Improvements in Upper Extremity Function Following Intensive Training Are Independent of Corticospinal Tract Organization in Children With Unilateral Spastic Cerebral Palsy: A Clinical Randomized Trial

Kathleen M Friel, Claudio L Ferre, Marina Brandao, Hsing-Ching Kuo, Karen Chin, Ya-Ching Hung, Maxime T Robert, Veronique H Flamand, Ana Smorenburg, Yannick Bleyenheuft, Jason B Carmel, Talita Campos, Andrew M Gordon, Kathleen M Friel, Claudio L Ferre, Marina Brandao, Hsing-Ching Kuo, Karen Chin, Ya-Ching Hung, Maxime T Robert, Veronique H Flamand, Ana Smorenburg, Yannick Bleyenheuft, Jason B Carmel, Talita Campos, Andrew M Gordon

Abstract

Background/Objectives: Intensive training of the more affected upper extremity (UE) has been shown to be effective for children with unilateral spastic cerebral palsy (USCP). Two types of UE training have been particularly successful: Constraint-Induced Movement Therapy (CIMT) and Bimanual training. Reorganization of the corticospinal tract (CST) early during development often occurs in USCP. Prior studies have suggested that children with an ipsilateral CST controlling the affected UE may improve less following CIMT than children with a contralateral CST. We tested the hypothesis that improvements in UE function after intensive training depend on CST laterality. Study Participants and Setting: Eighty-two children with USCP, age 5 years 10 months to 17 years, University laboratory setting. Materials/Methods: Single-pulse transcranial magnetic stimulation (TMS) was used to determine each child's CST connectivity pattern. Children were stratified by age, sex, baseline hand function and CST connectivity pattern, and randomized to receive either CIMT or Bimanual training, each of which were provided in a day-camp setting (90 h). Hand function was tested before, immediately and 6 months after the intervention with the Jebsen-Taylor Test of Hand Function, the Assisting Hand Assessment, the Box and Block Test, and ABILHAND-Kids. The Canadian Occupational Performance Measure was used to track goal achievement and the Pediatric Evaluation of Disability Inventory was used to assess functioning in daily living activities at home. Results: In contrast to our hypothesis, participants had statistically similar improvements for both CIMT and Bimanual training for all measures independent of their CST connectivity pattern (contralateral, ipsilateral, or bilateral) (p < 0.05 in all cases). Conclusions/Significance: The efficacy of CIMT and Bimanual training is independent of CST connectivity pattern. Children with an ipsilateral CST, previously thought to be maladaptive, have the capacity to improve as well as children with a contralateral or bilateral CST following intensive CIMT or Bimanual training. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918890.

Keywords: Hand-Arm Bimanual Intensive Therapy (HABIT); brain reorganization; constraint-induced movement therapy (CIMT); hemiplegia; neuroplasicity; physical rehabilitation; rehabilitation; transcramial magnetic stimulation.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Friel, Ferre, Brandao, Kuo, Chin, Hung, Robert, Flamand, Smorenburg, Bleyenheuft, Carmel, Campos and Gordon.

Figures

Figure 1
Figure 1
CONSORT flow diagram showing progress through the stages of the study, including flow of participants, withdrawals, and inclusion in analyses. A total of 212 individuals were screened by phone or e-mail. Of these 78 children did not meet the study criteria and 28 declined participation. The remaining 106 children potentially met the study criteria and were invited to undergo physical screening. Ten children were excluded and 13 who qualified declined to participate. The remaining 83 children were stratified by age, sex, baseline hand function and CST connectivity pattern, and randomized to receive either CIMT or HABIT. One child in the HABIT group dropped out before starting treatment, and 41 children in each group completed the intended treatments. We were unable to complete TMS or DTI on 3 participants due to exceedingly high thresholds or safety concerns, so only data of the 79 participants with CST determination were included (39 for CIMT, 40 for HABIT).
Figure 2
Figure 2
Raincloud Plot of Changes (Pre-test to Post-test) in AHA by Therapy Group and CST Connectivity. Dots represent raw change scores for individual children (positive scores = improvements). Horizontal colored lines represent mean of CST group. Boxplots represent median and quartiles of therapy group data. Curve represents probability distribution of therapy group data.
Figure 3
Figure 3
Raincloud Plot of Changes (Pre-test to Post-test) in JTTHF by Therapy Group and CST Connectivity (positive scores = improvements).
Figure 4
Figure 4
Plots showing correlations between laterality index and improvement in (A) AHA and (B) JTTHF immediately after the intervention. Note that one JTTHF change value was >3.5 SD from the mean and was excluded from the correlation.

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