Constraint-Induced Movement Therapy May Boost Neuroplasticity in MS

Nancy A. Melville

June 01, 2020

Neuroimaging of patients with progressive multiple sclerosis (MS) shows that physical behavioral change therapy, specifically, constraint-induced movement therapy (CIMT), leads to improvement in neuroplasticity compared to alternative interventions with medicines.

"The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder," say the authors of research presented as part of the Consortium of Multiple Sclerosis Centers (CMSC) 2020 Virtual Annual Meeting.

CIMT, an intervention involving 3.5 hours per day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.

For patients with asymmetric upper limb nonuse, the treatment "is highly successful for promoting increased use by the more-affected arm for everyday activities," first author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham, told Medscape Medical News.

"The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS," he said.

The team's previous research showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.

For the study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability.

The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.

Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared to the control group (d = 3.2, vs d = 0.7).

Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment.

Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.

"We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex)," Mark said.

"As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment," he said.

The results are important, Mark noted, "because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder."

In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.

The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, PT, of the UCHealth Yampa Valley Medical Center, in Steamboat Springs, Colorado.

"There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS," she told Medscape Medical News.

"If we're trying to find new avenues in the brain for better pathways, rather than using something that's damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you're doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning," she said.

Repetition, "Prevention of Compensation"

CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as "massed practice," involves intensive, repetitive arm movements of the affected arm. The second component involves "shaping," in which the patient is encouraged to perform his or her best attempts at the movements.

For the third component, described as "prevention of compensation," the patient's more functional arm is inhibited from being utilized in everyday activities by wearing of a padded mitt.

"This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm," Mark explained.

"The patient wears the padded mitt after hours, too, except when using water or when sleeping," he said.

The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.

Mark noted that the intervention could have benefits that are secondary to motor and movement function.

"We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity," he said.

Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Mark pointed out.

Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark's program at the University of Alabama in a semiannual, weeklong training course, which includes hands-on treatment practice with actual patients.

In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort.

"The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance," she told Medscape Medical News.

"It is important to take this information as 'proof of principle' of the importance of CIMT for improving upper limb activity," she said.

"Importantly, this team needs to move forward testing their hypothesis in a larger randomized clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen," she said.

Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS.

"Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person's abilities and interests," she said.

"Another important detail is that CIMT is also being explored for lower extremity use," she added. "This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability."

The authors, Bobryk, and Zackowski have disclosed no relevant financial relationships.

Consortium of Multiple Sclerosis Centers (CMSC) 2020 Virtual Annual Meeting: Abstract RH101.

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