Brain Reorganization Following Constraint-Induced Therapy in Children With Cerebral Palsy
Condition: Cerebral Palsy
MeSH terms: Cerebral Palsy
Study type: Observational

Summary: 
      This study will examine how therapy changes the way the brain controls movements in children
      with cerebral palsy. Normally, one side of the brain controls movements in the opposite side
      of the body. In cerebral palsy, however, this pattern may be different, with one side of the
      brain controlling movements on the same side of the body. This study will use magnetic
      resonance imaging (MRI) and transcranial magnetic stimulation (TMS) to study brain function
      in children with cerebral palsy before and after therapy.

      Children between 9 and 17 years of age with spastic hemiplegia type cerebral palsy will be
      recruited for this study from the National Rehabilitation Hospital and Georgetown University
      Center Medical Center in Washington, D.C., and the Sparks Center at UAB in Alabama. In
      addition, five healthy control children will be recruited from community groups, such as Cub
      Scouts, Brownies, and schools. Candidates are screened with a review of medical records and
      neurological and physical examinations.

      Healthy controls undergo MRI (described below) twice, 3 weeks apart. Children with cerebral
      palsy undergo the following tests and procedures:

        1. Rehabilitation evaluation at the NIH Clinical Center Rehabilitation Medicine Department.

        2. MRI: For this test, the child lies on a table that slides in and out of the MRI
           scanner-a metal cylinder surrounded by a strong magnetic field. He or she wears earplugs
           to muffle loud knocking sounds that occur during scanning. Images are obtained while the
           child performs simple finger tapping movements.

        3. Movement Testing:

             1. Finger tapping: The child taps buttons on a box hooked up to a computer

             2. Muscle reflex measurements: One method uses a small motor that makes the child's
                fingers move with sudden, small movements; a second method uses small shocks to the
                finger or wrist. The shocks feel like a buzz; most are gentle, but some might feel
                stronger.

        4. TMS: This procedure maps brain function. A wire coil is held on the scalp, and a brief
           electrical current is passed through the coil, creating a magnetic pulse that stimulates
           the brain. During the stimulation, the child may be asked to perform simple movements..
           The stimulation may cause a twitch in muscles of the face, arm, or leg, and the child
           may hear a click and feel a pulling sensation on the skin under the coil.

        5. Therapy: After these tests, children are randomly selected to receive either standard
           therapy (neurodevelopmental treatment) or constraint-induced therapy, as follows:

             1. Neurodevelopmental therapy uses principles of movement science to enhance the
                child's capacity to function. The child receives therapy a few times a week for 3
                weeks.

             2. Constraint-induced therapy uses a combination of motor learning method and
                constraint to teach the new motor skills in the child's affected hand. Children
                treated with this therapy must live near a special treatment center in Alabama for
                the 3 weeks of treatment. The child's good arm is constrained with a bivalve,
                removable cast. The cast is placed before therapy starts and remains in place
                except when the therapist removes it once a day to examine the good arm. With the
                cast on, children are encouraged to use their affected hand in new ways. The
                therapist then uses the motor learning method, building motor programs as a result
                of practice, to teach them new skills. Motor learning therapy is 6 hours a day.

        6. Post-treatment testing: After treatment, children undergo repeat rehabilitation
           assessment, MRI, TMS, and movement testing.
    

Detailed description: 
      Objective: To determine the underlying brain reorganization that occurs in children with
      hemiplegic cerebral palsy before and after pediatric Constraint-Induced therapy.

      Background: 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 with cerebral palsy treated with CI therapy show significant
      gains in motor skills after receiving this intensive and extended treatment.

      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 functional
      magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) studies
      demonstrate that it is associated with poor motor recovery in adults after a stroke and
      impaired hand function in patients with cerebral palsy. Thus, anomalous motor control of the
      affected hand by the unaffected cortex may reflect 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.

      Subject Population: Children with hemiplegic subtype of cerebral palsy; age-matched children
      with no neurological abnormalities

      Design: We will assess 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.

      Outcome measures: Patients will be stratified by the presence of mirror movements. Primary
      outcome measure will be laterality index on cortical activation of the fMRI before and after
      CI therapy. Secondary outcome measures will be standardized measures of sensory and motor
      function. We will examine the relationship between the presence of anomalous ipsilateral
      motor control and cortical reorganization following CI therapy.

      Significance: 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, future studies may need to stratify children on study
      entry according to types of brain reorganization.
    

Keywords: Rehabilitation; Forced Use; Hemiplegia; Magnetic Resonance Imaging; TMS; Cerebral Palsy; Spastic Hemiplegia; Healthy Volunteer; HV