Contribution of white matter lesions to gray matter atrophy in multiple sclerosis: evidence from voxel-based analysis of T1 lesions in the visual pathway

Arch Neurol. 2009 Feb;66(2):173-9. doi: 10.1001/archneurol.2008.562.


Background: The biological basis of gray matter (GM) atrophy in multiple sclerosis is not well understood, but GM damage seems to be the most critical factor leading to permanent disability.

Objective: To assess to what extent white matter (WM) lesions contribute to regional GM atrophy in multiple sclerosis.

Design: Because optic pathway GM atrophy and optic radiation lesions, rather than being related to each other, could be independent results of the disease, we applied a nonaprioristic WM method to analyze the interrelationships of both phenomena. On a voxel-by-voxel basis, we correlated T1 magnetic resonance imaging-derived lesion probability maps of the entire brain with atrophy of the lateral geniculate nuclei and calcarine/pericalcarine cortices.

Setting: Multiple sclerosis center, University of Navarra, Pamplona, Spain.

Patients: Sixty-one patients with multiple sclerosis.

Main outcome measure: Mapping of WM regions contributing to GM atrophy in the optic pathway.

Results: Patients with multiple sclerosis had lateral geniculate nucleus atrophy, which correlated with the presence of lesions specifically in the optic radiations but not in the rest of the brain. Optic pathway lesions explained up to 28% of the change of variance in lateral geniculate nucleus atrophy. Patients also had occipital cortex atrophy, which did not correlate with lesions in the optic radiations or any other WM region.

Conclusions: Focal WM damage is associated with upstream GM atrophy, suggesting that retrograde damage of the perikarya from axonal injury in multiple sclerosis plaques is one of the significant factors in the genesis of GM atrophy, although other neurodegenerative processes are probably at work as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy / pathology*
  • Atrophy / physiopathology
  • Axons / pathology
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Mapping / methods
  • Disease Progression
  • Female
  • Geniculate Bodies / pathology
  • Geniculate Bodies / physiopathology
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / physiopathology
  • Nerve Fibers, Myelinated / pathology*
  • Predictive Value of Tests
  • Retrograde Degeneration / etiology
  • Retrograde Degeneration / pathology
  • Retrograde Degeneration / physiopathology
  • Visual Cortex / pathology
  • Visual Cortex / physiopathology
  • Visual Pathways / pathology*
  • Visual Pathways / physiopathology