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 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 <0.001 and fewer cerebrovascular risk factors. In patients with PCS versus ACS, parenchymal hematoma occurred in 3.2% versus 7.9%, ATE (95% CI): −4.7% (−6.3% to 3.0%); SICH SITS-MOST in 0.6% versus 1.9%, ATE: −1.4% (−2.2% to −0.7%); SICH NINDS in 3.1% versus 7.8%, ATE: −3.0% (−6.3% to 0.3%); SICH ECASS II in 1.8% versus 5.4%, ATE: −2.3% (−5.3% to 0.7%). In PCS versus ACS, 3-month outcomes (70% data availability) were death 18.5% versus 20.5%, ATE: 6.0% (0.7%–11.4%); modified Rankin Scale score 0–1, 45.2% versus 37.5%, ATE: 1.7% (−6.6% to 3.2%); modified Rankin Scale score 0–2, 61.3% versus 49.4%, ATE: 2.4% (3.1%–7.9%). Meta-analysis showed relative risk for SICH in PCS versus ACS being 0.49 (95% CI, 0.32–0.75). 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.

The etiology of ischemic stroke is multifactorial. Although receiving less emphasis, genetic causes make a significant contribution to ischemic stroke genesis, especially in early-onset stroke. Several stroke classification systems based on genetic information corresponding to various stroke phenotypes were proposed. Twin and family history studies, as well as candidate gene approach, are common methods to discover genetic causes of stroke, however, both have their own limitations. Genome-wide association studies and next generation sequencing are more efficient, promising and increasingly used for daily diagnostics. Some monogenic disorders, despite covering only about 7% of stroke etiology, may cause well-known clinical manifestations that include stroke. Polygenic disorders are more frequent, causing about 38% of all ischemic strokes, and their identification is a rapidly developing field of modern stroke genetics. Current advances in human genetics provide opportunity for personalized prevention of stroke and novel treatment possibilities. Genetic risk scores (GRS) and extended polygenic risk scores (PRS) estimate cumulative contribution of known genetic factors to a specific outcome of stroke. Combining those scores with clinical information and risk factor profiles might result in better primary stroke prevention. Some authors encourage the use of stroke gene panels for stroke risk evaluation and further stroke research. Moreover, new biomarkers for stroke genetic causes and novel targets for gene therapy are on the horizon. In this article, we summarize the latest evidence and perspectives of ischemic stroke genetics that could be of interest to the practitioner and useful for day-to-day clinical work.