State of the Art
Treatment of acute ischemic stroke*,**

https://doi.org/10.1067/mem.2001.111573Get rights and content

Abstract

Acute ischemic stroke is the third leading cause of death in the United States and the leading cause of adult disability. The direct and indirect costs of stroke care exceed $51 billion annually. In 1996, the US Food and Drug Administration approved the first treatment for acute ischemic stroke, intravenous tissue plasminogen activator. Later that year, the National Institute of Neurologic Disorders and Stroke (a branch of the National Institutes of Health) convened a consensus conference on the Rapid Identification and Treatment of Acute Ischemic Stroke, setting goals for stroke care in the United States. Since then, it has become imperative that emergency physicians understand the pathophysiology of stroke, the basis and rationale for treatment, and the therapeutic approaches. This article reviews the state of the art of acute stroke treatment, its foundation, as well as its future. [Lewandowski C, Barsan W. Treatment of acute ischemic stroke. Ann Emerg Med. February 2001;37:202-216.]

Introduction

The US Food and Drug Administration (FDA) approved intravenous tissue plasminogen activator (tPA) as the first treatment for acute ischemic stroke in June 1996. Since then, stroke has been in the forefront of discussion not only because of this new treatment but also because it is a major and growing health problem in the United States.1 Stroke is a medical emergency that requires rapid initial evaluation and management to decrease its impact on patients and on society.2 Other therapies are being developed that may also require rapid emergency department evaluation and treatment.3

The National Institute of Neurologic Disorders and Stroke (NINDS) defines the term “stroke” as a sudden loss of brain function resulting from an interference with the blood supply to the brain. It limits stroke to an acute vascular phenomenon that includes both ischemic strokes and hemorrhagic strokes. Acute ischemic stroke makes up the majority (85%) of the annual 600,000 strokes in the United States, with a mortality rate of 20% to 50%, making it the third leading cause of death. Disability is the major sequela of stroke with 4.4 million survivors, 70% of whom do not return to gainful employment even 7 years after the stroke. Direct and indirect costs for stroke care in the United States exceed $51 billion per year.1

This article reviews the pathophysiology of acute ischemic stroke, its diagnosis, special issues in acute supportive care, acute primary therapy, and future directions.

Section snippets

Pathophysiology of acute ischemic stroke

Acute vascular occlusion is the central event in acute ischemic stroke precipitating the primary injury by limiting the flow of oxygen and glucose to a region of the brain. The occlusion is rarely complete. The residual cerebral blood flow (CBF) depends on the degree of obstruction and the availability of collateral flow. Because the brain does not store energy, it relies on a continuous supply of nutrients to meet its metabolic demands. Ultimately, the amount of injury is proportional to the

Clinical trials

Thrombolysis for acute ischemic stroke is a strategy that dates back to the 1950s. The first modern randomized trials, which involved intravenous streptokinase, failed. The Multicenter Acute Stroke Trial of Europe (MAST-E),11 the Multicenter Acute Stroke of Italy (MAST-I),12 and the Australian Streptokinase Trial (ASK)13 were stopped early because of increased early mortality and high intracerebral hemorrhage (ICH) rates. They used 1.5 million units of streptokinase over 1 hour started within 6

Diagnosis

Acute ischemic stroke occurs at a median age of 65 years, just at the beginning of the retirement years. It is characterized by a sudden onset of focal neurologic deficit, which is generally maximal at the time of onset, but can wax and wane over the initial few hours. Approximately 5% of patients with acute ischemic stroke present with a seizure, and up to 30% have a headache.31 Those at greatest risk often have risk factors similar to those for coronary artery disease, or a history of

Clinical experience

Clinical experience (phase 4 studies or postmarketing surveillance data) in treating acute stroke patients provides insight into the feasibility, safety, and efficacy of applying this therapy to daily practice.

The Standard Treatment with Alteplase to Reverse Stroke (STARS) study is the largest prospective report of consecutively treated patients.72 STARS reported 3.3% of 389 patients had a symptomatic ICH, with 35% having minimal or no disability, and 43% being independent at 30 days. Together

Future challenges

Despite recent advances, most stroke patients do not currently meet treatment inclusion criteria, mainly because of time of presentation. This provides 2 main arenas for future work regarding acute thrombolytic treatment of stroke. One is to find ways to better educate the public about the signs and symptoms of stroke and the need for rapid access to health care using the 911 system. Previous studies have shown that public education can have a dramatic effect on decreasing the time from symptom

References (83)

  • Major ongoing stroke trials

    Stroke

    (2000)
  • TH Jones et al.

    Thresholds of focal ischemia in awake monkeys

    J Neurosurg

    (1981)
  • WA Pulsinelli

    The ischemic penumbra in stroke

    Sci Med

    (1995)
  • AM Hakim

    Ischemic penumbra, the therapeutic window

    Neurology

    (1998)
  • J Astrup et al.

    Thresholds in cerebral ischemia—the ischemic penumbra

    Stroke

    (1981)
  • JA Zivin et al.

    Stroke therapy

    Sci Am

    (1991)
  • TJ. DeGraba

    The role of inflammation after acute stroke, utility of pursuing anti-adhesion molecule therapy

    Neurology

    (1998)
  • The Multicenter Acute Stroke Trail-Europe Study Group

    Thrombolytic therapy with streptokinase in acute ischemic stroke

    N Engl J Med

    (1996)
  • Multicenter Acute Stroke Trail-Italy (MAST-I) Group

    Randomize controlled trial of streptokinase aspirin and combination of both in treatment of acute ischemic stroke

    Lancet

    (1995)
  • GA Donnan et al.

    For the Australian Streptokinase (ASK) Trial Study Group. Streptokinase for acute ischemic stroke with relationship to time of administration

    JAMA

    (1996)
  • W Hacke et al.

    Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European cooperative acute stroke study (ECASS)

    JAMA

    (1995)
  • National Institute of Neurologic Disorders in Stroke rt-PA Stroke Study Group

    Tissue plasmigin activator for acute ischemic stroke

    N Engl J Med

    (1995)
  • WM Clark et al.

    Recombinant tissue plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset, The ATLANTIS Study: a randomized controlled trial

    JAMA

    (1999)
  • DG Shermann et al.

    Intravenous Ancrod for treatment of acute ischemic stroke The STAT Study: a randomized controlled trial

    JAMA

    (2000)
  • International Stroke Trial Collaborative Group

    The international stroke trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke

    Lancet

    (1997)
  • CAST (Chinese Acute Stroke Trial) Collaborative Group

    CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke

    Lancet

    (1997)
  • The NINDS t-PA Study Group

    Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke

    Stroke

    (1997)
  • The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators

    Low molecular weight heparinoid, ORG 10172 (Danaparoid), and outcome after acute ischemic stroke. A Randomized Controlled Trial

    JAMA

    (1998)
  • GJ del Zoppo

    Clinical trials in acute stroke. Why have they not been successful?

    Neurology

    (1998)
  • GJ del Zoppo et al.

    PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke

    Stroke

    (1998)
  • AJ Ferland et al.

    Intra-arterial Prourokinase for acute ischemic stroke. The PROACT II Study: a randomized controlled trial

    JAMA

    (1999)
  • TIMI Study Group

    The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings

    N Engl J Med

    (1985)
  • A Ferbert et al.

    Clinical features of proven basilar occlusion

    Stroke

    (1990)
  • W Hacke et al.

    Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease

    Stroke

    (1988)
  • CA Lewandowski et al.

    Combined intravenous and intra-arterial r-tPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial

    Stroke

    (1999)
  • T Brott et al.

    Measurements of acute cerebral infarction: a clinical examination scale

    Stroke

    (1989)
  • LB Goldstein et al.

    Interrater reliability of the NIH stroke scale

    Arch Neurol

    (1989)
  • HP Adams et al.

    Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the stroke council, American Heart Association

    Stroke

    (1994)
  • A Culbras et al.

    Practice guidelines for the use of imaging and transient ischemic attacks in acute stroke. Report of the Stroke Council, American Heart Association

    Stroke

    (1997)
  • JP Mohr et al.

    Magnetic resonance versus computed tomographic imaging in acute stroke

    Stroke

    (1995)
  • R von Kummer et al.

    Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk

    AJNR Am J Neuroradiol

    (1994)
  • Cited by (41)

    • Analysis of the demographic characteristics and clinical profile of acute ischemic strokes admitted to the emergency centre in the Somalia population

      2022, African Journal of Emergency Medicine
      Citation Excerpt :

      There was no significant difference in mortality rates between rtPA therapy administered ischemic stroke patients and not administered ones, too (10.6% vs 13.6%, P = 0.714). In the literature, it has been reported that 80-85% of stroke cases are ischemic and 15-20% are haemorrhagic [3]. In the INTERSTROKE study, this rate was found to be 78% [10].

    • Temporal sustainability of guideline based door-to-needle times for intravenous thrombolysis for acute ischemic stroke

      2020, Journal of Clinical Neuroscience
      Citation Excerpt :

      Organized changes had to be brought in hospital systems and education of stakeholders regarding the steps involved in IVT helped to reduce the DTN < 60 min worldwide. This involved pre-arrival notification to hospital, development of protocol for patient flow and management, single call activation of the hospital based stakeholders in acute care, emptying the CT gantry, rapid access to the Alteplase in emergency department, and synchronized teamwork development between physician, nurses, pharmacist, technologist of emergency, radiology and neurology departments [2–4]. Yet, there are unique challenges for implementation of the targets times for IVT in each country, each city and even to different hospitals in same city.

    • Imaging the Head and Brain

      2011, Diagnostic Imaging for the Emergency Physician
    View all citing articles on Scopus
    *

    Editor’s Note:This article continues a series of special contributions addressing state-of-the-art techniques, topics, or concepts. State-of-the-art articles will be featured in Annals on a regular basis in the next several volumes.

    **

    Address for reprints: Christopher Lewandowski, MD, Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202;,313-916-1553, fax 313-916-7437;,E-mail [email protected].

    View full text