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Clinical Trial
. 2025 Mar 1;82(3):267-275.
doi: 10.1001/jamaneurol.2024.4898.

Neuromodulation for Children With Hemiparesis and Perinatal Stroke: A Randomized Clinical Trial

Alicia J Hilderley  1   2 , Mary Dunbar  1   2 , John Andersen  3   4 , Darcy Fehlings  5   6 , Megan Metzler  7 , Helen L Carlson  1   2 , Ephrem Zewdie  1   2 , Jacquie Hodge  1 , Kathleen O'Grady  4 , Lisa Carsolio  8 , Nomazulu Dlamini  9   10 , Adrianna Giuffre  1   2 , Lauran Cole  1 , Hsing-Ching Kuo  1 , Anna Bourgeois  1 , Asha Hollis  1 , Meghan Maiani  1 , Patrick Ciechanski  1 , Zeanna Jadavji  1 , Brandon Craig  1 , Dion Kelly  1 , Joanna Keough  1 , James Wrightson  1 , Linda Fay  11 , Lauren Switzer  5 , Maya Pajevic  1 , Alana Ramsey  1 , Michael Sametz  1 , Brian L Brooks  2   12   13   14 , Maryna Yaskina  15 , Jesse Batara  15 , Michael D Hill  1   12 , Adam Kirton  1   2   12   13
Affiliations
Clinical Trial

Neuromodulation for Children With Hemiparesis and Perinatal Stroke: A Randomized Clinical Trial

Alicia J Hilderley et al. JAMA Neurol. .

Erratum in

  • Error in Author Name.
    [No authors listed] [No authors listed] JAMA Neurol. 2025 May 1;82(5):529. doi: 10.1001/jamaneurol.2025.0539. JAMA Neurol. 2025. PMID: 40094694 Free PMC article. No abstract available.

Abstract

Importance: Current upper-extremity therapies provide inconsistent outcomes for children with unilateral cerebral palsy. Noninvasive brain stimulation, specifically transcranial direct current stimulation, may enhance motor gains when combined with therapy.

Objective: To determine whether the addition of neurostimulation to upper-extremity therapy enhances motor function in children with perinatal stroke and unilateral cerebral palsy.

Design, setting, and participants: This multicenter, randomized, sham-controlled phase 3 trial was conducted from July 2017 through March 2023. Investigators, treating therapists, outcome assessors, parents, and participants were blinded to intervention allocation. The study took place at 3 tertiary care Canadian pediatric rehabilitation hospitals. From a population-based sample of children 6 to 18 years old with perinatal stroke and disabling unilateral cerebral palsy, 196 children were approached and 107 were excluded.

Intervention: Participants were randomly assigned in permuted blocks of 2 (1:1) to receive daily sham or cathodal stimulation to the contralesional motor cortex during 10 days of high-dose, child-centered intensive upper-extremity therapy.

Main outcomes and measures: The primary end points were changes from baseline to 6 months posttherapy in affected hand function and attainment of child-identified functional goals assessed by the Assisting Hand Assessment and Canadian Occupational Performance Measure. Safety was assessed, including any decrease in the function of either hand. Analysis was intention to treat.

Results: Eighty-nine children were enrolled with 45 randomized to sham (62% male, 38% female; mean [SD] age, 10.7 [2.8] years) and 44 to stimulation (52% male, 48% female; mean [SD] age, 10.7 [2.1] years). Eighty-three participants had complete outcome data (42 sham, 41 stimulation). High proportions of children in both groups demonstrated significant functional gains sustained at 6 months (P < .001) with large effect size (Cohen d > 1). There were no differences between groups for mean (SD) change in hand function (5.2 [5.3] vs 4.6 [5.7]; P = .63) or goal attainment (3.0 [2.0] vs 3.6 [2.3]; P = .25). Procedures were safe and well tolerated with no serious adverse events.

Conclusions and relevance: In this study, results showed that patient-centered intensive motor learning programs could produce marked and sustained improvements in upper-extremity function in children with perinatal stroke and unilateral cerebral palsy. The addition of 1 milliampere contralesional motor cortex transcranial direct current stimulation did not improve outcomes compared with sham stimulation.

Trial registration: ClinicalTrials.gov Identifier: NCT03216837.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Andersen reported grants from Alberta Innovates, Canadian Institutes of Health Research CHILD-BRIGHT SPORT Network, Glenrose Rehabilitation Hospital Foundation, and the Women and Children’s Health Research Institute during the conduct of the study. Dr Fehlings reported grants from CHILD-BRIGHT during the conduct of the study. Dr O’Grady reported grants from Glenrose Hospital Foundation and the CHILD-BRIGHT Network during the conduct of the study. Dr Kelly reported grants from the Canadian Institutes for Health Research during the conduct of the study. Dr Fay reported grants from CHILD-BRIGHT during the conduct of the study. Dr Switzer reported grants from CHILD-BRIGHT during the conduct of the study. Dr Brooks reported royalties from the Psychological Assessment Resources and Oxford University Press during the conduct of the study and fees from Brooks Assessment Private Practice outside the submitted work. Dr Hill reported grants from Medtronic, Boehringer Ingelheim, and the Canadian Institutes of Health Research to the University of Calgary outside the submitted work; and reported being president of the Canadian Neurological Sciences Federation (not-for-profit sector). Dr Kirton reported grants from the Canadian Institutes of Health Research during the conduct of the study and reported being a cofounder and minority shareholder of Possibility Neurotechnologies, a prerevenue tech start-up, unrelated to this trial, outside the submitted work. No other disclosures were reported.

References

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