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Epstein-Barr Virus is Associated with Gray Matter Atrophy in Multiple Sclerosis
  1. Robert Zivadinov (rzivadinov{at}bnac.net)
  1. Buffalo Neuroimaging Analysis Center, United States
    1. Marino Zorzon (m.zorzon{at}fmc.units.it)
    1. UCO di Clinica Neurologica, Italy
      1. Bianca Weinstock-Guttman (bweinstock-guttman{at}kaleidahealth.org)
      1. SUNY University at Buffalo, United States
        1. Maurizia Serafin (maurizia.serafin{at}fastwebnet.it)
        1. Cattinara Hospital, Trieste, Italy
          1. Antonio Bosco (boscoantonio{at}virgilio.it)
          1. Department of Clinical Medicine and Neurology of Trieste, Italy
            1. Alessio Bratina (abratina{at}hotmail.com)
            1. UCO di Clinica Neurologica, Italy
              1. Attlio Grop (gropattilio{at}hotmail.com)
              1. Department of Clinical Medicine and Neurology of Trieste, Italy
                1. Cosimo Maggiore (c.maggiore{at}qmul.ac.uk)
                1. Department of Clinical Medicine and Neurology of Trieste, Italy
                  1. Maria Antonietta Tommasi (maritommasi{at}hotmail.com)
                  1. Department of Clinical Medicine and Neurology of Trieste, Italy
                    1. Bhooma Srinivasaraghavan (sbhooma{at}gmail.com)
                    1. Buffalo Neuroimaging Analysis Center, United States
                      1. Murali Ramanathan (murali{at}buffalo.edu)
                      1. State University of New York, United States

                        Abstract

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

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

                        Results: The GMF (R2 = 0.24 for overall model and Standardized β = -0.26, p = 0.002) and BPF (R2 = 0.39 for overall model and Standardized β = -0.28, p < 0.001) showed negative associations with anti-EBV-VCA IgG levels. Higher decline in BPF was significantly associated with increased -3-year time point anti-EBV VCA IgG levels (p = 0.007).

                        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-year follow-up.

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