Jan 16, 2002
By Merritt McKinney
Reuters Health - NEW YORK
A common imaging technique may help identify patients in the early stages of multiple sclerosis (MS) who are most at risk of serious long-term complications, researchers report.
In a 14-year study of people with early signs of MS, 88% of people with abnormal results on a magnetic resonance imaging (MRI) scan eventually developed MS, compared with 19% of people with normal MRI results. The findings are published in the January 17th issue of The New England Journal of Medicine.
The results of the study raise the possibility of using the scan to identify people with early MS who might benefit most from therapies that slow the disease. But the connection between MRI-detected brain lesions and later development of MS was not strong enough to support the use of MRI results alone for making treatment decisions, the study's lead author told Reuters Health.
Multiple sclerosis slowly destroys myelin, the thin, protective coating that insulates nerve fibers in the brain and spine. The destruction of myelin can lead to numbness, muscle weakness and stiffness, impaired vision and coordination problems.
Most people who eventually develop MS first experience isolated symptoms, such as optic neuritis, an inflammation of the optic nerve that leads to the loss of central vision. Up to 70% of patients with isolated symptoms of MS have brain lesions that show up on an MRI.
Although MRI is sometimes used to select patients who might benefit from early treatment, the connection between early brain lesions and later MS-related disability is unclear.
In a study of 71 people who had isolated MS symptoms, 44 out of 50 patients who had abnormal MRI results at the start of the study developed MS compared with only 4 out of 21 people with normal MRI results, reports a team led by Dr. David H. Miller, of the NMR Research Unit at the Institute of Neurology in London.
The study shows a "moderate relationship between accumulation of MS lesions on MRI and disability," Miller told Reuters Health in an interview. This is the first long-term demonstration of this relationship, according to Miller.
"It therefore provides partial support for MRI as a laboratory tool which is clinically relevant," he said.
The UK researcher pointed out that early changes in MRI results were a "somewhat stronger" predictor of later MS-related disability than changes later in the study.
Participants underwent MRI at the start of the study and 5, 10 and 14 years later. The extent of disability at 14 years was most strongly associated with the size of lesions at 5 years and with how much the lesions changed during the first 5 years of the study.
This relationship, according to Miller, suggests that treatment to suppress lesions might stave off long-term disability when given in the early stages of MS. He stressed, however, that the connection between lesions and later disability is only moderate. He estimated that lesions contribute to "maybe a third" of disability.
This "suggests that there are other factors that we are missing," Miller said.
A second report in the journal suggests that the gradual deterioration of myelin in MS patients is not due simply to a lack of myelin-producing cells called oligodendrocytes. Dr. Bruce D. Trapp, of the Cleveland Clinic Foundation in Ohio, and colleagues detected oligodendrocytes in 34 out of 48 lesions taken from 10 people who had died with MS.
"Our studies demonstrate that the brains of multiple sclerosis patients are producing new cells that are destroyed by the disease process," Trapp told Reuters Health. The researchers also found that the new cells try to repair the damage inflicted by MS.
"They are, however, falling short of their goal," Trapp said.
It is possible, according to the Ohio researcher, that drugs could be developed that enable the newly formed cells to complete the repair process.
But the research raises questions about transplanting stem cells or other early-stage cells into the brains of people with MS, Trapp pointed out. Since the brains of people with MS continue to produce new cells, this type of transplantation "may not be necessary," he said. Or if the cells were transplanted into MS patients, Trapp said they might have to be used in combination with drugs that repair MS-related damage.
"We are trying to identify the source of the new cells in the hopes that we can manipulate the MS brain to make more," Trapp explained. The researchers are also looking for ways to direct the new cells to complete the repair process, he noted.
Both studies "make important contributions to the understanding of this enigmatic disease," according to Dr. Donald W. Paty of Vancouver Hospital in British Columbia, and Dr. Douglas L. Arnold of Montreal Neurological Hospital in Quebec, Canada.
Therapies designed to protect neurological cells from MS-related damage and to help restore myelin could have "an important place in future therapies for multiple sclerosis, particularly if they are used in the early phases," Paty and Arnold write in an accompanying editorial.
SOURCE: The New England Journal of
Medicine 2002;346:158-164, 165-173, 199-200.
Copyright © 2002 Reuters Limited