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Physicians Update

 
Summer 2006: Neuroscience

UCLA Stroke Program Brings Treatments to the Community

Acting on the adage that when it comes to stroke “time is brain,” the first large-scale trial of a neuroprotective drug to treat stroke patients on their way to the hospital is underway throughout Los Angeles County.

UCLA is spearheading the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial, sponsored by the National Institutes of Health, which brings together all of the county’s adult-receiving hospitals, the emergency medical system and fire department paramedics within the critical first two hours of stroke onset.

One in 15 Americans will die of stroke, which is the nation’s third-leading cause of death, after heart disease and cancer. Stroke is the leading cause of disability in this country, and the second-leading cause of dementia, after Alzheimer’s disease.

Currently, the only Food and Drug Administration (FDA)-approved treatment for the most common type of stroke is a clot-dissolving drug, tissue plasminogen activator (t-PA). Only a small percentage of stroke patients receive t-PA, in part because it can be safely administered only after a brainimaging test, and by the time most patients arrive at the hospital and take the test, they have missed the three-hour time window for effective management.

Magnesium sulfate, which works by dilating brain blood vessels and preventing buildup of damaging calcium in injured nerve cells, is felt to be safe to give to patients who have either major stroke categories—blocking or bleeding— making it appropriate to administer in the ambulance en route to the hospital, according to Jeffrey Saver, M.D., director of the UCLA Stroke Center and principal investigator of FAST-MAG.

Dr. Saver and colleagues recently found that during every minute of a stroke, more than 1 million nerve cells die. “In the most common type of stroke, an artery is blocked, and oxygen and nutrients are not delivered to a region of the brain,” he explains. “These nerve cells can tolerate low blood flow for a few minutes, or, at best, a few hours. That’s the brief time window in which we have to intervene.

More than 50 promising neuroprotective drugs for stroke that worked in animal models have failed in humans, Dr. Saver otes. “It’s become clear that we need to give drugs sooner after onset of stroke, before much of the irreversible damage has occurred,” he says. “Using paramedics—the first healthcare personnel to come into contact with the patient—is a promising strategy.”

The FAST-MAG trial is one of the latest proactive steps taken by UCLA to educate consumers and physicians about the signs and treatments of stroke. Strokes cause disruption of normal blood flow to the brain. The two most prevalent kinds of strokes are ischemic, in which a clot inside a brain blood vessel blocks blood flow, and the less common hemorrhagic stroke, in which a brain blood vessel bursts. Both cases lead to brain damage.

In the majority of cases, the deleterious effects of stroke can be greatly decreased, or even eliminated; to accomplish that requires knowledge of preventive measures, understanding stroke symptoms and immediate action. “‘Immediate’ is the key word,” says Sidney Starkman, M.D., head of UCLA’s Brain Attack Team, which is organized specifically to move with urgent speed and effectiveness to help stroke victims. “Stroke victims can help themselves by recognizing symptoms and acting fast. They can literally save their own brain cells from dying.”

Dr. Starkman, a faculty member in the Departments of Emergency Medicine and Neurology, leads a group of UCLA undergraduate students best known as “Sid’s Kids.” They have a rare opportunity for undergraduates: learning about clinical research through direct involvement with providing a potentially life-saving service.

From 8 a.m. until midnight, seven days a week, 365 days a year, one of Sid’s Kids volunteers in the UCLA Medical Center emergency department (ED), where he or she watches for potential stroke victims who might not yet have been fully evaluated by a doctor or nurse. Sid’s Kids are a selective group of students who are rigorously and extensively trained.

“The students play an invaluable role as the eyes and ears of the Brain Attack Team,” Dr. Starkman says. “They focus on two questions: Is this a stroke and when did it begin?

“Students can identify stroke victims or stroke mimics. I have them call me with anything that even looks like a stroke for two reasons: One, the call can save a life, and two, it provides a perfect teaching opportunity. I do a lot of teaching on the telephone.

“When a student contacts me, I immediately start for the ED and contact Judy Guzy, R.N., and Marina Shukman, R.N., who coordinate the stroke research. As I drive, I’m on the phone with the student, and I’m calling other members of the stroke team who will meet at the ED.”

Stroke team members include physicians with primary expertise in emergency neurology, vascular neurosurgery, stroke neurology, interventional neuroradiology and neurorehabilitation.

Signs of Stroke

  • Sudden weakness or numbness of face, arm or leg, especially on one side of the body (the most critical symptom)
  • Sudden confusion, trouble speaking or understanding
  • Sudden trouble seeing in one or both eyes
  • Sudden trouble walking, dizziness, loss of balance or coordination

Strokes can be indicated by any of the above symptoms in mild, moderate or severe degrees, and in any combination.

Taken primarily from guidelines published by the National Stroke Association (www.stroke.org)

Applying Research to Rehabilitation Following Stroke

As head of the UCLA Neurological Rehabilitation Unit, Bruce Dobkin, M.D., leads a team that begins working with brain-injured patients after the acute period has ended. As a better understanding of the role of chemical messengers in solidifying memories develops, Dr. Dobkin and his colleagues are laying the groundwork for therapeutic strategies to strengthen the memory in brain-injured patients through electrical stimulation or individually tailored medical regimens. In his studies of patients who are relearning how to walk, Dr. Dobkin has shown through functional magnetic resonance imaging (fMRI) that the brain changes as the skills are practiced.

"Rehabilitation efforts to improve the use of an affected arm, walking, speech and other disabilities depend on developing the best possible methods for practice and relearning within the amount of spared function that patients possess," Dr. Dobkin explains. "Learning a skill is accompanied by changes in brain physiology and structure, and rehab aims to drive those changes for lasting improvements."

To that end, Dr. Dobkin, and other research groups, have been testing treadmill training with partial body-weight support and robotic assistive devices for walking to determine if they can improve balance and speed after stroke. A multicenter clinical trial of treadmill training funded by the National Institutes of Health has been studying patients admitted for rehabilitation from West Los Angeles, Inglewood, Long Beach and San Diego who are either two or six months post stroke and still walk poorly. The trial, called LEAPS, will close in 2009. (See http://neurorehab.neurology.ucla.edu/)

Dr. Dobkin recently completed a multicenter trial of the technique for people with recent spinal cord injury, which did not reveal the method to be better than more common physical therapies, mostly because patients who received either treatment generally improved quite a bit. This new trial will also examine through fMRI adaptations that evolve in the brain as a consequence of training. Dr. Dobkin notes, "Insights from such studies may lead to better drug, physical and biological therapies for the future."





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