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Objectives: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). Methods: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. Results: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76–4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04–1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient‐years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient‐years). Interpretation: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high‐risk group. ANN NEUROL 2023;94:61–74 [ABSTRACT FROM AUTHOR]

Introduction: The pandemic of coronavirus disease 2019 (COVID-19) has had a significant impact on stroke healthcare, including the prehospital care system and in-hospital workflow. Japan experienced the outbreak of COVID-19, and the State of Emergency was declared during April 2020 and May 2020. The aim of the present study was to clarify the effect of the COVID-19 pandemic on a comprehensive stroke center in Japan. Methods: We retrospectively reviewed consecutive patients with acute ischemic stroke admitted in our institute between December 2019 and July 2020. The patients who underwent reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy) were divided into the pre-COVID-19 period (December 2019 to March 2020) and the With-COVID-19 period (April 2020 to July 2020). Study outcomes were the number of stroke admissions in our institute, workflow time metrics, the frequency of modified Rankin Scale score 0–2 at discharge, and brain imaging modalities before reperfusion therapy in patients who underwent reperfusion therapy. Results: In our institute, the number of stroke admissions decreased during the State of Emergency and then increased after the lifting of the State of Emergency. Among patients who underwent reperfusion therapy (median age, 77 years; female 27%; median baseline National Institutes of Health Stroke Scale score, 10), times from hospital arrival to imaging [25 (21–33) min vs. 30 (25–38) min, P = 0.03] and to thrombolysis [38 (31–52) min vs. 51 (37–64) min, P = 0.03] were prolonged compared with the pre-COVID-19 period. There was no significant difference in the frequency of modified Rankin Scale score 0–2 at discharge between the two periods (32 vs. 45%, P = 0.21). The proportion of computed tomography vs. magnetic resonance imaging as an emergency brain imaging tool before reperfusion therapy changed, with computed tomography having become predominant in the With-COVID-19 period. Conclusions: In our institute, the number of stroke admissions, workflow time metrics, and imaging modalities for reperfusion therapy were affected by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9–2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02–3.00). Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF. [ABSTRACT FROM AUTHOR]

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk.Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602.Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models.Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted.Funding: British Heart Foundation and Stroke Association. [ABSTRACT FROM AUTHOR]

Clinical outcomes of unknown onset stroke (UOS) are influenced by the enlargement of the therapeutic time window for reperfusion therapy. This study aimed to investigate and describe the characteristics and clinical outcomes of patients with UOS. Patients with acute ischemic stroke (AIS) who were admitted within 24 h of their last known well time, from January 2017 to December 2020, were included. Data were obtained from a long-lasting nationwide hospital-based multicenter prospective registry: the Japan Stroke Data Bank. The co-primary outcomes were the National Institutes of Stroke Scale (NIHSS) scores on admission and unfavorable outcomes at discharge, corresponding to modified Rankin Scale (mRS) scores of 3–6. Overall, 26,976 patients with AIS were investigated. Patients with UOS (N = 5783, 78 ± 12 years of age) were older than patients with known onset stroke (KOS) (N = 21,193, 75 ± 13 years of age). Age, female sex, higher premorbid mRS scores, atrial fibrillation, and congestive heart failure were associated with UOS in multivariate analysis. UOS was associated with higher NIHSS scores (median = 8 [interquartile range [IQR]: 3–19] vs. 4 [1–10], adjusted incidence rate ratio = 1.37 [95% CI: 1.35–1.38]) and unfavorable outcomes (52.1 vs. 33.6%, adjusted odds ratio = 1.27 [1.14–1.40]). Intergroup differences in unfavorable outcomes were attenuated among females (1.12 [0.95–1.32] vs. males 1.38 [1.21–1.56], P = 0.040) and in the subgroup that received reperfusion therapy (1.10 [0.92–1.33] vs. those who did not receive therapy 1.23 [1.08–1.39], P = 0.012). UOS was associated with unfavorable outcomes but to a lesser degree among females and patients receiving reperfusion therapy. [Display omitted] • Unknown onset stroke (UOS) accounted for 21.4% of acute ischemic stroke cases. • UOS was independently associated with unfavorable outcomes. • This association was attenuated in females and reperfusion therapy receivers. [ABSTRACT FROM AUTHOR]

As the number of patients with left ventricular assist device (LVAD) implantation has been increasing, treatment of LVAD-related ischemic stroke is becoming a critical issue. We sought to clarify the features of mechanical thrombectomy in LVAD-related stroke with large vessel occlusion. In a multi-center, retrospective case-control study, we compared 20 LVAD-related strokes with 33 non-LVAD strokes, all of which had large vessel occlusion in the anterior circulation treated with mechanical thrombectomy. A comparative histopathological examination of the retrieved thrombi was also performed. Successful reperfusion was achieved in 75% of the LVAD-related strokes. The time from onset to reperfusion was similar to that of non-LVAD strokes, but the total number of device passes required for reperfusion (median, 2.5 versus 1, P = 0.01) and the incidences of post-procedural parenchymal and subarachnoid hemorrhage (25% versus 3%, P = 0.02 and 55% versus 15%, P = 0.01, respectively) were higher in LVAD-related strokes. Symptomatic intracranial hemorrhage occurred in 4 patients (20%) with LVAD-related strokes. The histopathological analysis revealed that the ratio of erythrocyte components was significantly lower in thrombi retrieved from patients with LVAD-related stroke than in those with non-LVAD stroke (19 ± 6% versus 41 ± 17%, P = 0.01). Mechanical thrombectomy is feasible in patients with LVAD-related stroke. However, repetitive device passes are needed to achieve successful reperfusion mainly because of the structurally organized thrombi, and the higher risk of hemorrhagic complications should be considered, while offering this therapeutic alternative. • This study reveals that mechanical thrombectomy is feasible in LVAD-related stroke. • However, the incidence of hemorrhagic complications is high in LVAD-related stroke. • More device passes for reperfusion are required, owing to the organized embolus. • Risk of hemorrhagic complications should be considered, when offering thrombectomy. [ABSTRACT FROM AUTHOR]