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.

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.

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.

Diagnosis of acute ischemia typically relies on evidence of ischemic lesions on magnetic resonance imaging (MRI), a limited diagnostic resource. We aimed to determine associations of clinical variables and acute infarcts on MRI in patients with suspected low-risk transient ischemic attack (TIA) and minor stroke and to assess their predictive ability.

We conducted a post-hoc analysis of the Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study, a prospective, multicenter cohort study investigating the frequency of acute infarcts in patients with low-risk neurological symptoms. Primary outcome parameter was defined as diffusion-weighted imaging (DWI)-positive lesions on MRI. Logistic regression analysis was performed to evaluate associations of clinical characteristics with MRI-DWI-positivity. Model performance was evaluated by Harrel’s c-statistic.

In 1028 patients, age (Odds Ratio (OR) 1.03, 95% Confidence Interval (CI) 1.01–1.05), motor (OR 2.18, 95%CI 1.27–3.65) or speech symptoms (OR 2.53, 95%CI 1.28–4.80), and no previous identical event (OR 1.75, 95%CI 1.07–2.99) were positively associated with MRI-DWI-positivity. Female sex (OR 0.47, 95%CI 0.32–0.68), dizziness and gait instability (OR 0.34, 95%CI 0.14–0.69), normal exam (OR 0.55, 95%CI 0.35–0.85) and resolved symptoms (OR 0.49, 95%CI 0.30–0.78) were negatively associated. Symptom duration and any additional symptoms/symptom combinations were not associated. Predictive ability of the model was moderate (c-statistic 0.72, 95%CI 0.69–0.77).

Detailed clinical information is helpful in assessing the risk of ischemia in patients with low-risk neurological events, but a predictive model had only moderate discriminative ability. Patients with clinically suspected low-risk TIA or minor stroke require MRI to confirm the diagnosis of cerebral ischemia.

Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.

Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines > 1.5 SD from baseline were considered clinically significant.

Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values > 0.635). At the individual level, one patient with MCI declined > 1.5 SD on the verbal memory composite. No other patients showed declines > 1.5 SD.

Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.

Obstructive sleep apnea (OSA) is prevalent after stroke and associated with recurrent stroke, prolonged hospitalization, and decreased functional recovery. Sex differences in post-stroke OSA remain underexplored. The objective of this study was to evaluate sex differences in functional outcomes, stroke and OSA severity, and clinical manifestations of OSA in stroke patients with OSA.

We retrospectively evaluated data from three previously conducted studies. Study patients had an imaging-confirmed stroke and had been found to have OSA (apnea–hypopnea index [AHI] ≥ 5) on either in-laboratory polysomnography or home sleep apnea testing performed within 1 year of their stroke. Linear regression models were used to evaluate study outcomes.

In total, 171 participants with post-stroke OSA (117 males [68.4%] and 54 females [31.6%]) were included. Female sex was an independent predictor for greater functional impairment (β = 0.37, 95% CI 0.029–0.71, p = 0.03), increased stroke severity (β = 1.009, 95% CI 0.032–1.99, p = 0.04), and greater post-stroke depressive symptoms (β = 3.73, 95% CI 0.16–7.29, p = 0.04). Female sex was associated with lower OSA severity, as measured by the AHI (β = –5.93, 95% CI –11.21– –0.66). Sex was not an independent predictor of specific symptoms of OSA such as daytime sleepiness, snoring, tiredness, and observed apneas.

Females with post-stroke OSA had poorer functional outcomes and more severe strokes compared to males, despite having lower OSA severity. Females with post-stroke OSA also exhibited more depressive symptoms. Understanding sex differences in patients with post-stroke OSA will likely facilitate better recognition of OSA and potentially improve clinical outcomes.

Improvements in management of transient ischemic attack (TIA) have decreased stroke and mortality post-TIA. Studies examining trends over time on a provincial level are limited. We analyzed whether efforts to improve management have decreased the rate of stroke and mortality after TIA from 2003 to 2015 across an entire province.

Using administrative data from the Canadian Institute for Health Information’s (CIHI) databases from 2003 to 2015, we identified a cohort of patients with a diagnosis of TIA upon discharge from the emergency department (ED). We examined stroke rates at Day 1, 2, 7, 30, 90, 180, and 365 post-TIA and 1-year mortality rates and compared trends over time between 2003 and 2015.

From 2003 to 2015 in Ontario, there were 61,710 patients with an ED diagnosis of TIA. Linear regressions of stroke after the index TIA showed a significant decline between 2003 and 2015, decreasing by 25% at Day 180 and 32% at 1 year (p < 0.01). The 1-year stroke rate decreased from 6.0% in 2003 to 3.4% in 2015. Early (within 48 h) stroke after TIA continued to represent approximately half of the 1-year event rates. The 1-year mortality rate after ED discharge following a TIA decreased from 1.3% in 2003 to 0.3% in 2015 (p < 0.001).

At a province-wide level, 1-year rates of stroke and mortality after TIA have declined significantly between 2003 and 2015, suggesting that efforts to improve management may have contributed toward the decline in long-term risk of stroke and mortality. Continued efforts are needed to further reduce the immediate risk of stroke following a TIA.

Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke.

We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery.

We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone.

Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%.

The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.

Delayed presentation to the emergency department influences acute stroke care and can result in worse outcomes. Despite public health messaging, many young adults consider stroke as a disease of older people. We determined the differences in ambulance utilization and delays to hospital presentation between women and men as well as younger (18–44 years) versus older (≥45 years) patients with stroke.

We conducted a population-based retrospective study using national administrative health data from the Canadian Institute of Health Information databases and examined data between 2003 and 2016 to compare ambulance utilization and time to hospital presentation across sex and age.

Young adults account for 3.9% of 463,310 stroke/transient ischemic attack/hemorrhage admissions. They have a higher proportion of hemorrhage (37% vs. 15%) and fewer ischemic events (50% vs. 68%) compared with older patients. Younger patients are less likely to arrive by ambulance (62% vs. 66%, p < 0.001), with younger women least likely to use ambulance services (61%) and older women most likely (68%). Median stroke onset to hospital arrival times were 7 h for older patients and younger men, but 9 h in younger women. There has been no improvement among young women in ambulance utilization since 2003, whereas ambulance use increased in all other groups.

Younger adults, especially younger women, are less likely to use ambulance services, take longer to get to hospital, and have not improved in utilization of emergency services for stroke over 13 years. Targeted public health messaging is required to ensure younger adults seek emergency stroke care.

Endovascular thrombectomy (EVT) is effective in reducing disability in selected patients with stroke and large vessel occlusion (LVO), but access to this treatment is suboptimal.

We examined the proportion of patients with LVO who did not receive EVT, the reasons for non-treatment, and the association between time from onset and probability of treatment.

We conducted a retrospective cohort study of consecutive patients with acute stroke and LVO presenting between January 2017 and June 2018. We used multivariable log-binomial models to determine the association between time and probability of treatment with and without adjustment for age, sex, dementia, active cancer, baseline disability, stroke severity, and evidence of ischemia on computerized tomography.

We identified 256 patients (51% female, median age 74 [interquartile range, IQR 63.5, 82.5]), of whom 59% did not receive EVT. The main reasons for not treating with EVT were related to occlusion characteristics or infarct size. The median time from onset to EVT center arrival was longer among non-treated patients (218 minutes [142, 302]) than those who were treated (180 minutes [104, 265], p = 0.03). Among patients presenting within 6 hours of onset, the relative risk (RR) of receiving EVT decreased by 3% with every 10-minute delay in arrival to EVT center (adjusted RR 0.97 CI95 [0.95, 0.99]). This association was not found in the overall cohort.

The proportion of patients with acute stroke and confirmed LVO who do not undergo EVT is substantial. Minimizing delays in arrival to EVT center may optimize the delivery of this treatment.

Women are more likely to be admitted to nursing home after stroke than men. Differences in patient characteristics and outcomes by sex after institutionalization are less understood. We examined sex differences in the characteristics and care needs of patients admitted to nursing home following stroke and their subsequent survival.

We identified patients with stroke newly admitted to nursing home between April 2011 and March 2016 in Ontario, Canada, with follow-up until March 2018 using linked administrative data. We calculated prevalence ratios and 95% confidence intervals (CIs) for the primary outcomes of dependence for activities of daily living, cognitive impairment, frailty, health instability, and symptoms of depression or pain, comparing women to men. The secondary outcome was all-cause mortality.

Among 4831 patients, 60.9% were women. Compared to men, women were older (median age [interquartile range, IQR]: 84 [78, 89] vs. 80 [71, 86]), more likely to be frail (prevalence ratio 1.14, 95% CI [1.08, 1.19]), have unstable health (1.45 [1.28, 1.66]), and experience symptoms of depression (1.25 [1.11, 1.40]) or pain (1.21 [1.13, 1.30]), and less likely to have aggressive behaviors (0.87 [0.80, 0.94]). Overall median survival was 2.9 years. In a propensity-score-matched cohort, women had lower mortality than men (hazard ratio 0.85, 95% CI [0.77, 0.94]), but in the age-stratified survival analysis, the survival advantage in women was limited to those aged 75 years and older.

Despite lower subsequent mortality, women admitted to nursing home after stroke required more care than men. Pain and depression are two treatable symptoms that disproportionately affect women.

Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada.

We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers.

Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT).

Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.

Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.

Dementia prevalence is rising, and it will double in the next 20 years. This study sought to understand the prevalence of dementia in hospitalized patients with ischemic stroke, and its impact on outcomes.

Using the Canadian Institute of Health Information’s (CIHI) Discharge Abstract Database (DAD), all acute ischemic stroke admissions from April 2003 to March 2015 in Canada (excluding Quebec) were analyzed. Concurrent dementia at the time of admission was assessed based on hospital diagnostic codes. Characteristics and in-hospital outcomes were compared in patients with and without dementia using χ2 and negative binomial, as well as Poisson regression analysis.

During the observed period, 313,138 people were admitted to a hospital in Canada for an ischemic stroke. Of those, 21,788 (7.0%) had a concurrent diagnosis of dementia. People with dementia had older median age (84 vs. 76 years; p<0.0001), were more often female (59.6% vs. 48.4%; p<0.0001) and more often had Charlson-Deyo Comorbidity Index ≥2 (64.5% vs. 43.5%; p<0.0001). Patients with dementia were less likely to be discharged to a rehabilitation facility (adjusted risk ratio [RR] 3.089, 95% confidence interval [CI] 2.992-3.188, p<0.0001) or home independently (adjusted RR 0.756, 95% CI 0.737-0.776, p<0.0001).

Approximately 1 in 13 hospitalized ischemic stroke patients has coded dementia. Patients with ischemic stroke and concurrent dementia have higher mortality, face significantly more dependence after stroke and utilize greater healthcare resources than stroke patients without dementia. Causative conclusions are limited by the administrative data source. Early care planning and coordination could potentially optimize outcomes.