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24-Jun-2014

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Animal study unveils predictive marker for epilepsy development following febrile seizure

MRI may be able to predict those at heightened risk for developing epilepsy

Washington, DC Within hours of a fever-induced seizure, magnetic resonance imaging (MRI) may be able to detect brain changes that occur in those most likely to develop epilepsy later in life, according to an animal study published in the June 25 issue of The Journal of Neuroscience. The findings may one day help improve methods to detect children at a heightened risk for developing epilepsy and guide efforts to prevent epilepsy development in those at greatest risk.

Febrile seizures convulsions brought on by fever typically last only a few minutes and are relatively common in infants and small children. However, in some cases, children experience febrile seizures that last for more than 30 minutes (known as febrile status epilepticus, or FSE). Of these children, 40 percent will go on to develop temporal lobe epilepsy (TLE) a common and often treatment-resistant brain disorder. Physicians currently have no way to anticipate which of the children with a history of extended febrile seizures (FSE) will go on to develop TLE, and children typically do not experience the onset of the disease until 10-12 years after the onset of FSE.

In the current study, Tallie Z. Baram, MD, PhD, and her colleagues at the University of California-Irvine, used MRI to examine the brains of young rats shortly after FSE was induced to compare the brains of the animals that would go on to develop TLE and those that would not. The researchers tracked the animals as they developed over 10 months for signs of TLE. Of the animals that developed epilepsy over the course of the study, all had a distinctive MRI signal in a part of the brain called the amygdala when imaged within hours after the FSE. This signal was not visible in the animals that remained epilepsy-free for the duration of the experiment.

"This remarkable discovery got us to ask two key questions," Baram said. "First, can we figure out what is going on in the brain that causes this new signal? And second, can we detect a similar predictive signal in children after febrile status epilepticus?"

Further investigation into the origin of the MRI signal revealed that the brains of the rodents that went on to develop epilepsy were consuming more energy and using up more oxygen in the amygdala hours after long febrile seizures than the brains of the rats that did not develop epilepsy later in life.

"Detecting reduced oxygen may be an early marker of brain damage that leads to subsequent spontaneous seizures and epilepsy," explained Hal Blumenfeld, MD, PhD, who studies epilepsy at Yale University and was not involved in this study.

Although the current study was conducted in rats using a high-power laboratory scanner, additional studies by Baram's group revealed that the epilepsy-predicting signal could be detected using a conventional hospital MRI scanner. This suggests that similar evaluations could be conducted in children with FSE to begin to assess whether this signal appears in children after FSE and whether it predicts the emergence of epilepsy later in life.

"Preventive therapy development is hampered by our inability to identify early the individuals who will develop TLE," Baram explained. "Finding a predictive signal using clinically applicable noninvasive brain scans holds promise for predicting epilepsy after FSE."

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This research was funded by the National Institute of Neurological Disorders and Stroke, the Epilepsy Foundation of America, and the American Epilepsy Society.

The Journal of Neuroscience is published by the Society for Neuroscience, an organization of nearly 40,000 basic scientists and clinicians who study the brain and nervous system. Baram can be reached at tallie@uci.edu. More information on epilepsy can be found on BrainFacts.org.



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