New research presented at the American Stroke Association’s International Stroke Conference suggests a promising new approach to improving motor function in infants and toddlers who have experienced perinatal stroke. The treatment, a high-dose form of constraint-induced movement therapy (I-ACQUIRE), combines restricting the use of the stronger arm with intensive, task-oriented physical therapy, leading to improved skills and function in the affected limb compared to standard care.
Perinatal arterial ischemic stroke (PAIS) is the most common type of stroke in children, occurring before or shortly after birth (within the first 28 days). It often results in hemiparesis, characterized by weakness or impaired motor control on one side of the body. This can significantly impact a child’s development and ability to perform everyday tasks.
Constraint-induced movement therapy (CIMT) is a rehabilitation technique designed to improve the use of an impaired limb by restricting the stronger limb, forcing the brain to rewire itself and rely more on the affected side. The I-ACQUIRE protocol, specifically tailored for infants and toddlers, incorporates this principle alongside intensive, goal-directed therapy delivered in the child’s natural environment, such as their home and includes a program to support parents in implementing the therapy.
A Phase 3 randomized clinical trial, involving data, enrolled 216 children aged 8 months to 36 months from 15 U.S. Centers. Data from 167 children with confirmed PAIS were included in the analysis. Participants were randomly assigned to one of three groups: a high-dose I-ACQUIRE group, a moderate-dose I-ACQUIRE group, or a usual care group.
The high-dose group received six hours of therapy per day, five days a week, for four weeks, with the stronger arm constrained. The moderate-dose group received three hours of therapy per day, also five days a week for four weeks, with the stronger arm constrained. The usual care group received approximately one hour each of occupational and physical therapy per week, as typically provided in community settings.
Assessments of the children’s arm and hand skills were conducted before treatment, at the end of treatment, and six months after treatment by assessors who were unaware of which treatment group each child belonged to. These assessments focused on fine and gross motor skills. Parents also provided feedback on their child’s functional performance in daily activities.
The results showed that both the high-dose and moderate-dose I-ACQUIRE groups demonstrated improvements in neuromotor skills at the end of treatment, gaining a median of three new skills each, compared to only one new skill gained by the usual care group. However, the gains were smaller than initially anticipated.
More significant differences emerged at the six-month follow-up. Children in the high-dose group exhibited larger gains in skills and daily function compared to those in the moderate-dose or usual care groups, particularly those who closely adhered to the therapy protocol. Parents in both the high- and moderate-dose groups reported meaningful improvements in their children’s ability to use their weaker arm and hand in everyday activities, including playing with toys, communicating through gestures, and performing self-care tasks.
Interestingly, children in the usual care group also showed clinically significant improvements in their arm and hand skills at the six-month mark, demonstrating improvements in reaching, grasping, crawling, and protective movements. However, parents in this group did not report the same level of improvement in their children’s everyday use of the affected limb.
“This research fills a knowledge gap,” said Sharon Ramey, Ph.D., study author, co-director of the Fralin Biomedical Research Institute Neuromotor Research Clinic, and professor at Virginia Tech Carilion School of Medicine. “Previously, parents and physicians relied on findings from a mixed group of mostly older children with cerebral palsy and hemiparesis to make treatment recommendations. however, these findings lacked sufficient data about benefits for this clinical population of infants and toddlers. Now, we confidently know that this treatment, at both dosages, was well-received, safe and produced measurable benefits.”
Researchers noted that the response to I-ACQUIRE therapy may vary among children with PAIS, and identifying which children are most likely to benefit from the treatment will be an important area for future research. They also emphasized the potential for greater recovery from early stroke than previously believed.
“We think the potential for an infant to recover from an early stroke far exceeds what was once considered a fairly grim prognosis,” Ramey said. “We repeatedly heard from parents that the many changes they saw in their children exceeded what they had been told was likely for their child. In turn, when they saw these improvements, they increased their own expectations for the future and their child’s likely success in participating in a wider range of age-typical activities at home and in the community.”
The study demonstrated the feasibility of conducting rigorous research in this population and the effectiveness of implementing the treatment plan with families and clinicians. However, the researchers acknowledged some limitations. The study sites were selected based on their interest and resources, which may not be representative of all locations where children with PAIS receive care. A small number of children were enrolled whose stroke diagnosis was not confirmed by independent specialists, reducing the final sample size to 167.
The trial involved 167 children, with roughly half being male, ranging in age from 8 to 36 months. Participants were randomly assigned to one of the three treatment groups. The high-dose I-ACQUIRE group received a total of 120 hours of therapist-delivered treatment, while the moderate-dose group received 60 hours. The usual care group received an average of 2.2 hours of weekly therapy, typically involving both occupational and physical therapy.
Parents of children in the usual care group were offered the opportunity to enroll their children in a delayed treatment study, receiving either moderate- or high-dose I-ACQUIRE therapy after the six-month assessment. The trial was overseen by a Data Safety and Monitoring Board and an independent medical monitor, with any adverse events carefully documented and addressed.
