Background Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials. Methods The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography. Results Angiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90–99%, 2b67=67–89%, 2b50=50–66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014). Conclusions The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice.

Endovascular or intra-arterial treatment (IAT) increases the likelihood of recanalization in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion. However, a beneficial effect of IAT on functional recovery in patients with acute ischemic stroke remains unproven. The aim of this study is to assess the effect of IAT on functional outcome in patients with acute ischemic stroke. Additionally, we aim to assess the safety of IAT, and the effect on recanalization of different mechanical treatment modalities. A multicenter randomized clinical trial with blinded outcome assessment. The active comparison is IAT versus no IAT. IAT may consist of intra-arterial thrombolysis with alteplase or urokinase, mechanical treatment or both. Mechanical treatment refers to retraction, aspiration, sonolysis, or use of a retrievable stent (stent-retriever). Patients with a relevant intracranial proximal arterial occlusion of the anterior circulation, who can be treated within 6 hours after stroke onset, are eligible. Treatment effect will be estimated with ordinal logistic regression (shift analysis); 500 patients will be included in the trial for a power of 80% to detect a shift leading to a decrease in dependency in 10% of treated patients. The primary outcome is the score on the modified Rankin scale at 90 days. Secondary outcomes are the National Institutes of Health stroke scale score at 24 hours, vessel patency at 24 hours, infarct size on day 5, and the occurrence of major bleeding during the first 5 days. If IAT leads to a 10% absolute reduction in poor outcome after stroke, careful implementation of the intervention could save approximately 1% of all new stroke cases from death or disability annually. NTR1804 (7 May 2009)/ ISRCTN10888758 (24 July 2012).

Background and purpose Studying the imaging and histopathologic characteristics of thrombi in ischemic stroke could provide insights into stroke etiology and ideal treatment strategies. We conducted a systematic review of imaging and histologic characteristics of thrombi in acute ischemic stroke. Materials and methods We identified all studies published between January 2005 and December 2015 that reported findings related to histologic and/or imaging characteristics of thrombi in acute ischemic stroke secondary to large vessel occlusion. The five outcomes examined in this study were (1) association between histologic composition of thrombi and stroke etiology; (2) association between histologic composition of thrombi and angiographic outcomes; (3) association between thrombi imaging and histologic characteristics; (4) association between thrombi imaging characteristics and angiographic outcomes; and (5) association between imaging characteristics of thrombi and stroke etiology. A meta-analysis was performed using a random effects model. Results There was no significant difference in the proportion of red blood cell (RBC)-rich thrombi between cardioembolic and large artery atherosclerosis etiologies (OR 1.62, 95% CI 0.1 to 28.0, p=0.63). Patients with a hyperdense artery sign had a higher odds of having RBC-rich thrombi than those without a hyperdense artery sign (OR 9.0, 95% CI 2.6 to 31.2, p<0.01). Patients with a good angiographic outcome had a mean thrombus Hounsfield unit (HU) of 55.1±3.1 compared with a mean HU of 48.4±1.9 for patients with a poor angiographic outcome (mean standard difference 6.5, 95% CI 2.7 to 10.2, p<0.001). There was no association between imaging characteristics and stroke etiology (OR 1.13, 95% CI 0.32 to 4.00, p=0.85). Conclusions The hyperdense artery sign is associated with RBC-rich thrombi and improved recanalization rates. However, there was no association between the histopathological characteristics of thrombi and stroke etiology and angiographic outcomes.

For decades, intra-arterial treatment (IAT) was considered a potentially valuable expansion of the therapeutic options for acute ischemic stroke. However, until the end of 2014, IAT with mechanical devices had not been proven effective in randomized clinical trials.^1-3 The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial was a randomized clinical trial of IAT for acute ischemic stroke in patients with a confirmed intracranial occlusion in the anterior cerebral circulation who could be treated within 6 hours of onset. The intervention contrast was IAT vs no IAT against a background of best medical care, including intravenous alteplase if indicated. The trial demonstrated a shift in the distribution of functional outcomes on the modified Rankin Scale (mRS) in favor of the intervention, and this finding was consistent in almost all subgroup analyses.⁴ With IAT, the rate of patients achieving independence (mRS score, 0-2) increased from 19% to 33%. Four published trials^5-8 and 2 unpublished trials^9,10 confirmed the effect of IAT.

Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion and has recently revolutionized stroke care. Oftentimes, ischemic core extent on baseline imaging is used to determine endovascular treatment-eligibility. There are, however, 3 fundamental issues with the core concept: First, computed tomography and magnetic resonance imaging, which are mostly used in the acute stroke setting, are not able to precisely determine whether and to what extent brain tissue is infarcted (core) or still viable, due to variability in tissue vulnerability, the phenomenon of selective neuronal loss and lack of a reliable gold standard. Second, treatment decision-making in acute stroke is multifactorial, and as such, the relative importance of single variables, including imaging factors, is reduced. Third, there are often discrepancies between core volume and clinical outcome. This review will address the uncertainty in terminology and proposes a direction towards more clarity. This theoretical exercise needs empirical data that clarify the definitions further and prove its value.

Background and purpose Hemorrhagic transformation (HT) is a complication that may cause neurological deterioration in patients with acute ischemic stroke. Various radiological subtypes of HT can be distinguished. Their influence on functional outcome is currently unclear. The purpose of this study was to assess the associations between HT subtypes and functional outcome in acute ischemic stroke patients with proven large vessel occlusion included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic stroke in The Netherlands). Methods All patients with follow-up imaging were included. HT was classified on follow-up CT scans according to the European Cooperative Acute Stroke Study II classification. Functional outcome was assessed using the modified Rankin Scale (mRS) 90 days after stroke onset. Ordinal logistic regression analysis with adjustment for potential confounders was used to determine the association of HT subtypes with functional outcome. Results Of 478 patients, 222 had HT. Of these, 76 (16%) patients were classified as hemorrhagic infarction type 1, 71 (15%) as hemorrhagic infarction type 2, 36 (8%) as parenchymal hematoma type 1, and 39 (8%) as parenchymal hematoma type 2. Hemorrhagic infarction type 2 (adjusted common OR (acOR) 0.54, 95% CI: 0.32 to 0.89) and parenchymal hematoma type 2 (acOR 0.37, 95% CI 0.17 to 0.78) were significantly associated with a worse functional outcome. Hemorrhagic infarction type 1 and parenchymal hematoma type 1 were not significantly associated, although their point estimates pointed in the direction of worse outcome. Conclusion This study suggests that parenchymal hematoma type 2 is relevant for functional outcome after an acute ischemic stroke, and smaller HTs might also influence long term functional outcome. Trail registration number ISRCTN10888758.