Newswise — Progressive changes within the brain occur earlier in multiple sclerosis than previously supposed, according to a study presented October 4, 2004, at the 129th annual meeting of the American Neurological Association. Using sophisticated variations on magnetic resonance imaging (MRI) techniques, researchers described changes that appear in the first years of the disease, while disability is still minimal.
"The study showed that subtle abnormalities in the brain were steadily increasing during the first five years of multiple sclerosis, possibly reflecting changes to nerve fibers and their surrounding myelin sheathes," said Dr. Gerard Davies of the Institute of Neurology in London, lead author of the report.
Davies and colleagues also report preliminary evidence that the abnormalities may even pre-date the appearance of symptoms of the disorder.
Multiple sclerosis is an enigmatic disease of the nervous system and results in the loss of myelin, a substance that normally insulates nerve fibers and speeds electrical conduction through the fibers. Patches of inflammation (known as 'plaques') occur throughout the brain and spinal cord resulting in the loss of myelin and sometimes the nerve fibers themselves.
Depending on which nerve fibers are hindered, patients can experience problems ranging from weakness and clumsiness to numbness, visual disturbances, and even emotional and intellectual alterations. In patients such as the ones Davies and colleagues studied, MS manifests itself in cycles of relapse and remission and patients may show little sign of the disease between attacks.
The plaques are visible on standard MRI and are best seen within the 'white matter' areas of the brain and spinal cord, so called because they contain mostly nerve fibers, wrapped in light-colored mylein. This contrasts with the the 'gray matter', where the nerve cell bodies reside. Standard MRI can detect the white matter plaques but cannot pick up subtle changes that may be occurring between the plaques or in the gray matter.
As scientists have refined imaging techniques, they have begun to look at these previously unstudied areas and two important questions have emerged: How early does MRI-detectable damage occur, and, does the damage progress steadily during the first years after symptoms appear.
In the present study, Davies and colleagues employed a relatively recent MRI advance called magnetization transfer, which makes damaged tissue stand out more clearly against the backdrop of normal brain tissue. The study group included 23 patients who had experienced the first symptoms of relapsing/remitting MS less than three years earlier. The patients and 19 healthy control subjects received three yearly MRI scans.
The researchers found subtle changes in both the gray and white matter even at the first imaging, and noted in subsequent examinations that these changes were steadily increasing. Based on these data, they were able to extrapolate that some abnormality had been present in both the white and gray matter already at the time of symptom onset. Indeed, the analysis of the data suggested that white matter abnormality preceded the first symptoms.
Doctors would like to be able to predict the course of the disease, both to inform patients and to tailor more precisely current and future therapies. Ideally any tests would involve minimal invasion of the vulnerable nervous system, and magnetic transfer may fit this bill.
"MRI is useful, not just in diagnosing MS, but also in the monitoring of therapies in clinical trials," said Davies. "The changes that we have seen with magnetization transfer in this study raise the possibility that it might be a useful technique for monitoring new treatments in the future. However, there is still more work to be done to firmly establish whether this would be the case."
81. Progressive Grey and White Matter MTR Abnormality in Early Relapsing-Remitting MS
Gerard R. Davies, Daniel R. Altmann, Waqar Rashid, Declan T. Chard, Colette M. Griffin, Gareth J. Barker, Alan J. Thompson, and David H. Miller; London, United Kingdom
In early relapsing-remitting multiple sclerosis (RRMS), abnormality in normal-appearing grey and white matter (NAGM and NAWM) can be detected with the magnetization transfer ratio (MTR). However, it remains uncertain whether such changes progressively worsen prior to the onset of permanent disability and at what stage such abnormalities begin. Twenty three RRMS patients (mean disease duration 1.9 years, expanded disability status scale: 0-3.0) and 19 healthy controls were imaged yearly for two years using a magnetization transfer imaging sequence (21 patients and 10 controls were imaged at two years). Patient-vs.-control differences and change over time were assessed using a hierarchical regression model, adjusting for changes in brain volume. Baseline NAWM and NAGM MTR were reduced in patients vs. controls (p<0.001, p=0.004 respectively). In patients (but not in controls) NAWM and NAGM MTR declined progressively: -0.10pu/year, p=0.001 and -0.18pu/year, p<0.001. Backward extrapolation of the linear regression model suggested that NAWM abnormality began 2.9 years before symptom onset and NAGM abnormality began shortly after the first attack. Progressive MTR abnormalities in NAWM and NAGM occur in patients with early RRMS and minimal disability. The onset of NAWM abnormality may predate symptom onset. Study supported by Multiple Sclerosis Society of Great Britain and Northern Ireland .