LIFELONG LEARNING IN NEUROLOGY® ACUTE ISCHEMIC STROKE Volume 14 Number 6 December 2008 FACULTY STEVEN R. LEVINE, MD, FAAN, FAHA, Chair Professor of Neurology, Mount Sinai School of Medicine, New York, New York *Dr Levine has received personal compensation for activities with AstraZeneca and as an expert in medical legal cases. Dr Levine has received personal compensation in an editorial capacity for Stroke Clinical Updates and MedLink. †Dr Levine discusses the unlabeled use of experimental therapies for stroke. DAVID ADAMOWICZ Research Assistant, Mount Sinai Hospital, New York, New York *†Mr Adamowicz has nothing to disclose. KEVIN M. BARRETT, MD, MSC Senior Associate Consultant, Mayo Clinic, Jacksonville, Florida *†Dr Barrett has nothing to disclose. ANDREW M. DEMCHUK, MD, FRCPC Director, Calgary Stroke Program; Associate Professor, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada *Dr Demchuk has received personal compensation for activities with AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., and sanofi-aventis. Dr Demchuk has received grant support from Novo Nordisk, Inc. †Dr Demchuk discusses the unlabeled use of emerging therapies with numerous references to potential therapies. Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. RISHI GUPTA, MD Staff, Cerebrovascular Center Departments of Neurology and Neurosurgery; Director, Vascular Neurology Fellowship Program, The Cleveland Clinic Foundation, Cleveland, Ohio *Dr Gupta has received personal compensation for activities with Concentric Medical, Inc. †Dr Gupta has nothing to disclose. KAREN C. JOHNSTON, MD, MSC, FAAN Professor and Chair, Department of Neurology, University of Virginia, Charlottesville, Virginia *Dr Johnston has received personal compensation for activities with AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Diffusion Pharmaceuticals LLC, NIH–National Institute of Neurological Disorders and Stroke, Ono Pharmaceutical Co., Ltd, Remedy Pharmaceuticals, and sanofi-aventis. Dr Johnston has received personal compensation in an editorial capacity from Up-to-Date and Neurology. †Dr Johnston discusses the unlabeled use of investigational therapies. TUDOR G. JOVIN, MD Assistant Professor of Neurology and Neurosurgery, Co-director, UPMC Stroke Institute, UPMC Presbyterian Hospital, Center for Neuroendovascular Therapy, Pittsburgh, Pennsylvania *Dr Jovin has received personal compensation for activities with CoAxia and Concentric Medical, Inc. Dr Jovin has received personal compensation as associate editor of Journal of Neuroimaging. †Dr Jovin has nothing to disclose. JUNAID KALIA, MD Clinical Research Fellow, Department of Neurology/Neurosciences, Medical College of Wisconsin, Milwaukee, Wisconsin *†Dr Kalia has nothing to disclose. POOJA KHATRI, MD Assistant Professor, University of Cincinnati, Cincinnati, Ohio *Dr Khatri has nothing to disclose. †Dr Khatri discusses the unlabeled use of the Merci® device and intraarterial recombinant tissue-type plasminogen activator. Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. JOSHUA M. LEVINE, MD Assistant Professor, Co-director, Neurocritical Care Program, Department of Neurology, Neurosurgery, and Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania *†Dr Levine has nothing to disclose. JOHN R. LYNCH, MD, FAHA Assistant Professor of Neurology, Neurosurgery and Internal Medicine, Medical College of Wisconsin, Froedtert Hospital, Milwaukee, Wisconsin *†Dr Lynch has nothing to disclose. LAWRENCE R. WECHSLER, MD, FAAN Professor of Neurology, Director, UPMC Stroke Institute, University of Pittsburgh, Pittsburgh, Pennsylvania *Dr Wechsler has received personal compensation for activities with Abbott Laboratories, Inc., Bristol-Myers Squibb Company, Forest Laboratories, Inc., NMT Medical, Inc., Nuvelo Inc., and sanofi-aventis. Dr Wechsler has received personal compensation in an editorial capacity for Journal of Neuroimaging. Dr Wechsler has received research support from NMT Medical, Inc. †Dr Wechsler has nothing to disclose. OSAMA O. ZAIDAT, MD Director of Vascular and Interventional Program, Medical College of Wisconsin, Milwaukee, Wisconsin *†Dr Zaidat has nothing to disclose. SYED F. Z AIDI, MD Assistant Professor of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania *†Dr Zaidi has nothing to disclose. Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. MULTIPLE-CHOICE QUESTION WRITERS RONNIE BERGEN, MD Assistant Professor of Clinical Neurology, University of Arizona College of Medicine, Southern Arizona VA Hospital, Tucson, Arizona *Dr Bergen has received personal compensation for activities with Biogen Idec. †Dr Bergen has nothing to disclose. EDUARDO E. BENARROCH, MD, FAAN Professor of Neurology, Mayo Clinic, Rochester, Minnesota *Dr Benarroch has received personal compensation from the American Academy of Neurology for his role as a section editor of Neurology. †Dr Benarroch has nothing to disclose. *Relationship Disclosure †Unlabeled Use of Products/Investigational Use Disclosure Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. LIFELONG LEARNING IN NEUROLOGY® ACUTE ISCHEMIC STROKE EDITOR’S PREFACE Stroke has long been part of the “bread and butter” of practicing neurologists. For years, the management of acute ischemic stroke, which accounts for an overwhelming majority of cerebrovascular cases, has been a source of frustra- tion and dismay for patients, families, and physicians alike, as effective treat- ment to reverse a neurologic deficit was lacking. Now, however, despite the availability of thrombolytic therapy that can potentially lead to recovery or at least significant improvement, the exasperation continues as the percentage of patients receiving such treatment languishes in the single digits. The battle- grounds in the struggle to provide better care for the patient with ischemic stroke now include patient education, logistic organization both before and during hospitalization, economic and legal issues, as well as the continuing quest for more effective therapies. A touchstone for the improvement of stroke therapy lies with the education of physicians involved in the treatment of these patients. Indeed, if neurologists wish to retain acute stroke care as part of their “turf,” they must be knowledgeable about current best treatment and make themselves available to provide it. In this issue of , Dr Steven Levine has assembled his own “stroke team,” whose members have worked together throughout this issue to promote your understanding of modern acute ischemic stroke care. A key to more effective stroke management is its prompt recognition. Accurate, as well as rapid, diagnosis is essential. In the first chapter, Drs Kevin Barrett, Joshua Levine, and Karen Johnston review this critical matter, emphasizing not only the importance of distinguishing ischemic from hemorrhagic stroke, but 11 also the exclusion of a variety of conditions that can mimic ischemic stroke. Clearer understanding of the principles of treating stroke is enhanced in the next chapter in which Drs Tudor Jovin, Andrew Demchuk, and Rishi Gupta provide a lucid discussion of the pathophysiology of acute ischemic stroke. Recognition of the importance of the so-called ischemic penumbra should drive home the message that for many stroke patients salvation of critical brain tissues is possible. With these fundamentals under your belt, you will be better equipped to tackle the next three chapters, which address treatment directly, focusing pri- marily on thrombolytic therapy. First, Drs Pooja Khatri, Joshua Levine, and Jovin address “Intravenous Thrombolytic Therapy for Acute Ischemic Stroke,” and then Dr Barrett teams with Drs Khatri and Jovin to examine the very important subject of the prevention and management of the complications of acute ischemic stroke and its treatment. Time is brain has become an appro- priate mantra for the delivery of better acute stroke care, and the earlier chap- ters have emphasized its importance. Yet, no matter what we do, many Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited. ᮣ EDITOR’S PREFACE patients will fail to reach the hospital within the short timeframe currently recommended for administration of IV thrombolytic therapy. In the next chapter, Drs Demchuk, Gupta, and Khatri combine to discuss emerging therapies not only for hyperacute patients, but also for those whose treatment must be delayed beyond 6 hours. Contemporary effective stroke care is complex, and its optimization requires the coopera- tion and efforts of many individuals with different training and skills. Regulatory agencies, including the federal and local governments, have gotten into the act; and reimbursement conditions make it attractive for a hospital to be able to deliver topnotch stroke treatment. In the next chapter, Drs Steven Levine, David Adamowicz, and Johnston address many issues under the rubric of “Primary Stroke Center Certification.” In order for the development of more effective stroke therapy, much clinical research remains to be done. This will best be accomplished through the participation not only of “academic” neurologists, but also of those working in the trenches as “community” neurologists. In the final didactic chapter of this issue, Drs Steven Levine,