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.

Stroke clinical registries are critical for systems planning, quality improvement, advocacy and informing policy. We describe the methodology and evolution of the Registry of the Canadian Stroke Network/Ontario Stroke Registry in Canada.

At the launch of the registry in 2001, trained coordinators prospectively identified patients with acute stroke or transient ischemic attack (TIA) at comprehensive stroke centers across Canada and obtained consent for registry participation and follow-up interviews. From 2003 onward, patients were identified from administrative databases, and consent was waived for data collection on a sample of eligible patients across all hospitals in Ontario and in one site in Nova Scotia. In the most recent data collection cycle, consecutive eligible patients were included across Ontario, but patients with TIA and those seen in the emergency department without admission were excluded.

Between 2001 and 2013, the registry included 110,088 patients. Only 1,237 patients had follow-up interviews, but administrative data linkages allowed for indefinite follow-up of deaths and other measures of health services utilization. After a hiatus, the registry resumed data collection in 2019, with 13,828 charts abstracted to date with a focus on intracranial vascular imaging, identification of intracranial occlusions and treatment with thrombectomy.

The Registry of the Canadian Stroke Network/Ontario Stroke Registry is a large population-based clinical database that has evolved throughout the last two decades to meet contemporary stroke needs. Registry data have been used to monitor stroke quality of care and conduct outcomes research to inform policy.

The Edmonton-based mobile stroke unit (MSU), which transports patients to the University of Alberta Hospital (UAH), enrolled patients in the Intravenous Tenecteplase Compared with Alteplase for Acute Ischemic Stroke (AcT) trial. We examined the feasibility of trial enrollment in MSU, its impact on acute stroke workflow metrics and functional outcomes at 90–120 days.

In this post hoc analysis, patients were divided into three groups based on enrollment site: MSU (n = 43), UAH (n = 273) and non-UAH (n = 1261). All patients were enrolled with a deferred consent process. The primary outcome for this analysis was the feasibility of enrollment defined as the proportion of patients receiving intravenous thrombolysis (IVT) during the study period who were enrolled in the trial. Multiple linear and binary logistic regression was used to evaluate the adjusted effect of the study groups on acute stroke workflow metrics and functional outcomes at 90–120 days.

100% of eligible IVT-treated patients in the MSU during the study period were enrolled in the AcT trial. Covariate-adjusted linear regression showed shorter door-to-needle (17.2 [9.7–24.6] min) and CT-to-needle (10.7 [4.2–17.1] min) times in the MSU compared to UAH and non-UAH sites. There was no difference in the proportion of patients with an excellent functional outcome (mRS 0–1) at 90–120 days or symptomatic intracerebral hemorrhage (ICH) at 24 hours between groups.

Enrollment in the AcT trial from the MSU was feasible. MSU-enrolled patients demonstrated faster door-to-needle and CT-to-needle times, resulting in earlier IVT administration and similar rates of symptomatic ICH.

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.

Acute stroke treatments are highly time-sensitive, with geographical disparities affecting access to care. This study examined the impact of driving distance to the nearest comprehensive stroke center (CSC) and rurality on the use of thrombectomy or thrombolysis in Ontario, Canada.

This retrospective cohort study used administrative data to identify adults hospitalized with acute ischemic stroke between 2017 and 2022. Driving time from patients’ residences to the nearest CSC was calculated using the Ontario Road Network File and postal codes. Rurality was categorized using postal codes. Multivariable logistic regression, adjusted for baseline differences, estimated the association between driving distance and treatment with thrombectomy (primary outcome) or thrombolysis (secondary outcome). Driving time was modeled as a continuous variable using restricted cubic splines.

Data from 57,678 patients (median age 74 years, IQR 64–83) were analyzed. Increased driving time was negatively associated with thrombectomy in a nonlinear fashion. Patients living 120 minutes from a CSC were 20% less likely to receive thrombectomy (adjusted odds ratio [aOR] 0.80, 95% CI 0.62–1.04), and those 240 minutes away were 60% less likely (aOR 0.41, 95% CI 0.28–0.60). Driving time did not affect thrombolysis rates, even at 240 minutes (aOR 1.0, 95% CI 0.70–1.42). Thrombectomy use was similar in medium urban areas (aOR 0.80, 95% CI 0.56–1.16) and small towns (aOR 0.78, 95% CI 0.57–1.06) compared to large urban areas.

Thrombolysis access is equitable across Ontario, but thrombectomy access decreases with increased driving distance to CSCs. A multifaceted approach, combining healthcare policy innovation and infrastructure development, is necessary for equitable thrombectomy delivery.

Treatment of acute ischemic stroke is highly time dependent, which relies heavily on each hospital’s ability and capacity. Designated stroke centers have been established across Canada, but there is still a divide between urban and rural hospitals. This study aims to understand the similarities and differences in their stroke treatment process workflow, incorporation of best practices and data collection.

Interviews were conducted with clinicians in stroke centers across Canada to identify similarities and differences between provinces and hospital treatment capability. Semi-structured interviews were completed from September 15 to November 3, 2023, with clinicians and stroke coordinators using snowball and purposive sampling techniques. The interviews were analyzed using thematic analysis.

Fourteen participants were interviewed with representatives from four primary stroke centers and three comprehensive stroke centers across five provinces. Five primary themes were identified: 1) management of resources, 2) standardization of tasks, 3) data collection, 4) tool integration into workflow and 5) teamwork and experience. Participants in primary centers described limited resources to follow the patient through the entire treatment process, reliance on pre-notification times to prospectively search necessary patient information, using software to aid in calculating National Institute of Health Stroke Scale and being more cautious toward treating thrombolytics. Both center types discussed challenges with complete and accurate data collection.

The overall stroke treatment process and information required across primary and comprehensive centers are similar. However, differences occur in the process due to limitations in resources, pre-arrival notification time, completeness and accuracy of data collected and comfort in treating with thrombolytics.

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.

Published guidelines for conducting clinical trials for migraine therapeutics recommend recruiting participants based on disease epidemiology and including sex/gender-based subpopulation analyses. These recommendations aim to improve the quality and generalizability of migraine clinical trials. The aim of this study was to summarize participant demographics in migraine clinical trials for FDA-approved calcitonin gene-related peptide (CGRP)-targeting drugs (receptor antagonists [gepants], CGRP peptide or receptor monoclonal antibodies [mAbs]) and assess the use of sex/gender-based subpopulation analyses in these studies.

We conducted a review of industry-sponsored migraine clinical trials for FDA-approved CGRP-targeting medications. Demographic data (sex and/or gender) from phase II or III trials were abstracted, and the use of sex/gender-based analyses was recorded.

Fourteen trials of gepants were included in this analysis. Participants who were identified as females or women were more likely to participate in these trials (87.0 ± 2.2%). Twenty-four trials of CGRP mAbs were reviewed. These studies also reported that participants were predominantly identified as female or women (84.9 ± 2.3%). None of the clinical trials reviewed reported sex/gender-based analyses of their results.

This study suggests that men are underrepresented in migraine CGRP clinical trials. Greater attention to sex and gender is needed in migraine clinical trial design so that they better align with current recommendations made by headache societies and regulatory agencies.

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.

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.