A preclinical study suggests why some people with multiple sclerosis also suffer from seizures — a debilitating complication that can worsen cognitive outcomes and accelerate disease progression. The findings offer new opportunities for targeted treatments that address the root cause of seizures in MS without suppressing overall brain activity.

MS is a chronic autoimmune disorder that damages myelin, leading to symptoms such as vision issues, fatigue, coordination problems, cognitive decline, and, in some cases, seizures. According to the researchers, about 4 to 5 percent of people with MS develop seizures. It has been an understudied area, but these patients tend to experience worse cognitive outcomes and faster disease progression. Understanding what’s happening in the brain is crucial.

The research by biomedical scientists at the University of California, Riverside identified a strong connection between demyelination — the loss of the protective myelin sheath coating the axons of neurons — and seizure activity. Using a mouse model of MS, the researchers found that as myelin deteriorates, especially in the hippocampus, seizures become more likely. This brain region, a known hotspot for seizure activity, is essential for memory and learning.

To simulate progressive demyelination, the researchers used the toxic cuprizone diet mouse model. After 12 weeks of demyelination, nearly 80 percent of mice showed seizure activity, up from 40 percent earlier in the disease process. Brain recordings and behavioral assessments confirmed this increase.

The study’s authors note that as demyelination progressed, levels of glutamate, an excitatory neurotransmitter, rose, while GABA, the brain’s main inhibitory neurotransmitter, appears to decline. This imbalance makes the brain more excitable — a hallmark of epilepsy.

The study highlights the hippocampus as a key area affected. Inhibitory neurons in this region, some of which are myelinated, appear especially vulnerable.

Unlike traditional epilepsy models that rely on brain damage to trigger seizures, this study offers a more accurate model based on demyelination-induced seizure activity. 

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the team’s comparisons of mouse and human brain tissue are already underway. The researchers said the findings pave the way for targeted treatments. The team is now investigating changes in neural circuits and receptors in the hippocampus and how astrocyte dysfunction contributes to seizure risk. 

The study was published in the journal Neurobiology of Disease.