Why Patients With Multiple Sclerosis Have Seizures Discovered

Individuals with MS are 3 to 6 times more likely to develop seizures.

Individuals with multiple sclerosis (MS) are more likely to develop seizures compared with individuals without the disease.

For the first time, investigators have found that chronic demyelination is closely linked to these seizures, and most likely is the cause.

MS affects nearly 2.3 million people worldwide, and individuals with this disease are 3 to 6 times more likely to develop seizures.

In a study published in Neuroscience, investigators induced demyelination in mouse models by feeding them a diet that contained cuprizone—–a copper-binding substance that causes damage to oligodendrocytes.

“Demyelination causes damage to axons and neuronal loss, specifically parvalbumin interneurons are lost in mice, hyperactivity is no longer down but up, and this could be a cause of seizures,” said investigator Seema Tiwari-Woodruff. “It’s very likely this is what is occurring in those patients with MS who are experiencing seizures.”

Parvalbumin interneurons play an important role in keeping hyperactivity down, but they become modified and lost when extensive demyelination occurs in the brain’s cortex and hippocampus, the authors noted.

The results of the study showed that after 9 weeks of feeding the mice cuprizone, most of them started having seizures.

“Without myelin, axons are vulnerable,” Tiwari-Woodruff said. “They develop blebs—–ball-like structures that hinder transport of important proteins and conduction of electrical signals. In some instances, significant axon damage can lead to neuronal loss. In both MS and our mouse model, parvalbumin interneurons are more vulnerable and likely to die. This causes the inhibition to be removed and induced seizures. Thus, axonal and neuronal survival may be directly tied to the trophic support provided by myelin.”

In an additional study, the investigators stopped feeding the mice the cuprizone diet after 9 or 12 weeks. Oligodendrocytes began to repopulate the demyelinated areas and remyelinate the intact but myelin-stripped axons. In future studies, investigators plan to examine seizure activity with remyelination.

“Does remyelination affect seizure activity? Could we accelerate the remyelination with drugs? Can we thus provide some relief for MS patients? We are interested in addressing these questions,” Tiwari-Woodruff said.

Recently, the National Multiple Sclerosis Society awarded the investigative team with a pilot grant to compare postmortem brain tissue from MS patients with seizures to those who do not experience them to determine the cellular basis of seizures in MS.

The findings will be used to evaluate how efficaciously the cuprizone mouse model reproduces the changes seen in humans, the authors noted.

“We want to know if these tissues show what we are seeing in our mouse model,” Tiwari-Woodruff said. “Our preliminary data in postmortem tissue show considerable similarity between the 2. We now have a mouse model with which we can work to test and suggest some therapeutic cures. When developed, such drugs, which would be aimed at reducing hyperactivity to reduce the incidence of seizures, could also be extended to epilepsy patients.”