NASHVILLE, TENN. – Researchers have reported for the first time a process that may explain the progression of absence seizures that seems to provoke dysregulation of the insulating layer surrounding nerve fibers, perpetuating a cycle of increasing nerve damage and more frequent seizures later on.
“This study was the first to demonstrate that, at least in some forms of epilepsy, myelin plasticity is part of the maladaptive plasticity response that underlines epilepsy progression,” Juliet Knowles, MD, PhD, assistant professor at Stanford (Calif.) University, said in an interview. She reported the findings at the 2022 annual meeting of the American Epilepsy Society.
Knowles and colleagues made their discovery using laboratory mice. They used an imaging technique known as qMTI – quantitative magnetization transfer in conjunction with diffusion MRI – to map changes in myelin sheath thickness, or myelin plasticity, in major white matter tracks of the brain.
“Over the last decade we’ve come to understand that myelin, which is the insulating substance that coats the projections of brain cells or neurons, is more dynamic than we used to think,” she said. “In fact, throughout life, myelin’s structure in some regions of the brain can be changed in response to neuro activity. It’s a newly appreciated form of brain plasticity.”
However, she said, myelin plasticity has mostly been studied in healthy brains; “We don’t know very much about what role myelin plasticity might play in disease states like epilepsy,” Knowles said. The study’s goal was to investigate myelin plasticity specifically in absence seizures.
“We hypothesized that maybe absence seizures prompt activity-dependent myelin plasticity, but that maybe seizure-induced myelin plasticity alters the way that brain networks act in a way that contributes to the disease process,” she said.
Maladaptive Myelin Plasticity
The researchers found that absence seizures were infrequent when they first started, but then they rapidly progressed. “Over a couple of weeks, they’ll go from having very few seizures to having many seizures per hour,” Knowles said.
Using qMTI, the researchers found increased myelin sheath thickness across the longitudinal extent of the anterior corpus callosum, but they found myelin sheath thickness unchanged in brain regions where absence seizures weren’t prominent.
They also found that genetically blocking activity-dependent myelination markedly decreased seizure progression and decreased ictal somatosensory electroencephalography (EEG) coherence. Conversely, blocking myelin plasticity had no effect on ictal EEG coherence between visual cortices connected by the posterior corpus callosum.
The next step for the researchers is to develop MRI methods to use in human studies, Knowles said.
“We are working on developing an imaging approach in these same animal models that we hope we can use also to study in a detailed way white matter plasticity in humans with epilepsy and we’re also continuing our studies in animal models to try to identify ways to target maladaptive myelin plasticity, which ultimately we hope will inform treatment of people with epilepsy,” Knowles said.
Of Mice and Men
Although this study used mice, Chris Dulla, PhD, associate professor and director of the neuroscience graduate program at Tufts University in Boston, said the finding is “probably pretty transferable” to humans.
“This is the first study that really showed it,” he said of the link between myelin changes and seizure frequency. “I think people have suspected it, but that’s why this is kind of a big deal because this is one of the first studies to show it conclusively.”
He offered suggestions for validating the findings in humans. “The first thing would be to do imaging studies in people where you can examine to see if those white matter tracks are altered in a similar way in people with epilepsy,” he said. “I think now this study gives us good reason to undertake the work that it would take to ask that question and answer it in the human brain.”
Knowles and Dulla have no relevant relationships to disclose.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.