Nicolas Martinez‐Majander

<h3>Background and Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 <i>p</i> &lt; 0.001), whereas “other determined stroke” and “undetermined stroke” were higher in low and middle-income countries (LMICs; both <i>p</i> &lt; 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). <h3>Discussion</h3> 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.

BACKGROUND: It is unknown whether decompressive craniectomy improves clinical outcome for people with spontaneous severe deep intracerebral haemorrhage. The SWITCH trial aimed to assess whether decompressive craniectomy plus best medical treatment in these patients improves outcome at 6 months compared to best medical treatment alone. METHODS: In this multicentre, randomised, open-label, assessor-blinded trial conducted in 42 stroke centres in Austria, Belgium, Finland, France, Germany, the Netherlands, Spain, Sweden, and Switzerland, adults (18-75 years) with a severe intracerebral haemorrhage involving the basal ganglia or thalamus were randomly assigned to receive either decompressive craniectomy plus best medical treatment or best medical treatment alone. The primary outcome was a score of 5-6 on the modified Rankin Scale (mRS) at 180 days, analysed in the intention-to-treat population. This trial is registered with ClincalTrials.gov, NCT02258919, and is completed. FINDINGS: SWITCH had to be stopped early due to lack of funding. Between Oct 6, 2014, and April 4, 2023, 201 individuals were randomly assigned and 197 gave delayed informed consent (96 decompressive craniectomy plus best medical treatment, 101 best medical treatment). 63 (32%) were women and 134 (68%) men, the median age was 61 years (IQR 51-68), and the median haematoma volume 57 mL (IQR 44-74). 42 (44%) of 95 participants assigned to decompressive craniectomy plus best medical treatment and 55 (58%) assigned to best medical treatment alone had an mRS of 5-6 at 180 days (adjusted risk ratio [aRR] 0·77, 95% CI 0·59 to 1·01, adjusted risk difference [aRD] -13%, 95% CI -26 to 0, p=0·057). In the per-protocol analysis, 36 (47%) of 77 participants in the decompressive craniectomy plus best medical treatment group and 44 (60%) of 73 in the best medical treatment alone group had an mRS of 5-6 (aRR 0·76, 95% CI 0·58 to 1·00, aRD -15%, 95% CI -28 to 0). Severe adverse events occurred in 42 (41%) of 103 participants receiving decompressive craniectomy plus best medical treatment and 41 (44%) of 94 receiving best medical treatment. INTERPRETATION: SWITCH provides weak evidence that decompressive craniectomy plus best medical treatment might be superior to best medical treatment alone in people with severe deep intracerebral haemorrhage. The results do not apply to intracerebral haemorrhage in other locations, and survival is associated with severe disability in both groups. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Inselspital Stiftung, and Boehringer Ingelheim.

Background Recent studies have shown an increasing prevalence of vascular risk factors in young adults with ischemic stroke ( IS ). However, the strength of the association between all vascular risk factors and early-onset IS has not been fully established. Methods and Results We compared 961 patients with a first-ever IS at 25 to 49 years to 1403 frequency-matched stroke-free controls from a population-based cohort study ( FINRISK ). Assessed risk factors included an active malignancy, atrial fibrillation, cardiovascular disease, current smoking status, a family history of stroke, high low-density lipoprotein cholesterol, high triglycerides, low high-density lipoprotein cholesterol, hypertension, and type 1 and type 2 diabetes mellitus. We performed subgroup analyses based on age, sex, and IS etiology. In a fully adjusted multivariable logistic regression analysis, significant risk factors for IS consisted of atrial fibrillation (odds ratio [OR], 10.43; 95% confidence interval [ CI ], 2.33-46.77], cardiovascular disease (OR, 8.01; 95% CI , 3.09-20.78), type 1 diabetes mellitus (OR, 6.72; 95% CI , 3.15-14.33), type 2 diabetes mellitus (OR, 2.31; 95% CI , 1.35-3.95), low high-density lipoprotein cholesterol (OR, 1.81; 95% CI , 1.37-2.40), current smoking status (OR, 1.81; 95% CI , 1.50-2.17), hypertension (OR, 1.43; 95% CI , 1.17-1.75), and a family history of stroke (OR, 1.37; 95% CI , 1.04-1.82). High low-density lipoprotein cholesterol exhibited an inverse association with IS . In the subgroup analyses, the most consistent associations appeared for current smoking status and type 1 diabetes mellitus. Conclusions Our study establishes the associations between 11 vascular risk factors and early-onset IS , among which atrial fibrillation, cardiovascular disease, and both type 1 and 2 diabetes mellitus in particular showed strong associations.

BACKGROUND AND PURPOSE: Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)-treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care. METHODS: Data were obtained from IVT registries of 12 European tertiary hospitals. The primary outcome was poor functional outcome, defined as a modified Rankin scale score of 3 to 6 at 3 months. We stratified outcome by age in decades. Safety measures were symptomatic intracranial hemorrhage and mortality at 3 months. RESULTS: In this cohort, 9495 patients were treated with IVT, and 4170 (43.9%) were women with a mean age of 71.9 years. After adjustments for baseline differences, female sex remained associated with poor functional outcome (odds ratio, 1.15; 95% confidence interval, 1.02-1.31). There was no association between sex and functional outcome when data were stratified by age. Symptomatic intracranial hemorrhage rate was similar in both sexes (adjusted odds ratio, 0.93; 95% confidence interval, 0.73-1.19), whereas mortality was lower among women (adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99). CONCLUSIONS: In this large cohort of IVT-treated patients, women more often had poor functional outcome compared with men. This difference was not dependent on age.

Abstract Spontaneous (non-traumatic) intracerebral haemorrhage (ICH) affects ~3.4 million people worldwide each year, causing ~2.8 million deaths. Many randomised controlled trials and high-quality observational studies have added to the evidence base for the management of people with ICH since the last European Stroke Organisation (ESO) guidelines for the management of spontaneous ICH were published in 2014, so we updated the ESO guideline. This guideline update was guided by the European Stroke Organisation (ESO) standard operating procedures for guidelines and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, in collaboration with the European Association of Neurosurgical Societies (EANS). We identified 37 Population, Intervention, Comparator, Outcome (PICO) questions and prioritised clinical outcomes. We conducted systematic literature searches, tailored to each PICO, seeking randomised controlled trials (RCT) – or observational studies when RCTs were not appropriate, or not available – that investigated interventions to improve clinical outcomes. A group of co-authors allocated to each PICO screened titles, abstracts, and full texts and extracted data from included studies. A methodologist conducted study-level meta-analyses and created summaries of findings tables. The same group of co-authors graded the quality of evidence, and drafted recommendations that were reviewed, revised and approved by the entire group. When there was insufficient evidence to make a recommendation, each group of co-authors drafted an expert consensus statement, which was reviewed, revised and voted on by the entire group. The systematic literature search revealed 115,647 articles. We included 208 studies. We found strong evidence for treatment of people with ICH on organised stroke units, and secondary prevention of stroke with blood pressure lowering. We found weak evidence for scores for predicting macrovascular causes underlying ICH; acute blood pressure lowering; open surgery via craniotomy for supratentorial ICH; minimally invasive surgery for supratentorial ICH; decompressive surgery for deep supratentorial ICH; evacuation of cerebellar ICH &amp;gt; 15 mL; external ventricular drainage with intraventricular thrombolysis for intraventricular extension; minimally invasive surgical evacuation of intraventricular blood; intermittent pneumatic compression to prevent proximal deep vein thrombosis; antiplatelet therapy for a licensed indication for secondary prevention; and applying a care bundle. We found strong evidence against anti-inflammatory drug use outside of clinical trials. We found weak evidence against routine use of rFVIIa, platelet transfusions for antiplatelet-associated ICH, general policies that limit treatment within 24 h of ICH onset, temperature and glucose management as single measures (outside of care bundles), prophylactic anti-seizures medicines, and prophylactic use of temperature-lowering measures, prokinetic anti-emetics, and/or antibiotics. New evidence about the management of ICH has emerged since 2014, enabling this update of the ESO guideline to provide new recommendations and consensus statements. Although we made strong recommendations for and against a few interventions, we were only able to make weak recommendations for and against many others, or produce consensus statements where the evidence was insufficient to guide clinical decisions. Although progress has been made, many interventions still require definitive, high-quality evidence, underpinning the need for embedding clinical trials in routine clinical practice for ICH.