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Topiramate "may prevent" brain injury and seizures in newborns

17 June, 2004

The anti-epileptic drug topiramate may help prevent brain injury and seizures in newborn babies, according to a new study.

The report from the Children's Hospital Boston
suggests that topiramate may protect newborns from brain injury and
long-term neurological problems caused by excitotoxicity
(over-activation of neurons). The researchers hope these findings may
provide the basis for a treatment that could be given to babies
immediately after traumatic birth events that compromise the brain's
blood and oxygen supply. Such events can cause long-term neurological
problems that underlie serious conditions like cerebral palsy and
epilepsy. Premature babies, who are surviving in greater numbers, are
especially vulnerable to excitotoxicity.

When
the brain's blood and oxygen supply are compromised, a condition known
as hypoxia-ischemia occurs and the chemical glutamate accumulates in
brain tissues which can lead to excitotoxicity causing brain cells to
die. The study's authors found that the neurons of premature infants
and other newborns have more glutamate receptors than the adult brain,
making them very vulnerable to excitotoxic brain injury.

Published in journal Epilepsia,
the study found that topiramate may be useful in preventing epilepsy by
blocking glutamate receptors. This can dampen the harmful effects of
excitotoxicity in the brain of the newborn.

Dr Frances Jensen and her team investigated a condition called hypoxic
encephalopathy, the most common cause of seizures in newborns. Infants
with neonatal seizures due to hypoxia-ischemia can develop epilepsy and
Dr Jensen noted that currently there is no effective treatment for
these newborns to prevent brain injury and long-term brain
abnormalities.

Earlier
studies with animals have suggested that seizures in the immature brain
can cause permanent changes making the brain more prone to seizures.
Studies of rats treated with topiramate prior to perinatal
hypoxia-induced seizures indeed were less susceptible to seizures later
in life. More significantly, topiramate given for 48 hours after
hypoxia-induced seizures also reduced susceptibility to seizure-induced
damage later in life.

Dr Jensen said:

"In
human babies, pretreatment is not always clinically practical, so
post-seizure treatment would represent a therapeutic advance.
Appropriate intervention after early-life seizures may prevent the
development of epilepsy and neurocognitive deficits, as well as brain
injury associated with repeated seizures in adulthood."

While
therapeutic doses of the drug do not appear to alter normal brain
development in the rat, topiramate's safety in children under age three
has not been studied.

However Dr Jensen added:

"By
further studying unique mechanisms of injury in the newborn brain, we
hope to continue to elucidate new therapies for use in this age group.
However, since agents already approved for use in adults are also
effective, our results indicate that a clinical trial should be
considered to determine topiramate's safety and efficacy in newborns."