Brain Attack, Web Style
Marjorie Lazoff, MD
Emergency Medicine
Philadelphia, Pennsylvania
Medical Editor
Medical Computing Today

accepted for publication in Medical Computing Today November 1998
(updated) March 1999
Originally published in the November 1998 issue of Medical Software Reviews

The Online Storyline - Acute Stroke Sites

Few changes in medicine occur with the speed or drama that characterize the present revolution in the emergency treatment of brain attacks, or acute ischemic strokes. In just the last three years, the medical community has gone from debating the merits of heparinization vs. supportive care; to assessing the risks vs. benefits of thrombolytic therapy; to calculating the cost-effectiveness of stroke centers and subspecialists for patients suffering all kinds of strokes, from presentation to rehabilitation and beyond.

Attention to this third leading cause of death couldn‚t be timelier. Investigators at the University of Cincinnati Medical Center estimate 731,000 -- a 40% increase in -- acute strokes will occur in the United States annually. These figures are based on our increasing and diverse population that is living longer, the April 22, 1998, JAMA Medical News and Perspective, Rising Stroke Rates Spur Efforts to Identify Risks, Prevent Disease, explains.

For those health care professionals who blinked during the past three years and so missed part or all of the hoopla, the Web is a great place to play catch up. Presented here is just a sampling of relevant sites; it would take several NetViews to cover all the quality online information on acute management, not to mention stroke prevention and screening, rehabilitation, and support services.

Sections The Online Storyline

For most clinicians, the "brain attack" revolution began in late 1995, with the publication in JAMA and NEJM, respectively, of two multicentered clinical trials -- colloquially referred to as the European cooperative study, ECASS1 and the U.S. equivalent supported by the NIH center NINDS2.

Both studied the immediate and short-term outcomes of one thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), specifically Genentech‚s Activase, given within the first few hours of an acute ischemic stroke. Both were heralded as well designed and well executed, adding credibility to their results: treatment with intravenous rt-PA within three hours of onset of ischemic stroke increased the incidence of symptomatic intracerebral hemorrhage, but also suggested improved clinical outcome.

The above link to abstracts only, but the ECASS study is accompanied on line by a JAMA press release, and the NINDS study is discussed in the same issue‚s NEJM editorial. Further, ACP Journal Club summarizes and comments upon this latter study in Tissue plasminogen activator for acute ischemic stroke. Also online are Correspondence and replies to the NINDS study, and a letter pointing out some differences between the NINDS and ECASS studies. The February 1996 issue of Medical Science Bulletin (MSB) includes a readable review of all thrombolytic studies to date in Focus On...Stroke as a Medical Emergency.

Within six months, the FDA approved Activase for use in acute ischemic stroke, and committees within two specialty organizations quickly developed practice guidelines for its use: the 1996 supplement to the 1994 American Heart Association stroke guidelines, and the American Academy of Neurology‚s 1996 Practice Advisory for Thrombolytic Therapy for Acute Ischemic Stroke. A second MSB article, Focus on ... Stroke, published several months later, addressed these and other nonemergency stroke issues. Fans of American Family Physician will want to read Brain Attack: Emergency Treatment of Acute Stroke, a clinical review article published in June 1997. The full-text article describes the ECASS and NINDS studies and provides three concise tables combining AHA and AAN guidelines.

Beginning in early 1997, a flurry of news articles promoted the FDA approved use of rt-PA and new guidelines. The January 15, 1997, issue of JAMA posts the full-text Medical News and Perspective, New Era for Acute Stroke a basic overview of emergency issues involved in using thrombolytic therapy. Six stroke-related news articles from the AMA‚s Jan 29, 1997, Science News Update, emphasize the importance of public health education, and discuss favorable cost-effective analysis and the important role of primary care practitioners. Several months later, Annals of Internal Medicine published Currents: New Approaches to Stroke Require Immediate Action. BMJ noted this aggressive push across the Atlantic in its news item, U.S. doctors urged to treat stroke fast.

A spate of journal articles and commentaries followed, informing health professionals on the pros and cons of this FDA approved and hopeful, but risky and relatively untested, treatment outside acute stroke trials. The October 30, 1997, issue of NEJM includes Clinical Debate a wonderful point-counterpoint written by Louis Caplan, MD, of the New England Medical Center, and James Grotta, MD, from the University of Texas at Houston, generously available online. In December 1996, evidence-based medicine weighed in with its first meta-analysis, Cochrane Review on rt-PA vs control in stoke, presented months later in the ACP Journal Club as Thrombolytic therapy increases the risk for early death and intracranial hemorrhage after acute ischemic stroke. As the title suggests, the Cochrane Review concluded that more evidence is needed for this promising but potentially lethal therapy.

All the while, clinical research on acute stroke management continued to fill the medical journals. No clinical benefit was found using neuroprotective agents (a promising class of heterogeneous antagonists and free radical scavengers), heparin, or low molecular weight heparin. The July 18, 1996, issue of NEJM published another disappointing result of the European MAST-E multi-center trial; MAST studies another thrombolytic agent, streptokinase, and follows a different protocol than either ECASS or NINDS. Consistent with the evidence-based stance cited above, the ACP Journal Club early in 1997 published a summary and an accompanying commentary suggesting the results of all three studies were too disparate to recommend thrombolytic therapy. However, a May 3, 1997, BMJ paper arguing that in non-diabetic patients hyperglycemia is an independent risk factor in acute stroke, adds fuel to the debate on the need to control glucose levels during acute neurological events.

The Lancet's fine Web site allows free access to registered physicians to its two full-text studies on the role of aspirin in acute stroke care. In May 31, 1997, it published the International Stroke Trial study and an accompanying editorial, then the following week published the Chinese Acute Stroke Trial. Both studies suggest early aspirin as the sole treatment in acute stroke resulted in slightly improved mortality and incidence of recurrent stroke. A volley of correspondences helps clarify the issues, although the use of aspirin in management of acute stroke remains controversial.

Non-clinical factors are discussed as well. For example, a March 28, 1998, editorial in BMJ looks at the ethical issues in consenting patients for rt-PA treatment. As other papers and editorials warn, the combination of acutely ill and vulnerable patients, the use of potentially toxic drugs, and very short time frames for decision making and drug administration demand an especially careful evaluation of risk and benefit, the process of consent, and the permissible treatment of control patients.

The April 22, 1998, issue of JAMA reports on the Public Perception of Stroke Warning Signs and Knowledge of Potential Risk Factors. The full text version of this telephone survey study concludes that public health education is needed to increase the public's awareness of the warning signs and risk factors for stroke, particularly those statistically at greatest risk for stroke. A number of other studies and editorials echoed the importance of public education on brain attacks.

From the same issue, Cranial Computed Tomography Interpretation in Acute Stroke found that only 17% of emergency physicians, 40% of neurologists, and 52% of radiologists achieved 100% sensitivity for identification of hemorrhage, a critical step in the selection of candidates for thrombolytic therapy. Overall accuracy was only 77%. See too a third article from the JAMA issue, Further Evolution Toward Effective Therapy for Acute Ischemic Stroke.

Although subsequent clinical trials such as ECASS II fail to provide straightforward answers, emerging from all this work is a growing consensus that the best quality and most cost-effective stroke management -- including judicious use of thrombolytic therapy for acute ischemic stroke -- requires a stroke unit or center staffed with experienced physicians.

Among the many recent review articles is the excellent Stroke Treatment: Time is Brain from the October 24, 1998, issue of The Lancet. This full-text article from Canada is a scholarly yet readable summary of the work done over the past three years, from benign supportive care to aggressive, time-sensitive treatment. "Experimental and clinical data show that there is a variable therapeutic window that may exceed 6-8 h; that stroke units spare lives and reduce disability; and that thrombolysis with recombinant tissue plasminogen activator (rtPA) makes a difference in acute stroke." If I had a stroke..., a review written from a different perspective, appears in the same issue. (For those with limited time and interest, these are the articles to read or download, along with the American Family Physician review article and NEJM‚s Clinical Debate.)

Online resources make it easy to keep updated on new research. WebMedLit searches the abstracts of 23 current journals for "acute stroke." PubMed stroke search field allows users to add terms; try "acute stroke." The Professional section on UK Stroke forum includes a collection of abstracts from major and minor medical journals, with a European slant. Use "acute stroke" to search their updated papers section as well. PSL‚s Doctor‚s Guide to...Stroke Information maintains a collection of general news articles, and links to a variety of sites. Finally, The Cochrane Stroke Group abstracts several dozen of its systematic reviews, many on acute stroke, and more are added quarterly.

Sections Acute Stroke Sites

The Brain Attack Coalition of top government institutions, medical specialty associations, and universities maintains this Acute Stroke Toolbox of clinical resources for the rapid diagnosis and treatment of acute stroke. It‚s a good first stop for a variety of protocols from clinical trials, major universities, and managed care associations, in addition to stroke scales and patient education resources.

Guests of the American Academy of Neurology have access to AAN Stroke Patient Care Tools. In particular, the rt-PA Acute Treatment Guide takes the physician through the history, exam, and lab assessment, to the calculation of rt-PA dose. The remainder of the tool (ordering and monitoring) is under construction. The AAN also allows downloading of a Word document containing its 1996 Practice Advisory for Thrombolytic Therapy for Acute Ischemic Stroke. Scroll down the page for non-AAN links, including patient education resources.

National Institute of Neurological Disorders and Stroke (NINDS) Stroke Information Guide is a typical menu-driven government site with a number of physician and patient references. The Guide includes prevention and patient education resources, some translated into Spanish. In addition to trial centers, symposium and other guidelines, see the Child Neurology Society‚s excellent recognizing and treating strokes in children.

(Along a similar but lighter vein, NeuroscienceNow, a pharmaceutical-sponsored site with an independent physician editorial board, just posted a Q&A on Stroke in the Young.)

The American Heart Association posts its AHA Practice Guidelines for the use of imaging in TIAs and acute stroke, a paper summarizing new and emerging treatments in acute strokes, and its 1996 supplement to the 1994 stroke guidelines.

The StrokeCenter at Washington University is well-maintained by Barnes-Jewish Hospitals‚ stroke management and rehab group. Scroll past the excellent patient educational resources to its professional information such as comparison of various stroke scales, stroke guidelines, procedures, and educational sites for first and second year med students. In particular, visit Clinical Stroke Trials, a great collection of past and ongoing studies, and information on drugs used in acute stroke.

Founded in 1984, the independent not-for-profit National Stroke Association is dedicated to stroke prevention, treatment, rehabilitation, research, and support for stroke survivors and their families. The Professional Resources links via the left-hand frame to resources such as First Few Hours , authored by several leaders in the field, a periodically updated listing of center and ongoing research, and information for health professionals on setting up their own Stroke Center. Also available on line is information about its early response and public education Clinical Trials Acceleration Program.

1 Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European cooperative acute stroke study (ECASS). JAMA 1995;274:1017-1025. Return to article

2 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, Tissue Plasminogen Activator for Acute Ischemic Stroke N Engl J Med1995;333:1581-1587. Return to article

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