NASHVILLE, Tenn. ― Absence seizures create an unhealthy pattern of myelination, rewiring the brain for more seizures, according to a first-of-its kind study being presented at the American Epilepsy Society Annual Meeting.
In a healthy brain, continual formation (plasticity) of myelin ― the insulating layer around nerves cells ― in response to brain activity is necessary for optimal neurological function, from basic skills like walking, to learning a complex cognitive task, such as playing the piano. This research shows for the first time that absence seizures (brief lapses of consciousness) can cause unhealthy myelin plasticity, maladaptively leading to progressively more seizures. Myelin also plays a role in multiple sclerosis, which is caused by damage to the myelin (demyelination), a distinctly different process.
“To our knowledge, this is the first description of maladaptive myelin plasticity in epilepsy or any neurological disease,” said Juliet K. Knowles, M.D., Ph.D., lead author of the study and assistant professor of neurology at Stanford University, Palo Alto, California. “We hope this information will provide new insights for epilepsy that doesn’t respond to treatment.”
Researchers combined innovative magnetic resonance imaging (MRI) with established microscope-based methods to assess myelin structure in mice and rats with generalized epilepsy. They found that those who had absence seizures showed both more myelinated nerve cells and thickening of the myelin sheath in brain regions where seizures occurred. Blocking seizures with an antiseizure medication prevented the myelin changes, indicating that those changes were caused by epileptic brain activity (seizures). When the researchers blocked myelin plasticity in additional groups of mice ― either by introducing specific genetic changes or by giving a drug known to prevent myelin plasticity ― the opposite was true: blocking myelin plasticity reduced the number of seizures over time. Together, the findings suggest that seizures induce myelin plasticity, which, in turn, further reinforces the tendency to have seizures.
“We’re now studying specific mechanisms by which neurons involved in seizures communicate with myelin-forming cells, and different methods for interrupting maladaptive myelination,” said Dr. Knowles. “We also are developing MRI methods that may allow us to study this process in humans, including how myelin changes throughout the brain and over time.”
John Huguenard, Ph.D., Jennifer McNab, Ph.D. and Michelle Monje, M.D., Ph.D., are senior authors on the study.