European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Association of ever use of e-cigarettes with health and lifestyle variables among young adults: a Canadian health measure survey study.

Research suggests that vaping raises oxidative stress levels and has been implicated in poor mental health. The objective of this study is to assess cross-sectional associations between quality of life (QOL) indicators and e-cigarette (EC) use in young Canadian adults. We used data from the 2016-2017 Canadian Health Measures Survey. We compared physical activity (daily steps), physiological measurements (high-density lipoprotein for cholesterol level), self-perceived life stress, mental health, and QOL between ever-use EC users and non-users. Multivariable binary or ordinal logistic regressions were used to calculate odds ratios (OR) with 95% confidence intervals (CI). Analyses included 905 participants (15-30 years) with 115 (12.7%) reporting EC use and 790 non-users. After adjusting for confounders, compared to non-users, EC users had significantly higher odds of being physically active (OR = 2.19, 95%CI: 1.14-4.20) but also with self-reported extreme life stress (OR = 2.68, 95%CI: 1.45-4.92). Albeit statistically non-significant, EC users also had higher odds of poorer QOL (OR = 1.12, 95%CI: 0.64-1.95). No statistically significant interactions between EC use, cigarette smoking, cannabis consumption and health outcomes were observed. CONCLUSION: Our study found that EC use was independently and significantly associated with increased odds of life stress and an indication of poorer QOL. Ongoing surveillance on young EC users is important to measure the long-term impact of vaping on their physical, mental health and quality of life to target for interventions. WHAT IS KNOWN: • E-cigarette use has been associated with high-risk behaviours and adverse mental health outcomes, such as depression and anxiety. WHAT IS NEW: • E-cigarette users had significantly higher odds of being physically active and higher amounts of life stress.

2023 Canadian Thoracic Society Guideline on Pharmacotherapy in Patients With Stable COPD.

Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients.

Sex differences in outcome after carotid revascularization in symptomatic and asymptomatic carotid artery stenosis.

OBJECTIVE: Sex differences regarding the safety and efficacy of carotid revascularization in carotid artery stenosis have been addressed in several studies with conflicting results. Moreover, women are underrepresented in clinical trials, leading to limited conclusions regarding the safety and efficacy of acute stroke treatments. METHODS: A systematic review and meta-analysis was performed by literature search including four databases from January 1985 to December 2021. Sex differences in the efficacy and safety of revascularization procedures, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), for symptomatic and asymptomatic carotid artery stenoses were analyzed. RESULTS: Regarding CEA in symptomatic carotid artery stenosis, the stroke risk in men (3.6%) and women (3.9%) based on 99,495 patients (30 studies) did not differ (P = .16). There was also no difference in the stroke risk by different time frames up to 10 years. Compared with men, women treated with CEA had a significantly higher stroke or death rate at 4 months (2 studies, 2565 patients; 7.2% vs 5.0%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.04-2.12; I2 = 0%; P = .03), and a significantly higher rate of restenosis (1 study, 615; 17.2% vs 6.7%; OR, 2.81; 95% CI, 1.66-4.75; P = .0001). For CAS in symptomatic artery stenosis, data showed a non-significant tendency toward higher peri-procedural stroke in women, whereas for asymptomatic carotid artery stenosis, data based on 332,344 patients showed that women (compared with men) after CEA had similar rates of stroke, stroke or death, and the composite outcome stroke/death/myocardial infarction. The rate of restenosis at 1 year was significantly higher in women compared with men (1 study, 372 patients; 10.8% vs 3.2%; OR, 3.71; 95% CI, 1.49-9.2; P = .005). Furthermore, CAS in asymptomatic patients was associated with low risk of a postprocedural stroke in both sexes, but a significantly higher risk of in-hospital myocardial infarction in women than men (8445 patients, 1.2% vs 0.6%; OR, 2.01; 95% CI, 1.23-3.28; I2 = 0%; P = .005). CONCLUSIONS: A few sex-differences in short-term outcomes after carotid revascularization for symptomatic and asymptomatic carotid artery stenosis were found, although there were no significant differences in the overall stroke. This indicates a need for larger multicenter prospective studies to evaluate these sex-specific differences. More women, including those aged over 80 years, need to be enrolled in randomized controlled trials, to better understand if sex differences exist and to tailor carotid revascularization accordingly.

European Stroke Organisation (ESO) guidelines on management of unruptured intracranial aneurysms.

Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available.

European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease.

The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of patients with intracranial atherosclerotic disease (ICAD). The guidelines were prepared following the Standard Operational Procedure of the European Stroke Organisation guidelines and according to GRADE methodology. ICAD represents a major cause of ischemic stroke worldwide, and patients affected by this condition are exposed to a high risk for future strokes and other major cardiovascular events, despite best medical therapy available. We identified 11 relevant clinical problems affecting ICAD patients and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions. The first two questions refer to the asymptomatic stage of the disease, which is being increasingly detected thanks to the routine use of noninvasive vascular imaging. We were not able to provide evidence-based recommendations regarding the optimal detection strategy and management of asymptomatic ICAD, and further research in the field is encouraged as subclinical ICAD may represent a big opportunity to improve primary stroke prevention. The second block of PICOs (3-5) is dedicated to the management of acute large vessel occlusion (LVO) ischemic stroke caused by ICAD, a clinical presentation of this disease that is becoming increasingly relevant and problematic, since it is associated with more refractory endovascular reperfusion procedures. An operational definition of probable ICAD-related LVO is proposed in the guideline. Despite the challenging context, no dedicated randomized clinical trials (RCTs) were identified, and therefore the guideline can only provide with suggestions derived from observational studies and our expert consensus, such as the escalated use of glycoprotein IIb-IIIa inhibitors and angioplasty/stenting in cases of refractory thrombectomies due to underlying ICAD. The last block of PICOs is devoted to the secondary prevention of patients with symptomatic ICAD. Moderate-level evidence was found to recommend against the use of oral anticoagulation as preferred antithrombotic drug, in favor of antiplatelets. Low-level evidence based our recommendation in favor of double antiplatelet as the antithrombotic treatment of choice in symptomatic ICAD patients, which we suggest to maintain during 90 days as per our expert consensus. Endovascular therapy with intracranial angioplasty and or stenting is not recommended as a treatment of first choice in high-grade symptomatic ICAD (moderate-level evidence). Regarding neurosurgical interventions, the available evidence does not support their use as front line therapies in patients with high-grade ICAD. There is not enough evidence as to provide any specific recommendation regarding the use of remote ischemic conditioning in ICAD patients, and further RCTs are needed to shed light on the utility of this promising therapy. Finally, we dedicate the last PICO to the importance of aggressive vascular risk factor management in ICAD, although the evidence derived from RCTs specifically addressing this question is still scarce.

Aspirin for Primary Stroke Prevention; Evidence for a Differential Effect in Men and Women.

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). Methods: We 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. Results: From 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. Conclusion: Our 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.

European Stroke Organisation guidelines on stroke in women: Management of menopause, pregnancy and postpartum.

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.

ESO guideline for the management of extracranial and intracranial artery dissection.

The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of extracranial artery dissection (EAD) and intracranial artery dissection (IAD). EAD and IAD represent leading causes of stroke in the young, but are uncommon in the general population, thus making it challenging to conduct clinical trials and large observational studies. The guidelines were prepared following the Standard Operational Procedure for European Stroke Organisation guidelines and according to GRADE methodology. Our four recommendations result from a thorough analysis of the literature comprising two randomized controlled trials (RCTs) comparing anticoagulants to antiplatelets in the acute phase of ischemic stroke and twenty-six comparative observational studies. In EAD patients with acute ischemic stroke, we recommend using intravenous thrombolysis (IVT) with alteplase within 4.5 hours of onset if standard inclusion/exclusion criteria are met, and mechanical thrombectomy in patients with large vessel occlusion of the anterior circulation. We further recommend early endovascular or surgical intervention for IAD patients with subarachnoid hemorrhage (SAH). Based on evidence from two phase 2 RCTs that have shown no difference between the benefits and risks of anticoagulants versus antiplatelets in the acute phase of symptomatic EAD, we strongly recommend that clinicians can prescribe either option. In post-acute EAD patients with residual stenosis or dissecting aneurysms and in symptomatic IAD patients with an intracranial dissecting aneurysm and isolated headache, there is insufficient data to provide a recommendation on the benefits and risks of endovascular/surgical treatment. Finally, nine expert consensus statements, adopted by 8 to 11 of the 11 experts involved, propose guidance for clinicians when the quality of evidence was too low to provide recommendations. Some of these pertain to the management of IAD (use of IVT, endovascular treatment, and antiplatelets versus anticoagulation in IAD with ischemic stroke and use of endovascular or surgical interventions for IAD with headache only). Other expert consensus statements address the use of direct anticoagulants and dual antiplatelet therapy in EAD-related cerebral ischemia, endovascular treatment of the EAD/IAD lesion, and multidisciplinary assessment of the best therapeutic approaches in specific situations.

European Stroke Organisation and European Society for Swallowing Disorders guideline for the diagnosis and treatment of post-stroke dysphagia.

Post-stroke dysphagia (PSD) is present in more than 50% of acute stroke patients, increases the risk of complications, in particular aspiration pneumonia, malnutrition and dehydration, and is linked to poor outcome and mortality. The aim of this guideline is to assist all members of the multidisciplinary team in their management of patients with PSD. These guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. An interdisciplinary working group identified 20 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found moderate quality of evidence to recommend dysphagia screening in all stroke patients to prevent post-stroke pneumonia and to early mortality and low quality of evidence to suggest dysphagia assessment in stroke patients having been identified at being at risk of PSD. We found low to moderate quality of evidence for a variety of treatment options to improve swallowing physiology and swallowing safety. These options include dietary interventions, behavioural swallowing treatment including acupuncture, nutritional interventions, oral health care, different pharmacological agents and different types of neurostimulation treatment. Some of the studied interventions also had an impact on other clinical endpoints such as feedings status or pneumonia. Overall, further randomized trials are needed to improve the quality of evidence for the treatment of PSD.

European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage.

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.

European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage.

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.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60-99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70-99% symptomatic stenosis, and we suggest CEA for patients with 50-69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50-99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50-99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.

European Stroke Organisation (ESO) guidelines on the management of space-occupying brain infarction.

Space-occupying brain oedema is a potentially life-threatening complication in the first days after large hemispheric or cerebellar infarction. Several treatment strategies for this complication are available, but the size and quality of the scientific evidence on which these strategies are based vary considerably. The aim of this Guideline document is to assist physicians in their management decisions when treating patients with space-occupying hemispheric or cerebellar infarction. These Guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A working group identified 13 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. An expert consensus statement was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high-quality evidence to recommend surgical decompression to reduce the risk of death and to increase the chance of a favourable outcome in adult patients aged up to and including 60 years with space-occupying hemispheric infarction who can be treated within 48 hours of stroke onset, and low-quality evidence to support this treatment in older patients. There is continued uncertainty about the benefit and risks of surgical decompression in patients with space-occupying hemispheric infarction if this is done after the first 48 hours. There is also continued uncertainty about the selection of patients with space-occupying cerebellar infarction for surgical decompression or drainage of cerebrospinal fluid. These Guidelines further provide details on the management of specific subgroups of patients with space-occupying hemispheric infarction, on the value of monitoring of intracranial pressure, and on the benefits and risks of medical treatment options. We encourage new high-quality studies assessing the risks and benefits of different treatment strategies for patients with space-occupying brain infarction.

European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60-99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70-99% symptomatic stenosis, and we suggest CEA for patients with 50-69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50-99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50-99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

European Stroke Organisation (ESO) guidelines on the management of space-occupying brain infarction.

Space-occupying brain oedema is a potentially life-threatening complication in the first days after large hemispheric or cerebellar infarction. Several treatment strategies for this complication are available, but the size and quality of the scientific evidence on which these strategies are based vary considerably. The aim of this Guideline document is to assist physicians in their management decisions when treating patients with space-occupying hemispheric or cerebellar infarction. These Guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A working group identified 13 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. An expert consensus statement was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high-quality evidence to recommend surgical decompression to reduce the risk of death and to increase the chance of a favourable outcome in adult patients aged up to and including 60 years with space-occupying hemispheric infarction who can be treated within 48 hours of stroke onset, and low-quality evidence to support this treatment in older patients. There is continued uncertainty about the benefit and risks of surgical decompression in patients with space-occupying hemispheric infarction if this is done after the first 48 hours. There is also continued uncertainty about the selection of patients with space-occupying cerebellar infarction for surgical decompression or drainage of cerebrospinal fluid. These Guidelines further provide details on the management of specific subgroups of patients with space-occupying hemispheric infarction, on the value of monitoring of intracranial pressure, and on the benefits and risks of medical treatment options. We encourage new high-quality studies assessing the risks and benefits of different treatment strategies for patients with space-occupying brain infarction.

Concussion Guidelines Step 2: Evidence for Subtype Classification.

BACKGROUND: Concussion is a heterogeneous mild traumatic brain injury (mTBI) characterized by a variety of symptoms, clinical presentations, and recovery trajectories. By thematically classifying the most common concussive clinical presentations into concussion subtypes (cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood) and associated conditions (cervical strain and sleep disturbance), we derive useful definitions amenable to future targeted treatments. OBJECTIVE: To use evidence-based methodology to characterize the 5 concussion subtypes and 2 associated conditions and report their prevalence in acute concussion patients as compared to baseline or controls within 3 d of injury. METHODS: A multidisciplinary expert workgroup was established to define the most common concussion subtypes and their associated conditions and select clinical questions related to prevalence and recovery. A literature search was conducted from January 1, 1990 to November 1, 2017. Two experts abstracted study characteristics and results independently for each article selected for inclusion. A third expert adjudicated disagreements. Separate meta-analyses were conducted to do the following: 1) examine the prevalence of each subtype/associated condition in concussion patients using a proportion, 2) assess subtype/associated conditions in concussion compared to baseline/uninjured controls using a prevalence ratio, and 3) compare the differences in symptom scores between concussion subtypes and uninjured/baseline controls using a standardized mean difference (SMD). RESULTS: The most prevalent concussion subtypes for pediatric and adult populations were headache/migraine (0.52; 95% CI = 0.37, 0.67) and cognitive (0.40; 95% CI = 0.25, 0.55), respectively. In pediatric patients, the prevalence of the vestibular subtype was also high (0.50; 95% CI = 0.40, 0.60). Adult patients were 4.4, 2.9, and 1.7 times more likely to demonstrate cognitive, vestibular, and anxiety/mood subtypes, respectively, as compared with their controls (P < .05). Children and adults with concussion showed significantly more cognitive symptoms than their respective controls (SMD = 0.66 and 0.24; P < .001). Furthermore, ocular-motor in adult patients (SMD = 0.72; P < .001) and vestibular symptoms in both pediatric and adult patients (SMD = 0.18 and 0.36; P < .05) were significantly worse in concussion patients than in controls. CONCLUSION: Five concussion subtypes with varying prevalence within 3 d following injury are commonly seen clinically and identifiable upon systematic literature review. Sleep disturbance, a concussion-associated condition, is also common. There was insufficient information available for analysis of cervical strain. A comprehensive acute concussion assessment defines and characterizes the injury and, therefore, should incorporate evaluations of all 5 subtypes and associated conditions.

European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage.

The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.