Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

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.

Deep Learning Versus Neurologists: Functional Outcome Prediction in LVO Stroke Patients Undergoing Mechanical Thrombectomy.

BACKGROUND: Despite evolving treatments, functional recovery in patients with large vessel occlusion stroke remains variable and outcome prediction challenging. Can we improve estimation of functional outcome with interpretable deep learning models using clinical and magnetic resonance imaging data? METHODS: In this observational study, we collected data of 222 patients with middle cerebral artery M1 segment occlusion who received mechanical thrombectomy. In a 5-fold cross validation, we evaluated interpretable deep learning models for predicting functional outcome in terms of modified Rankin scale at 3 months using clinical variables, diffusion weighted imaging and perfusion weighted imaging, and a combination thereof. Based on 50 test patients, we compared model performances to those of 5 experienced stroke neurologists. Prediction performance for ordinal (modified Rankin scale score, 0-6) and binary (modified Rankin scale score, 0-2 versus 3-6) functional outcome was assessed using discrimination and calibration measures like area under the receiver operating characteristic curve and accuracy (percentage of correctly classified patients). RESULTS: In the cross validation, the model based on clinical variables and diffusion weighted imaging achieved the highest binary prediction performance (area under the receiver operating characteristic curve, 0.766 [0.727-0.803]). Performance of models using clinical variables or diffusion weighted imaging only was lower. Adding perfusion weighted imaging did not improve outcome prediction. On the test set of 50 patients, binary prediction performance between model (accuracy, 60% [55.4%-64.4%]) and neurologists (accuracy, 60% [55.8%-64.21%]) was similar when using clinical data. However, models significantly outperformed neurologists when imaging data were provided, alone or in combination with clinical variables (accuracy, 72% [67.8%-76%] versus 64% [59.8%-68.4%] with clinical and imaging data). Prediction performance of neurologists with comparable experience varied strongly. CONCLUSIONS: We hypothesize that early prediction of functional outcome in large vessel occlusion stroke patients may be significantly improved if neurologists are supported by interpretable deep learning models.

Machine-learning-based outcome prediction in stroke patients with middle cerebral artery-M1 occlusions and early thrombectomy.

BACKGROUND AND PURPOSE: Clinical outcomes vary substantially among individuals with large vessel occlusion (LVO) stroke. A small infarct core and large imaging mismatch were found to be associated with good recovery. The aim of this study was to investigate whether those imaging variables would improve individual prediction of functional outcome after early (<6 h) endovascular treatment (EVT) in LVO stroke. METHODS: We included 222 patients with acute ischemic stroke due to middle cerebral artery (MCA)-M1 occlusion who received EVT. As predictors, we used clinical variables and region of interest (ROI)-based magnetic resonance imaging features. We developed different machine-learning models and quantified their prediction performance according to the area under the receiver-operating characteristic curves and the Brier score. RESULTS: The rate of successful recanalization was 78%, with 54% patients having a favorable outcome (modified Rankin scale score 0-2). Small infarct core was associated with favorable functional outcome. Outcome prediction improved only slightly when imaging was added to patient variables. Age was the driving factor, with a sharp decrease in likelihood of favorable functional outcome above the age of 78 years. CONCLUSIONS: In patients with MCA-M1 occlusion strokes referred to EVT within 6 h of symptom onset, infarct core volume was associated with outcome. However, ROI-based imaging variables led to no significant improvement in outcome prediction at an individual patient level when added to a set of clinical predictors. Our study is in concordance with current practice, where imaging mismatch or collateral readouts are not recommended as factors for excluding patients with MCA-M1 occlusion for early EVT.

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke.

BACKGROUND: An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS: CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS: 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION: Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT.

Brush Sign Is Associated With Increased Severity in Cerebral Venous Thrombosis.

Background and Purpose- The brush sign (BS) is an abnormally accentuated signal drop of the subependymal and deep medullary veins in paramagnetic-sensitive magnetic resonance sequences, previously described in acute ischemic stroke. We aimed to describe the BS in patients with thrombosis of the cerebral veins and sinuses and explore its association with clinical severity, thrombosis extent, parenchymal brain lesion, and clinical prognosis. Methods- We assessed consecutive adult patients admitted to 2 university hospitals with diagnosis of acute thrombosis of the cerebral veins and sinuses and imaging assessment with magnetic resonance imaging, including paramagnetic-sensitive sequences. Demographics, imaging findings, clinical presentation, and functional outcome at 3 months were analyzed according to the presence of BS. Results- In 118 patients included, BS was observed in gradient-echo T2*weighted (T2*WI) in 16% and susceptibility-weighted imaging in 13% of cases. All patients with BS had thrombosis of the superior sagittal sinus, straight sinus, or deep venous system. BS was associated with ipsilateral parenchymal lesion (odds ratio, 6.4; 95% CI, 1.9-21.1; P=0.002) and higher thrombus load (median [interquartile range] 5 [4-6] versus 2 [2-4]); P<0.0001). BS was also associated with focal neurological deficits (OR 4.2; 95%CI, 1.4-12.7, P=0.01). The functional outcome at 3 months was not significantly different in patients with BS. Conclusions- BS in T2*WI and susceptibility-weighted imaging was observed in approximately one in 7 patients with acute thrombosis of the cerebral veins and sinuses. BS was significantly associated with ipsilateral parenchymal brain lesion, extent of thrombosis, and manifestation with focal neurological deficits. This suggests that BS can represent a marker of severity in thrombosis of the cerebral veins and sinuses.

Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0-5.

Background and Purpose- If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0-5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0-5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods- Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration-URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0-3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0-2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results- Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0-5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363-12.961), functional independence (aOR, 5.583; 95% CI, 1.964-15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083-0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062-0.887). The mortality-reducing effect remained in patients with ASPECTS 0-4 (aOR, 0.167; 95% CI, 0.056-0.499). Sensitivity analyses did not change the primary results. Conclusions- In patients presenting with ASPECTS 0-5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.

Predictors of Unexpected Early Reocclusion After Successful Mechanical Thrombectomy in Acute Ischemic Stroke Patients.

Background and Purpose- Sustained successful reperfusion is an important prognostic factor for good clinical outcome in acute ischemic stroke. We aimed to identify the prevalence, clinical impact, and predictors of early reocclusion after initially successful thrombectomies within a prospective cohort. Methods- A total of 711 stroke patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b/3) followed with magnetic resonance or computed tomographic angiography at 24 to 48 hours were included. Multivariable logistic regression analysis was used to evaluate associated factors and clinical impact. Results are displayed as adjusted odds ratio (aOR) and 95% CI. Improvement in accuracy of additional imaging findings on angiography control runs after the intervention was evaluated by area under the curve. Results- Early reocclusion was observed in 16 of 711 successfully reperfused patients (2.3%; 95% CI, 1.1-3.3; median delay: 20 hours). Suggestive predictors were higher platelets on admission (aOR, 1.01; 95% CI, 1.01-1.02), prestroke functional dependence (aOR, 7.12; 95% CI, 1.49-34.03), and stroke of undetermined or other specified pathogenesis in the TOAST classification (aOR, 7.19; 95% CI, 1.10-47.05 and aOR, 36.50; 95% CI, 4.47-298.11, respectively). When implementing residual embolic fragments or stenosis at the thrombectomy site into the logistic regression model, discrimination between patients with and without reocclusion improved significantly (area under the curve, 0.955 versus 0.854; P=0.023). Early reocclusion was an independent predictor of unfavorable outcome at 90 days (aOR for modified Rankin Scale ≤2, 0.13; 95% CI, 0.03-0.57). Conclusions- Early reocclusion within 48 hours after successful mechanical thrombectomy is rare but associated with poor outcome. Patients with high platelets on admission and residual embolic fragments or stenosis at the thrombectomy site are at high risk for reocclusion, which may be prevented or corrected after carefully re-evaluating the last angiographic run.

Neurovascular Adverse Effects of Sars-Cov-2 Vaccination.

The global deployment of SARS-CoV-2 vaccines has been pivotal in curbing the COVID-19 pandemic, reducing morbidity and mortality associated with the virus. While most of these vaccines have demonstrated high efficacy and overall safety, emerging reports have highlighted potential neurovascular adverse effects, albeit uncommon, associated with these vaccinations. This review aims to assess and summarize the current knowledge on the neurovascular complications arising post-SARS-CoV-2 vaccination. We conducted an extensive literature review, focusing on clinical studies and case reports to identify reported neurovascular events, such as ischemic stroke, cerebral sinus venous thrombosis, intracerebral hemorrhage, pituitary apoplexy and primary CNS angiitis Despite the relative rarity of these events, their impact on affected individuals underscores the importance of ongoing surveillance, early detection, and management strategies. We aim to provide healthcare professionals with the latest evidence on neurovascular adverse effects, facilitating informed decision-making in the context of SARS-CoV-2 vaccination programs. Furthermore, we highlight areas requiring further research to understand the pathophysiology of these adverse events better and to develop targeted prevention and treatment strategies.

Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally. This review offers a detailed analysis of stem cell applications in stroke (ischemic and hemorrhagic) recovery. It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), and Granulocyte-Colony Stimulating Factor (G-CSF) based stem cells, focusing on cell types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear Stem Cells (BMMSCs), and Neural Stem/Progenitor Cells (NSCs). The paper compiles clinical trial data to evaluate their effectiveness and safety and addresses the ethical concerns of these innovative treatments. By explaining the mechanisms of stem cell-induced neurological repair, this review underscores stem cells' potential in revolutionizing stroke rehabilitation and suggests avenues for future research.

Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis.

BACKGROUND AND OBJECTIVES: In patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA. METHODS: We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events (intracranial hemorrhage [ICrH], IS, or any stroke [ICrH or IS]), and mortality. We calculated incidence rates (IRs) and performed univariable and multivariable Cox regression analyses. RESULTS: Of 12,669 patients (mean age 70.4 ± 12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24 ± 17 months, IS was more frequent than ICrH in both cSS (IR 57.1 vs 14.6 per 1,000 patient-years) and non-cSS (33.7 vs 6.3 per 1,000 patient-years) groups. Compared with the non-cSS group, cSS was associated with any stroke on multivariable analysis {IR 83 vs 42 per 1,000 patient-years, adjusted hazard ratio [HR] for cSS 1.62 (95% CI: 1.14-2.28; p = 0.006)}. This association was not significant in subgroups of patients treated with antiplatelet drugs (n = 6,554) or with anticoagulants (n = 4,044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n = 1,569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1,000 patient-years, adjusted HR 13.26; 95% CI: 2.90-60.63; p = 0.001) and of any stroke (IR 198.8 vs 34.7 per 1,000 patient-years, adjusted HR 5.03; 95% CI: 2.03-12.44; p < 0.001) compared with the non-cSS group. DISCUSSION: Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials.

Early and delayed neurological manifestations of cardiac myxomas.

Cardiac myxoma can embolize and cause early and delayed sequelae including stroke, growth into intracranial fusiform aneurysms and cerebral tumors with risk of hemorrhage and mass effect. Here, we report the rare coincidence of all these manifestations in a 63-year-old man who presented with cognitive and behavioral changes, and seizures 9 months after an embolic stroke from the heart tumor. C-reactive protein (CRP) was elevated at the time of stroke and cardiac myxoma diagnosis but was normal at late neurologic manifestation with isolated myxoma-related intracranial tumors and aneurysms. Low-dose whole-brain radiotherapy can be helpful to diminish cerebral myxoma tumors and fusiform aneurysms despite reported increased risk of aneurysm rupture.

Outcome of patients with large vessel occlusion in the anterior circulation and low NIHSS score.

BACKGROUND: Optimal management of patients with large vessel occlusion (LVO) and low NIHSS score is unknown, which was the aim to investigate in this study. METHODS: This is a retrospective analysis of a prospective single tertiary care centre 14-year cohort of patients with LVO in the anterior circulation and NIHSS score ≤ 5 on admission. Outcome was analysed according to primary intended therapy. RESULTS: Among 185 patients (median age 67.4 years), 52.4% received primary conservative therapy (including 26.8% secondary reperfusion in case of secondary neurological deterioration), 12.4% IV thrombolysis (IVT) only and 35.1% primary endovascular therapy (EVT). 95 (51.4%) patients experienced neurological deterioration until 3 months. Primary-IVT-only and primary-EVT compared to conservative-therapy patients had better 3 months' outcome (54.5% vs. 30.8%: adjustedOR 6.02; adjustedp = 0.004 for mRS 0-1 and 54.7% vs. 30.8%: adjustedOR 5.09; adjustedp = 0.002, respectively). Also mRS shift analysis favored primary-IVT-only and primary-EVT patients (adjustedOR 6.25; adjustedp = 0.001 and adjustedOR 3.14; adjustedp = 0.003). Outcome in primary-IVT-only vs. primary-EVT patients did not differ significantly. Patients who received secondary EVT because of neurological deterioration after primary-conservative-therapy had worse 3 months' outcome than primary-EVT patients (20.8% vs. 30.8%: adjustedOR 0.24; adjustedp = 0.047 for mRS 0-1 and adjustedOR 0.31; adjustedp = 0.019 in mRS shift analysis). Survival and symptomatic intracranial haemorrhage did not differ amongst groups. CONCLUSIONS: Our data indicate that primary IVT and/or EVT may be better than primary conservative therapy in patients with LVO in the anterior circulation and low NIHSS score. Furthermore, primary EVT was better than secondary EVT in case of neurological deterioration. There is an unmet need for RCTs to find the optimal therapy for this patient group.

Clinical effect of successful reperfusion in patients presenting with NIHSS < 8: data from the BEYOND-SWIFT registry.

BACKGROUND AND PURPOSE: If patients presenting with large vessel occlusions (LVO) and mild symptoms should be treated with endvoascular treatment (EVT) remains unclear. Aims of this study were (1) assessing the safety and technical efficacy of EVT in patients with NIHSS < 8 as opposed to a comparison group of patients presenting with NIHSS ≥ 8 and (2) evaluation of the clinical effect of reperfusion in patients with NIHSS < 8. METHODS: Patients included into the retrospective multicenter BEYOND-SWIFT registry (NCT03496064) were analyzed. Clinical effect of achieving successful reperfusion (defined as modified Thrombolysis in Cerebral Infarction grade 2b/3) in patients presenting with NIHSS < 8 (N = 193) was evaluated using multivariable logistic regression analyses (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI). Primary outcome was excellent functional outcome (modified Rankin Scale, mRS 0-1) at day 90. Safety and efficacy of mechanical thrombectomy in patients with NIHSS < 8 was compared to patients presenting with NIHSS ≥ 8 (N = 1423). RESULTS: Among patients with NIHSS < 8 (N = 193, 77/193, 39.9% receiving pre-interventional IV-tPA), successful reperfusion was significantly related to mRS 0-1 (aOR 3.217, 95%-CI 1.174-8.816) and reduced the chances of non-hemorrhagic neurological worsening (aOR 0.194, 95%-CI 0.050-0.756) after adjusting for prespecified confounders. In interaction analyses, the relative merits of achieving successful reperfusion were mostly comparable between patients presenting with NIHSS < 8 and NIHSS ≥ 8 as evidenced by non-significantly different aOR. Interventional safety and efficacy metrics were similar between patients with NIHSS < 8 and NIHSS ≥ 8. CONCLUSIONS: Achieving successful reperfusion is beneficial in patients with persisting LVO presenting with NIHSS < 8 and reduces the risk of non-hemorrhagic neurological worsening.

Mechanical thrombectomy for basilar artery occlusion: efficacy, outcomes, and futile recanalization in comparison with the anterior circulation.

BACKGROUND: Performing mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based. OBJECTIVE: To compare patients' outcome, relative merits of achieving recanalization, and predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT. METHODS: In the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms. RESULTS: MT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 - 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 - 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO. CONCLUSIONS: In selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR. TRIAL REGISTRATION NUMBER: NCT03496064.

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

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 [1·23-1·82]). 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 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.