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What
Research is Being Done (from
National Institute of Neurological Disorders
& Stroke)
Investigators
from many arenas of medicine and health
are using their expertise to help improve
treatment and prevention of cerebral palsy.
Much of their work is supported through
the National Institute of Neurological
Disorders and Stroke (NINDS), the National
Institute of Child Health and Human Development,
other agencies within the Federal Government,
nonprofit groups such as the United Cerebral
Palsy Research Foundation, and private
institutions.
The
ultimate hope for overcoming cerebral
palsy lies with prevention. In order to
prevent cerebral palsy, however, scientists
must first understand the complex process
of normal brain development and what can
make this process go awry.
Between
early pregnancy and the first months of
life, one cell divides to form first a
handful of cells, and then hundreds, millions,
and, eventually, billions of cells. Some
of these cells specialize to become brain
cells. These brain cells specialize into
different types and migrate to their appropriate
site in the brain. They send out branches
to form crucial connections with other
brain cells. Ultimately, the most complex
entity known to us is created: a human
brain with its billions of interconnected
neurons.
Mounting
evidence is pointing investigators toward
this intricate process in the womb for
clues about cerebral palsy. For example,
a group of researchers has recently observed
that more than one-third of children who
have cerebral palsy also have missing
enamel on certain teeth. This tooth defect
can be traced to problems in the early
months of fetal development, suggesting
that a disruption at this period in development
might be linked both to this tooth defect
and to cerebral palsy.
As
a result of this and other research, many
scientists now believe that a significant
number of children develop cerebral palsy
because of mishaps early in brain development.
They are examining how brain cells specialize,
how they know where to migrate, how they
form the right connections -- and they
are looking for preventable factors that
can disrupt this process before or after
birth.
Scientists
are also scrutinizing other events --
such as bleeding in the brain, seizures,
and breathing and circulation problems
-- that threaten the brain of the newborn
baby. Through this research, they hope
to learn how these hazards can damage
the newborn's brain and to develop new
methods for prevention.
Some
newborn infants, for example, have life-threatening
problems with breathing and blood circulation.
A recently introduced treatment to help
these infants is extra corporeal membrane
oxygenation, in which blood is routed
from the patient to a special machine
that takes over the lungs' task of removing
carbon dioxide and adding oxygen. Although
this technique can dramatically help many
such infants, some scientists have observed
that a substantial fraction of treated
children later experience long-term neurological
problems, including developmental delay
and cerebral palsy. Investigators are
studying infants through pregnancy, delivery,
birth, and infancy, and are tracking those
who undergo this treatment. By observing
them at all stages of development, scientists
can learn whether their problems developed
before birth, result from the same breathing
problems that made them candidates for
the treatment, or spring from errors in
the treatment itself. Once this is determined,
they may be able to correct any existing
problems or develop new treatment methods
to prevent brain damage.
Other
scientists are exploring how brain insults
like hypoxic-ischemic encephalopathy (brain
damage from a shortage of oxygen or blood
flow), bleeding in the brain, and seizures
can cause the abnormal release of brain
chemicals and trigger brain damage. For
example, research has shown that bleeding
in the brain unleashes dangerously high
amounts of a brain chemical called glutamate.
While glutamate is normally used in the
brain for communication, too much glutamate
over stimulates the brain's cells and causes
a cycle of destruction. Scientists are
now looking closely at glutamate to detect
how its release harms brain tissue and
spreads the damage from stroke. By learning
how such brain chemicals that normally
help us function can hurt the brain, scientists
may be equipped to develop new drugs that
block their harmful effects.
In
related research, some investigators are
already conducting studies to learn if
certain drugs can help prevent neonatal
stroke. Several of these drugs seem promising
because they appear to reduce the excess
production of potentially dangerous chemicals
in the brain and may help control brain
blood flow and volume. Earlier research
has linked sudden changes in blood flow
and volume to stroke in the newborn.
Low
birth weight itself is also the subject
of extensive research. In spite of improvements
in health care for some pregnant women,
the incidence of low birth-weight babies
born each year in the United States remains
at about 7 1/2 percent. Some scientists
currently investigating this serious health
problem are working to understand how
infections, hormonal problems, and genetic
factors may increase a woman's chances
of giving birth prematurely. They are
also conducting more applied research
that could yield: 1) new drugs that can
safely delay labor, 2) new devices to
further improve medical care for premature
infants, and 3) new insight into how smoking
and alcohol consumption can disrupt fetal
development.
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 the
information they need to 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 root rhizotomy,
a recently introduced surgery that is
becoming increasingly in demand for reduction
of spasticity.
Similarly,
although physical therapy programs are
a popular and widespread approach to managing
cerebral palsy, little scientific evidence
exists to help physicians, other health
professionals, and parents determine how
well physical therapy works or to choose
the best approach among many. Current
research on cerebral palsy aims to provide
this information through careful studies
that compare the abilities of children
who have had physical and other therapy
with those who have not.
As
part of this effort, scientists are working
to create new measures to judge the effectiveness
of treatment, as in ongoing research to
precisely identify the specific brain
areas responsible for movement may yield
one such approach. Using magnetic pulses,
researchers can locate brain areas that
control specific actions, such as raising
an arm or lifting a leg, and construct
detailed maps. By comparing charts made
before and after therapy among children
who have cerebral palsy, researchers may
gain new insights into how therapy affects
the brain's organization and new data
about its effectiveness.
Investigators
are also working to develop new drugs
-- and new ways of using existing drugs
-- to help relieve cerebral palsy's symptoms.
In one such set of studies, early research
results suggest that doctors may improve
the effectiveness of the anti-spasticity
drug called baclofen by giving the drug
through spinal injections, rather than
by mouth. In addition, scientists are
also exploring the use of tiny implanted
pumps that deliver a constant supply of
anti-spasticity drugs into the fluid around
the spinal cord, in the hope of improving
these drugs' effectiveness and reducing
side effects, such as drowsiness.
Other
experimental drug development efforts
are exploring the use of minute amounts
of the familiar toxin called botulinum.
Ingested in large amounts, this toxin
is responsible for botulism poisoning,
in which the body's muscles become paralyzed.
Injected in tiny amounts, however, this
toxin has shown early promise in reducing
spasticity in specific muscles.
A
large research effort is also directed
at producing more effective, nontoxic
drugs to control seizures. Through its
Anti epileptic Drug Development Program,
the NINDS screens new compounds developed
by industrial and university laboratories
around the world for toxicity and anticonvulsant
activity and coordinates clinical studies
of efficacy and safety. To date, this
program has screened more than 13,000
compounds and, as a result, five new antiepileptic
drugs -- carbamazepine, clonazepam, valproate,
clorazepate, and felbamate -- have been
approved for marketing. A new project
within the program is exploring how the
structure of a given anti seizure medication
relates to its effectiveness. If successful,
this project may enable scientists to
design better anti seizure medications
more quickly and cheaply.
As
researchers continue to explore new treatments
for cerebral palsy and to expand our knowledge
of brain development, we can expect significant
medical advances to prevent cerebral palsy
and many other disorders that strike in
early life.
RESEARCH
UPDATE: June 2000
Magnesium sulfate and decreased risk of cerebral palsy
Research
conducted and supported by the National
Institute of Neurological Disorders and
Stroke (NINDS) continuously seeks to uncover
new clues about cerebral palsy (CP). Investigators
from the NINDS and the California Birth
Defects Monitoring Program (CBDMP) presented
data suggesting that very low birth weight
babies have a decreased incidence of CP
when their mothers are treated with magnesium
sulfate soon before giving birth. The
results of this study, which were based
on observations of a group of children
born in four Northern California counties,
were published in the February 1995 issue
of Pediatrics.*
Low
birth weight babies are 100 times more
likely to develop CP than normal birth weight
infants. If further research confirms
the study's findings, use of magnesium
sulfate may prevent 25 percent of the
cases of CP in the approximately 52,000
low birth weight babies born each year
in the United States.
Magnesium
is a natural compound that is responsible
for numerous chemical processes within
the body and brain. Obstetricians in the
United States often administer magnesium
sulfate, an inexpensive form of the compound,
to pregnant women to prevent pre term labor
and high blood pressure brought on by
pregnancy. The drug, administered intravenously
in the hospital, is considered safe when
given under medical supervision.
Scientists
speculate that magnesium may play a role
in brain development and possibly prevent
bleeding inside the brains of pre term
infants. Previous research has shown that
magnesium may protect against brain bleeding
in very premature infants. Animal studies
have demonstrated that magnesium given
after a traumatic brain injury can reduce
the severity of brain damage.
Despite
these encouraging research findings, pregnant
women should not change their magnesium
intake because the effects of high doses
have not yet been studied and the possible
risks and benefits are not known.
Researchers
caution that more research will be required
to establish a definitive relationship
between the drug and prevention of the
disorder. Clinical trials now underway,
one of them a collaboration between the
NINDS and the National Institute of Child
Health and Human Development, are evaluating
magnesium for the prevention of cerebral
palsy in prematurely born babies. top
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