title: Relevance of spinal cord abnormalities to clinical disability in multiple sclerosis: MR imaging findings in a large cohort of patients.
abstract: OBJECTIVE
  To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers.
  
  
  METHODS
  The institutional review board approved the study; all subjects gave written informed consent. Upper cervical cord cross-sectional area (UCCA), brain and spinal cord lesion loads, and brain atrophy were measured in 440 patients with MS (311 with relapsing-remitting [RR] MS, 92 with secondary-progressive [SP] MS, and 37 with primary-progressive [PP] MS) studied in two centers. Disability was scored with the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (TWT), and the nine-hole peg test. UCCA was compared between groups with the Mann-Whitney U test. Correlations were assessed with the Spearman ρ test. Multivariate associations between UCCA and clinical and other MR imaging parameters, including number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord, were assessed by using multiple linear regression, adjusted for study center site.
  
  
  RESULTS
  The UCCA in patients with SP MS (median, 79 mm(2); interquartile range, 72.4-84.9 mm(2)) and PP MS (median, 77.3 mm(2); interquartile range, 69-82.5 mm(2)) was significantly smaller (P < .001) than that in patients with RR MS (median, 84 mm(2); interquartile range, 78.7-89.3 mm(2)). UCCA was inversely correlated with EDSS score, TWT, and nine-hole peg test findings (ρ ≤ -0.29, P < .001 for all comparisons). UCCA, number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord were found to be significant explanatory factors for clinical disability (R(2) = 0.564). The UCCA and the number of hypointense brain lesions on T1-weighted images were the strongest MR imaging parameters for explaining physical disability, as measured with the EDSS.
  
  
  CONCLUSIONS
  Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.
authors.affiliation: Department of Diagnostic and Interventional Radiology and Nuclear Medicine, St Josef Hospital, Ruhr University Bochum, Gudrunstr. 56, 44791 Bochum, Germany; Departments of Neurology, Radiology, Epidemiology and Biostatistics, Anatomy and Neurosciences, Section of Clinical Neuroscience, and Physics and Medical Technology, MS Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Fraunhofer MEVIS, Institute for Medical Image Computing, Bremen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Lukas
authors.forename: Madeleine H
authors.initials: MH
authors.lastname: Sombekke
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellenberg
authors.forename: Horst K
authors.initials: HK
authors.lastname: Hahn
authors.forename: Veronica
authors.initials: V
authors.lastname: Popescu
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bendfeldt
authors.forename: Ernst W
authors.initials: EW
authors.lastname: Radue
authors.forename: Achim
authors.initials: A
authors.lastname: Gass
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Borgwardt
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Naegelin
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Knol
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology*