High-dose therapy boosts arm function in infants after perinatal stroke

In infants and toddlers who experienced a stroke before birth or within the first 28 days of life, high-dose constraint-induced movement therapy delivered in the home was associated with greater motor gains at 6 months compared with moderate-dose therapy or usual care, according to preliminary late-breaking science presented at the American Stroke Association’s International Stroke Conference 2026.¹ Findings are based on a phase 3 randomized clinical trial evaluating the I-ACQUIRE intervention and were reported in an American Heart Association news release.²

Perinatal arterial ischemic stroke (PAIS) is the most common type of stroke in children and frequently results in hemiparesis, characterized by impaired voluntary motor control on 1 side of the body. Constraint-induced movement therapy (CIMT) aims to improve use of the affected upper extremity by restricting the stronger arm while providing intensive, task-oriented therapy to promote motor learning.

The I-ACQUIRE protocol evaluated in this trial was designed specifically for infants and toddlers and included a structured parent component. Therapy was delivered in the child’s home or natural environment. Investigators enrolled 216 children aged 8 months to 36 months across 15 US centers; outcomes from 167 children with confirmed PAIS were included in the presentation.

Participants were randomly assigned to 1 of 3 groups: high-dose I-ACQUIRE (6 hours daily, 5 days per week for 4 consecutive weeks; 120 total hours), moderate-dose I-ACQUIRE (3 hours daily, 5 days per week for 4 consecutive weeks; 60 total hours), or usual care (approximately 1 hour each of weekly occupational and physical therapy in community settings). All interventions focused on improving functional use of the more-impaired arm and hand.

Blinded assessors evaluated upper extremity skills at baseline, at the end of treatment, and at 6 months post-treatment. Parents also reported on their child’s functional performance in daily activities.

At the end of treatment, both I-ACQUIRE dose groups demonstrated greater gains in neuromotor skills compared with usual care. The median gain was 3 new skills in both active treatment groups (mean gain 2.94 in the moderate-dose group and 3.30 in the high-dose group) compared with a median gain of 1 skill in the usual care group. Investigators noted that the magnitude of skill acquisition was smaller than anticipated.

At 6 months, children in the high-dose group had significantly larger skill gains than those in the moderate-dose or usual care groups. These differences were more pronounced among participants whose treatment closely adhered to the protocol.

Parent-reported outcomes indicated meaningful improvements in daily functional use of the affected limb among children in both I-ACQUIRE groups. Newly acquired skills included exploring and manipulating toys, communication gestures, and self-help tasks not previously performed.

“Unexpectedly, children in the usual care group also showed clinically important improvement in their arm and hand skills at 6 months,” said Sharon Ramey, PhD, co-director of the Fralin Biomedical Research Institute Neuromotor Research Clinic. These improvements included reaching, grasping and releasing objects, and using the affected arm in balance-related activities. However, parent ratings did not reflect sustained real-world functional improvements in the usual care group at either assessment point.

“This research fills a knowledge gap,” Ramey said. “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.”

Ramey also noted variability in treatment response. “We had expected a larger number of skills to be gained from the I-ACQUIRE therapy,” she said. “We think this finding may reflect 2 likely reasons: first, as a group, children with Perinatal Arterial Ischemic Stroke may show greater differences in their responses to this treatment – some benefit much more than others – compared to findings from prior studies on other clinical populations. Identifying which children benefit the most, or the least, will be very important going forward.”

Regarding prognosis, Ramey added, “We think the potential for an infant to recover from an early stroke far exceeds what was once considered a fairly grim prognosis.” She further stated, “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 trial was overseen by a Data Safety and Monitoring Board, and statisticians at the National Data Management Center conducted the analyses. A physician served as an independent medical monitor, and adverse events were documented and managed as needed.

Limitations included site selection based on available resources and interest, which may affect generalizability. Additionally, some enrolled participants were later determined not to have confirmed PAIS, reducing the analytic sample to 167 children.

The authors reported funding from the National Institute of Neurological Disorders and Stroke. As noted in the release, findings presented at scientific meetings are preliminary until published in a peer-reviewed journal.

References

1. American Heart Association. High-dose therapy had lasting benefits for infants with stroke before or soon after birth. American Heart Association. February 6, 2026. Accessed February 6, 2026. https://newsroom.heart.org/news/high-dose-therapy-had-lasting-benefits-for-infants-with-stroke-before-or-soon-after-birth
2. i-Acquire. NIH. 2026. Accessed February 6, 2026. https://www.nihstrokenet.org/trials/i-acquire/home