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Background: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied., Methods: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage., Results: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group., Conclusions: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19., Methods: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes., Results: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054)., Conclusion: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19., Competing Interests: Declaration of Competing Interest Authors reports no disclosures., (Copyright © 2021. Published by Elsevier Inc.)

Background: The smoking-paradox of a better outcome in ischemic stroke patients who smoke may be due to increased efficacy of thrombolysis. We investigated the effect of smoking on outcome following endovascular therapy (EVT) with mechanical thrombectomy alone versus in combination with intra-arterial (IA-) thrombolysis., Methods: The primary endpoint was defined by three-month modified Rankin Scale (mRS). We performed a generalized linear model and reported relative risks (RR) for smoking (adjustment for age, sex, hypertension, atrial fibrillation, stroke severity, time to EVT) in patient data stemming from the Virtual International Stroke Trials Archive-Endovascular database., Results: Among 1,497 patients, 740(49.4%) were randomized to EVT; among EVT patients, 524(35.0%) received mechanical thrombectomy alone and 216(14.4%) received it in combination with IA-thrombolysis. Smokers (N = 396) had lower mRS scores (mean 2.9 vs. 3.2; p = 0.02) and mortality rates (10% vs. 17.3%; p<0.001) in univariate analysis. In all patients and in patients treated with mechanical thrombectomy alone, smoking had no effect on outcome in regression analyses. In patients who received IA-thrombolysis (N = 216;14%), smoking had an adjusted RR of 1.65 for an mRS≤1 (95%CI 0.77-3.55). Treatment with IA-thrombolysis itself led to reduced RR for favorable outcome (adjusted RR 0.30); interaction analysis of IA-thrombolysis and smoking revealed that non-smokers with IA-thrombolysis had mRS≤2 in 47 cases (30%, adjusted RR 0.53 [0.41-0.69]) while smokers with IA-thrombolysis had mRS≤2 in 23 cases (38%, adjusted RR 0.61 [0.42-0.87])., Conclusions: Smokers had no clear clinical benefit from EVT that incorporates IA-thrombolysis., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: JBF reports consulting and advisory board fees from Abbvie, AC Immune, Artemida, BioClinica, Biogen, BMS, Brainomix, Cerevast, Daiichi-Sankyo, EISAI, Guerbet, Ionis Pharmaceuticals, Julius Clinical, jung diagnostics, Eli Lilly, Merck, and Tau Rx, all outside of the submitted work. M. Endres reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, and Novartis, all outside of the submitted work. DSL reports research funding as an imaging core lab from Cerenovus, Genentech, Medtronic and Stryker. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC)., Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution., Results: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008)., Conclusion: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019., (© 2021 S. Karger AG, Basel.)

Background and Purpose: More than half of patients with acute ischemic stroke have minor neurological deficits; however, the frequency and outcomes of reperfusion therapy in regular practice has not been well-delineated., Methods: Analysis of US National Inpatient Sample of hospitalizations with acute ischemic stroke and mild deficits (National Institutes of Health Stroke Scale [NIHSS] score 0-5) from October 1, 2016, to December 31, 2017. Patient- and hospital-level characteristics associated with use and outcome of reperfusion therapies were analyzed. Primary outcomes included excellent discharge disposition (discharge to home without assistance); poor discharge disposition (discharge to facility or death); in-hospital mortality; and radiological intracranial hemorrhage., Results: Among 179 710 acute ischemic stroke admissions with recorded NIHSS during the 15-month study period, 103 765 (57.7%) had mild strokes (47.3% women; median age, 69 [interquartile range, 59-79] years; median NIHSS score of 2 [interquartile range, 1-4]). Considering reperfusion therapies among strokes with documented NIHSS, mild deficit hospitalizations accounted for 40.0% of IVT and 10.7% of mechanical thrombectomy procedures. Characteristics associated with IVT and with mechanical thrombectomy utilization were younger age, absence of diabetes, higher NIHSS score, larger/teaching hospital status, and Western US region. Excellent discharge outcome occurred in 48.2% of all mild strokes, and in multivariable analysis, was associated with younger age, male sex, White race, lower NIHSS score, absence of diabetes, heart failure, and kidney disease, and IVT use. IVT was associated with increased likelihood of excellent outcome (odds ratio, 1.90 [95% CI, 1.71-2.13], P <0.001) despite an increased risk of intracranial hemorrhage (odds ratio, 1.41 [95% CI, 1.09-1.83], P <0.001)., Conclusions: In national US practice, more than one-half of acute ischemic stroke hospitalizations had mild deficits, accounting for 4 of every 10 IVT and 1 of every 10 mechanical thrombectomy treatments, and IVT use was associated with increased discharge to home despite increased intracranial hemorrhage.

The 14th International Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy (TTST) took place in Houston, Texas on 21-22 October 2018. Attended by 150+ invited global experts, the objectives of TTST 2018 were to explore the changing landscape of acute ischemic stroke therapy and to address current controversies in thrombolysis and thrombectomy, including expanding access and systems of care with global relevance. This article summarizes the proceedings of TTST 2018. The key points of each session are listed below, the full text of presentations and discussion are available in the online supplement, and the full list of contributing authors appear in the Appendix at the end of this article.

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., Competing Interests: Competing interests: DSL reports having received grant funding from NINDS and consulting fees as an imaging core laboratory from Stryker and Medtronic. RJ reports consulting with Medtronic. CBLMM reports having received grant funding from the Dutch Heart Foundation and European Commission and an unrestricted grant from Stryker. AvdL reports consulting fees from Stryker and grant funding from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Top Medical/Concentric, and Stryker, received by the Erasmus University Medical Center. LSR proctors for Stryker and Medtronic. PW discloses institutional research grant support within the last 2 years from Microvention Terumo. He declares the following relevant professional relationships: Chair of the European Society of Minimally Invasive Neurotherapeutics Guidelines Committee, sits on the Policy Working Group for Thrombectomy of NHS England and represents the Royal College of Radiologists on the UK Intercollegiate Stroke Working party (none of these are associated with financial reimbursement). He reports the following modest consultancy work: member of Stryker’s Global Hemorrhagic Stroke Advisory Board and educational consultancy work for Microvention Terumo. He has no other interests to declare. MG reports being the principal investigator of an unrestricted research grant to the University of Calgary for the HERMES collaboration by Medtronic. He also reports consulting services with Medtronic, Stryker, Microvention, Cerenovus and a licensing agreement with GE Healthcare re systems of acute stroke diagnosis., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion., Methods: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered., Findings: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69-2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0-4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94-16·49; p interaction =0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30-13·44, p interaction =0·012)., Interpretation: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline., Funding: Medtronic., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to examine the impact of corticospinal tract (CST) involvement in acute ischaemic stroke (AIS) patients on functional outcome and the interaction with reperfusion., Methods: We retrospectively examined data in consecutive anterior circulation AIS patients undergoing thrombolysis. MR perfusion (time to maximum of tissue residue function, Tmax) and apparent diffusion coefficient (ADC) images were transformed into standard space and the volumes of CST involvement by Tmax > 6 s (CST-Tmax) and ADC < 620 × 10 -6 mm 2 /s (CST-ADC) lesions were calculated. Good outcome was defined as modified Rankin scale ≤ 2 at 3 months. Reperfusion was defined as a reduction in Tmax > 6 s lesion volume of ≥70% between baseline and 24 h., Results: 82 patients were included. Binary logistic regression revealed that both CST-Tmax and CST-ADC volume at baseline were significantly associated with poor outcome (p < 0.05). The 24-h CST-ADC volume was correlated with baseline CST-ADC volume in patients with reperfusion (r = 0.79, p < 0.001) and baseline CST-Tmax volume in patients without reperfusion (r = 0.67, p < 0.001). In patients with CST-Tmax volume > 0 mL and CST-ADC volume < 3 mL, the rate of good outcome was higher in patients with reperfusion than those without (70.4% vs 38.1%, p = 0.04)., Conclusions: The use of CST-Tmax in combination with CST-ADC provides prognostic information in patients considered for reperfusion therapies., Key Points: • Examine the impact of corticospinal tract involvement in acute ischaemic stroke patients. • Spatially registered Tmax images can identify corticospinal tract hypoperfusion injury. • Corticospinal tract salvage through reperfusion is associated with improved outcome.

Objective: Blood-brain barrier (BBB) permeability has been proposed as a predictor of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) administration; however, the reliability of perfusion computed tomography (PCT) permeability imaging for predicting HT is uncertain. We aimed to determine the performance of high-permeability region size on PCT (HPrs-PCT) in predicting HT after intravenous tPA administration in patients with acute stroke., Methods: We performed a multimodal CT protocol (non-contrast CT, PCT, CT angiography) to prospectively study patients with middle cerebral artery occlusion treated with tPA within 4.5 hours of symptom onset. HT was graded at 24 hours using the European-Australasian Acute Stroke Study II criteria. ROC curves selected optimal volume threshold, and multivariate logistic regression analysis identified predictors of HT., Results: The study included 156 patients (50% male, median age 75.5 years). Thirty-seven (23,7%) developed HT [12 (7,7%), parenchymal hematoma type 2 (PH-2)]. At admission, patients with HT had lower platelet values, higher NIHSS scores, increased ischemic lesion volumes, larger HPrs-PCT, and poorer collateral status. The negative predictive value of HPrs-PCT at a threshold of 7mL/100g/min was 0.84 for HT and 0.93 for PH-2. The multiple regression analysis selected HPrs-PCT at 7mL/100g/min combined with platelets and baseline NIHSS score as the best model for predicting HT (AUC 0.77). HPrs-PCT at 7mL/100g/min was the only independent predictor of PH-2 (OR 1, AUC 0.68, p = 0.045)., Conclusions: HPrs-PCT can help predict HT after tPA, and is particularly useful in identifying patients at low risk of developing HT.

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.

Background: Advances in diagnostic imaging of stroke include multimodal techniques such as noninvasive angiography and perfusion imaging. We aimed to characterize trends in neuroimaging utilization among acute stroke patients. Utilization of multimodal imaging for acute stroke in the community has remained largely uncharacterized despite its increased adoption at academic medical centers., Methods: We quantified neuroimaging utilization in the emergency department (ED) for 1,700 hyperacute stroke patients presenting <2 hours after symptom onset who participated in the National Institutes of Health Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study throughout Los Angeles and Orange Counties. FAST-MAG provided no recommendation as to imaging utilization., Results: A total of 1,700 cases were imaged a median (interquartile range [IQR]) of 92 (74-120) minutes after last known well time and 28 (19-41) minutes after ED arrival. The initial scanner used in the ED was computed tomography (CT) in a preponderance of cases (N = 1,612, 95%), with magnetic resonance imaging (MRI) in 88 cases (5%). CT angiography (CTA) was obtained in 192 (11%) and perfusion CT (CTP) in 91 (5.4%) cases. MRI imaging was universally obtained using diffusion-weighted images, 60% with MR angiography and 33% included perfusion imaging. Rates of concomitant CTA or CTP use increased in the later years of the study from 4% in 2005-2006, 2% in 2007-2008, 8% in 2009-2010, and 26% in 2011-2012 (P for trend < .001)., Conclusions: Among acute stroke patients, noncontrast CT was the most common initial imaging strategy in clinical practice in the 2005-2012 time period, though use of concomitant CTA grew to one-quarter of cases, suggestive of an upward trend., (Copyright © 2016 by the American Society of Neuroimaging.)

Objectives: We evaluated the rate of late recanalisation beyond 24 h after intravenous thrombolysis (IVT) and its relationship with haemorrhagic transformation and outcome., Methods: We reviewed prospectively collected clinical and imaging data from acute ischaemic stroke patients with distal internal carotid artery or proximal middle cerebral artery occlusion who underwent angiography on admission, 24 h and 1 week after IVT. Patients were trichotomised according to vascular status: timely recanalisation (<24 h), late recanalisation (24 h-7 days), and no recanalisation., Results: Non-invasive angiography revealed timely recanalisation in 52 (50.0 %) patients, late recanalisation in 25 (24.0 %) patients, and no recanalisation in 27 (26.0 %) patients. Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation (odds ratio 6.674; 95 % CI: 1.197 to 37.209; p = 0.030). In patients without timely recanalisation, shift analysis indicated that late recanalisation led to a worse modified Rankin Scale score (odds ratio 6.787; 95 % CI: 2.094 to 21.978; p = 0.001)., Conclusions: About half of all patients without recanalisation by 24 h after IVT may develop late recanalisation within 1 week, along with higher mRS scores by 3 months. Pre-existing atrial fibrillation is an independent predictor for late recanalisation., Key Points: • About half of patients may develop late recanalisation within 1 week. • Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation. • Late recanalisation led to a higher mRS score than no recanalisation.

Background and Purpose: In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment., Methods: We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography., Results: Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019)., Conclusions: Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion., (© 2016 American Heart Association, Inc.)

Background and Purpose: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials., Methods: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials., Results: The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials., Conclusions: Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials., (© 2016 American Heart Association, Inc.)

Objective: To assess the impact of diabetes on neurological outcome and recanalization in acute ischemic stroke (AIS) after intravenous thrombolysis (IVT)., Methods: Clinical data of 419 consecutive patients with AIS who received IVT between June 2009 and April 2014. Based on the medical history and new diagnosis, the patients were divided into groups with and without diabetes. Neurological outcomes at 24 h, 7 days and 3 months after IVT were evaluated. Favorable outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score decrease ≥4 points from baseline or 0 at 24 h, NIHSS decrease ≥8 points or 0 at day 7, or modified Rankin scale ≤1 at 3 months after IVT. Recanalization on non-invasive imaging was evaluated in patients with large vessel occlusion (LVO) according to thrombolysis in myocardial infarction grades., Results: Among 419 patients, 98 (23.4%) had diabetes. Multivariable analyses showed that comorbidity of diabetes was an independent predictor of unfavorable outcome at 24 h (OR=0.534, 95% CI 0.316 to 0.903, p=0.019), at day 7 (OR=0.382, 95% CI 0.220 to 0.665, p=0.001), and at 3 months (OR=0.464, 95% CI 0.266 to 0.808, p=0.007). In patients with LVO, diabetes was an independent predictor of incomplete recanalization 24 h after IVT (OR=0.268, 95% CI 0.075 to 0.955, p=0.042)., Conclusions: Diabetic patients with AIS had unfavorable neurological outcome, potentially linked to incomplete recanalization after IVT., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: Thrombolysis-related haemorrhagic transformation (HT) subtypes may have different prognostic implications. We aimed to analyse the impact of cerebral microbleeds (CMBs) burden on HT subtypes and outcome after intravenous thrombolysis., Methods: We retrospectively examined clinical and radiological data from 333 consecutive patients with acute ischaemic stroke who underwent susceptibility-weighted imaging before intravenous thrombolysis. Logistic regression analysis was used to determine the impact of CMBs on HT subtypes and neurological outcome., Results: We observed 596 CMBs in 119 (39.7%) patients on initial gradient-recalled echo scans. HT occurred in 88 (29.3%) patients, among which 62 were haemorrhagic infarction and 26 were parenchymal haemorrhage (PH). Logistic regression analysis indicated that the presence of extensive (≥ 3) CMBs was independently associated with PH (OR 6.704; 95% CI 2.054 to 21.883; p = 0.002) and poor clinical outcome (OR 2.281; 95% CI 1.022 to 5.093; p = 0.044)., Conclusions: The presence of extensive (≥ 3) CMBs increased the risk of PH 24 h after intravenous thrombolysis, and predicted poor clinical outcome independently., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Purpose: Emergency medical services routing of patients with acute stroke to designated centers may increase the proportion of patients receiving care at facilities meeting national standards and augment recruitment for prehospital stroke research., Methods: We analyzed consecutive patients enrolled within 2 hours of symptom onset in a prehospital stroke trial, before and after regional Los Angeles County Emergency Medical Services implementation of preferentially routing patients with acute stroke to approved stroke centers (ASCs). From January 2005 to mid-November 2009, patients were transported to the nearest emergency department, whereas from mid-November 2009 to December 2012, patients were preferentially transported to first 9, and eventually 29, ASCs., Results: There were 863 subjects enrolled before and 764 after emergency medical service preferential routing, with implementation leading to an increase in the proportion cared for at an ASC from 10% to 91% (P<0.0001), with a slight decrease in paramedic on-scene to emergency department arrival time (34.5 [SD, 9.1] minutes versus 33.5 [SD, 10.3] minutes; P=0.045). The effects of routing were immediate and included an increase in proportion of receiving ASC care (from 17% to 88%; P<0.001) and a greater number of enrollments (18.6% increase) when comparing 12 months before and after regional stroke system implementation., Conclusions: The establishment of a regionalized emergency medical services system of acute stroke care dramatically increased the proportion of patients with acute stroke cared for at ASCs, from 1 in 10 to >9 in 10, with no clinically significant increase in prehospital care times and enhanced recruitment of patients into a prehospital treatment trial., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332., (© 2015 American Heart Association, Inc.)

We aim to investigate whether the phenomenon of "sudden drop" in blood pressure (BP) within the first 2 hours is associated with vessel recanalization.We retrospectively examined clinical and imaging data from a consecutive series of patients with stroke with large vessel occlusion treated with intravenous thrombolysis (IVT). BP was monitored every 15 minutes during the first 2 hours, then every 30 minutes for 6 hours, and then every hour for 16 hours.We observed the phenomenon of "sudden drop" in systolic BP (≥20 mm Hg) in 82 (50.9%) patients in the first 2 hours and vessel recanalization in 87 (54.0%) patients 24 hours after treatment. This phenomenon was independently associated with recanalization (odds ratio 2.100; 95% confidence interval: 1.085-4.062; P = 0.028) after adjusting for the history of atrial fibrillation, coronary heart disease, and hypertension.The phenomenon of "sudden drop" in systolic BP with 20 mm Hg or greater between 2 continuous measurements within the first 2 hours is associated with recanalization after IVT in patients with large vessel occlusion, especially for middle cerebral artery occlusion.

Background: To assess the differences across continental regions in terms of stroke imaging obtained for making acute revascularization therapy decisions, and to identify obstacles to participating in randomized trials involving multimodal imaging., Methods: STroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA)-Imaging circulated an online survey through its website, through the websites of national professional societies from multiple countries as well as through email distribution lists from STIR and the above mentioned societies., Results: We received responses from 223 centers (2 from Africa, 38 from Asia, 10 from Australia, 101 from Europe, 4 from Middle East, 55 from North America, 13 from South America). In combination, the sites surveyed administered acute revascularization therapy to a total of 25,326 acute stroke patients in 2012. Seventy-three percent of these patients received intravenous (i.v.) tissue plasminogen activator (tPA), and 27%, endovascular therapy. Vascular imaging was routinely obtained in 79% (152/193) of sites for endovascular therapy decisions, and also as part of standard IV tPA treatment decisions at 46% (92/198) of sites. Modality, availability and use of acute vascular and perfusion imaging before revascularization varied substantially between geographical areas. The main obstacles to participate in randomized trials involving multimodal imaging included: mainly insufficient research support and staff (50%, 79/158) and infrequent use of multimodal imaging (27%, 43/158) ., Conclusion: There were significant variations among sites and geographical areas in terms of stroke imaging work-up used tomake decisions both for intravenous and endovascular revascularization. Clinical trials using advanced imaging as a selection tool for acute revascularization therapy should address the need for additional resources and technical support, and take into consideration the lack of routine use of such techniques in trial planning., Competing Interests: Conflicts of Interest: None declared., (© 2015 World Stroke Organization.)

Background and Purpose: Until recently, acute ischemic stroke (AIS) trials have failed to show a benefit of endovascular therapy compared with standard therapy, leading some authors to recommend decreasing the time from ictus to revascularization to improve outcomes. We hypothesize that improving patient selection using the capillary index score (CIS) may also be a useful strategy., Methods: CIS was calculated, blinded to outcome, from pretreatment diagnostic cerebral angiograms for 78 subjects in the Interventional Management of Stroke III database with internal carotid artery and middle cerebral artery trunk occlusion. The CIS was dichotomized into favorable (fCIS=2 or 3) and poor (pCIS=0 or 1). Outcomes were categorized based on the modified Rankin Scale score at 90 days (0-2 considered a good outcome). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. Multivariable logistic regression was performed to relate CIS, time from ictus to revascularization, modified thrombolysis in cerebral infarction score, and National Institue of Health Stroke Scale score to good outcomes., Results: Only CIS and modified thrombolysis in cerebral infarction scores were correlated with good outcomes (P<0.01). Patients with fCIS and good revascularization achieved 71% modified Rankin Scale≤2, compared with 13% for patients with pCIS and good revascularization., Conclusions: In this subset of patients from the Interventional Management of Stroke III Trial, CIS and modified thrombolysis in cerebral infarction were strong predictors of outcome after endovascular reperfusion. Using the CIS to improve patient selection could be a powerful strategy to improve rate of good outcomes in endovascular therapy. A randomized trial is needed., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424., (© 2015 American Heart Association, Inc.)

Background and Purpose: We aim to investigate whether lower admission serum calcium levels are associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT)., Methods: A total of 362 patients treated with IVT was divided into 4 quartiles based on admission serum calcium levels (Q1[<2.16], Q2[2.16, 2.23], Q3[2.24, 2.31], and Q4[>2.31] mmol/L). HT was classified as hemorrhagic infarction and parenchymal hemorrhage. Logistic regression was applied to assess the association between serum calcium levels and the incidence of HT., Results: Compared with Q4, HT was more common in Q1 (odds ratio, 2.580; 95% CI, [1.258-5.292]; P=0.010), Q2 (odds ratio, 2.382; 95% CI, [1.163-4.877]; P=0.018), and Q3 (odds ratio, 2.293; 95% CI, [1.133-4.637]; P=0.021). Hemorrhagic infarction was more common in Q1 (P=0.037), and Q2 (P=0.018), compared with Q4, and parenchymal hemorrhage was more common in Q1 (P=0.029) than Q4., Conclusions: Lower admission serum calcium level is independently associated with HT after IVT, and this hypothesis needs larger confirmatory trials., (© 2015 American Heart Association, Inc.)

Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal computed tomography and magnetic resonance imaging, angiography, and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size, and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management., (© 2014 World Stroke Organization.)

Purpose of Review: Endovascular therapy is a promising aspect of acute ischemic stroke treatment. The ideal population of patients who benefit from treatment remains undefined, and the status of collateral circulation at presentation may be a key feature in their identification., Recent Findings: Adequate collateral flow has been recently demonstrated to be associated with improved clinical status on presentation, increased likelihood of recanalization with endovascular therapy, and better functional outcome at 3 months., Summary: In this review, we define the collateral circulation, review methods of its measurement, and present recent clinical data on its impact in endovascular therapy for acute ischemic stroke. We outline our current understandings and discuss their relevance in future directions with clinical stroke management.

Background: Lesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis., Aims: The aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns., Methods: Consecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days., Results: Among the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047)., Conclusions: Specific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients., (© 2015 S. Karger AG, Basel.)

Background and Purpose: Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy., Methods: Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score ≥3) and mortality., Results: There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67±15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13-20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001)., Conclusions: Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the 'benign' nature of HI suggested by earlier studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We aimed to determine the frequency of new microbleeds after intravenous thrombolysis using contiguous thin-slice 3T magnetic resonance imaging. We retrospectively examined clinical and imaging data from 121 consecutive acute ischemic stroke patients who underwent magnetic resonance imaging before and 24 hours after intravenous thrombolysis. Of the included patients, 44 (36.4%) were women, with a median age of 69 years (range, 35-94 years). A total of 363 baseline microbleeds were observed in 57 patients and 8 new microbleeds in 6 patients. Multiple regression analysis indicated that baseline infarct volume (odds ratio, 1.556/10 mL; 95% CI, 1.017-2.379; P = 0.04) and systolic blood pressure (odds ratio, 1.956/10 mm Hg; 95% CI, 1.056-3.622; P = 0.03), but not the presence of baseline microbleeds, were independently associated with new microbleeds. The frequency of neither symptomatic intracranial hemorrhage nor remote hemorrhage or any hemorrhagic transformation was different between patients with and without new microbleeds (0.0% vs 1.7%, P > 0.99; 0.0% vs 1.7%, P > 0.99; 50.0% vs 28.7%, P =0.36). New microbleeds developed rapidly 24 hours after intravenous thrombolysis. The significance of these new microbleeds and their effect on cognitive and functional outcome merits further investigation.

Background and Purpose: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative., Methods: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6)., Results: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01)., Conclusions: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis., (© 2014 American Heart Association, Inc.)

Background and Purpose: We aimed to evaluate the predictive value of susceptibility vessel sign (SVS) burden and morphology in middle cerebral artery recanalization., Methods: We retrospectively examined clinical and imaging data from 72 consecutive patients with acute ischemic stroke with middle cerebral artery occlusion and examined the association of recanalization with SVS length and shape., Results: None of the patients with a middle cerebral artery SVS >20 mm in length achieved recanalization. For patients with a relatively short SVS (length <20 mm), irregular shape was a strong independent predictor for no recanalization (odds ratio, 6.891; 95% confidence interval, 1.441-32.950; P=0.016)., Conclusions: Irregular shape and long length (>20 mm) of SVS decrease the potential to recanalize the occluded middle cerebral artery with intravenous thrombolysis., (© 2014 American Heart Association, Inc.)

Background and Purpose: High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy., Methods: We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization., Results: Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence., Conclusions: One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867., (© 2014 American Heart Association, Inc.)

Background and Purpose: Intra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions., Methods: Patients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University., Results: A total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (<150=0, ≥150=1), National Institute Health Stroke Scale (≤10=0, 11-20=1, ≥21=2), the Alberta Stroke Program Early CT Score (8-10=0, ≤7=3). Patients with HIAT2≥5 were more likely to have poor outcomes at discharge (odds ratio, 6.43; 95% confidence interval, 2.75-15.02; P<0.001). After adjusting for reperfusion (Thrombolysis in Cerebral Infarction score≥2b) and time from symptom onset to recanalization, HIAT2≥5 remained an independent predictor of poor outcome (odds ratio, 5.88; 95% confidence interval, 1.96-17.64; P=0.02). Results from the cohort of Emory (198 patients) were consistent; patients with HIAT2 score≥5 had 6× greater odds of poor outcome at discharge and at 90 days. HIAT2 outperformed other previously published predictive scores., Conclusions: The HIAT2 score, which combines clinical and imaging variables, performed better than all previous scores in predicting poor outcome after IAT for anterior circulation large artery occlusions.

Rationale: Twelve million people develop ischemic stroke each year world over and 30-40% of them do not have arterial occlusions at presentation. Trials conducted to study the efficacy of thrombolytic drug reported better outcome with use of thrombolytic drug but none studied the subtypes of ischemic strokes specifically and adequately. The subgroups of patients with no arterial occlusion at presentation continue to receive thrombolytic therapy without proven benefit and with some risk., Aim: The aim of this article is to study whether intravenous thrombolysis with alteplase improves clinical outcome in ischemic stroke patients who do not have arterial occlusion at presentation., Design: A retrospective medical record-based observational multicenter, multinational study., Outcomes: Primary outcome measure would be clinical outcome at three-months from stroke onset measured by modified Rankin Scale and National Institute of Health Stroke Scale. Secondary outcome measure will be frequency of intracerebral hemorrhage causing worsening of clinical deficit defined as increase in National Institute of Health Stroke Scale by >4., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Background: More than a quarter of patients with ischemic stroke (IS) are excluded from thrombolysis because of an unknown time of symptom onset. Recent evidence suggests that a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging could be used as a surrogate for the time of stroke onset. We compared used the DWI-FLAIR mismatch and the FLAIR/DWI ratio to estimate the time of onset in a group of patients with nocturnal strokes and unknown time of onset., Methods: We used a prospectively collected acute IS patient database with MRI as the initial imaging modality. Nineteen selected nocturnal stroke patients with unknown time of onset were compared with 22 patients who had an MRI scan within 6 hours from stroke onset (control A) and 19 patients who had an MRI scan between 6 and 12 hours (control B). DWI and FLAIR signal was rated as normal or abnormal. FLAIR/DWI ratio was calculated from independent DWI and FLAIR ischemic lesion volumes using semiautomatic software., Results: The DWI-FLAIR mismatch was different among groups (unknown 43.7%; control A 63.6%; control B 10.5%; Fisher-Freeman-Halton test; P = .001). There were significant differences in FLAIR/DWI ratio among the 3 groups (unknown 0.05 ± 0.12; control A 0.17 ± 0.15; control B 0.04 ± 0.06; Kruskal-Wallis test; P < .0001). Post-hoc pairwise comparisons revealed that FLAIR/DWI ratio from the unknown group was significantly different from the control B group (P = .0045) but not different from the control A group. DWI volumes were not different among the 3 groups., Conclusions: A large proportion of patients with nocturnal IS and an unknown time of stroke initiation have a DWI-FLAIR mismatch, suggesting a recent onset of stroke., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Angiographic revascularization grading after intra-arterial stroke therapy is limited by poor standardization, making it unclear which scale is optimal for predicting outcome. Using recently standardized criteria, we sought to compare the prognostic performance of 2 commonly used reperfusion scales., Methods: Inclusion criteria for this multicenter retrospective study were acute ischemic stroke attributable to middle cerebral artery M1 occlusion, intra-arterial therapy, and 90-day modified Rankin scale score. Post-intra-arterial therapy reperfusion was graded using the Thrombolysis in Myocardial Infarction (TIMI) and Modified Thrombolysis in Cerebral Infarction (mTICI) scales. The scales were compared for prediction of clinical outcome using receiver-operating characteristic analysis., Results: Of 308 patients, mean age was 65 years, and median National Institutes of Health Stroke Scale score was 17. The mean time from stroke onset to groin puncture was 305 minutes. There was no difference in the time to treatment between patients grouped by final TIMI (ie, 0 versus 1 versus 2 versus 3) or mTICI grades (ie, 0 versus 1 versus 2a versus 2b versus 3). Good outcome (modified Rankin scale, 0-2) was achieved in 32.5% of patients, and mortality rate was 25.3% at 90 days. There was a 6.3% rate of parenchymal hematoma type 2. In receiver-operating characteristic analysis, mTICI was superior to TIMI for predicting 90-day modified Rankin scale 0 to 2 (c-statistic: 0.74 versus 0.68; P<0.0001). The optimal threshold for identifying a good outcome was mTICI 2b to 3 (sensitivity 78.0%; specificity 66.1%)., Conclusions: mTICI is superior to TIMI for predicting clinical outcome after intra-arterial therapy. mTICI 2b to 3 is the optimal biomarker for procedural success.

Background and Purpose: We aimed to evaluate safety and tolerability of a novel operator-independent ultrasound device among stroke-free volunteers., Methods: A headframe containing 18 ultrasound transducers (each operating at 2 MHz, pulsed-wave) was used to expose both temporal windows and the suboccipital window. The transmission characteristics were set to emulate the acoustic characteristics of the exposure levels in the Combined Lysis of Thrombus in Brain Ischemia using Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial and to never exceed Food and Drug Administration mandated diagnostic ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Safety was captured using serial neurological examinations and pre- and postinsonation MRI for detection of the blood brain barrier permeability., Results: A total of 15 volunteers (40% men; 49 ± 16 years; 27% black; all pre-exposure National Institutes of Health Stroke Scale scores 0) were enrolled. Five volunteers received pulsed-wave ultrasound via the best pair temporal transducers, 5 via sequential activation of the suboccipital transducers, and 5 via sequential activation of all bilateral temporal and suboccipital transducers. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure, and at 24 hours, and no abnormality of the blood brain barrier was found on any of the MRIs., Conclusions: Our novel device was well tolerated by stroke-free volunteers and did not cause any neurological dysfunction nor did it affect blood brain barrier integrity. The safety and efficacy of the device are now being tested in stroke patients receiving intravenous tissue-type plasminogen activator in phase II-III clinical trials.

Background and Purpose: Although thrombolysis in cerebral infarction (TICI) 2b/3 has been regarded as a successful angiographic outcome, the definition or subclassification of TICI 2 has differed between the original (o-TICI) and modified TICI (m-TICI). We sought to compare interobserver variability for both scores and analyze the subgroups of the TICI 2., Methods: Five readers interpreted angiographies independently using a 6-point scale as follows: grade 0, no antegrade flow; grade 1, flow past the initial occlusion without tissue reperfusion; grade 2, partial reperfusion in <50% of the affected territory; grade 3, partial reperfusion in 50% to 66%; grade 4, partial reperfusion in ≥ 67%; grade 5, complete perfusion. Readings using this scale were then converted into o-TICI and m-TICI score. Statistical analysis was performed according to TICI 2 subgroups., Results: Interobserver agreement was good for the o-TICI and m-TICI scores (intraclass correlation coefficient, 0.73 and 0.67, respectively). Our grade 3 (partial perfusion with 50% to 66%) occupied 19% of total readings, which would have been classified as grade 2a in o-TICI, but as 2b in m-TICI. The m-TICI was more likely to predict good clinical outcome than o-TICI (odds ratio, 2.01 versus 1.63, in reads with TICI 2b/3 versus 0/2a)., Conclusions: Both TICI scales showed good agreement among readers. However, the variability in partial perfusion thresholds leads to different grading in ≈ 20% of cases and may result in significantly different rates of accurate outcome prediction.

Background and Purpose: The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of acute and restorative stroke therapies. Summary of Review- At the STAIR VII recommendations for strategies to maximize the use of intravenous thrombolytics through targeting public education, and the refinement of current treatment exclusion criteria were proposed. Increased utilization of mechanical devices for intra-arterial recanalization can be achieved by obtaining more definitive evidence of efficacy in randomized clinical trials, identification of patient characteristics associated with treatment efficacy, optimization of technical approaches, clarification of effective time windows, and development of approaches to limit complications. Neuroprotective strategies remain viable; recommendations for further study of these agents include an emphasis on rapid administration, consideration of the systemic effects of ischemic stroke, prevention of complications associated with early reperfusion, a focus on agents with multiple mechanisms of action, and consideration of possible interactions between neuroprotective and thrombolytic therapies., Conclusions: Extending intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies, and further development of neuroprotective therapies were the key recommendations from STAIR VII.

Background and Purpose: Collaterals sustain the ischemic penumbra to limit growth of the infarct core before revascularization, yet the impact of baseline collateral flow on hemorrhagic transformation (HT) after endovascular therapy remains unknown., Methods: A collaborative study from 2 stroke centers in distinct geographic regions included 222 consecutive patients who received endovascular therapy for acute cerebral ischemia. The influence of collaterals on HT was analyzed in distinct case scenarios relative to baseline collateral grade at angiography (0 to 1 versus 2 to 4) and recanalization (Thrombolysis in Myocardial Ischemia scale, 0 to 1 versus 2 to 3): good collaterals and successful recanalization (n=98), poor collaterals with successful recanalization (n=43), good collaterals and no recanalization(n=46), and poor collaterals and no recanalization (n=35)., Results: HT after endovascular therapy occurred in 103 (46.4%) patients; 42 (18.9%) were symptomatic. HT was more frequently observed in patients with poor collaterals and recanalization than in other groups (P=0.048). When revascularization was achieved, patients with poorer collaterals were more likely to have symptomatic worsening with HT (r=-0.181, P=0.032). Multiple logistic regression analysis identified aggressive treatment (OR, 2.558 for Merci clot retrieval; 95% CI, 1.153 to 5.678; OR, 3.618 for combined fibrinolytics and mechanical therapy; 95% CI, 1.551 to 8.437; and OR, 2.085 for intravenous thrombolysis before endovascular therapy; 95% CI, 1.096 to 3.969), poor collaterals and recanalization (OR, 2.666; 95% CI, 1.163 to 6.113), and serum glucose levels (OR, 1.007; 95% CI, 1.000 to 1.014) as independent predictors of HT., Conclusions: Angiographic grade of collateral flow strongly influences the rate of HT after therapeutic recanalization for acute ischemic stroke. Collateral status readily available from baseline angiography may therefore refine therapeutic decision-making in acute cerebral ischemia.

Background and Purpose: Current selection criteria for intra-arterial therapies in the anterior circulation use time windows of 8 hours. Modern neuroimaging techniques have identified individuals with salvageable penumbra who present beyond this timeframe. We sought to assess safety, procedural, and clinical outcomes of MRI or CT perfusion imaging-based endovascular therapy in patients with anterior circulation stroke treated beyond 8 hours from time last seen well., Methods: We conducted a multicenter retrospective review of consecutive patients meeting the following criteria: (1) acute proximal intracranial anterior circulation occlusion; (2) endovascular treatment initiated >8 hours from time last seen well; and (3) treatment selection based on MRI or CT perfusion imaging., Results: Two hundred thirty-seven patients were identified (mean age, 63.8 ± 16 years; mean baseline National Institutes of Health Stroke Scale, 15 ± 5.5; mean time last seen well to treatment, 15 ± 11.2 hours; male gender, 46%). Successful revascularization was achieved in 175 of 237 (73.84%) patients. Parenchymal hematoma occurred in 21 of 237 (8.86%) patients. The 90-day mortality rate was 21.5% (51 of 237). The rate of good outcomes was 45% (100 of 223) in the 223 patients with available modified Rankin Scale data at 90 days or time of hospital discharge. In multivariate analyses, age (OR, 0.96; 95% CI, 0.94 to 0.98; P=0.002), admission National Institutes of Health Stroke Scale (OR, 0.93; 0.87 to 0.98; P=0.016), and successful revascularization (OR, 4.32; 1.99 to 9.39; P<0.0001) were identified as independent predictors of good outcomes., Conclusions: Endovascular therapy can be instituted with acceptable safety beyond 8 hours from time last seen well when selection is based on advanced neuroimaging. Successful revascularization is significantly associated with higher rates of good outcomes. The benefit of this approach compared with standard medical therapy should be assessed in a prospective randomized trial.

Object: The authors evaluated the prognostic significance of blood glucose level at admission (BGA) and change in blood glucose at 48 hours from the baseline value (CG48) in nondiabetic and diabetic patients before and after endovascular therapy for acute ischemic stroke (AIS)., Methods: The BGA and CG48 data were analyzed in 614 patients with AIS who received endovascular therapy at 7 US centers between 2006 and 2009. Data reviewed included demographics, stroke risk factors, diabetic status, National Institutes of Health Stroke Scale (NIHSS) score at presentation, recanalization grade, intracranial hemorrhage (ICH) rate, and 90-day outcomes (mortality rate and modified Rankin Scale score of 3-6 [defined as poor outcome]). Variables with p values < 0.2 in univariate analysis were included in a binary logistic regression model for independent predictors of 90-day outcomes., Results: The mean patient age was 67.3 years, the median NIHSS score was 16, and 27% of patients had diabetes. In nondiabetic patients, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) and failure of glucose level to drop > 30 mg/dl (> 1.7 mmol/L) from the admission value were both significant predictors of 90-day poor outcome and death (p < 0.001). In patients with diabetes, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) was an independent predictor of poor outcome (p = 0.001). The CG48 was not a predictor of outcome in diabetic patients. A simplified 6-point scale including BGA, Thrombolysis in Myocardial Infarction (TIMI) Grade 2-3 Reperfusion, Age, presentation NIHSS score, CG48, and symptomatic ICH (BRANCH) corresponded with poor outcomes at 90 days; the area under the curve value was > 0.79., Conclusions: Failure of blood glucose values to decrease in the first 48 hours after AIS intervention correlated with poor 90-day outcomes in nondiabetic patients. The BRANCH scale shows promise as a simple prognostication tool after endovascular therapy for AIS, and it merits prospective validation.

Background: Reperfusion therapy for acute ischemic stroke (AIS) is rapidly evolving, with the development of multiple endovascular modalities that can be used alone or in combination., Objective: To determine which pharmacologic or mechanical modality may be associated with increased rates of recanalization., Methods: A cohort of 1122 patients with AIS involving the anterior circulation treated at 13 stroke centers underwent intra-arterial (IA) therapy within 8 hours of symptom onset. Demographic information, admission National Institutes of Health Stroke Scale (NIHSS), mechanical and pharmacologic treatments used, recanalization grade, and hemorrhagic complications were recorded., Results: The mean age was 67 ± 16 years and the median NIHSS was 17. The sites of arterial occlusion before treatment were M1 middle cerebral artery (MCA) in 561 (50%) patients, carotid terminus in 214 (19%) patients, M2 MCA in 171 (15%) patients, tandem occlusions in 141 (13%) patients, and isolated extracranial internal carotid artery occlusion in 35 (3%) patients. Therapeutic interventions included multimodal therapy in 584 (52%) patients, pharmacologic therapy only in 264 (24%) patients, and mechanical therapy only in 274 (24%) patients. Patients treated with multimodal therapy had a significantly higher Thrombolysis in Myocardial Infarction 2 or 3 recanalization rate (435 patients [74%]) compared with pharmacologic therapy only (160 patients, [61%]) or mechanical only therapy (173 patients [63%]), P<.001. In binary logistic regression modeling, independent predictors of Thrombolysis in Myocardial Infarction 2 or 3 recanalization were use of IA thrombolytic OR 1.58 (1.21-2.08), P<.001 and stent deployment 1.91 (1.23-2.96), P<.001., Conclusion: Multimodal therapy has significantly higher recanalization rates compared with pharmacologic or mechanical therapy. Among the individual treatment modalities, stent deployment or IA thrombolytics increase the chance of recanalization., (Copyright © 2011 by the Congress of Neurological Surgeons)

Background and Purpose: Subarachnoid hemorrhage (SAH) is a potential hemorrhagic complication after endovascular intracranial recanalization. The purpose of this study was to describe the frequency and predictors of SAH in acute ischemic stroke patients treated endovascularly and its impact on clinical outcome., Methods: Acute ischemic stroke patients treated with primary mechanical thrombectomy, intra-arterial thrombolysis, or both were analyzed. Postprocedural computed tomography and magnetic resonance images were reviewed to identify the presence of SAH. We assessed any decline in the National Institutes of Health Stroke Scale score 3 hours after intervention and in the outcomes at discharge., Results: One hundred twenty-eight patients were treated by primary thrombectomy with MERCI Retriever devices, whereas 31 were treated by primary intra-arterial thrombolysis. Twenty patients experienced SAH, 8 with pure SAH and 12 with coexisting parenchymal hemorrhages. SAH was numerically more frequent with primary thrombectomy than in the intra-arterial thrombolysis groups (14.1% vs 6.5%, P = 0.37). On multivariate analysis, independent predictors of SAH were hypertension (odds ratio = 5.39, P = 0.035), distal middle cerebral artery occlusion (odds ratio = 3.53, P = 0.027), use of rescue angioplasty after thrombectomy (odds ratio = 12.49, P = 0.004), and procedure-related vessel perforation (odds ratio = 30.72, P < 0.001). Patients with extensive SAH or coexisting parenchymal hematomas tended to have more neurologic deterioration at 3 hours (28.6% vs 0%, P = 0.11), to be less independent at discharge (modified Rankin Scale ≤ 2; 0% vs 15.4%, P = 0.5), and to experience higher mortality during hospitalization (42.9% vs 15.4%, P = 0.29)., Conclusions: Procedure-related vessel perforation, rescue angioplasty after thrombectomy with MERCI devices, distal middle cerebral artery occlusion, and hypertension were independent predictors of SAH after endovascular therapy for acute ischemic stroke. Only extensive SAH or SAH accompanied by severe parenchymal hematomas may worsen clinical outcome at discharge.

Background and Purpose: Hemorrhagic transformation (HT) after fibrinolytic therapy may be less common in patients with acute cerebral ischemia confined to single penetrator artery (SPA) territories than in patients with large artery ischemia. Previous investigations of HT diagnosed small vessel ischemia based on lacunar clinical syndromes, an approach known to yield misdiagnosis in one-third to one-half of cases., Methods: Consecutive intravenous tissue plasminogen activator-treated patients in a prospectively maintained hospital registry were analyzed. Patients were classified as having SPA ischemia if they had imaging evidence of: (1) deep location; (2) diameter ≤ 1.5 cm; and (3) distribution in a single penetrator territory, regardless of presenting clinical syndrome. Lacunar clinical syndrome was defined according to the Oxfordshire Community Stroke Project classification., Results: Among 93 intravenous tissue plasminogen activator-treated patients, mean age was 71.5, 62.4% were female, and median pretreatment National Institutes of Health Stroke Scale score was 14. Single penetrator artery ischemia was imaged in 13 (14.0%) and large artery ischemia was imaged in 75 (80.6%), with no visualized ischemic injury in 5 (5.4%). Lacunar clinical syndromes were present in 23 (24.7%), including 10 with SPA ischemia and 9 with large artery ischemia. No patient with imaging-confirmed SPA infarcts experienced any hemorrhagic transformation, whereas any radiological HT occurred in 29.3% of large artery infarcts (P=0.03). Symptomatic intracerebral hemorrhage occurred in 0% of SPA infarcts vs 4.0% of large artery infarcts., Conclusions: HT after lytic therapy in imaging-confirmed SPA infarcts is uncommon. Imaging demonstration of ischemia confined to SPA territory better-identifies this population at low risk for hemorrhagic complications than clinical lacunar syndromes.