Table of Contents
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Abstract
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Case Presentations
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Introduction
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Abbreviations
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Review Of The Literature
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Pathophysiology
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Section I: The Expanding Window Of Opportunity In Acute Stroke: The Extended Window For Intravenous rt-PA Use
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Extending The Time Window
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Early Thrombolytic Studies: ECASS I, ECASS II, ATLANTIS
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Later Thrombolytic Studies: ECASS III, SITS-MOST, IST-3
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Summary: The Extended Window For Intravenous rt-PA Use
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Section II: The Use Of Multimodal Computed Tomography In Acute Stroke Imaging
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Description And Potential Clinical Implications Of Multimodal Computed Tomographic Imaging
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Evolving Imaging Strategies: A New Acute Stroke Treatment Paradigm?
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Potential Limitations To Multimodal Neuroimaging
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Summary: Multimodal Computed Tomography In Acute Stroke Imaging
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Section III: Endovascular Therapies For Acute Ischemic Stroke
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Intra-Arterial Thrombolysis
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Mechanical Thrombectomy
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Angioplasty And Cervico-Cerebral Stenting
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Summary: The Future Of Stroke Revascularization Therapy
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Section IV: Stroke Systems Of Care
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Background And Significance
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Primary Stroke Centers
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Comprehensive Stroke Centers
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Stroke Systems Of Care
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Evidence-Based Outcome Measures
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Summary: Stroke Systems Of Care
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Conclusion
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Risk Management Pitfalls For Acute Ischemic Stroke
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Case Conclusion
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Clinical Pathway For Management Of Acute Ischemic Stroke In The Emergency Department
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Tables and Figures
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Table 1. Trials Of Extended Windows For Intravenous rt-PA
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Table 2. Major Elements Of A Primary Stroke Center
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Table 3. Proposed Components Of A Comprehensive Stroke Center
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Table 4. Final Certification Eligibility Criteria For Comprehensive Stroke Centers
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Figure 1. Middle Cerebral Artery Occlusion On CT Angiogram
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Figure 2. Cerebral Blood Flow On CT Perfusion Study
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Figure 3. Cerebral Blood Volume On CT Perfusion Study
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Figure 4. Mean Transit Time On CT Perfusion Study
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Figure 5. Perfusion Mapping On CT Perfusion Study
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Figure 6. Merci Clot Retriever Deployment
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Figure 7. Middle Cerebral Artery Occlusion On Cerebral Angiogram
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Figure 8. Restoration Of Middle Cerebral Artery Flow On Cerebral Angiogram
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Figure 9. Before And After Images Of Penumbra System Intervention On Cerebral Anglogram
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References
Abstract
Stroke is the leading cause of long-term disability in the United States and is the fourth leading cause of death, affecting nearly 800,000 patients each year. The physical, emotional, and financial toll stroke inflicts on patients and their families cannot be overstated. At the forefront of acute stroke care, emergency clinicians are positioned to have a major impact on the quality of care that stroke patients receive. This issue outlines and reviews the literature on 4 evolving strategies reflecting developing advancements in the care of acute ischemic stroke and their potential to impact patients in the emergency department setting: (1) the expanding window for intravenous rt-PA, (2) the use of multimodal computed tomographic scanning in emergent diagnostic imaging, (3) endovascular therapies for stroke, and (4) stroke systems of care. Whether practicing in a tertiary care environment or in a remote emergency department, emergency clinicians will benefit from familiarizing themselves with these advancements and should consider how these new approaches might influence their management of patients with acute ischemic stroke.
Case Presentations
A 64-year-old male presents to the ED with the acute onset of profound right-sided motor weakness and expressive aphasia. The patient has no headache, no history of trauma, and no other problems upon presentation. His only chronic medical problem is hypertension that is well controlled on his medications. His wife witnessed the onset of his symptoms while they were eating dinner 3.5 hours prior to arrival. He has normal vital signs, and a stat CT scan of the head is normal as are his laboratory studies. His deficits have persisted throughout his expedited workup and he is now 4 hours into an acute ischemic stroke (an hour beyond the FDA-approved treatment window for intravenous rt-PA), with a calculated NIHSS score of 16. What emergent treatment options, if any, do you have for this patient?
A 56-year-old male presents to the ED with a dense right-sided hemiparesis along with global aphasia and a leftward gaze deviation. He appears anxious, but otherwise he is in no acute distress and has normal vital signs. He was last seen normal approximately 9 hours ago, as he and his wife were going to bed. Upon awakening in the morning, he exhibited symptoms and was rushed to your hospital. His significant neurologic deficits persist, and his head CT shows only a hyperdense MCA sign on the left. What further diagnostic and therapeutic measures can be utilized to manage this patient’s severe ischemic stroke?
A 72-year-old female presents to your ED with a severe left-sided hemiparesis, rightward gaze deviation, and hemineglect. She is a highly functioning lady and very active in her community. She had originally presented to an outside clinic and was then transferred to your ED. Her witnessed onset of symptoms occurred 6.5 hours prior to arrival, and her workup is negative other than a slight loss of grey-white differentiation in her right middle cerebral artery distribution on noncontrasted head CT. What therapeutic options might you employ to best emergently manage this woman’s condition?
Introduction
Stroke is the fourth leading cause of death in the United States and the leading cause of long-term disability in adults.1 Every year in the United States, approximately 795,000 individuals experience a new or a recurrent stroke.2 Of these episodes, 77% (610,000) are initial attacks; 23% (185,000) are recurrent attacks. The risk of stroke is higher in men than in women, in blacks than in whites, and in older than in younger individuals. Stroke imparts a tremendous medical, emotional, and fiscal burden to society; annual costs for stroke care in the United States alone exceed $73 billion.1 Clearly, improvements in early stroke care may reduce not only the morbidity and mortality of this devastating disease but also the significant financial cost.
Strokes may be classified as ischemic (87%), hemorrhagic (10%), or subarachnoid hemorrhage (3%). The distinction between these stroke subtypes is paramount, given the distinctly different diagnostic imaging modalities, treatment paradigms, and preventative measures used in their management. The important role played by emergency clinicians in the care of acute ischemic stroke cannot be overemphasized. Because they are always on the front lines of acute illness, emergency clinicians serve a critical role in the appropriate triage, workup, management, and disposition of acute stroke patients. Without the expertise and skill of emergency medicine providers, patients affected by stroke have little hope of receiving an expedited workup, much less the rapid and appropriate treatment decision that offers their best hope for neurological recovery.
Recent years have seen an explosion of advancements in the care of acute ischemic stroke patients. This article reviews 4 of the major evolving key elements that are changing the emergent management of acute ischemic stroke and are forming the basis of emergent stroke care for the future. Sections include:
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Section I: The Expanding Window Of Opportunity In Acute Stroke: The Extended Window For Intravenous rt-PA Use
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Section II: The Use Of Multimodal Computed Tomography In Acute Stroke Imaging
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Section IV: Stroke Systems Of Care
Whether practicing in a major tertiary care center or in a remote emergency department (ED) setting, emergency clinicians must be familiar with advances in stroke care and how to best apply these advances to their practice setting.
There continue to be many controversies related to acute stroke care, and the authors recognize that there is significant regional and local variation in practice. Many considerations must be taken into account when tailoring a management strategy for the individual patient. The authors recommend that every hospital proactively develop protocols that address likely scenarios and thus maximize the delivery of care and minimize liability.
Risk Management Pitfalls For Acute Ischemic Stroke
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“I realized that the patient met criteria for thrombolytics, but I was afraid she would have a hemorrhage if I gave thrombolytics, and I would get sued.”
There are far more lawsuits filed against emergency physicians for failure to administer thrombolytic therapy than for complications of the treatment. Adherence to a well-developed acute stroke protocol agreed upon by local practice is the best defense in any malpractice scenario.
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“I didn’t realize the patient was anticoagulated before I gave thrombolytic therapy.”
A thorough review of the patient’s medication and allergy list is always indicated prior to the administration of any drug. If a patient is on warfarin, the patient’s INR must be known before thrombolytics are administered. If the patient is on warfarin and is beyond the 3-hour treatment window, IV thrombolytics are contraindicated, per ECASS III guidelines.
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“I gave the patient thrombolytics for the stroke, but the patient had a massive gastrointestinal hemorrhage. I didn’t realize he had a significant gastrointestinal bleed a week ago.”
A thorough review of the indications and contraindications of thrombolytic therapy is always indicated prior to the initiation of treatment. Careful attention to the contraindications for therapy will help the practitioner avoid pitfalls.
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“I didn’t see the hemorrhage on the CT scan.”
Rapid interpretation of the noncontrasted head CT for hemorrhage is essential to successful thrombolytic therapy. The expertise to identify acute hemorrhage is paramount when interpreting this study prior to the administration of thrombolytic therapy. If one is uncomfortable making this determination, rapid access to adequate radiologic expertise must be a part of any acute stroke treatment protocol.
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“We didn’t realize the patient was having a stroke until it was too late. The symptoms were mild, and the patient was in our waiting room for 3 hours before he was brought back.”
In the era of significant ED overcrowding, accurate and timely triage is paramount. Easy-to-follow information on the signs and symptoms of stroke should be made available to all triage personnel, with an understanding to immediately bring any patient meeting suspicion for acute stroke to the attention of the attending ED physician.
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“I really thought it was conversion disorder.”
A robust knowledge of the signs and symptoms of stroke as well as insight into more unusual presentations for stroke, coupled with a thorough and expert neurological examination, are critical in avoiding the misdiagnosis of an acute stroke as a manifestation of psychiatric illness. Beware of cognitive biases, and make sure that all patients with any alterations in baseline function receive very careful consideration.
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“It seemed like benign positional vertigo to me.”
Vertigo can be very difficult to differentiate in its etiology. When in doubt, consider posterior circulation ischemia as an etiology, especially when additional symptoms (double vision, coordination problems, difficulty walking, etc.) are present.
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“The patient came into the ED 5 hours into his acute stroke. It was too late to do anything.”
Be aware of surrounding resources in acute stroke care. If you do not practice in a center that offers endovascular therapies that can be deployed long after IV thrombolytic windows close, know whether or not surrounding facilities offer such therapies. Some lawsuits arise because of a failure to consider transferring a patient to a higher level of care when the patient remains within endovascular therapeutic windows but does not receive an opportunity for treatment.
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“Everything was going fine, but it took too long to get the CT done.”
Time targets for the completion of emergent studies are well-established. Delays in the acquisition of emergent studies are commonly cited as deviations in the standard of care by plaintiffs. Well-designed acute stroke protocols — in place and rehearsed prior to patient arrival — serve to streamline the care of stroke patients, optimizing care and minimizing delays.
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“I can’t believe she had a stroke. The neck pain seemed musculoskeletal.”
Remember that cerebrocervical arterial dissections may occur following blunt trauma to the neck as well as spontaneously. Know the risk factors for carotid and vertebral artery dissections and consider the diagnosis in any case of headache, neck pain, or vertigo or with any neurologic symptoms, especially following trauma to the head or neck or in any other risk-associated scenario.
Tables and Figures
References
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, are noted by an asterisk (*) next to the number of the reference.
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Lloyd-Jones D, Adams RJ, Brown TM, et al. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121(7):948. (Statistical update)
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Broderick J, Brott T, Kothari R, et al. The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks. Stroke. 1998;29(2):415-421. (Retrospective; 1000 patients)
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Thurman RJ, Jauch EC. Acute ischemic stroke: emergent evaluation and management. Emerg Med Clin N America. 2002;20(3):609-630. (Review)
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* NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM. 1995;333:1581-1587. (Prospective randomized placebo controlled phase III trial, 624 patients)
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Schwamm LH, Fonarow GC, Reeves MJ, et al. Get With the Guidelines-Stroke is associated with sustained improvement in care for patients hospitalized with acute stroke or transient ischemic attack. Circulation. 2009;119(1):107-115. (Prospective; 323,000 patients)
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Lellis JC, Brice JH, Evenson KR, et al. Launching online education for 911 telecommunicators and EMS personnel: experiences from the North Carolina Rapid Response to Stroke Project. Prehosp Emerg Care. 2007;11(3):298-306. (Prospective educational intervention)
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The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;23.
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Heiss WD. The ischemic penumbra: correlates in imaging and implications for treatment of ischemic stroke. The Johann Jacob Wepfer award 2011. Cerebrovasc Dis. 2011;32(4):307-320. (Lecture)
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Strbian D, Meretoja A, Ahlhelm FJ, et al. Predicting outcome of IV thrombolysis-treated ischemic stroke patients: the DRAGON score. Neurology. 2012;78(6):427-432. (Retrospective eview for prognosis prediction)
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Demchuk AM, Tanne D, Hill MD, et al. Predictors of good outcome after intravenous tPA for acute ischemic stroke. Neurology. 2001;57(3):474-480. (Retrospective review for prognosis prediction)
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Appelros P, Nydevik I, Viitanen M. Poor outcome after first-ever stroke: predictors for death, dependency, and recurrent stroke within the first year. Stroke. 2003;34(1):122-126. (Retrospective review for prognosis prediction)
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Bruno A, Levine SR, Frankel MR, et al. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology. 2002;59(5):669-674.
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Ford GA, Ahmed N, Azevedo E, et al. Intravenous alteplase for stroke in those older than 80 years old. Stroke. 2010;41(11):2568-2574.
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Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008;372(9646):1303-1309. (Observational registry; 664 patients)
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Larrue V, von Kummer R, del Zoppo G, et al. Hemorrhagic transformation in acute ischemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study. Stroke. 1997;28(5):957-960. (Retrospective reanalysis; 620 patients)
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Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004;363(9411):768-774. (Meta-analysis; 2775 patients)
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Larrue V, von Kummer RR, Muller A, et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke. 2001;32(2):438-441. (Retrospective reanalysis; 800 patients)
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Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274(13):1017-1025. (Prospective randomized placebo controlled phase III trial; 620 patients)
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Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998;352(9136):1245-1251. (Prospective randomized placebo controlled phase III trial; 800 patients)
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Clark WM, Wissman S, Albers GW, et al. Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA. 1999;282(21):2019-2026. (Prospective randomized placebo-controlled phase III trial; 613 patients)
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Ringleb PA, Schellinger PD, Schranz C, et al. Thrombolytic therapy within 3 to 6 hours after onset of ischemic stroke: useful or harmful? Stroke. 2002;33(5):1437-1441. (Retrospective review for prognosis prediction)
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Kent DM, Ruthazer R, Selker HP. Are some patients likely to benefit from recombinant tissue-type plasminogen activator for acute ischemic stroke even beyond 3 hours from symptom onset? Stroke. 2003;34(2):464-467. (Retrospective review for prognosis prediction)
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Kent DM, Selker HP, Ruthazer R, et al. The stroke--thrombolytic predictive instrument: a predictive instrument for intravenous thrombolysis in acute ischemic stroke. Stroke. 2006;37(12):2957-2962. (Retrospective review for prognosis prediction)
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* Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. (Prospective randomized placebo-controlled phase III trial; 821 patients)
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* del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke. 2009. 40(8):2945-2948. (Guideline)
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Lansberg MG, Bluhmki E, Thijs VN. Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a meta-analysis. Stroke. 2009;40(7):2438-2441. (Meta-analysis)
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The IST-3 Collaborative Group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;23:23. (Randomized controlled trial; 3035 patients)
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* Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. May 23, 2012. (Epub ahead of print) (Meta-analysis; 7012 patients)
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Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587. (Prospective randomized double-blind placebo- controlled clinical trial; 624 patients)
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* Adams HP, Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38(5):1655-1711. (Consensus statement; guidelines)
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Tomura N, Uemura K, Inugami A, et al. Early CT finding in cerebral infarction: obscuration of the lentiform nucleus. Radiology. 1988;168(2):463-467. (Retrospective; 25 patients)
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Patel SC, Levine SR, Tilley BC, et al. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke. JAMA. 2001;286(22):2830-2838.
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* Ledezma CJ, Wintermark M. Multimodal CT in stroke imaging: new concepts. Radiol Clin North Am. 2009;47(1):109-116. (Review)
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Mukherjee S, Raghavan P, Phillips CD. Computed tomography perfusion: acute stroke and beyond. Semin Roentgenol. 2010;45(2):116-125. (Review)
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* Gonzalez RG. Imaging-guided acute ischemic stroke therapy: from “time is brain” to “physiology is brain.” AJNR Am J Neuroradiol. 2006;27(4):728-735. (Review)
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Hacke W, Furlan AJ, Al-Rawi Y, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurology. 2009;8(2):141-150. (Randomized controlled trial; 193 patients)
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* Konstas AA, Wintermark M, Lev MH. CT perfusion imaging in acute stroke. Neuroimaging Clin N Am. 2011;21(2):215-238. (Review)
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* Wintermark M, Flanders AE, Velthuis B, et al. Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke. Stroke. 2006;37(4):979 -985. (Prospective multicenter trial; 130 patients)
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Schaefer PW, Roccatagliata L, Ledezma C, et al. First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy. AJNR Am J Neuroradiol. 2006;27 (1):20-25. (Prospective; 14 patients)
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Lima FO, Lev MH, Levy RA, et al. Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy. AJNR Am J Neuroradiol. 2010;31(5):817-821. (Retrospective; 575 patients)
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Bettmann MA. Frequently asked questions: iodinated contrast agents. Radiographics. 2004;24 Suppl 1:s3-s10. (Review)
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Barber PA, Zhang J, Demchuk AM, et al. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology. 2001;56(8):1015-1020. (Prospective; 2165 patients)
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Alexandrov AV, Grotta JC. Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology. 2002;59(6):862-867. (Prospective; 60 patients)
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Janjua N, Alkawi A, Suri MF, et al. Impact of arterial reocclusion and distal fragmentation during thrombolysis among patients with acute ischemic stroke. AJNR Am J Neuroradiol. 2008;29(2):253-558. (Retrospective; 100 patients)
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Saqqur M, Molina CA, Salam A, et al. Clinical deterioration after intravenous recombinant tissue plasminogen activator treatment: a multicenter transcranial Doppler study. Stroke. 2007;38(1):69-74. (Prospective; 374 patients)
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Wolpert SM, Bruckmann H, Greenlee R, et al. Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group. AJNR Am J Neuroradiol. 1993;14(1):3- 13. (Prospective; 93 patients)
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Arnold M, Nedeltchev K, Mattle HPet al. Intra-arterial thrombolysis in 24 consecutive patients with internal carotid artery T occlusions. J Neurol Neurosurg Psychiatry. 2003;74(6):739-742. (Prospective; 24 patients)
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Jansen O, von Kummer R, Forsting M, et al. Thrombolytic therapy in acute occlusion of the intracranial internal carotid artery bifurcation. AJNR Am J Neuroradiol. 1995;16(10):1977-1986. (Prospective; 32 patients)
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Sorimachi T, Fujii Y, Tsuchiya N, et al. Recanalization by mechanical embolus disruption during intra-arterial thrombolysis in the carotid territory. AJNR Am J Neuroradiol. 2004;25(8):1391-1402. (Prospective; 23 patients)
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Zaidat OO, Suarez JI, Santillan C, et al. Response to intra-arterial and combined intravenous and intra-arterial thrombolytic therapy in patients with distal internal carotid artery occlusion. Stroke. 2002;33(7):1821-1826. (Retrospective; 18 patients)
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* Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke. 2007;38(3):967-973. (Meta-analysis; 2066 patients)
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del Zoppo GJ, Higashida RT, Furlan AJ, et al. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in acute cerebral thromboembolism. Stroke. 1998;29(1):4-11. (Randomized controlled trial; 46 patients)
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* Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA. 1999;282(21):2003-2011. (Randomized controlled trial; 180 patients)
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Smith WS, Sung G, Starkman S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005;36(7):1432-1438. (Prospective; 151 patients)
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Gobin YP, Starkman S, Duckwiler GR, et al. MERCI 1: a phase 1 study of mechanical embolus removal in cerebral ischemia. Stroke. 2004;35(12):2848-2854. (Prospective; 30 patients)
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Smith WS, Sung G, Saver J, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi-MERCI trial. Stroke. 2008;39(4):1205-1212. (Prospective; 164 patients)
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