Natural Course of Multiple Sclerosis Redefined


Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) today presented evidence that multiple sclerosis (MS) is a progressive disease even in its earliest stages.

Until recently, MS was thought to be active only during attacks. Now, using magnetic resonance imaging (MRI), NINDS scientists have shown that, even when patients' symptoms are stable, their MS can be active: Clinically silent lesions occur in their brains frequently and continuously throughout the course of the disease. The findings were presented today at the 115th Annual Meeting of the American Neurological Association in Atlanta, Georgia.
Six patients with early MS were followed over 12 months in a study conducted in the NINDS Neuroimmunology Branch by Jonathan O. Harris, M.D. Dr. Harris used gadolinium to "enhance" monthly MRI scans of the patients' brains. Gadolinium, a chemical compound used to increase the contrast between tissues, doesn't ordinarily enhance MRI brain images because it is unable to cross the blood/brain barrier, a protective shield that controls the passage of substances from the blood into the central nervous system.

But when the scientists scanned gadolinium-injected patients, white spots appeared on the scans, showing that the gadolinium had gained access to the brain. "This phenomenon is probably due to a breakdown of the blood/brain barrier early in the development of MS lesions," said Branch Chief Dale E. McFarlin,M.D., "and it makes MRI a highly sensitive method for both detecting MS lesions and monitoring their evolution. Furthermore, because the spots come and go over time, the barrier probably closes at some point; only new and active lesions enhance."
According to Dr. McFarlin, these findings have significant implications for treating the disease more effectively. "It looks like we've been treating the wrong patients at the wrong time, which may be why the treatments haven't been very successful," said Dr. McFarlin. "We hope to begin therapeutic trials of patients with very early MS in the near future. We also plan to examine the relationship between disease activity and the onset of symptoms through the use of MRI."

In the past, physicians have been reluctant to treat patients with early MS because the side effects of most MS drugs can be worse than the symptoms of the disease, which often takes a relatively benign early course. MRI may solve this problem by allowing scientists to monitor the effect of treatment: They will be able to estimate the degree of disease activity by viewing the number, size, and location of lesions.

In the first study to compare an MS patient's brain tissue with MRI scans taken 2 and 4 weeks prior to death, the scientists found evidence correlating the intense disease activity shown on the scans with damage to the tissue.
The National Institute of Neurological Disorders and Stroke, one of 13 of the National Institutes of Health in Bethesda, Maryland, is the primary supporter of brain and nervous system research in the United States.