CIMT Benefits Patients Months After Stroke

Rehabilitative therapy may be effective in patients many months after stroke. Patients who underwent constraint-induced movement therapy (CIMT) within 3 to 9 months after stroke showed significant rehabilitation of the affected limb in a study led by Steven Wolf, PhD, professor of rehabilitation medicine at Emory University in Atlanta.¹

"Neurologists have traditionally been nihilistic about therapeutic interventions, especially in patients 3 to 9 months after stroke--a period in which most neurologists believe improvement has plateaued or stopped," said David C. Good, MD, a member of the study's research team and director of neurorehabilitation and professor and chair of the Department of Neurology at Penn State Milton S. Hershey Medical Center. "We've shown that these patients can still make significant improvement."

This was the first nationally randomized single-blind study to examine a specific neurorehabilitation method in stroke patients, he said.

Researchers in the Extremity Constraint-Induced Therapy Evaluation (EXCITE) trial evaluated the effects of CIMT in patients who had weakness in one arm caused by a stroke. In CIMT, the unaffected limb is restrained with a mitt, forcing the patient to use the affected hand and arm through repetitive exercises.

The 12-month study involved 169 patients; about half of these patients received customary care, ranging from no treatment to standard physical therapy, while the other half received 2 weeks of intense CIMT for several hours each day. Patients were evaluated immediately after treatment and again at 4, 8, and 12 months using the Wolf Motor Function Test and interview.

After 12 months of follow-up, the CIMT group showed greater improvement than the control group. The CIMT group reported a 50% greater ability to use the affected arm to perform tasks and 65% reported increased usage of the affected arm in daily activities. Patients with the highest and lowest amount of function before undergoing CIMT showed the least improvement after the therapy.

According to Wolf, CIMT should only be used in patients who have the potential for meaningful clinical improvement, which he defines as the ability to use the impaired extremity in everyday function. That may only constitute 5% to 30% of the stroke population, he said.

Wolf is careful to point out that not all patients who have had strokes and still have some movement in their upper extremity are going to respond to CIMT. "I think the important message is that there is a subset of patients who are many, many months poststroke who still may have the opportunity for improvement," he said. "Patients will have to meet the criteria that we refer to in this study."

Wolf offered a "quick and dirty" method for physicians to identify patients who may benefit from CIMT:

• Seat the patient with his or her affected forearm on the table so that the wrist is hanging over the edge of the table, palm down.
• Ask the patient to raise his fingers and wrist without picking up the forearm.
• If the patient can raise his fingers and wrist at least 10 degrees 3 times over the course of 1 minute, he can be considered for CIMT.

Patient self-motivation is also key, according to Good. "This is a very frustrating procedure because it forces patients to use a limb that they have difficulty using," he said. "I had a patient who tried the therapy; after the third day, she took the mitt off her good arm and threw it across the room. She said, 'That's it, I've had enough.' So, self-motivation may be the most important criterion of all."

This is one reason why treatment with CIMT only lasts 2 weeks, said Wolf. "We learned in many efforts in the past that 2 weeks of intense therapy is in the upper limits of what the patient is willing to tolerate," he said. "It is also the average threshold in which patients learn to use their impaired extremity in activities of daily living and begin to overcome whatever learned nonuse or inhibitory mechanisms had prevented them from using the impaired limb."

A NEW UNDERSTANDING OF NEUROPLASTICITY

Good said that the results of this study will force neurologists to change their view about the potential for neurorehabilitation in patients who have had a stroke. "The things we were brought up with as neurologists really don't hold true anymore," Good said. "The brain is incredibly plastic, and people can show improvement much longer than neurologists had assumed following stroke."

Other studies have shown that cortical motor networks can be reorganized not only in primate models but also in humans, with very specific, intensive task-directed training programs including CIMT.^2-4 "We can now show changes in excitability in motor maps, and additional areas may be recruited that did not normally participate in upper extremity activity following the CIMT training program," said Good.

During the 12-month follow-up in the EXCITE trial, Wolf and colleagues conducted an ancillary study using transcranial magnetic stimulation (TMS) and functional MRI (fMRI) to examine the physical changes in the brain after treatment with CIMT. The results of this ancillary study have not yet been published.

However, both physicians believe that imaging will be an important resource for understanding the effects of CIMT. "Going forward, we should be able to predict exactly which intervention will benefit individual patients. Whether we choose them using TMS, fMRI, or clinical criteria remains to be seen," said Good.

EXCITEing FUTURE

According to Wolf, a great deal of data have not yet been released from the EXCITE trial, and researchers are still monitoring patients in the study to examine effects of CIMT. For example, those patients in the customary-care group within the first year of the EXCITE trial have now received CIMT in the second year of the trial. "This allows us to see the magnitude of improvement in those people who received this intervention more chronically compared with those who received it more acutely, but they have all undergone treatment from the same groups of physicians, standardized continuously throughout the course of the EXCITE trial," Wolf said.

In the next phase of the EXCITE trial, Wolf plans to examine the results of CIMT in patients 1 to 3 months after stroke. "The typical length of reimbursable physical therapy for stroke patients is now down to 1 month, which is pretty bad," said Wolf. "So this allows us a window of trying to do a modification of this intervention even earlier. We're kind of climbing up the acute ladder, so to speak."

Eventually, he hopes to study the effects of CIMT in patients who have responded to botulinum toxin (Botox) for treatment of spasticity resulting from stroke. His team is discussing this with Allergan.

Also, Wolf and colleagues will continue to explore how patients improve through CIMT. Wolf will continue to examine whether patient improvement is caused by the intensity of the rehabilitation, whether the patient is merely "figuring out" new ways to use his affected limb, or a combination of both. "Everyone presumes that intense therapy is good, but we may find that there is no relationship between the actual number of minutes or hours of rehabilitation over those 2 weeks and the final outcome," Wolf said. "If there isn't a relationship, then our focus should be on the rehabilitation methods used during that time," to identify how they contribute to improvement.

Wolf's team will be examining the relationship of the outcome measures and the amount of time the patient actually spent training. "Not everyone can do the same number of minutes per day over those 2 weeks, so we're going to look at linear relationships between the amount of training and the outcome," Wolf said. "It may be that what the therapists do in problem solving may be part of the key to neuroplasticity, as opposed to the amount of time that is spent. We don't know the answer to that question yet.

"I have my ideas--I'm not convinced that more is necessarily better. If that turns out to be the case, we have to figure out the actual ingredients for unmasking or releasing the potential that patients might have," Wolf continued. "My intuition and my experience tell me that in the end--and there are animal models of stroke to support this contention--problem solving is what actually drives the behavior."

Good hopes these studies will help physicians treat patients after stroke who were not treated in the past. "I foresee a day in the future [when] specific physical intervention may be coupled with pharmacologic intervention to enhance learning for many people who suffer a stroke," he said. "Of course, prevention is most important, but neurologists need to turn their attention to what they can do for someone who has already suffered a stroke."

REFERENCES1. Wolf SL, Winstein CJ, Miller JP, et al; EXCITE Investigators. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke. The EXCITE Randomized Clinical Trial. JAMA. 2006;296:2095-2104.
2. Dong Y, Dobkin BH, Cen SY, et al. Motor cortex activation during treatment may predict therapeutic gains in paretic hand function after stroke. Stroke. 2006;37:1552-1555.
3. Schaechter JD, Kraft E, Hilliard TS, et al. Motor recovery and cortical reorganization after constraint-induced movement therapy in stroke patients: a preliminary study. Neurorehabil Neural Repair. 2002;16:326-338.
4. Ro T, Noser E, Boake C, et al. Functional reorganization and recovery after constraint-induced movement therapy in subacute stroke: case reports. Neurocase. 2006;12:50-60.