title: Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event: results from the multi-center set study.
abstract: OBJECTIVE
  To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.
  
  
  METHODS
  We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.
  
  
  RESULTS
  Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions.
  
  
  CONCLUSIONS
  Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA; Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Chin
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Tamaño-Blanco
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Badgett
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hagemeier
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Carl
authors.affiliation: Department of Radiology, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: Department of Radiology, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Radiology, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dwyer
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA; Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA. Electronic address: Murali@Buffalo.Edu.
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use*; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology / Q000821:virology; D036022:Capsid Proteins / Q000276:immunology; D003711:Demyelinating Diseases / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D006564:Herpesviridae / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D056784:Leukoencephalopathies / Q000209:etiology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D019636:Neurodegenerative Diseases / Q000209:etiology*; D019370:Observation; D013788:Thalamus / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000998:Antiviral Agents; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; D016899:Interferon-beta
keywords: Cytomegalovirus; Deep gray matter atrophy; Environmental factors; Epstein–Barr virus