Scientists have uncovered why some people with multiple sclerosis experience seizures, identifying demyelination as the key trigger behind this complication.
Between four and five per cent of people with MS experience seizures, which can worsen cognitive decline and accelerate disease progression.
The study found that as the protective myelin sheath around neurons deteriorates — particularly in the hippocampus — seizure activity rises sharply.
Demyelination is the loss of myelin, a fatty coating that helps electrical signals travel efficiently through the brain and nervous system.
Seema Tiwari-Woodruff is professor of biomedical sciences at the University of California, Riverside School of Medicine and lead author of the study.
The researcher said: “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.”
Researchers at the University of California, Riverside, used the cuprizone diet mouse model of MS to examine how myelin loss leads to seizure development.
After 12 weeks of progressive demyelination, nearly 80 per cent of mice showed seizure activity, compared with 40 per cent earlier in the disease course.
The hippocampus, a brain region vital for learning and memory, was especially affected.
As demyelination progressed, levels of glutamate — an excitatory neurotransmitter — increased, while GABA, the brain’s main inhibitory neurotransmitter, decreased.
This imbalance makes the brain more excitable, a hallmark of epilepsy.
Tiwari-Woodruff said: “Myelin doesn’t just speed up signal transmission; it also helps maintain neuron health.
“Damage to GABA-producing neurons in the hippocampus due to demyelination could explain seizure susceptibility in MS.”
Unlike traditional epilepsy models that rely on brain injury to provoke seizures, this study used a model based solely on myelin loss.
“We’re not destroying brain tissue,” Tiwari-Woodruff explained.
“We’re modelling the gradual myelin loss seen in MS. That makes it a powerful tool for future research.”
Current anti-seizure drugs suppress overall brain activity, often leading to fatigue and cognitive side effects.
The team is now studying changes in neural circuits and receptors in the hippocampus, and how astrocyte dysfunction contributes to seizure risk.
Comparisons between mouse and human brain tissue are already underway.
“If the same transporters and receptors are affected in humans, they could become clear therapeutic targets,” Tiwari-Woodruff said.
