094-AP-99 EMBARGOED UNTIL 2 P.M. PDT MONDAY, JULY 26, 1999
PROLONGED FEVER-INDUCED SEIZURES IN CHILDREN CAN RESULT IN LONG-TERM ALTERATIONS TO THE BRAIN
Findings Show Changes in Brain Function May Last into Adulthood
Irvine, Calif. -- Seizures induced by fever, which each year afflict half a million infants and young children in the country, can cause long-term alterations in the way certain nerve cells work in the brain, UC Irvine researchers have found.
The UCI study marks the first time any long-term brain alterations have been linked directly to prolonged febrile convulsions and indicate that certain childhood seizures--especially those lasting more than 20 minutes--could make children more susceptible to epileptic seizures in adulthood. The findings appear in the August edition of Nature Medicine.
Dr. Tallie Z. Baram and Ivan Soltesz, professors at UCI's College of Medicine, and Kang Chen, postdoctoral fellow at UCI, found that the combination of fever and seizures in young rats resulted in changes in the way certain nerve cells in the brain communicate with each other. These changes lasted until adulthood.
The study suggests that the rats are more susceptible to seizures as adults after enduring febrile convulsions at a young age. The researchers stressed that the study does not show that febrile seizures actually cause epilepsy or other adult seizures.
"There is an ongoing debate among researchers on whether prolonged febrile seizures in children actually cause epilepsy in adults," said Baram, the Danette (Dee Dee) Shepard Chair in Neurology. "While there is evidence that these seizures don't cause anatomical damage, we're now seeing evidence that--at least in animals--prolonged febrile seizures can result in permanent changes in the way the brain functions. We still need to find out exactly what these changes may be in humans."
By raising the body temperatures of the rats, the researchers induced seizures that simulated febrile convulsions seen in young human children. The researchers saw that these seizures increased the activity of nerve cells within the hippocampus, an area of the brain's temporal lobe that is damaged in adult epilepsy (also known as temporal lobe epilepsy) and that plays important roles in memory.
The nerve cells in the hippocampus that are affected by seizures secrete an inhibitory neurotransmitter called GABA (short for "gamma-amino-butyric acid"), and make up a major network of cells that regulate the overall activity of cells within this area of the brain.
"We were able to identify, for the first time, a specific increase in the activity in GABA-regulated inhibitory nerve cells in the hippocampus after the seizures," Soltesz said. "This activity continued into adulthood."
Baram and Soltesz are now studying how the brain responds to this change in nerve cell function and looking into whether their findings can be applied to humans. If successful, their research could lead to more effective treatments for childhood seizures. Currently, only drugs that treat adult epilepsy are available for childhood seizures.
"We seem to have discovered a very specific change in the balance between stimulation and inhibition among nerve cells," Baram said. "Someday, this information may be able to tell us how to prevent specific nerve cells from being altered, which may, in turn, help us prevent childhood seizures."
The study was funded by a grant from the National Institutes of Health. The researchers have been working for many years to find the causes of childhood convulsions and determine whether those convulsions result in adult epilepsy. Baram and Soltesz head a group that last year received a grant from the University of California Biotechnology Research and Education Program that allows them to forge links with private biotechnology companies to develop drugs that would more effectively control the unique seizures that can take place in the developing brain.
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Contact: Andrew Porterfield
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