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Contains fulltext : 215629.pdf (publisher's version ) (Open Access), INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

Background: Carotid artery stenting (CAS) is an established treatment for carotid artery stenosis, typically in a semielective or elective setting. The growth of mechanical thrombectomy for acute stroke has led to an increased use of emergent carotid artery stenting (eCAS). This single-center retrospective case series evaluates the safety and efficacy of eCAS using a dual-layer micromesh nitinol stent to treat carotid artery stenosis in the acute stroke setting. Method(s): Ethics approval was granted by the institutional review board. Clinical data of all patients who underwent CAS using the Casper dual-layer micromesh nitinol stent system (MicroVention, Terumo, Tustin, California, USA) at a tertiary level 24-hour endovascular thrombectomy service over a 2-year period (June 2016-June 2018) were retrospectively obtained and reviewed. Result(s): Twenty eCAS procedures were performed in 19 patients over the study period. Most patients had tandem lesions (12/20; 60%). Median National Institute of Health Stroke Scale score on admission was 17 (interquartile range 9-22). Stent deployment was technically successful in all patients. Recanalization rate was 95%. Symptomatic intracranial hemorrhage occurred in 2 patients (10%), both resulting in death. No other procedure-related deaths occurred. Stent thrombosis occurred in 2 patients. One delayed embolic stroke occurred. No other stent-related complications occurred. Median National Institute of Health Stroke Scale score at 24 hours postprocedure was 3 (interquartile range 1-12). Six patients had a good clinical outcome (modified Rankin Scale score between 0 and 2) at 3- to 6-month follow-up (38%). Conclusion(s): eCAS using the Casper stenting system is effective and technically feasible in the acute stroke setting, although the ideal antiplatelet and anticoagulation regime is not clearly established.Copyright © 2019

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Method(s): We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Finding(s): Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of

Purpose: Worldwide, stroke is a leading cause of disease burden. Many survivors have unmet needs after discharge from hospital. Electronic communication technology to support post-discharge care has not been used for patients with stroke. In this paper, we describe the development of a novel electronic messaging system designed for survivors of stroke to support their goals of recovery and secondary prevention after hospital discharge. Participants and methods: This was a formative evaluation study. The design was informed by a literature search, existing data from survivors of stroke, and behavior change theories. We established two working groups; one for developing the electronic infrastructure and the other (comprising researchers, clinical experts and consumer representatives) for establishing the patient-centered program. Following agreement on the categories for the goal-setting menu, we drafted relevant messages to support and educate patients. These messages were then independently reviewed by multiple topic experts. Concurrently, we established an online database to capture participant characteristics and then integrated this database with a purpose-built messaging system. We conducted alpha testing of the approach using the first 60 messages. Result(s): The initial goal-setting menu comprised 26 subcategories. Following expert review, another 8 goal subcategories were added to the secondary prevention category: managing cholesterol; smoking; physical activity; alcohol consumption; weight management; medication management; access to health professionals, and self-care. Initially, 455 health messages were created by members of working group 2. Following refinement and mapping to different goals by the project team, 980 health messages across the health goals and 69 general motivational messages were formulated. Seventeen independent reviewers assessed the messages and suggested adding 73 messages and removing 16 (2%). Overall, 1,233 messages (18 administrat

Background and Aims: Our large international RCT of early rehabilitation (AVERT), provided evidence that early high intensity training interferes with stroke recovery (The Lancet, 2015), and that most patients may be responsive to therapy if the right dose is provided. (Neurology 2016). The aim of AVERT DOSE is to define the optimal early training regimens for people with mild and moderate ischaemic stroke. Method(s): Multi-Arm, Multi-Stage, Covariate-Adjusted, Response- Adaptive, randomised trial in two specified stroke severity strata. (Mild: NIHSS 0-7; Moderate: NIHSS 8-16). Patients are randomised to one of four mobility training regimens in each strata (including a pre-specified reference group), and the intervention is delivered for up to 14 days. Inclusion criteria: Ischaemic stroke within 48 hours, >=18 years. Exclusion criteria: Severe stroke, medically unwell, no evident mobility problems. We will recruit 2,700 patients from 8 countries. Primary Outcome: Identification of the intervention regimen that results in fewer disabled patients (mRS 0-2) at 3 months post-stroke. Blinded assessments will occur at 3 and 6 months. An adaptive sample size re-estimation provides 80% power to detect a 10% absolute treatment effect or larger compared to the pre-specified reference group, with a significance threshold of p=0.025 per stratum. Analyses will be intention-to-treat. Result(s): Australian National Mutual Acceptance HREC approval for Australia has been received. International collaborations, site selection and development of an online database are underway. Conclusion(s): AVERT DOSE will provide information about the dose and timing of early rehabilitation after ischaemic stroke onset. The results will be generalisable globally.

Background: The quality of stroke care may diminish on weekends. Aim(s): We aimed to compare the quality of care and outcomes for patients with stroke/transient ischemic attack discharged on weekdays compared with those discharged on weekends. Method(s): Data from the Australian Stroke Clinical Registry from January 2010 to December 2015 (n = 45 hospitals) were analyzed. Differences in processes of care by the timing of discharge are described. Multilevel regression and survival analyses (up to 180 days postevent) were undertaken. Result(s): Among 30,649 registrants, 2621 (8.6%) were discharged on weekends (55% male; median age 74 years). Compared to those discharged on weekdays, patients discharged on weekends were more often patients with a transient ischemic attack (weekend 35% vs. 19%; p < 0.001) but were less often treated in a stroke unit (69% vs. 81%; p < 0.001), prescribed antihypertensive medication at discharge (65% vs. 71%; p < 0.001) or received a care plan if discharged to the community (47% vs. 53%; p < 0.001). After accounting for patient characteristics and clustering by hospital, patients discharged on weekends had a 1 day shorter length of stay (coefficient = -1.31, 95% confidence interval [CI] = -1.52, -1.10), were less often discharged to inpatient rehabilitation (aOR = 0.39, 95% CI = 0.34, 0.44) and had a greater hazard of death within 180 days (hazard ratio = 1.22, 95% CI = 1.04, 1.42) than those discharged on weekdays. Conclusion(s): Patients with stroke/transient ischemic attack discharged on weekends were more likely to receive suboptimal care and have higher long-term mortality. High quality of stroke care should be consistent irrespective of the timing of hospital discharge.Copyright © 2018 World Stroke Organization.

Objective: Endovascular clot retrieval (ECR) is the standard of care for acute ischemic stroke due to large vessel occlusion. Performing ECR is a time critical and complex process involving many specialized care providers and resources. Maximizing patient benefit while minimizing service cost requires optimization of human and physical assets. The aim of this study is to develop a general computational model of an ECR service, which can be used to optimize resource allocation. Method(s): Using a discrete event simulation approach, we examined ECR performance under a range of possible scenarios and resource use configurations. Result(s): The model demonstrated the impact of competing emergency interventional cases upon ECR treatment times and time impact of allocating more physical (more angiographic suites) or staff resources (extending work hours). Conclusion(s): Our DES model can be used to optimize resources for interventional treatment of acute ischemic stroke and large vessel occlusion. This proof-of-concept study of computational simulation of resource allocation for ECR can be easily extended. For example, center-specific cost data may be incorporated to optimize resource allocation and overall health care value.Copyright © 2019 Huang, Maingard, Kok, Barras, Thijs, Chandra, Brooks and Asadi.

Objectives The present Bayesian network meta-analysis aimed to compare the various strategies for acute ischemic stroke: direct endovascular thrombectomy within the thrombolysis window in patients with no contraindications to thrombolysis (DEVT); (2) direct endovascular thrombectomy secondary to contraindications to thrombolysis (DEVTc); (3) endovascular thrombectomy in addition to thrombolysis (IVEVT); and (4) thrombolysis without thrombectomy (IVT). Methods Six electronic databases were searched from their dates of inception to May 2017 to identify randomized controlled trials (RCTs) comparing IVT versus IVEVT, and prospective registry studies comparing IVEVT versus DEVT or IVEVT versus DEVTc. Network meta-analyses were performed using ORs and 95% CIs as the summary statistic. Results We identified 12 studies (5 RCTs, 7 prospective cohort) with a total of 3161 patients for analysis. There was no significant difference in good functional outcome at 90 days (modified Rankin Scale score <=2) between DEVT and IVEVT. There was no significant difference in mortality between all treatment groups. DEVT was associated with a 49% reduction in intracranial hemorrhage (ICH) compared with IVEVT (OR 0.51; 95% CI 0.33 to 0.79), due to reduction in rates of asymptomatic ICH (OR 0.47; 95% CI 0.29 to 0.76). Patients treated with DEVT had higher rates of reperfusion compared with IVEVT (OR 1.73; 95% CI 1.04 to 2.94). Conclusions To our knowledge, this is the first network meta-analysis to be performed in the era of contemporary mechanical thrombectomy comparing DEVT and DEVTc. Our analysis suggests the addition of thrombolysis prior to thrombectomy for large vessel occlusions may not be associated with improved outcomes.Copyright © 2019 Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ.

Background: Endovascular thrombectomy (EVT) for management of large vessel occlusion (LVO) acute ischaemic stroke is now current best practice. Aim(s): To determine if bridging intravenous (i.v.) alteplase therapy confers any clinical benefit. Method(s): A retrospective study of patients treated with EVT for LVO was performed. Outcomes were compared between patients receiving thrombolysis and EVT with EVT alone. Primary end-points were reperfusion rate, 90-day functional outcome and mortality using the modified Rankin Scale (mRS) and symptomatic intracranial haemorrhage (sICH). Result(s): A total of 355 patients who underwent EVT was included: 210 with thrombolysis (59%) and 145 without (41%). The reperfusion rate was higher in the group receiving i.v. tissue plasminogen activator (tPA) (unadjusted odds ratio (OR) 2.2, 95% confidence interval (CI): 1.29-3.73, P = 0.004), although this effect was attenuated when all variables were considered (adjusted OR (AOR) 1.22, 95% CI: 0.60-2.5, P = 0.580). The percentage achieving functional independence (mRS 0-2) at 90 days was higher in patients who received bridging i.v. tPA (AOR 2.17, 95% CI: 1.06-4.44, P = 0.033). There was no significant difference in major complications, including sICH (AOR 1.4, 95% CI: 0.51-3.83, P = 0.512). There was lower 90-day mortality in the bridging i.v. tPA group (AOR 0.79, 95% CI: 0.36-1.74, P = 0.551). Fewer thrombectomy passes (2 versus 3, P = 0.012) were required to achieve successful reperfusion in the i.v. tPA group. Successful reperfusion (modified thrombolysis in cerebral infarction >=2b) was the strongest predictor for 90-day functional independence (AOR 10.4, 95% CI:3.6-29.7, P < 0.001). Conclusion(s): Our study supports the current practice of administering i.v. alteplase before endovascular therapy.Copyright © 2018 Royal Australasian College of Physicians

Objective To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10-8; and LINC00539/ZDHHC20, p = 5.82 x 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 x 10-25; p [SSBI] = 5.23 x 10-14 for hypertension), smoking (p[BI]= 4.4 x 10-10; p [SSBI] = 1.2 x 10 -4), diabetes (p[BI] = 1.7 x 10 -8; p [SSBI] = 2.8 x 10 -3), previous cardiovascular disease (p [BI] = 1.0 x 10-18; p [SSBI] = 2.3 x 10-7), stroke (p [BI] = 3.9 x 10-69; p [SSBI] = 3.2 x 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 x 10-157; p [SSBI] = 3.16 x 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p <= 0.0022), without indication of directional pleiotropy. Conclusion In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significa

ObjectiveTo assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT).MethodsIn a retrospective, multicenter, blinded, case-control study of patients with recent onset (<2 weeks) CVT, 3 readers assessed (1) the accuracy of the visual impression of CVT based on a combination of direct and indirect signs, (2) the accuracy of attenuation values of the venous sinuses in Hounsfield units (with adjustment for hematocrit levels), and (3) the accuracy of attenuation ratios of affected vs unaffected sinuses in comparison with reference standard MRI or CT angiography. Controls were age-matched patients with (sub)acute neurologic presentations.ResultsWe enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74-0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74-0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8-0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70-0.81).ConclusionSemiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT.Classification of evidenceThis study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT.Copyright © 2019 American Academy of Neurology.

Background: Up to 20% of patients fail to achieve reperfusion with modified Thrombolysis in Cerebral Infarction (mTICI) scores of 0-1 after mechanical thrombectomy (MT). Furthermore, underlying intracranial atherosclerotic disease, particularly when associated with >70% residual or flow limiting stenosis, is associated with higher rates of failed MT and high failure risk MT. The aim of this study was to systematically review the procedural and clinical outcomes in patients with failed MT and high failure risk MT. We also explored differences between patients receiving acute rescue stenting compared with medical management alone. Method(s): A systematic literature search was conducted in Ovid MEDLINE, PubMed, Embase, and Cochrane online scientific publication databases for English language publications from their date of inception until October 2018. Studies including adult patients with acute ischemic stroke because of emergent large vessel occlusion with failed (mTICI score 0-1) or high failure risk MT within the anterior circulation who underwent rescue stenting were included. A systematic review and meta-analysis of proportions was performed. Result(s): Rescue intracranial stenting after failed MT or high failure risk MT results in improved clinical outcomes compared with patients without stenting (48.5% vs. 19.7%, respectively; P < 0.001), without an increase in the rate of symptomatic intracranial hemorrhage, despite additional use of antiplatelet agents (9.7% vs. 14.1%, respectively; P = 0.04). Conclusion(s): In patients who fail initial attempts at MT or are high risk for acute reocclusion, rescue intracranial stenting could be considered with the aim to improve functional outcomes. Antiplatelet agents do not increase the risk of hemorrhage in these patients.Copyright © 2019 Elsevier Inc.

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long-term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in-stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.Copyright © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Background and purpose Endovascular thrombectomy (EVT) has revolutionized the management of acute ischemic stroke. Landmark clinical trials have shown EVT to be one of the most efficacious interventions in clinical medicine over the past 5 years. A method of recognition for an article in the scientific community is to use a citation rank list, in order to identify the seminal works in the academic medical literature. The objective of this study was to characterize the 100 most highly cited articles assessing endovascular management of acute ischemic stroke. Methods We conducted a retrospective bibliometric analysis using the Web of Science Citation Index Expanded database for the most cited works in the endovascular management of acute ischemic stroke. Citation count was used to rank the top 100 articles, which were then analyzed for authorship, year of publication, subject, study type, level of evidence, and subject. Results The mean number of citations was 245 (range 65-1726) and 394 on Google Scholar. The top 100 articles were cited an average of 43.9 times per year and published in 21 journals in the past two decades. The majority of papers (62) were classified as constituting levels 1, 2, or 3 evidence, and included 17 randomized controlled trials. Approximately two-thirds of the top 100 articles originated from the USA. Conclusions This study details the most cited articles in the endovascular management of acute ischemic stroke, and furthermore shows that a high proportion of level I evidence exists for this intervention.Copyright © 2019 Author(s).

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or

Background: To estimate the additional impact of coping and of being dependent on caregivers, over and above the large effects of disability on utility after ischemic stroke. Methods: A total of 539 patients were recruited into an observational, retrospective study when returning for a check-up between 3 and 36 months after an ischemic stroke. Patients' modified Rankin Scale (mRS), dependency on caregivers, the Brandtstädter and Renner Coping questionnaire (with summary scores: Tenacity of Goal Pursuit (TGP) and Flexible Goal Adjustment (FGA) coping styles), EQ-5D-3 L and co-morbidities were evaluated. Results: In multivariable regression, greater disability (mRS) resulted in large utility losses, between 0.06 for mRS 1 to 0.65 for mRS 5 (p < 0.0001). Dependency on caregivers caused an additional dis-utility of 0.104 (p = 0.0006) which varied by mRS (0.044, 0.060, 0.083, 0.115, 0.150 and 0.173 for mRS 0-5). The effect of coping on utility varied by coping style, by the disability level of the patient and by his or her dependency on caregivers. FGA coping was associated with additional increases in utility (p < 0.0001) over and above the effect of disability and dependency, whereas TGA had no significant impact. FGA coping was associated with larger utility changes among more disabled patients (0.018 to 0.105 additional utility, for mRS 0 to mRS 5 respectively). Dependent patients had more to gain from FGA coping than patients who function independently of caregivers: utility gains were between 0.049 and 0.072 for moderate to high levels of FGA coping. In contrast, the same positive evolution in FGA coping resulted in 0.039 and 0.057 utility gain among independent patients. Finally, we found that important stroke risk factors and co-morbidities, such as diabetes and atrial fibrillation, were not predictors of EQ-5D utility in a multivariable setting. Conclusions: This study suggests that treatment strategies targeting flexible coping styles and decreasing

Corticospinal tract integrity after stroke has been widely investigated through the evaluation of fibres descending from the primary motor cortex. However, about half of the corticospinal tract is composed by sub-pathways descending from premotor and parietal areas, to which damage may play a more specific role in motor impairment and recovery, particularly post-stroke. Therefore, the main aim of this study was to investigate lesion load within corticospinal tract sub-pathways as predictors of upper limb motor impairment after stroke. Motor impairment (Fugl-Meyer Upper Extremity score) was evaluated in 27 participants at one week and six months after stroke, together with other clinical and demographic data. Neuroimaging data were obtained within the first week after stroke. Univariate regression analysis indicated that among all neural correlates, lesion load within premotor fibres explained the most variance in motor impairment at six months (R2 = 0.44, p < 0.001). Multivariable regression analysis resulted in three independent, significant variables explaining motor impairment at six months; Fugl-Meyer Upper Extremity score at one week, premotor dorsal fibre lesion load at one week, and age below or above 70 years (total R2 = 0.81; p < 0.001). Early examination of premotor dorsal fibre integrity may be a promising biomarker of upper limb motor impairment after stroke.

White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype linked to prediction of diagnosis and prognosis of diseases, such as acute ischemic stroke (AIS). However, current approaches to its quantification on clinical MRI often rely on time intensive manual delineation of the disease on T2 fluid attenuated inverse recovery (FLAIR), which hinders high-throughput analyses such as genetic discovery. In this work, we present a fully automated pipeline for quantification of WMH in clinical large-scale studies of AIS. The pipeline incorporates automated brain extraction, intensity normalization and WMH segmentation using spatial priors. We first propose a brain extraction algorithm based on a fully convolutional deep learning architecture, specifically designed for clinical FLAIR images. We demonstrate that our method for brain extraction outperforms two commonly used and publicly available methods on clinical quality images in a set of 144 subject scans across 12 acquisition centers, based on dice coefficient (median 0.95; inter-quartile range 0.94-0.95; p < 0.01) and Pearson correlation of total brain volume (r = 0.90). Subsequently, we apply it to the large-scale clinical multi-site MRI-GENIE study (N = 2783) and identify a decrease in total brain volume of -2.4 cc/year. Additionally, we show that the resulting total brain volumes can successfully be used for quality control of image preprocessing. Finally, we obtain WMH volumes by building on an existing automatic WMH segmentation algorithm that delineates and distinguishes between different cerebrovascular pathologies. The learning method mimics expert knowledge of the spatial distribution of the WMH burden using a convolutional auto-encoder. This enables successful computation of WMH volumes of 2533 clinical AIS patients. We utilize these results to demonstrate the increase of WMH burden with age (0.950 cc/year) and show that single site estimates can be biased by the number of sub

Introduction: In WAKE-UP (Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke), patients with an acute stroke of unknown onset time were randomized to treatment with intravenous alteplase or placebo, guided by MRI. Methods: In this exploratory post-hoc secondary analysis we compared clinical and imaging data, as well as treatment effects and safety of intravenous thrombolysis between patients with infra- vs. supratentorial stroke. Results: Forty-eight out of 503 randomized patients (9.5%) presented with a stroke involving the cerebellum or brainstem. Patients with infratentorial stroke were younger compared to patients with supratentorial stroke (mean age 60 vs. 66 years), more frequently male (85 vs. 62%), and less severely affected (median NIHSS 4.5 vs. 6.0). There was no heterogeneity for treatment effect between supratentorial (OR 1.67 95% CI 1.11-2.51) and infratentorial (OR 1.31 95% CI 0.41-4.22) sub-groups (test for interaction p = 0.70). In patients with infratentorial stroke, favorable outcome [a score of 0-1 on the modified Rankin scale (mRS) at 90 days] was observed in 12/22 patients (54.5%) in the alteplase group and in 13/25 patients (52.0%) in the placebo group (p = 0.59). The primary safety endpoint (death or mRS 4-6 at day 90) occurred in three patients of the alteplase group (13.6%) and three patients in the placebo group (12.0%); p = 0.74. Discussion: WAKE-UP was underpowered for demonstrating treatment effect in subgroup analyses however, based on our current results, there is no evidence to recommend withholding MRI-guided thrombolysis in patients with unknown onset stroke of infratentorial localization.

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most si

BACKGROUND: Endovascular thrombectomy (EVT) for management of large vessel occlusion (LVO) acute ischaemic stroke is now current best practice. AIM: To determine if bridging intravenous (i.v.) alteplase therapy confers any clinical benefit. METHODS: A retrospective study of patients treated with EVT for LVO was performed. Outcomes were compared between patients receiving thrombolysis and EVT with EVT alone. Primary end-points were reperfusion rate, 90-day functional outcome and mortality using the modified Rankin Scale (mRS) and symptomatic intracranial haemorrhage (sICH). RESULTS: A total of 355 patients who underwent EVT was included: 210 with thrombolysis (59%) and 145 without (41%). The reperfusion rate was higher in the group receiving i.v. tissue plasminogen activator (tPA) (unadjusted odds ratio (OR) 2.2, 95% confidence interval (CI): 1.29-3.73, P = 0.004), although this effect was attenuated when all variables were considered (adjusted OR (AOR) 1.22, 95% CI: 0.60-2.5, P = 0.580). The percentage achieving functional independence (mRS 0-2) at 90 days was higher in patients who received bridging i.v. tPA (AOR 2.17, 95% CI: 1.06-4.44, P = 0.033). There was no significant difference in major complications, including sICH (AOR 1.4, 95% CI: 0.51-3.83, P = 0.512). There was lower 90-day mortality in the bridging i.v. tPA group (AOR 0.79, 95% CI: 0.36-1.74, P = 0.551). Fewer thrombectomy passes (2 versus 3, P = 0.012) were required to achieve successful reperfusion in the i.v. tPA group. Successful reperfusion (modified thrombolysis in cerebral infarction ≥2b) was the strongest predictor for 90-day functional independence (AOR 10.4, 95% CI:3.6-29.7, P < 0.001). CONCLUSION: Our study supports the current practice of administering i.v. alteplase before endovascular therapy.

BACKGROUND: A revised classification of cerebellar infarctions (CI) may uncover unrecognized associations with etiologic stroke subtypes. We hypothesized that obliquely oriented small cortical cerebellar infarction (SCCI) representing end zone infarctions on MRI would be associated with cardiac embolism. METHODS: We retrospectively analyzed consecutive stroke patients recruited between January-December 2016 in our center. Analyzed baseline characteristics: sex, age, cardiovascular risk factors, history of stroke or atrial fibrillation (AF). TOAST classification was used for determining stroke subtype. Acute infarction location (anterior/posterior/mixed anterior-posterior circulation), acute uni- or multiterritorial infarction, and acute or chronic CI/SCCI/non-SCCI were assessed by MRI, and vertebrobasilar stenosis/occlusion by vessel imaging. Pre-specified analysis was also performed in patients without known high cardioembolic risk (known AF history or acute multiterritorial infarction). RESULTS: We included 452 patients (CI in 154, isolated SCCI in 55, isolated non-SCCI in 50, and mixed SCCI/non-SCCI in 49). Both SCCI and non-SCCI were associated with AF history (SCCI, p = 0.021; non-SCCI, p = 0.004), additional acute posterior circulation infarction (p < 0.001 both CI-subtypes), multiterritorial infarctions (SCCI, p = 0.003; non-SCCI, p < 0.001) and cardioembolic more frequent than large-artery atherosclerosis origin (p < 0.001 for both CI-subtypes). SCCI was associated with older age (p < 0.001), whereas non-SCCI was associated with stroke history (p = 0.036) and vertebrobasilar stenosis/occlusion (p = 0.002). SCCI were older (p = 0.046) than non-SCCI patients, had less frequently prior stroke (p < 0.001), and more frequent cardioembolic infarction (p = 0.025). In patients without known high cardioembolic risk (n = 348), SCCI was strongly associated with subsequent cardioembolism diagnosis (OR 3.00 [CI 1.58-5.73, p < 0.001]). No such association was present in n

Introduction: Effective, time-critical intervention in acute stroke is crucial to mitigate mortality rate and morbidity, but delivery of reperfusion treatments is often hampered by pre-, in-, or inter-hospital system level delays. Disjointed, repetitive, and inefficient communication is a consistent contributor to avoidable treatment delay. In the era of rapid reperfusion therapy for ischemic stroke, there is a need for a communication system to synchronize the flow of clinical information across the entire stroke journey. Material/Methods: A multi-disciplinary development team designed an electronic communications platform, integrated between web browsers and a mobile application, to link all relevant members of the stroke treatment pathway. The platform uses tiered notifications, geotagging, incorporates multiple clinical score calculators, and is compliant with security regulations. The system safely saves relevant information for audit and research. Results: Code Stroke Alert is a platform that can be accessed by emergency medical services (EMS) and hospital staff, coordinating the flow of information during acute stroke care, reducing duplication, and error in clinical information handover. Electronic data logs provide an auditable trail of relevant quality improvement metrics, facilitating quality improvement, and research. Discussion: Code Stroke Alert will be freely available to health networks globally. The open-source nature of the software offers valuable potential for future development of plug-ins and add-ons, based on individual institutional needs. Prospective, multi-site implementation, and measurement of clinical impact are underway.

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intr

OBJECTIVE: To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. METHODS: The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 × 10-8. RESULTS: We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10-9). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p < 10-5), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1). CONCLUSIONS: In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.

Patients at short-term risk of paroxysmal atrial fibrillation (PAF) often exhibit increased RR interval variability during sinus rhythm. We studied if RR dynamic analysis, applied in the first hours after stroke unit (SU) admission, identified acute ischemic stroke patients at higher risk for subsequent PAF episodes detected within the SU hospitalization. Acute ischemic stroke patients underwent continuous cardiac monitoring (CCM) using standard bedside monitors immediately after SU admission. The CCM tracks from the first 48 h were analyzed using a telemedicine service (SRA clinic, Apoplex Medical, Germany). Based on the RR dynamics, the stroke risk analysis (SRA) algorithm stratified the risk for PAF as follows: low risk for PAF, high risk for PAF, presence of manifest AF. The subsequent presence/absence of PAF during the whole SU hospitalization was ruled out using all available CCMs, standard ECGs, or 24-h Holter ECGs. Two hundred patients (40% females, mean age 71 ± 16 years) were included. According to the initial SRA analysis, 111 patients (56%) were considered as low risk for PAF, 52 (26%) as high risk while 37 patients (18%) had manifest AF. A low-risk level SRA was associated with a reduced probability for subsequent PAF detection (1/111, 0.9%, 95% CI 0-4.3%) while a high-risk level SRA predicted an increased probability (20/52, 38.5% (95% CI 25-52%). RR dynamic analysis performed in the first hours after ischemic stroke may stratify patients into categories at low or high risk for forthcoming paroxysmal AF episodes detected within the SU hospitalization.

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) are common treatments for carotid artery stenosis. Several randomized controlled trials (RCTs) have compared CEA to CAS in the treatment of carotid artery stenosis. These studies have suggested that CAS is more strongly associated with periprocedural stroke; however, CEA is more strongly associated with myocardial infarction. Published long-term outcomes report that CAS and CEA are similar. A reduction in complications associated with CAS has also been demonstrated over time. The symptomatic status of the patient and history of previous CEA or cervical radiotherapy are significant factors when deciding between CEA or CAS. Numerous carotid artery stents are available, varying in material, shape and design but with minimal evidence comparing stent types. The role of cerebral protection devices is unclear. Dual antiplatelet therapy is typically prescribed to prevent in-stent thrombosis, and however, evidence comparing periprocedural and postprocedural antiplatelet therapy is scarce, resulting in inconsistent guidelines. Several RCTs are underway that will aim to clarify some of these uncertainties. In this review, we summarize the development of varying techniques of CAS and studies comparing CAS to CEA as treatment options for carotid artery stenosis.

Objective: Endovascular clot retrieval (ECR) is the standard of care for acute ischemic stroke due to large vessel occlusion. Performing ECR is a time critical and complex process involving many specialized care providers and resources. Maximizing patient benefit while minimizing service cost requires optimization of human and physical assets. The aim of this study is to develop a general computational model of an ECR service, which can be used to optimize resource allocation. Methods: Using a discrete event simulation approach, we examined ECR performance under a range of possible scenarios and resource use configurations. Results: The model demonstrated the impact of competing emergency interventional cases upon ECR treatment times and time impact of allocating more physical (more angiographic suites) or staff resources (extending work hours). Conclusion: Our DES model can be used to optimize resources for interventional treatment of acute ischemic stroke and large vessel occlusion. This proof-of-concept study of computational simulation of resource allocation for ECR can be easily extended. For example, center-specific cost data may be incorporated to optimize resource allocation and overall health care value.

AIMS/INTRODUCTION: Diabetes mellitus is an established risk factor for stroke and maybe associated with poorer outcomes after stroke. The aims of the present literature review were to determine: (i) the prevalence of diabetes in acute stroke patients through a meta-analysis; (ii) the association between diabetes and outcomes after ischemic and hemorrhagic stroke; and (iii) to review the value of glycated hemoglobin and admission glucose-based tests in predicting stroke outcomes. MATERIALS AND METHODS: Ovid MEDLINE and EMBASE searches were carried out to find studies relating to diabetes and inpatient stroke populations published between January 2004 and April 2017. A meta-analysis of the prevalence of diabetes from included studies was undertaken. A narrative review on the associations of diabetes and different diagnostic methods on stroke outcomes was carried out. RESULTS: A total of 66 eligible articles met inclusion criteria. A meta-analysis of 39 studies (n = 359,783) estimated the prevalence of diabetes to be 28% (95% confidence interval 26-31). The rate was higher in ischemic (33%, 95% confidence interval 28-38) compared with hemorrhagic stroke (26%, 95% confidence interval 19-33) inpatients. Most, but not all, studies found that acute hyperglycemia and diabetes were associated with poorer outcomes after ischemic or hemorrhagic strokes: including higher mortality, poorer neurological and functional outcomes, longer hospital stay, higher readmission rates, and stroke recurrence. Diagnostic methods for establishing diagnosis were heterogeneous between the reviewed studies. CONCLUSIONS: Approximately one-third of all stroke patients have diabetes. Uniform methods to screen for diabetes after stroke are required to identify individuals with diabetes to design interventions aimed at reducing poor outcomes in this high-risk population.

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this associ

Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To compare the benefits, harm and the atrial high-rate episode (AHRE) detection rate of implantable cardiac monitors against conventional methods (such as electrocardiogram, ambulatory Holter monitors, event monitors and real-time telemetry) in participants with embolic stroke of unknown source.

© 2019 American Heart Association, Inc. Background and Purpose-Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods-Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. Results-There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81; 95% CI, 0.98-3.35; P=0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P=0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57; 95% CI, 1.05-6.25; P=0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81; 95% CI, 0.95-3.46; P=0.08). Conclusions-We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent