PLoS ONE (Jan 2013)

Environmental factors associated with disease progression after the first demyelinating event: results from the multi-center SET study.

  • Dana Horakova,
  • Robert Zivadinov,
  • Bianca Weinstock-Guttman,
  • Eva Havrdova,
  • Jun Qu,
  • Miriam Tamaño-Blanco,
  • Darlene Badgett,
  • Michaela Tyblova,
  • Niels Bergsland,
  • Sara Hussein,
  • Laura Willis,
  • Jan Krasensky,
  • Manuela Vaneckova,
  • Zdenek Seidl,
  • Petra Lelkova,
  • Michael G Dwyer,
  • Ming Zhang,
  • Haoying Yu,
  • Xiaotao Duan,
  • Tomas Kalincik,
  • Murali Ramanathan

DOI
https://doi.org/10.1371/journal.pone.0053996
Journal volume & issue
Vol. 8, no. 1
p. e53996

Abstract

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To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.