Epilepsy research
Pursing the link between fevers and epilepsy: Multicenter study seeks
answers
Despite the latest diagnostic technology such as video electroencephalogram
(EEG), positron emission tomography (PET) scans and more than 50 medications at
physicians' disposal, the number of children who develop intractable epilepsy -
the kind that doesn't respond to treatment - hasn't changed in half a century,
says Douglas R. Nordli, Jr., MD, who holds the Lorna S. and James P. Langdon
Chair in Pediatric Epilepsy.
"Seizures are very disabling," says Nordli, who is also associate professor
of pediatrics at Northwestern University's Feinberg School of Medicine. "They
interfere with getting an education, driving a car, maintaining a job and social
relationships." But Nordli also believes in the potential of research to some
day eliminate the threat of epilepsy to children. "Ideally, we'd prevent the
development of epilepsy in the first place. The second best thing would be to
cure it once it develops, and the third would be to treat it more effectively."
In a new National Institutes of Health-funded, multi-center clinical study,
Nordli and colleagues are pursuing one of epilepsy's many causes. Neurologists
have long debated whether prolonged febrile seizures lead to epilepsy. Febrile
or "fever" seizures are very common among children under five years old. They
occur in approximately 100,000 U.S. children annually when body temperatures
rapidly rise above 101 degrees Fahrenheit. Studies on animals have shown an
association between a rapid rise in body temperature and seizure activity. In
most children these seizures have no lasting consequences. But the study will
focus on the three percent of children who have a febrile seizure lasting more
than 30 minutes and develop scar tissue in the brain.
"This is a landmark study," says Nordli, the central EEG reader for the
study. "It will show if this population develops epilepsy as a result of
scarring, and if so, what the risk factors are," says Nordli. "Principal
investigator Shlomo Shinnar, MD, at Einstein Medical School in New York, has
assembled a first-class team."
Previous studies have attempted to find a link between febrile seizures and
epilepsy, but have lacked the funding, methodology and patient population large
enough to answer the question. With six medical centers participating in the
current study, investigators hope to enroll 200 children and track them for five
years. In addition to collecting traditional data such as a medical history,
magnetic resonance images (MRIs), and EEG analysis, two new vital pieces of
information will be gathered from each of the patients - evidence of previous
viral infection and genetic markers. Leon G. Epstein, MD, head of the division
of neurology, is leading the viral component of the study.
"With this information," says Nordli, "we'll be able to determine who's at
risk by recognizing if it's this particular set of clinical characteristics,
infection with this virus, or this genetic pre-disposition. Then we can do
something about it." Nordli points to his basic science research colleagues at
Children's Memorial and throughout the country who are investigating
"neuroprotective strategies" such as diet and medications that might prevent the
development of epilepsy in patients identified as high-risk.
Though it is still in the very preliminary stages, Nordli says he is
encouraged by the design of the febrile seizure study. "We've learned that it is
practical to do collaborative studies in the field of epilepsy," he says. "Even
in one very large institution you won't have enough patients to answer a
question. It's critical for this kind of research to be conducted
multi-institutionally."
[Note: This article appeared in the Spring 2004 issue of Carousel, the
magazine of Children's Memorial Hospital.