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Background and purpose: Better characterization of the thrombus could be useful to determine acute ischaemic stroke (AIS) aetiology and predict response to thrombolysis and endovascular therapy (EVT). To test the hypothesis that susceptibility vessel sign (SVS) on baseline magnetic resonance imaging (MRI) is related to red blood cell (RBC) content of AIS thrombi, the total haemoglobin contents (HbCs) of AIS thrombi retrieved by EVT from patients with or without SVS or two‐layered SVS (TLSVS) were compared. Methods: Baseline MRI of 84 anterior AIS patients was reviewed by neuro‐radiologists blinded to clinical and biochemical data. Thrombi from these patients were retrieved by EVT and analysed for HbC by quantitative enzyme‐linked immunosorbent assay and measurement of haem concentration. Results: Susceptibility vessel sign and TLSVS were respectively observed in 85.7% and 50.0% of cases. The median HbC content was 253 µg/mg thrombus (interquartile range 177–333) and the median haem content was 219 µg/mg thrombus (131–264). Thrombus HbC and haem content were highly correlated with thrombus RBC content determined by flow cytometry (r = 0.94). Thrombi from patients with TLSVS weighed more [31.1 (16.5–68.3) mg vs. 17.7 (11.7–33.3) mg; P = 0.005] and had a higher HbC content [278 (221–331) µg/mg vs. 196 (139–301) µg/mg; P = 0.010] compared to thrombi from patients without TLSVS. There was no difference in thrombus weight or HbC content according to SVS status. Conclusions: Our study shows that TLSVS is significantly associated with a higher thrombus weight and RBC content, as determined by quantitative assays. [ABSTRACT FROM AUTHOR]

Spinal cord stimulation (SCS) is an effective surgical therapy used for the treatment of chronic neuropathic pain. Tonic SCS is safe and improve not only gait disorders, motor symptoms, but also quality of life in Parkinson patients even with dopa-resistant symptoms with or without associated deep brain stimulation. [ABSTRACT FROM AUTHOR]

Background: Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however., Objectives: We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients., Patients/methods: For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen., Results: COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients., Conclusions: These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection., (© 2022 International Society on Thrombosis and Haemostasis.)

Background and Purpose: The Blood Pressure Target in Acute Ischemic Stroke to Reduce Hemorrhage After Endovascular Therapy (BP TARGET) trial evaluated whether an intensive systolic blood pressure (SBP) target resulted in reduced rates of intracranial hemorrhage (ICH) after successful endovascular therapy (EVT) but did not assess the effect of blood pressure variability (BPV) on functional outcomes and ICH occurrence. We sought to evaluate this question in the BP TARGET trial., Methods: We performed a post hoc analysis of the BP TARGET trial and included patients with at least 50% of blood pressure (BP) recordings during the first 24 h after EVT. BPV parameters were SBP and diastolic BP (DBP) coefficient of variation (CV), standard deviation (SD), maximum-minimum (max-min), successive variation (SV), and time rate. The primary outcome was favorable functional outcome (3-month modified Rankin Scale between 0 and 2); the secondary outcome was the rate of ICH at 24 h., Results: We included 290 patients (mean number of BP measures = 30.4, SD = 8.0). BPV parameters (SBP SD , SBP max-min , SBP CV ) were higher in the intensive SBP target group. Only DBP BPV parameters were associated with worse functional outcomes in the unadjusted model (DBP SD , DBP max-min , DBP CV , and DBP SV ), but not after adjustment. Higher SBP max-min was associated with worse functional outcomes in Thrombolysis in Cerebral Infarction 2B patients (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.38-1.02), but not in patients with complete reperfusion (OR = 1.27, 95% CI = 0.80-2.02, p for heterogeneity (p het =0.037). None of the BPV parameters was associated with ICH, regardless of the randomization group or the reperfusion grade., Conclusions: BPV was significantly higher in the intensive SBP target group but was not associated with functional outcome or ICH., (© 2021 European Academy of Neurology.)

Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. In vitro , the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization ( p < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.

Importance: Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation large vessel occlusion, but the additional benefit of combining contact aspiration with stent retriever is uncertain., Objective: To determine whether mechanical thrombectomy for treatment of anterior circulation large vessel occlusion stroke with initial contact aspiration and stent retriever combined results in better final angiographic outcome than with standard stent retriever alone., Design, Setting, and Participants: This trial was a multicenter randomized, open-label, blinded end point evaluation that enrolled 408 patients from October 16, 2017, to May 29, 2018, in 11 French comprehensive stroke centers, with a 12-month outcome follow-up. Patients with a large vessel occlusion in the anterior circulation were included up to 8 hours after symptom onset. The final date of follow-up was June, 19, 2019., Interventions: Patients were randomly assigned (1:1 allocation) to receive initial thrombectomy with contact aspiration and stent retriever combined (205) or stent retriever alone (203)., Main Outcomes and Measures: The primary outcome was the rate of expanded Thrombolysis In Cerebral Infarction score of 2c or 3 (eTICI 2c/3; ie, scores indicate near-total and total reperfusion grades) at the end of the procedure., Results: Among the 408 patients who were randomized, 3 were excluded, and 405 (99.3%) patients (mean age, 73 years; 220 [54%] women and 185 [46%] men) were included in the primary analysis. The rate of eTICI 2c/3 at the end of the endovascular procedure was not significantly different between the 2 thrombectomy groups (64.5% [131 of 203 patients] for contact aspiration and stent retriever combined vs 57.9% [117 of 202 patients] for stent retriever alone; risk difference, 6.6% [95% CI, -3.0% to 16.2%]; adjusted odds ratio [OR], 1.33 [95% CI, 0.88 to 1.99]; P = .17). Of 14 prespecified secondary efficacy end points, 12 showed no significant difference. A higher rate of successful reperfusion was achieved in the contact aspiration combined with stent retriever group vs the stent retriever alone group (eTICI 2b50/2c/3, 86.2% vs 72.3%; adjusted OR, 2.54 [95% CI, 1.51 to 4.28]; P < .001) and of near-total or total reperfusion (eTICI 2c/3, 59.6% vs 49.5%; adjusted OR, 1.52 [95% CI, 1.02 to 2.27]; P = .04) after the assigned initial intervention alone., Conclusions and Relevance: Among patients with acute ischemic stroke due to large vessel occlusion, an initial thrombectomy technique consisting of contact aspiration and stent retriever combined, compared with stent retriever alone, did not significantly improve the rate of near-total or total reperfusion (eTICI 2c/3) at the end of the endovascular procedure, although the trial may have been underpowered to detect smaller differences between groups., Trial Registration: ClinicalTrials.gov Identifier: NCT03290885.

Mechanical thrombectomy is now the standard of care for acute ischemic stroke patients with large vessel occlusions, and can be performed with several devices and techniques. One of these techniques, direct aspiration (DA), consists of navigating a large-bore catheter up to the face of the clot and initiating forceful suction. This comprehensive review has three objectives: (1) to describe the direct aspiration technique; (2) to present the available evidence regarding predictive factors of DA success and performance compared with other techniques; and (3) to discuss the forthcoming improvements in distal aspiration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Endovascular navigation through tortuous vessels can be complex. Tools that can optimise this access phase need to be developed. Our aim was to evaluate the feasibility of supra-aortic vessel catheterization guidance by means of live fluoroscopy fusion with MR angiography or CT angiography., Materials and Methods: Twenty-five patients underwent preinterventional diagnostic MRA, and 8 patients underwent CTA. Fusion guidance was evaluated in 35 sessions of catheterization, targeting a total of 151 supra-aortic vessels. The time for MRA/CTA segmentation and fluoroscopy with MRA/CTA coregistration was recorded. The feasibility of fusion guidance was evaluated by recording the catheterizations executed by interventional neuroradiologists according to a standard technique under fluoroscopy and conventional road-mapping independent of the fusion guidance. Precision of the fusion roadmap was evaluated by measuring (on a semiquantitative 3-point scale) the maximum offset between the position of the guidewires/catheters and the vasculature on the virtual CTA/MRA images. The targeted vessels were divided in 2 groups according to their position from the level of the aortic arch., Results: The average time needed for segmentation and image coregistration was 7 ± 2 minutes. The MRA/CTA virtual roadmap overlaid on live fluoroscopy was considered accurate in 84.8% (128/151) of the assessed landmarks, with a higher accuracy for the group of vessels closer to the aortic arch (92.4%; OR, 4.88; 95% CI, 1.83-11.66; P = .003)., Conclusions: Fluoroscopy with MRA/CTA fusion guidance for supra-aortic vessel interventions is feasible. Further improvements of the technique to increase accuracy at the cervical level and further studies are needed for assessing the procedural time savings and decreasing the x-ray radiation exposure., (© 2020 by American Journal of Neuroradiology.)

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), ( P <0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time ( P <0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

Rationale: Mechanical thrombectomy (MT) using a stent retriever (SR) device is currently the recommended treatment in ischemic stroke due to anterior circulation large vessel occlusion. Combining contact aspiration (CA) with SR is a promising new treatment, although it was not found to be superior to SR alone as first-line treatment for achieving successful reperfusion., Aim: To determine whether endovascular treatment combining first-line use of CA and SR is more efficient than SR alone., Methods: The ASTER 2 clinical trial is a prospective, randomized, multicenter, open-label trial with a blinded endpoint. We included patients admitted with suspected anterior circulation ischemic stroke secondary to large vessel occlusion <8 hours from symptom onset. They were randomly allocated in a 1:1 ratio to one of two treatment groups (combined CA and SR or SR alone). In the case of failure of the assigned technique after three attempts, other adjunctive techniques were applied., Study Outcome: The primary outcome is the rate of successful/complete reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score 2c/3) after the entire endovascular procedure. Secondary outcomes include reperfusion rates after the assigned first-line intervention alone and at the end of the procedure, procedural times, change in NIH Stroke Scale score at 24 hours, intracerebral hemorrhage at 24 hours, procedure-related serious adverse events, the modified Rankin Scale score, and all-cause mortality at 90 days and 1 year. The cost effectiveness of the two procedures will also be analyzed., Discussion: This is the first head-to-head randomized trial to directly compare the efficacy of the combined use of CA and SR versus SR alone. This prospective trial aims to demonstrate the synergistic effects of CA and SR devices in first-line endovascular treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The 'first pass effect' (FPE), which was originally described with stent retrievers, designates a (near-)complete revascularization obtained after a single device pass with no rescue therapy, and is associated with improved clinical outcome and decreased mortality., Objective: We report the rate and benefits of FPE in the Aspiration versus Stent Retriever (ASTER) trial., Materials and Methods: ASTER is a randomized trial comparing angiographic revascularization with the stent retriever (SR) and contact aspiration (CA) thrombectomy techniques, assessed by an external core laboratory using the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Rates of FPE (defined by mTICI 2c/3 after a single pass with no rescue therapy) were compared between patients treated with SR and CA techniques. Outcomes were compared between FPE-SR and FPE-CA patients, and between FPE and non-FPE patients., Results: FPE was achieved in 97/336 patients (28.9%), with no significant difference between SR and CA (respectively 53/169 patients (31.3%) vs 44/167 patients (26.3%), adjusted RR for CA versus SR 0.84, 95% CI 0.54 to 1.31; p=0.44). After prespecified adjustment for allocated arm and randomization stratification factors, FPE in patients was associated with a significantly improved clinical outcome and a decreased mortality, and a significantly lower rate of hemorrhagic transformation and procedural complications than in non-FPE patients., Conclusion: In the ASTER trial, similar rates of FPE were achieved with SR and CA, and FPE was associated with a significantly improved outcome. New techniques and devices to improve the rate of FPE are warranted., Trial Registration Number: Unique identifier: NCT02523261., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The DAWN trial (Diffusion weighted imaging or CT perfusion Assessment with clinical mismatch in the triage of Wake-up and late presenting strokes undergoing Neurointervention with Trevo) has demonstrated the benefits of thrombectomy in patients with unknown or late onset strokes, using automated software (RAPID) for measurement of infarct volume. Because RAPID is not available in all centers, we aimed to assess the accuracy and repeatability of visual infarct volume estimation by clinicians and the consequences for thrombectomy decisions based on the DAWN criteria., Materials and Methods: 18 physicians, who routinely depend on MRI for acute stroke imaging, assessed 32 MR scans selected from a prospective databaseover two independent sessions. Raters were asked to visually estimate the diffusion weighted imaging (DWI) infarct volume for each case. Sensitivity, specificity, and accuracy of the estimated volumes were compared with the available RAPID measurements for various volume cut-off points. Thrombectomy decisions based on DAWN criteria with RAPID measurements and raters' visual estimates were compared. Inter-rater and intra-rater agreement was measured using kappa statistics., Results: The mean accuracy of raters was <90% for all volume cut-points. Inter-rater agreement was below substantial for each DWI infarct volume cut-off points. Intra-rater agreement was substantial for 55-83% of raters, depending on the selected cut-off points. Applying DAWN criteria with visual estimates instead of RAPID measurements led to 19% erroneous thrombectomy decisions, and showed a lack of reproducibility., Conclusion: The visual assessment of DWI infarct volume lacks accuracy and repeatability, and could lead to a significant number of erroneous decisions when applying the DAWN criteria., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify early prognostic factors of poor clinical outcome in patients treated by endovascular therapy (EVT) with successful recanalization., Methods: We reviewed our monocentric prospectively collected EVT database of patients with anterior circulation acute ischemic stroke (AIS) from January 2016 to April 2018 who had achieved successful recanalization (Thrombolysis in Cerebral Infarction score ≥ 2b) at the end of the procedure. A poor outcome was defined as a 3-month modified Rankin Scale score of ≥3., Results: A total of 324 patients were included, among whom 186 (57.4%) had a poor outcome. Multivariate logistic regression indicated that age (per 10-year increase, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.12-1.60), baseline NIH Stroke Scale score (per 1-unit increase, OR 1.09, 95% CI 1.04-1.15), initial infarct volume (per a log+1 increase, OR 1.34, 95% CI 1.05-1.67), blood glucose level (per a log+1 increase, OR 2.60, 95% CI 1.01-6.66), and neutrophil count (per 1,000-unit increase, OR 1.08, 95% CI 1.01-1.17) were all associated with poor clinical outcome., Conclusions: In addition to baseline severe AIS criteria, high neutrophil count and high blood glucose, known from experimental studies to be associated with downstream microvascular thromboinflammation, are independently associated with poor outcome. These findings support a deleterious role of thromboinflammation in patient recovery despite successful recanalization., (© 2019 American Academy of Neurology.)

Background and Purpose: Hemorrhagic transformation (HT) is a complication of stroke that can occur spontaneously or after treatment. We aimed to assess the inter- and intrarater reliability of HT diagnosis., Methods: Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification of HT or of the presence (yes/no) of HT were systematically reviewed. A total of 18 raters independently examined 30 post-thrombectomy computed tomography scans selected from the Aspiration versus STEnt-Retriever (ASTER) trial. They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) (HI indicates hemorrhagic infarctions and PH indicates parenchymal hematomas) was and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement was measured with Fleiss' and Cohen's κ statistics., Results: The systematic review yielded four studies involving few (≤3) raters with heterogeneous results. In our 18-rater study, agreement for the presence of HT was moderate [κ = 0.55; 95% confidence interval (CI), 0.41-0.68]. Agreement for ECASS classification was only fair for all five categories, but agreement improved to substantial (κ = 0.72; 95% CI, 0.69-0.75) after dichotomizing the ECASS classification into 0/HI1/HI2/PH1 versus PH2. The inter-rater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ = 0.70; 95% CI, 0.57-0.84)., Conclusion: The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma., (© 2018 EAN.)

Objectives: To assess whether performing a pre-intervention gadolinium-enhanced extracranial magnetic resonance angiogram (MRA) in addition to intracranial vascular imaging is associated with improved thrombectomy time metrics. Methods: Consecutive patients treated by MT at a large comprehensive stroke center between January 2012 and December 2017 who were screened using pre-intervention MRI were included. Patients characteristics and procedural data were collected. Univariate and multivariate analysis were performed to compare MT speed, efficacy, complications, and clinical outcomes between patients with and without pre-intervention gadolinium-enhanced extracranial MRA. Results: A total of 912 patients were treated within the study period, including 288 (31.6%) patients with and 624 (68.4%) patients without extracranial MRA. Multivariate analysis showed no significant difference between groups in groin puncture to clot contact time (RR = 0.93 [0.85-1.02], p = 0.14) or to recanalization time (RR = 0.92 [0.83-1.03], p = 0.15), rates of successful recanalization (defined as a mTICI 2b or 3, RR = 0.93 [0.62-1.42], p = 0.74), procedural complications (RR = 0.81 [0.51-1.27], p = 0.36), and good clinical outcome (defined by a mRS ≤ 2 at 3 months follow-up, RR = 1.05 [0.73-1.52], p = 0.79). Conclusion: Performing a pre-intervention gadolinium-enhanced extracranial MRA in addition to non-contrast intracranial MRA at stroke onset does not seem to be associated with a delay or shortening of procedure times.

Purpose: We aimed to assess the agreement between study investigators and the core laboratory (core lab) of a thrombectomy trial for imaging scores., Methods: The Alberta Stroke Program Early CT Score (ASPECTS), the European Collaborative Acute Stroke Study (ECASS) hemorrhagic transformation (HT) classification, and the Thrombolysis In Cerebral Infarction (TICI) scores as recorded by study investigators were compared with the core lab scores in order to assess interrater agreement, using Cohen's unweighted and weighted kappa statistics., Results: There were frequent discrepancies between study sites and core lab for all the scores. Agreement for ASPECTS and ECASS HT classification was less than substantial, with disagreement occurring in more than one-third of cases. Agreement was higher on MRI-based scores than on CT, and was improved after dichotomization on both CT and MRI. Agreement for TICI scores was moderate (with disagreement occurring in more than 25% of patients), and went above the substantial level (less than 10% disagreement) after dichotomization (TICI 0/1/2a vs 2b/3)., Conclusion: Discrepancies between scores assessed by the imaging core lab and those reported by study sites occurred in a significant proportion of patients. Disagreement in the assessment of ASPECTS and day 1 HT scores was more frequent on CT than on MRI. The agreement for the dichotomized TICI score (the trial's primary outcome) was substantial, with less than 10% of disagreement between study sites and core lab., Trial Registration Number: NCT02523261, Post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: Neutrophil Extracellular Traps (NETs) are DNA extracellular networks decorated with histones and granular proteins produced by activated neutrophils. NETs have been identified as major triggers and structural factors of thrombosis. A recent study designated extracellular DNA threads from NETs as a potential therapeutic target for improving tissue-type plasminogen activator (tPA)-induced thrombolysis in acute coronary syndrome. The aim of this study was to assess the presence of NETs in thrombi retrieved during endovascular therapy in patients with acute ischemic stroke (AIS) and their impact on tPA-induced thrombolysis., Methods: We analyzed thrombi from 108 AIS patients treated with endovascular therapy. Thrombi were characterized by hematoxylin/eosin staining, immunostaining, and ex vivo enzymatic assay. Additionally, we assessed ex vivo the impact of deoxyribonuclease 1 (DNAse 1) on thrombolysis of AIS thrombi., Results: Histological analysis revealed that NETs contributed to the composition of all AIS thrombi especially in their outer layers. Quantitative measurement of thrombus NETs content was not associated with clinical outcome or AIS pathogenesis but correlated significantly with endovascular therapy procedure length and device number of passes. Ex vivo, recombinant DNAse 1 accelerated tPA-induced thrombolysis, whereas DNAse 1 alone was ineffective., Conclusions: This study suggests that thrombus NETs content may be responsible for reperfusion resistance, including mechanical or pharmacological approaches with intravenous tPA, irrespectively of their etiology. The efficacy of a strategy involving an administration of DNAse 1 in addition to tPA should be explored in the setting of AIS., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02907736., (© 2018 American Heart Association, Inc.)

Background and Purpose: We aimed to study the intrarater and interrater agreement of clinicians attributing DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Scores) and DWI-FLAIR (Diffusion-Weighted Imaging-Fluid Attenuated Inversion Recovery) mismatch in patients with acute ischemic stroke referred for mechanical thrombectomy., Methods: Eighteen raters independently scored anonymized magnetic resonance imaging scans of 30 participants from a multicentre thrombectomy trial, in 2 different reading sessions. Agreement was measured using Fleiss κ and Cohen κ statistics., Results: Interrater agreement for DWI-ASPECTS was slight (κ=0.17 [0.14-0.21]). Four raters (22.2%) had a substantial (or higher) intrarater agreement. Dichotomization of the DWI-ASPECTS (0-5 versus 6-10 or 0-6 versus 7-10) increased the interrater agreement to a substantial level (κ=0.62 [0.48-0.75] and 0.68 [0.55-0.79], respectively) and more raters reached a substantial (or higher) intrarater agreement (17/18 raters [94.4%]). Interrater agreement for DWI-FLAIR mismatch was moderate (κ=0.43 [0.33-0.57]); 11 raters (61.1%) reached a substantial (or higher) intrarater agreement., Conclusions: Agreement between clinicians assessing DWI-ASPECTS and DWI-FLAIR mismatch may not be sufficient to make repeatable clinical decisions in mechanical thrombectomy. The dichotomization of the DWI-ASPECTS (0-5 versus 0-6 or 0-6 versus 7-10) improved interrater and intrarater agreement, however, its relevance for patients selection for mechanical thrombectomy needs to be validated in a randomized trial., (© 2017 American Heart Association, Inc.)