Recovery Road

With the number of stroke patients doubling over the next 50 years, researchers are focusing interdisciplinary endeavors on innovative rehabilitation programs to treat survivors.

By Lori Oliwenstein

It begins with numbness in your face, a tingling arm, some dizziness. You might stumble or drop the cup of coffee you are carrying. Maybe your vision is a bit off, maybe you are a little confused about where you are. You might notice a bit of a headache coming on, or maybe you have been slammed by the worst headache you have ever known.

You are having a stroke—a brain attack. Somewhere in the blood-filled thoroughfares of your brain there is a clot that is stopping the blood flow, or perhaps there is a sudden leak in a blood vessel wall, letting blood rush out into the brain’s tissue. In either case—blockage or bleeding—cells are beginning to suffocate and, deprived of oxygen, are unable to function. After just a few minutes, those cells will die. Included among these cells will be the neurons that send vital messages to other parts of your body.

Death and stroke are often considered to be synonymous. And stroke is an indiscriminate killer, not only of brain cells, but also of people. Brain attacks are the third leading cause of death in our country—trailing behind only heart disease and cancer—and take the life of someone in the United States every 3.1 minutes.

Still, thanks to education and advanced medical therapies, about two-thirds of people who suffer a stroke survive it. But that upside carries with it a harsh reality: Stroke is now the number-one cause of serious, long-term disability in the United States.

Physicians and researchers are realizing that saving the lives of stroke victims is one thing; preserving the quality of those lives is another thing altogether.

“Each year in the United States, over 700,000 people suffer a stroke, and nearly 450,000 survive with some form of neurological impairment,” says Thomas McNeill, Ph.D., professor of cell and neurobiology and neurology at the Keck School of Medicine of USC. “In addition, with the population progressively getting older, and obesity and heart disease on the rise, it is estimated that the number of stroke patients will more than double over the next 50 years, making the need to develop new and innovative rehabilitation programs to treat the growing number of stroke survivors a national priority.”

McNeill, along with scientists from a wide-ranging list of departments and disciplines at USC and at the University of Texas in Austin, have banded together to create a new research center that will use an interdisciplinary approach to give stroke survivors the best possible chance at the fullest possible recovery.

Their passion and their ideas are so strong and unique that the National Institutes of Health (NIH) recently named them one of only 21 groups nationwide eligible for a brand-new grant program. Called P20 grants, they are designed to encourage interdisciplinary endeavors in medicine and biology.
Using the $1.8 million awarded to them, this interdisciplinary research team has created an NIH Exploratory Center for Interdisciplinary Research at USC. As NIH Director Elias A. Zerhouni, M.D., explains,“With these new Exploratory Centers, we hope to remove roadblocks to collaboration so that a true meeting of minds can take place that will broaden the scope of investigation, yield fresh and possibly unexpected insights, and create solutions to biomedical problems that have not been solved using traditional, disciplinary approaches.”

The importance of this new type of grant cannot be understated, notes McNeill. Not only are they the first grants of their kind, but they work to promote research efforts that ignore traditional academic boundaries, and are the first step for scientists hoping to capture a more traditional and highly coveted NIH center grant.

Strong-arming stroke recovery


With NIH funding at their disposal, the scientists involved in USC’s Exploratory Center are investigating new directions in stroke neurorehabilitation, says Carolee Winstein, Ph.D., associate professor of biokinesiology and physical therapy at USC and McNeill’s co-principal investigator.

The researchers will begin by focusing on rehabilitation strategies for the arm and hand in people who have survived a stroke. It is no small goal, says McNeill.

“Statistics indicate that almost 80 percent of people who suffer a first-time stroke have impairment of the upper limb that significantly impacts their functional independence, health and quality of life,” he says.
“Still, we know that a recovery of function can occur, and that it requires retraining the brain to move the arm and hand in the correct fashion. We’re looking for better ways to enhance that recovery. We need to figure out how intense the training should be, what skills we need to focus on, and what the physical therapist’s practice strategies should be.”

Ongoing clinical trials at USC are looking at arm and hand rehabilitation on a number of different levels of task specificity and training intensity, Winstein notes.

“It’s clear that no one really understands the parameters of training that are necessary to enhance recovery,” Winstein says. “The simplistic view is that more is better, but that may not be true at all. Our studies are titrating the challenge level and the amount of repetition; we think that too much intensity can be detrimental. For instance, we’re learning that after training, there needs to be a time for consolidation, which happens during sleep. So instead of six hours a day for two weeks, maybe we need to cut it back to two or three hours a day for a longer period of time.”

The first month or so after a stroke is the most critical time for recovery of function, according to the American Heart Association, because it is the time period during which “spontaneous recovery” is most likely to occur. In other words, it is the time during which neurons that might have been presumed to be dead may show signs of life, or when blood-soaked tissues dry out a bit and spring back into action.
But 30 days post-stroke is not the end of the road by any means, says Winstein. In fact, most of the clinical trials she and her colleagues are conducting require that patients be at least three months post-stroke to enroll. “They need to be settled with the initial shock of having had a stroke,” Winstein says. “It can be a devastating event, and in the beginning, the patients and their families need to focus on dealing with that upset, and with the changes in lifestyle it is likely to bring. All of that takes precedence over any participation in a very focused intervention like the ones we explore.”

Through participation in national clinical trials, Winstein and other members of the USC Exploratory Center have already begun to show that there are a number of ways in which stroke recovery in the upper limb can be enhanced by using novel and state-of-the-art techniques. With the NIH grant, they can take the next steps.

For example, Winstein and Helena Chui, M.D., chair of the Keck School Department of Neurology, will use both regular and functional MRI techniques on patients to look at the severity and location of the damage done by the stroke, and how the brain changes after task-specific training in these patients. Over time, this will allow them to assess how specific types of rehabilitative therapies, their intensity and the severity of the initial stroke-related injury affect the level of effectiveness in retraining the upper limb in stroke survivors.

Other studies will approach arm rehabilitation from entirely different angles. For instance, researchers from the University of Texas will look at animal models they have developed, and will address “fundamental questions related to timing and duration of rehabilitative training,” the scientists explain. Having an animal model is useful, notes McNeill, because it not only allows the team to test new treatment strategies but also to look, on a cellular level, at the mechanisms that drive the recovery process.

Virtual testing and molecular mining

There are other ways to peer inside the brain aside from observing and examining living creatures. Many studies at the center will rely on computer modeling and other high-tech methods. “In parallel with our clinical and animal studies, we will develop novel virtual environment tests that can assess and rehabilitate human functional performance under a range of conditions that are not easily deliverable and controllable in the real world, as well as computational models of reach and grasp,” McNeill explains. These models might be able to predict ways the brain recovers, both naturally and after rehabilitation.
In addition, Stan Azen, Ph.D., professor of preventive medicine at the Keck School, will develop new “data-mining tools for sharing and analyzing data between projects,” McNeill says. McNeill and his group will be doing some molecular-level mining of their own, looking for molecules in the brain that help injured neurons grow, and trying to apply their findings to existing pharmacological and behavioral interventions in such a way that survivors of stroke will have a better chance of a more complete recovery of function not only in the upper limb, but throughout the body.

Winstein believes that this sort of interdisciplinary research paradigm, as put forth by the NIH, is going tobe crucial for the field of rehabilitation in the 21st Century.


“It is well known that the translation of basic science discoveries to clinical practice through a systematic progression of developmental steps can take anywhere from seven to 11 years,” Winstein says. “If the pre-clinical human studies can be conducted in parallel with the animal studies, we may be able to effectively reduce the bench-to-bedside translation time by 50 percent.”

Of course, that reduction will require a significant effort. “For our center to be effective, we will need to foster the environment to encourage the cross-fertilization of ideas between the clinical and basic sciences,” McNeill notes. “This is the major challenge for us, but also a tremendous opportunity to reap the rewards of a truly interdisciplinary collaboration.”

The people who will really reap the rewards of this collaboration, of course, will be the people whose lives are enhanced by the techniques and findings that come out of it—the people whose rehabilitation and quality of life are better because of the work these scientists do.

For more information about the NIH Exploratory Center for Interdisciplinary Research at USC, visit www.usc.edu/medicine/isnsr or contact Thomas McNeill or Carolee Winstein at 1-800-USC CARE (1-800-872-2273). For more information about current clinical trials for post-stroke arm and hand rehabilitation, call project coordinator Samantha Underwood at (323) 442-2899.

 

Mapping Out Success

The USC Exploratory Center is one of 21 Exploratory Centers for Interdisciplinary Research being funded by the National Institutes of Health (NIH) through its brand-new P20 grant system. And it is all part of the NIH’s Roadmap for Medical Research, developed by Director Elias Zerhouni, M.D., to transform the nation’s medical research capabilities and speed the movement of research discoveries from the bench to the bedside.

“Biomedical research traditionally has been organized much like a series of cottage industries, lumping researchers into broad areas of scientific interest and then grouping them into distinct, departmentally based specialties,” Zerhouni said when introducing the new grants. “To remove these organizational barriers and advance science, the new specialized centers will make it easier for scientists to conduct interdisciplinary research and will help them to forge new disciplines from existing ones.”

For more information about the NIH Roadmap or the Exploratory Centers for interdisciplinary Research, visit www.nihroadmap.nih.gov.