title: White-matter lesions drive deep gray-matter atrophy in early multiple sclerosis: support from structural MRI.
abstract: BACKGROUND
  In MS, the relationship between lesions within cerebral white matter (WM) and atrophy within deep gray matter (GM) is unclear.
  
  
  OBJECTIVE
  To investigate the spatial relationship between WM lesions and deep GM atrophy.
  
  
  METHODS
  We performed a cross-sectional structural magnetic resonance imaging (MRI) study (3 Tesla) in 249 patients with clinically-isolated syndrome or relapsing-remitting MS (Expanded Disability Status Scale score: median, 1.0; range, 0-4) and in 49 healthy controls. Preprocessing of T1-weighted and fluid-attenuated T2-weighted images resulted in normalized GM images and WM lesion probability maps. We performed two voxel-wise analyses: 1. We localized GM atrophy and confirmed that it is most pronounced within deep GM; 2. We searched for a spatial relationship between WM lesions and deep GM atrophy; to this end we analyzed WM lesion probability maps by voxel-wise multiple regression, including four variables derived from maxima of regional deep GM atrophy (caudate and pulvinar, each left and right).
  
  
  RESULTS
  Atrophy of each deep GM region was explained by ipsilateral WM lesion probability, in the area most densely connected to the respective deep GM region.
  
  
  CONCLUSIONS
  We demonstrated that WM lesions and deep GM atrophy are spatially related. Our results are best compatible with the hypothesis that WM lesions contribute to deep GM atrophy through axonal pathology.
authors: Department of Neurology, Technische Universität München, Munich, Germany.
authors: Mark
authors: M
authors: Mühlau
authors: Dorothea
authors: D
authors: Buck
authors: Annette
authors: A
authors: Förschler
authors: Christine C
authors: CC
authors: Boucard
authors: Milan
authors: M
authors: Arsic
authors: Paul
authors: P
authors: Schmidt
authors: Christian
authors: C
authors: Gaser
authors: Achim
authors: A
authors: Berthele
authors: Muna
authors: M
authors: Hoshi
authors: Angela
authors: A
authors: Jochim
authors: Helena
authors: H
authors: Kronsbein
authors: Claus
authors: C
authors: Zimmer
authors: Bernhard
authors: B
authors: Hemmer
authors: Rüdiger
authors: R
authors: Ilg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D055815:Young Adult
keywords: Multiple sclerosis; brain damage; clinically-isolated syndrome; gray-matter atrophy; magnetic resonance imaging; relapsing–remitting multiple sclerosis; voxel-based morphometry; white-matter lesions