Treatment for stroke patients moves from bench to bedside

Technique appears to improve arm and leg use.

By Beth Azar
Monitor staff

A behavioral technique that is showing promise for restoring arm use and mobility after a stroke may work by changing the way the brain is organized, according to a new study by psychologist Edward Taub, PhD, and his colleagues.

The findings are the culmination of research that Taub, now at the University of Alabama at Birmingham, started more than 20 years ago. At the time, he had no interest in applying his work to the real world. He just wanted to study the role of sensory feedback and reflexes in limb movement.

Today, his research is largely applied, focusing on a neurore-habilitation technique for chronic stroke patients. He and his colleagues have mounting evidence that the technique can restore some use of the arms and improve use of the legs in people who have long-lasting stroke damage. And they have preliminary evidence that the technique may work by increasing the amount of brain area devoted to moving the damaged limb.

The route from bench to bedside has been a long and sometimes arduous one?including a now-famous battle with animal rights activists. But Taub?s work is a perfect example of how basic research can engender useful applications, says Yale University psychologist Neal Miller, PhD.

Building on basic research

Taub developed his behavioral rehabilitation technique based on research he conducted on monkeys that had the sensory roots of the spinal nerves innervating one arm severed. The procedure left the monkeys with intact motor nerves but no feeling in the affected arm. The initial shock to the nervous system prevented arm movement. But even after the nervous system recovered, the monkeys failed to use the arms.

Taub theorized that the monkeys were victims of 'learned nonuse': Initially, they couldn?t move their arms when they tried and so learned not to try. Taub was able to gradually bring back arm movement by tying down the monkeys? healthy arms and forcing them to use the damaged limbs. This research, funded by basic research grants from the National Institutes of Health (NIH), led researchers to re-evaluate their theories of limb movement and to posit the idea that the central nervous system houses central-pattern generators that control intentional movement.

It wasn?t until years later that Taub began to imagine that humans might experience learned nonuse after nervous system damage as with a stroke. Using small grants from his university for pilot studies, he then began to develop a behavioral technique for retraining people to use damaged limbs similar to the one he used in monkeys.

The key is to increase a person?s motivation to use the affected limb, says Taub. The original technique used a sling to immobilize patients? good arms. They had to wear the sling for two weeks during 90 percent of their waking hours. And they spent six hours a day for 10 consecutive days exposed to shaping therapy, a technique derived from operant conditioning methodology, which forced them to practice arm and hand movements and increase their proficiency.

Other techniques also work. For example, instead of the sling, Taub puts a padded safety mitt on the good hands of patients with balance problems to prevent them from using their fingers while saving them from the disequilibrium caused by having one arm tied up. Shaping or intense physical therapy alone also seems to work. All the techniques last only two weeks.

Dramatic improvements

Taub and his colleagues at the university have seen improvements in all 73 patients they?ve treated with the techniques?regardless of how long ago the stroke damage occurred (several patients were more than 15 years post-stroke). They see statistically significant results in patients? ability to perform motor tasks in the lab as well as dramatic improvements in daily use of their arms. On a 5-point scale with 0 representing no use of the extremity and 5 representing normal use, the average patient begins therapy at 1.5?very little to a little use for 14 daily activities, including hair combing, using a fork or spoon and donning a shirt. After two weeks, the average patient improves to a level of moderate to almost normal use?3.7?and 30 percent of patients gain close to normal use of the affected arm. These results last for up to two years?as long as the researchers have followed any of them?with no decrease in use for patients receiving constraint along with shaping and some decrease for patients receiving shaping alone.

The most recent outcome study was published in Topics in Stroke Rehabilitation (Vol. 3, p. 38?61) and two replication studies from other laboratories are in press. Much of the research is now funded by the Veterans Affairs Administration and the NIH?s National Center for Medical Rehabilitation Research.

'The [clinical] results seem to be indicating that this therapy is going to be quite an addition to rehabilitating people who have strokes or other neural injuries,' says Miller. 'It?s a nice example of how clinical research can grow directly out of basic research.'

Reorganizing the brain

Along with evidence that the techniques improve functioning, Taub and his colleagues Joachim Liepert, PhD, Wolfgang Miltner, PhD, Cornelius Weiller, PhD, and others at the University of Jena in Germany have evidence that the therapy is having an effect on the brain areas that control hand and arm movement. After treatment, there is a 122 percent increase in the area of the cerebral cortex devoted to generating a contraction in the hand muscle of the affected arm compared with before treatment, the researchers report in an article in press in Neuroscience Letters. To measure this change, the researchers used Focal Transcranial Magnetic Stimulation (TMS); a technique that stimulates portions of the motor cortex with a magnetic stream that penetrates the skull and results in a peripheral muscular response in the part of the body stimulated.

Their findings are 'consistent with the huge increase in motor function that we get with the therapy,' says Taub.

Expanding the client base

When Taub started testing his rehabilitation technique, he worked only with stroke patients who, along a continuum of recovered function, ranked in the top 25th percentile. Recently he, Sherry Yakley and others at UAB have begun testing the technique in people who rank in the next 25th percentile. The nine patients treated so far have benefited as much as higher functioning patients. 'We appear to be able to produce a very substantial increase in about 50 percent of chronic stroke patients in the United States,' says Taub.

Along with Michelle Spear and Danna Kay King, Taub is now testing whether shaping can produce improved leg movement in patients. Most stroke patients regain their ability to walk but they often use unnatural movements, what Taub calls 'learned misuse.' Preliminary evidence from five patients indicates that treating the legs may work even better than treating the arms.

Taub, Steven Wolf, PhD, and their colleagues are initiating a six-site national clinical trial of their rehabilitation technique. The American Physical Therapy Association funded the pilot phase of the trial, and they hope the National Center for Rehabilitation Research will fund the trial itself.

'Taub?s work is absolutely first-rate,' says Paul Bach-y-Rita, MD, a prominent rehabilitation physician at the University of Wisconsin. 'His work is what rehabilitation needs, research with theoretical underpinnings.'