It finds the tissue that protects the nerves isn't the first to be destroyed
Feb. 23, 2004
A rare look at the brain lesions characteristic of multiple sclerosis may provide new insight into the biological origins of the disease.
A new study, prompted by the death of a teenager with the disease, challenges a long-held notion on how it develops. It found that myelin, the fatty sheath that protects nerve fibers, was not the first casualty of the condition and was not -- at least at first -- an inside job by the immune system, as researchers had thought.
In people suffering from multiple sclerosis (MS), myelin is destroyed. Taking its place is scar tissue, or sclerosis. The damaged areas are also known as plaques or lesions. Without myelin, the nerves lose much of their ability to conduct electrical impulses to and from the brain. As a result, patients can suffer a variety of symptoms, including weakness, clumsiness, numbness, blurred vision or fatigue.
The course of the disease varies widely from person to person. The most common type at the time of diagnosis (representing about 80 percent of cases) is relapsing-remitting MS, in which periods of remission are punctuated by flare-ups. Other forms of MS involve slow but continuous progression of the disease.
"There has always been an attempt to try and understand why one person follows a relapse and remitting course and another person follows a progressive course," says Patricia O'Looney, director of biomedical research at the National Multiple Sclerosis Society (NMSS) in New York City. "Perhaps one way to try to answer that is to look at the damage that's being done." The NMSS was a co-supporter of this study.
But because MS is not generally considered to be a fatal disease, scientists rarely have the opportunity to actually study what is happening with the lesions inside the brain in the early stages of lesion formation.
The untimely death of a 14-year-old girl with relapsing and remitting MS afforded one such opportunity. The girl died within 24 hours of the onset of an acute lesion in her brain stem, a rare occurrence (MS more commonly occurs in adults).
"Acute lesions are not that common among people with MS, but this did give [the study authors] an opportunity to study a lesion very early in its development because the person died so quickly," O'Looney says.
"This patient proved to be unique in the history of multiple sclerosis in that there was lesion available for study that was less than a day old," study author Dr. John W. Prineas, a professor of neurology at the University of Sydney in Australia, says in a statement. The paper appears in the Feb. 23 online edition of the Annals of Neurology.
Unexpectedly, the myelin in the lesion was still intact when the researchers investigated, and no immune system cells were yet in the vicinity. The researchers found that oligodendrocytes, the cells that produce the myelin, were dying at this early stage of lesion formation.
Scientists have long believed the earliest event in MS was an immune system attack on the myelin. In this case at least, it appears the cells that produce myelin die first, perhaps prompting an invasion by immune system cells.
They decided to look at autopsied brain tissue in their brain bank and found similar patterns among some individuals who had died shortly after a relapse. "This allowed us to conclude that the changes observed probably occur at the onset of any typical new lesion," Prineas says.
There is no question there is an immunological basis to MS, O'Looney says. But for the first time, the destruction of oligodendrocytes is linked to the earliest stage in the formation of a lesion.
"He's putting the loss of oligodendrocytes early on, while the immune system is still normal," O'Looney says.
"This is an important area of our understanding of MS, to try to understand what is happening in terms of damage and does it differ from person to person," O'Looney says. "Certainly understanding what's happening would help us also have a more painless therapy if it indeed is different from person to person."
On the other hand, O'Looney stresses, this is a small group of patients and the results do need confirmation. And the results do not necessarily agree with what other researchers have seen.
"There are some differences and some agreements, which simply indicates
we're in a learning process here," O'Looney says. "It needs further exploration."
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