title: Atrophy and structural variability of the upper cervical cord in early multiple sclerosis.
abstract: BACKGROUND
  Despite agreement about spinal cord atrophy in progressive forms of multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) are conflicting.
  
  
  OBJECTIVE
  To determine the onset of spinal cord atrophy in the disease course of MS.
  
  
  METHODS
  Structural brain magnetic resonance imaging (MRI) was acquired from 267 patients with CIS (85) or RRMS (182) and 64 healthy controls (HCs). The upper cervical cord cross-sectional area (UCCA) was determined at the level of C2/C3 by a segmentation tool and adjusted for focal MS lesions. The coefficient of variation (CV) was calculated from all measurements between C2/C3 and 13 mm above as a measure of structural variability.
  
  
  RESULTS
  Compared to HCs (76.1±6.9 mm(2)), UCCA was significantly reduced in CIS patients (73.5±5.8 mm(2), p=0.018) and RRMS patients (72.4±7.0 mm(2), p<0.001). Structural variability was higher in patients than in HCs, particularly but not exclusively in case of focal lesions (mean CV HCs/patients without/with lesions: 2.13%/2.55%/3.32%, all p-values<0.007). UCCA and CV correlated with Expanded Disability Status Scale (EDSS) scores (r =-0.131/0.192, p=0.044/<0.001) and disease duration (r=-0.134/0.300, p=0.039/< 0.001). CV additionally correlated with hand and arm function (r=0.180, p=0.014).
  
  
  CONCLUSIONS
  In MS, cervical cord atrophy already occurs in CIS. In early stages, structural variability may be a more meaningful marker of spinal cord pathology than atrophy.
authors.affiliation: Technische Universität München, Germany/TUM-Neuroimaging Center, Technische Universität München, Germany biberacher@lrz.tum.de.
authors.forename: Viola
authors.initials: V
authors.lastname: Biberacher
authors.affiliation: Technische Universität München, Germany/TUM-Neuroimaging Center, Technische Universität München, Germany.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Boucard
authors.affiliation: Technische Universität München, Germany/TUM-Neuroimaging Center, Technische Universität München, Germany/Ludwig-Maximilians-University München, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Schmidt
authors.affiliation: Technische Universität München, Germany/TUM-Neuroimaging Center, Technische Universität München, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Engl
authors.affiliation: Department of Neurology, Technische Universität München, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Buck
authors.affiliation: Department of Neurology, Technische Universität München, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Berthele
authors.affiliation: Department of Neurology, Technische Universität München, Germany.
authors.forename: Muna-Miriam
authors.initials: MM
authors.lastname: Hoshi
authors.affiliation: Technische Universität München, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Zimmer
authors.affiliation: Technische Universität München, Germany/Munich Cluster for Systems Neurology (SyNergy), Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.affiliation: Technische Universität München, Germany/TUM-Neuroimaging Center, Technische Universität München, Germany/Munich Cluster for Systems Neurology (SyNergy), Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Mühlau
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D066193:Cervical Cord / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D055815:Young Adult
keywords: Cervical cord; clinically isolated syndrome; magnetic resonance imaging; relapsing–remitting multiple sclerosis