Research: the beginnings of the MS lesion

#MSBlog: Is MS triggered by abnormalities in lipids?

Epub: Laule et al. Diffusely Abnormal White Matter in Multiple Sclerosis: Further Histologic Studies Provide Evidence for a Primary Lipid Abnormality With Neurodegeneration. J Neuropathol Exp Neurol. 2012 Dec 13.

Background: Although MS lesions have been studied extensively using histology and MRI, little is known about diffusely abnormal white matter (DAWM). Diffusely abnormal white matter, regions with reduced mild MRI hyperintensity and ill-defined boundaries, show reduced myelin water fraction, and decreased Luxol fast blue staining of myelin phospholipids, with relative preservation of myelin basic protein and 2',3'-cyclic-nucleotide 3'-phosphohydrolase. Because DAWM may be important in MS disability and progression, further histologic characterization is warranted. 

Methods: The MRI data were collected on 14 formalin-fixed MS brain samples that were then stained for myelin phospholipids, myelin proteins, astrocytes and axons. 

Results: Diffusely abnormal white matter showed reduced myelin water fraction (-30%, p < 0.05 for 13 samples). Myelin phospholipids showed the most dramatic and consistent histologic reductions in staining optical density (-29% Luxol fast blue and -24% Weil's, p < 0.05 for 13 and 14 samples, respectively) with lesser myelin protein involvement (-11% myelin-associated glycoprotein, -10% myelin basic protein, -8% myelin-oligodendrocyte glycoprotein, -7% proteolipid protein, -5% 2',3'-cyclic-nucleotide 3'-phosphohydrolase, p < 0.05 for 3, 3, 1, 2, and 3 samples, respectively). Axonal involvement was intermediate. Diffusely abnormal white matter lipid and protein reductions occurred independently. 

Conclusions: These findings suggest a primary lipid abnormality in DAWM that exceeds protein loss and is accompanied by axonal degeneration. These phenomena may be important in MS pathogenesis and disease progression, which is prominent in individuals with DAWM.


"We know that the normal appearing white matter is MS is abnormal. This study suggests that the defect is in the lipid or myelin fraction and that it occurs independently of protein loss. Both these processes are accompanied by axonal degeneration. Unfortunately  as with all pathological studies this study provides no information on the temporal nature of these abnormalities, i.e. what order they occur in. The latter information is vital to know what came first; it is the old chicken or egg argument."

Labels: