June 2, 2000
By SANDRA BLAKESLEE
Using a new kind of stroke rehabilitation therapy, scientists have shown for the first time that the brain can be coaxed into reorganizing its circuitry so that people can regain nearly full use of their paralyzed limbs in just two to three weeks, even if the stroke happened years ago. The rehabilitation involves immobilizing a good arm or leg so that the patient is forced to use the paralyzed arm or leg for familiar tasks.
By intensively using the paralyzed limb, people can literally rewire parts of their brains, researchers said, and overcome a kind of learned helplessness that prevented their limbs from moving. Moreover, the technique works for patients who had their strokes even decades ago and have had limited use of their limbs ever since.
The findings, by scientists at the University of Alabama and the Freidrich Schiller University of Jena in Germany, involved only the arms of 13 patients, but the researchers say similar methods will also work for paralyzed legs.
Several studies are under way in an effort to confirm the findings and test the theory that paralyzed legs can also be restored.
But the results involving the 13 patients, reported today in the June issue of Stroke: Journal of the American Heart Association, join a growing body of evidence that the adult brain is capable of reorganizing itself after injury. The newly reported study made maps of an area of the brain in the 13 chronic stroke patients before and after the intensive therapy, called constraint-induced-movement therapy. Researchers found that the area, which was responsible for arm movements on the injured side of the brain, had nearly doubled in size after the therapy.
The therapy only works, researchers said, if it is given six hours a day for at least two weeks.
When similarly intense therapy is offered only two or three days a week, they said, the brain is not sufficiently stimulated to reorganize itself.
But Dr. Larry Goldstein, a professor at Duke University Medical Center in Durham, N.C., and an expert on stroke, said it was too soon to say whether the new approach would find widespread use. While the study is interesting, Dr. Goldstein said, it has some "big limitations," in that it is based on a very small number of patients and they were not compared with a control group.
"Is it promising?" he asked.
"Yes. Is it proven? No."
Four million people now live with the effects of stroke, two-thirds of whom are moderately or severely impaired.
The fact that an adult brain can rewire itself after injury has been shown in animals for over 50 years, said Dr. Edward Taub, a neurologist at the University of Alabama in Birmingham and an author of the study. This led researchers to wonder if ways could be found to promote such rewiring in human stroke patients.
After a stroke, some cells die but many more are left in a state of shock, Dr. Taub said.
Sometimes these stunned cells recover spontaneously and the patient gets better. But more often, the cells, which might make up networks that control limb movements, remain stunned, in a state of permanent inhibition. Every time a patient tries to use his bad arm and fails, Dr. Taub said, the failure is reinforced. The ability to move gets suppressed, in a kind of learned helplessness.
The ability to move has not been abolished, he said, but the patient has given up trying.
Meanwhile, Dr. Taub said, patients start to depend on their good arms to carry out everyday tasks and those movements are similarly reinforced.
This state of affairs is reflected in brain organization.
For example, cellular networks responsible for arm movements on the injured side of the brain will often shrink by 70 percent whereas the same networks on the uninjured side will expand in size, though not as much.
To see if injured networks can be made to expand, Dr. Taub and his colleagues came up with what they called constraint-induced-movement therapy. It involves strapping down a patient's good arm and forcing the bad arm to do all the work. This, they reasoned, should force the brain to give up its learned helplessness.
The therapy worked, Dr. Taub said. About 250 patients have been treated in several research laboratories nationwide with excellent results, he said.
The National Institute of Health is about to begin multicenter clinical trials of the therapy.
Many other studies of the therapy are now under way, Dr. Taub said.
The 13 men and women in Dr. Taub's study had an arm paralyzed from strokes suffered 6 months to 17 years ago.
Before the therapy, these patients came into the laboratory where their brains were mapped with a special magnetic device that detects the area of the brain where various muscles are represented. In this study, the researchers made maps of the small muscle that connects the thumb to the rest of the hand and used it as a surrogate for the paralyzed arm.
If the representation of this muscle could be made to expand in the brain, Dr. Taub said, all the stimulated arm muscles should also expand. Before therapy, the thumb muscle of paralyzed patients showed activity at only 12 positions on the magnetic map, Dr. Taub said.
A normal thumb muscle might show up to 30 active positions.
During the therapy, patients had their good arms secured in a splint and sling for 90 percent of their waking hours. They went to the rehabilitation laboratory for eight weekdays of treatment, lasting six hours each day. In therapy, they practiced tiny movements that would allow them to reach out, grasp and move objects.
The day after the training ended, the patients' brains were remapped. The thumb muscles on their paralyzed sides showed an average of 22 active positions, nearly double the earlier number, Dr. Taub said.
The patients regained three-quarters of the normal use of their paralyzed arms in just two weeks, he said.
Greatly increased use of the paralyzed arm is what drives the brain to change, Dr. Taub said.
It is not enough to tie down the good arm.
Six months after therapy the patients brains were remapped and the changes
appeared to be permanent, he said. The researchers do not know if even
more therapy would result in complete use of the arm.