Children With New Epilepsy Often Have Delayed Brain Development
By Allison Gandey
Medscape Medical News
June 3, 2010 — Recent-onset epilepsy can alter brain development and delay increases in white matter volume, report researchers. These new findings have implications for the cognitive development of children with newly diagnosed epilepsy who may experience reduced brain connectivity and impairments in executive function.
Modest abnormalities have already been reported in adults with chronic epilepsy. "One of the purposes of our research has been to search for the origin of such abnormalities," lead investigator Bruce Hermann, PhD, from the University of Wisconsin at Madison, told Medscape Neurology. "It does appear that these changes can be seen early on in the course of childhood epilepsy."
The results are available online and will appear in the July issue of Epilepsia.
The researchers evaluated 38 children with newly diagnosed epilepsy and compared them to 34 healthy cousins. More than half of the children with epilepsy had localization-related disorder, and the remainder had idiopathic generalized disease.
Participants underwent 1.5T magnetic resonance imaging at baseline and 2 years later. Investigators compared total cerebral and lobar gray and white matter volumes.
They found changes in gray matter volume were comparable for epilepsy and control groups. There was a significant reduction in total cerebral gray matter primarily due to decreases in the frontal and parietal lobes.
This was not the case with white matter volume, where changes differed between groups. Controls experienced a significant increase in total cerebral white matter volume (P = .0012). These volume increases were greatest in the frontal, parietal, and temporal lobes (P < .001). In contrast, epilepsy patients experienced a nonsignificant white matter volume change in the total cerebrum (P = .51) and across all lobes (P > .06).
Table. Prospective Change in White Matter Lobar Volumes
Lobe
Control
Epilepsy
Frontal
3.97
1.54
Parietal
2.42
1.02
Temporal
1.71
0.74
Occipital
0.03
?1.21
"Two core findings emerge from this investigation," the investigators report. "First, prospective changes in cerebral gray matter volumes appear to be proceeding at a normal rate in children with epilepsy compared to healthy controls," they note. "Second, there appears to be a significant delay in the rate of white matter volume increase among children with epilepsy compared to controls."
These modest abnormalities in brain development are more evident, they add, in children with idiopathic generalized epilepsies.
During an interview, Dr. Hermann pointed out the sample size for the study is modest and the 2-year follow-up short. "One question is the permanence of the findings," he noted. "If the epilepsy becomes completely controlled or remits and medications are no longer needed, will there be normalization of development?"
Dr. Hermann proposes that interest will be high in understanding the origin of these findings — is it due to seizures, medications, or other factors? His team is currently researching what the practical complications of these developmental abnormalities will be.
Risk for Epileptic Encephalopathy
Developmental abnormalities are something most clinicians are concerned about. Gary Mathern, MD, from the University of California at Los Angeles, who recently spoke to Medscape Neurology about his new paper on surgical outcomes for pediatric epilepsy patients, was emphatic about the issue.
"These children are at risk for epileptic encephalopathy and an IQ less than 50," Dr. Mathern said. "We know when a medication has failed within months, yet I'm often seeing patients 4 or 5 years later. We have to get in there to stop the seizures and give the rest of the brain a chance to develop," he said.
Dr. Mathern's new paper appears in the June 1 issue of Neurology. He is a member of an International League Against Epilepsy task force that developed the first-ever global consensus definition of drug-resistant epilepsy.
The task force is urging clinicians to consider this approach: after 2 adequate trials of appropriate and well-tolerated drugs, patients who continue to have seizures should be referred to a specialist.
"Two strikes and they're in for referral," Patrick Kwan, MD, task force chair, from the Chinese University of Hong Kong, said in an interview when the group's new definition was first unveiled in December. The goal, he said, is to avoid unnecessary delays in altering the course of disease.
The researchers have disclosed no relevant financial relationships. Dr. Mathern reports he is on the data management committee of Neuropace Inc. Dr. Kwan has disclosed no competing interests.
