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Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of

OBJECTIVE: To analyze time trends in incidence, causes and risk factors for traumatic spinal cord injuries (TSCI) in Estonia between 1997–2007 and 2008–2018. DESIGN: Retrospective, population-based cohort study. SETTING: Specialized trauma centres in Estonia. PARTICIPANTS: Medical records of patients with TSCI from 1997 to 2018. INTERVENTION: None. OUTCOME MEASURES: Demographical data, crude and age- and sex-adjusted incidence rates, causes of TSCI, level and extent of injury, associated injuries. RESULTS: A total of 940 new patients with TSCI were identified for the period of 1997–2018. The average annual incidence rate (standardized to the Estonian population by age and sex in 2011) decreased significantly from 37.8 (95% confidence interval (CI) 34.6–41.1) in the first period (1997–2008) to 28.2 per million population (95% CI 25.3–31.0) during the second period (2008–2018) (incidence rate ratio 0.74 (95% CI 0.65–0.85), P

Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT.TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890).From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64).In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT.Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Background Neurology is a field of increasing subspecialization. There is no published data regarding the proportion of neurology subspecialists in the Baltic States. The aim of this cross-sectional study was to identify factors associated with neurology subspecialty choice, to examine possible differences between neurology residents' and junior neurologists' view of subspecialty, and to assess perceived subspecialty acquisition opportunities and subspecialty attractiveness. Methods The research was conducted as an anonymous online survey between December 28, 2020, and January 24, 2021 of neurology residents and neurologists who completed their residency during the last 5 years in the Baltic States. Results In total, 72 residents and 65 neurologists participated. "Cerebrovascular diseases" and "multiple sclerosis and autoimmune diseases of the nervous system" were rated as the two most attractive subspecialties by residents, whereas "headache" and "clinical neurophysiology" were the most attractive among junior neurologists. "Vertigo and dizziness" and "dementia" were ranked the least attractive among both groups. "Cerebrovascular diseases" were perceived as having the most acquisition opportunities. The two most common determinants of subspecialty choice were "medical content of the subspecialty" and "influence of mentor during undergraduate studies or residency ". Conclusions Two-thirds of junior neurologists subspecialize in at least one subspecialty, and one-third of residents are already determined to pursue subspecialty training. Junior neurologists rated most outpatient-related subspecialties as more attractive than neurology residents. Between the Baltic States' universities, there was a significant difference in the number of residents who were determined to pursue subspecialty training.

Background: Monitoring and measuring different aspects of stroke care pathway is the cornerstone for improvement of quality. We aim to analyze and give an overview of improvements of stroke care quality in Estonia. Patients and methods: National stroke care quality indicators are collected and reported using reimbursement data and include all adult stroke cases. In Estonia, five stroke-ready hospitals are participating in Registry of Stroke Care Quality (RES-Q), providing data on all stroke patients 1 month every year. Data from the national quality indicators and RES-Q from 2015 to 2021 are presented. Results: The proportion of intravenous thrombolysis for all Estonian hospitalized ischemic stroke cases increased from 16% (95% Confidence Interval, CI 15%–18%) in 2015 to 28% (95% CI 27%–30%) in 2021. Mechanical thrombectomy was provided to 9% (95% CI 8%–10%) in 2021. The 30-day mortality rate has decreased from 21% (95% CI 20%–23%) to 19% (95% CI 18%–20%). More than 90% of patients with cardioembolic stroke are prescribed anticoagulants at discharge, but only 50% are on anticoagulant treatment 1 year after stroke. Also, the availability of inpatient rehabilitation needs improvement, being 21% (95% CI 20%–23%) in 2021. A total of 848 patients are included in the RES-Q. The proportion of patients receiving recanalization therapies was comparable to the national stroke care quality indicators. All stroke-ready hospitals show good onset-to-door times. Conclusion: The overall stroke care quality in Estonia is good, especially the availability of recanalization treatments. However, secondary prevention and the availability of rehabilitation services need improvement in the future.

Background Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events. Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone. Design CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat. Outcome The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). Summary CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. Schedule First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.

Background and purpose Previous studies conducted elsewhere in the world have demonstrated an increase in the incidence of ischemic stroke (IS) in younger ages. We sought to determine stroke incidence and 28-day case-fatality rates in 15- to 54-year-old residents of Tartu, Estonia from 2013 to 2017. Methods All stroke cases that were the first ever in a lifetime (IS, nontraumatic intracerebral hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) in 15- to 54-year-old residents of Tartu, Estonia were prospectively registered from January 1, 2013 to December 31, 2017. Several additional overlapping data sources were used for case ascertainment including other departments of the Tartu University Hospital and outpatient clinic, Estonian Cause of Death Registry, and the Estonian Electronic Health Record. All cases were thoroughly validated before inclusion. Results We identified 110 cases (43.6% female) of first-ever stroke (IS 72.7%, ICH 12.7%, SAH 14.6%), out of which 85.5% were included prospectively. The mean age at onset was 44.3 ± 8.5 (SD) years. The mean age at onset was higher for men than for women (p = 0.046). The incidence of stroke standardized to the 1976 European standard population (EUR) was 46.1/100,000 (95% confidence interval [CI]: 37.4-54.8). IS incidence was 33.4/100,000 EUR (95% CI: 26-40.7). The total stroke incidence was higher in 45- to 54-year-old men than in women in the same age group (rate ratio, 2.24; 95% CI: 1.35-3.71). There were no more significant differences between sexes or age groups. The 28-day case-fatality rate was 10.9% for all strokes. Conclusions Our study shows higher crude incidence and case fatality of stroke in the young compared to studies from other high-income countries.

[Backgroun] Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke., [Aims] Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS)., [Methods] We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 h, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. Multivariable linear and logistic regression and propensity score matching (PSM) was used to quantify the effect of statin pre-treatment., [Results] Of 93,849 patients, 23,651 (25.2%) were treated with statins prior the AIS. Statin pre-treatment group was older and had higher comorbidity. Median NIHSS at baseline was similar between groups. In the adjusted and PSM analysis, statin pre-treatment was inversely associated with baseline NIHSS (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.6–0.99 and OR for PSM 0.73, 95% CI = 0.54–0.99, p = 0.004) and independently associated with mild stroke defined as NIHSS ⩽8 in adjusted and PSM analysis (OR = 1.21, 95% CI = 1.1–1.34, p, [Conclusion] Prior treatment with statins was associated with lower NIHSS at baseline. However, this association did not translate into any difference regarding functional outcome at 90 days. No association was found regarding SICH. These findings indicate the need of further studies to assess the effect on statin pre-treatment on initial stroke severity.

BackgroundThere are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability.AimWe aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability.MethodsWe analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3–5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h).ResultsPatients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60–1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83–1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73–0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21–1.61) (10.40% vs. 4.93%)).ConclusionsIntravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.

Background and purpose: Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis. Methods: We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses ( P Results: We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%–7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96–3.54], P P P P P P Conclusions: The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.

Objectives This study aimed to determine short- and long-term mortality, clinical determinants and causes of death in young patients with ischaemic stroke. Materials and methods We performed a hospital-based study of 18- to 54-year-old consecutive patients with ischaemic stroke, who were treated in the two largest hospitals in Estonia from 2003 to 2012. All cases were reviewed by the authors. Survival data and causes of death were obtained from the Estonian Population Registry and the Causes of Death Registry, respectively. Logistic regression and Cox proportional hazard models with backwards stepwise analysis were used to identify determinants of mortality. Results We identified 738 patients, of whom 124 died during the 5-year follow-up. Cumulative mortality rates at 30 days and 5 years were 4.5% (95% confidence interval [CI], 3.0%-6.0%) and 16.8% (95% CI, 14.1%-19.5%), respectively. The proportion of deaths due to vascular causes was 87.9% at 1 month and 54.6% at 5 years. Thirty-day mortality was independently associated with severe stroke, with a National Institutes of Health Stroke Scale (NIHSS) score >15, and post-stroke infections. The determinants of 5-year mortality were post-stroke infections, structural cardiac diseases and moderate stroke severity with NIHSS score of 7-15. Conclusion The mortality rate among young patients with ischaemic stroke in Estonia is higher than that reported in previous studies and is associated with increased stroke severity, post-stroke infections and structural cardiac diseases. These results emphasize the need for more effective preventive strategies in these patient groups.

Background Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT. Methods/design TWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase ( n = 300) versus standard care ( n = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0–6) at three months. Discussion TWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT. Trial registration ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.

Background and aims The aim of the present study was to assess the risk factor burden and stroke etiology of young stroke patients in Estonia and to compare the results with similar cohorts from other countries. Methods This study includes ischemic stroke patients aged 18–54 years from the prospective Estonian Young Stroke Registry between 2013 and 2020. All patients were managed in a stroke unit following a prespecified detailed protocol. Data on stroke risk factors, etiology, and stroke severity were analyzed. Results A total of 437 patients (mean age 44.7 ± 8.3 years; 62% males) were included in the registry during the 8-year study period. A total of 50.2% of patients had ≥ 3 well-documented risk factors (higher for men: odds ratio (OR) 3.8; 95% confidence interval (CI) 1.8–8.3; p < .001) and 6.2% of patients had ≥ 3 less well-documented risk factors. While 42% of patients had undetermined cause of stroke (34% of them cryptogenic), the second most frequent etiologies were large-artery atherosclerosis and cardioembolism (both 19%). 60 percent of cardioembolic strokes were due to high-risk causes. Large-artery atherosclerosis was more prevalent in men (OR 1.8; 95% CI 1–3.3; p = .05) and among older patients (OR 6.2; 95% CI 1.8–21.4; p = .008). The median National Institutes of Health Stroke Scale score on admission was 3 (interquartile ranges 2–6), stroke was more severe in men ( p = .05). Conclusions Our study revealed that young patients with stroke in Estonia have higher burden of well-documented risk factors, higher prevalence of high-risk cardioembolic causes and higher prevalence of large-artery stroke compared to other young stroke cohorts.

Background There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. Methods We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. Results Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. Conclusion Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

International audience; The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of extracranial artery dissection (EAD) and intracranial artery dissection (IAD). EAD and IAD represent leading causes of stroke in the young, but are uncommon in the general population, thus making it challenging to conduct clinical trials and large observational studies. The guidelines were prepared following the Standard Operational Procedure for European Stroke Organisation guidelines and according to GRADE methodology. Our four recommendations result from a thorough analysis of the literature comprising two randomized clinical trials (RCTs) comparing anticoagulants to anti-platelets in the acute phase of ischemic stroke and twenty-six comparative observational studies. In EAD patients with acute ischemic stroke we recommend using intravenous thrombolysis (IVT) with alteplase within 4.5 hours of onset if standard inclusion/exclusion criteria are met, and mechanical thrombectomy in patients with large vessel occlusion of the anterior circulation. We further recommend early endovascular or surgical intervention for IAD patients with subarachnoid hemorrhage (SAH). Based on evidence from two phase 2 RCTs that have shown no difference between the benefits and risks of anticoagulants versus anti-platelets in the acute phase of symptomatic EAD, we strongly recommend that clinicians can prescribe either option. In post-acute EAD patients with residual stenosis or dissecting aneurysms and in symptomatic IAD patients with an intracranial dissecting aneurysm and isolated headache, there is insufficient data to provide a recommendation on the benefits and risks of endovascular/surgical treatment. Finally, nine expert consensus statements, adopted by 8 to 11 of the 11 experts involved, propose guidance for clinicians when the quality of evidence was too low to provide recommendations. Some of these pertain to the management of IAD (use of IVT, endovascular treatment, and antiplatelets versus anticoagulation in IAD with ischemic stroke and use of endovascular or surgical interventions for IAD with headache only). Other expert consensus statements address the use of direct anticoagulants and dual antiplatelet therapy in EAD-related cerebral ischemia, endovascular treatment of the EAD/IAD lesion and multidisciplinary assessment of the best therapeutic approaches in specific situations.

The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.

Introduction The initiation and conduct of randomised clinical trials are complicated by multiple barriers, including delays in obtaining regulatory approvals. Quantitative data on the extent of the delays due to national or local review in randomised clinical trials is scarce. Materials and methods We assessed the times needed to obtain regulatory approval and to initiate a trial site for an academic, EU-funded, phase III, randomised clinical trial of pharmacological prevention of complications in patients with acute stroke in over 80 sites in nine European countries. The primary outcome was the time from the first submission to a regulatory authority to initiation of a trial site. Secondary outcomes included time needed to complete each individual preparatory requirement and the number of patients recruited by each site in the first 6 and 12 months. Results The median time from the first submission to a regulatory authority to initiation of a trial site was 784 days (IQR: 586–1102). The single most time-consuming step was the conclusion of a clinical trial agreement between the national coordinator and the trial site, which took a median of 194 days (IQR: 93–293). A longer time to site initiation was associated with a lower patient recruitment rate in the first six months after initiation (B = –0.002; p = 0.02). Discussion Conclusion In this EU-funded clinical trial, approximately 26 months were needed to initiate a trial site for patient recruitment. The conclusion of a contract with a trial site was the most time-consuming activity. To simplify and speed up the process, we suggest that the level of detail of contracts for academic trials should be proportional to the risks and commercial interests of these trials.

Background: Outcomes after subarachnoid hemorrhage (SAH) have been rarely examined in large cohorts. Methods: This is an extension of the International Stroke Outcomes Study (INSTRUCT) pooling 13 ‘ideal’ stroke incidence studies (n=657 with SAH from 1993-2017, median age 56 years; 46% men). The primary outcomes were mortality and functional outcome (mRS score 3-5). Harmonized study factors included age, sex, behaviors (current smoking, alcohol intake), comorbidities (history of hypertension, ischemic heart disease, atrial fibrillation), stroke severity (e.g. NIHSS score) and year of stroke. In the pooled dataset, we estimated predictors of mortality using Poisson regression, to estimate incidence rate ratio (IRR) at 1 month (11 studies), 1 year (12 studies) and 5 years (7 studies). Generalized equation estimates in the log-binomial family were used to calculate risk ratios (RRs) for predictors of poor functional outcome at 1 month (5 studies) and 1 year (8 studies). Results: Mortality was 33% at 1 month, 43% at 1 year, and 47% at 5 years (Fig 1). Poor functional outcome was 25% at 1 month and 15% at 1 year (Fig 1). In multivariable analysis, age and stroke severity were associated with mortality at all time points, together with current smoking at 1 and 5 years, and history of hypertension at 5 years (Fig 2). Poor functional outcome was predicted by age (RR 1.03; 95% CI 1.01-1.04) at 1 month and by age (RR 1.04; 95% CI 1.00-1.08) and stroke severity (RR 1.94; 95% CI 1.02-2.87) at 1 year. Conclusion: Risk factors that predict SAH incidence including hypertension and smoking make outcomes worse. Better management of older patients and those with severe strokes could improve outcomes after SAH.

Background and ObjectivesThere is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide.MethodsWe performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18–50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression.ResultsWe included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas “other determined stroke” and “undetermined stroke” were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42–4.36).DiscussionEthnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

This study aimed to assess long-term, health-related quality of life (HRQOL) in a young ischemic stroke cohort, and to identify factors associated with poor HRQOL.We conducted a survey with ischemic stroke survivors in Estonia aged 18-54 years at the time of stroke, measuring HRQOL with the three-level version of the five-dimension EuroQol (EQ-5D-3L). The control group comprised the participants of the Health Behavior among Estonian Adult Population study. A tobit regression model with a backward stepwise analysis was used to identify factors associated with low EQ-5D-3L utility scores.In total, 352 patients with a mean follow-up time from the qualifying event of 5.7 years and 2304 controls were included. The mean EQ-5D-3L utility score in stroke survivors was significantly lower compared with that in the general population (0.71 vs. 0.87, respectively, p0.001). However, the subgroup with excellent functional outcome had a significantly higher mean EQ-5D-3L utility score compared with non-stroke counterparts (0.91 v 0.87, respectively, p0.001). The largest differences between stroke survivors and the general population were in the physical domains. Coronary heart disease at the index event, and higher follow-up duration, functional disability, depressive symptoms, recurrent stroke, and not being fully employed at follow-up, were independently associated with lower HRQOL.Young ischemic stroke survivors have long-term decreased HRQOL, except for those with excellent functional recovery. Our results prioritize motor rehabilitation and highlight the importance of secondary prevention, treatment of depression, and career counselling as potential ways of increasing HRQOL.

Objectives: To examine sex differences in disease profiles, management, and survival at 1 and 5 years after ischemic stroke (IS) among people with atrial fibrillation (AF). Methods: We performed a systematic literature search of reports of AF at IS onset according to sex. We undertook an individual participant data meta-analysis (IPDMA) of nine population-based stroke incidence studies conducted in Australasia, Europe, and South America (1993–2014). Poisson regression was used to estimate women:men mortality rate ratios (MRRs). Study-specific MRRs were combined using random effects meta-analysis. Results: In our meta-analysis based on aggregated data from 101 studies, the pooled AF prevalence was 23% (95% confidence interval [CI]: 22%–25%) in women and 17% (15%–18%) in men. Our IPDMA is of 1,862 IS-AF cases, with women (79.2 ± 9.1, years) being older than men (76.5 ± 9.5, years). Crude pooled mortality rate was greater for women than for men (1-year MRR 1.24; 1.01–1.51; 5-year 1.12; 1.03–1.22). However, the sex difference was greatly attenuated after accounting for age, prestroke function, and stroke severity (1-year 1.09; 0.97–1.22; 5-year 0.98; 0.84–1.16). Women were less likely to have anticoagulant prescription at discharge (odds ratio [OR] 0.94; 95% CI: 0.89–0.98) than men when pooling IPDMA and aggregated data. Conclusions: AF was more prevalent after IS among women than among men. Among IS-AF cases, women were less likely to receive anticoagulant agents at discharge; however, greater mortality rate in women was mostly attributable to prestroke factors. Further information needs to be collected in population-based studies to understand the reasons for lower treatment of AF in women.

Background and Purpose— Mobile stroke units (MSUs) are known to increase the proportion of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) in the first golden hour (GH) after onset compared with hospital settings (HS). However, because of the low number of AIS patients treated with intravenous thrombolysis within this ultraearly time window in conventional care, characteristics, and outcome of this subgroup of AIS patients have not been compared between MSU and HS. Methods— MSU-GH patients were selected from the Berlin-based MSU (STEMO [Stroke Emergency Mobile]), whereas HS-GH patients were selected from the SITS-EAST (Safe Implementation of Treatments in Stroke-East) registry. The outcome events of interest included the rates of favorable functional outcome (modified Rankin Scale scores of 0 or 1), distribution of the modified Rankin Scale scores, and mortality after 3 months between MSU-GH and HS-GH groups. Results— We identified 117 MSU-GH (38.4% of 305 MSU-treated patients) and 136 HS-GH (0.9% of 15 591 HS-treated patients) eligible patients without prestroke disability. No significant differences were documented in the rates of favorable functional outcome (51.3% versus 46.2%, P =0.487) and mortality (7.7% versus 9.9%, P =0.576) at 3 months, or in the distribution of 3-month modified Rankin Scale scores between the 2 groups ( P =0.196). In multivariable logistic regression analyses, adjusting for potential confounders, MSU treatment was not associated with a significantly different likelihood of favorable functional outcome (odds ratio, 1.84 for MSU patients; 95% CI, 0.86–3.96) or mortality (odds ratio, 0.95; 95% CI, 0.28–3.20) at 3 months. Conclusions— There is no evidence that safety and efficacy of ultraearly intravenous thrombolysis for AIS differs when used in MSUs or in HS.

Background Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency. Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier. Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression. Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs. Planning: First patient included in May 2016; final follow-up of the last patient by April 2020. Registration: ISRCTN, ISRCTN82217627, https://doi.org/10.1186/ISRCTN82217627

Background and purposeThe reduction of delay between onset and hospital arrival and adequate pre-hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence-based practices for the management of patients with suspected stroke in the pre-hospital setting.MethodsThe GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations.ResultsDespite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre-hospital code stroke' including highest priority dispatch, pre-hospital notification and rapid transfer to the closest stroke-ready' centre. Insufficient evidence was found to recommend a pre-hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre-hospital telemedicine during ambulance transport.ConclusionsThese guidelines inform on the contemporary approach to patients with suspected stroke in the pre-hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome.Click for the corresponding questions to this CME article.

Background and purposeRecent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry. MethodsWe compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months, (iii) functional independence defined as an mRS score of 0-2 at 3 months and (iv) 3-month mortality. ResultsOut of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P > 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60-140) vs. 65 (IQR, 47-95) min, P < 0.001] and door-to-imaging [40 (IQR, 20-90) vs. 24 (IQR, 15-35) min, P < 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273). ConclusionsOur findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS.

As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset ("golden hour"), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(-)] the "golden hour" by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24 h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24 h, respectively. A relative reduction in NIHSS-score of ≥40% at 2 h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0-1 at 3 months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(-) patients, with no differences in baseline characteristics (p 0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p 0.001) and 24 h (41 vs. 27%; p = 0.010), CREC at 2 h (39 vs. 21%; p 0.001) and FFO (46.5 vs. 34.0%; p = 0.028) at 3 months. The rates of sICH and 3-month mortality did not differ (p 0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53-11.03) and CREC (OR: 2.38; 95% CI 1.38-4.09), 24-h CR (OR: 1.88; 95% CI 1.08-3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15-3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement.

Background Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice. Methods This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle. Results Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years. Conclusions Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction. Electronic supplementary material The online version of this article (10.1007/s00415-019-09527-2) contains supplementary material, which is available to authorized users.

Background— Women are reported to have greater mortality after stroke than men, but the reasons are uncertain. We examined sex differences in mortality at 1 and 5 years after stroke and identified factors contributing to these differences. Methods and Results— Individual participant data for incident strokes were obtained from 13 population-based incidence studies conducted in Europe, Australasia, South America, and the Caribbean between 1987 and 2013. Data on sociodemographics, stroke-related factors, prestroke health, and 1- and 5-year survival were obtained. Poisson modeling was used to estimate the mortality rate ratio (MRR) for women compared with men at 1 year (13 studies) and 5 years (8 studies) after stroke. Study-specific adjusted MRRs were pooled to create a summary estimate using random-effects meta-analysis. Overall, 16 957 participants with first-ever stroke followed up at 1 year and 13 216 followed up to 5 years were included. Crude pooled mortality was greater for women than men at 1 year (MRR 1.35; 95% confidence interval, 1.24–1.47) and 5 years (MRR 1.24; 95% confidence interval, 1.12–1.38). However, these pooled sex differences were reversed after adjustment for confounding factors (1 year MRR, 0.81; 95% confidence interval, 0.72–0.92 and 5-year MRR, 0.76; 95% confidence interval, 0.65–0.89). Confounding factors included age, prestroke functional limitations, stroke severity, and history of atrial fibrillation. Conclusions— Greater mortality in women is mostly because of age but also stroke severity, atrial fibrillation, and prestroke functional limitations. Lower survival after stroke among the elderly is inevitable, but there may be opportunities for intervention, including better access to evidence-based care for cardiovascular and general health.

Background Women have worse outcomes after stroke than men, and this may be partly explained by stroke severity. We examined factors contributing to sex differences in severity of acute stroke assessed by the National Institutes of Health Stroke Scale. Methods and Results We pooled individual participant data with National Institutes of Health Stroke Scale assessment (N=6343) from 8 population‐based stroke incidence studies (1996–2014), forming part of INSTRUCT (International Stroke Outcomes Study). Information on sociodemographics, stroke‐related clinical factors, comorbidities, and pre‐stroke function were obtained. Within each study, relative risk regression using log‐binominal modeling was used to estimate the female:male relative risk ( RR ) of more severe stroke (National Institutes of Health Stroke Scale>7) stratified by stroke type (ischemic stroke and intracerebral hemorrhage). Study‐specific unadjusted and adjusted RR s, controlling for confounding variables, were pooled using random‐effects meta‐analysis. National Institutes of Health Stroke Scale data were recorded in 5326 (96%) of 5570 cases with ischemic stroke and 773 (90%) of 855 participants with intracerebral hemorrhage. The pooled unadjusted female:male RR for severe ischemic stroke was 1.35 (95% CI 1.24–1.46). The sex difference in severity was attenuated after adjustment for age, pre‐stroke dependency, and atrial fibrillation but remained statistically significant (pooled RR adjusted 1.20, 95% CI 1.10–1.30). There was no sex difference in severity for intracerebral hemorrhage ( RR crude 1.08, 95% CI 0.97–1.21; RR adjusted 1.08, 95% CI 0.96–1.20). Conclusions Although women presented with more severe ischemic stroke than men, much although not all of the difference was explained by pre‐stroke factors. Sex differences could potentially be ameliorated by strategies to improve pre‐stroke health in the elderly, the majority of whom are women. Further research on the potential biological origin of sex differences in stroke severity may also be warranted.

Contains fulltext : 215573.pdf (Publisher’s version ) (Closed access) Patients with ischemic stroke or transient ischemic attack and non-valvular atrial fibrillation have a high risk of recurrent stroke and other vascular events. The aim of this guideline is to provide recommendations on antithrombotic medication for secondary prevention of stroke and other vascular outcomes in these patients. The working group identified questions and outcomes, graded evidence, and developed recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach and the European Stroke Organisation (ESO) standard operating procedure for guidelines. The guideline was reviewed and approved by the ESO guideline board and the ESO executive committee. In patients with atrial fibrillation and previous stroke or transient ischemic attack, oral anticoagulants reduce the risk of recurrence over antiplatelets or no antithrombotic treatment. Non-vitamin K antagonist oral anticoagulants are preferred over vitamin K antagonists because they have a lower risk of major bleeding and death. Recommendations are weak regarding timing of treatment, (re-)starting oral anticoagulants in patients with previous intracerebral haemorrhage, and treatment in specific patient subgroups of those of older age, with cognitive impairment, renal failure or small vessel disease, because of a lack of strong evidence. In conclusion, for patients with atrial fibrillation and ischemic stroke or transient ischemic attack, non-vitamin K antagonist oral anticoagulants are the preferred treatment for secondary prevention of recurrent stroke or thromboembolism. Further research is required to determine the best timing for initiating oral anticoagulants after an acute ischemic stroke, whether or not oral anticoagulants should be (re)started in patients with a history of intracerebral haemorrhage, and the best secondary preventive treatment in specific subgroups.

IntroductionWorldwide, 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 analysisThe 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 disseminationEthical 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 Risk factor management is the key to stroke prevention. Although several studies have assessed the awareness of different risk factors in the general public, there are limited data available on how well acute stroke patients know their own risk factors. The aim of this study was to assess stroke patients' informedness of their own stroke risk factors. Methods All consecutive eligible acute stroke and transient ischemic attack patients hospitalized at the Tartu University Hospital, Department of Neurology, during 9 months in 2010 were interviewed about different stroke risk factors within 72 hours from hospitalization. The respective information was also retrieved from medical records. Results Of the 341 patients admitted during the study period, 195 were eligible for the interview. Diabetes was the best known risk factor (89%) followed by hypertension (80%), atrial fibrillation (78%), previous stroke (77%), and heart failure and/or ischemic heart disease (66%). Conclusions We found that acute stroke patients are best informed of their diabetes and worst informed of their ischemic heart disease and/or heart failure. There is, however, room for amelioration in the awareness of all of the studied risk factors. More attention should be addressed to explaining the risks and treatment options to patients at risk of stroke and the general population.

Background and Purpose— A recent meta-analysis investigating the association between statins and early outcomes in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) indicated that prestroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage. We investigated the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT. Methods— We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) registry on consecutive AIS patients treated with IVT during an 8-year period. Early clinical recovery within 24 hours was defined as reduction in baseline National Institutes of Health Stroke Scale score of ≥10 points. Favorable functional outcome at 3 months was defined as modified Rankin Scale scores of 0 to 1. Symptomatic intracranial hemorrhage was diagnosed using National Institute of Neurological Disorders and Stroke, European-Australasian Acute Stroke Study-II and SITS definitions. Results— A total of 1660 AIS patients treated with IVT fulfilled our inclusion criteria. Patients with statin pretreatment (23%) had higher baseline stroke severity compared with cases who had not received any statin at symptom onset. After adjusting for potential confounders, statin pretreatment was not associated with a higher likelihood of symptomatic intracranial hemorrhage defined by any of the 3 definitions. Statin pretreatment was not related to 3-month all-cause mortality (odds ratio, 0.92; 95% confidence interval, 0.57–1.49; P =0.741) or 3-month favorable functional outcome (odds ratio, 0.81; 95% confidence interval, 0.52–1.27; P =0.364). Statin pretreatment was independently associated with a higher odds of early clinical recovery (odds ratio, 1.91; 95% confidence interval, 1.25–2.92; P =0.003). Conclusions— Statin pretreatment seems not to be associated with adverse outcomes in AIS patients treated with IVT. The effect of statin pretreatment on early functional outcomes in thrombolysed AIS patients deserves further investigation.

INTRODUCTION Cardioembolic stroke (CS) in patients without thrombolytic treatment is associated with a worse clinical outcome and higher mortality compared to other types of stroke. The aim of this study was to determine the clinical outcome of CS in patients treated by intravenous thrombolysis (IVT). MATERIAL AND METHODOLOGY Data of patients from the SITS-EAST register (Safe Implementation of Treatments in Stroke) were analyzed in patients who received IVT treatment from 2000 to April 2014. The effect of the stroke etiology according to ICD-10 classification on outcome was analyzed using a univariate and multivariate analysis. The outcomes were assessed as follows: excellent clinical outcome (modified Rankin scale (mRS) 0-1) at 3 months, the rate of symptomatic intracranial hemorrhage (sICH), mortality, and improvement at 24 hours after IVT. RESULTS Data of 13 772 patients were analyzed. CS represented 30% of all strokes. The mean age of patients with CS, atherothrombotic stroke, lacunar stroke, and other stroke was 70.8, 66.7, 66.2, and 63.3 years, respectively (P

ObjectiveTo examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke.MethodsIndividual participant data on long-term functional outcome or participation restriction (i.e., handicap) were obtained from 11 stroke incidence studies (1993–2014). Multivariable log-binomial regression was used to estimate the female:male relative risk (RR) of poor functional outcome (modified Rankin Scale score >2 or Barthel Index score ResultsIn unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RRunadjusted 1.32, 95% confidence interval [CI] 1.18–1.48; 5 years: RRunadjusted 1.31, 95% CI 1.16–1.47). However, this difference was greatly attenuated after adjustment for age, prestroke dependency, and stroke severity (1 year: RRadjusted 1.08, 95% CI 0.97–1.20; 5 years: RRadjusted 1.05, 95% CI 0.94–1.18). Women also had greater participation restriction than men (pooled MDunadjusted −5.55, 95% CI −8.47 to −2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MDadjusted −2.48, 95% CI −4.99 to 0.03).ConclusionsWorse outcomes after stroke among women were explained mostly by age, stroke severity, and prestroke dependency, suggesting these potential targets to improve the outcomes after stroke in women.

Objectives. Reports on young patients with ischemic stroke from Eastern Europe have been scarce. This study aimed to assess risk factors and etiology of first-ever and recurrent stroke among young Estonian patients. Methods. We performed a retrospective study of consecutive ischemic stroke patients aged 18–54 years who were treated in our two hospitals from 2003 to 2012. Results. We identified 741 patients with first-ever stroke and 96 patients with recurrent stroke. Among first-time patients, men predominated in all age groups. The prevalence of well-documented risk factors in first-time stroke patients was 83% and in the recurrent group 91%. The most frequent risk factors were hypertension (53%), dyslipidemia (46%), and smoking (35%). Recurrent stroke patients had fewer less well-documented risk factors compared to first-time stroke patients (19.8 versus 30.0%, P=0.036). Atrial fibrillation was the most common cause of cardioembolic strokes (48%) and large-artery atherosclerosis (LAA) was the cause in 8% among those aged P=0.01) and less often by other definite etiology (8.5 versus 1.0%, P=0.01). Conclusions. The prevalence of vascular risk factors among Estonian young stroke patients is high. Premature atherosclerosis is a cause in a substantial part of very young stroke patients.

Introduction: As women suffer worse functional outcomes of stroke than men, they may also face more challenges with community reintegration but data are scarce. We examined sex differences in participation after stroke and which factors might account for these disparities. Methods: INSTRUCT is an individual participant data pooling study of incident strokes obtained from 13 population-based cohorts worldwide. Two of the cohorts (Melbourne ’96-‘99 and Auckland ’02-‘03) included assessment of participation at 5 years after stroke using the London Handicap Scale (LHS). The LHS is used to assess the individual’s perspective of their involvement in life situations including orientation (person’s awareness of surroundings), physical independence, mobility, occupation, social interaction and economic self-efficiency. The total score ranges from 0 (worst disadvantage) to 100 (no disadvantage). Linear regression was used to compare LHS total scores and sub-domains for women compared to men. Study-specific multivariable models incorporated adjustment for socio-demographics, stroke-related factors, pre-stroke health and post-stroke factors were combined using random-effects meta-analysis. Results: At 5 years after stroke, there were data on participation for 351/592 (59%) of survivors in Melbourne and 266/881 (30%) of survivors in Auckland. Women suffered greater participation restriction than men (total LHS, pooled mean difference, MD -5.55 [95% CI -8.47, -2.63]). The magnitude of the difference attenuated after adjusting for covariates (pooled MD -2.48 [-4.99, 0.03]). Significant confounders in study-specific models included age, stroke severity, pre-stroke dependency and pre-stroke dementia for Melbourne; and age, stroke severity and pre-stroke dependency for Auckland. In sub-dimensions, women had greater restriction than men in mobility, physical independence and occupation. Additionally, women in Melbourne experienced poorer social integration and orientation than men. Conclusion: Greater restriction in participation after stroke among women than men was mostly attributable to their advanced age and greater pre-stroke dependency. Interventions targeting participation could reduce the impact of stroke in women.

Background & Purpose: There are scarce data regarding outcomes of AIS patients treated with IVT within 60 min from symptom onset (“golden hour”). We sought to compare outcomes between AIS patients treated within (OTT≤60 min) and outside (OTT: 61-270min) the “golden hour” [GH(+) & GH (-)] using a propensity score matching approach. Methods: Patients were evaluated during a 12-year period in a large, international, prospective registry of IVT (SITS-EAST). They underwent serial NIHSS-score assessments at baseline, 2 hrs and 24 hrs following tPA-bolus. Clinical recovery (CR) at 2 and 24 hrs was defined as a reduction of ≥10 points in NIHSS-score compared with baseline, or a NIHSS-score of ≤3 at 2 and 24 hrs respectively. A relative reduction in NIHSS-score of ≥40% at 2 hrs was predictive of complete recanalization (CREC). sICH was defined using SITS-MOST criteria; 3-month favourable functional outcome (FFO) was defined as a mRS-score of 0-1. The two groups were matched for demographics, risk factors, baseline NIHSS, admission blood pressure and serum glucose. Results: Out of 19.077 tPA-treated AIS patients, 71 patients in GH(+) group [mean age 67±13 years; median NIHSS-score 12 points (IQR 10); median onset to treatment time (OTT) 55min, (IQR 10)] were matched to 6882 patients in GH(-) group (mean age 67±12 years; median NIHSS-score 11 points (IQR 9); median OTT 155min (IQR 55)]. The two groups did not differ in any of the matched characteristics (p>0.1). GH(+) had significantly (p0.2) in the two groups. GH(+) was independently (p Conclusions: AIS patients treated with IVT within the GH have substantially higher odds of early CR and FFO. These findings highlight the potential of mobile stroke units to further improve AIS outcomes by increasing the rates of tPA delivery within the GH.