J Neurol Neurosurg Psychiatry 80:620-625 doi:10.1136/jnnp.2008.154906
  • Research paper

Epstein–Barr virus is associated with grey matter atrophy in multiple sclerosis

  1. R Zivadinov1,2,
  2. M Zorzon3,
  3. B Weinstock-Guttman2,4,
  4. M Serafin5,
  5. A Bosco3,
  6. A Bratina3,
  7. C Maggiore3,
  8. A Grop3,
  9. M A Tommasi3,
  10. B Srinivasaraghavan1,
  11. M Ramanathan2,6
  1. 1
    Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, New York, USA
  2. 2
    The Jacobs Neurological Institute, Department of Neurology, State University of New York, Buffalo, New York, USA
  3. 3
    Department of Clinical Medicine and Neurology, Trieste, Italy
  4. 4
    Baird Multiple Sclerosis Center, Department of Neurology, State University of New York, Buffalo, New York, USA
  5. 5
    Laboratory of Clinical Research, Cattinara Hospital, Trieste, Italy
  6. 6
    Department of Pharmaceutical Sciences, State University of New York, Buffalo, New York, USA
  1. Dr M Ramanathan, Departments of Pharmaceutical Sciences and Neurology, State University of New York, 427 Cooke Hall, Buffalo, NY 14260, USA; Murali{at}
  • Received 29 May 2008
  • Revised 9 December 2008
  • Accepted 8 January 2009
  • Published Online First 23 January 2009


Objective: The aim of the study was to determine whether the presence of anti-Epstein–Barr virus (EBV) antibodies is associated with MRI measures of brain injury and neurodegeneration in patients with multiple sclerosis (MS).

Methods: 135 patients with MS (86 women, 49 men) underwent brain MRI and testing for antibodies against EBV. MRI measurements included gadolinium enhancing lesion volume, T1 and T2 lesion volumes and fractions of whole brain parenchyma (BPF), white matter and grey matter (GMF). The anti-EBV panel included anti-EBV early antigen IgG, anti-EBV nuclear antigen IgG and anti-EBV viral capsid antigen (VCA) IgG levels. The relationships between antibody levels and MRI measurements were assessed in regression analysis. Repeat measurements of anti-EBV VCA IgG and MRI measures were available for a subset of 50 patients after a mean follow-up of 3.1 years.

Results: GMF (R2 = 0.24 for overall model, p = 0.002) and BPF (R2 = 0.39 for overall model, p<0.001) showed negative associations with anti-EBV-VCA IgG levels. A greater decline in BPF over 3 years was significantly associated with increased 3 years prior time point anti-EBV VCA IgG levels (p<0.001).

Conclusions: The results suggest that the presence of anti-EBV antibodies is associated with MRI markers of GM atrophy in MS and with increased loss of brain volume over 3 years.


  • Funding: This work was supported in part by the Consortium for International Development of the University of Trieste, Italy through a research fellowship to Dr Robert Zivadinov. Additional support from the National Multiple Sclerosis Society (RG3743 and a Pediatric MS Center of Excellence Center Grant) is gratefully acknowledged.

  • Competing interests: Several of the authors have served as consultants, speakers or have received research funding for pharmaceutical companies, including Biogen Idec, EMD Serono, Teva Neuroscience and others. However, the funding was unrelated to the research presented here.

  • Ethics approval: Ethics approval was obtained.

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