title: Association Between Thoracic Spinal Cord Gray Matter Atrophy and Disability in Multiple Sclerosis.
abstract: OBJECTIVE
  In multiple sclerosis (MS), upper cervical cord gray matter (GM) atrophy correlates more strongly with disability than does brain or cord white matter (WM) atrophy. The corresponding relationships in the thoracic cord are unknown owing to technical difficulties in assessing GM and WM compartments by conventional magnetic resonance imaging techniques.
  
  
  OBJECTIVE
  To investigate the associations between MS disability and disease type with lower thoracic cord GM and WM areas using phase-sensitive inversion recovery magnetic resonance imaging at 3 T, as well as to compare these relationships with those obtained at upper cervical levels.
  
  
  METHODS
  Between July 2013 and March 2014, a total of 142 patients with MS (aged 25-75 years; 86 women) and 20 healthy control individuals were included in this cross-sectional observational study conducted at an academic university hospital.
  
  
  METHODS
  Total cord areas (TCAs), GM areas, and WM areas at the disc levels C2/C3, C3/C4, T8/9, and T9/10. Area differences between groups were assessed, with age and sex as covariates.
  
  
  RESULTS
  Patients with relapsing MS (RMS) had smaller thoracic cord GM areas than did age- and sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm2 [9.2%]; P = .003 at T8/T9 and 0.93 mm2 [8.0%]; P = .01 at T9/T10); however, there were no significant differences in either the WM area or TCA. Patients with progressive MS showed smaller GM areas (mean differences [COV]: 1.02 mm2 [10.6%]; P < .001 at T8/T9 and 1.37 mm2 [13.2%]; P < .001 at T9/T10) and TCAs (mean differences [COV]: 3.66 mm2 [9.0%]; P < .001 at T8/T9 and 3.04 mm2 [7.2%]; P = .004 at T9/T10) compared with patients with RMS. All measurements (GM, WM, and TCA) were inversely correlated with Expanded Disability Status Scale score. Thoracic cord GM areas were correlated with lower limb function. In multivariable models (which also included cord WM areas and T2 lesion number, brain WM volumes, brain T1 and fluid-attenuated inversion recovery lesion loads, age, sex, and disease duration), cervical cord GM areas had the strongest correlation with Expanded Disability Status Scale score followed by thoracic cord GM area and brain GM volume.
  
  
  CONCLUSIONS
  Thoracic cord GM atrophy can be detected in vivo in the absence of WM atrophy in RMS. This atrophy is more pronounced in progressive MS than RMS and correlates with disability and lower limb function. Our results indicate that remarkable cord GM atrophy is present at multiple cervical and lower thoracic levels and, therefore, may reflect widespread cord GM degeneration.
authors.affiliation: Department of Neurology, University of California, San Francisco2Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Regina
authors.initials: R
authors.lastname: Schlaeger
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Nico
authors.initials: N
authors.lastname: Papinutto
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Zhu
authors.affiliation: Department of Neurology, University of California, San Francisco3Departments of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Lobach
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Bevan
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Monica
authors.initials: M
authors.lastname: Bucci
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castellano
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gelfand
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Graves
authors.affiliation: Department of Neurology, University of California, San Francisco4Department of Ophthalmology, University of California, San Francisco.
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Green
authors.affiliation: Department of Neurology, University of California, San Francisco5Bioengineering Graduate Group, University of California, San Francisco and Berkeley.
authors.forename: Kesshi M
authors.initials: KM
authors.lastname: Jordan
authors.affiliation: Department of Neurology, University of California, San Francisco5Bioengineering Graduate Group, University of California, San Francisco and Berkeley.
authors.forename: Anisha
authors.initials: A
authors.lastname: Keshavan
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Valentina
authors.initials: V
authors.lastname: Panara
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: William A
authors.initials: WA
authors.lastname: Stern
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: H-Christian
authors.initials: HC
authors.lastname: von Büdingen
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Goodin
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.affiliation: Department of Neurology, University of California, San Francisco.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.affiliation: Department of Neurology, University of California, San Francisco5Bioengineering Graduate Group, University of California, San Francisco and Berkeley6Department of Radiology and Biomedical Imaging, University of California, San Francisco.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Henry
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology*; D013904:Thoracic Vertebrae