Combining constraint-induced movement therapy and action-observation training in children with unilateral cerebral palsy: a randomized controlled trial

Cristina Simon-Martinez, Lisa Mailleux, Els Ortibus, Anna Fehrenbach, Giuseppina Sgandurra, Giovanni Cioni, Kaat Desloovere, Nicole Wenderoth, Philippe Demaerel, Stefan Sunaert, Guy Molenaers, Hilde Feys, Katrijn Klingels, Cristina Simon-Martinez, Lisa Mailleux, Els Ortibus, Anna Fehrenbach, Giuseppina Sgandurra, Giovanni Cioni, Kaat Desloovere, Nicole Wenderoth, Philippe Demaerel, Stefan Sunaert, Guy Molenaers, Hilde Feys, Katrijn Klingels

Abstract

Background: Upper limb (UL) deficits in children with unilateral cerebral palsy (uCP) have traditionally been targeted with motor execution treatment models, such as modified Constraint-Induced Movement Therapy (mCIMT). However, new approaches based on a neurophysiological model such as Action-Observation Training (AOT) may provide new opportunities for enhanced motor learning. The aim of this study is to describe a randomised controlled trial (RCT) protocol investigating the effects of an intensive treatment model, combining mCIMT and AOT compared to mCIMT alone on UL function in children with uCP. Additionally, the role of neurological factors as potential biomarkers of treatment response will be analysed.

Methods: An evaluator-blinded RCT will be conducted in 42 children aged between 6 and 12 years. Before randomization, children will be stratified according to their House Functional Classification Scale, age and type of corticospinal tract wiring. A 2-week day-camp will be set up in which children receive intensive mCIMT therapy for 6 hours a day on 9 out of 11 consecutive days (54 h) including AOT or control condition (15 h). During AOT, these children watch video sequences showing goal-directed actions and subsequently execute the observed actions with the more impaired UL. The control group performs the same actions after watching computer games without human motion. The primary outcome measure will be the Assisting Hand Assessment. Secondary outcomes comprise clinical assessments across body function, activity and participation level of the International Classification of Function, Disability and Health. Furthermore, to quantitatively evaluate UL movement patterns, a three-dimensional motion analysis will be conducted. UL function will be assessed at baseline, immediately before and after intervention and at 6 months follow up. Brain imaging comprising structural and functional connectivity measures as well as Transcranial Magnetic Stimulation (TMS) to evaluate corticospinal tract wiring will be acquired before the intervention.

Discussion: This paper describes the methodology of an RCT with two main objectives: (1) to evaluate the added value of AOT to mCIMT on UL outcome in children with uCP and (2) to investigate the role of neurological factors as potential biomarkers of treatment response.

Trial registration: NCT03256357 registered on 21st August 2017 (retrospectively registered).

Keywords: Brain injuries; Intensive therapy; Neuroimaging; Treatment outcome; Unilateral cerebral palsy; Upper extremity.

Conflict of interest statement

Author’s information

Cristina Simon-Martinez is a physiotherapist and is currently doing her PhD in the Neuromotor Rehabilitation Research Group at the KU Leuven.

Lisa Mailleux is MSc in Physiotherapy and is currently doing her PhD in the Neuromotor Rehabilitation Research Group at the KU Leuven.

Els Ortibus works as a neuropediatrician and the Director of the Centre for Developmental Disorders at the University Hospitals Leuven. She is also Assistant Professor in the Department of Development and Regeneration at the KU Leuven.

Anna Fehrenbach is MSc in Physiotherapy specialized in paediatric rehabilitation.

Giuseppina Sgandurra is a child neurologist and psychiatrist and holds a PhD on new strategies on biomedical research. Currently, she is a university researcher at the University of Pisa and at the IRCCS Fondazione Stella Maris.

Giovanni Cioni is Full Professor of Child Neurology and Psychiatry, University of Pisa and Scientific Director of IRCCS Fondazione Stella Maris.

Kaat Desloovere is Full Professor at the Department of Rehabilitation Sciences at the KU Leuven and Head of the Clinical Motion Analysis Laboratory at the University Hospitals Leuven.

Nicole Wenderoth is Full Professor of Neural Control of Movement in the Department of Health Sciences and Technology at ETH Zurich.

Philippe Demaerel is Full Professor in the Department of Imaging and Pathology at the KU Leuven and a radiologist at the Department of Radiology of the University Hospitals Leuven.

Stefan Sunaert is Professor in the Department of Imaging and Pathology at the KU Leuven and a radiologist at the Department of Radiology of the University Hospitals Leuven.

Guy Molenaers is an orthopaedic surgeon at the University Hospitals Leuven and Professor in the Department of Development and Regeneration at the KU Leuven.

Hilde Feys is Full Professor of Rehabilitation Sciences and Physiotherapy and Head of the Department of Rehabilitation Sciences at the KU Leuven.

Katrijn Klingels is Professor of Rehabilitation Sciences and Physiotherapy at the University of Hasselt and postdoctoral researcher in the Department of Rehabilitation Sciences at the KU Leuven.

Ethics approval and consent to participate

Ethical approval was obtained by the Ethical Committee of the University Hospitals Leuven (S56513). Before entering the study, written informed consent from all parents or care givers and verbal assent from all the participants will be obtained. Through the insurance taken by the University of Leuven, the children are insured for possible injuries as a result of their participation in the experimental measurements.

If any important modifications of the protocol are required, both the Ethical Committee of the University Hospitals Leuven and the trial registries will be informed. An annual progress report is submitted to the Ethical Committee of the University Hospitals Leuven, where the progression of the experiments, the protocol violations, and a list of serious adverse events are documented. This document can be found in this link:

https://www.uzleuven.be/sites/default/files/ethische-commissie/Annual%20progress%20report.docx

Consent for publication

Not applicable.

Competing interests

The authors declare they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig 1
Fig 1
Flow-chart of the described RCT following the CONSORT guidelines. Abbreviations: uCP, unilateral cerebral palsy; CST, corticospinal tract; mCIMT, modified constraint-induced movement therapy; AOT, Action-Observation Training

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