title: Early CNS neurodegeneration in radiologically isolated syndrome.
abstract: OBJECTIVE
  Increasing evidence indicates that the thalamus may be a location of early neurodegeneration in multiple sclerosis (MS). Our objective was to identify the presence of gray matter volume loss and thinning in patients with radiologically isolated syndrome (RIS).
  
  
  METHODS
  Sixty-three participants were included in this case-control study. Twenty-one patients with RIS were age- and sex-matched to 42 healthy controls in a 1:2 ratio. All participants underwent brain MRIs on a single 3T scanner. After lesion segmentation and inpainting, 1 mm(3)-isometric T1-weighted images were submitted to FreeSurfer (v5.2). Normalized cortical and deep gray matter volumes were compared between patients with RIS and controls using t tests, and thalamic volumes were correlated with white matter lesion volumes using Pearson correlation. Exploratory cortical thickness maps were created.
  
  
  RESULTS
  Although traditional normalized total gray and white matter volumes were not statistically different between patients with RIS and controls, normalized left (0.0046 ± 0.0005 vs 0.0049 ± 0.0004, p = 0.006), right (0.0045 ± 0.0005 vs 0.0048 ± 0.0004, p = 0.008), and mean (0.0045 ± 0.0005 vs 0.0049 ± 0.0004, p = 0.004) thalamic volumes were significantly lower in patients with RIS (n = 21, mean age 41.9 ± 12.7 years) than in controls (n = 42, mean age 41.4 ± 11.2 years). Thalamic volumes correlated modestly with white matter lesion volumes (range: r = -0.35 to -0.47).
  
  
  CONCLUSIONS
  Our data provide novel evidence of thalamic atrophy in RIS and are consistent with previous reports in early MS stages. Thalamic volume loss is present early in CNS demyelinating disease and should be further investigated as a metric associated with neurodegeneration.
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Azevedo
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Eve
authors.initials: E
authors.lastname: Overton
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Sankalpa
authors.initials: S
authors.lastname: Khadka
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Jessica
authors.initials: J
authors.lastname: Buckley
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Mehul
authors.initials: M
authors.lastname: Sampat
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Orhun
authors.initials: O
authors.lastname: Kantarci
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Christine
authors.initials: C
authors.lastname: Lebrun Frenay
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Aksel
authors.initials: A
authors.lastname: Siva
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Darin T
authors.initials: DT
authors.lastname: Okuda
authors.affiliation: Department of Neurology (C.J.A., E.O., S.K., J.B., S.L., M.S., D.P.) and Department of Diagnostic Radiology (D.P.), Yale University, New Haven, CT; Department of Neurology (O.K.), Mayo Clinic College of Medicine, Rochester, MN; Service de Neurologie (C.L.F.), Hospital Pasteur, Nice, France; Department of Neurology (A.S.), Cerrahpasa School of Medicine, University of Istanbul, Turkey; and Department of Neurology (D.T.O.), University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier