Using ultrasound in combination with the drug t-PA can improve response to an ischemic stroke, according to a study involving 126 patients. This first-of-its-kind human trial compared the safety and efficacy of ultrasound and t-PA versus use of t-PA alone. The trial was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH). The finding appears in the November 18, 2004, issue of the New England Journal of Medicine.
Since 1996, the clot-busting drug t-PA (tissue plasminogen activator) has been the only FDA-approved therapy for acute ischemic stroke. Previous studies have shown that t-PA, when administered within 3 hours of onset of ischemic stroke, can greatly improve a patient's chance for a full recovery. t-PA cannot be used to treat the less common hemorrhagic stroke.
Researchers wanted to test the effectiveness of using transcranial Doppler ultrasound (TCD) in combination with t-PA, and to ensure that ultrasound did not cause bleeding into the brain. Utrasound is a safe, non-invasive, FDA-approved diagnostic test that uses sound waves to measure blood flow velocity in large arteries. An international team led by Andrei Alexandrov, M.D., associate professor of neurology at the University of Texas-Houston School of Medicine, examined 126 patients who suffered an ischemic stroke. All patients received intravenous t-PA within 3 hours of stroke onset. The 63 patients in the control group received t-PA alone, while the other 63 patients received t-PA in combination with continuous TCD monitoring that started shortly before the patients received the drug. A small device attached to a head frame was used to deliver the ultrasound.
Results showed that 49 percent of patients who received continuous ultrasound and t-PA showed dramatic clinical improvement and little or no blockage within 2 hours after therapy began compared to 30 percent who received t-PA alone. Notably, 38 percent of the patients who received continuous ultrasound and t-PA showed no blockage within two hours, compared to 13 percent who received t-PA alone. In all, 73 percent of patients who received the combined therapy showed complete or partial clearance of the clot, compared to 50 percent in the control group. Bleeding into the brain was experienced by 4.8 percent of patients in both groups. This early improvement of blood flow to the brain resulted in a trend that 13.5 percent more patients who received continuous ultrasound and t-PA had recovered completely by 3 months after stroke.
The team also found that patients who experienced complete clearance of their clot within 2 hours following treatment had the greatest likelihood of regaining body strength, speech, and other functions affected by stroke. Researchers named the trial CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia Using transcranial ultrasound and Systemic t-PA).
It will be cheap and easy to implement the lessons learned from this discovery and the benefits will be enormous.
This discovery was made by accident by an observant nurse. Emergency room nurse Patti Bratina observed that the stroke patients which were being monitored by Dr. Alexandrov using ultrasound recovered much better than typical stroke patients.
It happened at the University of Texas-Houston Medical School about five years ago, when Dr. Andrei V. Alexandrov, newly arrived from the University of Toronto, was using ultrasound technology to monitor the progress of stroke patients treated with tissue plasminogen inhibitor (tPA), a clot-dissolving drug that had just been given approval by the U. S. Food and Drug Administration for use against strokes (it had been approved for use in heart attacks more than a decade earlier). The nurse, Patti Bratina, noticed that many of the patients being monitored by Alexandrov were making remarkable recoveries, regaining use of their limbs and other faculties much faster than could be expected. Perhaps, she suggested, ultrasound had something to do with that.
Dr. Alexandrov wisely followed up on her suggestion. The result is a NEJM paper entitled Ultrasound-Enhanced Systemic Thrombolysis for Acute Ischemic Stroke.
Stroke is the third leading cause of death in the United States. It is the leading cause of long-term disability in the United States. Each year, more than 600,000 people suffer a stroke in the United States, resulting in approximately 150,000 deaths. The yearly cost of stroke in the United States is more than 40 billion dollars. Yet, one cannot fully measure the cost of stroke in dollars. The effects of stroke are felt not only by the patient, but also by the patient's family and friends, and by society in general.
There are about 4.4 million stroke survivors in the United States today and likely tens of millions more in the rest of the world. Imagine higher rates of recovery for the future millions of stroke sufferers. Costs in physical therapy, nursing services, and other costs will be reduced by a cheap and easy improvement in how stroke is initially treated in emergency wards.
Of course, the ideal solution to stroke will be therapies that prevent it from happening in the first place. My guess is we will need gene therapies or cell therapies to repair the cardiovascular system perhaps along with gene therapies to change blood chemistry in such a way that prevents cholesterol build-up. My guess is the liver would be the target for the latter category of gene therapies but the blood vessels would be the target of gene therapies designed to repair them.
|Share |||Randall Parker, 2004 November 18 05:47 PM Biotech Therapies|