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For the Clinician

Stroke: Rapid Diagnosis, New Treatments

by Alison E. Baird, M.D., Ph.D.

Geriatric Times March/April 2001 Vol. II Issue 2

Over the past decade, there have been significant advances in the diagnosis and treatment of acute stroke. Stroke, or "brain attack," is now recognized as a medical emergency, and patients need to reach the hospital as early as possible after the onset of symptoms to receive optimal treatment.

Stroke occurs when a region of the brain is deprived of its blood supply, either through blockage of an artery-"ischemic stroke" (80%)-or by rupture of a blood vessel into or around the brain-"hemorrhagic stroke" (20%). The first acute ischemic stroke therapy-recombinant tissue plasminogen activator (rt-PA)-became available five years ago, but treatment must commence within three hours of stroke onset. Yet rt-PA is still not reaching many of those who need it most. Better awareness of the symptoms of stroke and the need to seek urgent medical attention are required at all levels of the medical and wider community.

Stroke is the third leading cause of death and disability in the United States. The incidence of stroke rises exponentially with age, and with the expected aging of the population, the burden of stroke is likely to become even greater. There are approximately 731,000 new and recurrent strokes in the United States per year (Broderick et al., 1998). In the United States, stroke kills 16% of women and 8% of men. Stroke is the leading cause of adult disability and is complicated by high rates of depression and dementia. It is estimated that there are more than 500,000 stroke survivors in the United States. The resulting cost to communities is in excess of $40 billion per year.

Scientific Advances

Prior to the 1970s, it was believed that brain tissue deprived of its blood supply could survive for approximately eight minutes. Research showed, however, that not all of the brain tissue involved in an ischemic stroke is irreparably damaged. Symon et al. (1974) demonstrated that some tissue on the outer borders of the brain lesion may be viable for up to three hours after stroke onset. Later, in the 1990s, improved radiological techniques, particularly magnetic resonance imaging (MRI), allowed the damaged brain tissue to be visualized and measured. Researchers found that in many cases of ischemic stroke, the lesion in the brain consisted of a core, which may survive for one hour or less, and a penumbra-tissue that can potentially be salvaged if the blood flow can be restored in time-which can survive for three hours or even longer.

These scientific advances provided the stimulus for many new trials of stroke treatments. The first therapy approved by the U.S. Food and Drug Administration for stroke was rt-PA, a clot-buster therapy for opening up blocked brain arteries. With rt-PA, the earlier the treatment commences, the better the likelihood of a favorable outcome (Marler et al., 2000) (Figure). In a 1995 study, researchers found that patients treated with rt-PA within three hours of ischemic stroke onset were 30% more likely to have a good outcome than untreated patients (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, 1995). Half the patients in this study were treated within 90 minutes of onset.

Rt-PA carries risks. It is not suitable for hemorrhagic strokes that are detected on an urgent computed tomography (CT) scan when the patient first reaches the hospital. It is contraindicated for patients on warfarin (Coumadin) therapy or who have had a recent stroke and/or recent major surgery. The risk of bleeding into the brain following rt-PA therapy is around 6%, and the risk rises if treatment is given later than three hours following stroke onset or is not administered according to protocol (Albers et al., 2000; Buchan et al., 2000; Katzan et al., 2000).

Understanding stroke risk factors such as hypertension, smoking, diabetes and heart disease has become of paramount importance. Attention to these risk factors can significantly lower an individual's risk of having a stroke. Research into the effects of other potential stroke risk factors, including estrogens and over-the-counter medications, is underway. After stroke, there is a significant risk of recurrent stroke, with rates of up to 10% in the first 12 months. Aspirin, coumadin and carotid endarterectomy have been traditionally used for secondary stroke prevention. New treatments include the combination of aspirin and dipyridamole (Aggrenox, Persantine), clopidogrel (Plavix) and ticlopidine (Ticlid).

Managing patients in designated stroke units analogous to coronary care units saves lives and improves the likelihood of a return to functional independence (Alberts et al., 2000; Langhorne et al., 1993). These units are staffed by specialist physicians, nurses and ancillary medical staff, and they have specific protocols for managing patients and access to rapid diagnostics. Through a coordinated stroke-team approach, rehabilitation can commence as early as possible with a program targeted to the patient's individual needs. It is of prime importance that each individual's quality of life is maximized. Assessment and upgrading of aftercare facilities are also important.

New Treatments

There are a number of new treatments on the horizon for ischemic stroke (Furlan et al., 1999; Sherman et al., 2000). New agents with lower hemorrhagic risks than rt-PA are being investigated, as are intra-arterial thrombolysis and augmentation of clot busting with high frequency ultrasound and other mechanical devices. Other therapies include viper venom, hypothermia, cell transplants, gene therapy and neuroprotective agents. A stroke vaccine is a future possibility.

Advances in MRI techniques provide images of very high quality that provide additional information to that obtained by CT. These images allow a more refined diagnosis of the stroke subtype and approach to individual patient management. Developing brain ischemic lesions can be visualized within minutes using a technique known as diffusion-weighted imaging (Le Bihan et al., 1986; Moseley et al., 1990), along with multiple other aspects of the acute ischemic process such as perfusion and arterial anatomy. MRI techniques may also allow more selective treatment to reduce associated risks, to extend the time window for treatment or even to administer new treatments (Baird and Warach, 1998).

Better public knowledge and education about developments in stroke diagnosis and treatment and a change in the approach to stroke is vitally important. The Brain Attack Coalition describes the symptoms and signs of stroke as:

If a person suffers from any of the symptoms listed above, 911 should be called immediately. Calling the local doctor or waiting for symptoms to go away results in excessive delay. (For more information about the Brain Attack Coalition, please visit www.stroke-site.org-Ed.)

Even a transient ischemic attack (TIA or warning stroke in which the symptoms usually resolve within minutes) is an emergency with a higher stroke rate in the first two days and a stroke rate of 10.5% in the following three months (Johnston et al., 2000).

Conclusion

Acute ischemic stroke is now, in many cases, a treatable condition, but the diagnosis must be made rapidly for treatment to be given. Unfortunately, rt-PA treatment cannot be given to everyone, and stroke remains a major cause of death and disability in the community. Exciting new treatments are on the horizon but prevention is critical. More research is needed to better understand and treat this complex disease.

Dr. Baird is a stroke neurologist and a visiting scientist at the National Institutes of Health.

References

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