Summary Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19–2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20–1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82–3·29) for intracranial haemorrhage and 1·23 (1·08–1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08–6·72] for intracranial haemorrhage vs 1·47 [1·19–1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36–9·05] vs 1·43 [1·07–1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69–15·81] vs 1·86 [1·23–2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48–84] per 1000 patient-years vs 27 intracranial haemorrhages [17–41] per 10...

Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

BackgroundMalignant profiles were identified by imaging profiles and unfavorable outcomes that have poor response to reperfusion therapy. Many trials have used this profile in their inclusion criteria including large‐vessel occlusion acute ischemic stroke trials. We aimed to redefine the cutoff values for malignant profile in acute ischemic stroke patients with large‐vessel occlusion regardless of reperfusion therapy.Methods and ResultsConsecutive acute ischemic stroke patients with anterior large‐vessel occlusion were prospectively extracted from the National Cerebral and Cardiovascular Center Stroke Registry between March 2014 and December 2017. Diffusion‐Weighted Imaging‐Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) and diffusion‐weighted imaging lesion ischemic core volume (VolDWI) were measured in acute ischemic stroke patients with large‐vessel occlusion with or without treatment. Unfavorable outcome was defined as a modified Rankin Scale score 5 to 6 at 3 months, and optimal DWI‐ASPECTS and VolDWI for unfavorable outcome were assessed. In total, 198 patients (111 men, 77±13 years old) were enrolled. Median DWI‐ASPECTS was 7 (5‐9), and median VolDWI was 55 (6‐134) mL. Among the patients, 72 (36%) patients underwent reperfusion therapy, and 83 (42%) had unfavorable outcomes. The threshold values for a malignant profile on receiver operating characteristic curve analysis for DWI‐ASPECTS and VolDWI were 4 (area under the curve 0.78, P<0.01; sensitivity 0.71, specificity 0.75) and 71 mL (area under the curve 0.80, P<0.01; sensitivity 0.76, specificity 0.77), respectively.ConclusionsThe cutoff values for our redefined malignant profile were DWI‐ASPECTS 4 and VolDWI 71 mL with no selection bias for reperfusion therapy in the real‐world clinical practice.Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02251665

Research in context panel: 445Identifying people at highest risk of ICH may facilitate timely and accurate prognostication to allow mitigation of reversible risk factors for bleeding (e.g. intensive blood pressure control), and selection of participants for clinical trials. While more complex combinations of clinical, biochemical, and radiological markers might further improve stroke risk prediction, balancing accuracy with simplicity will remain important.

Background and Purpose— We aimed to evaluate the effect of chronic hypertension on acute leptomeningeal collateral flow in patients with large-vessel ischemic stroke using digital subtraction angiography, which is the gold standard for the assessment of collateral circulation. Methods— Of the consecutive ischemic stroke patients from October 2011 to December 2017 seen in our institution, patients with acute occlusion of the M1 segment of the middle cerebral artery confirmed on initial digital subtraction angiography were enrolled. Chronic hypertension was defined as its documentation before the index stroke or as the administration of antihypertensive medications before onset. Angiographic leptomeningeal collateral flow was evaluated according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology Collateral Flow Grading System and dichotomized the findings into excellent (grade 3–4) or poor (grade 0–2) collateral status for analysis. Results— Of the 3759 consecutive ischemic stroke patients, 100 patients were analyzed. Thirty-nine patients (39%) had poor collateral status. Patients with poor collateral status were older, more frequently male, and had chronic hypertension more frequently, shorter time from onset to angiography, and higher admission systolic blood pressure than those with excellent collateral status. Multivariable logistic analysis with prespecified covariates showed a significantly positive association between chronic hypertension and poor collateral status (odds ratio, 2.80; 95% CI, 1.08–7.70; P =0.034). This association was independent of admission systolic blood pressure. The proportion of patients with poor collateral status increased in a stepwise manner in patients without chronic hypertension, hypertensive patients with premorbid antihypertensive medications, and hypertensive patients without antihypertensive medications ( P for trend <0.001). Conclusions— Our data suggest that chronic hypertension has a detrimental effect on acute leptomeningeal collateral flow in patients with cerebral large-vessel occlusion. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02251665.

Background We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42–0.81; P =0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16–0.97; P =0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20–6.15; P =0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

Background and Purpose: Outcomes in patients ≥90 years of age with stroke due to large vessel occlusion were compared between endovascular therapy (EVT) and medical management. Methods: Of 2420 acute ischemic stroke patients with large vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients aged ≥90 years with occlusion of the internal carotid artery or M1 segment of the middle cerebral artery were included. The primary effectiveness outcome was a favorable outcome at 3 months, defined as achieving a modified Rankin Scale score of 0 to 2 or return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage within 72 hours after onset. Intergroup biases were adjusted by multivariable adjustment with inverse probability of treatment weighting. Results: A total of 150 patients (median age, 92 [interquartile range, 90–94] years; median prestroke modified Rankin Scale score, 2 [interquartile range, 0–4]) were analyzed. EVT was performed in 49 patients (32.7%; mechanical thrombectomy, n=43). The EVT group showed shorter time from onset to hospital arrival ( P =0.03), higher Alberta Stroke Program Early Computed Tomography Score ( P <0.01), and a higher rate of treatment with intravenous thrombolysis ( P <0.01) than the medical management group. The favorable outcome was seen in 28.6% of the EVT group and 6.9% of the medical management group ( P <0.01). EVT was associated with the favorable outcome (adjusted odds ratio, 8.44 [95% CI, 1.88–37.97]). Rates of symptomatic intracranial hemorrhage were similar between the EVT group (0.0%) and the medical management group (3.9%; P =0.30). Conclusions: Patients who underwent EVT showed better functional outcomes than those with medical management without increased symptomatic intracranial hemorrhages. Given proper patient selection, withholding EVT solely on the basis of the age of patients may not offer the best chance of good outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.

Background and Objectives:Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).Methods:We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.Results:There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p<0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p<0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p<0.0001). Larger declines were observed at high volume compared to low volume centers (all p<0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations.Discussion:There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.Trial Registration Information:This study is registered underNCT04934020.