Thrombolytic Therapy for Acute Stroke

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Front Matter

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Background and Basic Investigations > 1-1

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Mechanisms of Thrombolysis

Gregory J. Zoppo, Naohisa Hosomi

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Background and Basic Investigations > 3-27

The pharmacological use of plasminogen activators is associated with symptomatic improvement in patients with coronary artery thrombosis, peripheral arterial occlusions, and thrombosis of the venous system. Based on prospective angiographic studies and planned programs (1–5), thrombolysis is the only approved treatment of acute ischemic stroke (6–8) under limited circumstances. Currently, recombinant...

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Pathology of Cervico-Cranial Artery Occlusion

Louis R. Caplan

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Background and Basic Investigations > 29-42

Brain ischemia is caused by a heterogeneous array of different vascular disorders. The general categories of vascular disorders most often used are embolism, “thrombosis” (referring to a local in situ process that narrows and often occludes an artery or vein), and systemic hypoperfusion. Systemic disorders that lead to brain ischemia include cardiac disorders (cardiac arrest, arrythmias, low cardiac...

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The Ischemic Penumbra and Neuronal Salvage

Patrick Lyden

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Background and Basic Investigations > 43-62

The majority of focal cerebral ischemic events result from arterial occlusion caused by embolism or in situ thrombosis. This interruption in blood flow, if severe and prolonged, leads to cerebral infarction. Brain infarction results from a disruption in blood flow, which causes a reduction in oxygen and glucose supplied to the tissue. Glucose and oxygen deprivation causes a metabolic shift toward...

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Front Matter

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 63-63

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Preclinical Testing of Thrombolytic Therapy for Acute Ischemic Stroke

Steven R. Levine

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 65-76

Prior to definitive human trials, considerable effort was expended in the laboratory perfecting thrombolytic therapy. The essential literature that provided the experimental impetus for proceeding to human trials is summarized in this chapter. From this experience, two important lessons emerged. First, thorough exploration of drug risks and benefits should be performed in relevant animal models prior...

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Combination of Thrombolytic Therapy With Neuroprotectants

James C. Grotta, Lise A. Labiche

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 77-93

Thrombolysis is the first scientifically established treatment for acute ischemic stroke, but we now need to build on that success. One possible way this might be accomplished is by combining thrombolysis with neuroprotection (see Chapter 3 ). Such combination therapy might reduce complications of thrombolysis, especially hemorrhage, by protecting damaged endothelium or reducing the volume of tissue...

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Pilot and Preliminary Studies of Thrombolytic Therapy for Stroke

Steven R. Levine, E. Clarke Haley, Patrick Lyden

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 95-110

The demonstration that tissue plasminogen activator (t-PA) is clinically effective for acute ischemic stroke was based on many important studies over the past two decades that then led to groundbreaking preliminary clinical trials. This chapter highlights and discusses these studies and their historical significance. Thrombolytic therapy is an inherently attractive treatment for ischemic stroke based...

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Intravenous Thrombolytic Therapy for Acute Ischemic Stroke

Matthew L. Flaherty, Edward C. Jauch, Rashmi U. Kothari, Joseph P. Broderick

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 111-127

Prior to the availability of computed tomography (CT) imaging, seven case series had reported the use of various thrombolytic agents for 249 patients with ischemic strokes(1–7). Mortality ranged from 20 to 50% and intracranial hemorrhage (ICH) rates from 11 to 35% in these studies (see Chapter 6 ). These discouraging results reflected the fact that patients were treated days to weeks after symptom...

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Further Analysis of NINDS Study

Susan C. Fagan, Thomas Kwiatkowski, Patrick D. Lyden

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 129-147

Following the initial publication of the National Institute of Neurological Disorders and Stroke (NINDS) tissue-plasminogen activator (t-PA) Stroke Trial results, the NINDS investigators published a series of additional data and analyses. These analyses were necessary because not all the relevant data could be included in the primary report, and to answer criticisms of the original article. Some of...

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Community Experience With Intravenous Thrombolysis for Acute Stroke

Lama Al-Khoury, Christy M. Jackson

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 149-158

The US Food and Drug Administration (FDA) approved intravenous tissue plasminogen activator (t-PA) as treatment for acute ischemic stroke in June 1996, based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) study (see Chapter 7 ). The next important question was whether t-PA treatment could be applied in nonstudy community medical centers with a feasibility,...

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Intra-Arterial Thrombolysis in Acute Ischemic Stroke

Anthony J. Furlan, Randall Higashida, Irene Katzan, Alex Abou-Chebl, more

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 159-184

Intra-arterial (IA) thrombolysis provides an alternative to intravenous (iv) thrombolysis in selected patients with acute ischemic stroke. Recent advances in the field of neuro-interventional radiology, with the development of extremely soft, compliant microcatheters and steerable microguidewires, along with high-resolution fluoroscopy and digital imaging, and nonionic contrast agents, have made it...

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Combinations of Intravenous and Intra-Arterial Thrombolysis

Matthew L. Flaherty, Joseph Broderick

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Scientific Rationale and Clinical Trials > 185-200

The purpose of this chapter is to introduce physicians to the concept of a combined intravenous/intra-arterial (IA) approach to vascular recanalization. Current experience is limited but the concept is attractive and worthy of further study. To understand the potential advantages of a combined approach, it is helpful to first examine the known advantages and limitations of intravenous and IA delivery...

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Front Matter

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 201-201

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Thrombolysis in Vertebrobasilar Occlusive Disease

Louis R. Caplan

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 203-209

Most experience with thrombolysis involves patients with cerebral hemisphere ischemia related to thromboembolic disease within the anterior (carotid arterial) territory (see Chapters 2 and 7 ). Although less experience has been gained in patients with posterior circulation (vertebrobasilar [VB] arterial) thromboembolism, most such data has concerned patients whose arterial lesions were documented...

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Thrombolytic Therapy in Stroke Patients

Patrick D. Lyden

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 211-221

The use of tissue plasminogen activators (t-PA) for acute stroke was proven safe and effective in the National Institutes of Neurologic Disorders and Stroke (NINDS) study of t-PA for acute stroke, published in 1995 (1). The therapy was approved by the US Food and Drug Administration (FDA) in 1996, and endorsed by the American Heart Association, American Academy of Neurology, and National Stroke Association...

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Stroke Thrombolysis

Louis R. Caplan

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 223-234

Although 8 yr have passed since the Food and Drug Administration (FDA) released tissue plasminogen activator (t-PA) for use in the United States to treat patients with acute ischemic stroke, thrombolysis is still very controversial. Clearly, thrombolysis is a step forward but there remain problems with its use, and with the guidelines and policies that direct its application.

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How to Run a Code Stroke

Askiel Bruno

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 235-247

The demonstration that early thrombolytic therapy for acute cerebral infarction improves outcomes and the Food and Drug Administration (FDA) approval of intravenous recombinant tissue plasminogen activator (rt-PA) for acute cerebral infarction (see Chapter 7 ) stimulated establishment of rapid response stroke teams and certified stroke centers in the United States. The positive results from thrombolytic...

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The Impact of Computed Tomography on Acute Stroke Treatment

Rüdiger Kummer

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 249-278

Computed tomography (CT) was the first modality to image the brain and its pathology in vivo. Before the invention of CT in the early 1970s, brain diseases were categorized according to their clinical phenotype. The term “stroke” originates from these old days of medicine, when brain hemorrhages could not be differentiated from ischemic brain diseases. It is unfortunate that we still use the term...

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Using Magnetic Resonance Imaging to Select and Manage Patients for Treatment

Peter D. Schellinger, Chelsea S. Kidwell, Steven Warach

Current Clinical Neurology > Thrombolytic Therapy for Acute Stroke > Using Thombolysis for Acute Stroke > 279-297

Thrombolysis is the treatment of choice for eligible acute stroke within 3 h after symptom onset. However, in the United States, only 2–5% of acute stroke patients receive this therapy, and among those patients who are treated there remains a risk of developing a symptomatic intracerebral hemorrhage (ICH) (1–3). Moreover, no treatment beyond 3 h has been approved by regulatory agencies. Thus, there...

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Thrombolytic Therapy for Acute Stroke

Front Matter

Mechanisms of Thrombolysis

Pathology of Cervico-Cranial Artery Occlusion

The Ischemic Penumbra and Neuronal Salvage

Front Matter

Preclinical Testing of Thrombolytic Therapy for Acute Ischemic Stroke

Combination of Thrombolytic Therapy With Neuroprotectants

Pilot and Preliminary Studies of Thrombolytic Therapy for Stroke

Intravenous Thrombolytic Therapy for Acute Ischemic Stroke

Further Analysis of NINDS Study

Community Experience With Intravenous Thrombolysis for Acute Stroke

Intra-Arterial Thrombolysis in Acute Ischemic Stroke

Combinations of Intravenous and Intra-Arterial Thrombolysis

Front Matter

Thrombolysis in Vertebrobasilar Occlusive Disease

Thrombolytic Therapy in Stroke Patients

Stroke Thrombolysis

How to Run a Code Stroke

The Impact of Computed Tomography on Acute Stroke Treatment

Using Magnetic Resonance Imaging to Select and Manage Patients for Treatment

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Thrombolytic Therapy for Acute Stroke