is critical to addressing the unique needs of both males and females from acute care through to rehabilitation. Epidemiological studies suggest that 7 of every 10 persons with moderate-to-severe TBI are male, with females representing about 30%–33%.

To examine the proportion of female and male individuals included in randomized controlled trials (RCTs) of interventions for moderate-to-severe TBI.

A systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up to and including December 2022 using MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO databases. Studies were included if they met the following criteria: (1) human participants with a mean age ≥18 years, (2) ≥50% of the sample had moderate-to-severe TBI and (3) the study design was a RCT. Data extracted included author, year, country, sample size, number of female/male participants and time post-injury.

595 RCTs met the criteria for inclusion, published between 1978 and 2022, totaling 86,662 participants. The average proportion of female participants was 23.14%, and the percentage increased a small but significant amount over time. There was a significantly lower percentage of female participants in RCTs initiated in the acute phase (≤ 1 month) when compared with RCTs conducted in the chronic phase (≥ 6 months) post-injury (p < 0.001).

Female participants are underrepresented in RCTs of moderate-to-severe TBI. Addressing this underrepresentation is critical to establish effective treatments for all persons with TBI.

Parkinson’s disease (PD) chronic L-Dopa treatment often triggers motor complications, such as L-Dopa-induced dyskinesias (LID). LID are reported to be associated with abnormal glutamatergic activity between the striatum and primary motor cortex (M1), resulting in M1 hyperactivation. Beneficial noninvasive brain stimulation (NIBS) paradigms were reported to normalize glutamatergic activity. The objective of the present study was thus to set up a NIBS paradigm in parkinsonian monkeys to investigate motor behavior under basal conditions and with L-Dopa treatment-inducing dyskinesias.

Motor behavior was investigated in five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dyskinetic female Macaca fascicularis monkey models of PD, allowing us to monitor the administration of NIBS and drugs. NIBS used were inhibitory protocols, that is, cathodal transcranial direct current stimulation (c-tDCS) and continuous theta-burst stimulation (cTBS). A procedure of three weeks was developed to progressively acclimate animals to the experimental conditions, equipment and noise of c-tDCS and cTBS before stimulating them with either vehicle or L-Dopa.

One session of c-tDCS with L-Dopa yielded no effect, whereas five sessions briefly reduced LID but decreased the duration of L-Dopa anti-PD effects. cTBS alone improved (decreased) parkinsonian scores as compared to sham stimulation or vehicle alone. Two sessions of cTBS with L-Dopa decreased LID without affecting L-Dopa anti-PD effects.

This is the first study testing c-tDCS and cTBS on the motor behavior of MPTP dyskinetic monkeys. As compared to medicated patients, MPTP monkeys offer the opportunity to evaluate NIBS after-effects in drug-free and LID conditions, which are critical in the search for new PD treatment.

Identifying a patient’s dominant language hemisphere is an important evaluation performed prior to epilepsy surgery and is commonly assessed using functional magnetic resonance imaging (fMRI). However, the lack of standardization and resultant heterogeneity of fMRI paradigms used in clinical practice limits the ability of cross-center comparisons to be made regarding language laterality results.

Through surveying Canadian Epilepsy Centres in combination with reviewing supporting literature, current fMRI language lateralization practices for the clinical evaluation of patients with epilepsy were assessed. To encourage standardization of this practice, we outlined a two-part paradigm series that demonstrates widespread acceptance, reliability and accessibility in lateralizing various aspects of language functioning in individuals with average or near-average IQ and normal literacy skills.

The collected data confirm a lack of standardization in fMRI laterality assessments leading to clinical heterogeneity in stimulation and control tasks, paradigm design and timing, laterality index calculations, thresholding values and analysis software and technique. We suggest a Sentence Completion (SC) and Word Generation (WG) paradigm series as it was most commonly employed across Canada, demonstrated reliability in lateralizing both receptive and expressive language areas in supporting literature, and could be readily intelligible to an inclusive population.

Through providing recommendations for a two-part paradigm series, we hope to contribute to the standardization of this practice across Canada to reduce clinical heterogeneity, encourage communicability between institutions, and enhance methodologies for the surgical treatment of epilepsy for the benefit of all individuals living with epilepsy in Canada.

Depressive symptoms are common in stroke survivors. While obesity has been associated with stroke and depression, its influence on the association between stroke and depressive symptoms is unknown.

Cross-sectional data from 2015 to 2016 Canadian Community Health Survey was used. History of stroke was self-reported and our outcome of interest was depressive symptoms in the prior 2 weeks, measured using the 9-item Patient Health Questionnaire. Self-reported body mass index (BMI) was modeled as cubic spline terms to allow for nonlinear associations. We used multivariable logistic regression to evaluate the association between stroke and depressive symptoms and added an interaction term to evaluate the modifying effect of BMI.

Of the 47,521 participants, 694 (1.0%) had a stroke and 3314 (6.5%) had depressive symptoms. Those with stroke had a higher odds of depressive symptoms than those without (aOR = 3.13, 95% CI 2.48, 3.93). BMI did not modify the stroke-depressive symptoms association (P interaction = 0.242) despite the observed variation in stroke-depressive symptoms association across BMI categories,: normal BMI [18.5–25 kg/m2] (aOR† = 3.91, 95% CI 2.45, 6.11), overweight [25–30 kg/m2] (aOR† = 2.63, 95% CI 1.58, 4.20), and obese [>30 kg/m2] (aOR† = 2.76, 95% CI 1.92, 3.94). Similar results were found when depressive symptoms were modeled as a continuous measure.

The association between stroke and depressive symptoms is not modified by BMI, needing additional work to understand the role of obesity on depression after stroke.

Disease-modifying therapies (DMTs) for Alzheimer’s disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.

The workgroup employed a Delphi process to develop these recommendations. Experts from radiology, neurology, biomedical engineering, nuclear medicine, MRI and medical physics were recruited. Surveys and meetings were conducted to achieve consensus on key issues, including protocol standardization, scanner strength, monitoring protocols based on risk profiles and optimal protocol lengths. Draft recommendations were refined through multiple iterations and expert discussions.

The recommendations emphasize standardized acquisition imaging protocols across manufacturers and scanner strengths to ensure consistency and reliability of clinical treatment decisions, tailored monitoring protocols based on DMTs’ safety and efficacy profiles, consistent monitoring regardless of perceived treatment efficacy and MRI screening on 1.5T or 3T scanners with adapted protocols. An optimal protocol length of 20–30 minutes was deemed feasible; specific sequences are suggested.

The guidelines aim to enhance imaging data quality and consistency, facilitating better clinical decision-making and improving patient outcomes. Further research is needed to refine these protocols and address evolving challenges with new DMTs. It is recognized that administrative, financial and logistical capacity to deliver additional MRI and positron emission tomography scans require careful planning.