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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— Posterior circulation stroke (PCS) accounts for 5% to 19% of patients with acute stroke receiving intravenous thrombolysis. We aimed to compare safety and outcomes following intravenous thrombolysis between patients with PCS and anterior circulation stroke (ACS) and incorporate the results in a meta-analysis. Methods— We included patients in the Safe Implementation of Treatments in Stroke Thrombolysis Registry 2013 to 2017 with computed tomography/magnetic resonance angiographic occlusion data. Outcomes were parenchymal hematoma, symptomatic intracerebral hemorrhage (SICH) per SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study), ECASS II (Second European Co-operative Stroke Study) and NINDS (Neurological Disorders and Stroke definition), 3-month modified Rankin Scale score, and death. Adjustment for SICH risk factors (age, sex, National Institutes of Health Stroke Scale, blood pressure, glucose, and atrial fibrillation) and center was done using inverse probability treatment weighting, after which an average treatment effect (ATE) was calculated. Meta-analysis of 13 studies comparing outcomes in PCS versus ACS after intravenous thrombolysis was conducted. Results— Of 5146 patients, 753 had PCS (14.6%). Patients with PCS had lower median National Institutes of Health Stroke Scale: 7 (interquartile range, 4–13) versus 13 (7–18), P Conclusions— The risk of bleeding complications after intravenous thrombolysis in PCS was half that of ACS, with similar functional outcomes and higher risk of death, acknowledging limitations of the National Institutes of Health Stroke Scale for stroke severity or infarct size adjustment.

Background: Neurological deterioration (ND) after mechanical thrombectomy (MT) of acute ischemic stroke (AIS) in anterior circulation is an important complication associated with a poor outcome. Moreover, evident causes of ND may remain unexplained (UnND). Objective: We sought to evaluate the association of the systolic blood pressure (SBP) parameters before MT, during MT, and during a 24-h period after MT with UnND. Methods: We analyzed 382 MT-treated AIS patients in two stroke centers from 2017 to 2019. The patients with unsuccessful recanalization and/or with symptomatic intracerebral hemorrhage after MT were excluded. Multivariate logistic regression analysis was used to identify the SBP parameters that predict UnND. Results: There were 5.9% patients with UnND within 24 h after MT among patients with successful recanalization what comprises 4.9% of all patients who had undergone MT. SBP > 180 mmHg on admission (odds ratio (OR): 4, 95% confidence interval (CI): 1.6–10, p = 0.004) and a drop of SBP below100 mmHg during MT (OR: 4.7, 95% CI: 1.3–17, p = 0.019) were associated with UnND occurrence within 7 days without a significant association with UnND within 24 h. UnND within 7 days was predicted by the episodes of SBP exceeding the level of SBP observed before the groin puncture and occurring over the first 2 h following recanalization (OR: 5, 95% CI: 1.3–19, p = 0.021), an increase of SBP of more than 20% within 2–24 h after MT (OR: 3.4, 95% CI: 1.1–10, p = 0.035), and a drop of SBP below 100 mmHg after MT (OR: 3.2, 95% CI: 1.1–9, p = 0.039). Conclusion: The association between the SBP parameters and UnND depends on the treatment period and the time of UnND occurrence. The J/U resembling relationship between SBP and UnEND was established during a 24-h period after MT.

Background: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, reduced admissions for cerebrovascular events were identified, but acute ischaemic stroke (AIS) has remained one of the leading causes of death and disability for many years. The aim of this article is to review current literature data for multidisciplinary team (MDT) coordination, rational management of resources and facilities, ensuring timely medical care for large vessel occlusion (LVO) AIS patients requiring endovascular treatment during the pandemic. Methods: A detailed literature search was performed in Google Scholar and PubMed databases using these keywords and their combinations: acute ischaemic stroke, emergency, anaesthesia, airway management, mechanical thrombectomy, endovascular treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19. Published studies and guidelines from inception to April 2021 were screened. The following nonsystematic review is based on a comprehensive literature search of available data, wherein 59 were chosen for detailed analysis. Results: The pandemic has an impact on every aspect of AIS care, including prethrombectomy, intraprocedural and post-thrombectomy issues. Main challenges include institutional preparedness, increased number of AIS patients with multiorgan involvement, different work coordination principles and considerations about preferred anaesthetic technique. Care of these patients is led by MDT and nonoperating room anaesthesia (NORA) principles are applied. Conclusions: Adequate management of AIS patients requiring mechanical thrombectomy during the pandemic is of paramount importance to maximise the benefit of the endovascular procedure. MDT work and familiarity with NORA principles decrease the negative impact of the disease on the clinical outcomes for AIS patients.

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 and Objectives: The aim of this survey was to assess the impact of epidural analgesia on post-partum back pain in post-partum women. Materials and Methods: The questionnaire was completed by post-partum women during the first days after delivery. Six months later, the women were surveyed again. The response rate was 70.66%, a total of 212 cases were included in the statistical analysis. The statistical analysis of the data was conducted using SPSS&reg, Results. Seventy-nine (37.26%) women received epidural analgesia, 87 (41.04%) intravenous drugs, and 46 (21.7%) women gave birth without anesthesia. The prevalence of post-partum back pain was observed in 24 (30.38%) women of the epidural analgesia group, in 24 (27.58%) subjects of the intravenous anesthesia group, and in 14 (30.43%) women attributed to the group of subjects without anesthesia. The correlation between post-partum back pain and the type of anesthesia was not statistically significant (p = 0.907). Six months later, the prevalence of back pain was found in 31.65% of women belonging to the epidural analgesia group, in 28.74% of women with intravenous anesthesia, and in 23.91% of women without anesthesia. The correlation between complaints of back pain six months after delivery and the type of anesthesia applied was not statistically significant (p = 0.654). Conclusions. The labor pain relief technique did not trigger the increased risk of back pain in the early post-partum period and six months after delivery.

Objectives To determine the temporal changes in incidence rates of multiple sclerosis (MS) over the past 15 years in Lithuania with prediction up to 2020, and to estimate female‐to‐male sex ratio and its changes among MS patients. Materials and Methods We conducted a descriptive incidence study. The crude incidence rates (CIR) were calculated using 15‐year period, sex, age‐groups, and the number of newly registered MS patients. Standardized incidence rates (SIR) were calculated using European standard in order to evaluate the influence of resident structure changes on incidence of MS during the last 15 years. The data were processed using Minitab set to estimate a linear trend model for the temporal changes of 16 parameters. Results The data showed a substantial growth of the incidence rate of MS in Lithuania during the period of 2001–2015. In 2001, MS was diagnosed to 162 new individuals, whereas 343 new cases of MS were diagnosed in 2015. During 2001–2015, the incidence of MS was on average 6.5 (95% CI 5.70–7.30) cases per 100,000 residents, and 4.9 (95% CI 4.46–5.34) and 8.1 (5.86–9.34) for 100,000 male and female, respectively. Female‐to‐male sex ratio in MS in Lithuania had a tendency to increase over the period. Females were affected from 1.5 to 2 times more often than males. Conclusions In 2020, the incidence rate of MS is estimated to reach 13 cases per 100,000 persons and females are expected to be diagnosed with MS two times more often than males.

Introduction: Despite the proven efficacy of anti-thrombotic, lipid-lowering, anti-hypertensive therapies and lifestyle modification changes for secondary ischemic stroke prevention, the risk of recurrent stroke, coronary events and vascular death remains substantial even for patients treated with high rates of established secondary preventive medications. Methods: In the present review, we summarize available literature data on the association between systemic inflammation and symptomatic atherosclerosis including recurrent cerebral ischemia. We also highlight the potential role of colchicine in the suppression of atherosclerosis-induced inflammation, plaque stabilization and thromboembolism prevention. Results: Accumulating evidence suggests that inflammation is of key importance in the pathophysiology of atherosclerotic plaque de-stabilization and thromboembolism, with inflammatory cells being involved in all stages of atherosclerosis development. Therefore, anti-inflammatory therapies targeting the atherosclerotic plaque inflammation may be important contributors in plaque stabilization and in the prevention of thromboembolic events. Colchicine is known to have multiple anti-inflammatory properties including inhibition of microtubule polymerization, leading to reduced secretion in monocyte-macrophages. Currently the randomized controlled CONVINCE trial is enrolling stroke patients to evaluate the effect of a daily low-dose of colchicine in reducing the rate of recurrent stroke and major vascular events. Conclusion: Inflammatory pathways seem to be key mediators in the development of atherosclerotic process, atheromatous plaque destabilization and thromboembolism. Colchicine as a novel therapeutic agent could be a safe and effective inhibitor of the inflammation cascade in patients with extra- or intracranial atherosclerosis or arteriolosclerosis, resulting in reduced vascular events.

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.

Atrial fibrillation is the most common cardiac arrhythmia and a known risk factor for cerebrovascular stroke. Atrial fibrillation and longstanding hypertension may produce ischemic lesions leading to progressive cognitive impairment. The impact of atrial fibrillation alone on cognitive impairment has not been evaluated. Our objective was to compare cognitive function, quality of life, psychological distress, and impulsiveness in people with atrial fibrillation and a matched control group.The study included 60 patients. The first group of patients were ≥55 years of age, with ≥5 years history of atrial fibrillation, without hypertension (or with well-controlled hypertension), without previous dementia, compared with a matched group of 30 healthy control participants. Demographic and clinical characteristics were recorded. Subjects underwent the following rating scales: Mini-Mental State Examination, Hospital Anxiety and Depression, Heart Quality of Life, and Barratt Impulsiveness Scale.In the atrial fibrillation group there were 63% male (n = 19) and 37% female (n = 11) patients; the control group was 33% male (n = 10) and 67% female (n = 20). Age range was from 55 to 81 years in both groups, mean = 63.9 years (±6.4) in the atrial fibrillation group and 66.1 years (±8.0) in controls. In the atrial fibrillation group, 23.3% had primary or general education, college - 23.3% and university - 53.3%; in the control group - 20%, 23.3%, and 56.7%, respectively. Mini-Mental State Examination score was 27.6 (±1.6) in the atrial fibrillation group vs 29.5 (±0.73) in the control group (P .0001). Anxiety disorders were observed in 20 patients (66.7%) in atrial fibrillation vs 8 patients (26.67%) in the control group (P = .009). Heart Quality of Life mean score was 1.4 (±0.65) in the atrial fibrillation and 2.6 (±0.35) in the control group (P .0001). Physical subscale mean scores were 1.4 (±0.74) in atrial fibrillation vs 2.8 (±0.18) in the control group (P .0001).Individuals with atrial fibrillation are more likely to develop anxiety disorder. Cognitive status is significantly lower in the atrial fibrillation group. In comparison with healthy subjects, individuals with atrial fibrillation have worse quality of life.

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

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.

Background Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged Key hypotheses/aims (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

Stroke is a major burden to patients and society, and resources spent on stroke research must be used efficiently and produce good value in terms of improvements in human health. However, many instances of poor value from stroke research funding have resulted from the way in which stroke research topics have been chosen and how studies have been designed, conducted, analysed, regulated, managed, disseminated, or reported. A cooperative effort of European stroke researchers aimed to identify sources of inefficiency and waste, recommend approaches to increase value, and highlight examples of best practice in stroke research. Evidence suggests that progress has been made, but there is room for much improvement; researchers, funders, regulators, and other stakeholders in stroke research might consider these recommendations when planning new research.

Background and purpose The outcome of thrombolysis for early morning and sleep time strokes may be worse because of uncertainty of stroke onset time or differences in logistics. The aim of the study was to analyze if stroke outcome after intravenous thrombolysis differs depending on time of day when the stroke occurs. Methods The data collected in the Safe Implementation of Treatments in Stroke − Eastern Europe (SITS-EAST) Registry between September 2000 and December 2011 were used. Strokes were categorized as night-time 00:00–07:59, day-time 08:00–15:59 and evening-time 16:00–23:59 and were compared in terms of several outcome measures. All results were adjusted for baseline differences. Results A total of 8878 patients were enrolled: 18% had night-time, 54% day-time and 28% evening-time strokes. Onset-to-treatment time in patients with night-time strokes was 10 min longer than in day-time and evening-time strokes (P

Human gait is cyclic process, which is affected by various neurological disorders like Parkinson's disease (PD) or multiple sclerosis (MS). Instrumented gait analysis facilitate monitoring and diagnosing motor deficiencies; it may serve as a tool for clinicians evaluating the patients. This study aims at finding biomechanical parameters that allow separating pathological gaits via application of inertial sensors to capture the gait. The experiment involved 33 subjects divided in three groups PD, MS and healthy controls (CO). The analysis showed the statistically significant difference between stride time of the right leg in MS and CO groups, left stride time between PD and CO, stance time difference between PD and CO group, right and left leg. Hip flexion and extensions amplitudes difference was between CO and PD group, left hip flexion and extension.

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:center dot Functional status at 6-months, measured by the modified Rankin Scale, and center dot vascular death, myocardial infarction or stroke during the first 6-months.Secondary outcome variables:Secondary effect variables include center dot the Barthel index (functional status)center dot EuroQol (quality of life) and center dot Mini-mental state examination (cognition) at 6-months center dot 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.

Introduction: Shorter door-to-needle time (DNT) improves treatment efficacy in acute ischemic stroke (AIS) patients. Still, there are groups of patients at increased risk of longer DNT. The goal of our study was to determine temporal trends of DNT. The second goal was to identify if baseline characteristics of patients treated with intravenous thrombolysis changed throughout the years and if such change (e.g. treating older patients) could have affected DNT. Methods: Prospectively collected data from the Safe Implementation of Treatments in Stroke - EAST (12 Central/Eastern European countries) registry between January 2005 and August 2013 were analyzed. Baseline patient characteristics over period 2005-2013 were analyzed descriptively and using ANOVA. DNT and association between DNT and the patient characteristics were analyzed using linear logistic regression. Obtained regression coefficients and descriptive statistics were used to simulate average DNT values in individual years during 2005-2013. Several simulations were performed (e.g. for patients above 80 years). Results: Altogether, all 13401 patients treated with thrombolysis within 4.5 hours of symptom onset between January 2005 and August 2013 with available DNT were analyzed. Mean DNT during 2005-2013 was 74.4min with slightly improving trend over time. We found almost 6-fold increased proportion of octogenarians in 2013 compared to 2005. Patients with lower and higher NIHSS, prestroke mRS 0-2, arriving sooner to hospital, and treated in a center with less experience ( Conclusions: Although DNT is improving, it remains long especially for some subgroups of patients, e.g. those arriving early to hospital after symptom onset. Every AIS patient should be treated as fast as possible.

Objectives. Impairment of long-term recall may worsen everyday functioning of patients with epilepsy even if the standard short-term or delayed recall tests do not show significant abnormalities. We evaluated prospectively the decay of memory between delayed and long-term recall in patients with temporal lobe epilepsy (TLE) and controls with the aim of identifying the determinants of long-term memory impairment. Methods. Seventy patients with TLE and 59 controls underwent neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions at visit 1. Long-term verbal and nonverbal memory was tested with the same word list, verbal logical story, and Rey–Osterrieth complex figure test 4 weeks later at visit 2. The decay in memory was estimated as information recalled at visit 2 as a percentage of the delayed recall at visit 1. Results. Frequent seizures (P4 per month) during the study period were related to poor long-term recall, even for those patients who did relatively well on delayed recall tests. On all long-term memory tests, patients with complex partial and/or secondary generalized seizures did significantly worse than patients with simple partial seizures. The presence of interictal generalized or focal temporal epileptiform activity was associated with more accelerated forgetting of the word list and complex figure. Multiple regression analysis confirmed that number of complex partial seizures, age of patient, and abnormal interictal EEG are significant predictors of accelerated forgetting. Conclusions. Uncontrolled seizures, especially with ictal impairment of consciousness, can be a significant factor in the accelerated decay of memory, although subclinical interictal epileptiform EEG activity may also be relevant. 2005 Elsevier Inc. All rights reserved.

Summary Headache is the common symptom in patients with cervical artery dissection. However, it rarely occurs in isolation, without focal neurological signs, and even more rarely mimics migraine. We present a clinical case of young woman with new severe throbbing unilateral headache which started one week after cervical manipulative therapy. No history of migraine was present. Vertebral artery dissection was diagnosed after duplex ultrasound and CT angiography. Local symptoms and signs were absent, and diffusion-weighted MRI did not show any acute brain ischemic lesions. Throbbing headache gradually resolved in 10 days. Follow-up 5 months later showed near-complete normalization of lumen and flow of dissected vertebral artery. The possibility of extracranial dissection should be considered in patients with first attack of migraine-like hemicrania, especially if cervical manipulations or trauma occurred recently.

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.

Background&Purpose: A recent meta-analysis investigating the association between statin pretreatment and early outcomes in patients with AIS indicated that pre-stroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage (sICH). We sought to investigate the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT. Subjects&Methods: We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) on consecutive AIS patients treated with IVT during a seven-year period. We used three widely accepted definitions for sICH from NINDS-rtPA-Stroke Study, ECASS II trial and SITS registry. Dramatic clinical recovery (DCR) within 24 hours was defined as reduction in the baseline NIHSS-score of ≥10 points. Favorable functional outcome (FFO) at three months was defined as modified Rankin Scale score of 0-1. Results: We analyzed a total of 1660 AIS patients (mean age 67±13 years, median baseline NIHSS-score 11 points, interquartile range 5-16). Patients with statin pretreatment (n=373, 23%) had higher (p=0.019) baseline stroke severity compared to cases who had not received any statin at symptom onset. After adjusting for demographics, baseline stroke severity, onset-to-treatment time, history of previous stroke, risk factors, and admission blood pressure levels, statin pretreatment was not associated with a higher likelihood of sICH defined by the NINDS (OR: 1.41; 95%CI: 0.83-2.39; p=0.201), ECASS II (OR: 1.13; 95%CI: 0.60-2.14; p=0.712) or SITS (OR: 1.89; 95%CI: 0.75-4.77; p=0.178) criteria. Statin pretreatment was not related to three-month all-cause mortality (OR: 0.92; 95%CI: 0.57-1.49; p=0.741) or three-month FFO (OR: 0.81; 95%CI: 0.52-1.27; p=0.364). Statin pretreatment was independently associated with a higher odds of DCR (OR: 1.91; 95%CI: 1.25-2.92; p=0.003). Conclusions: Our findings indicate that statin therapy at symptom onset is not associated with adverse outcomes in AIS patients treated with IVT, while statin pretreatment almost doubles the likelihood of DCR during the first hours following tPA-infusion.

Background and Purpose— The SEDAN score is a prediction rule for assessment of the risk of symptomatic intracerebral hemorrhage (SICH) per the European Cooperative Acute Stroke Study (ECASS) II definition in patients with acute ischemic stroke treated with intravenous thrombolysis. We assessed the performance of the score in predicting SICH per the ECASS II and Safe Implementation of Treatments in Stroke Monitoring Study (SITS-MOST) definitions in the SITS–International Stroke Thrombolysis Register (SITS-ISTR). Methods— We calculated the SEDAN score in 34 251 patients with complete data, enrolled into the SITS-ISTR. The risk for SICH by both definitions was calculated per score category. Odds ratios for SICH per point increase of the score were obtained using logistic regression. The predictive performance was assessed using area under the curve of the receiver operating characteristic (AUC-ROC). Results— The predictive capability for SICH per ECASS II was moderate at AUC-ROC=0.66. With rising scores, there was a moderate increase in risk for SICH per ECASS II (odds ratio, 1.65 per point; 95% confidence interval, 1.59–1.72; P P Conclusions— In this very large data set, the predictive and discriminatory performances of the SEDAN score were only moderate for SICH per ECASS II and low for SICH per SITS–Monitoring Study.

Introduction: There is no conclusive evidence if the association between status of brain artery and risk of intracerebral hemorhage after intravenous thrombolysis (IVT) exists. Therefore, we explored if the hyperdense cerebral artery sign (HCAS) on CT or CT-angiography (CTA)-evidenced occlusion at baseline and follow-up after intravenous thrombolysis (IVT) is associated with symptomatic intracerebral hemorrhage (SICH). Methods: The study population was the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) database with all stroke patients between February 2003 and December 2011 receiving IVT up to 4.5 hours after symptom onset. SICH was distinguished as per NINDS, ECASS II and SITS-MOST definitions. Arterial patency at baseline and on follow-up was assessed by the presence of HCAS on CT or by CTA. Logistic regression was used to adjust for differences in the following baseline variables: NIHSS baseline, age, sex, onset to treatment time, weight, early ischemic changes on CT, systolic blood pressure, glucose, actilyse dose, treatment with anticoagulation or antiplatelets, stroke subtype by ICD classification, history of hypertension, diabetes mellitus, atrial fibrillation, congestive heart failure, and previous stroke. Results: Of 8878 cases, baseline CT scans revealed HCAS in 1553 (19%) of 8375 patients and CTA-evidenced occlusion in 1606 (57%) of 2809 cases. On follow-up CT after IVT, HCAS persisted in 477 (36%) of 1327 cases and CTA-evidenced occlusion persisted in 185 (45%) of 411 cases. After adjustment, SICH per the NINDS definition was independently predicted at baseline both by the presence of HCAS (OR 1.57, 95%CI 1.20 to 2.05) and occlusion on CTA (OR 2.87, 95%CI 1.69 to 4.87). Also SICH per the ECASS II definition was independently predicted by the presence of occlusion on CTA (OR 2.61, 95%CI 1.34 to 5.05). In contrast, at follow-up neither persistent HCAS nor persistent CTA-evidenced occlusion was associated with SICH per any definition. Conclusions: In stroke patients receiving IVT, presence of clot at admission was an independent predictor of SICH. Persistent occlusion after IVT was not, however, associated with SICH.

Background The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's discretion. Aim Our aim was to evaluate safety and effectiveness of intravenous alteplase in patients not fully adhering to the drug license compared with those treated strictly according to the license in Central and Eastern Europe. Methods We analyzed the data contributed to Safe Implementation of Thrombolysis in Stroke registry from nine countries between February 2003 and February 2010. Statistical analysis included multivariate logistic regression. Results Of 5594 consecutive patients, 1919 patients (34·3%) not fully adhered to the license. The most frequent deviations were: time-to-treatment >3 h (13·1%), use of intravenous antihypertensives (8·3%), age >80 years (7·3%), oral anticoagulation (4·2%), a previous stroke with concomitant diabetes (3·9%), and previous stroke 3 h was an independent predictor of unfavorable outcome (odds ratio 1·32; 95% confidence interval: 1·01–1·71). Conclusion Our findings show that patients not fully adhering to the European license are not at increased risk of symptomatic intracranial haemorrhage but achieve less favorable outcome. Some contraindications appear more redundant than others. However, the final conclusions about safety and effectiveness should be based on the results of ongoing randomized trials.

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 P P 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.

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.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 ISRCTN13643354.2029 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; p0·0001). 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.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.South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.

Summary: Purpose: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions. Methods: During this multicenter, double-blind, placebocontrolled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis. Results: Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p = 0.0023) and 600 mg/day (p = 0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p = 0.0038) and 600 mg/day (p = 0.0141). Adverse events that appeared doserelated included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs. Conclusions: In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED. Key Words: Epilepsy— Partial-onset seizures—Lacosamide—Antiepileptic drugs— Randomized controlled trials. Lacosamide (SPM 927, formerly harkoseride), the R-enantiomer of 2-acetamido-N-benzyl-3-methoxypropionamide, is a new chemical entity being developed as an oral formulation (Bialer et al., 2004) for the treatment of epilepsy and neuropathic pain. In addition, an intravenous formulation is being developed for short-term replacement of oral lacosamide in patients with partial-onset seizures. Based on recent experimental studies, lacosamide appears to have a dual mode of action—enhancement of sodium-channel slow inactivation and modulation of collapsin response mediator protein-2 (CRMP-2) (Stoehr et al., 2006)—both of which are novel mechanisms for an antiepileptic drug (AED). Without affecting fast inactivation, lacosamide appears to selectively enhance sodium

Background: Common carotid artery intima-media thickness (cIMT) is an accepted ultrasound marker of subclinical atherosclerosis. It is argued that increase in cIMT may also reflect nonatherosclerotic thickening, thus, lumen diameter could be taken into account. A common approach to account for lumen diameter is wall-to-lumen ratio (WLR), however, its precise relations to cardiovasular risk factors remain unclear. We attempted to compare the contribution of cardiovascular risk factors to the variance in cIMT and WLR. Methods: Noninvasive measurements of cIMT and WLR were made with high-resolution ultrasonography in 5,983 subjects. They were male aged 40 to 55 and female aged 50 to 65 without previous cardiovascular events, participating in the Lithuanian High Cardiovascular Risk primary prevention program. We performed a multiple linear regression on cIMT and WLR incorporating traditional and less traditional cardiovascular risk factors. Results: Mean left and right cIMT was 0.66 ± 0.12 mm and 0.65 ± 0.11 mm respectively, whereas mean WLR was 0.092 ± 0.015. We found that cardiovascular risk factors could explain 8.9% of left cIMT and 8.3% of right cIMT. Strikingly, traditional and less traditional factors (namely age, male sex, LDL/HDL ratio, mean arterial blood pressure and triglyceride) contributed to a significantly larger proportion of WLR variance, amounting to 14.2%. Conclusions: Adjustment for carotid lumen diameter in analyses evaluating common carotid artery intima-media thickness should be considered. The precise role of WLR as an ultrasound marker of subclinical atherosclerosis remains a topic of interest for future research.

Perioperative carotid cross-clamping might induce low stump pressures as well as hypoperfusion of the middle cerebral artery. In this study blood flow velocities in the middle cerebral artery were compared with intraoperative measurements of the poststenotic carotid blood pressure.Forty-one patients with internal carotid artery stenosis were operated on without shunting, under general anesthesia. Poststenotic carotid pressures and middle cerebral artery flow velocities were measured before and during cross-clamping. The hemodynamic responses to preoperative carotid compressions and intraoperative cross-clamping were evaluated.In seven patients the poststenotic carotid blood pressure decreased on clamping despite unchanged or even increased middle cerebral artery blood flow velocities. In all other patients, pressure changes were significantly correlated to the decrease in middle cerebral artery blood flow velocities. Autoregulatory blood flow velocity responses after preoperative common carotid artery compression were not reproducible by cross-clamping.Stump blood pressure measurements may not reflect middle cerebral artery perfusion in about 20% of thrombendarterectomies performed under general anesthesia. A possible explanation might be dimished cerebral autoregulation and changes in collateral flow distributions.

Purpose Investigations of the posterior cerebral arteries (PCA) by transcranial Doppler sonography (TCD) may be less reliable than investigations of the anterior part of the circle of Willis. Nevertheless, a true PCA may be identified by manual compression of the proximal common carotid artery (CCA) during TCD. Therefore, we used CCA compression in clinically indicated TCD studies and assessed retrospectively its risks and prospectively its benefits for PCA evaluations. Methods Using the transtemporal approach, we prospectively assessed flow velocities in posteriorly located blood vessels in 180 consecutive patients before and during CCA compression. The complications of CCA compression were retrospectively reviewed in all 3,383 clinical TCD investigations performed over an 8-year period. Results Decreased flow velocities during ipsilateral CCA compression occurred in 17% of patients. A PCA-like vessel with perfusion from the carotid artery or PCA supply from the carotid circulation was unmasked. Mixed distal PCA support by the posterior communicating artery and proximal PCA could not be shown by TCD. Transient cerebral symptoms occurred in less than 0.4% of the 3,383 retrospectively reviewed TCD investigations; no other adverse effects were seen. Conclusions TCD without CCA compression may lead to false identification of the PCA. Since transient cerebral symptoms during CCA compression are rare, CCA compression can be used when a clinical TCD investigation of intracranial collateral blood flow compensation is indicated or when the identification of a cerebral artery is uncertain. © 2000 John Wiley & Sons, Inc. J Clin Ultrasound 28:452–460, 2000

ANGIOTENSIN RECEPTOR BLOCKADE IN ACUTE STROKE : AN UPDATE ON THE SCANDINAVIAN CANDESARTAN ACUTE STROKE TRIAL (SCAST)