Understanding How Myelin Damage in the Brain Can Trigger Seizures in Multiple Sclerosis

A recent study conducted by biomedical researchers at the University of California, Riverside, sheds light on why some individuals with multiple sclerosis (MS) also experience seizures—a serious complication that can negatively impact cognition and expedite disease progression.

Published in Neurobiology of Disease, the research highlights the critical link between demyelination—the loss or damage of the protective myelin sheath surrounding nerve fibers—and seizure activity. Using a mouse model that mimics MS, scientists observed that as demyelination advances, particularly in the hippocampus—a brain region vital for memory, learning, and a common site for seizure initiation—the likelihood of seizures increases. Their findings demonstrate that after 12 weeks of induced demyelination using a cuprizone diet, nearly 80% of the mice exhibited seizure activity, compared to 40% at earlier stages. Electrophysiological recordings and behavioral assessments confirmed this escalation.

The study reveals that demyelination causes an imbalance in neurotransmitters: levels of glutamate, an excitatory neurotransmitter, rise, while GABA, the brain’s primary inhibitory neurotransmitter, diminishes. This shift results in heightened brain excitability, a hallmark characteristic of epilepsy. Notably, the hippocampus, especially the inhibitory GABA-producing neurons within it, appears particularly vulnerable to demyelination, which may compromise neural regulation and facilitate seizure development.

Traditionally, seizures in MS patients have been managed with general anticonvulsant medications that suppress overall brain activity, often leading to side effects such as fatigue and cognitive clouding. This new research suggests potential targeted therapies that address the underlying cause—demyelination—possibly offering more effective and precise treatment options.

Lead author Seema Tiwari-Woodruff emphasizes the importance of understanding these mechanisms: "Myelin does more than just speed up nerve signal transmission; it also plays a crucial role in maintaining neuron health. Damage to GABAergic neurons due to demyelination could explain why seizures occur in MS."

Furthermore, the study highlights the role of astrocytes—supportive glial cells responsible for clearing excess glutamate from the extracellular space. Impaired astrocyte function might lead to glutamate accumulation, further increasing neural excitability and seizure risk. The precise modulation of glutamate, without entirely blocking its function, could pave the way for novel treatments.

This research enhances understanding of the neurological complications associated with MS and opens avenues for targeted interventions that could mitigate seizure risk by preserving myelin integrity and restoring neurotransmitter balance. The ongoing investigation into the molecular and cellular changes within neural circuits aims to identify specific receptors and transporters involved, potentially providing new therapeutic targets for MS-related seizures.