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Tuesday, September 16, 2014

Myelin Measure in MS Tracks Patient Disability

September 11, 2014










BOSTON -- Whole-brain measures of myelin water fraction (MWF) -- reflecting the amount of myelin present in brain tissue -- correlated significantly with disease duration and disability levels inmultiple sclerosis, supporting a role for MWF in patient management and as an outcome in clinical trials, a researcher said here.
In a cross-sectional study of 141 MS patients and 10 neurologically healthy controls, the "skew" of one of two peaks seen in the distribution of MWF across the brain, including normal-appearing white matter as well in MS-type lesions, was associated with Expanded Disability Status Scale (EDSS) score (P=0.000039) and with the number of years since symptom onset (P=0.012), said Elizabeth Monohan, of Weill Cornell Medical College in New York City.
"To date, our study is the first to demonstrate an approach to modeling white matter myelin water fraction to explore clinical variables that may be driving myelin content," she said at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting,held jointly this year with its North American counterpart.
"These observations promote the use of myelin water fraction as a biomarker for myelin," she added, noting that the relationship between MWF on the one hand and EDSS and disease duration on the other suggests that "myelin loss is accumulated during the disease and perhaps contributes to the progressive nature of MS."
Demyelination is the chief pathology in MS and is believed to be the driving force behind the physical disabilities that mark the disease in its later stages. Nerve fibers are sheathed in a protective layer of proteins dominated by myelin; its progressive loss leaves nerve axons vulnerable to various insults such that eventually they break down, leading to loss of nerve function.
However, this process has been impossible to witness or measure directly in human patients. Recently, MWF -- measurable with MRI scans as the amount of water within myelin versus the total amount of water in the tissue scanned -- has emerged as a quantitative marker of myelin that can be assessed noninvasively in living patients.
Up till now, though, its clinical applicability has been uncertain, Monohan explained, because it was unclear whether focusing on MWF in lesioned areas was sufficient and also because the scans took a long time to perform and data analysis was difficult.
She said her group had developed a more practical approach to the scans that cut the image acquisition time to just 10 minutes for the whole brain. Moreover, she and her colleagues determined that scanning the whole brain was the right way to go, because there was no solid evidence to indicate that the clinically relevant demyelination occurs only in lesions.
The whole-brain MWF measurement, Monohan said, provides an "unbiased approach" for studying myelin dynamics.
An important finding in the study was that patients showed a "bimodal" distribution in histograms of MWF values -- a small spike in relatively low values and another larger spike in mid-range values. Monohan said that 94% of the patients showed this type of pattern, compared with just one of the 10 controls.











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