Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis

M. Mateo Paz Soldán, Mekala R. Raman, Jeffrey D. Gamez, Anne K. Lohrey, Yi Chen, Istvan Pirko, Aaron J. Johnson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)595-599
Number of pages5
JournalJournal of Neuroimaging
Volume25
Issue number4
DOIs
StatePublished - Jul 1 2015

Keywords

  • Atrophy
  • Disability
  • Magnetic resonance imaging
  • Multiple sclerosis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology

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