Imaging May Identify Epilepsy Risk After Febrile Seizures

Megan Brooks

November 12, 2012

Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) soon after febrile status epilepticus (FSE) may help identify children at greatest risk of developing epilepsy, new research shows.

New EEG findings from the Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT) study show the most important acute EEG finding after febrile status epilepticus is focal slowing, which correlates with acute MRI abnormalities and may be a sensitive marker for hippocampal injury, according to study investigator, Douglas R. Nordli, Jr, MD, neurologist, Children's Memorial Hospital, Chicago, Illinois.

"Further follow-up is in progress to determine if this finding is predictive of future mesial temporal sclerosis, temporal lobe epilepsy or both," Dr. Nordli told Medscape Medical News.

The EEG findings from the FEBSTAT study were published online November 7 in Neurology. and add to MRI findings published in the same journal in August.

Hippocampal Injury

Within days of FSE some children show signs of acute brain injury, abnormal brain anatomy, altered brain activity, or a combination.

"The important message is that children with FSE, unlike children with brief febrile seizure, have a substantial rate of pre-existing abnormalities of the temporal lobe and hippocampus and also have a significant rate of demonstrating acute hippocampal injury," FEBSTAT investigator Shlomo Shinnar, MD, PhD, told Medscape Medical News.

"Therefore, some children may be predisposed, but all are susceptible to seizure-induced injury," said Dr. Shinnar, director, Comprehensive Epilepsy Management Center, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.

Febrile seizures affect 3% to 4% of all children. Most children recover rapidly with no long-term health consequences. However, FSE increases the risk for subsequent epilepsy by an estimated 30% to 40%. "While the majority of children fully recover from FSE, some will go on to develop epilepsy. We have no way of knowing yet who they will be," Dr. Shinnar said.

The FEBSTAT study is focused specifically on FSE and the risk for temporal lobe epilepsy. A total of 199 children age 1 month to 5 years presenting with FSE were enrolled within 72 hours of the FSE episode.

Low-Cost, Noninvasive, and Available

The researchers report that 22 of 191 (11.5%) children who underwent MRI had definitely abnormal (17 children) or equivocal (5 children) increased T2 signal in the hippocampus after FSE compared with none of 96 control children with a first simple febrile seizure (P < .0001).

Developmental abnormalities of the hippocampus were also more common in the FSE group (20 children [10.5%]) than in the control group (2 children [2.1%]) (P = .0097). Hippocampal malrotation was the most common abnormality seen (15 cases, 2 controls).

Extrahippocampal imaging abnormalities of the temporal lobe were also more common in the FSE group than in the control group (7.9% vs 1.0%; P = .015).

All 199 children underwent EEG and 90 (45.2%) had abnormal findings. The most significant abnormalities consisted of focal slowing, attenuation, or both, present in 30.2%, and most commonly involving the temporal regions. EEG findings were "highly associated" with MRI evidence of acute hippocampal injury, the researchers say.

Dr. Shinnar said the results suggest that for some children, FSE injures the brain. For others, preexisting abnormalities could make the brain susceptible to febrile seizures. Both of these paths could in turn lead to epilepsy, but more study is needed to confirm this.

"This study may give us insights into how epilepsy develops" after FSE, Vicky Whittemore, PhD, from the National Institute of Neurological Disorders and Stroke, who was not involved in the study, said in a statement.

"If MRI and EEG findings associated with FSE ultimately do correlate with epilepsy, they could be used to identify kids who are at risk and who might benefit from research on preventative therapies for epilepsy," Dr. Whittemore added. "EEG could be especially useful since it is low cost, non-invasive, and readily available at most hospitals."

The FEBSTAT study is funded by National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. Dr. Shinnar serves on the Data Safety Monitoring Board for King Pharmaceuticals; has received personal compensation for serving on Scientific Advisory Boards for Questcor and Sunovion and for consulting for Eisai, Questcor, and Neuronex, and has received speaker honoraria from Eisai, Questcor, and UCB. A complete list of author disclosures is provided with the original article.

Neurology. 2012;79:1-7. Published online November 7, 2012. Abstract