Cerebral palsy (CP) is the most common pediatric movement disorder, affecting 3.6/1000 children in the US, with 11,000 new diagnoses every year. Motor and sensory dysfunction in CP often worsen over time, leading to costly lifelong physical, social and emotional disabilities. However, interventions that take advantage of activity-dependent brain plasticity can result in lasting improvements of movement execution and extremity use that optimize motor and social function into adulthood. Among the greatest challenges in the rehabilitation of children with CP is overcoming developmental disregard (DD). This form of neglect starts in infancy impairs the ability to infer new and effective movements and contributes to neurodevelopmental trajectories that rarely equal those of typically developing children. The sooner a therapy can overcome DD, the greater its impact on later neurodevelopment, especially if it can start before 3 years old, when neural plasticity is greatest Constraint-induced movement therapy (CIMT), well-studied in adults, improves upper extremity function through forced-use and sensory exposure of a neglected extremity. The short-term objective of this proposal is to show that CIMT at or before 2 years old can improve upper extremity sensory and motor function and thereby mitigate DD. To accomplish this, the study uses a randomized controlled trial (RCT) design with a wait- list control, in children 12-24 months with asymmetric CP. The CIMT intervention includes 1 month of soft constraint wear on the less affected arm (1/2 day sessions, electronically-monitored) combined with a validated parent-implemented home-based program of reach training and sensory exposures for the more affected extremity, in addition to routine therapy sessions (current standard CP treatment). Children with CP will be assessed at baseline, and at 1 and 7 months. Children assigned to the control group will receive CIMT after the RCT is finished and be assessed again. Typically developing (TD) age-matched children will also be tested. The RCT phase of the trial will demonstrate that CIMT improves the sensory and motor function of an affected upper extremity. The comparison of TD children and CP children before treatment will answer mechanistic questions about how the relationship between sensory and motor function contributes to impairments. Finally, referencing all CP children to TD children will provide new information on how the severity of CP and the timing of CIMT may change the neurodevelopmental trajectories of treated children. This will inform the evidence-based design of future trials of rehabilitation n developing children with disabilities. Importantly, the CIMT intervention itself does not involve extensive material and intellectual resources and focuses instead on implementing a carefully monitored home-based program, allowing an application to settings with limited access to resources. The overarching goals of this proposal are therefore to address gaps in the continuum of translational research in the field of pediatric cerebral palsy in order to increase the clinical and societal relevance of this type of rehabilitation research.

Public Health Relevance

Cerebral palsy (CP) is the most common pediatric movement disorder in the US, affecting more than 3 of every 1000 children, and is even more common in the developing world. The current proposal uses rigorous scientific methods to test an inexpensive rehabilitative strategy for CP (constraint-induced movement therapy), easily adapted to settings with limited resources. The study focuses on helping very young children who can benefit most from this intervention and on providing essential information about the mechanisms of disability in CP to help plan future therapeutic studies.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD081120-04
Application #
9502297
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Marden, Susan F
Project Start
2015-08-21
Project End
2020-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
147212963
City
Columbus
State
OH
Country
United States
Zip Code
43205
Chorna, Olena D; Guzzetta, Andrea; Maitre, Nathalie L (2017) Vision Assessments and Interventions for Infants 0-2 Years at High Risk for Cerebral Palsy: A Systematic Review. Pediatr Neurol 76:3-13
Maitre, Nathalie L; Key, Alexandra P; Chorna, Olena D et al. (2017) The Dual Nature of Early-Life Experience on Somatosensory Processing in the Human Infant Brain. Curr Biol 27:1048-1054
Benninger, Kristen L; Ruess, Lynne; Slaughter, Laurel A et al. (2017) Neonatal Vein of Labbé Infarction Size is Associated With Long-Term Language Outcomes. Pediatr Neurol 72:70-75.e1
Maitre, Nathalie L; Stark, Ann R; McCoy Menser, Carrie C et al. (2017) Cry presence and amplitude do not reflect cortical processing of painful stimuli in newborns with distinct responses to touch or cold. Arch Dis Child Fetal Neonatal Ed 102:F428-F433
Maitre, Nathalie L; Williams, John V (2016) Human metapneumovirus in the preterm neonate: current perspectives. Res Rep Neonatol 6:41-49
Maitre, Nathalie L; Chorna, Olena; Romeo, Domenico M et al. (2016) Implementation of the Hammersmith Infant Neurological Examination in a High-Risk Infant Follow-Up Program. Pediatr Neurol 65:31-38
Chorna, Olena; Heathcock, Jill; Key, Alexandra et al. (2015) Early childhood constraint therapy for sensory/motor impairment in cerebral palsy: a randomised clinical trial protocol. BMJ Open 5:e010212