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Pregnancy, postpartum and menopause are regarded as periods women are more vulnerable to ischaemic events. There are conflicting results regarding stroke risk and hormone replacement therapy (HRT) during menopause. Stroke in pregnancy is generally increasing with serious consequences for mother and child; therefore, recommendations for acute treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) are needed. The aim of this guideline is to support and guide clinicians in treatment decisions in stroke in women. Following the “Grading of Recommendations and Assessment, Development and Evaluation (GRADE)” approach, the guidelines were developed according to the European Stroke Organisation (ESO) Standard Operating Procedure. Systematic reviews and metanalyses were performed. Based on available evidence, recommendations were provided. Where there was a lack of evidence, an expert consensus statement was given. Low quality of evidence was found to suggest against the use of HRT to reduce the risk of stroke (ischaemic and haemorrhagic) in postmenopausal women. No data was available on the outcome of women with stroke when treated with HRT. No sufficient evidence was found to provide recommendations for treatment with IVT or MT during pregnancy, postpartum and menstruation. The majority of members suggested that pregnant women can be treated with IVT after assessing the benefit/risk profile on an individual basis, all members suggested treatment with IVT during postpartum and menstruation. All members suggested treatment with MT during pregnancy. The guidelines highlight the need to identify evidence for stroke prevention and acute treatment in women in more vulnerable periods of their lifetime to generate reliable data for future guidelines.

Background:The use of aspirin for primary prevention of cardiovascular events in men and women remains controversial. Our study aimed to investigate the role of aspirin in primary stroke prevention in men and women and the effect of aspirin on risk of ischemic stroke in patients with covert cerebral small vessel disease (ccSVD).MethodsWe performed systematic searches of the PubMed, and Cochrane Library databases, covering the period from the inception of each database to May 2021. The incidence of any ischemic stroke (IS) or hemorrhagic stroke (HS) was the main outcome. The incidence of stroke overall, both ischemic (IS) and hemorrhagic (HS), was the main outcome.ResultsFrom 531 abstracts, 11 randomized control trials which assessed primary prevention of cardiovascular events in men and women were included. Only one study assessed the risk of aspirin in people with ccSVD. In women, there was significant decrease in the risk of stroke (OR 0.85 [95% CI 0.73, 0.99], p = 0.03) and IS (OR 0.76 [0.63, 0.93], p = 0.008) with aspirin compared to placebo while no increase in the risk of HS was found (OR 1.78 [0.61, 5.19], p = 0.29). In men, aspirin did not affect the risk of stroke (OR 1.13 [0.97, 1.31], p = 0.12) and IS (OR 0.94 [0.67, 1.32], p = 0.72) but increased the risk of HS with borderline statistical significance (OR 1.99 [0.99, 4.03], p = 0.05) compared to placebo. Aspirin significantly increased major bleedings in both sexes (p < 0.05). We found no evidence to support the use of aspirin in patients with ccSVD.ConclusionOur meta-analysis suggests aspirin is effective in primary prevention of stroke and IS in women with no clear increased risk of HS. However, it was associated with an overall increased risk of bleeding. Aspirin is not recommended in ccSVD.

Supplemental Material, sj-pdf-1-eso-10.1177_23969873221078696 for European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum by Christine Kremer, Zuzana Gdovinova, Yannick Bejot, Mirjam R. Heldner, Susanna Zuurbier, Silke Walter, Avtar Lal, Corina Epple, Svetlana Lorenz, Marie-Luise Mono, Theodore Karapanayiotides, Kailash Krishnan, Dejana Jovanovic, Jesse Dawson, Valeria Caso in European Stroke Journal

Supplemental Material, sj-pdf-2-eso-10.1177_23969873221078696 for European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum by Christine Kremer, Zuzana Gdovinova, Yannick Bejot, Mirjam R. Heldner, Susanna Zuurbier, Silke Walter, Avtar Lal, Corina Epple, Svetlana Lorenz, Marie-Luise Mono, Theodore Karapanayiotides, Kailash Krishnan, Dejana Jovanovic, Jesse Dawson, Valeria Caso in European Stroke Journal

Supplemental material, sj-docx-1-eso-10.1177_23969873221099715 for European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease by Marios Psychogios, Alex Brehm, Elena López-Cancio, Gian Marco De Marchis, Elena Meseguer, Aristeidis H Katsanos, Christine Kremer, Peter Sporns, Marialuisa Zedde, Adam Kobayashi, Jildaz Caroff, Daniel Bos, Sabrina Lémeret, Avtar Lal and Juan F Arenillas in European Stroke Journal

Supplemental material, sj-docx-1-eso-10.1177_23969873221099736 for European Stroke Organisation (ESO) guidelines on management of unruptured intracranial aneurysms by Nima Etminan, Diana Aguiar de Sousa, Cindy Tiseo, Romain Bourcier, Hubert Desal, Anttii Lindgren, Timo Koivisto, David Netuka, Simone Peschillo, Sabrina Lémeret, Avtar Lal, Mervyn DI Vergouwen and Gabriel JE Rinkel in European Stroke Journal

Supplemental material, sj-pdf-1-eso-10.1177_23969873211014112 for European Stroke Organisation (ESO) guidelines on the management of space-occupying brain infarction by H Bart van der Worp, Jeannette Hofmeijer, Eric Jüttler, Avtar Lal, Patrik Michel, Paola Santalucia, Silvia Schönenberger, Thorsten Steiner and Götz Thomalla in European Stroke Journal

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.

Supplemental Material, sj-pdf-1-eso-10.1177_23969873211046475 for ESO guideline for the management of extracranial and intracranial artery dissection by Stephanie Debette, Mikael Mazighi, Philippe Bijlenga, Alessandro Pezzini, Masatoshi Koga, Anna Bersano, Janika Kõrv, Julien Haemmerli, Isabella Canavero, Piotr Tekiela, Kaori Miwa, David J Seiffge, Sabrina Schilling, Avtar Lal, Marcel Arnold, Hugh S Markus, Stefan T Engelter and Jennifer J Majersik in European Stroke Journal

Supplemental material, sj-pdf-1-eso-10.1177_23969873211012133 for European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage by Else Charlotte Sandset, Craig S Anderson, Philip M Bath, Hanne Christensen, Urs Fischer, Dariusz Gąsecki, Avtar Lal, Lisa S Manning, Simona Sacco, Thorsten Steiner and Georgios Tsivgoulis in European Stroke Journal

Supplemental material, sj-pdf-1-eso-10.1177_2396987321992905 for European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack by Ana Catarina Fonseca, Áine Merwick, Martin Dennis, Julia Ferrari, José M Ferro, Peter Kelly, Avtar Lal, Angel Ois, Jean Marc Olivot and Francisco Purroy in European Stroke Journal

Supplemental Material, sj-pdf-1-eso-10.1177_23969873211039721 for European Stroke Organisation and European Society for Swallowing Disorders guideline for the diagnosis and treatment of post-stroke dysphagia by Rainer Dziewas, Emilia Michou, Michaela Trapl-Grundschober, Avtar Lal, Ethem Murat Arsava, Philip MW Bath, Pere Clavé, Jörg Glahn, Shaheen Hamdy, Sue Pownall, Antonio Schindler, Margaret Walshe, Rainer Wirth, David Wright and Eric Verin in European Stroke Journal

Supplemental material, Supplemental Material2 for European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage by Hanne Christensen, Charlotte Cordonnier, Janika Kõrv, Avtar Lal, Christian Ovesen, Jan C Purrucker, Danillo Toni and Thorsten Steiner: on behalf of the VISTA-ICH Collaborators in European Stroke Journal

Supplemental Material for Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: A European Stroke Organisation guideline by Catharina JM Klijn, Maurizio Paciaroni, Eivind Berge, Eleni Korompoki, Janika Kõrv, Avtar Lal, Jukka Putaala and David J Werring in European Stroke Journal

Background Self-monitoring of blood glucose levels is commonly performed by patients with diabetes mellitus. However, there is debate surrounding the clinical utility and cost-effectiveness of this practice among patients with type 2 diabetes managed without insulin. We conducted a systematic review and meta-analysis to determine the effect of self-monitoring versus no self-monitoring, and the optimal frequency of self-monitoring, in this population. Methods MEDLINE, EMBASE, BIOSIS Previews, CINAHL and PsycINFO were searched for randomized controlled trials (RCTs) and observational studies published in English from January 1990 to March 2009. Additional citations were obtained through searches of the Internet and conference proceedings, and from stakeholder feedback. Two reviewers independently selected studies, extracted data and performed an assessment of the methodologic quality of the studies. Key outcomes of interest were hemoglobin A1c (HbA1c) concentration, hypoglycemia, quality of life, long-term complications of diabetes and death. Where appropriate, we pooled data using random-effects meta-analysis. Results We identified 1624 citations through the literature search and selected 25 articles for inclusion. We observed a statistically significant improvement in the HbA1c concentration across RCTs that compared self-monitoring of blood glucose levels with no self-monitoring among patients taking oral antidiabetes drug therapy (weighted mean difference ­–0.25%, 95% confidence interval –0.36% to –0.15%). Subgroup analysis indicated that results from RCTs that provided patients with education on how to interpret and apply self-monitoring test results were similar to those from RCTs that did not. On the basis of limited evidence, self-monitoring of blood glucose levels did not demonstrate consistent benefits in terms of quality of life, patient satisfaction, prevention of hypoglycemia or long-term complications of diabetes, or reduction of mortality. There was insufficient evidence pertaining to the optimal frequency of self-monitoring. Interpretation Self-monitoring of blood glucose levels was associated with a modest, statistically significant reduction in hemoglobin A1c concentrations, regardless of whether patients were provided with education on how to interpret and use the test results. Further studies are required to determine whether self-monitoring reduces the risk of long-term complications of diabetes and to identify patients most likely to benefit from self-monitoring.

High salt diet cardiac fibrosis by activating cardiac aldosterone . We hypothesized that enhanced cardiac aldosterone production by high salt intake may increase left ventricle (LV) weight and cardiomyocyte size and induce fibrosis in both ventricles. Regular salt (0.6%) or high salt (8%) diet, either without or with spironolactone (20 or 80 mg/kg/day) were given to Wistar rats for 4 and 8 weeks. Both LV weight and cardiomyocyte cross-sectional diameter were increased significantly by high salt diet after 4 and 8 weeks. Both LV and right ventricle (RV) collagen and fibrosis as well as mean arterial pressure (MAP) remained unchanged after 4 weeks, but increased significantly after 8 weeks on high salt diet. Spironolactone (80 mg/kg) prevented the high salt-induced increases in LV weight and cardiomyocyte cross-sectional diameter as well as LV and RV collagen and fibrosis, and attenuated the increase in MAP. Spironolactone (20 mg/kg) was somewhat less effective. The high salt induced changes in cardiac and cardiomyocyte hypertrophy, and cardiac fibrosis were prevented by spironolactone, which is consistent with the concept that cardiac aldosterone mediates these cardiac effects of high salt diet. Role of brain renin-angiotensin-aldosterone-system (RAAS) in cardiac remodeling post-MI. To assess the contribution of the brain RAAS in the activation of the cardiac RAAS and remodeling post-MI, Wistar rats with intracerebroventricular (icv) infusion of spironolactone and transgenic (TG) rats deficient in brain angiotensinogen were studied. An MI was induced by acute coronary artery ligation. Spironolactone was administered by icv infusion (100 ng/h) or orally (80 mg/kg/day) for 6 weeks post-MI in Wistar rats. TG rats and control Sprague-Dawley (SD) rats were followed for 8 weeks. MI decreased LV peak systolic pressure (LVPSP) and LV dP/dt max and increased LV end diastolic pressure (LVEDP) and plasma catecholamines and serum aldosterone, which were prevented or attenuated by both icv and oral spironolactone at 6 weeks post-MI. MI increased internal circumferences, cardiomyocyte diameter, fibrosis, laminin and fibronectin, and aldosterone in the LV or and RV, which were also significantly prevented/inhibited by both icv and oral spironolactone at 6 weeks post-MI in Wistar rats as well as at 8 weeks post-MI in TG rats. Magnitude of beneficial effects of icv spironolactone at low doses was largely equal to that achieved with its oral administration at much higher doses, indicating that in addition to other sites of actions, aldosterone appears to activate central nervous system (CNS) pathways and thereby influences peripheral mechanisms involved in cardiac remodeling. The findings in TG rats support the pivotal role of locally produced angiotensin II in the brain in cardiac remodeling post-MI. The brain RAAS appears to activate a cascade of events, among others an increase in cardiac aldosterone, which play a major role in cardiac remodeling post-MI.