Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

Background and Purpose-Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. Methods-All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (nϭ1104). After excluding basilar artery occlusions (nϭ119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. Results-One or more license contraindications to thrombolysis was present in 51% of our patients (nϭ499). The most common of these were age Ͼ80 years (nϭ159), mild stroke National Institutes of Health Stroke Scale score Ͻ5 (nϭ129), use of intravenous antihypertensives prior to treatment (nϭ112), symptom-to-needle time Ͼ3 hours (nϭ95), blood pressure Ͼ185/110 mm Hg (nϭ47), and oral anticoagulation (nϭ39). Age Ͼ80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. Conclusions-Off-license thrombolysis was not associated with poorer clinical outcome, except for age Ͼ80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available. (Stroke.

which has the only neurological emergency room with 24/7 service in a catchment area of 1.5 million inhabitants. We retrospectively analyzed all consecutive primary Background and Purpose-Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients.

I schemic stroke remains a leading cause of death and disability worldwide.1 Planning cost-effective preventive strategies requires precise knowledge of stroke risk factors. 2 Approximately 10% of ischemic strokes occur at ages <45 years, 3 with major long-term socioeconomic con sequences. 4 Stroke prevention results in greater quality-weighted life-yearBackground and Purpose-Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood. Methods-The Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large multinational European cohort of patients with cerebrovascular events aged 18 to 55 years to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke or transient ischemic attack, we studied age-and sex-specific prevalences of various risk factors. Results-Among 4467 patients (median age, 47 years; interquartile range, 40-51), the most frequent well-documented and modifiable risk factors were smoking (55.5%), physical inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and obesity (22.3%). Modifiable less well-documented or potentially modifiable risk factors like high-risk alcohol consumption (33.0%) and short sleep duration (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in women. Women were more often physically inactive, most pronouncedly at ages <35 years (18-24: 38.2%; 25-34: 51.7%), and had high proportions of abdominal obesity at age 25 years or older (74%). Physical inactivity, arterial hypertension, dyslipidemia, obesity, and diabetes mellitus increased with age. Conclusions-In this large European cohort of young patients with acute ischemic cerebrovascular events, modifiable risk factors were highly prevalent, particularly in men and older patients. These data emphasize the need for vigorous primary and secondary prevention measures already in young gain in younger patients than in elderly patients, but has received less attention.In the general population and in patient cohorts, risk factor profiles changed with increasing age. 5,6 Most studies of stroke patients aged <50 years were small and methodologically heterogeneous. [7][8][9][10] In the largest single-center study including 1008 ischemic stroke patients aged 15 to 49 years, 7 the most common risk factors were dyslipidemia (60%), smoking (44%), and arterial hypertension (39%), with accumulation in men and increasing age. However, only scarce data exist on the prevalence and risk potential of lifestyle risk factors such as physical inactivity, obesity, 7,8,11 body mass index, waist circumference, 12 and sleep pattern 13,14 in the young. The Stroke in Young Fabry Patients (sifap1) study 15 prospectively recruited a large multinational European cohort of patients aged 18 to 55 years with cerebrovascular event (CVE) to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke and transient ischemic attack (TIA), we investigate...

Background and Purpose-Data on mortality and its prognostic factors after an acute ischemic stroke in young adults are scarce and based on relatively small heterogeneous patient series. Methods-We analyzed 5-year mortality data of all consecutive patients aged 15 to 49 with first-ever ischemic stroke treated at the Department of Neurology, Helsinki University Central Hospital, from January 1994 to September 2003. We followed up the patients using data from the mortality registry of Statistics Finland. We used life table analyses for calculating mortality risks. Kaplan-Meier method allowed comparisons of survival between clinical subgroups. We used the Cox proportional hazard model for identifying predictors of mortality. Stroke severity was measured using the National Institutes of Health Stroke Scale and the Glasgow Coma Scale. Results-Among the 731 patients (mean age, 41.5Ϯ7.4 years; 62.8% males) followed, 78 died. Cumulative mortality risks were 2.7% (95% CI, 1.5% to 3.9%) at 1 month, 4.7% (3.1% to 6.3%) at 1 year, and 10.7% (9.9% to 11.5%) at 5 years with no gender difference. Those Ն45 years of age had lower probabilities of survival. Among the 30-day survivors (nϭ711), stroke caused 21%, cardioaortic and other vascular causes 36%, malignancies 12%, and infections 9% of the deaths. Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes, increasing age, and large artery atherosclerosis causing the index stroke independently predicted 5-year mortality adjusted for age, gender, relevant risk factors, stroke severity, and etiologic subtype. Conclusions-Despite the overall low mortality after an ischemic stroke in young adults, several recognizable subgroups had substantially increased risk of death in the long term.

Background and Purpose-The purpose of this study was to provide a simple and practical clinical classification for the etiology of intracerebral hemorrhage (ICH). Methods-We performed a retrospective chart review of consecutive patients with ICH treated at the Helsinki University Central Hospital, January 2005 to March 2010 (nϭ1013). We classified ICH etiology by predefined criteria as structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). Clinical and radiological features and mortality by SMASH-U (Structural lesion, Medication, Amyloid angiopathy, Systemic/other disease, Hypertension, Undetermined) etiology were analyzed. Results-Structural lesions, namely cavernomas and arteriovenous malformations, caused 5% of the ICH, anticoagulation 14%, and systemic disease 5% (23 liver cirrhosis, 8 thrombocytopenia, and 17 various rare conditions). Amyloid angiopathy (20%) and hypertensive angiopathy (35%) were common, but etiology remained undetermined in 21%.Interrater agreement in classifying cases was high (, 0.89; 95% CI, 0.82-0.96). Patients with structural lesions had the smallest hemorrhages (median volume, 2.8 mL) and best prognosis (3-month mortality 4%), whereas anticoagulationrelated ICHs were largest (13.4 mL) and most often fatal (54%). Overall, median ICH survival was 5 1 ⁄2 years, varying strongly by etiology (PϽ0.001). After adjustment for baseline characteristics, patients with structural lesions had the lowest 3-month mortality rates (OR, 0.06; 95% CI, 0.01-0.37) and those with anticoagulation (OR, 1.9; 1.0 -3.6) or other systemic cause (OR, 4.0; 1.6 -10.1) the highest. Conclusions-In our patients, performing the SMASH-U classification was feasible and interrater agreement excellent. A plausible etiology was determined in most patients but remained elusive in one in 5. In this series, SMASH-U based etiology was strongly associated with survival. (Stroke. 2012;43:2592-2597.)

No abstract

No abstract