Objectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic... Show moreObjectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics. Methods Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R-2. For patients with available thin-slice (<= 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus). Results In 332 included patients, the presence of HAS (a beta 7.8 [95% CI 3.9-11.7]) and shift towards a more proximal occlusion location (a beta 3.9 [95% CI 0.6-7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors. Conclusions Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future. Show less
Background Pre-stroke dependent patients (modified Rankin Scale score (mRS) >= 3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior... Show moreBackground Pre-stroke dependent patients (modified Rankin Scale score (mRS) >= 3) were excluded from most trials on endovascular treatment (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Therefore, little evidence exists for EVT in those patients. We aimed to investigate the safety and benefit of EVT in pre-stroke patients with mRS score 3. Methods We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in the Netherlands (MR CLEAN) Registry. All patients treated with EVT for anterior circulation AIS with pre-stroke mRS 3 were included. We assessed causes for dependence and compared patients with successful reperfusion (defined as expanded Thrombolysis in Cerebral Ischemia scale (eTICI) 2b-3) to patients without successful reperfusion. We used regression analyses with pre-specified adjustments. Our primary outcome was 90-day mRS 0-3 (functional improvement or return to baseline). Results A total of 192 patients were included, of whom 82 (43%) had eTICI <2b and 108 (56%) eTICI >= 2b. The median age was 80 years (IQR 73-87). Fifty-one of the 192 patients (27%) suffered from previous stroke and 36/192 (19%) had cardiopulmonary disease. Patients with eTICI >= 2b more often returned to their baseline functional state or improved (n=26 (26%) vs n=15 (19%); adjusted odds ratio (aOR) 2.91 (95% CI 1.08 to 7.82)) and had lower mortality rates (n=49 (49%) vs n=50 (64%); aOR 0.42 (95% CI 0.19 to 0.93)) compared with patients with eTICI Conclusions Although patients with AIS with pre-stroke mRS 3 comprise a heterogenous group of disability causes, we observed improved outcomes when patients achieved successful reperfusion after EVT. Show less
Background Randomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen... Show moreBackground Randomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice. Methods The Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0-2), and death. Results Of 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9-10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, p<0.04) and had slightly lower ASPECTS (median 8 vs 9, p<0.01), but better collateral status (collateral score 2-3: 68.3% vs 57.7%, p=0.03). No differences were observed in proportions of functional independence (43.3% vs 40.5%, p=0.57) or death (24.0% vs 28.9%, p=0.28). After matching, outcomes remained similar (adjusted common OR for 1 point improvement in mRS 1.04, 95% CI 0.56 to 1.93). Conclusions Without the use of CT perfusion selection criteria, EVT in the 6.5-24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window. Show less
Background: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not... Show moreBackground: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT.Methods: MR CLEAN-MED is a multicenter phase III trial with a prospective, 2 x 3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300 mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS >= 2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6 h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24 h and at 5-7 days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality.Discussion: Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA. Show less
