Early Childhood Constraint Therapy in Cerebral Palsy

Cerebral palsy (CP) is the most common physical disability in childhood.1 It affects 3.6/100
children in the US2 with ~10,000 new diagnoses every year. The prevalence of CP in developing
countries is estimated to be ~5-10 times greater. CP is a disorder resulting from sensory and
motor impairments due to perinatal brain injury, with lifetime consequences that range from
poor adaptive and social function to communication and emotional disturbances,9 all
contributing to a shortened life expectancy. The societal costs are difficult to estimate but
the financial burden is well over $1 M per life affected. A growing number of evidence-based
therapies aim to improve gross motor function through changes in body structures and function
in children with CP (e.g. hip surveillance, surgery). However, infants with CP have a
fundamental disadvantage in recovering motor function: they do not receive accurate sensory
feedback from their movements, leading to neglect of an affected extremity and difficulty
learning new movements, a process called developmental disregard (DD). As a consequence, even
children who receive time- and resource-intensive standard therapies have stable or declining
motor function and developmental trajectories that do not "catch up" to those of typically
developing children. DD can then lead to school-age learning problems, decreased
participation in physical and social activities and costly long-term mental and physical
morbidities.

Constraint-Induced Movement Therapy (CIMT) is one of the few effective neurorehabilitative
strategies shown to improve upper extremity motor function in adults and older children with
CP, potentially overcoming developmental disregard. It is mainly applicable to CP patients
who are diagnosed with asymmetric or hemiparetic forms of the disorder, in which one side of
the body is more affected than the other. CIMT is based on the premise that preferential use
of an affected upper extremity (by constraining the less affected one), and shaping with
repetition of movement by skilled therapists, can overcome neglect and restore function of
that extremity.

The investigators are conducting a randomized trial of CIMT in children with CP using a
wait-list control group. This design allows every child with CP to eventually receive the
treatment and avoids issues of equipoise. The RCT portion of the study extends only for a
7-month period, from baseline to 6 months after the 1-month CIMT ends. For CP wait-listed
controls, the study continues for 6 months following the CMIT intervention, separate from the
completed RCT. We will reference data from both groups to a cohort of typically developing
(TD) children to determine developmental trajectories.

Inclusion Criteria:

- CP children (n=72): Inclusion criteria will be diagnosis of hemiparetic or asymmetric
CP as determined by published algorithms and neurologic exam.

- TD children (n=144): Inclusion criteria will be GA and sex-matched compared to the CP
group, with CA at assessment matched to the CP group at baseline (72 children) and at
the 7-month assessment (72 children). Exclusion criteria will be any motor or sensory
impairment as defined by neurologic exam and/or scaled motor scores below 8 for CA on
the Bayley III and cognitive impairment or delays as described for the CP group.

Exclusion Criteria:

- CP children: exclusion criteria will be CP with Gross Motor Function Classification
Score (GMFCS) of 4-5, corresponding to poor or absent mobility and neck control;
receipt of Botox to the affected extremity within 3 months of study entry; or scores
of <70 on the Bayley Scales of Infant Development (Bayley III) cognitive composite.

- TD children: Exclusion criteria will be any motor or sensory impairment as defined by
neurologic exam and/or scaled motor scores below 8 for CA on the Bayley III and
cognitive impairment or delays as described for the CP group.