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
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
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
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.
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
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.
- INCLUSION CRITERIA:
1. Children 9 to 17 years of age.
Cerebral palsy patients:
2. Children previously diagnosed with spastic hemiplegia subtype of cerebral palsy
3. Children with non-progressive cerebral lesions acquired pre-, peri- or
post-natally, before 1 year of age.
Typically Developing subjects:
1. Scores below 60 on Connor's attention deficit/hyperactivity disorder (ADHD)
2. Normal neurological history and examination
1. Any child who is pregnant
2. Patients with Development Quotient (DQ) or Intelligence Quotient (IQ) below 50 on
Cerebral palsy patients:
3. Children with subtypes of cerebral palsy that are not hemiplegia.
4. Children with uncontrolled seizures within the last 6 months
5. Children with progressive or neurodegenerative disorders; underlying known genetic or
chromosomal disorders, familial or non-familial syndromes (without known chromosomal
or genetic defect)
6. Patients with cerebral lesions caused by sickle cell disease or by emboli associated
with congenital cardiac lesions
7. Patients incapable of voluntary movement or with severe cognitive deficits who cannot
follow simple verbal commands
Typically Developing Children:
1. Children with chronic medical disorders or any neurological and /or psychiatric
disorder including attention deficit hyperactivity disorder or learning disorder
2. Children taking regular medications, including medications for allergies, hormonal
oral contraceptives, or over-the-counter medications
3. Children born before 36 weeks gestation as estimated by dates, ultrasound or other
methods (if a discrepancy exists, then the ultrasound estimation will be taken as
Exclusionary criteria for clinical MRI studies:
1. Any child with metal objects in the body such as pacemakers, aneurysm clips (metal
clips on the wall of a large artery), metallic prostheses, cochlear implants, or
2. Any child with permanent tattoos on the eyelids (ferromagnetic iron oxide-based)
tattoo pigments can interact with the static magnetic field of an MRI imager.
Exclusionary criteria for TMS:
1. Children with hearing loss (greater than 15 dB at any individual frequency) in either
ear (as evaluated in the Audiology Department, CC, NIH).