BACKGROUND: The hypointense blooming signal of thrombi on susceptibility-weighted imaging (SWI), known as the susceptibility vessel sign (SVS), is predictive of cardioembolic stroke. The SVS originates from the local magnetic susceptibility effect; thus, the susceptibility value of thrombi may provide useful information in discriminating stroke etiology. We aim to utilize quantitative susceptibility mapping (QSM) to assess thrombuss susceptibility value in acute ischemic stroke patients and explore the relationship of thrombus susceptibility with cardioembolic stroke. METHODS: From 2018 to 2020, 132 consecutive acute ischemic stroke patients with middle cerebral artery occlusion were recruited within 48 hours of onset. All patients underwent a three-dimensional multi-echo SWI scan using a 3 Tesla magnetic resonance imaging scanner. The SVS presence and the diameter of the SVS-related hypointense signal were assessed on SWI. QSM was applied to compute the susceptibility value of the thrombus. The receiver operating characteristic (ROC) methodology was used to define the optimal cutoff value of the susceptibility in QSM and the diameter on SWI for predicting cardioembolic stroke. RESULTS: The SVS was identified in 93 (70.5%) patients with symptomatic middle cerebral artery occlusion and was significantly associated with cardioembolism. The hyperintense signal on QSM in the corresponding middle cerebral artery occlusion was present in 116 (87.9%) patients. ROC analysis indicated that thrombus susceptibility had a greater area under the curve than that of the SVS diameter (0.88 vs. 0.70, P<0.001) and that the optimal cutoff value of thrombus susceptibility for cardioembolism was 0.35 ppm. Multivariate analysis demonstrated that thrombus susceptibility (≥0.35 ppm) was an independent predictor of cardioembolic stroke (odds ratio =20.75; 95% CI, 7.19-59.87; P<0.001), with sensitivity, specificity, a positive predictive value, and a negative predictive value of 85.2%, 80.8%, 75.4%, and 88.7%, respectively, while the SVS presence showed sensitivity, specificity, a positive predictive value, and a negative predictive value of 90.7%, 43.6%, 87.2%, and 52.7%, respectively. CONCLUSIONS: Thrombus susceptibility provides superior diagnostic performance over the SVS for discriminating between cardioembolism and other stroke subtypes. Quantitative susceptibility measurements of thrombi may help predict cardioembolic stroke in patients with acute middle cerebral artery occlusion.

The susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) in the middle cerebral artery is a reliable biomarker for cardioembolic ischemic stroke. As for the basilar artery (BA), the magnetic susceptibility-related image signs, the quantitative evaluation of the corresponding thrombus, and their prediction of cardioembolism require further study. This study aimed to assess thrombus susceptibility-related image characteristics using susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) MRI in acute BA occlusion and analyze their associations with cardioembolic ischemic stroke. A total of 41 consecutive acute ischemic stroke patients with BA occlusion within 48 h of onset were recruited. A three-dimensional (3D) multi-echo scan on a 3.0T MRI scanner was applied to all participants, and the quantitative susceptibility value of the BA thrombus was computed using QSM. The presence and diameter of SWI SVS in patients with cardioembolic stroke were not significantly different from those with other etiologies. While BA thrombuss susceptibility in patients with cardioembolic stroke was significantly higher than that in patients with non-cardioembolic stroke (0.42±0.09 vs. 0.22±0.11 ppm, P<0.001). Receiver operating characteristic (ROC) curve analysis showed that the optimal cutoff value for the QSM susceptibility of BA thrombus in the identification of cardioembolic stroke was 0.33 ppm, with sensitivity, specificity, positive predictive value, and negative predictive value of 81.8% (95% CI: 48.2% to 97.7%), 81.3% (95% CI: 63.6% to 92.8%), 60.0% (95% CI: 40.9% to 76.5%), and 92.9% (95% CI: 78.6% to 97.9%), respectively. Magnetic susceptibility in BA thrombus could discriminate cardiogenic embolism from other stroke subtypes, thus becoming a novel biomarker of cardiogenic stroke in acute BA occlusion.

Background: The benefits of heparization during mechanical thrombectomy (MT) with newer generation thrombectomy devices, and if it is counterbalanced by the increased risk of intracranial hemorrhage (ICH) remain unknown. Methods: We included eligible patients who underwent MT from the ANGEL registry study (2015-2017) in China. Subjects in the current analysis were dichotomized into two groups according to whether adequate heparinization during MT was performed. In the heparinization group, unfractionated heparin was infused at 50-100 IU/Kg at first and additional 1,000 IU at intervals of an hour during the operation. Safety outcomes (symptomatic intracerebral hemorrhage [sICH], ICH and distal embolization) and efficacy outcomes (artery recanalization and functional outcomes at 3-month follow-up) were compared between groups. Results: We included 619 patients from the entire cohort of 917 patients. The average age of them was 63.9 ± 13.7 years, 269 (43.5%) were treated with heparinization during MT. Heparinization during MT didnt significantly influence recanalization rates, total ICH and long-term mortality (adjusted p > 0.05 for all). But sICH and distal embolization occurred more frequently (9.3 vs. 5.1%, adjusted p = 0.02; 7.1 vs. 3.1%, adjusted p = 0.04, respectively), while functional independence appeared less likely (39.8 vs. 47.4%, adjusted p = 0.01) in heparinization group than that in non-heparinization group. Multivariable logistic regression analyses showed that heparinization during MT was an independent predictor for sICH (Odds ratio 2.36 [1.19-4.67], p = 0.01) in addition to cardio-embolism stroke and posterior circulation stroke (PCS), and an independent predictor for poor outcome (Odds ratio 1.79 [1.23-2.59], p < 0.01) besides age, bridging intravenous thrombolysis, admission NIHSS, drinking and PCS. Conclusion: Heparinization during MT may be associated with increased risk of safety outcomes over sICH and distal embolization, as well as efficacy outcomes over long-term poor outcome. Further randomized controlled trials are needed.

In acute ischemic stroke patients with large vessel occlusion, the characteristics of the occluding thrombus on neuroimaging may be associated with recanalization after endovascular thrombectomy (EVT); however, the relationship between magnetic susceptibility of thrombus and clinical outcome remains unclear. We utilized quantitative susceptibility mapping (QSM) MRI to assess the magnetic susceptibility of thrombus in acute ischemic stroke patients undergoing EVT, and to evaluate its relationship with recanalization and functional outcomes. Patients with documented intracranial artery occlusion were consecutively recruited from one research center of the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). All the recruited patients underwent a 3D multi-echo MRI scan on a 3.0 T scanner for both susceptibility-weighted imaging (SWI) and QSM quantification of the thrombus. Among 61 patients included in the analyses, 51 (75.0 %) patients achieved thrombolysis in cerebral infarction (TICI) 2b/3 and 22 (36.1 %) patients had favorable functional outcomes. Successful recanalization was significantly associated with a higher thrombus magnetic susceptibility mean value (0.27 ± 0.09 vs 0.20 ± 0.09 ppm, p = 0.020) and lower coefficient of variation (0.42 ± 0.12 vs 0.52 ± 0.19, p = 0.024). ROC curve analysis showed the optimal cutoff value for thrombus susceptibility for predicting good clinical outcomes was 0.25 ppm (sensitivity 86.4 %, specificity 69.2 %). In multivariable logistic regression analyses, increased thrombus magnetic susceptibility was independently and significantly associated with good functional outcomes (adjusted odds ratio 15.11 [95 % confidence interval 2.64-86.46], p = 0.002). This study demonstrated that the increased thrombus magnetic susceptibility is associated with successful recanalization and favorable functional outcomes for intracranial artery occluded stroke patients.

Background and Purpose: Our aim was to investigate the frequency of dehydration at admission and associations with in-hospital mortality in patients with intracerebral hemorrhage (ICH). Methods: Data of consecutive patients with ICH between August 2015 and July 2019 from the China Stroke Center Alliance (CSCA) registry were analyzed. The patients were stratified based on the blood urea nitrogen (BUN) to creatinine (CR) ratio (BUN/CR) on admission into dehydrated (BUN/CR ≥ 15) or non-dehydrated (BUN/CR < 15) groups. Data were analyzed with multivariate logistic regression models to investigate admission dehydration status and the risks of death at hospital. Results: A total number of 84,043 patients with ICH were included in the study. The median age of patients on admission was 63.0 years, and 37.5% of them were women. Based on the baseline BUN/CR, 59,153 (70.4%) patients were classified into dehydration group. Patients with admission dehydration (BUN/CR ≥ 15) had 13% lower risks of in-hospital mortality than those without dehydration (BUN/CR < 15, adjusted OR = 0.87, 95%CI 0.78-0.96). In patients aged <65 years, admission dehydration was associated with 19% lower risks of in-hospital mortality (adjusted OR = 0.81, 95%CI 0.70-0.94. adjusted p = 0.0049) than non-dehydrated patients. Conclusion: Admission dehydration is associated with significantly lower in-hospital mortality after ICH, in particular, in patients <65 years old.

BACKGROUND: The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs). AIM: To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS. DESIGN: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35-80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%-99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years. STUDY OUTCOMES: Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome. DISCUSSION: BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS. TRIAL REGISTRATION NUMBER: NCT03703635; https://www. CLINICALTRIALS: gov.

Background

Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity.

Methods

In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated.

Results

Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient -0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values.

Conclusions

Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.

BACKGROUND: The benefit of stroke thrombectomy for large infarct core still lacks robust randomised controlled studies. AIM: To demonstrate the design of a clinical trial on endovascular therapy for acute anterior circulation large vessel occlusion (LVO) patients with large infarct core volume. DESIGN: ANGEL-ASPECT is a multicentre, prospective, randomised, open-label, blinded End-point trial to evaluate whether best medical management (BMM) combined with endovascular therapy improves neurological functional outcomes as compared with BMM alone in acute LVO patients with Alberta Stroke Program Early CT Score (ASPECTS) of 3-5 on non-contrast CT or infarct core volume range of 70-100 mL (defined as rCBF <30% on CT perfusion or ADC <620 on MRI) up to 24 hours from symptom onset or last seen well. STUDY OUTCOMES: The primary efficacy outcome is 90 (±7) days modified Rankin Scale. Symptomatic intracranial haemorrhage within 48 hours from randomisation is the primary safety outcome. DISCUSSION: The ANGEL-ASPECT trial will screen patients with large infarct core (ASPECTS 3-5 or 70-100 mL) through image evaluation criteria within 24 hours and explore the efficacy and safety of endovascular therapy compared with BMM.

Objective

We compared the effect of clopidogrel plus aspirin vs aspirin alone on functional outcome and quality of life in the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial of aspirin-clopidogrel vs aspirin alone after acute minor stroke or TIA.

Methods

Participants were assessed at 90 days for functional outcome using the modified Rankin Scale (mRS) and quality of life using the EuroQol-5 Dimension (EQ-5D). Poor functional outcome was defined as mRS score of 2-6 at 90 days and poor quality of life as EQ-5D index score of 0.5 or less.

Results

Poor functional outcome occurred in 254 patients (9.9%) in the clopidogrel-aspirin group, as compared with 299 (11.6%) in the aspirin group (p = 0.046). Poor quality of life occurred in 142 (5.5%) in the clopidogrel-aspirin group and in 175 (6.8%) in the aspirin group (p = 0.06). Disabling stroke at 90 days occurred in 166 (6.5%) in the clopidogrel-aspirin group and in 219 (8.5%) in the aspirin group (p = 0.01). In stratified analysis by subsequent stroke, there was no difference in 90-day functional outcome and quality of life between the 2 groups.

Conclusions

In patients with minor stroke or TIA, the combination of clopidogrel and aspirin appears to be superior to aspirin alone in improving the 90-day functional outcome, and this is consistent with a reduction in the rate of disabling stroke in the dual antiplatelet arm.

Classification of evidence

This study provides Class II evidence that for patients with acute minor stroke or TIA, clopidogrel plus aspirin compared to aspirin alone improves 90-day functional outcome (absolute reduction of poor outcome 1.70%, 95% confidence interval 0.03%-3.42%).

Brain ischemia and reperfusion activate the immune system. The abrupt development of brain ischemic lesions suggests that innate immune cells may shape the outcome of stroke. Natural killer (NK) cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses, but their role during stroke remains unknown. Herein, we found that NK cells infiltrated the ischemic lesions of the human brain. In a mouse model of cerebral ischemia, ischemic neuron-derived fractalkine recruited NK cells, which subsequently determined the size of brain lesions in a T and B cell-independent manner. NK cell-mediated exacerbation of brain infarction occurred rapidly after ischemia via the disruption of NK cell tolerance, augmenting local inflammation and neuronal hyperactivity. Therefore, NK cells catalyzed neuronal death in the ischemic brain.