Andrei V. Alexandrov

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P=0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden: A Meta-analysis.

IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with ≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95% CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95% CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95% CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95% CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95% CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence of CMB and high CMB burdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.

Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities.

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.

THRIVE Score Predicts Ischemic Stroke Outcomes and Thrombolytic Hemorrhage Risk in VISTA

Background and Purpose— In previous studies, the Totaled Health Risks in Vascular Events (THRIVE) score has shown broad utility, allowing prediction of clinical outcome, death, and risk of hemorrhage after tissue-type plasminogen activator (tPA) treatment, irrespective of the type of acute stroke therapy applied to the patient. Methods— We used data from the Virtual International Stroke Trials Archive to further validate the THRIVE score in a large cohort of patients receiving tPA or no acute treatment, to confirm the relationship between THRIVE and hemorrhage after tPA, and to compare the THRIVE score with several other available outcome prediction scores. Results— The THRIVE score strongly predicts clinical outcome (odds ratio, 0.55 for good outcome [95% CI, 0.53–0.57]; P<0.001), mortality (odds ratio, 1.57 [95% confidence interval, 1.50–1.64]; P<0.001), and risk of intracerebral hemorrhage after tPA (odds ratio, 1.34 [95% confidence interval, 1.22–1.46]; P<0.001). The relationship between THRIVE score and outcome is not influenced by the independent relationship of tPA administration and outcome. In receiver operator characteristic curve analysis, the THRIVE score was superior to several other available outcome prediction scores in the prediction of clinical outcome and mortality. Conclusions— The THRIVE score is a simple-to-use tool to predict clinical outcome, mortality, and risk of hemorrhage after thrombolysis in patients with ischemic stroke. Despite its simplicity, the THRIVE score performs better than several other outcome prediction tools. A free Web calculator for the THRIVE score is available at http://www.thrivescore.org.

Adherence to a Mediterranean Diet and Prediction of Incident Stroke

Background and Purpose— There are limited data on the potential association of adherence to Mediterranean diet (MeD) with incident stroke. We sought to assess the longitudinal association between greater adherence to MeD and risk of incident stroke. Methods— We prospectively evaluated a population-based cohort of 30 239 individuals enrolled in REasons for Geographic and Racial Differences in Stroke (REGARDS) study, after excluding participants with stroke history, missing demographic data or food frequency questionnaires, and unavailable follow-up information. Adherence to MeD was categorized using MeD score. Incident stroke was adjudicated by expert panel review of medical records during a mean follow-up period of 6.5 years. Results— Incident stroke was identified in 565 participants (2.8%; 497 and 68 cases of ischemic stroke [IS] and hemorrhagic stroke, respectively) of 20 197 individuals fulfilling the inclusion criteria. High adherence to MeD (MeD score, 5–9) was associated with lower risk of incident IS in unadjusted analyses (hazard ratio, 0.83; 95% confidence interval, 0.70–1.00; P=0.046). The former association retained its significance (hazard ratio, 0.79; 95% confidence interval, 0.65–0.96; P=0.016) after adjustment for demographics, vascular risk factors, blood pressure levels, and antihypertensive medications. When MeD was evaluated as a continuous variable, a 1-point increase in MeD score was independently associated with a 5% reduction in the risk of incident IS (95% confidence interval, 0–11%). We documented no association of adherence to MeD with incident hemorrhagic stroke. There was no interaction of race (P=0.37) on the association of adherence to MeD with incident IS. Conclusions— High adherence to MeD seems to be associated with a lower risk of incident IS independent of potential confounders. Adherence to MeD is not related to the risk of incident hemorrhagic stroke.

Posterior circulation CT angiography collaterals predict outcome of endovascular acute ischemic stroke therapy for basilar artery occlusion

Introduction The natural history of acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) is poor. Endovascular reperfusion therapy (EVT) improves recanalization rates in patients with emergent large vessel intracranial occlusion. Objective To examine the hypothesis that good collateral patterns identified by pretreatment CT angiography (CTA) might be associated with favorable outcomes after EVT. Methods We conducted a retrospective chart review of patients presenting with AIS due to BAO in a tertiary care stroke center during a 4-year period. BAO was diagnosed by CTA in all cases. Admission stroke severity was documented using the National Institute of Health Stroke Scale (NIHSS) score. Pretreatment collateral score for posterior circulation was defined as follows: 0, no posterior communicating artery (PCOM); 1, unilateral PCOM; 2, bilateral PCOM. Favorable outcome was defined as modified Rankin Scale score of 0–2 at 3 months. Results A total of 21 patients with AIS due to BAO (age range 31–84 years, median admission NIHSS score: 18 points, range 2–38) underwent EVT. Eleven of 21 patients (52.4%) had bilateral PCOMs, while unilateral PCOM was seen in 3 patients (14.3%). Patients with bilateral PCOMs tended (p=0.261) to have less severe stroke at admission than those with absent/unilateral PCOM (median NIHSS score 18 vs 27 points). Neurological improvement during hospitalization (quantified by the median decrease in NIHSS score) and the rate of 3-month functional independence were greater in patients with good collaterals (16 vs 0 points (p=0.016) and 72.7% vs 0% (p=0.001)). Conclusions The presence of bilateral PCOMs on pretreatment CTA appears to be associated with more favorable outcomes in BAO treated with EVT.

Reperfusion therapies of acute ischemic stroke: potentials and failures.

Over the past 20 years, clinical research has focused on the development of reperfusion therapies for acute ischemic stroke (AIS), which include the use of systemic intravenous thrombolytics (alteplase, desmoteplase, or tenecteplase), the augmentation of systemic intravenous recanalization with ultrasound, the bridging of intravenous with intra-arterial thrombolysis, the use of multi-modal approaches to reperfusion including thrombectomy and thromboaspiration with different available retrievers. Clinical trials testing these acute reperfusion therapies provided novel insight regarding the comparative safety and efficacy, but also raised new questions and further uncertainty on the field. Intravenous alteplase (tPA) remains the fastest and easiest way to initiate acute stroke reperfusion treatment, and should continue to be the first-line treatment for patients with AIS within 4.5 h from onset. The use of tenecteplase instead of tPA and the augmentation of systemic thrombolysis with ultrasound are both novel therapeutical modalities that may emerge as significant options in AIS treatment. Endovascular treatments for AIS are rapidly evolving due to technological advances in catheter-based interventions and are currently emphasizing speed in order to result in timely restoration of perfusion of still-salvageable, infarcted brain tissue, since delayed recanalization of proximal intracranial occlusions has not been associated with improved clinical outcomes. Comprehensive imaging protocols in AIS may enable better patient selection for endovascular interventions and for testing multi-modal combinatory strategies.

Safety of intravenous thrombolysis for acute ischemic stroke in specific conditions

Introduction: Intravenous administration of tissue-type plasminogen activator (IV-tPA) remains the only approved therapy that may reverse neurological deficit in patients with acute ischemic stroke (AIS). During the past 20 years, accumulating real-word experience have provided additional information regarding its safety and efficacy in various clinical settings that were originally considered as contraindications for systemic thrombolysis. Areas covered: In this narrative review, we address the safety of intravenous thrombolysis (IVT) in specific conditions: dissection of the aortic arch of extracranial and intracranial arteries, concomitant presence of unruptured intracranial aneurysms, arteriovenous malformations and dural fistulas, co-existing brain tumors as well as in conditions mimicking AIS. The review systematically evaluates the safety of off-label use of IVT and summarizes data from case reports of uncommon complications of systemic thrombolysis administration in the setting of acute cerebral ischemia. Expert opinion: The present narrative review summarizing 20 years of clinical experience with IVT for AIS highlights that many of the current guidelines and protocols should be adjusted to accommodate recent data from registries and real-world experience underscoring the safety of IVT in numerous conditions of AIS that were originally considered as relative or absolute contraindications for administration of IV-tPA.

Mechanical thrombectomy for emergent large vessel occlusion: A critical appraisal of recent randomized controlled clinical trials

After numerous attempts to prove efficacy for endovascular treatment of ischemic stroke, a series of recent randomized controlled clinical trials (RCTs) established fast mechanical thrombectomy (MT) as a safe and effective novel treatment for emergent large vessel occlusion (ELVO) in the anterior cerebral circulation.

Safety of Intravenous Thrombolysis among Stroke Patients Taking New Oral Anticoagulants—Case Series and Systematic Review of Reported Cases

BACKGROUND Current guidelines do not recommend the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke (AIS) who take new oral anticoagulants (NOACs). We present a multicenter case series of IV-tPA use while the patients are on NOACs, as well as a systematic review of the literature. METHODS We reviewed the medical records of consecutive patients on NOACs who received IV-tPA for symptoms of AIS at four participating stroke centers in the United States and Europe. Safety endpoints were post-thrombolysis symptomatic intracranial hemorrhage (sICH) or other serious systemic bleeding. RESULTS Between October 2010 and October 2014, 6 patients received IV-tPA for possible AIS while taking dabigatran. None of the patients had sICH or any other hemorrhagic complication. Literature review resulted in a total of 26 patients receiving IV-tPA while on NOACs (dabigatran: 15, rivaroxaban: 10, apixaban: 1). Among them, two patients experienced sICH and died. None of the patients experienced major extracranial hemorrhage; however, minor and asymptomatic hemorrhagic complications were described in 7 patients. Pooled analysis indicates an sICH rate of 6.45% (95% CI by the adjusted Wald method: .8-21.7%). The mean interval between the last dose of NOAC and IV thrombolysis was 12 ± 7.8 [4-28.3] hours. CONCLUSIONS Although the safety of IV-tPA cannot be definitively confirmed in a small series, consideration of stroke severity and management of hemorrhage risk with general precautions with post-tPA management protocols can justify treatment in the absence of coagulopathy.