title: Regional grey matter atrophy in clinically isolated syndromes at presentation.
abstract: BACKGROUND
  The presence and degree of neuronal degeneration already existing in patients at their initial presentation with a clinically isolated syndrome suggestive of multiple sclerosis (CIS) is unclear, and whole brain or whole normalised grey matter analyses have not demonstrated significant atrophy in CIS cohorts at clinical presentation. Voxel-based analyses allow detection of regional atrophy throughout the brain and, therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability.
  
  
  METHODS
  This study used a modified voxel-based morphometry (VBM) method to correct for lesion effects to analyse regional atrophy and perform voxel-wise correlations between volume and clinical metrics in 41 untreated CIS patients at presentation compared with 49 healthy controls.
  
  
  RESULTS
  The results confirmed that there was no significant difference in whole normalised grey matter volume between CIS and controls, whereas VBM showed significant areas of bilateral thalamic, hypothalamic, putamen and caudate atrophy. Voxel-wise correlations with clinical measures showed that cerebellar volumes correlated with clinical cerebellar function, nine-hole peg test scores and the Multiple Sclerosis Functional Composite (MSFC) score, and that the MSFC score was also correlated with putamen volume. Lastly, T1 lesion volumes were found to correlate with thalamic and hippocampal atrophy, suggesting a link between white matter lesions and grey matter degeneration at the earliest stages of multiple sclerosis.
  
  
  CONCLUSIONS
  Atrophy is present in CIS patients at presentations, particularly in the thalamus, and other deep grey matter structures. Furthermore, the correlations with clinical metrics suggest the importance of this atrophy to clinical status and the correlation with T1 lesion load suggests a possible role of Wallerian degeneration.
authors.affiliation: Department of Radiology, University of California at San Francisco, California, USA. Roland.Henry@radiology.ucsf.edu
authors.forename: R G
authors.initials: RG
authors.lastname: Henry
authors.forename: M
authors.initials: M
authors.lastname: Shieh
authors.forename: D T
authors.initials: DT
authors.lastname: Okuda
authors.forename: A
authors.initials: A
authors.lastname: Evangelista
authors.forename: M L
authors.initials: ML
authors.lastname: Gorno-Tempini
authors.forename: D
authors.initials: D
authors.lastname: Pelletier
mesh_terms: D000328:Adult; D001284:Atrophy / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001933:Brain Stem / Q000473:pathology; D002421:Caudate Nucleus / Q000473:pathology; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000473:pathology; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D011699:Putamen / Q000473:pathology; D013788:Thalamus / Q000473:pathology; D014855:Wallerian Degeneration / Q000150:complications / Q000473:pathology / Q000503:physiopathology