title: Contribution of white matter lesions to gray matter atrophy in multiple sclerosis: evidence from voxel-based analysis of T1 lesions in the visual pathway.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Multiple sclerosis center, University of Navarra, Pamplona, Spain.
  
  
  METHODS
  Sixty-one patients with multiple sclerosis.
  
  
  METHODS
  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.
authors.affiliation: Departamento de Neurología, Clínica Universitaria de Navarra, Universidad de Navarra, Pío XII 36, 31008 Pamplona, Navarra, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sepulcre
authors.forename: Joaquín
authors.initials: J
authors.lastname: Goñi
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Masdeu
authors.forename: Bartolome
authors.initials: B
authors.lastname: Bejarano
authors.forename: Nieves
authors.initials: N
authors.lastname: Vélez de Mendizábal
authors.forename: Juan B
authors.initials: JB
authors.lastname: Toledo
authors.forename: Pablo
authors.initials: P
authors.lastname: Villoslada
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology* / Q000503:physiopathology; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D018450:Disease Progression; D005260:Female; D005829:Geniculate Bodies / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011237:Predictive Value of Tests; D012183:Retrograde Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D014793:Visual Cortex / Q000473:pathology / Q000503:physiopathology; D014795:Visual Pathways / Q000473:pathology* / Q000503:physiopathology