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Background and Objectives: The objective of this study was to assess the relationship between blood biomarkers of inflammation and lesion growth within the penumbra in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT)., Methods: The HIBISCUS-STROKE cohort enrolled patients admitted in the Lyon Stroke Center for an anterior circulation AIS treated with MT after brain MRI assessment. Lesion growth within the penumbra was assessed on day 6 MRI using a voxel-based nonlinear coregistration method and dichotomized into low and high according to the median value. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2 (sST2), soluble P-selectin, vascular cellular adhesion molecule-1, and matrix metalloproteinase-9 were measured in sera at 4 time points within the first 48 hours. Reperfusion was considered as successful if Thrombolysis in Cerebral Infarction score was 2b/2c/3. A multiple logistic regression model was performed to detect any association between area under the curve (AUC) of these biomarkers within the first 48 hours and a high lesion growth within the penumbra., Results: Ninety patients were included. The median lesion growth within the penumbra was 2.3 (0.7-6.2) mL. On multivariable analysis, a high sST2 AUC (OR 3.77, 95% CI 1.36-10.46), a high baseline DWI volume (OR 3.65, 95% CI 1.32-10.12), and a lack of successful reperfusion (OR 0.19, 95% CI 0.04-0.92) were associated with a high lesion growth within the penumbra. When restricting analyses to patients with successful reperfusion (n = 76), a high sST2 AUC (OR 5.03, 95% CI 1.64-15.40), a high baseline DWI volume (OR 3.74, 95% CI 1.22-11.53), and a high penumbra volume (OR 3.25, 95% CI 1.10-9.57) remained associated with a high lesion growth within the penumbra., Discussion: High sST2 levels within the first 48 hours are associated with a high lesion growth within the penumbra., (© 2022 American Academy of Neurology.)

Inflammation is involved in small vessel disease (SVD). We aim to clarify whether inflammation related to white matter hyperintensities (WMH), a key component of SVD, may affect the inflammatory response in acute ischemic stroke (AIS) patients. For this, we sequentially measured 10 circulating inflammatory markers and assessed WMH burden on admission MRI in AIS patients treated with thrombectomy. Of 149 patients, 57 (38.3%) had a high WMH burden (Fazekas≥3). A high WMH burden was associated with 4 markers levels but this association did not remain following multivariable analyses. WMH burden is not associated with a specific inflammatory profile in AIS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Background: First-pass effect (FPE) defined as a complete or near-complete reperfusion achieved after a single thrombectomy pass is predictive of favorable outcome in acute ischemic stroke (AIS) patients. We aimed to assess whether admission levels of inflammatory markers are associated with FPE., Methods: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes AIS patients with large vessel occlusion treated with mechanical thrombectomy following brain MRI. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2, matrix metalloproteinase-9 (MMP-9), soluble P-selectin, and vascular cellular adhesion molecule-1 were measured in admission sera using an ELISA assay. FPE was defined as a complete or near-complete reperfusion (thrombolysis in cerebral infarction scale (TICI) 2c or 3) after the first pass. A multivariate logistic regression analysis was performed to assess independent factors associated with FPE., Results: A total of 151 patients were included. Among them, 43 (28.5%) patients had FPE. FPE was associated with low admission levels of IL-6, MMP-9, and platelet count, an older age, lack of hypertension, lack of tandem occlusion, a shorter thrombus length, and a reduced procedural time. Following multivariate analysis, a low admission level of IL-6 was associated with FPE (OR 0.66, 95% CI 0.46 to 0.94). Optimal cut-off of IL-6 level for distinguishing FPE from non-FPE was 3.0 pg/mL (sensitivity 92.3%, specificity 42.3%)., Conclusion: A lower admission level of IL-6 is associated with FPE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Embolic stroke of undetermined source (ESUS) accounts for up to 25% of ischemic strokes. Identification of biomarkers that could improve the prediction of stroke subtype and subsequently of stroke prevention still remains a major issue., Methods: The HIBISCUS-STROKE cohort includes ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. Presence and length of susceptibility vessel sign (SVS) were assessed by gradient-recalled echo T2*-weighted imaging. Matrix metalloproteinase-9 (MMP-9) was measured on sera collected at admission. A multiple logistic regression model was performed to detect independent markers distinguishing cardioembolic (CE) from large-artery atherosclerosis (LAA) subtype., Results: A total of 147 patients were included, of them the etiology was distributed as follows: 86 (58.5%) CE, 26 (17.7%) LAA, and 35 (23.8%) ESUS. The optimal cutoff for differentiating CE from LAA subtype was 14.5 mm for SVS length (sensitivity, 79.7%; specificity, 72.7%) and 1110 ng/ml for admission MMP-9 level (sensitivity, 85.3%; specificity, 52.2%). Multivariate analysis revealed that current smoking (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.93), tandem occlusion (OR 0.01, 95% CI 0.01-0.21), SVS length (OR 0.78, 95% CI 0.63-0.97), and admission MMP-9 level (OR 0.99, 95% CI 0.99-1.00) were inversely associated with CE subtype. SVS length and MMP-9 level did not differ between ESUS and CE subtypes., Conclusion: SVS length and admission MMP-9 level may improve the prediction of CE subtype whose profile is close to ESUS, thus suggesting a common cardiac embolic source., (© 2021 European Academy of Neurology.)

Background and Purpose: In ischemic stroke, inflammatory status may condition the development of collateral circulation. Here we assessed the relationship between systemic inflammatory biomarkers and collateral status in large vessel occlusion before mechanical thrombectomy., Methods: HIBISCUS-STROKE is a cohort study including acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. MMP-9 (matrix metalloproteinase-9) and MCP-1 (monocyte chemoattractant protein-1) were measured on blood sampling collected at admission. Collateral status was assessed on pretreatment Digital subtraction angiography and categorized into poor (Higashida score, 0-2) and good (Higashida score, 3-4). A multiple logistic regression model was performed to detect independent markers of good collateral status., Results: One hundred and twenty-two patients were included, of them 71 patients (58.2%) had a good collateral status. In univariate analysis, low MMP-9 levels ( P =0.01), high MCP-1 levels ( P <0.01), a low National Institute of Health Stroke Score ( P =0.046), a high diastolic blood pressure ( P =0.049), the absence of tandem occlusion ( P =0.046), a high Alberta Stroke Program Early CT Score ( P <0.01) and a low volume on the diffusion-weighted imaging ( P <0.01) were associated with good collateral status. Following multivariate analysis, low MMP-9 levels ( P =0.02) and high MCP-1 levels ( P <0.01) remained associated with good collateral status., Conclusions: Low MMP-9 and high MCP-1 levels were associated with good pretreatment collateral status in patients with acute ischemic stroke with large vessel occlusion. These results might suggest a relationship between collateral status and inflammation.