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Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbased ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.The full document which is available as online supplement contains background, issues, conclusions and references used to establish ESO-Karolinska recommendations for each session (except for the short sessions).

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120003.

Stroke is the second largest cause of disability-adjusted life-years lost worldwide. The prevalence of stroke in women is predicted to rise rapidly, owing to the increasing average age of the global female population. Vascular risk factors differ between women and men in terms of prevalence, and evidence increasingly supports the clinical importance of sex differences in stroke. The influence of some risk factors for stroke - including diabetes mellitus and atrial fibrillation - are stronger in women, and hypertensive disorders of pregnancy also affect the risk of stroke decades after pregnancy. However, in an era of evidence-based medicine, women are notably under-represented in clinical trials - despite governmental actions highlighting the need to include both men and women in clinical trials - resulting in a reduced generalizability of study results to women. The aim of this Review is to highlight new insights into specificities of stroke in women, to plan future research priorities, and to influence public health policies to decrease the worldwide burden of stroke in women.

Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ to alarm clinicians in recognizing COVID-19-related stroke.

Objective:To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).Methods:Associations between ICH sites and poor outcomes (death [6] or major disability [3–5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models.Results:Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score (≤0.7 [median]; OR 1.87, 2.14, and 2.81, respectively). Posterior limb of internal capsule involvement was strongly associated with low scores across all health-related quality of life domains. ICH encompassing the thalamus and posterior limb of internal capsule were associated with death or major disability, major disability, and poor EQ-5D utility score (OR 1.72, 2.26, and 1.71, respectively).Conclusion:Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule.ClinicalTrials.gov registration:NCT00716079.

The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.