title: Environmental factors associated with disease progression after the first demyelinating event: results from the multi-center SET study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors: Dana
authors: D
authors: Horakova
authors: Robert
authors: R
authors: Zivadinov
authors: Bianca
authors: B
authors: Weinstock-Guttman
authors: Eva
authors: E
authors: Havrdova
authors: Jun
authors: J
authors: Qu
authors: Miriam
authors: M
authors: Tamaño-Blanco
authors: Darlene
authors: D
authors: Badgett
authors: Michaela
authors: M
authors: Tyblova
authors: Niels
authors: N
authors: Bergsland
authors: Sara
authors: S
authors: Hussein
authors: Laura
authors: L
authors: Willis
authors: Jan
authors: J
authors: Krasensky
authors: Manuela
authors: M
authors: Vaneckova
authors: Zdenek
authors: Z
authors: Seidl
authors: Petra
authors: P
authors: Lelkova
authors: Michael G
authors: MG
authors: Dwyer
authors: Ming
authors: M
authors: Zhang
authors: Haoying
authors: H
authors: Yu
authors: Xiaotao
authors: X
authors: Duan
authors: Tomas
authors: T
authors: Kalincik
authors: Murali
authors: M
authors: Ramanathan
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000276:immunology; D018450:Disease Progression; D004777:Environment; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology* / Q000276:immunology / Q000821:virology; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; C417029:EBV-encoded nuclear antigen 1