Update on Treatment of Acute Ischemic Stroke.

EDITOR'S NOTE: The article "Update on Treatment of Acute Ischemic Stroke" by Dr Rabinstein was first published in the February 2017 Cerebrovascular Disease issue of Continuum: Lifelong Learning in Neurology as "Treatment of Acute Ischemic Stroke" and has been updated by Dr Rabinstein for this issue at the request of the Editor-in-Chief. ABSTRACT: PURPOSE OF REVIEWThis article provides an update on the state of the art of the treatment of acute ischemic stroke with particular emphasis on the indications for reperfusion therapy.RECENT FINDINGSIn addition to the previously established indications for intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of stroke symptom onset and endovascular therapy with mechanical thrombectomy for patients with large artery occlusion who can be treated within 6 hours of symptom onset, recent randomized controlled trials have now established new indications for emergency reperfusion in patients with wake-up stroke or delayed presentation (up to 24 hours from last known well in the case of mechanical thrombectomy). Identification of patients who may benefit from acute reperfusion therapy within this extended time window requires screening with perfusion brain imaging or, in the case of IV thrombolysis for wake-up strokes, emergency brain MRI. Collateral status and time to reperfusion remain the primary determinants of outcome.SUMMARYTimely successful reperfusion is the most effective treatment for patients with acute ischemic stroke. Recent evidence supports the expansion of the time window for reperfusion treatment in carefully selected patients.

European Stroke Organisation (ESO)- European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke.

BACKGROUND: Mechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians in their clinical decisions with regard to MT. METHODS: These guidelines were developed based on the standard operating procedure of the European Stroke Organisation, and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. RESULTS: We found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24 hour time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities. CONCLUSIONS: MT is the standard of care in patients with LVO related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision making with regard to the mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Unresolved Issues in Thrombectomy.

PURPOSE OF REVIEW: Trials demonstrating marked benefit of mechanical thrombectomy (MT) for acute stroke caused by large vessel occlusion (LVO) in the anterior circulation have been the most significant advance in acute ischemic stroke in the past 20 years. However, despite this marked advance, there are still many hurdles to improving access to thrombectomy worldwide. Additionally, despite these advances, a substantial portion of patients with LVO still are left disabled. RECENT FINDINGS: The major randomized trials focused on patients within 6 h from symptom onset, with occlusion of the ICA or proximal MCA, small amount of permanently damaged brain, and a moderate to large clinical deficit. We will explore the role of thrombectomy outside of these areas, but also explore larger issues as they pertain to re-organization of stroke systems of care to improve access to this remarkable therapy. Now that we have proven, without a shadow of doubt, that rapid revascularization with mechanical thrombectomy improves outcomes in LVO stroke, we must reorganize our systems of care to improve access and assess the role for MT outside of the patients who meet trial criteria.

Monitored Anesthesia Care vs Intubation for Vertebrobasilar Stroke Endovascular Therapy.

Importance: No consensus regarding the ideal sedation treatment for stroke endovascular therapy has been reached, and practices remain largely based on local protocols and clinician preferences. Most studies have focused on anterior circulation strokes; therefore, little is known regarding the optimal anesthesia type for vertebrobasilar occlusion strokes. Objective: To compare clinical and angiographic outcomes between monitored anesthesia care (MAC) and general anesthesia (GA) in patients presenting with vertebrobasilar occlusion strokes. Design, Setting, and Participants: Retrospective, matched, case-control study of consecutive vertebrobasilar occlusion strokes treated with endovascular therapy at 2 academic institutions. The study took place between September 2005 and September 2015 at University of Pittsburgh Medical Center Stroke Institute, Pittsburgh, Pennsylvania, and between September 2010 and September 2015 at the Marcus Stroke and Neuroscience Center at Grady Memorial Hospital, Atlanta, Georgia. Patients requiring emergent intubation prior to endovascular therapy were excluded. The remaining patients were categorized into (1) MAC and (2) elective intubation for the procedure (elective GA). Patients who converted from MAC to GA during the procedure were included in the MAC group. The 2 groups were matched for age, baseline National Institutes of Health Stroke Scale score, and glucose levels. Baseline characteristics and outcomes were compared. Main Outcomes and Measures: The primary outcome measure was the shift in the degree of disability among the 2 groups as measured by the modified Rankin scale at 90 days. Results: A total of 215 patients underwent endovascular therapy for vertebrobasilar occlusion strokes during the study period. Thirty-nine patients were excluded owing to emergent pre-endovascular therapy intubation. Sixty-three patients had MAC (36%) and 113 patients had GA (64%). The conversion rate from MAC to GA was 13% (n = 8). After matching, 61 pairs of patients (n = 122) underwent primary analysis. The 2 groups were well balanced in terms of baseline characteristics. Median age was 69 years (interquartile range, 60-75 years) in the MAC group vs 67 years (interquartile range, 55.5-78.5 years) in the GA group (P = .83). Fifty-four percent of the patients in the MAC group were men vs 41% in the GA group (P = .44). When compared with the elective GA group, patients who underwent the procedure with MAC had similar rates of successful reperfusion, good clinical outcomes, hemorrhagic complications, and mortality. The modality of anesthesia was not associated with any significant changes in the modified Rankin scale score distribution (MAC: OR, 1.52; 95% CI, 0.80-2.90; P = .19). Conclusions and Relevance: In endovascular therapy for acute posterior circulation stroke, MAC is feasible and appears to be as safe and effective as GA. Future clinical trials are warranted to confirm our findings.

Trombólisis fármaco-mecánica: una técnica a considerar en el tratamiento de la trombosis venosa profunda iliofemoral aguda / Pharmaco-mechanical thrombolysis: A technique to consider in the treatment of acute iliofemoral deep vein thrombosis

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Rapid Systematic Review: Intra-Arterial Thrombectomy ("Clot Retrieval") for Selected Patients with Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality. However, precisely defining the optimal treatment for individual patients early after AIS onset remains elusive. There has recently been a surge in published studies documenting the effectiveness of mechanical intra-arterial thrombectomy for treatment of a subset of patients with AIS. This therapy has been proposed and studied for the small (<1.2%) subgroup of patients with ischemic strokes who have "large vessel" strokes or strokes that fail to improve after the administration of tissue plasminogen activator (t-PA). The current rapid systematic review provides practicing emergency physicians updated information regarding mechanical thrombectomy as a treatment option for carefully selected AIS patients. METHODS: A PubMed literature search was conducted from January 1996 to June 2016 and limited to human clinical trials written in English with relevant keywords. High-quality randomized controlled studies identified then underwent a structured review. RESULTS: In total, 179 papers fulfilling the search criteria were screened and 8 appropriate articles were rigorously reviewed in detail and recommendations given on the effectiveness and indication of mechanical intra-arterial thrombectomy for the treatment of AIS. CONCLUSIONS: Mechanical intra-arterial thrombectomy reduces long-term disability in a properly selected subset of patients who have an AIS caused by large vessel occlusion. Many of these patients will have failed to improve after intravenous administration of t-PA, and mortality is not increased when combined with t-PA. Careful screening criteria should be in place to identify the limited subset of patients to whom this therapy is delivered to derive optimal treatment benefits.

What is the definition of successful lysis: reporting standard?

Deep vein thrombosis, and the resultant development of post-thrombotic syndrome, is a significant health issue. Recent evidence demonstrates that the severity of post-thrombotic syndrome symptoms is directly related to the level of venous thrombosis and following treatment these subsequent symptoms are inversely related to the degree of thrombus removal. If we can improve, and preferably standardise the terminology associated with pre-treatment assessment of thrombus load and post-treatment success of thrombus removal techniques, we should then be able to choose more tailor-made techniques to greater benefit our patients. A number of scoring systems have been devised for the assessment of venous thrombus burden, with a majority impractical for everyday usage. In order to provide a more practical solution, the lower extremity thrombosis classification has been developed, using information on anatomical location for venous thrombus combined with a clinical indicator as to the likely sequelae. Anatomical success following venous thrombolysis can be defined by assessing restoration of anterograde flow in the treated vein or the percentage degree of thrombolysis, using venography. The second option is the method most frequently utilised, with the Venous Registry grading system applied. Data from recent trials have given us conflicting and confusing data mainly because we are not using standardised terminology. We urgently need to agree on a standard method of description of thrombus removal before stent placement which also incorporates the likely clinical impact of the area involved in the thrombosis.

[Technical standards for the interventional treatment of acute ischemic stroke]. / Technische Standards bei der interventionellen Behandlung des akuten ischämischen Schlaganfalls.

Acute ischemic stroke is the leading cause of acquired disability and its treatment is still a major challenge. For more than a decade, various mechanical devices have been developed for the recanalization of proximal artery occlusions in acute ischemic stroke but most of them have been approved for clinical use, only on the basis of uncontrolled case series. Intravenous thrombolysis with recombinant tissue-specific plasminogen activator administered (iv rtPA) within 4.5 h of symptom onset is so far the only approved medicinal treatment in the acute phase of cerebral infarction. With the introduction of stent retrievers, mechanical thrombectomy has demonstrated substantial rates of partial or complete arterial recanalization and improved outcomes compared with iv rtPA and best medical treatment alone in multiple randomized clinical trials in select patients with acute ischemic stroke and proximal artery occlusions. This review discusses the evolution of endovascular stroke therapy followed by a discussion of the current technical standards of mechanical thrombectomy that have to be considered during endovascular stroke therapy and the updated treatment recommendations of the ESO Karolinska stroke update.

Endothelial trauma from mechanical thrombectomy in acute stroke: in vitro live-cell platform with animal validation.

BACKGROUND AND PURPOSE: Endovascular thrombectomy has shown promise for the treatment of acute strokes resulting from large-vessel occlusion. Reperfusion-related injury may contribute to the observed decoupling of angiographic and clinical outcomes. Iatrogenic disruption of the endothelium during thrombectomy is potentially a key mediator of this process that requires further study. METHODS: An in vitro live-cell platform was developed to study the effect of various commercially available endovascular devices on the endothelium. In vivo validation was performed using porcine subjects. RESULTS: This novel in vitro platform permitted high-resolution quantification and characterization of the pattern and timing of endothelial-cell injury among endovascular thrombectomy devices and vessel diameters. Thrombectomy devices displayed heterogeneous effects on the endothelium; the device performance assessed in vitro was substantiated by in vivo findings. CONCLUSIONS: In vitro live-cell artificial vessel modeling enables a detailed study of the endothelium after thrombectomy and may contribute to future device design. Large animal studies confirm the relevance of this in vitro system to investigate endothelial physiology. This artificial vessel model may represent a practical, scalable, and physiologically relevant system to assess new endovascular technologies.

Clinical, angiographic and radiographic outcome differences among mechanical thrombectomy devices: initial experience of a large-volume center.

BACKGROUND AND PURPOSE: Higher reperfusion rates have been established with endovascular treatment of acute ischemic stroke (AIS). There are limited data on the comparative performance of mechanical thrombectomy devices. METHODS: A retrospective single-center analysis was undertaken of all consecutive patients who underwent thrombectomy using Merci, Penumbra or stent retrievers (SR) from September 2010 to November 2012. Baseline characteristics, rates of successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) score 2b-3), symptomatic intracerebral hemorrhage (sICH), final infarct volume, 90-day mortality and independent functional outcomes at 90 days were compared across the three devices. RESULTS: Our cohort included 287 patients. There were mild imbalances in baseline characteristics with trends towards higher National Institutes of Health Stroke Scale (NIHSS) score in patients in the Merci group (SR=18 vs Merci=21 vs Penumbra=19, p=0.06) and lower Alberta Stroke Program Early CT Score (ASPECTS) in patients in the SR group (>7: SR=51% vs Merci=61% vs Penumbra=62%, p=0.12). On univariate analysis there were no differences in the rate of sICH (SR=7% vs Merci=7% vs Penumbra=6%, p=0.921) and infarct volume (SR=61.5 mL vs Merci=69.5 mL vs Penumbra=59.2 mL, p=0.621). Trends towards better functional outcomes were found with Penumbra and SR vs Merci (41% vs 36% vs 25%, respectively, p=0.079). Complete or near complete reperfusion (mTICI 2b-3) was higher in the SR and Penumbra groups than in the Merci group (86% vs 78% vs 70%, respectively, p=0.027). Binary logistic regression showed that SR was an independent predictor of good functional outcome (OR 2.27, 95% CI 1.018 to 5.048; p=0.045). CONCLUSIONS: Although our initial data confirm the superiority of SR technology over the Merci device, there was no significant difference in near complete/complete reperfusion, final infarct volumes or clinical outcomes between SR and Penumbra thromboaspiration.