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Background: Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication., Aims: We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase., Methods: Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0-4 vs 5-7 vs 8-10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity., Results: Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65-84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17-19)) with anterior circulation stroke were included. mRS 0-1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0-4, 5-7, and 8-10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes., Conclusion: Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase., Data Access Statement: Data shall made available on reasonable request from the PI (BMM)., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.C. received payments from Servier, consulting fees from iSchemaView RAPID, Circle Neurovascular Imaging (NVI), and Canadian Medical Protective Association. T.T.S. has received consulting fees from Circle NVI. R.H.S. has stock options in FollowMD and gets salary support for research from the Heart and Stroke Foundation of Canada, the Sandra Black Center for Brain Resilience & Recovery, and Ontario Brain Institute. B.M. has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. M.A. reports grants from Canadian Institute of Health Research during the conduct of the study. No other disclosures are reported. N.S. gets salary support for research from the Heart and Stroke Foundation of Canada, Research Manitoba and University of Manitoba.

Background: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion., Aims: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL., Methods: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed., Results: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group., Conclusion: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Y.P. is the Principal investigator of the EASI-TOC trial of carotid stenting, partially funded by Stryker, Brain Canada, Heart and Stroke Foundation of Canada, and the Canadian Stroke Consortium and is in the advisory board of and receives speaker honoraria from Roche Canada. Other authors report no conflict of interest.

Background: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke., Methods: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume., Results: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P  = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted β = .008, η 2  = .03; P  = .04), independently of brain atrophy., Conclusions: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

The 2019 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Mood, Cognition and Fatigue following Stroke is a comprehensive set of evidence-based guidelines addressing three important issues that can negatively impact the lives of people who have had a stroke. These include post-stroke depression and anxiety, vascular cognitive impairment, and post-stroke fatigue. Following stroke, approximately 20% to 50% of all persons may be affected by at least one of these conditions. There may also be overlap between conditions, particularly fatigue and depression. If not recognized and treated in a timely matter, these conditions can lead to worse long-term outcomes. The theme of this edition of the CSBPR is Partnerships and Collaborations, which stresses the importance of integration and coordination across the healthcare system to ensure timely and seamless care to optimize recovery and outcomes. Accordingly, these recommendations place strong emphasis on the importance of timely screening and assessments, and timely and adequate initiation of treatment across care settings. Ideally, when screening is suggestive of a mood or cognition issue, patients and families should be referred for in-depth assessment by healthcare providers with expertise in these areas. As the complexity of patients treated for stroke increases, continuity of care and strong communication among healthcare professionals, and between members of the healthcare team and the patient and their family is an even bigger imperative, as stressed throughout the recommendations, as they are critical elements to ensure smooth transitions from acute care to active rehabilitation and reintegration into their community.

Background: Independence and reintegration into community roles are important patient-centered outcomes after stroke. Depression and cognitive impairment are common post-stroke conditions that may impair long-term function even years after a stroke. However, screening for these post-stroke comorbidities remains infrequent in stroke prevention clinics and the utility of this screening for predicting long-term higher-level function has not been evaluated., Aims: To evaluate the ability of a validated brief Depression, Obstructive sleep apnea, and Cognitive impairment screen (DOC screen) to predict long-term (2-3 years after stroke) community participation and independence in instrumental activities of daily living post stroke., Methods: One hundred twenty-four patients (mean age, 66.3 [standard deviation = 15.7], 52.4% male) completed baseline depression and cognitive impairment screening at first stroke clinic visit, and telephone interviews 2 to 3 years post stroke to assess community independence (Frenchay Activities Index [FAI]) and participation (Reintegration to Normal Living Index [RNLI]). A subset of these patients also consented to complete detailed neuropsychological testing at baseline. Univariate and multivariate linear (FAI) and logistic (RNLI) regression analyses were used to determine the individual relationship between baseline data (predictors) and follow-up scores., Results: Older age (β = -0.17, P = .001), greater stroke severity (β = 1.84, P = .015), more depressive (β = -2.41, P = .023), and cognitive (β = -2.15, P = .046) symptoms independently predicted poor instrumental activity ( R 2 = .27; P < .001). Measures of executive dysfunction were the strongest correlates of poor instrumental activity. Higher depression risk was the only significant predictor of participation on the RNLI in regression modeling (odds ratio = 0.46, P = .028)., Conclusions: Baseline DOC screening in stroke prevention clinics shows that symptoms of depression and cognitive impairment are independent predictors of impaired higher-level functioning and community reintegration 2 to 3 years after stroke. Novel rehabilitation and psychological interventions targeting people with these conditions are needed to improve long-term patient-centered outcomes.

Objective: Impaired attentional processes have been linked with poor outcomes after stroke, but their radiographical correlates have been infrequently studied. Our objective was to assess the relationship between stroke location and vigilant attention., Methods: A total of 39 patients presenting within 2 weeks of a minor stroke were prospectively recruited. Vigilant attention was assessed using the psychomotor vigilance task (PVT), and neuroimaging was used to assess stroke location, white matter hyperintensity (WMH) burden, and ischemic stroke involvement within lateral cholinergic projections. Correlational analyses and linear regression models tested the association between PVT performance and our neuroimaging parameters of interest. Subtractions of lesion overlays were used to identify brain regions of acute stroke patients who performed most poorly on the PVT., Results: Subcortical stroke location was a predictor of PVT performance in this cohort of acute stroke patients. Patients who performed most poorly on the PVT had lesions in the corona radiata, internal capsule, globus pallidus, and thalamus. Global WMH burden and cerebrovascular disease in lateral cholinergic pathways were not significant predictors of PVT performance., Interpretation: Subcortical stroke location was associated with impaired vigilant attention. The poorest PVT performers had stroke lesions involving the corona radiata, internal capsule, globus pallidus, and thalamus, suggesting that vigilance depends on the integrity of subcortical structures and their connections with cortical brain regions.

The Canadian Stroke Best Practice Consensus Statement Acute Stroke Management during Pregnancy is the second of a two-part series devoted to stroke in pregnancy. The first part focused on the unique aspects of secondary stroke prevention in a woman with a prior history of stroke who is, or is planning to become, pregnant. This document focuses on the management of a woman who experiences an acute stroke during pregnancy. This consensus statement was developed in recognition of the need for a specifically tailored approach to the management of this group of patients in the absence of any broad-based, stroke-specific guidelines or consensus statements, which do not exist currently. The foundation for the development of this document was the concept that maternal health is vital for fetal well-being; therefore, management decisions should be based first on the confluence of two clinical considerations: (a) decisions that would be made if the patient wasn't pregnant and (b) decisions that would be made if the patient hadn't had a stroke, then nuanced as needed. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include initial emergency management, diagnostic imaging, acute stroke treatment, the management of hemorrhagic stroke, anesthetic management, post stroke management for women with a stroke in pregnancy, intrapartum considerations, and postpartum management. These statements are appropriate for healthcare professionals across all disciplines and system planners to ensure pregnant women who experience a stroke have timely access to both expert neurological and obstetric care.

The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy, is the first of a two-part series devoted to stroke in pregnancy. This document focuses on unique aspects of secondary stroke prevention in a woman with a prior history of stroke or transient ischemic attack who is, or is planning to become, pregnant. Although stroke is relatively rare in this cohort, several aspects of pregnancy can increase stroke risk during or immediately after pregnancy. The rationale for the development of this consensus statement is based on the premise that stroke in this group requires a specifically-tailored management approach. No other broad-based, stroke-specific guidelines or consensus statements exist currently. Underpinning the development of this document was the concept that maternal health is vital for fetal wellbeing; therefore, management decisions should be based on the confluence of two clinical considerations: (a) decisions that would be made if the patient was not pregnant and (b) decisions that would be made if the patient had not had a stroke. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include general management considerations for secondary stroke prevention, the use of antithrombotics, blood pressure management, lipid management, diabetes care, and management for specific ischemic stroke etiologies in pregnancy. The focus is on maternal and fetal health while minimizing risks of a recurrent stroke, through counseling, monitoring, and the safety of select pharmacotherapy. These statements are appropriate for health care professionals across all disciplines.

Background The incidence of stroke in young adults is increasing. While many young survivors are able to achieve a good physical recovery, subtle dysfunction in other domains, such as cognition, often persists, and could affect return to work. However, reported estimates of return to work and factors affecting vocational outcome post-stroke vary greatly. Aims The aims of this systematic review were to determine the frequency of return to work at different time points after stroke and identify predictors of return to work. Summary of review Two electronic databases (Medline and Embase) were systematically searched for articles according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 6473 records were screened, 68 were assessed for eligibility, and 29 met all inclusion criteria (working-age adults with stroke, return to work evaluated as an outcome, follow-up duration reported, and publication within the past 20 years). Return to work increased with time, with median frequency increasing from 41% between 0 and 6 months, 53% at 1 year, 56% at 1.5 years to 66% between 2 and 4 years post-stroke. Greater independence in activities of daily living, fewer neurological deficits, and better cognitive ability were the most common predictors of return to work. Conclusion This review highlights the need to examine return to work in relation to time from stroke and assess cognition in working age and young stroke survivors. The full range of factors affecting return to work has not yet been explored and further evaluations of return to work interventions are warranted.

Background Stroke risk is increased during pregnancy, but estimates of pregnancy-related stroke incidence vary widely. Aims A systematic review and meta-analysis was conducted to assess the incidence of stroke during pregnancy and the puerperium. Ovid Medline, EMBASE, and ISI Web of Science were searched for studies published between 1990 and January 2017 reporting stroke incidence during pregnancy and postpartum, from defined pregnancy populations. Pooled analyses were conducted using a random effects approach and expressed as an incidence rate per 100,000 pregnancies, with 95% confidence intervals. Subgroup analyses of stroke type and timing were conducted. Summary of review Eleven studies met inclusion criteria. Variation in estimated rates was noted based on geography and study methodology. The pooled crude rate of pregnancy-related stroke was 30.0 per 100,000 pregnancies (95% confidence interval 18.8-47.9). The pooled crude rates from nonhemorrhagic stroke (arterial and cerebral venous sinus thrombosis) were 19.9 (95% confidence interval 10.7-36.9) and from hemorrhage 12.2 (95% confidence interval 6.4-23.2) per 100,000 pregnancies. For studies separately reporting cerebral venous sinus thrombosis, the rates were roughly equal between ischemic stroke (12.2, 95% confidence interval 6.7-22.2), cerebral venous sinus thrombosis (9.1, 95% confidence interval 4.3-18.9), and hemorrhage (12.2, 95% confidence interval 6.4-23.2). The crude stroke rate for antenatal/perinatal stroke was 18.3 (95% confidence interval 11.9-28.2), and for postpartum stroke was 14.7 (95% confidence interval 8.3-26.1). Conclusions Stroke affects 30.0 per 100,000 pregnancies, with ischemia, cerebral venous sinus thrombosis, and hemorrhage causing roughly equal numbers and with highest risk peripartum and postpartum. Organized approaches to the management of this high-risk population, informed by existing evidence from stroke and obstetrical care are needed.

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease., (© The Author(s) 2016.)

Stroke can cause neurological impairment ranging from mild to severe, but the impact of stroke extends beyond the initial brain injury to include a complex interplay of devastating comorbidities including: post-stroke depression, obstructive sleep apnea, and cognitive impairment ("DOC"). We reviewed the frequency, impact, and treatment options for each DOC condition. We then used the Ottawa Model of Research Use to examine gaps in care, understand the barriers to knowledge translation, identification, and addressing these important post-stroke comorbidities. Each of the DOC conditions is common and result in poorer recovery, greater functional impairment, increased stroke recurrence and mortality, even after accounting for traditional vascular risk factors. Despite the strong relationships between DOC comorbidities and these negative outcomes as well as recommendations for screening based on best practice recommendations from several countries, they are frequently not assessed. Barriers related to the nature of the screening tools (e.g., time consuming in high-volume clinics), practice environment (e.g., lack of human resources or space), as well as potential adopters (e.g., equipoise surrounding the benefits of treatment for these conditions) pose challenges to routine screening implementation. Simple, feasible approaches to routine screening coupled with appropriate, evidence-based treatment protocols are required to better identify and manage depression, obstructive sleep apnea, and cognitive impairment symptoms in stroke prevention clinic patients to reduce the impact of these important post-stroke comorbidities. These tools may in turn facilitate large-scale randomized controlled treatment trials of interventions for DOC conditions that may help to improve cardiovascular outcomes after stroke or TIA., (© 2016 World Stroke Organization.)

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge., (© 2015 World Stroke Organization.)

Rationale: In acute stroke, time is brain: faster tissue plasminogen activator treatment improves patient outcomes. Published guidelines for door-to-scanner time are <25 minutes, and for door-to-needle time <60 minutes. These benchmarks are rarely met. Paradoxically, the earlier a stroke patient arrives to hospital, the longer treatment takes. There is an urgent need to shift focus away from the 4.5 hour time window, towards treatment times <60 minutes., Aims: The objective of the Countdown Lights to Optimize Quality in acute Stroke (CLOQS) trial is to determine whether a simple, low-cost organizational behavior intervention, a large, red stopwatch timer attached to the stretcher upon arrival, will decrease door-to-scanner and door-to-needle treatment times for tissue plasminogen activator-treated patients., Design: A multicenter, time-clustered randomized control trial. The stopwatch timers will be used in Emergency Departments for all acute stroke patients across the University of Toronto Stroke Program. The order of intervention (ON) and control (OFF) blocks will be randomly assigned in a 1:1 ratio over an 18 month period. Blocks will be weighted in a 2:1 ratio of ON/OFF using a permuted block design (ON blocks last two weeks; OFF blocks last one week)., Study Outcomes: The primary end-point is percentage of patients achieving best-practice guidelines (door-to-needle treatment time <60 minutes). Secondary end-points are median time intervals for 1) door-to-scanner and 2) door-to-needle times during ON versus OFF blocks. Tertiary end-points are in-hospital mortality and time series analysis to determine change in treatment times from prior to study onset through study completion., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)