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Investigators from many fields of medicine and health are using their expertise to help improve the treatment and diagnosis of cerebral palsy. Much of their work is supported through the NINDS, the National Institute of Child Health and Human Development (NICHD), other agencies within the federal government, nonprofit groups such as the United Cerebral Palsy Research and Educational Foundation, and other private institutions.

The ultimate hope for curing cerebral palsy rests with prevention. In order to prevent cerebral palsy, however, scientists have to understand normal fetal brain development so that they can understand what happens when a baby's brain develops abnormally.

Between conception and the birth of a baby, one cell divides to form a handful of cells, and then hundreds, millions, and, eventually, billions of cells. Some of these cells specialize to become brain cells, and then specialize even further into particular types of neurons that travel to their appropriate place in the brain (a process that scientists call neuronal migration). Once they are in the right place, they establish connections with other brain cells. This is how the brain develops and becomes able to communicate with the rest of the body -- through overlapping neural circuits made up of billions of interconnected and interdependent neurons.

Many scientists now think that a significant number of children develop cerebral palsy because of mishaps early in brain development. They are examining how brain cells specialize and form the right connections, and they are looking for ways to prevent the factors that disrupt the normal processes of brain development.

Genetic defects are sometimes responsible for the brain malformations and abnormalities that cause cerebral palsy. Scientists funded by the NINDS are searching for the genes responsible for these abnormalities by collecting DNA samples from people with cerebral palsy and their families and using genetic screening techniques to discover linkages between individual genes and specific types of abnormality primarily those associated with abnormal neuronal migration.

Scientists are scrutinizing events in newborn babies' brains, such as bleeding, epileptic seizures, and breathing and circulation problems, which can cause the abnormal release of chemicals that trigger the kind of damage that causes cerebral palsy. For example, research has shown that bleeding in the brain unleashes dangerously high amounts of a brain chemical called glutamate. Although glutamate is necessary in the brain to help neurons communicate, too much glutamate overexcites and kills neurons. Scientists are now looking closely at glutamate to detect how its release harms brain tissue. By learning how brain chemicals that are normally helpful become dangerously toxic, scientists will have opportunities to develop new drugs to block their harmful effects.

Scientists funded by the NINDS are also investigating whether substances in the brain that protect neurons from damage, called neurotrophins, could be used to prevent brain damage as a result of stroke or oxygen deprivation. Understanding how these neuroprotective substances act would allow scientists to develop synthetic neurotrophins that could be given immediately after injury to prevent neuron death and damage.

The relationship between uterine infections during pregnancy and the risk of cerebral palsy continues to be studied by researchers funded by the NIH. There is evidence that uterine infections trigger inflammation and the production of immune system cells called cytokines, which can pass into an unborn baby's brain and interrupt normal development. By understanding what cytokines do in the fetal brain and the type of damage these immune system cells cause, researchers have the potential to develop medications that could be given to mothers with uterine infections to prevent brain damage in their unborn children.

Approximately 10 percent of newborns are born prematurely, and of those babies, more than 10 percent will have brain injuries that will lead to cerebral palsy and other brain-based disabilities. A particular type of damage to the white matter of the brain, called periventricular leukomalacia (PVL), is the predominant form of brain injury in premature infants. NINDS-sponsored researchers studying PVL are looking for new strategies to prevent this kind of damage by developing safe, nontoxic therapies delivered to at-risk mothers to protect their unborn babies.

Although congenital cerebral palsy is a condition that is present at birth, a year or two can pass before any disabilities are noticed. Researchers have shown that the earlier rehabilitative treatment begins, the better the outcome for children with cerebral palsy. But an early diagnosis is hampered by the lack of diagnostic techniques to identify brain damage or abnormalities in infants.

Research funded by the NINDS is using imaging techniques, devices that measure electrical activity in the brain, and neurobehavioral tests to predict those preterm infants who will develop cerebral palsy. If these screening techniques are successful, doctors will be able to identify infants at risk for cerebral palsy before they are born.

Noninvasive methods to record the brain activity of unborn babies in the womb and to identify those with brain damage or abnormalities would also be a valuable addition to the diagnostic tool kit. Another NINDS-funded study focuses on the development of fetal magnetoencephalography (fMEG) - a technology that would allow doctors to look for abnormalities in fetal brain activity.

Epidemiological studies - studies that look at the distribution and causes of disease among people -- help scientists understand risk factors and outcomes for particular diseases and medical conditions. Researchers have established that preterm birth (when a baby is born before 32 weeks' gestation) is the highest risk factor for cerebral palsy. Consequently, the increasing rate of premature births in the United States puts more babies at risk. A large, long-term study funded by the NIH is following a group of more than 400 mothers and their infants born between 24 and 31 weeks' gestation. They are looking for relationships between preterm birth, maternal uterine infection, fetal exposure to infection, and short-term and long-term health and neurological outcomes. The researchers are hoping to discover environmental or lifestyle factors, or particular characteristics of mothers, which might protect preterm babies from neurological disabilities.

While this research offers hope for preventing cerebral palsy in the future, ongoing research to improve treatment brightens the outlook for those who must face the challenges of cerebral palsy today. An important thrust of such research is the evaluation of treatments already in use so that physicians and parents have valid information to help them choose the best therapy. A good example of this effort is an ongoing NINDS-supported study that promises to yield new information about which patients are most likely to benefit from selective dorsal rhizotomy, a surgical technique that is increasingly being used to reduce spasticity (see Surgery).

Similarly, although physical therapy programs are used almost universally to rehabilitate children with cerebral palsy, there are no definitive studies to indicate which techniques work best. For example, constraint-induced therapy (CIT) is a type of physical therapy that has been used successfully with adult stroke survivors and individuals who have traumatic brain injury and are left with a weak or disabled arm on one side of the body. The therapy involves restraining the stronger arm in a cast and forcing the weaker arm to perform 6 hours of intensive "shaping" activities every day over the course of 3 weeks. The researchers who conducted the clinical trials in adult stroke survivors realized CIT's potential for strengthening children's arms weakened by cerebral palsy.

In a randomized, controlled study of children with cerebral palsy funded by the NIH, researchers put one group of children through conventional physical therapy and another group through 21 consecutive days of CIT. Researchers looked for evidence of improvement in the movement and function of the disabled arm, whether the improvement lasted after the end of treatment, and if it was associated with significant gains in other areas, such as trunk control, mobility, communication, and self-help skills.

Children receiving CIT outperformed the children receiving conventional physical therapy across all measures of success, including how well they could move their arms after therapy and their ability to do new tasks during the study and then at home with their families. Six months later they still had better control of their arm. The results from this study are the first to prove the benefits of a physical therapy. Additional research to determine the optimal length and intensity of CIT will allow doctors to add this therapy to the cerebral palsy treatment toolbox.

Studies have shown that functional electrical stimulation is an effective way to target and strengthen spastic muscles, but the method of delivering the electrical pulses requires expensive, bulky devices implanted by a surgeon, or skin surface stimulation applied by a trained therapist. NINDS-funded researchers have developed a high-tech method that does away with the bulky apparatus and lead wires by using a hypodermic needle to inject microscopic wireless devices into specific muscles or nerves. The devices are powered by a telemetry wand that can direct the number and strength of their pulses by remote control. The device has been used to activate and strengthen muscles in the hand, shoulder, and ankle in people with cerebral palsy as well as in stroke survivors.

As researchers continue to explore new treatments for cerebral palsy and to expand our knowledge of brain development, we can expect significant improvements in the care of children with cerebral palsy and many other disorders that strike in early life.

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