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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
09:41

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

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Diffusely abnormal white matter in multiple sclerosis: further histologic studies provide evidence for a primary

Cornelia Laule1, Vlady Pavlova, Esther Leung

  • 1Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada. claule@physics.ubc.ca

Journal of Neuropathology and Experimental Neurology
|December 18, 2012
PubMed

Insights

Diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) shows significant myelin lipid loss, exceeding protein reduction and accompanied by axonal degeneration, impacting MS progression.

Area of Science:

  • Neuroscience
  • Neuropathology
  • Neuroimaging

Background:

  • Multiple sclerosis (MS) lesions are well-studied, but diffusely abnormal white matter (DAWM) remains poorly understood.
  • DAWM regions exhibit subtle MRI hyperintensity and ill-defined borders, suggesting distinct pathological processes.
  • Understanding DAWM is crucial as it may significantly contribute to MS disability and disease progression.

Purpose of the Study:

  • To histologically characterize diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) brain samples.
  • To investigate the specific changes in myelin lipids, proteins, and axons within DAWM.
  • To correlate histological findings with magnetic resonance imaging (MRI) data.

Main Methods:

  • Analysis of 14 formalin-fixed MS brain samples.
  • Histological staining for myelin phospholipids (Luxol fast blue, Weil's stain), myelin proteins (myelin-associated glycoprotein, myelin basic protein, myelin-oligodendrocyte glycoprotein, proteolipid protein, 2',3'-cyclic-nucleotide 3'-phosphohydrolase), astrocytes, and axons.
  • Quantitative assessment of myelin water fraction using MRI data.

Main Results:

  • DAWM showed a significant reduction in myelin water fraction (-30%).
  • Histology revealed substantial decreases in myelin phospholipids (up to -29%), with lesser reductions in myelin proteins.
  • Axonal involvement was intermediate, and lipid and protein reductions occurred independently, suggesting primary lipid abnormality.

Conclusions:

  • Diffusely abnormal white matter (DAWM) in MS is characterized by a primary myelin lipid abnormality that surpasses protein loss.
  • The observed lipid and protein changes, coupled with axonal degeneration, may be key drivers of MS pathogenesis and progression.
  • Further research into DAWM is warranted to understand its role in MS disability.

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