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MS May Take a Different Pathway Than Previously Thought
Date:12/7/2011

By Mary Brophy Marcus
HealthDay Reporter

WEDNESDAY, Dec. 7 (HealthDay News) -- Multiple sclerosis may begin in the outer layer of the brain and work its way into the deep interior, according to a new study that upends long-held beliefs about the nervous system disease.

The new findings, which could spur changes in the way MS is diagnosed and treated, appear to solidify a theory that's emerged in recent years. This new premise suggests that gray matter, the outer covering of the brain called the cortex, and the fluid that surrounds and cushions it, is where MS originates, not in the bulky white matter that composes most of the brain's core.

It's an "outside-in" process in other words, said study co-author Dr. Claudia Lucchinetti, a professor of neurology at the Mayo Clinic in Rochester, Minn.

"We already recognized before this study that the cortex -- the superficial layer where cells control memory, attention, and other key pathways in the nervous system -- was involved in MS. But most of what we knew came from autopsy studies, from patients who had longstanding disease, 30 to 50 years," said Lucchinetti. The new findings show the cortex is involved early on and may even be the initial target of the disease, she added.

Lucchinetti and her colleagues analyzed brain tissue of early MS patients obtained through biopsies. The tissue was primarily white matter, but about one-fourth of the biopsies (138 of 563 patient screenings) also included tiny fragments of cortex. The scientists used that tissue as the focus of their study.

The cortical tissues were viewed on a microscopic level. "The early lesions were highly inflammatory," said Lucchinetti, whose research is published in the Dec. 8 issue of the New England Journal of Medicine.

The authors also noted that inflammation was also present in the meninges, the protective membranes that cover the surface of the brain and spinal cord, and was strongly associated with inflammation in the cortex tissue.

About 400,000 Americans have MS, according to the National Multiple Sclerosis Society. Its cause is unknown, but it is believed to occur when the body's immune system chips away at the protective myelin sheath, a fatty insulator that covers nerves, and it can be debilitating. Symptoms can include weakness and numbness, paralysis, poor vision, fatigue, dizziness, and tremor. Its severity varies widely in patients, said Lucchinetti.

Lucchinetti said if scientists can understand the genesis of the disease, better diagnostic procedures and treatments could be developed.

"The findings are provocative," said Dr. Peter Calabresi, professor of neurology and director of the MS Center at Johns Hopkins Hospital, who wrote an accompanying editorial.

"It's an exciting study. For many years we thought MS was predominantly a disease of the white matter. More recently people have found there are some changes in the gray matter. This is the first time that anyone has definitively shown there's extensive inflammation in the gray matter early on in the disease," said Calabresi.

Calabresi likens the findings to leaves on a tree. "Everyone thought the attack was on the leaves, the white matter, but now people think it's more likely the trunk," he said.

Should patients get excited?

Dr. Jerome Graber, an assistant professor of neurology at Albert Einstein College of Medicine in the Bronx, N.Y., said it's a good study, but suggests no immediate clinical benefits. "My answer to my patients is that it doesn't have an immediate implication for them yet. I have no new treatment for you because of this study. But I think it opens a lot of doors for researchers to ask a whole new set of questions," he said. And the link with the meninges is also intriguing, he said.

Calabresi agreed it offers hope. "I think it gives us a lot of hope," he said. "It gives us yet one more tool to follow the disease. There's a mysterious aspect to MS. It's hard to quantify. But now we know gray matter is definitely involved, and we can track it and see if a therapy is working or not, and if not, move on to the next therapy."

Ultimately, this research "will allow us to understand [MS] better and track and treat it better," he said.

More information

For more on multiple sclerosis, visit the U.S. National Library of Medicine.

SOURCES: Claudia Lucchinetti, M.D., professor and consultant, department of neurology, Mayo Clinic, Rochester, Minn.; Peter Calabresi, professor of neurology and director, MS Center, Johns Hopkins Hospital, Baltimore; Jerome Graber, M.D., assistant professor of neurology, Albert Einstein College of Medicine, Bronx, N.Y.; Dec. 8, 2011, New England Journal of Medicine


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