Fever-induced seizures cause brain changes.

Convulsions triggered by high fevers strike up to 5 percent of infants and young children. Physicians generally regard such episodes as benign because they seldom lead to neurological problems in adulthood. A new study in rats, however, indicates that prolonged fever-induced convulsions, or febrile seizures, cause long-lasting changes in the brain, perhaps rendering it more prone to epilepsy.

"It's quite likely that if what we see in rats holds true in children, these fever-induced seizures lower the threshold for later seizures," says Ivan Soltesz of the University of California, Irvine, one of the study's investigators. Some researchers disagree with that interpretation of the findings, however.

Soltesz and his team used a procedure established by their Irvine coauthor Tallie Z. Baram to mimic a fever, or hyperthermia. By raising body temperatures in 10-day-old rat pups to about 41 [degrees] C, comparable to children's high fevers, they stimulated seizures lasting at least 20 minutes. One week later, the researchers measured the chemistry of neurons in the hippocampus, the part of the brain involved in the most common form of adult epilepsy.

In the August NATURE MEDICINE, the team reports that the rat pups showed pronounced changes in communication between nerve cells in the hippocampus. These changes persisted even 10 weeks later, when the animals had reached maturity.

The rats showed long-lasting increases in an enzyme called protein kinase A, which in turn caused greater release of the chemical messenger GABA. When GABA floods the gaps, or synapses, between neurons, it inhibits activity in the hippocampus. Rats in a group that was not induced to have seizures showed no rise in protein kinase A or GABA.

The effects the scientists observed appear to be unique to heat-induced convulsions. When they gave another group of rat pups a drug that causes seizures, they later found no difference between animals that had had convulsions and those that hadn't. Similarly, pups that were exposed to heat but given a drug to prevent seizures exhibited no changes in brain activity.

In an editorial accompanying the article, Matthew C. Walker and Dimitri M. Kullmann of University College London disagree with Soltesz's view that the changes caused by febrile seizures might make further seizures more likely. They suggest that febrile seizures may instead protect the brain. "Whether something is benign or malignant should be determined on the grounds of whether there's some evidence that the alterations have consequences for the health of the animal," Kullmann told SCIENCE NEWS.

Soltesz notes, however, that preliminary results of further experiments suggest that the pups that experienced heat-induced seizures may become more prone to seizures as adults. The researchers speculate that the GABA inhibition sets the stage for further seizures by priming cells in the hippocampus to fire simultaneously.

"It's a very interesting study because it shows that, at least in animals, febrile seizures can lead to long-lasting changes in neuronal excitability in the hippocampus," comments William H. Theodore of the National Institute of Neurological Disorders and Stroke in Bethesda, Md. "It's impossible to know, of course, whether you would see the same kinds of changes in humans, but one can certainly speculate that a similar mechanism might occur."

"The question of whether febrile seizures cause epilepsy has been incredibly controversial," says Baram. "We don't think all prolonged febrile seizures actually cause epilepsy. However, we can take a normal brain where there are no predisposing [abnormalities] and induce persistent changes in it with these seizures. We now need to know what those changes mean."