title: Gray and white matter volume changes in early RRMS: a 2-year longitudinal study.
abstract: BACKGROUND
  Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis (RRMS). Previous work has suggested that at this stage of the disease, gray matter (GM) atrophy progresses more rapidly than the white matter (WM) atrophy.
  
  
  OBJECTIVE
  To characterize the evolution of GM and WM volumes over 2 years, and their associations with lesion loads in a cohort of patients with clinically early RRMS.
  
  
  METHODS
  Twenty-one patients with RRMS (mean age 37.5 years, mean disease duration from symptom onset 2.1 years) and 10 healthy control subjects (mean age 37.1 years) were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1- and 2-year follow-up. Brain parenchymal fractions (BPF), GM fractions (GMF), and WM fractions (WMF) were estimated. In subjects with MS, brain lesion loads were determined on conventional T2-weighted along with pre- and post-gadolinium (Gd) enhanced T1-weighted images at each timepoint.
  
  
  RESULTS
  A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study (mean -2.1% vs -1.0%, p = 0.044), while no change was seen in WMF over the same period (mean -0.09% vs +0.09%, p = 0.812). However, when the MS cohort was divided in half, dependent upon change in Gd-enhancing lesion load over 2 years (n = 20), a decrease in WMF was seen in the group (n = 10) with the largest decline in Gd volume, whereas WMF increased in the other half (n = 10) concurrent with a net increase in volume of Gd-enhancing lesions (difference between groups: p = 0.034).
  
  
  CONCLUSIONS
  Increasing gray matter but not white matter (WM) atrophy was observed early in the clinical course of relapsing-remitting multiple sclerosis. Fluctuations in inflammatory WM lesions appear to be related to volume changes in WM over this time period.
authors.affiliation: NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, London WC1N 3BG, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tiberio
authors.forename: D T
authors.initials: DT
authors.lastname: Chard
authors.forename: D R
authors.initials: DR
authors.lastname: Altmann
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.forename: C M
authors.initials: CM
authors.lastname: Griffin
authors.forename: W
authors.initials: W
authors.lastname: Rashid
authors.forename: J
authors.initials: J
authors.lastname: Sastre-Garriga
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D001284:Atrophy / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D042241:Early Diagnosis; D004660:Encephalitis / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000592:standards*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000503:physiopathology; D009187:Myelitis / Q000175:diagnosis / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D013997:Time Factors