Principal Investigator: Marjorie A. Garvey, MD,
National Rehabilitation Hospital, Neuroscience Research Center, Washington, DC

Abstract: A promising new therapy for adults with hemiparesis consequent to stroke, known as Constraint-Induced Movement (CI) therapy, has recently been modified for use in children with cerebral palsy. Children treated with CI therapy show significant gains in motor skills after receiving this intensive and extended treatment. However, little is known about the neurophysiologic mechanisms which mediate the appearance of these novel motor skills.

Functional magnetic resonance imaging (fMRI) and neurophysiologic tests including transcranial magnetic stimulation (TMS) and muscle reflex studies can help determine the brain reorganization that occurs after an injury and the response of the brain to intervention. There is evidence to suggest that, after an acute stroke in adults, the undamaged motor cortex exerts greater control over movements in the affected hand than is normally seen in neurologically intact subjects. While this might seem to be an advantage, combined fMRI and TMS studies demonstrate that it is associated with poor motor recovery in adults after a stroke and worse hand function in patients with cerebral palsy. This suggests that anomalous ipsilateral activation of movements of the affected hand reflects a less efficient cortical reorganization process.

There is controversy about how CI therapy produces an improvement in motor function. Conflicting evidence from fMRI and TMS studies in adult patients with stroke have shown that patients may have either an increase in ipsilateral motor cortical activation or an increase in activation in the damaged hemisphere. The answer to this controversy may be related to the presence of ipsilateral projections. Since ipsilateral projections are associated with worse functional outcome, determining the type of response to CI therapy may give insights into those patients who need more intense therapy.

The specific aim of this application is to determine the underlying brain reorganization that occurs in children with hemiplegic cerebral palsy when they demonstrate an improvement in motor skills after pediatric Constraint-Induced therapy. We hypothesize that the type of reorganization that occurs after CI therapy in patients with hemiplegia is related to the presence or absence of anomalous ipsilateral control of movements in the affected hand by the undamaged motor cortex. Specifically, we expect that after CI therapy patients with anomalous ipsilateral motor control of the affected hand will show an increase in activation in the undamaged hemisphere, while those who do not have anomalous ipsilateral motor control of the affected hand will show an increase in activation in the damaged hemisphere.

We will test this hypothesis by assessing motor cortex activation before and after CI therapy using fMRI and neurophysiologic tests including TMS and muscle reflex studies in children with hemiplegic cerebral palsy with and without evidence for ipsilateral projections. We will then examine the relationship between the presence of anomalous ipsilateral motor control and cortical reorganization following CI therapy. Understanding this relationship is essential for planning large randomized controlled trials. Since anomalous ipsilateral cortical reorganization reflects an inefficient cortical reorganization process, treatment outcome of CI therapy may also be worse in this group. In this case, children may need to be stratified according to types of brain reorganization.