This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.

Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

Background and Purpose— Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored. Objective and Methods— The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) is a randomized, double-blind, placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9% physiological serum) in addition to optimal care. A sample size of 240 patients was calculated to identify a 15% absolute risk reduction of the primary outcome measure, which was the incidence of infection at day 7 after stroke. Secondary outcome measures were neurological outcome and mortality at day 90. Results— Based on a preplanned futility analysis, the study was interrupted prematurely when 136 patients had been included. Levofloxacin and placebo patients had a cumulative rate of infection of 6% and 6% ( P =0.96) at day 1; 10% and 12% ( P =0.83) at day 2; 12% and 15% ( P =0.66) at day 3; 16% and 19% ( P =0.82) at day 7; and 30% and 33% ( P =0.70), at day 90. Using logistic regression, favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale (OR, 0.72; 95% CI, 0.59 to 0.89; P =0.002) and allocation to levofloxacin (OR, 0.19; 95% CI, 0.04 to 0.87; P =0.03). Conclusions— Prophylactic administration of levofloxacin (500 mg/100 mL/day for 3 days) is not better than optimal care for the prevention of infections in patients with acute stroke.

Background and Purpose: The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center. Methods: On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic. Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19. From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona. We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes. Data were compared with March 2019 using parametric or nonparametric methods as appropriate. Results: At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity. Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426). Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population. Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64–73] versus 75 [73–80] years, P =0.009). In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge. Conclusions: The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics. During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients. Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

Background and Purpose-We sought to assess in 881 consecutive patients with acute ischemic stroke the clinical relevance in regard to functional outcome of the natural antioxidant uric acid measured at hospital admission. Methods-Patients had serum uric acid (mg/dL) measured by standard procedures 18.2Ϯ15.5 hours from clinical onset.At hospital discharge (11.0Ϯ6.0 days), neurological impairment was classified as moderate/severe (Mathew score Յ75; nϭ304) or mild/absent (Mathew score Ͼ75; nϭ577). Demographics, atherosclerotic risk factors, history of organ disease, baseline neurological score, stroke subtype, infarction size, renal function, aspirin use before stroke, stroke therapy, diuretic use, and laboratory markers, including erythrocyte sedimentation rate, were analyzed in both outcome groups with the use of backward logistic regression. Results-Increased uric acid values were found in men, hypertensives, alcohol drinkers, and patients with coronary, pulmonary, or renal diseases. Diabetic patients had lower uric acid levels on admission. Uric acid was directly associated with hematocrit (Pϭ0.001), sodium (Pϭ0.001), creatinine (Pϭ0.001), and triglycerides (Pϭ0.001) and inversely related with nonfasting glucose (Pϭ0.001) levels. Neurological impairment on admission (Pϭ0.001) and final infarction size on CT/MRI (Pϭ0.01) were also inversely associated with uric acid. A logistic regression adjusted for confounders confirmed the following independent (odds ratio, 95% CI) good outcome predictors: age (0.97, 0.96 to 0.99), Mathew score on admission (1.14, 1.12 to 1.17), erythrocyte sedimentation rate (0.98, 0.97 to 0.99), infarction volume (0.98, 0.98 to 0.99), and uric acid (1.12, 1.00 to 1.25). Conclusions-In patients with acute ischemic stroke, there is a 12% increase in the odds of good clinical outcome for each milligram per deciliter increase of serum uric acid. This finding reinforces the relevance of oxidative damage in ischemic stroke.

The number of circulating monocytes increases after stroke. In this study, we assessed the time course and phenotype of monocyte subsets and their relationship with the clinical course and outcome in 46 consecutive stroke patients and 13 age-matched controls. The proportion of the most abundant 'classical' CD14 high CD16À monocytes did not change after stroke, whereas that of CD14 high CD16 + monocytes increased and CD14 dim CD16 + monocytes decreased. CD14 high CD16 + monocytes had the highest expression of TLR2, HLA-DR and the angiogenic marker, Tie-2; CD14 dim CD16 + monocytes had the highest expression of costimulatory CD86 and adhesion molecule CD49d. Platelet-monocyte interactions were highest in CD14 high CD16À monocytes and lowest in CD14 dim CD16 + monocytes. In adjusted models, 1/CD14 high CD16À monocytes were associated with poor outcome (OR: 1.38), higher mortality (OR: 1.40) and early clinical worsening (OR: 1.29); 2/CD14 high CD16 + monocytes were inversely related to mortality (OR: 0.32); and 3/CD14 dim CD16 + monocytes were inversely related to poor outcome (OR: 0.74) and infarction size (r = À0.45; P = 0.02). These results illustrate that the predominant monocyte subtype conveys harmful effects after stroke, which include stronger interaction with platelets. Alternatively, rarer subpopulations of monocytes are beneficial with a phenotype that could promote tissue repair and angiogenesis. Therefore, monitoring of monocyte subtypes may emerge as a useful tool at the bedside for stroke patients.

Background and Purpose-Monocytes participate in adaptive and innate immune responses. Monocyte numbers increase in patients with stroke associated infection (SAI) or severe stroke. Whether changes in monocytes are related to specific effects, or simply mark brain damage, remains unsettled. Methods-We used flow cytometry in 45 consecutive strokes and 12 healthy controls to assess the time course of monocytes, their phenotype, and the production of cytokines after stimulation. Cortisol, TNF-␣, IFN-␥, and IL-10 were measured in serum and metanephrine in plasma. The effects of humoral and cellular parameters on the risk of SAI and poor outcome were tested in multivariate analyses adjusted for confounders (NIHSS score, age, and tube feeding). Results-Surface expression of human leukocyte antigen-DR, Toll-like receptor-2, and production of TNF-␣ in monocytes were independently associated with stroke. Distinct immune mechanisms were related with functional outcome and the risk of SAI; the signature of SAI included an increase of cortisol, metanephrine, and IL-10 in serum, and reduced production of TNF-␣ in monocytes; poor outcome was associated with increased expression of Toll-like receptor-4 in monocytes (OR, 9.61; 95% CI, 1.27-72.47). SAI did not predict poor outcome (OR, 5.63; 95% CI, Pϭ0.18). Conclusions-In human stroke, poor outcome is associated to innate responses mediated by Toll-like receptor-4 in monocytes. SAI may result from the immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL-10, and deactivated monocytes. Early treated SAI does not contribute significantly to additional brain damage. These findings encourage the exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in acute stroke. (Stroke.