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Gray Matter Damage Linked to MS

Previous research had focused on the brain's white matter

TUESDAY, Oct. 21, 2003 (HealthDayNews) -- The cognitive problems and walking difficulties experienced by multiple sclerosis patients is caused by damage in the brain's gray matter.

And that damage may be due to toxic deposits of iron.

That's the conclusion of a study by Dr. Rohit Bakshi, an associate professor of neurology, and his fellow researchers at the University of Buffalo. They presented their findings Oct. 21 at the annual meeting of the American Neurological Association in San Francisco.

"Conventional thinking has it that multiple sclerosis is a disease of white matter lesions or plaque detected by MRI [magnetic resonance imaging]," says Bakshi. "In the last five years, growing evidence suggests that MS is not just a white matter disease, but that gray is also involved. We now know it's a global disease of the brain and spinal cord. And it targets not only white matter but gray."

"Gray matter is the command-and-control center of the brain, where all the nerve centers are housed," Bakshi adds. "White matter simply connects the gray matter together."

Multiple sclerosis is believed to be an autoimmune disease of the central nervous system, including the brain, spinal cord and optic nerves. Surrounding the nerve fibers is protective fatty tissue called myelin, which helps nerve fibers conduct electrical impulses. Myelin is lost in numerous areas in MS patients, leaving behind scar tissue called sclerosis.

The damage to the myelin is the result, most experts believe, of an abnormal response by the immune system. Several factors are thought to be involved in the onset of MS, including genetics and environmental triggers such as viruses or trauma.

In one of two studies presented at the meeting, Bakshi and his team evaluated 47 people with multiple sclerosis who completed a timed 25-foot walk, commonly used to assess physical functioning in patients with the disease. The times were compared with the amount of unnatural darkness of each patient's gray matter, a condition called T2 hypointensity, which was detected on MRIs. The times were also compared with brain shrinking or atrophy and other brain changes known to occur with MS.

The amount of T2 hypointensity was the only brain change directly associated with impaired walking, Bakshi and his team found. The strongest association was with hypointensity in the dentate nucleus, a structure deep within the brain's cerebellum responsible for coordination and smooth limb movement, Bakshi says.

"That's a major finding and a completely new finding," he says.

In a second study, Bakshi evaluated 34 MS patients, some of them the same ones in the walking study, and 16 healthy controls, testing them for working memory and attention, and performing MRIs to evaluate hypointensity.

He found the hypointensity was independently related to problems with attention and memory and predicted the problems in the MS patients.

"The more hypointensity, the more impairment," he says.

Excess iron entering the brain may be what is damaging the gray matter, Bakshi says. Or, the high levels of iron -- which can increase as people age -- might be the result of the degenerative process that occurs in MS. For instance, high iron levels are seen in Alzheimer's disease, Bakshi says, and experts still debate the cause-and-effect of iron in that disorder.

Stephen Reingold, vice president of research programs for the National Multiple Sclerosis Society, says, "Gray matter damage in MS has been a topic of concern for some time, and it is important that this research group is pursing this systematically. The relative contributions of white matter and gray matter damage to the disease is an important issue that has yet to be determined," he says.

The potential role of iron, whether cause or effect, also remains unclear, Reingold adds.

In another study presented at the meeting, researchers from the University of California, San Francisco reported they have produced an MS-like condition in laboratory animals by exposing them to a virus called herpes hominis virus 6. It is one of several viruses believed by some to play a role in triggering MS.

More information

For more information on multiple sclerosis, check with the National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society.

SOURCES: Stephen Reingold, Ph.D., vice president, research programs, National Multiple Sclerosis Society, New York City; Rohit Bakshi, M.D., associate professor, neurology, University of Buffalo, N.Y.; Oct. 21, 2003, presentation, American Neurological Association annual meeting, San Francisco
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