One of the major causes of epilepsy in children is an abnormal development of the cerebral cortex (the bumpy surface of the brain). The cortex holds a large percentage of brain cells, and plays a vital role in the generation of thoughts and voluntary actions. It is a highly complicated structure and there are many factors that can hinder its development. In many cases faulty genes are at the root of the problem.

Abnormal development of the cerebral cortex is known as cortical dysplasia, and this is found in 25 to 40 percent of children with the most severe and difficult-to-treat forms of epilepsy. These children often come to the attention of specialists due to a lack of progress with language and balance, as well as their epilepsy. The seizures they experience range from very subtle, e.g. small muscle jerks or eyelid fluttering, to dramatic whole body, tonic-clonic spasms.

Researchers at the University of California San Diego School of Medicine have been studying a condition called lissencephaly. Children with lissencephaly have an abnormal brain cortex, in that they have a smooth brain surface that lacks the usual characteristic 'bumps', and it is usually accompanied by a severe form of epilepsy. The causes of lissencephaly have not been fully established, but several genes have been linked to it.

The group recently developed an animal model that showed some of the features of lissencephaly. This is usually the first step in understanding the cause of a genetic disorder. However, interestingly, these models did not show any signs of epilepsy. Therefore the scientists removed gene after gene, until they found one that was responsible for epilepsy.

Geraldine Kerjan, Lead Author on this project commented on their findings:

"We studied the gene "doublecortin," which is defective in some forms of epilepsy and mental retardation in humans. However, only after we removed a combination of two of the genes in the doublecortin family did we uncover epilepsy."

Professor Joseph Gleeson, Senior Author and director of the Neurogenetics Laboratory at the UC San Diego School of Medicine, considered this to be a dramatic discovery, because almost none of these new models survived to adulthood. Suspecting that the deaths were due to epilepsy, the scientists decided to take EEG recordings of their subjects. As predicted, they found evidence of severe epilepsy in all of the models tested.

Surprisingly, the epileptic focus (the site from which the seizures arose) was consistently found to be beneath the surface of the brain in the hippocampus, and not in the defective cortex, as originally expected.

Professor Gleesen is quoted "Researchers had thought that the cause of the seizures in this disease must be the brain surface, since this is the part that looks the most abnormal on brain MRI scans. However, we found that the epilepsy focus was actually deeper in the brain, within the hippocampus, the main memory-forming site."

These findings have enhanced our understanding of childhood epilepsy and seizure focus. The research team intends to continue studying these models, and hope that their findings will open will lead to improved treatments for childhood epilepsy.

Click here for further information