Cause of Epilepsy
In some cases, the brain's attempts to repair itself after a head injury, stroke, or other problem may inadvertently generate abnormal nerve connections that cause epilepsy. Abnormalities in brain wiring that occur during brain development also may disturb neuronal activity and lead to epilepsy.
Research has shown that the cell membrane that surrounds each neuron plays an important role in epilepsy. Cell membranes are crucial for a neuron to generate electrical impulses. For this reason, researchers are studying details of the membrane structure, how molecules move in and out of membranes, and how the cell nourishes and repairs the membrane. A disruption in any of these processes may lead to epilepsy. Studies in animals have shown that because the brain continually adapts to changes in stimuli, a small change in neuronal activity, if repeated, may eventually lead to full-blown epilepsy. Researchers are investigating whether this phenomenon, called kindling, may also occur in humans.
In some cases, epilepsy may result from changes in non-neuronal brain cells called glia. These cells regulate concentrations of chemicals in the brain that can affect neuronal signaling.
Research suggests that genetic abnormalities may be some of the most important factors contributing to epilepsy. Some types of epilepsy have been traced to an abnormality in a specific gene. Many other types of epilepsy tend to run in families, which suggests that genes influence the brain disorder. Some researchers estimate that more than 500 genes could play a role in this disorder; however, it is increasingly clear that for many forms of epilepsy, genetic abnormalities play only a partial role, perhaps by increasing a person's susceptibility to seizures that are triggered by an environmental factor.
Several types of epilepsy have now been linked to defective genes for ion channels, the "gates" that control the flow of ions in to and out of cells and that regulate neuron signaling. Another gene, which is missing in people with progressive myoclonus epilepsy, codes for a protein called cystatin B. This protein regulates enzymes that break down other proteins. Another gene, which is altered in a severe form of epilepsy called Lafora's disease, has been linked to a gene that helps to break down carbohydrates.
While abnormal genes sometimes cause epilepsy, they also may influence the disorder in subtler ways. For example, one study showed that many people with epilepsy have an abnormally active version of a gene that increases resistance to drugs. This may help explain why anticonvulsant drugs do not work for some people. Genes also may control other aspects of the body's response to medications and each person's susceptibility to seizures, or seizure threshold. Abnormalities in the genes that control neuronal migration -- a critical step in brain development -- can lead to areas of misplaced or abnormally formed neurons, or dysplasia, in the brain that can cause epilepsy. In some cases, genes may contribute to the development of epilepsy, even in people with no family history of the disorder. These people may have a newly developed abnormality, or mutation, in an epilepsy-related gene.