” I get a sense that you are frustrated with my sceptical, and at times cynical, position on remyelination in MS. The reasons are captured in this study below of alemtuzumab and the MRI metric called MTR. MTR is a marker of tissue integrity and correlates with myelin in pathological studies (see Schmierer et al below) . Interestingly, single MS lesion MTR changes are being used as the exploratory outcome to test remyelination strategies in MS. If remyelination treatments work they will improve the MTR of individual lesions better than control treatments or placebo.”
“The million, or billion, dollar question is do we need to stimulate remyelination? In most studies done in inflammatory models remyelination is the norm. Stop inflammation and remyelination occurs. The one caveat is ageing; older animals remyelinate slower than younger animals, but they still remyelinate. So may be we need an anti-ageing strategy rather than a remyelination strategy?”
The magnetization transfer ratio reflects the integrity of tissue structure, including myelination and axonal density. Mean magnetization transfer ratio fell in 18 untreated patients with multiple sclerosis both in normal appearing grey (-0.25 pu/year, p < 0.001) and white matter (-0.12 pu/year, p = 0.004). Conversely, mean magnetization transfer ratio was stable in 20 alemtuzumab-treated patients (grey matter: -0.01 pu/year, p = 0.87; white matter: -0.02 pu/year, p = 0.51). The gradient difference in grey matter was 0.25 pu/year (p < 0.001) after age-adjustment. These data suggest that in multiple sclerosis alemtuzumab protects against tissue damage in normal-appearing grey matter, perhaps by preventing new lesion formation.
Schmierer et al. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol. 2004 Sep;56(3):407-15.
Several quantitative magnetic resonance (MR) measures are used to investigate multiple sclerosis (MS) in vivo. Precise quantitative investigation of the histopathological correlates of such measures has, to date, been limited. This study investigates the relationship of quantitative measures of myelin content, axonal density, and gliosis with quantitative MR measures in postmortem (PM) MS tissue. MR imaging (MRI) was performed on a 1.5T scanner and T1-relaxation time (T1-RT) and magnetization transfer ratio (MTR) maps were acquired in fresh PM brain of 20 MS subjects. Myelin content, axonal counts, and the extent of gliosis all were quantified using morphometric and digital imaging techniques. MRI and pathological data were in most cases coregistered using stereotactic navigation. Using multiple regression analysis, we detected significant correlations between myelin content (Tr(myelin)) and MTR (r = -0.84, p < 0.001) and myelin content and axonal count (-0.80, p < 0.001); MTRcorrelated with T1-RT (r = -0.79, p < 0.001). No association was detected between the extent of gliosis and either MR measure. MTR was significantly higher in remyelinated than demyelinated lesions (means: 30.0 [standard deviation, 2.9] vs 23.8 [standard deviation, 4.3], p = 0.008). In conclusion, MTR is affected by myelin content in MS white matter.