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BackgroundThe influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial.ObjectiveTo investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy.MethodsWe analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome.ResultsCMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0-3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy.ConclusionsPatients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study.

BackgroundSelection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution.MethodsDemographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012.ResultsAmong patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs. 74 years; p

ObjectiveTo assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL).MethodsWe pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions.ResultsAmong 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7).ConclusionsThe association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

ImportanceAtherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk.ObjectiveTo test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke.Design, setting, and participantsA prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015.ExposureStandard medical management of stroke risk factors.Main outcomes and measuresThe primary outcome was VB-territory stroke.ResultsOf the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P = .008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location.Conclusions and relevanceDistal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.

Imaging of stroke and neurovascular disorders has profoundly enhanced clinical practice and related research during the last 40 years since the introduction of computed tomography (CT) and magnetic resonance imaging (MRI) enabled mapping of the brain. We highlight recent advances in neurovascular imaging. We describe how the convergence of readily available data and new clinical trial paradigms will recast our methods for studying the neurovascular patient. The application of a precision medicine approach to the collaterome, a comprehensive synthesis of neurovascular pathophysiology, will entail novel methods for clinical trial randomization, collection of routine and clinical trial imaging results, data archiving, and analysis.

Background and purposeCollateral flow can determine ischemic core and tissue at risk. Using the Interventional Management of Stroke (IMS) III trial data, we explored the relationship between computed tomography angiogram (CTA) collateral status and CT perfusion (CTP) parameters.MethodsBaseline CTA collaterals were trichotomized as good, intermediate, and poor, and CTP studies were analyzed to quantify ischemic core, tissue at risk, and mismatch ratios. Kruskal-Wallis and Spearman tests were used to measure the strength of association and correlation between CTA collaterals and CTP parameters.ResultsA total of 95 patients had diagnostic CTP studies in the IMS III trial. Of these, 53 patients had M1/M2 middle cerebral artery±intracranial internal carotid artery occlusion, where baseline CTA collateral grading was performed. CTA collaterals were associated with smaller CTP measured ischemic core volume (P=0.0078) and higher mismatch (P=0.0004). There was moderate negative correlation between collaterals and core (rs=-0.45; 95% confidence interval, -0.64 to -0.20) and moderate positive correlation between collaterals and mismatch (rs=0.53; 95% confidence interval, 0.29-0.71).ConclusionBetter collaterals were associated with smaller ischemic core and higher mismatch in the IMS III trial. Collateral assessment and perfusion imaging identify the same biological construct about ischemic tissue sustenance.

Background and purposeThree-dimensional pseudocontinuous arterial spin labeling with multiple postlabeling delays has been used to assess cerebral blood flow (CBF). We used this modality to estimate antegrade and collateral flow in patients with unilateral middle cerebral artery stenosis.MethodsConsecutive patients with unilateral middle cerebral artery 50% to 99% stenosis at 2 centers underwent pseudocontinuous arterial spin labeling with a postlabeling delays of 1.5 and 2.5 s. Mean CBF of bilateral middle cerebral artery territory at the postlabeling delays 1.5 and 2.5 s was measured. Early-arriving flow proportion was defined as (CBF 1.5 s at lesion side/CBF 2.5 s at normal side)×100%. Late-arriving retrograde flow proportion was defined as ([CBF 2.5 s-CBF 1.5 s] at lesion side-[CBF 2.5 s-CBF 1.5 s] at normal side)/CBF 2.5 s at normal side×100%. Antegrade and collateral scales were evaluated in patients with conventional angiography. Spearman correlation coefficients were calculated between early-arriving flow and late-arriving retrograde flow proportions on arterial spin labeling and antegrade and collateral scales on conventional angiography, respectively.ResultsForty-one patients (46.0±12.0 years) were enrolled. The mean early-arriving flow proportion was 78.3±14.9%. The mean late-arriving retrograde flow proportion was 16.1±10.2%. In 21 patients with conventional angiography, Spearman correlation coefficient was 0.53 (95% confidence interval, 0.11-0.79) between antegrade grade and early-arriving flow proportion (P=0.01) and 0.81 (95% confidence interval, 0.56-0.92) between collateral grade and late-arriving retrograde flow proportion (P

Background and purposeThe enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated.MethodsThe Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening process-paramedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded.ResultsFrom 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%).ConclusionsIn this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

BackgroundEndovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome.MethodsDemographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010.ResultsHigher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival.ConclusionsImproved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome.

ImportanceTreatments for symptomatic intracerebral hemorrhage (sICH) are based on expert opinion, with limited data available on efficacy.ObjectiveTo better understand the natural history of thrombolysis-related sICH, with a focus on the efficacy of various treatments used.Design, setting, and participantsMulticenter retrospective study between January 1, 2009, and April 30, 2014, at 10 primary and comprehensive stroke centers across the United States. Participants were all patients with sICH, using the definition by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), which included a parenchymal hematoma type 2 and at least a 4-point increase in the National Institutes of Health Stroke Scale score.Main outcomes and measuresThe primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion, defined as a 33% increase in the hematoma volume on follow-up imaging.ResultsOf 3894 patients treated with intravenous recombinant tissue plasminogen activator (rtPA) within 4½ hours after symptom onset of ischemic stroke, 128 (3.3%) had sICH. The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes (range, 30-2572 minutes), and the median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes). The in-hospital mortality rate was 52.3% (67 of 128), and 26.8% (22 of 82) had hematoma expansion. In the multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality (odds ratio, 3.6; 95% CI, 1.2-10.6). Severe hypofibrinogenemia (fibrinogen level,

BackgroundExternal counterpulsation (ECP) increases perfusion to a variety of organs and may be helpful for acute stroke.MethodsWe conducted a single-blinded, prospective, randomized controlled feasibility and safety trial of ECP for acute middle cerebral artery (MCA) ischemic stroke. Twenty-three patients presenting within 48 hours of symptom onset were randomized into one of two groups. One group was treated with ECP for 1 hour at a pressure of up to 300 mmHg ("full pressure"). During the procedure, we also determined the highest possible pressure that would augment MCA mean flow velocity (MFV) by 15%. The other group was treated with ECP at 75 mmHg ("sham pressure"). Transcranial Doppler MCA flow velocities and National Institutes of Health Stroke Scale (NIHSS) scores of both groups were checked before, during, and after ECP. Outcomes were assessed at 30 days after randomization.ResultsAlthough the procedures were feasible to implement, there was a frequent inability to augment MFV by 15% despite maximal pressures in full-pressure patients. In sham-pressure patients, however, MFV frequently increased as shown by increases in peak systolic velocity and end diastolic velocity. In both groups, starting ECP was often associated with contemporaneous improvements in NIHSS stroke scores. There were no between-group differences in NIHSS, modified Rankin Scale Scores, and Barthel Indices, and no device or treatment-related serious adverse events, deaths, intracerebral hemorrhages, or episodes of acute neuro-worsening.ConclusionsECP was safe and feasible to use in patients with acute ischemic stroke. It was associated with unexpected effects on flow velocity, and contemporaneous improvements in NIHSS score regardless of pressure used, with a possibility that even very low ECP pressures had an effect. Further study is warranted.

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2*-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13-13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome.

Background and purposeEmergency 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.MethodsWe 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.ResultsThere 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% (P9 in 10, with no clinically significant increase in prehospital care times and enhanced recruitment of patients into a prehospital treatment trial.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Despite significant quality improvement efforts to streamline in-hospital acute stroke care in the conventional model, there remain inherent layers of treatment delays, which could be eliminated with prehospital diagnostics and therapeutics administered in a mobile stroke unit. Early diagnosis using telestroke and neuroimaging while in the ambulance may enable targeted routing to hospitals with specialized care, which will likely improve patient outcomes. Key clinical trials in telestroke, mobile stroke units with prehospital neuroimaging capability, prehospital ultrasound and co-administration of various classes of neuroprotectives, antiplatelets and antithrombin agents with intravenous thrombolysis are discussed in this article.

ObjectEncephaloduroarteriosynangiosis (EDAS) is a form of revascularization that has shown promising early results in the treatment of adult patients with moyamoya disease (MMD) and more recently in patients with intracranial atherosclerotic steno-occlusive disease (ICASD). Herein the authors present the long-term results of a single-center experience with EDAS for adult MMD and ICASD.MethodsPatients with ischemic symptoms despite intensive medical therapy were considered for EDAS. All patients undergoing EDAS were included. Clinical data, including recurrence of transient ischemic attack (TIA) and/or stroke, functional status, and death, were collected from a retrospective data set and a prospective cohort. Perren revascularization and American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grades were recorded from angiograms.ResultsA total of 107 EDAS procedures were performed in 82 adults (36 with ICASD and 46 with MMD). During a median follow-up of 22 months, 2 (2.4%) patients had strokes; both patients were in the ICASD group. TIA-free survival and stroke-free survival analyses were performed using the product limit estimator (Kaplan-Meier) method. The probability of stroke-free survival at 2 years in the ICASD group was 94.3% (95% CI 80%-98.6%). No patient in the MMD group suffered a stroke. The probability of TIA-free survival at 2 years was 89.4% (95% CI 74.7%-96%) in ICASD and 99.7% (95% CI 87.5%-99.9%) in MMD. There were no hemorrhages or stroke-related deaths. Angiograms in 85.7% of ICASD and 92% of MMD patients demonstrated Perren Grade 3 and improvement in ASITN/SIR grade in all cases.ConclusionsEDAS is well tolerated in adults with MMD and ICASD and improves collateral circulation to territories at risk. The rates of stroke after EDAS are lower than those reported with other treatments, including intensive medical therapy in patients with ICASD.

BackgroundTo 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.MethodsSTroke 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.ResultsWe 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) .ConclusionThere 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.

The recent culmination of imaging-endowed endovascular stroke trials has decisively proven the utility of clinically relevant neuroimaging in improving the outcome of patients with potentially debilitating neurological disorders. These large multicenter trials conducted across several continents notably utilized a variety of multimodal CT/MRI modalities to rapidly identify a favorable collateral profile that presages clinically beneficial revascularization. The modern clinical neuroimager may accelerate complex decision-making through the rational use of a variety of imaging modalities and an active feedback loop of imaging at the bedside. The modern clinical neuroimager is often the initial care provider for a wide range or type of stroke patients from hemorrhage to ischemia, armed with the incredibly important aspects of clinical history and examination findings and best poised to utilize imaging to guide therapy from acute stroke to recovery and prevention. The next generation in stroke should not exclusively focus on whether to order a CT or MRI counting minutes at the bedside, but actively and efficiently integrate the vast wealth of information available when imaging is used in the proper clinical context. The novel endovascular era in stroke provides an ideal venue for the synergistic goals of translating research advances, improving patient outcomes and ongoing education as a modern neuroimager.

Background and purposeAtherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort.MethodsPatients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was assessed using quantitative MRA.ResultsThe cohort (n=72; 44% women) had a mean age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows correlated negatively with percentage stenosis in the affected vessel and positively to the minimal diameter at the stenosis site (P

Ischemic stroke remains a leading cause of death and disability worldwide. Various endovascular trials have addressed clinical outcomes without elucidating the impact of imaging studies in patient selection. The success of recent endovascular trials was bolstered by the use of advanced imaging techniques for optimal selection of reperfusion candidates. This seminal juncture in the history of stroke trials warrants further consideration on the use of imaging to guide future refinements in the treatment of acute stroke. In this article, we systematically review the imaging methodology and key facets used in all published endovascular stroke trials to date, discuss the success of recent trials using latest advanced imaging techniques and focus on the importance of imaging studies for future patient selection.

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.

BackgroundThe ideal population of patients for endovascular therapy (ET) in acute ischemic stroke remains undefined. Recent ET trials have moved towards selecting patients with proximal middle cerebral artery (MCA) or internal carotid artery occlusions, which will likely leave a gap in our understanding of the treatment outcomes of M2 occlusions.Objective and methodsTo examine the presentation, treatment, and outcomes of M2 compared with M1 MCA occlusions in patients undergoing ET by assessing comprehensive MRI, angiography, and clinical data.ResultsWe found that M2 occlusions can lead to massive strokes defined by hypoperfused and infarcted volumes as well as death or moderate to severe disability in nearly 50% of patients at discharge. Compared with M1 occlusions, M2 occlusions achieved similar Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization rates, with significantly less hemorrhage. M2 occlusions presented with smaller infarct and hypoperfused volumes and had smaller final infarct volumes regardless of recanalization. TICI 2b/3 recanalization of M2 occlusions was associated with smaller infarct volumes compared with TICI 0-2a recanalization, as well as less infarct expansion, in patients who received IV tissue plasminogen activator as well as those that did not. Successful reperfusion of M2 occlusions was associated with improved discharge modified Rankin scale.ConclusionsIf suitable as targets of ET, M2 occlusions should be given the same consideration as M1 occlusions.

Background and purposeUntil 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.MethodsCIS 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.ResultsOnly CIS and modified thrombolysis in cerebral infarction scores were correlated with good outcomes (P

BackgroundCollaterals may affect revascularization, ischemic severity, and clinical outcomes in acute stroke owing to internal carotid artery (ICA) occlusion.ObjectiveTo examine the hypothesis that morphology of occlusive thrombus and collateral flow patterns may influence the outcome of ICA occlusions after mechanical thrombectomy.MethodsPooled analyses of ICA occlusions in the MERCI and Multi-MERCI trials employed central angiography review readings to categorize lesions as I, L, or T clots and functional lesions based on collateral flow patterns. Demographic variables, procedural details, and clinical outcomes were compared across ICA lesion types.ResultsA total of 72 subjects (mean age 67 years (SD 16), 51% female, median National Institutes of Health Stroke Scale 20 (range 8-35)) were included, with 90-day modified Rankin score ≤2 in 28% and 51% mortality. Clots were categorized as an I lesion in 9/72 (12.5%), L lesion in 12/72 (16.7%), and T lesion in 51/72 (70.8%). Based on collateral flow patterns, cases were categorized as having a functional I lesion in 7/72 (9.7%), functional L in 38/72 (52.8%), and functional T in only 27/72 (37.5%). Multivariate analyses showed that a functional T lesion, with insufficient collateral flow to ipsilateral anterior cerebral arteries via the contralateral ICA, was a strong predictor of both revascularization success and subsequent clinical outcomes.ConclusionsCollateral flow patterns distinguish the nature and impact of ICA occlusions on expected revascularization and subsequent clinical outcomes in acute ischemic stroke. The nomenclature of terminal ICA occlusions introduced here (carotid I's, L's, and T's) may enhance future endovascular trials targeting such proximal occlusions.Trial registration numberNCT00318071 (http://clinicaltrials.gov). MERCI was not registered because enrollment began before July 1, 2005.

Background and purposeWe aim to investigate whether lower admission serum calcium levels are associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT).MethodsA total of 362 patients treated with IVT was divided into 4 quartiles based on admission serum calcium levels (Q1[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.ResultsCompared 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.ConclusionsLower admission serum calcium level is independently associated with HT after IVT, and this hypothesis needs larger confirmatory trials.

Background and purposeHigh periprocedural complication rate is a key limitation of endovascular treatment of intracranial atherosclerotic disease (ICAD), despite potential risk reduction of recurrent stroke. Taking lessons from the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Arterial Stenosis (SAMMPRIS) trial, targeting a selected patient population, we prospectively evaluated the feasibility and safety of tailored angioplasty and/or stenting for patients with ICAD.MethodsFrom November 2011 to October 2012, 158 patients with symptomatic ICAD caused by hypoperfusion combined with poor collateral flow were consecutively recruited into a prospective single center study. Patients were divided into three groups based on arterial access and lesion morphology: balloon mounted stent group (group BS) for smooth access and Mori A lesion, angioplasty plus self-expanding stent group (group AS) for tortuous access and Mori B or C lesion, and angioplasty group (group AG) for tortuous access and Mori A lesion. The primary endpoints were successful procedure rate and any vascular event within 30 days.ResultsOverall technical success rate was 96.3% (154/158). There were significant differences in the technical success rate: 89.7% (35/39) in group AG compared with 97.5% (79/81) in group BS and 100% (38/38) in group AS (p=0.042). The 30 day composite stroke, myocardial infarction, or death rate was 4.4% (7/158). Stroke within 30 days occurred in four patients in group BS and in three patients in group AS.ConclusionsIndividualized treatment of ICAD using tailored devices according to arterial access and lesion morphology was feasible and safe in symptomatic patients caused by hypoperfusion with poor collateral flow.

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.

The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P

Imaging protocols of acute ischemic stroke continue to hold significant uncertainties regarding patient selection for reperfusion therapy with thrombolysis and mechanical thrombectomy. Given that patient inclusion criteria can easily introduce biases that may be unaccounted for, the reproducibility and reliability of the patient screening method is of utmost importance in clinical trial design. The optimal imaging screening protocol for selection in targeted populations remains uncertain. Acute neuroimaging provides a snapshot in time of the brain parenchyma and vasculature. By identifying the at-risk but still viable penumbral tissue, imaging can help estimate the potential benefit of a reperfusion therapy in these patients. This paper provides a perspective about the assessment of the penumbral tissue in the context of acute stroke and reviews several neuroimaging models that have recently been developed to assess the penumbra in a more reliable fashion. The complexity and variability of imaging features and techniques used in stroke will ultimately require advanced data driven software tools to provide quantitative measures of risk/benefit of recanalization therapy and help aid in making the most favorable clinical decisions.

Recent successful endovascular stroke trials have provided unequivocal support for these therapies in selected patients with large-vessel occlusive acute ischemic stroke. In this piece, we briefly review these trials and their utilization of advanced neuroimaging techniques that played a pivotal role in their success through targeted patient selection. In this context, the unique challenges and opportunity for advancement in current stroke networks' routine delivery of care created by these trials are discussed and recommendations to change current national stroke system guidelines are proposed.

BackgroundLesion 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.AimsThe 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.MethodsConsecutive 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.ResultsAmong 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).ConclusionsSpecific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients.

BackgroundPrecision medicine in cerebrovascular disorders may be greatly advanced by the use of innovative interventional and imaging-intensive registries. Registries have remained subsidiary to randomized controlled trials, yet vast opportunities exist to leverage big data in stroke.SummaryThis overview builds upon the rationale for innovative, imaging-intensive interventional registries as a pivotal step in realizing precision medicine for several cerebrovascular disorders. Such enhanced registries may serve as a model for expansion of our translational research pipeline to fully leverage the role of phase IV investigations. The scope and role of registries in precision medicine are considered, followed by a review on the history of stroke and interventional registries, data considerations, critiques or barriers to such initiatives, and the potential modernization of registry methods into efficient, searchable, imaging-intensive resources that simultaneously offer clinical, research and educational added value.Key messagesRecent advances in technology, informatics and endovascular stroke therapies converge to provide an exceptional opportunity for registries to catapult further progress. There is now a tremendous opportunity to deploy registries in acute stroke, intracranial atherosclerotic disease and carotid disease where other clinical trials leave questions unanswered. Unlike prior registries, imaging-intensive and modernized methods may leverage current technological capabilities around the world to efficiently address key objectives and provide added clinical, research and educational value.