title: Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis.
abstract: BACKGROUND
  Disability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability.
  
  
  METHODS
  Infected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4-5 spinal cord cross-sectional area measurements were performed using Analyze 10.
  
  
  RESULTS
  At 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post-infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross-sectional area was 25.6% reduced (P = .001) among cases.
  
  
  CONCLUSIONS
  Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: M Mateo
authors.initials: MM
authors.lastname: Paz Soldán
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mekala R
authors.initials: MR
authors.lastname: Raman
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Gamez
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Lohrey
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Istvan
authors.initials: I
authors.lastname: Pirko
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D008279:Magnetic Resonance Imaging; D051379:Mice; D009069:Movement Disorders / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis*; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology; D013223:Statistics as Topic
keywords: Multiple sclerosis; atrophy; disability; magnetic resonance imaging