title: Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study.
abstract: BACKGROUND
  Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution.
  
  
  OBJECTIVE
  To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS).
  
  
  METHODS
  Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions. A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study.
  
  
  RESULTS
  At baseline, patients with PPMS displayed bilateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up.
  
  
  CONCLUSIONS
  Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.
authors.affiliation: Institute of Neurology, University College of London, 23 Queen Square, London WC1N 3BG, England.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sepulcre
authors.forename: Jaume
authors.initials: J
authors.lastname: Sastre-Garriga
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Ingle
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D001284:Atrophy / Q000453:epidemiology / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000453:epidemiology / Q000473:pathology*