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Background and Purpose: Several risk factors of symptomatic intracerebral hemorrhage (SICH) following intravenous thrombolysis for acute ischaemic stroke have been established. However, potential predictors of good functional outcome post-SICH have been less studied., Methods: Patient data registered in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) from 2005 to 2021 were used. Acute ischaemic stroke patients who developed post intravenous thrombolysis SICH according to the SITS Monitoring Study definition were analyzed to identify predictors of functional outcomes., Results: A total of 1679 patients with reported SICH were included, out of which only 2.8% achieved good functional outcome (modified Rankin Scale scores of 0-2), whilst 80.9% died at 3 months. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score and 24-h ΔNIHSS score were independently associated with a lower likelihood of achieving both good and excellent functional outcomes at 3 months. Baseline NIHSS and hematoma location (presence of both SICHs, defined as remote and local SICH concurrently; n = 478) were predictors of early mortality within 24 h. Independent predictors of 3-month mortality were age, baseline NIHSS, 24-h ΔNIHSS, admission serum glucose values and hematoma location (both SICHs). Age, baseline NIHSS score, 24-h ΔNIHSS, hyperlipidemia, prior stroke/transient ischaemic attack, antiplatelet treatment, diastolic blood pressure at admission, glucose values on admission and SICH location (both SICHs) were associated with reduced disability at 3 months (≥1-point reduction across all modified Rankin Scale scores). Patients with remote SICH (n = 219) and local SICH (n = 964) had comparable clinical outcomes, both before and after propensity score matching., Conclusions: Symptomatic intracerebral hemorrhage presents an alarmingly high prevalence of adverse clinical outcomes, with no difference in clinical outcomes between remote and local SICH., (© 2023 European Academy of Neurology.)

Background: Having a stroke at a young age has a huge socioeconomic impact. Data on the trends of stroke incidence in young adults from prospective population-based studies are scarce., Aims: The aim of this study was to analyze the trends in stroke incidence in 15- to 54-year-old residents of Tartu, Estonia from 1991 to 2017., Methods: Three population-based studies with identical study protocols determining the incidence of first-ever stroke have previously been conducted in Tartu, Estonia (1991-1993, 2001-2003, and 2013-2017). All residents of Tartu with first-ever stroke (ischemic stroke, spontaneous intracerebral hemorrhage, and subarachnoid hemorrhage) who were hospitalized to the Department of Neurology, Tartu University Hospital in respective study periods were included prospectively. Overlapping data sources for case ascertainment were used to include both hospitalized and non-hospitalized cases. Trends in first-ever stroke incidence in 15- to 54-year-old residents of Tartu were calculated and compared using rate ratio (RR)., Results: Altogether 259 strokes were identified. From 1991 to 2017, the proportion of women increased from 38.3% to 43.6%. Mean age at onset in women decreased from 46.9 (standard deviation (SD): 7.3) to 42.6 (SD: 8.9). Overall crude incidence rates per 100,000 decreased significantly from 1991 to 2003 (from 57.2 (95% confidence interval (CI): 46.9-69.1) to 35.7 (95% CI: 25.7-48.3)); RR: 0.62 (95% CI: 0.44-0.89). While also present in women, the decrease was most notable in 45- to 54-year-old men (RR: 0.55 (95% CI: 0.30-0.99)). In 35- to 44-year-old men, the incidence rates decreased significantly from 2001 to 2017 (RR: 0.37 (95% CI: 0.14-0.99))., Conclusion: The overall first-ever stroke incidence rates decreased from 1991 to 2003 and remained stable thereafter.

Background: Behavioral risk factors are common among young patients with stroke. This study aimed to compare the health behavior of patients and healthy controls and develop a combined risk score of health behavior., Methods: The health behavior of patients aged 18-54 years who suffered an ischemic stroke from 2013 to 2020 in Estonia was compared to the Health Behavior among Estonian Adult Population 2014 study sample. We chose five risk factors for comparison: smoking status, body mass index, physical exercise, diet (salt use and vegetable consumption), alcohol intake (quantity and frequency), and composed a summary score., Results: Comparing 342 patients and 1789 controls, daily smoking (49.0% vs. 22.7%), obesity (33.4% vs. 15.9%), low physical activity (< twice/week) (72.2% vs. 60.5%), excessive salt use (8.6% vs. 4.5%), and frequent alcohol use (≥ weekly) (39.9% vs. 34.0%) were more prevalent among patients. The differences in infrequent vegetable consumption (<6 days/week) and excessive alcohol consumption (7 days, >8 units/females, >16 units/males) were not significant. The observed differences were similar for age groups 18-44 years and 45-54 years. The average Health Behavior Stroke Risk Score (0-10) was 4.6 points (CI 4.4-4.8, SD ± 1.97) for patients and 3.5 points (CI 3.4-3.6, SD ± 1.90) for controls., Conclusions: Before stroke, young patients displayed significantly worse health behavior than the general population. The largest differences were found for smoking and obesity, and a cumulation of risk factors was observed via the HBSR score., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

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 <4.5 h duration who are eligible for IVT, tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS of <4.5 h duration who are eligible for IVT, we recommend against using tenecteplase at a dose of 0.40 mg/kg (low evidence, strong recommendation). For patients with AIS of <4.5 h duration with prehospital management with a mobile stroke unit who are eligible for IVT, we suggest tenecteplase 0.25 mg/kg over alteplase 0.90 mg/kg (low evidence, weak recommendation). For patients with large vessel occlusion (LVO) AIS of <4.5 h duration who are eligible for IVT, we recommend tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS on awakening from sleep or AIS of unknown onset who are selected with non-contrast CT, we recommend against IVT with tenecteplase 0.25 mg/kg (low evidence, strong recommendation). Expert consensus statements are also provided. Tenecteplase 0.25 mg/kg may be favoured over alteplase 0.9 mg/kg for patients with AIS of <4.5 h duration in view of comparable safety and efficacy data and easier administration. For patients with LVO AIS of <4.5 h duration who are IVT-eligible, IVT with tenecteplase 0.25 mg/kg is preferable over skipping IVT before MT, even in the setting of a direct admission to a thrombectomy-capable centre. IVT with tenecteplase 0.25 mg/kg may be a reasonable alternative to alteplase 0.9 mg/kg for patients with AIS on awakening from sleep or AIS of unknown onset and who are IVT-eligible after selection with advanced imaging., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Intellectual and financial disclosures of the module working group members are presented in Supplemental Table., (© European Stroke Organisation 2023.)

Background: 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  < 0.001 and OR for PSM 1.17, 95% CI = 1.05-1.31, p  = 0.007). Regarding secondary outcomes, there were no differences in functional outcomes, death nor SICH rates between groups., 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.

Background: 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., Methods: 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)., Findings: 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)., Interpretation: 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., Funding: 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., Competing Interests: Declaration of interests MBR reports a grant from the Norwegian National Association for Public Health. HC reports grants from the Velux-foundation, Helse-fonden, and Tværs-fonden; personal speaker honoraria from Bayer and Bristol Myers Squibb; and personal fees from the American Heart Association. STE reports advisory board compensation from Boehringer Ingelheim and Bayer; and grants from Daiichy-Sankyo. JK reports personal fees and non-financial support from Boehringer Ingelheim, Servier, and Pfizer. JPe reports grants from the Swedish ALF and the Southern Healthcare Region. JPu reports personal fees from Boehringer Ingelheim, Portola, Herantis Pharma, and Terve Media; is an honorary speaker, on the advisory board, and received personal fees and a research grant from Bristol Myers Squibb (Pfizer), Bayer, and Abbott (St Jude Medical); research collaboration, and stock ownership from Vital Signum; and grants from Business Finland and Amgen. DJW is an honorary speaker for Bayer, Portola, and Novo Nordisk; and reports consultancy fees from Alnylam, Portola, Alexion, and Novo Nordisk. EBM reports grants from the Norwegian Clinical Therapy Research in the Specialist Health Services Research Programme and the Northern Norway Regional Health Authority., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings., Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding., Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting., Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses., Trial Registration: ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 ., (© 2022. The Author(s).)

Background and Objectives: There 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., Methods: We 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., Results: We 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)., Discussion: Ethnoracial 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., (© 2021 American Academy of Neurology.)

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., Competing Interests: Conflict of interest The Authors declare no conflict of interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability., Aim: We aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability., Methods: We 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)., Results: Patients 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%))., Conclusions: Intravenous 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: 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., (© 2021 European Academy of Neurology.)

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 <0.05). Main outcomes were incidence of END, associated predictors of END, ordinal day-90 mRS, and day-90 mortality., 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 <0.001), large vessel disease (LVD) with carotid stenosis (OR, 2.97 [95% CI, 2.45-3.61], P <0.001), other LVD (OR, 2.41 [95% CI, 2.03-2.88], P <0.001), and ischemic stroke versus transient ischemic attack (TIA)/stroke mimics (OR, 16.14 [95% CI, 3.99-65.3], P <0.001). END was associated with worse outcome on ordinal mRS: adjusted OR 2.48 (95% CI, 2.39-2.57, P <0.001) by day-90 compared with no END. The adjusted OR for day-90 mortality was 9.70 (95% CI, 8.36-11.26, P <0.001)., 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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

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: 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., (© 2017 American Heart Association, Inc.)

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., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: According to the European license, alteplase can be given no sooner than 3 months after previous stroke. However, it is not known whether past history of stroke influences the effect of treatment. Our aim was to evaluate safety and functional outcome after intravenous thrombolysis administered in everyday practice to patients with previous stroke≤3 months compared with those with first-ever stroke., Methods: We analyzed consecutive cases treated with alteplase between October 2003 and July 2014 contributed to the Safe Implementation of Thrombolysis for Stroke-Eastern Europe registry from 12 countries. Odds ratios were calculated using unadjusted and adjusted logistic regression., Results: Of 13,007 patients, 11,221 (86%) had no history of stroke and 249 (2%) experienced previous stroke≤3 months before admission. Patients with previous stroke≤3 months had a higher proportion of hypertension and hyperlipidemia. There were no significant differences in outcome, including symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study (unadjusted odds ratio 1.27, 95% confidence interval: 0.74-2.15), and being alive and independent at 3 months (odds ratio 0.81, 95% confidence interval: 0.61-1.09)., Conclusions: Patients currently treated with alteplase, despite a history of previous stroke≤3 months, do not seem to achieve worse outcome than those with first-ever stroke. Although careful patient selection was probably of major importance, our findings provide reassurance that this group of patients may safely benefit from thrombolysis and should not be arbitrarily excluded as a whole. Further studies are needed to identify the shortest safe time lapse from the previous event to treatment with alteplase., (© 2015 American Heart Association, Inc.)

Stroke is one of the leading causes of disability in Europe. Central and Eastern European countries have the highest incidence and mortality rates through Europe. The improvements in stroke prevention and treatment in Central and Eastern European countries did not completely reach the quality parameters present in Western European countries. We present features of current management of stroke in Central and Eastern European countries., (© 2015 World Stroke Organization.)

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., (© 2015 American Heart Association, Inc.)

The aim of this study was to evaluate which factors are associated with early hospital arrival and help-seeking delays in acute stroke. All consecutive eligible patients were interviewed face-to-face within 72 h of admission. Factors associated with early arrival were assessed by univariate and multivariate analysis. The data of 195 patients were analysed. The patients who first called the emergency medical services rather than the family physician arrived earlier (odds ratio 15.9, 95% confidence interval 3.23-78.3, P<0.01). Those who contacted the emergency medical services within 30 min of symptom onset were more likely to receive thrombolysis (odds ratio 6.9, 95% confidence interval 2.6-18.4, P<0.01). The most common reasons for delaying seeking help were the hope for spontaneous recovery and perceiving the elapsed time as insignificant. The patients who call their family physician lose valuable time and their chance for thrombolysis. Many patients probably neglect symptoms because of stroke itself and therefore do not act fast enough.

Background: The hyperdense cerebral artery sign (HCAS) on unenhanced computed tomography (CT) in acute ischemic stroke is a valuable clinical marker, but it remains unclear if HCAS reflects clot composition or stroke etiology. Therefore, variables independently associated with HCAS were identified from a large international data set of patients treated with intravenous thrombolysis., Methods: All stroke patients undergoing intravenous thrombolysis from the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) database between February 2003 and December 2011 were analyzed. A general estimating equation model accounting for within-center clustering was used to identify factors independently associated with HCAS., Results: Of all 8878 consecutive patients, 8375 patients (94%) with available information about HCAS were included in our analysis. CT revealed HCAS in 19% of patients. Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 12, mean age was 67 ± 12 years, and 3592 (43%) patients were females. HCAS was independently associated with baseline NIHSS (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.10-1.12), vessel occlusion (OR, 5.02; 95% CI, 3.31-7.63), early ischemic CT changes (OR, 1.63; 95% CI, 1.31-2.04), year (OR, 1.07; 95% CI, 1.02-1.12), and age (10-year increments; OR, .90; 95% CI, .84-.96). Cardioembolic stroke was not associated with HCAS independently of baseline NIHSS. In different centers, HCAS was reported in 0%-50% of patients., Conclusions: This study illustrates significant variation in detection of HCAS among stroke centers in routine clinical practice. Accounting for within-center data clustering, stroke subtype was not independently associated with HCAS; HCAS was associated with the severity of neurologic deficit., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Brain imaging is logistically the most difficult step before thrombolysis. To improve door-to-needle time (DNT), it is important to understand if (1) longer door-to-imaging time (DIT) results in longer DNT, (2) hospitals have different DIT performances, and (3) patient and hospital characteristics predict DIT., Methods: Prospectively collected data in the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) registry from Central/Eastern European countries between 2008 and 2011 were analyzed. Hospital characteristics were obtained by questionnaire from each center. Patient- and hospital-level predictors of DIT of 25 minutes or less were identified by the method of generalized estimating equations., Results: Altogether 6 of 9 SITS-EAST countries participated with 4212 patients entered into the database of which 3631 (86%) had all required variables. DIT of 25 minutes or less was achieved in 2464 (68%) patients (range, 3%-93%; median, 65%; and interquartile range, 50%-80% between centers). Patients with DIT of 25 minutes or less had shorter DNT (median, 60 minutes) than patients with DIT of more than 25 minutes (median, 86 minutes; P < .001). Four variables independently predicted DIT of 25 minutes or less: longer time from stroke onset to admission (91-180 versus 0-90 minutes; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.8), transport time of 5 minutes or less (OR, 2.9; 95% CI, 1.7-4.7) between the place of admission and a computed tomography (CT) scanner, no or minimal neurologic deficit before stroke (OR, 1.3; 95% CI, 1.02-1.5), and diabetes mellitus (OR, .8; 95% CI, .7-.97)., Conclusions: DIT should be improved in patients arriving early and late. Place of admission should allow transport time to a CT scanner under 5 minutes., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Little is known about the effect of thrombolysis in patients with preexisting disability. Our aim was to evaluate the impact of different levels of prestroke disability on patients' profile and outcome after intravenous thrombolysis., Methods: We analyzed the data of all stroke patients admitted between October 2003 and December 2011 that were contributed to the Safe Implementation of Treatments in Stroke-Eastern Europe (SITS-EAST) registry. Patients with no prestroke disability at all (modified Rankin Scale [mRS] score, 0) were used as a reference in multivariable logistic regression., Results: Of 7250 patients, 5995 (82%) had prestroke mRS 0, 791 (11%) had prestroke mRS 1, 293 (4%) had prestroke mRS 2, and 171 (2%) had prestroke mRS≥3. Compared with patients with mRS 0, all other groups were older, had more comorbidities, and more severe neurological deficit on admission. There was no clear association between preexisting disability and the risk of symptomatic intracranial hemorrhage. Prestroke mRS 1, 2, and ≥3 were associated with increased risk of death at 3 months (odds ratio, 1.3, 2.0, and 2.6, respectively) and lower chance of achieving favorable outcome (achieving mRS 0-2 or returning to the prestroke mRS; 0.80, 0.41, 0.59, respectively). Patients with mRS≥3 and 2 had similar vascular profile and favorable outcome (34% versus 29%), despite higher mortality (48% versus 39%)., Conclusions: Prestroke disability does not seem to independently increase the risk of symptomatic intracranial hemorrhage after thrombolysis. Despite higher mortality, 1 in 3 previously disabled patients may return to his/her prestroke mRS. Therefore, they should not be routinely excluded from thrombolytic therapy.

Estonia is the smallest of the three Baltic countries. The decline in incidence of first-ever stroke during the 1990s has left Tartu, Estonia with a relatively low stroke incidence. However, the incidence rates for younger age groups, and the 28-day case fatality rate are higher compared with several other studies. Developments in the national health care system in recent years have been positive: the decline of mortality rate of stroke in Estonia is greater than the European Union average. However, the mortality of cardiovascular diseases is higher compared with several European countries. The prevalence of most stroke risk factors is comparable with European Union countries, while atrial fibrillation is somewhat more frequent (30%) among the patients having suffered from ischemic stroke. The management of stroke in Estonia has been in accordance with European and national stroke guidelines. Stroke units are organized in regional and central hospitals in bigger cities. A well-developed and free ambulance service, and a high priority of stroke code, enable a quick transportation of patients to the nearest hospital providing thrombolytic therapy. The number of thrombolyzed stroke cases has increased since 2003. The Estonian Stroke Initiative was founded in 2008 to improve stroke care, promote regional networks, and increase stroke knowledge among the general population and medical professionals. Since then, several activities regarding stroke awareness have been organized., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Objectives: This study was undertaken to assess stroke awareness of the Estonian population., Methods: Investigators were asked to fill in an original, closed-ended multiple-choice questionnaire about the definition, risk factors, symptoms and behavior at the onset of stroke by randomly selected subjects in public places of the two biggest cities in Estonia (Tallinn and Tartu)., Results: The study included 355 persons. Most of the respondents knew that stroke is an acute disease and that one should call the ambulance at the onset of a stroke. Speech disorder and paresis were the best known symptoms, while hypertension was the best known risk factor. There were no differences between the sexes, but advanced age and higher level of education were related to higher awareness., Conclusions: The overall knowledge was better compared to many other studies. Future awareness campaigns should be addressed to younger subjects with lower education., (Copyright © 2012 S. Karger AG, Basel.)

Background and Purpose: Shortening door-to-needle time (DNT) for the thrombolytic treatment of stroke can improve treatment efficacy by reducing onset-to-treatment time. The goal of our study was to explore the association between DNT and outcome and to identify factors influencing DNT to better understand why some patients are treated late., Methods: Prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST: 9 central and eastern European countries) on all patients treated with thrombolysis between February 2003 and February 2010 were analyzed. Multiple logistic regression analysis was used to identify predictors of DNT ≤ 60 minutes., Results: Altogether, 5563 patients were treated with thrombolysis within 4.5 hours of symptom onset. Of these, 2097 (38%) had DNT ≤ 60 minutes. In different centers, the proportion of patients treated with DNT ≤ 60 minutes ranged from 18% to 84% (P<0.0001). Patients with longer DNT (in 60-minute increments) had less chance of achieving a modified Rankin Scale score of 0 to 1 at 3 months (adjusted OR, 0.86; 95% CI, 0.77-0.97). DNT ≤ 60 minutes was independently predicted by younger age (in 10-year increments; OR, 0.92; 95% CI, 0.87-0.97), National Institutes of Health Stroke Scale score 7 to 24 (OR, 1.44; 95% CI, 1.2-1.7), onset-to-door time (in 10-minute increments; OR, 1.19; 95% CI, 1.17-1.22), treatment center (P<0.001), and country (P<0.001)., Conclusions: Thrombolysis of patients with older age and mild or severe neurological deficit is delayed. The perception that there is sufficient time before the end of the thrombolytic window also delays treatment. It is necessary to improve adherence to guidelines and to treat patients sooner after arrival to hospital.

Background: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure., Methods: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered, number NCT00120003 (ClinicalTrials.gov), and ISRCTN13643354., Findings: 2029 patients were randomly allocated to treatment groups (1017 candesartan, 1012 placebo), and data for status at 6 months were available for 2004 patients (99%; 1000 candesartan, 1004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg [SD 23/14] in the candesartan group on day 7 vs 152/84 mm Hg [22/14] in the placebo group; p<0·0001). During 6 months' follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events, vs placebo, 111 events; adjusted hazard ratio 1·09, 95% CI 0·84-1·41; p=0·52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1·17, 95% CI 1·00-1·38; p=0·048 [not significant at p≤0·025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo., Interpretation: There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect., Funding: South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Elevated blood pressure following acute stroke is common, and yet early antihypertensive treatment is controversial. ACCESS suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials., Aims and Design: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure ≥140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland., Study Outcomes: There are two co-primary effect variables: • Functional status at 6-months, measured by the modified Rankin Scale, and • vascular death, myocardial infarction or stroke during the first 6-months. Secondary outcome variables: Secondary effect variables include • the Barthel index (functional status) • EuroQol (quality of life) and • Mini-mental state examination (cognition) at 6-months • Health economic costs during the first 6-months, Funding: The Scandinavian Candesartan Acute Stroke Trial receives basic funding from Norwegian health authorities. AstraZeneca supplies the trial drugs, and AstraZeneca and Takeda support the trial with limited, unrestricted grants., Summary: The Scandinavian Candesartan Acute Stroke Trial is the first large trial of angiotensin receptor blockers in patients with elevated blood pressure and acute stroke, and aims to answer whether treatment with angiotensin receptor blockers is beneficial for this indication.

Objectives: The goal of our study was to investigate the associations of oxidized LDL (apoB100 aldehyde-modified form) and acute phase proteins (fibrinogen, CRP) with acute ischemic stroke severity and outcome., Materials and Methods: The study included 61 ischemic stroke patients and 64 controls. Strokes were subtyped according to TOAST criteria, the severity and outcome of stroke (at 1 year) were measured., Results: The mean triglyceride, fibrinogen, CRP and glucose values were significantly higher among cases. The median oxLDL value for patients with large artery atherosclerosis (LAA) type of stroke was significantly higher than for other subtypes. The oxLDL values did not correlate with age, stroke severity and outcome., Conclusions: Inflammatory markers (fibrinogen and CRP) predicted the stroke severity and outcome whereas elevation of oxLDL levels did not. Our data refer to possibility that there may exist some links between the LAA subtype of stroke and elevated oxLDL (apoB100 aldehyde-modified form).

Background and Purpose: The purpose of the present study was to estimate the time trends of stroke during the last 10 years in an Estonian population by comparison of the results from the 2 previous stroke registries from Tartu., Methods: The Third Stroke Registry in Tartu was conducted from January 12, 2001, to November 30, 2003. The previous registry was composed from January 1, 1991, to December 31, 1993. The design of both studies is similar, using the same study criteria and classification schemes., Results: A total of 1280 patients with first-ever stroke were registered during the 5-year study period. The overall incidence rate of 230 per 100,000 declined between the studies to 188 per 100,000 age-standardized to the European standard population. The age-adjusted incidence rate for women decreased from 204 to 164 per 100,000 between the 2 periods. In most of the age groups, the overall case-fatality rates declined during the second period; the trend in the age group 75 to 84 years was statistically significant., Conclusions: The incidence of first-ever stroke in Tartu has declined significantly during the past decade and reached the level of the first registry. The 28-day case-fatality rate has declined from 30% to 26%. The prevalence of cardiovascular risk factors, incidence of stroke, and ischemic heart disease has been high in Eastern European countries. Our data show that the situation has improved.

Background and Purpose: Previous studies in the United States and the United Kingdom have shown that stroke research is underfunded compared with coronary heart disease (CHD) and cancer research despite the high clinical and financial burden of stroke. We aimed to determine whether underfunding of stroke research is a Europe-wide problem., Methods: Data for the financial year 2000 to 2001 were collected from 9 different European countries. Information on stroke, CHD, and cancer research funding awarded by disease-specific charities and nondisease-specific charity or government- funded organizations was obtained from annual reports, web sites, and by direct communication with organizations., Results: There was marked and consistent underfunding of stroke research in all the countries studied. Stroke funding as a percentage of the total funding for stroke, CHD, and cancer was uniformly low, ranging from 2% to 11%. Funding for stroke was less than funding for cancer, usually by a factor of > or =10. In every country except Turkey, funding for stroke research was less than that for CHD., Conclusions: This study confirms that stroke research is grossly underfunded, compared with CHD and cancer, throughout Europe. Similar data have been obtained from the United States suggesting that relative underfunding of stroke research is likely to be a worldwide phenomenon.

Background: The main goal of the Third Stroke Registry in Tartu was to determine the incidence and 28-day case-fatality rates for first-ever stroke in an Estonian population., Methods: The data collection started on 01.12.2001. All patients with first-ever stroke living in Tartu were registered., Results: During the first year, 234 first-ever stroke cases were registered. The incidence rate of first-ever stroke age-standardised to the European population was 195/100,000, 214 (95% CI, 185-243) for men and 181 (95% CI, 155-208) per 100,000 for women. Sixty-eight patients (29%) died within 28 days of stroke onset., Conclusions: The incidence and 28-day case-fatality rate of stroke in Estonia are high compared to other countries. It might be related to higher risk factor prevalence, stress and socioeconomic status., (Copyright 2004 S. Karger AG, Basel)

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Brain ischemia results in the activation of a cascade of inflammatory responses, contributing to the pathogenesis of stroke. This study aimed to assess the patterns of possible changes in the expression of specific inflammation-associated protein-encoding genes and miRNAs in the peripheral blood between the acute and chronic phase of young-onset cryptogenic (Cryp) and large-artery atherosclerotic (LAA) stroke. Blood and serum were collected from patients with cryptogenic and large-artery atherosclerotic stroke at the stroke onset and 1-year follow-up. The relative expression of inflammation-related genes was analysed at the mRNA and miRNA levels using real-time quantitative PCR. Moreover, the relationship between the relative gene expression levels and clinical data was assessed using several different statistical approaches. Seventy-three patients were included in this study, with a median age of 47 (IQR, 9) years. Approximately 72% were men. In patients with cryptogenic stroke, at the mRNA level, ICAM1, CXCL8, TNF, NFKBIA, PYCARD, IL1B, and IL18 were observed to be upregulated at the stroke onset compared to the 1-year follow-up. In patients with LAA stroke, only the expression of NFKBIA was significantly higher during acute stroke. Further, the miRNA serum levels of miR-21, miR-122, and miR-155 were higher at the onset of stroke in patients with cryptogenic stroke but not in those with LAA stroke. The differences between the relative gene expression levels during acute stroke and at the 1-year follow-up were more pronounced in patients with cryptogenic stroke with no cardiovascular risk factors. The expression changes of inflammatory genes in whole blood and miRNAs in the serum differ in patients with cryptogenic and LAA stroke. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses several reports within the journal on topics including factors associated with social problems in young perinatal stroke patients, distribution of risk factors in stroke patients of different age groups and ischemic stroke.

Introduction. In Estonia, stroke is in a third place of death causes. It is important to pay more attention to informing the public about stroke. It will help to speed up hospitalization time. For the patient, it is important, that their relatives know, what to do, when stroke occurs. It is important to educate children how to act in case of stroke. The aim of this study was to evaluate the awareness of stroke among school children in Tartu county. Methods. To assess students' knowledge about stroke, questionnaire were used. Statistical analysis were made using StatCrunch website. Results. A total of 526 6 to 11th year students participated. 11 different schools from Tartu city or county took part in the program. Half of the students thought that stroke is a vascular disorder of the brain. Most of students knew that stroke appears suddenly. Speech disorder, one side of the face paralysis and one side of the body or limb paralysis were considered as stroke symptoms. Students thought that stroke risk factors are high blood pressure, insufficient physical activity, smoking, arrhythmia, and abuse of alcohol. 97% of students knew that when stroke occurs, there is need to call ambulance immediately. Conclusion. It was surprising that the students knowledge about stroke were so good. Such educational programs should be continuous to promote healthy lifestyle, prevent cardiovascular diseases, to recognize stroke symptoms and to encourage people to seek immediate help in case of stroke. [ABSTRACT FROM AUTHOR]

Introduction. In Estonia, intravenous thrombolysis (ivTP) has been available for acute stroke treatment since 2003 and thrombectomy from 2009. The population of Estonia is 1.3 million inhabitants. We have 4 stroke units (3 per million), 6 ivTP centers, 3 centers providing thrombectomy (two of them 24/7). In 2017, 21% of all ischaemic stroke patients in Estonia received revascularisation treatment (ivTP or thrombectomy). Materials and methods. A study assessing the clinical characteristics and outcome of patients treated with thrombectomy from 2015 to 2017 in two main interventional stroke centers (North-Estonian Medical Center and Tartu University Clinics) in Estonia was conducted using the SITS registry. Patients with large artery occlusion treated with intraveonous thrombolysis and thrombectomy or only by thrombectomy were included. Results. During the study period, 287 patients were included with mean age 72 years and median NIHSS on admission of 17 points. The majority of patients (72%) received ivTP treatment prior to thrombectomy. A TICI score of 2b or 3 was reached in 77% of patients. The proportion of patients with mRS 0-2 at 90 days was 32%. Also the 90-day mortality was 32%. Conclusion. The outcome of stroke patients treated with thrombectomy in Estonia is comparable to previous studies. The overall availability of acute stroke treatments is good, but a governmental strategy is needed to further improve the treatment of stroke in Estonia. [ABSTRACT FROM AUTHOR]