Neurology September 2012 Volume 79 Issue 13_Suppl_1

: Though rarely considered in the clinical decision algorithm, issues of cost-effectiveness assume critical importance for the sustainability of a widely used therapy that entails considerable cost and has unproven benefit. Although current data are limited, we review the studies that have demonstrated via modeling that endovascular stroke treatment may generate significant future economic benefits, even if these treatments have a high price and result in relatively small initial reductions in disability. We highlight important considerations that, on the basis of the logistics and protocols of current neuroendovascular practices, should be included in future cost-effectiveness analyses of endovascular therapy for acute ischemic stroke.GLOSSARY: IA: intra-arterialICER: incremental cost effectiveness ratioLVO: large vessel occlusionMERCI: Mechanical Embolus Removal in Cerebral IschemiamRS: modified Rankin ScaleNIHSS: NIH Stroke ScalePROACT: Prolyse in Acute Cerebral ThromboembolismQALYs: quality-adjusted life-yearsSWIFT: SOLITAIRE FR With the Intention For ThrombectomytPA: tissue plasminogen activatorTREVO2: Randomized Trial Evaluating Performance of the Trevo Retriever Versus the Merci Retriever in Acute Ischemic Stroke.(C)2012 American Academy of Neurology

Background: Despite recent advances in acute stroke therapy, only a small proportion of patients with acute ischemic stroke receive IV and endovascular revascularization therapies. This article provides an overview of factors influencing access to stroke therapy.Methods: The key factors influencing access to stroke care highlighted during the Society of Vascular and Interventional Neurology (SVIN) roundtable meeting are summarized. Pertinent selected references on prehospital, hospital, and legislative and economic factors influencing access to stroke care, from the Medline database (between 1995 to 2011), are included. A brief summary of these key factors in improving access to stroke therapy is provided.Results: Prehospital factors include the community; education of hospital administrators and health care personnel; dispatchers; the medical transport system; and preparedness and stroke education of emergency medical services (EMS). Stroke-ready hospitals and networking with other regional tertiary stroke hospitals play important roles in increasing access to stroke care. In addition, legislation at the state and federal levels is a key factor in providing high-quality, timely access to stroke care for the population in general. Strategies to facilitate access to stroke therapy are critical to improving mortality and functional outcome and increasing the proportion of patients treated by systemic thrombolysis and endovascular approaches.Conclusion: This is a brief overview and summary of selected factors influencing access to stroke care. These factors are divided into prehospital, hospital, legislative, and economic categories. Multilevel education of the population, public health care personnel, hospital preparedness, and legislative and economic factors are important in improving access to stroke care.GLOSSARY: AIS: acute ischemic strokeAST: acute stroke teamBAC: Brain Attack CoalitionCSCs: comprehensive stroke centersEMS: emergency medical servicesGH: general hospitalIA: intra-arterialJC: Joint CommissionLR: likelihood ratioNINDS: National Institute of Neurological Disorders and StrokeOSH: outside spoke hospitalPSCs: primary stroke centersrtPA: recombinant tissue plasminogen activatorsICH: symptomatic intracranial hemorrhageSLBSI: St. Luke Brain and Stroke InstituteSVIN: Society of Vascular and Interventional Neurology(C)2012 American Academy of Neurology

: Endovascular therapy has become a promising alternative for patients who are ineligible for IV thrombolysis or for whom it has failed. Greater knowledge about the composition of thromboembolic material underlying the vascular occlusion in stroke patients may provide the means for improving existing endovascular therapies and developing new treatment strategies. The objective of this article is to provide a review of clinical and experimental animal studies on the histology, imaging correlation, and ultrastructure of thromboemboli retrieved during acute ischemic stroke.GLOSSARY: ECASS: European Cooperative Acute Stroke StudyHMCAS: hyperdense middle cerebral artery signIA: intra-arterialICA: internal carotid arteryMCA: middle cerebral arteryMR: magnetic resonanceRBC: red blood cellrtPA: recombinant tissue plasminogen activatorSEM: scanning electron microscopyTIMI: Thrombolysis in Myocardial Ischemia(C)2012 American Academy of Neurology

: Due to the dynamic and versatile characteristics of ischemic penumbra, selecting the right acute ischemic stroke (AIS) patients for revascularization therapy (RT) based on initial available imaging can be challenging. The main patient selection criterion for RT is the size of the mismatch between the potentially salvageable tissue (penumbra) and the irreversibly damaged tissue (core). The goal of revascularization RT is to "freeze" the core and prevent it from extending to the penumbral tissue. Penumbral imaging selection of AIS patients for RT, using magnetic resonance or CT-based studies, may provide more clinical benefit to the appropriate patients, although direct evidence is pending. Not all penumbra-core mismatches beyond 3 hours are equal and need treatment, and defining which mismatches to target for RT is the current goal of ongoing clinical trials. In addition to "penumbral"-based imaging, large vessel occlusion and clot length estimation based on CT angiography and noncontrasted ultrathin CT scan has been used to identify patients who are refractory to systemic thrombolysis and may be eligible for endovascular therapy. The application of various imaging modalities in selecting and triaging AIS patients for RT is discussed in this review. Larger prospective randomized trials are needed to better understand the role of various imaging modalities in selecting AIS patients for RT and to understand its influence on clinical outcome.GLOSSARY: AIS: acute ischemic strokeBBB: blood-brain barrierCBF: cerebral blood flowCBV: cerebral blood volumeCTA: CT angiographyCTP: CT perfusionDWI: diffusion-weighted imagingET: endovascular therapyICM: imaging-clinical mismatchMCA: middle cerebral arteryMERCI: Mechanical Embolus Removal in Cerebral IschemiaMRA: magnetic resonance angiographyMRP: magnetic resonance perfusionmRS: modified Rankin ScaleMTT: mean transit timeNCCT: noncontrasted CTPWI: perfusion-weighted imagingrtPA: recombinant tissue plasminogen activatorsICH: symptomatic intracranial hemorrhageSVIN: Society of Vascular and Interventional NeurologyTHERAPY Trial: Assess the Penumbra System in the Treatment of Acute Stroke trialT-max: time to maximum(C)2012 American Academy of Neurology

Objective: We sought to identify pretreatment neuroimaging markers associated with intracerebral hemorrhage (ICH) after reperfusion therapy for acute ischemic stroke.Methods: A literature review using available online medical literature databases was performed to identify noninvasive imaging markers correlated with ICH after reperfusion therapy. Key words, including different neuroimaging modalities such as noncontrast CT, multimodal CT, and MRI techniques, were queried. The review included randomized, controlled trials, post hoc studies, and institutional registries. Studies of IV as well as intra-arterial reperfusion therapies were considered. Articles were organized on the basis of imaging modality and type of treatment. Each imaging modality was given 1 of 3 grades for consideration of use in clinical practice (grade 1: a modality whose use for hemorrhage prediction is supported by randomized controlled trials or post hoc studies from prospective trials; grade 2: a modality that is largely available but requires further prospective validation; and grade 3: a modality which is rarely used and has limited clinical utility).Results: Grade 1 imaging modalities included the size of infarction as seen on noncontrast CT or diffusion MRI. Higher hemorrhagic risk has been seen with larger infarctions, suggesting that these imaging modalities may be effective screening tests to exclude specific patients. Perfusion imaging using CT or MRI was considered to have a grade 2 recommendation, pending further validation. The use of xenon CT, radionuclide imaging, voxel-based MRI analysis, and blood-brain barrier disruption imaging still require further design improvements (grade 3).Conclusions: Future reperfusion trials require clearly defined protocols for imaging and determination of symptomatic ICH. Future trials may consider the use of perfusion imaging and the inclusion of patients without large territorial infarctions to accurately predict those at risk for ICH with reperfusion therapy.GLOSSARY: ADC: acquired diffusion coefficientASPECTS: Alberta Stroke Program Early CT ScoreBBB: blood-brain barrierCBF: cerebral blood flowCBV: cerebral blood volumeDEFUSE: Diffusion and Perfusion Imaging Evaluation for Understanding Stroke EvolutionECASS: European Cooperative Acute Stroke StudyFLAIR: fluid-attenuated inversion recoveryHARM: hyperintense acute reperfusion markerHI: hemorrhagic infarctionIA: intra-arterialICH: intracerebral hemorrhageMCA: middle cerebral arteryNINDS: National Institute of Neurological Disorders and StrokePH: parenchymal hematomaPROACT: Prolyse in Acute Cerebral ThromboembolismPWI: perfusion-weighted imagingtPA: tissue plasminogen activatorXeCT: xenon-enhanced CT(C)2012 American Academy of Neurology

Background: Recanalization and angiographic reperfusion are key elements to successful endovascular and interventional acute ischemic stroke (AIS) therapy. Intravenous recombinant tissue plasminogen activator (rt-PA), the only established revascularization therapy approved by the US Food & Drug Administration for AIS, may be less effective for large artery occlusion. Thus, there is enthusiasm for endovascular revascularization therapies, which likely provide higher recanalization rates, and trials are ongoing to determine clinical efficacy and compare various methods. It is anticipated that clinical efficacy will be well correlated with revascularization of viable tissue in a timely manner.Method: Reporting, interpretation, and comparison of the various revascularization grading methods require agreement on measurement criteria, reproducibility, ease of use, and correlation with clinical outcome. These parameters were reviewed by performing a Medline literature search from 1965 to 2011. This review critically evaluates current revascularization grading systems.Results and Conclusion: The most commonly used revascularization grading methods in AIS interventional therapy trials are the thrombolysis in cerebral ischemia (TICI, pronounced "tissy") and thrombolysis in myocardial ischemia (TIMI) scores. Until further technical and imaging advances can incorporate real-time reliable perfusion studies in the angio-suite to delineate regional perfusion more accurately, the TICI grading system is the best defined and most widely used scheme. Other grading systems may be used for research and correlation purposes. A new scale that combines primary site occlusion, lesion location, and perfusion should be explored in the future.GLOSSARY: AIS: acute ischemic strokeAOL: arterial occlusive lesionASITN/SIR: American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional RadiologyDSA: digital subtraction angiographyERT: endovascular revascularization therapyMCA: middle cerebral arteryrt-PA: recombinant tissue plasminogen activatorSVIN: Society of Vascular & Interventional NeurologyTIBI: thrombolysis in brain ischemiaTICI: thrombolysis in cerebral ischemiaTIMI: thrombolysis in myocardial ischemia.(C)2012 American Academy of Neurology

: Over the past 50 years, thrombolytic agents have been devised with the aim of recanalizing occluded coronary vessels, and later on, applied in the setting of acute ischemic stroke. Pharmacologic agents have generally targeted the plasminogen-plasmin transformation, facilitating the natural process of fibrinolysis. Newer agents with varying degrees of fibrin selectivity and pharmacologic half-life have influenced both recanalization rates and hemorrhagic complications, inside and outside the CNS. Intra-arterial (IA) administration of fibrinolytic agents increases delivery of the drug to the thrombus at a higher concentration with smaller quantities and therefore lowers systemic exposure. Mechanical thrombus disruption or extraction allows for drug delivery to a greater surface area of the thrombus. Delays associated with IA therapy may worsen the risk/benefit ratio of thrombolysis; therefore, combinations of IA-IV treatments have been studied. To date, there are no direct comparative trials to show that endovascular administration is more efficacious or carries a lower risk of hemorrhagic complications than IV tissue plasminogen activator.GLOSSARY: AIS: acute ischemic strokeDIAS: Desmoteplase in Acute Ischemic Stroke TrialECASS: European Cooperative Acute Stroke StudiesFDA: US Food and Drug AdministrationIA: intra-arterialICH: intracerebral hemorrhageMCA: middle cerebral arteryMMPs: matrix metalloproteinasesMRA: magnetic resonance angiographyNIHSS: NIH Stroke ScaleNINDS: National Institute of Neurological Disorders and StrokePROACT: Prolyse in Acute Cerebral ThromboembolismrtPA: recombinant tissue plasminogen activatorTIMI: thrombolysis in myocardial ischemiatPA: tissue plasminogen activator(C)2012 American Academy of Neurology

Background: Efficacy of IV systemic thrombolysis is limited in patients with severe acute ischemic stroke and large-vessel occlusion. Mechanical thrombectomy has been the mainstay therapy in large-vessel occlusion. This review focuses on the Penumbra aspiration device.Method: Literature review.Results: The Penumbra prospective studies were reviewed and results are presented. The pivotal single-arm prospective trial that led to its approval by the US Food and Drug Administration enrolled 125 patients within 8 hours of symptom onset and demonstrated an 82% recanalization rate, to Thrombolysis in Myocardial Ischemia (TIMI) scores of 2 and 3. The risk of symptomatic intracranial hemorrhage was 10%, and modified Rankin Scale (mRS) score of <=2 was 25%. In the postmarketing registry, 157 vessels were treated, with 87% achieving TIMI 2 and 3 recanalization and 41% having an mRS score of <=2.Conclusion: The Penumbra aspiration system is an effective tool to safely revascularize large-vessel occlusions in patients within 8 hours of onset of acute ischemic stroke who are either refractory to or excluded from IV thrombolytic therapy. Further prospective, randomized controlled trials will be needed to address whether this ability translates into neurologic improvement and better functional outcomes for our patients.GLOSSARY: AIS: acute ischemic strokeBA: basilar arteryFDA: US Food and Drug AdministrationIA: intra-arterialICA: internal carotid arteryICH: intracerebral hemorrhageID: inner diameterIMS: Interventional Management of StrokeMCA: middle cerebral arteryMERCI: Mechanical Embolus Removal in Cerebral IschemiamRS: modified Rankin ScaleNIHSS: NIH Stroke ScalePROACT: Prolyse in Acute Cerebral ThromboembolismPS: Penumbra aspiration systemrtPA: recombinant tissue plasminogen activatorSAH: subarachnoid hemorrhagesICH: symptomatic intracranial hemorrhageTIMI: Thrombolysis in Myocardial Ischemia(C)2012 American Academy of Neurology

: Endovascular therapy for acute ischemic stroke continues to evolve to improve both efficacy and safety. In the late 1990s, intra-arterial chemical thrombolysis with prourokinase was shown to be effective in achieving partial recanalization and improving clinical outcome, in comparison with intra-arterial heparin administration. However, this was at the expense of an increase in the rate of symptomatic intracranial hemorrhage to 10%. To improve the rate of recanalization, expand the time window, and reduce the risk of symptomatic intracranial hemorrhage, mechanical thrombectomy was introduced, with initial approval of the Merci clot retriever, a corkscrew-like device, and then more recently with approval of the Penumbra thromboaspiration system. Both devices are associated with a high rate of recanalization (total, partial, and complete). However, time to recanalization was on average 45 minutes, with a low rate of complete clot resolution, given that the majority of patients achieved only partial recanalization. More recently, retrievable stents have shown promise in reducing the time to recanalization, and they achieve a higher rate of complete clot resolution with improved feasibility. The retrievable stent can be opened within the clot to engage it within the stent struts, and subsequently it is retrieved by pulling it under flow arrest. The retrievable stents provide a new tool in the armamentarium of devices that can be used to achieve safe and timely clot removal. This review provides the historical evolution of endovascular therapy to use of stentreivers.GLOSSARY: AIS: acute ischemic strokeCI: confidence intervalECASS: European Cooperative Acute Stroke StudyFDA: US Food and Drug AdministrationIA: intra-arterialICA: internal carotid arteryICH: intracerebral hemorrhageIMS: Interventional Management of StrokeMCA: middle cerebral arterymRS: modified Rankin ScaleNIHSS: NIH Stroke ScaleNINDS: National Institute of Neurological Disorders and StrokeOR: odds ratioPROACT: Prolyse in Acute Cerebral ThromboembolismRSs: retrievable stentsrtPA: recombinant tissue plasminogen activatorSESs: self-expanding stentsSWIFT: Solitaire FR With the Intention for ThrombectomyTICI: thrombolysis in cerebral ischemiaTIMI: thrombolysis in myocardial infarction(C)2012 American Academy of Neurology

: In patients undergoing endovascular therapy for acute ischemic stroke, antithrombotic therapies are utilized to prevent distal embolization, arterial reocclusion, or catheter-related embolism. However, this must be weighed against the risk of hemorrhagic complications secondary to existing and ongoing ischemia or silent vessel perforation. In this article, we present an overview of the available literature evaluating antithrombotic therapy in patients undergoing endovascular therapy for acute ischemic stroke and discuss the emerging role of these agents.GLOSSARY: ACT: activated clotting timeADP: adenosine diphosphateAIS: acute ischemic strokeCI: confidence intervalGP: glycoproteinIA: intra-arterialIAT: intra-arterial therapyIMS: Interventional Management of StrokeIU: international unitsMCA: middle cerebral arteryMERCI: Mechanical Embolus Removal in Cerebral IschemiaOR: odds ratioPCI: percutaneous coronary interventionPROACT: Prolyse in Acute Cerebral Thromboembolismrpro-UK: recombinant pro-urokinasertPA: recombinant tissue plasminogen activatorsICH: symptomatic intracerebral hemorrhageTIMI: thrombolysis in myocardial ischemiaUK: urokinase(C)2012 American Academy of Neurology