title: Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome.
abstract: OBJECTIVE
  The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months.
  
  
  METHODS
  Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon β-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period.
  
  
  RESULTS
  In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period.
  
  
  CONCLUSIONS
  Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (M.V., T.U., J.H., N.B., M.G.D., R.Z.), Department of Neurology, University at Buffalo SUNY, Buffalo, New York.
authors.forename: M
authors.initials: M
authors.lastname: Varosanec
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (M.V., T.U., J.H., N.B., M.G.D., R.Z.), Department of Neurology, University at Buffalo SUNY, Buffalo, New York Department of Neurology and Center of Clinical Neuroscience (T.U., D.H., M.T., E.H.).
authors.forename: T
authors.initials: T
authors.lastname: Uher
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience (T.U., D.H., M.T., E.H.).
authors.forename: D
authors.initials: D
authors.lastname: Horakova
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (M.V., T.U., J.H., N.B., M.G.D., R.Z.), Department of Neurology, University at Buffalo SUNY, Buffalo, New York.
authors.forename: J
authors.initials: J
authors.lastname: Hagemeier
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (M.V., T.U., J.H., N.B., M.G.D., R.Z.), Department of Neurology, University at Buffalo SUNY, Buffalo, New York IRCCS "Santa Maria Nascente" (N.B.), Don Gnocchi Foundation, Milan, Italy.
authors.forename: N
authors.identifier: http://orcid.org/0000-0002-7792-0433
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience (T.U., D.H., M.T., E.H.).
authors.forename: M
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Department of Radiology (Z.S., M.V., J.K.), Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: Z
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Department of Radiology (Z.S., M.V., J.K.), Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Radiology (Z.S., M.V., J.K.), Charles University in Prague, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (M.V., T.U., J.H., N.B., M.G.D., R.Z.), Department of Neurology, University at Buffalo SUNY, Buffalo, New York.
authors.forename: M G
authors.initials: MG
authors.lastname: Dwyer
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience (T.U., D.H., M.T., E.H.).
authors.forename: E
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: From the Buffalo Neuroimaging Analysis Center (M.V., T.U., J.H., N.B., M.G.D., R.Z.), Department of Neurology, University at Buffalo SUNY, Buffalo, New York rzivadinov@bnac.net.
authors.forename: R
authors.initials: R
authors.lastname: Zivadinov
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D001284:Atrophy / Q000473:pathology; D001927:Brain Diseases / Q000188:drug therapy / Q000473:pathology*; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D000276:Adjuvants, Immunologic; D000068556:Interferon beta-1a