The presence of an intraluminal thrombus in acutely symptomatic carotid stenosis is thought to represent a high-risk lesion for short-term stroke reccurrence though evidence on natural history and treatment is lacking, leading to equipoise and much variation in practice. The objective of this study was to map these variations in practice (medical management and timing of revascularization), determine the considerations that influence clinician decision-making in this condition and gather opinions that inform the development and design of future trials in the area.

This was a mixed-methods study using both quantitative survey methods and qualitative interview-based methods. International perspectives were gathered by distributing a case-based survey via the “Practice Current” section of Neurology: Clinical Practice and interviewing international experts using established qualitative research methods.

The presence of an intraluminal thrombus significantly increased the likelihood of using a regimen containing anticoagulation agents (p < 0.001) in acutely symptomatic carotid stenosis in the case-based survey. Themes that emerged from qualitative interview analysis were therapeutic uncertainty regarding anticoagulation, decision to reimage, revascularization choices and future trial design and anticipated challenges.

Results of this study demonstrate a preference for anticoagulation and delayed revascularization after reimaging to examine for clot resolution, though much equipoise remains. While there is interest from international experts in future trials, further study is needed to understand the natural history of this condition in order to inform trial design.

Clinical trials often struggle to recruit enough participants, with only 10% of eligible patients enrolling. This is concerning for conditions like stroke, where timely decision-making is crucial. Frontline clinicians typically screen patients manually, but this approach can be overwhelming and lead to many eligible patients being overlooked.

To address the problem of efficient and inclusive screening for trials, we developed a matching algorithm using imaging and clinical variables gathered as part of the AcT trial (NCT03889249) to automatically screen patients by matching these variables with the trials’ inclusion and exclusion criteria using rule-based logic. We then used the algorithm to identify patients who could have been enrolled in six trials: EASI-TOC (NCT04261478), CATIS-ICAD (NCT04142125), CONVINCE (NCT02898610), TEMPO-2 (NCT02398656), ESCAPE-MEVO (NCT05151172), and ENDOLOW (NCT04167527). To evaluate our algorithm, we compared our findings to the number of enrollments achieved without using a matching algorithm. The algorithm’s performance was validated by comparing results with ground truth from a manual review of two clinicians. The algorithm’s ability to reduce screening time was assessed by comparing it with the average time used by study clinicians.

The algorithm identified more potentially eligible study candidates than the number of participants enrolled. It also showed over 90% sensitivity and specificity for all trials, and reducing screening time by over 100-fold.

Automated matching algorithms can help clinicians quickly identify eligible patients and reduce resources needed for enrolment. Additionally, the algorithm can be modified for use in other trials and diseases.

Cerebral microbleeds are associated with an increased risk of hemorrhagic transformation (HT) following acute ischemic stroke. We investigated whether the effect of dabigatran (vs. aspirin) in patients with acute minor non-cardioembolic ischemic stroke/transient ischemic attack (TIA) is modified by baseline microbleeds on MRI.

The Dabigatran Treatment of Acute Stroke II trial randomized 305 patients with acute minor non-cardioembolic ischemic stroke/TIA to dabigatran (150/110 mg twice daily) or aspirin (81 mg daily) for 30 days. Microbleeds were centrally adjudicated in patients with an interpretable blood-sensitive sequence on baseline MRI. In this post hoc analysis, we used multivariable regression models to determine the association between microbleeds and any incident HT on day-30 MRI and excellent functional outcome (modified Rankin scale = 0–1) at 90 days.

A total of 251 (82.3%) participants (mean age = 66 ± 13 years, 36% women, median [IQR] onset-to-randomization time = 40[27–55] hours; median [IQR] NIHSS = 1 [0–2]) were included, of whom 82 (33%) had microbleeds. On day-30 MRI, 6% (n = 14) developed HT, and 80% (n = 191) achieved 90-day mRS of 0–1. We found no association between microbleed presence and HT (adjusted OR = 0.84; 95%CI:0.21–3.25) or excellent functional outcome (adjusted RR = 1.09; 95%CI:0.94–1.26). The rate of HT in patients with microbleeds was 3% with dabigatran and 4% with aspirin (OR = 0.85; 95%CI:0.11–6.75). Excellent functional outcome occurred in 74% and 84% of dabigatran and aspirin-treated patients, respectively (RR = 0.88; 95%CI:0.69–1.12). The presence, severity or location of microbleeds did not modify the effect of dabigatran on these outcomes (p-interaction > 0.05).

Early dabigatran treatment appears safe in patients with acute minor non-cardioembolic ischemic stroke/TIA and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI.

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.

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.

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.

Migraine management involves a wide range of clinical rehabilitation practices. This variability hampers the clinical applicability of these protocols. Before proposing any recommendations for migraine interventions, one needs to identify how interventions are generally structured. This study aimed to systematically map the activities in multidisciplinary rehabilitation programs for people with migraine.

We conducted a scoping review from January 2002 to April 2024 in MEDLINE®, CINAHL, Academic Search Complete, AMED, APA PsycInfo and Academic Search Complete databases. Search terms were related to (i) migraine or headache, (ii) intervention and (iii) multidisciplinary or interdisciplinary care. Language and population inclusion criteria were applied. Two researchers independently screened titles, abstracts and full-text articles and extracted data according to three topics: (i) activities and their modalities, (ii) professionals involved and (iii) tools used.

The activities identified ranged from medication management and a variety of exercise types and lifestyle changes using education strategies to stress management techniques. Psychological interventions were rarely defined and appeared to overlap with education and stress management techniques. Information on treatment delivery was scarce. Professionals from many disciplines were mentioned. The outcomes assessed included migraine or headache characteristics, psychological symptoms, disability and quality of life. No explicit theoretical models were found.

The results highlight the heterogeneity of activities in multidisciplinary interventions for people with migraine. Operationalizing an intervention based on a theoretical model is essential for allowing replications, evaluation and implementation in rehabilitation settings.

Deep brain stimulation (DBS) is an important treatment for Parkinson’s disease, tremor and dystonia in appropriately selected patients. The Canada Health Act emphasizes equity and “reasonable access to medically necessary hospital and physician services.” How to define “reasonable access” has not been well studied. We aimed to assess access to DBS implantation surgery and to determine the time required from initial assessment through to surgery and which step(s) delay the implantation.

DBS implants from 2016 to 2023 at the University of Alberta were analyzed. The neurologists’ decision to proceed with DBS marks the start of the workup. The time required to see a neurosurgeon, psychiatrist, neuropsychologist and healthcare allies and to receive DBS surgery was assessed. The impact of COVID-19 was studied.

The total time from starting the workup to DBS surgery was 387.76 ± 125.19 days prior to COVID-19, and marked delay occurred during and post-COVID-19 (840.15 ± 165.41 days and 839.78 ± 300.66 days, respectively). Most workups were done within 6 months pre-COVID-19, although a big range existed due to variable factors. The longest delay to surgery was from consent to DBS implantation, owing to a lack of operative time. There has not been a recovery post-pandemic.

Time to DBS implantation surgery from initial decision is lengthy and more than doubled over the course of the COVID-19 pandemic. The biggest delay was in the time from consent to implantation surgery, which has not improved despite the pandemic having ended.

Parkinson disease (PD) is a neurological disorder that affects more than 10 million people worldwide, impacting both quality of life and marital relationships. Divorce rates are higher in Western compared to Eastern countries. However, it is unclear if there are differences in marital status after PD onset between the two regions.

We searched MEDLINE and Embase from inception to March 31, 2024. Original studies discussing marital status in participants with PD were included. An unmarried status includes single, widowed, divorced or separated. Outcomes included the prevalence of being unmarried, measured as proportions, and the risk ratio (RR) of being unmarried in participants with PD relative to controls.

Out of 567 studies screened initially, 55 studies involving 3,723,966 participants were included. The prevalence of being unmarried was evaluated in 55 studies (25.16%; 95% CI: 21.52–29.18). The prevalence of being unmarried was significantly higher in countries in the West compared to the East (28.83%; 95% CI: 25.09–32.89 vs 17.47%; 95% CI: 12.10–24.57, p < 0.01). Compared to controls, the risk of being unmarried in PD participants after the onset of PD was significantly higher in the East (RR: 1.21, 95% CI: 0.91–1.60) compared to the West (RR: 0.87, 95% CI: 0.65–1.15).

Our meta-analysis showed significantly higher rates of being unmarried in Western compared to Eastern countries. After PD onset, participants in the East were at significantly higher risk of being unmarried compared to participants in the West, suggesting that differences in cultural practices, societal norms and healthcare systems may affect marital status outcomes in PD participants.

PRKN-related parkinsonism represents one of the most common types of genetically determined Parkinson’s disease (PD). However, the literature among the Asian ethnicity, particularly in the Indian context, is limited.

To study the clinico-genetic profile of patients with PRKN-related parkinsonism and to review the previously reported cases of PRKN-related parkinsonism from Asia.

A retrospective chart review from a tertiary neurology centre of patients with genetically confirmed PRKN-related parkinsonism. Additionally, we consolidated the Asian cohort from a detailed systematic review of the literature. We utilised the Movement Disorders Society gene cohort for comparison with the world literature.

We recruited 16 cases (males = 10, Early onset Parkinson disease (21 to <50 years age at onset)) of PRKN-related parkinsonism with a median age at onset of 28.5 years (range 14–46). Symptoms included parkinsonism (n = 15), dystonia (n = 10), postural instability (n = 7), freezing of gait (n = 5) and non-motor symptoms (NMS) (n = 10). The commonest symptom at onset was tremors (n = 10). Levodopa responsiveness was observed in all cases with drug-induced dyskinesia in eight (50%). Thirteen cases were homozygous, while three were compound heterozygotes, resulting in 19 variants (novel = 5). Exon deletion was the most common (n = 12). The extended Asian cohort comprising 294 cases had a high prevalence of EOPD (n = 186/257, 72.4%) and familial cases (n = 166/252, 65.9%). Deletion/duplication was the common mutation detected (n = 215, 73.1%). The presumed familial cases had a significantly higher frequency of rest tremors, bradykinesia, postural instability, NMS, dyskinesia and sleep disorders.

This largest single-centre study from India adds 16 new cases and five novel variants to PRKN literature. In addition, it consolidates the Asian cohort of PRKN elucidating its unique attributes.

We sought to compare whether quality of life (QOL) in patients with subjective cognitive impairment (SCI) who performed normally on a neuropsychological battery significantly differed from those diagnosed with mild cognitive impairment (MCI), Alzheimer’s disease (AD) or non-Alzheimer’s dementia (non-AD) at initial assessment in a Rural and Remote Memory Clinic (RRMC).

610 patients referred to our RRMC between 2004 and 2019 were included in this study. We compared self-reported and caregiver-reported patient QOL scores in those with SCI (n = 166) to those diagnosed with MCI (n = 98), AD (n = 228) and non-AD (n = 118).

Patients with SCI self-reported significantly lower QOL compared to patients with AD. Interestingly, the reverse was seen in caregivers: SCI caregivers rated patient QOL higher than AD caregivers. Patients with SCI also reported lower QOL than patients with MCI. SCI caregivers reported higher patient QOL than their non-AD counterparts. Caregiver-rated patient QOL was higher in those with MCI compared to AD. Patients with MCI self-reported higher QOL scores compared to patients with non-AD dementias. Similarly, MCI caregivers reported higher patient QOL than non-AD caregivers. No other comparisons were statistically significant.

Although they lacked clinically significant cognitive deficits, patients with SCI self-reported significantly lower QOL than patients with MCI and AD. Conversely, caregiver-reported patient QOL was higher for patients with SCI than for patients with AD and non-AD. This shows that SCI seriously impacts QOL. More research is needed on how we can better support patients with SCI to improve their QOL.