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Showing papers in "International Journal of Stroke in 2018"


Journal ArticleDOI
TL;DR: The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack.
Abstract: The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for ...

260 citations


Journal ArticleDOI
TL;DR: From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), and World Stroke Organization (WSO).
Abstract: ASPECTS : Alberta Stroke Program Early Computed Tomography Score EVT : endovascular therapy mRS : modified Rankin Scale mTICI : modified thrombolysis in cerebral infarction NIHSS : National Institutes of Health Stroke Scale QI : quality improvement SAH : subarachnoid hemorrhage SICH

218 citations


Journal ArticleDOI
TL;DR: The frequency of complications of MT in the treatment of acute ischemic stroke is examined with an emphasis on periprocedural complications and the management of complications is discussed.
Abstract: Endovascular mechanical thrombectomy (MT) for the treatment of acute stroke due to large vessel occlusion has evolved significantly with the publication of multiple positive thrombectomy trials. MT is now a recommended treatment for acute ischemic stroke. Mechanical thrombectomy is associated with a number of intra-procedural or post-operative complications, which need to be minimized and effectively managed to maximize the benefits of thrombectomy. Procedural complications include: access-site problems (vessel/nerve injury, access-site hematoma and groin infection); device-related complications (vasospasm, arterial perforation and dissection, device detachment/misplacement); symptomatic intracerebral hemorrhage; subarachnoid hemorrhage; embolization to new or target vessel territory. Other complications include: anesthetic/contrast-related, post-operative hemorrhage, extra-cranial hemorrhage and pseudoaneurysm. Some complications are life-threatening and many lead to increased length of stay in intensive care and stroke units. Complications increase costs and delay the commencement of rehabilitation. Some may be preventable; the impact of others can be minimized with early detection and appropriate management. Both neurointerventionists and stroke specialists need to be aware of the risk factors, strategies for prevention, and management of these complications. With the increasing use of mechanical thrombectomy for the treatment of acute ischemic stroke, incidence and outcome of complications will need to be carefully monitored by stroke teams. In this narrative review, we examine the frequency of complications of MT in the treatment of acute ischemic stroke with an emphasis on periprocedural complications. Overall, from recent randomized controlled trials, the risk of complications with sequelae for patient from mechanical thrombectomy is ∼15%. We discuss the management of complications and identify areas with limited evidence, which need further research. Search strategy and selection criteria Relevant evidence was found by searches of Medline and Cochrane Library, reference list, cross-referencing and main journal content pages. Search terms included "brain ischemia", "acute ischemic stroke", "cerebral infarction" AND "mechanical thrombectomy", "endovascular therapy", "endovascular treatment", "endovascular embolectomy", "intra-arterial" AND "randomized controlled trial", "non-randomised trials", "observational studies" AND "complications", "procedural complications", "peri-procedural complications", "device-related complications", "management", "treatment", "outcome". The search included only human studies, and was limited to studies published in English between January 2014 and November 2016. The final reference list was selected on the basis of relevance to the topics covered in the Review. Guidelines for management of acute ischaemic stroke by the American Heart Association, the European Stroke Organisation, multi-disciplinary guidelines and the National Institute for Health and Care Excellence (NICE) were also reviewed.

174 citations


Journal ArticleDOI
TL;DR: The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians across a wide range of settings to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors.
Abstract: The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians across a wide range of settings. The goal is to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations include those related to diagnostic testing, diet and lifestyle, smoking, hypertension, hyperlipidemia, diabetes, antiplatelet and anticoagulant therapies, carotid artery disease, atrial fibrillation, and other cardiac conditions. Notable changes in this sixth edition include the development of core elements for delivering secondary stroke prevention services, the addition of a section on cervical artery dissection, new recommendations regarding the management of patent foramen ovale, and the removal of the recommendations on management of sleep apnea. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographic barriers to ensure equity in access within a universal health care system.

168 citations


Journal ArticleDOI
TL;DR: There are a wide range of resources which can support the planning and completion of systematic reviews, and these should be considered when planning a systematic review relating to stroke.
Abstract: High quality up-to-date systematic reviews are essential in order to help healthcare practitioners and researchers keep up-to-date with a large and rapidly growing body of evidence. Systematic reviews answer pre-defined research questions using explicit, reproducible methods to identify, critically appraise and combine results of primary research studies. Key stages in the production of systematic reviews include clarification of aims and methods in a protocol, finding relevant research, collecting data, assessing study quality, synthesizing evidence, and interpreting findings. Systematic reviews may address different types of questions, such as questions about effectiveness of interventions, diagnostic test accuracy, prognosis, prevalence or incidence of disease, accuracy of measurement instruments, or qualitative data. For all reviews, it is important to define criteria such as the population, intervention, comparison and outcomes, and to identify potential risks of bias. Reviews of the effect of rehabilitation interventions or reviews of data from observational studies, diagnostic test accuracy, or qualitative data may be more methodologically challenging than reviews of effectiveness of drugs for the prevention or treatment of stroke. Challenges in reviews of stroke rehabilitation can include poor definition of complex interventions, use of outcome measures that have not been validated, and poor generalizability of results. There may also be challenges with bias because the effects are dependent on the persons delivering the intervention, and because masking of participants and investigators may not be possible. There are a wide range of resources which can support the planning and completion of systematic reviews, and these should be considered when planning a systematic review relating to stroke.

156 citations


Journal ArticleDOI
TL;DR: Greater independence in activities of daily living, fewer neurological deficits, and better cognitive ability were the most common predictors of return to work.
Abstract: 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.

104 citations


Journal ArticleDOI
TL;DR: In patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged pervascular spaces in the basal ganglia are associated with cognitive impairment after one year.
Abstract: Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22-2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03-2.31). Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

81 citations


Journal ArticleDOI
TL;DR: A large meta-analysis of all published cohorts shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings, supporting cerebralmicrobleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.
Abstract: __Background:__ Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies. __Methods:__ Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results: We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. __Conclusions:__ Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

74 citations


Journal ArticleDOI
TL;DR: There is a need for studies reporting longer term effects of acute interventions, especially EVT, to reduce the vascular and non-vascular mortality long after stroke.
Abstract: BackgroundDespite improved survival and short-term (90-day) outcomes of ischemic stroke patients, only sparse data exist describing the sustained benefits of acute stroke care interventions and lon

72 citations


Journal ArticleDOI
TL;DR: Cerebral amyloid angiopathy associated with inflammation is an important and increasingly recognized clinical condition, which affects the older patient population and presents most commonly with cognitive decline, seizures, and headaches.
Abstract: Background Cerebral amyloid angiopathy associated with inflammation is an increasingly recognized condition, characterized by an inflammatory response to the vascular deposits of β-amyloid within the brain that are the hallmark of cerebral amyloid angiopathy. Two main patterns of this inflammatory response have been identified to date: one involving a perivascular inflammatory cell infiltrate (cerebral amyloid angiopathy-related inflammation); the other a transmural vasculitic process (A-beta related angiitis). Unlike cerebral amyloid angiopathy itself, which predisposes to intracerebral hemorrhage and has no known treatment, cerebral amyloid angiopathy associated with inflammation typically presents in diverse ways and diagnosis may be challenging and delayed. Aims We sought to summarize the clinical features, imaging appearances and available data on outcome and treatment responses, using information derived from a systematic review of pathologically proven cases of cerebral amyloid angiopathy associated with inflammation. Summary of review We identified 213 distinct pathologically proven cases of cerebral amyloid angiopathy-related inflammation/A-beta related angiitis, from 104 publications. The clinical presentation, imaging features, pathology, treatment, and outcomes of cerebral amyloid angiopathy associated with inflammation are described. Conclusions Cerebral amyloid angiopathy associated with inflammation is an important and increasingly recognized clinical condition, which affects the older patient population and presents most commonly with cognitive decline, seizures, and headaches. Future research is required to develop and validate diagnostic criteria and determine optimum treatment strategies.

61 citations


Journal ArticleDOI
TL;DR: Data indicate that estimated ischemic core volume, in conjunction with patient factors and expected time delay to reperfusion, forms one of the most useful prognostic assessments that could alter decision-making for patients within 6 h of stroke onset.
Abstract: This review summarizes the current state of knowledge regarding the use of imaging to guide stroke treatment. Brain imaging plays a central role in the diagnosis of stroke and identification of the mechanism of stroke, which is relevant to acute treatment, prognosis, and secondary prevention. The chief potential modalities are computed tomography (CT) and magnetic resonance imaging (MRI). Currently, most imaging occurs in hospital but mobile stroke units have expanded CT brain imaging into the prehospital field. The proven therapies for ischemic stroke are based on achieving reperfusion and the DAWN and DEFUSE 3 trials have now firmly established a need for imaging selection based on estimated ischemic core volume to guide reperfusion decisions in patients beyond 6 h of stroke onset. However, data also indicate that estimated ischemic core volume, in conjunction with patient factors and expected time delay to reperfusion, forms one of the most useful prognostic assessments that could alter decision-making for patients within 6 h. Current trials are also investigating agents that aim to achieve neuroprotection, reduction in edema or prevention of hemorrhagic transformation. Imaging may play a role in identifying patients likely to benefit from this next generation of interventions for stroke patients.

Journal ArticleDOI
TL;DR: The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively, suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis.
Abstract: Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.

Journal ArticleDOI
TL;DR: This is the first randomized study to test for disability, healthcare utilization, and cost-effectiveness of a mobile stroke unit, and the progress of the study suggests that it is feasible.
Abstract: Rationale Mobile stroke units speed treatment for acute ischemic stroke, thereby possibly improving outcomes. Aim To compare mobile stroke unit and standard management clinical outcomes, healthcare utilization, and cost-effectiveness in tissue plasminogen activator-eligible acute ischemic stroke patients calling 911. Sample size 693. Eighty percent power with 0.05 type I error rate to detect a difference of 0.09 in mean utility-weighted modified Rankin scale between groups. Design Phase III, multicenter, prospective cluster-randomized (mobile stroke unit versus standard management weeks) comparative effectiveness study in tissue plasminogen activator-eligible patients. Outcomes Primary: Ninety-day mean utility-weighted modified Rankin scale. Coprimary: cost-effectiveness based on EQ5D quality of life and one year poststroke costs. Analysis Two-sample t-test and linear regression adjusting for covariates; incremental cost-effectiveness ratio and net benefit regression. Results As of March 2017, 288 tissue plasminogen activator-eligible patients have been enrolled (173 in the mobile stroke unit arm and 115 in the standard management arm). Two new centers start in early 2017 with target end of recruitment September 2019. Conclusion This is the first randomized study to test for disability, healthcare utilization, and cost-effectiveness of a mobile stroke unit. The progress of the study suggests that it is feasible. Management of tissue plasminogen activator eligible acute ischemic stroke patients by a mobile stroke unit could potentially result in less disability and healthcare utilization, and be cost effective. Mobile stroke units are very costly. This trial may determine if the fixed cost can be justified by a reduction in disability and healthcare utilization. Clinical Trial Registration NCT02190500.

Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

Journal ArticleDOI
TL;DR: It is hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy.
Abstract: Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061.

Journal ArticleDOI
TL;DR: There is now a broad understanding of the causes of delays to fast treatment and the strategies that can be employed to improve door-to-needle time such that most centers could achieve median door- to-needling time of 30 min.
Abstract: BackgroundThe effectiveness of thrombolysis is highly time dependent. For this reason, short target times have been set to reduce time to treatment from hospital arrival, which is called door-to-ne...

Journal ArticleDOI
TL;DR: To understand racial differences, further well-designed studies on various risk and genetic factors should be performed in patients with cerebral atherosclerosis and improvements in diagnostic accuracy via advancements in imaging technologies and increased genetic data will aid in the differentiation of Atherosclerosis from non-atherosclerotic intracranial diseases.
Abstract: Intracranial atherosclerosis is more prevalent in Asian patients, whereas extracranial atherosclerosis is more common in individuals from western countries. The reasons for this discrepancy remain unknown. We reviewed the relevant literature and discussed the currently available information. Although the study population, diagnostic modality, and risk factor definitions differ between studies, hypercholesterolemia is more correlated with extracranial atherosclerosis than intracranial atherosclerosis. The difference in hypercholesterolemia prevalence is one of the main reasons for racial differences. Intracranial arteries contain higher antioxidant level than extracranial arteries and may be more vulnerable to risk factors for antioxidant depletion (e.g., metabolic syndrome and diabetes mellitus). Intracranial arteries may be vulnerable to factors associated with hemodynamic stress (e.g., advanced, salt-retaining hypertension and arterial tortuosity) because of a smaller diameter, thinner media and adventitia, and fewer elastic medial fibers than extracranial arteries. Additionally, non-atherosclerotic arterial diseases (e.g., moyamoya disease) that commonly occur in the intracranial arteries of East Asians may contaminate the reports of intracranial atherosclerosis cases. Genes, including RNF 213 or those associated with high salt sensitivity, may also explain racial differences in atherosclerotic location. To understand racial differences, further well-designed studies on various risk and genetic factors should be performed in patients with cerebral atherosclerosis. Additionally, improvements in diagnostic accuracy via advancements in imaging technologies and increased genetic data will aid in the differentiation of atherosclerosis from non-atherosclerotic intracranial diseases.

Journal ArticleDOI
TL;DR: An effective and well-tolerated protocol for measurement of cerebrovascular reactivity was developed for use in ongoing and future trials to investigate small vessel disease pathophysiology and to measure treatment effects.
Abstract: BackgroundImpaired autoregulation may contribute to the pathogenesis of cerebral small vessel disease. Reliable protocols for measuring microvascular reactivity are required to test this hypothesis...

Journal ArticleDOI
TL;DR: Air pollution should be considered as a new modifiable cerebrovascular and neurodegenerative risk factor for stroke and dementia, and this massive worldwide public health problem requires environmental health policies able to reduce air pollution and thus the Stroke and dementia burden.
Abstract: Background Outdoor air pollution is now a well-known risk factor for morbidity and mortality, and is increasingly being identified as a major risk factor for stroke. Methods A narrative literature review of the effects of short and long-term exposure to air pollution on stroke and dementia risk and cognitive functioning. Results Ten papers on stroke and 17 on dementia were selected. Air pollution, and in particular small particulate matter, contributes to about one-third of the global stroke burden and about one-fifth of the global burden of dementia. It particularly affects vulnerable patients with other vascular risk factors or a prior history of stroke in low- and medium-income countries. New pathophysiological mechanisms of the cause-effect associations are suggested. Conclusion Air pollution should be considered as a new modifiable cerebrovascular and neurodegenerative risk factor. This massive worldwide public health problem requires environmental health policies able to reduce air pollution and thus the stroke and dementia burden.

Journal ArticleDOI
TL;DR: Whether daily active treatment of 100 mg enteric-coated aspirin will extend the duration of disability-free life in healthy older participants and a range of subgroup and sensitivity analyses is assessed.
Abstract: Rationale Aspirin has positive and negative effects on a number of age-related chronic conditions and there is uncertainty regarding its role in primary prevention in people aged 70 years and over. Aims To assess whether daily active treatment of 100 mg enteric-coated aspirin will extend the duration of disability-free life in healthy older participants. Design A double-blind, randomized, placebo-controlled primary prevention trial undertaken in Australia and the United States with careful adjudication of endpoints including stroke. Study outcome In Australia 16,703 individuals were recruited through general practices across five states and territories, and in the United States, 2411 participants were recruited through 34 clinical sites across the country. Follow-up of participants will finish at the end of 2017 with average follow-up exceeding 4.25 years per person. Discussion The statistical analysis plan for ASPREE, finalized after closure of recruitment but before the end of patient follow-up, outlines the primary analyses and a range of subgroup and sensitivity analyses. (International Standard Randomized Controlled Trial Number Register ISRCTN83772183 and clinicaltrials.gov Number NCT01038583).

Journal ArticleDOI
TL;DR: Frequent, short bouts of light-intensity physical activity decreases systolic blood pressure in stroke survivors, and before translation into clinical practice, the optimal duration and timing of physical activity bouts needs to be determined.
Abstract: BackgroundStroke survivors sit for long periods each day. Uninterrupted sitting is associated with increased risk of cardiovascular disease. Breaking up uninterrupted sitting with frequent, short b...

Journal ArticleDOI
TL;DR: Combined efforts from policy makers and health care professionals in Africa are needed to improve, and ensure access, to organized stroke care in as many settings as possible.
Abstract: Background Appropriate systems of stroke care are important to manage the increasing death and disability associated with stroke in Africa. Information on existing stroke services in African countries is limited. Aim To describe the status of stroke care in Africa. Summary of review We undertook a systematic search of the published literature to identify recent (1 January 2006-20 June 2017) publications that described stroke care in any African country. Our initial search yielded 838 potential papers, of which 38 publications were eligible representing 14/54 African countries. Across the publications included for our review, the proportion of stroke patients reported to arrive at hospital within 3 h from stroke onset varied between 10% and 43%. The median time interval between stroke onset and hospital admission was 31 h. Poor awareness of stroke signs and symptoms, shortages of medical transportation, health care personnel, and stroke units, and the high cost of brain imaging, thrombolysis, and outpatient physiotherapy rehabilitation services were reported as major barriers to providing best-practice stroke care in Africa. Conclusions This review provides an overview of stroke care in Africa, and highlights the paucity of available data. Stroke care in Africa usually fell below the recommended standards with variations across countries and settings. Combined efforts from policy makers and health care professionals in Africa are needed to improve, and ensure access, to organized stroke care in as many settings as possible. Mechanisms to routinely monitor usual care (i.e., registries or audits) are also needed to inform policy and practice.

Journal ArticleDOI
TL;DR: The Air-MSU is envisioned not only to allow intravenous thrombolysis in the field but also to allow prehospital triage to a comprehensive stroke center through use of contrast intracerebral vascular imaging.
Abstract: Background In recent years, important progress has been made in effective stroke treatment, however, patients living in rural and remote areas have nil or very limited access to timely reperfusion therapies. Aims Novel systems of care to overcome the detrimental treatment gap for stroke patients living in rural and remote regions need to be developed. Summary of review A possible solution to the treatment disparity between stroke patients living in metropolitan and rural areas may involve the use of specially designed aircrafts equipped with the ability to diagnose and treat acute stroke at remote emergency sites. We describe technical solutions for an Air-Mobile Stroke Unit (Air-MSU) concept, where an aircraft is customized with the ability to perform multimodal computed tomography, in addition to onboard laboratory equipment and telemedicine connection. The Air-MSU is envisioned not only to allow intravenous thrombolysis in the field but also to allow prehospital triage to a comprehensive stroke center through use of contrast intracerebral vascular imaging. Several options for the Air-MSU approach are described, and issues regarding the potential medical benefit, optimal operating environment, technical realization, and integration in pre-existing solutions (e.g., flying doctor service) are addressed. Conclusion The Air-MSU may represent a novel tool to reduce treatment disparity for stroke patients in rural and remote areas. However, this approach requires further implementation research to determine the overall benefit to these communities.

Journal ArticleDOI
TL;DR: Tenecteplase is established as the first-line intravenous thrombolytic drug for myocardial infarction, where it has been shown to achieve comparable reperfusion with reduced risk of systemic bleeding in comparison to alteplase.
Abstract: Alteplase has been the mainstay of thrombolytic treatment since the National Institutes of Neurological Disorders and Stroke trial was published in 1995 Over recent years, several trials have investigated alternative thrombolytic agents Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, allowing single intravenous bolus administration without infusion, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor compared to alteplase Tenecteplase is established as the first-line intravenous thrombolytic drug for myocardial infarction, where it has been shown to achieve comparable reperfusion with reduced risk of systemic bleeding in comparison to alteplase We review the literature on tenecteplase for the treatment of acute ischemic stroke, with a focus on the major completed and ongoing trials Overall, tenecteplase shows promise for treatment of acute ischemic stroke, both in populations currently eligible for alteplase and also in groups not currently treated with thrombolysis

Journal ArticleDOI
TL;DR: If cognitive impairment can be shown to be reversible by revascularization, then this work can redefine “symptomatic carotid stenosis” to include cognitive impairment and identify a new population of patients likely to benefit from rev vascularization.
Abstract: RationaleFor patients with asymptomatic high-grade carotid stenosis, clinical investigations have focused on preventing cerebral infarction, yet stenosis that reduces cerebral blood flow may indepe...

Journal ArticleDOI
TL;DR: An international panel of clinicians-researchers active in the field presents their consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy.
Abstract: Cerebral amyloid angiopathy is a common hemorrhagic small vessel disease of the brain, often associated with high risk of spontaneous lobar intracerebral hemorrhage. When the suspicion of cerebral amyloid angiopathy is raised, clinicians are hesitant in prescribing oral anticoagulation in patients in whom it is otherwise indicated, including the case of non-valvular atrial fibrillation. This is one of the thorniest clinical dilemmas in the field currently. In this short Leading Opinion piece by an international panel of clinicians-researchers active in the field, we present our consistent approach and future outlook on oral anticoagulation post intracerebral hemorrhage and in the setting of clinical-radiologic evidence of cerebral amyloid angiopathy. We discuss recent advances and support a more balanced approach with implications for the wider neurological clinical community in regards to successful recruiting this patient population in ongoing and future randomized trials.

Journal ArticleDOI
TL;DR: The effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h were compared.
Abstract: Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

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TL;DR: Neither reduction of endoplasmic reticulum stress nor induction of autophagy demonstrated neuroprotection in vitro, highlighting their complex role in neuronal biology following ischemia.
Abstract: BackgroundCornu ammonis 3 (CA3) hippocampal neurons are resistant to global ischemia, whereas cornu ammonis (CA1) 1 neurons are vulnerable. Hamartin expression in CA3 neurons mediates this endogeno...

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TL;DR: The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy as discussed by the authors is the first of a two-part series devoted to stroke in pregnancy, focusing 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.
Abstract: 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.

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TL;DR: This study responds to a knowledge gap in the post-acute management of cerebral vein thrombosis patients by comparing short- versus long-term anticoagulation for the prevention of venous thromboembolic event recurrence.
Abstract: Rationale After a cerebral vein thrombosis, there is an increased risk of further venous thromboembolic events. The optimal duration of anticoagulation after cerebral vein thrombosis is unknown. Aim To compare efficacy and safety of a policy of short- (3-6 months) versus long-term (12 months) anticoagulation (any type venous thromboembolic events) after cerebral vein thrombosis for the prevention of venous thromboembolic events. Sample size estimates A sample of 1428 patients (749 per arm) allows detecting a reduction from 10 to 5% in the risk of venous thromboembolic event recurrence with 80% power at 5% significance, with 3% dropout rate. Methods and design An international multicenter, prospective cluster-randomized trial with equal allocation between both interventions (ISRCTN25644448). Each cluster is a participating center, which accepted to be randomly allocated to one of the anticoagulation policies. Eligible patients are adults with radiologically confirmed cerebral vein thrombosis within 30 days, and stable to initiate post-acute anticoagulation. Patients judged by the investigator to be an absolute indication for permanent anticoagulation are excluded. Follow-up is at 6, 12 and 24 months. Study outcomes Primary efficacy outcome is any symptomatic and confirmed fatal/nonfatal venous thromboembolic event (recurrent-cerebral vein thrombosis or non-cerebral venous thromboembolic event). Primary safety outcomes include bleeding events during treatment periods and death from any cause. Discussion This study responds to a knowledge gap in the post-acute management of cerebral vein thrombosis patients by comparing short- versus long-term anticoagulation for the prevention of venous thromboembolic event recurrence.