title: Cervical cord lesion load is associated with disability independently from atrophy in MS.
abstract: OBJECTIVE
  To investigate whether spinal cord (SC) lesion load, when quantified on axial images with high in-plane resolution, is associated with disability in multiple sclerosis (MS).
  
  
  METHODS
  Twenty-eight healthy controls and 92 people with MS had cervical SC 3T MRI with axial phase sensitive inversion recovery, T2, and magnetization transfer (MT) sequences. We outlined all visible focal lesions from C2 to C4 to obtain lesion load and also measured upper cervical cord area. We measured MT ratio in normal-appearing cord tissue and in lesions. Disability was recorded using the Expanded Disability Status Scale (EDSS) and MS Functional Composite. We used linear regression models to determine associations with disability.
  
  
  RESULTS
  SC lesion load was significantly higher in both secondary progressive MS (SPMS) (p = 0.008) and primary progressive MS (PPMS) (p = 0.02) compared to relapsing-remitting MS (RRMS); in each comparison, adjustment was made for age, sex, and brain volume. These differences were not evident when EDSS was added as a covariate. SC area was significantly lower in both SPMS (p < 0.001) and PPMS (p = 0.009) compared to RRMS. In a multiple regression model, cord lesion load (p < 0.001), cord area (p = 0.003), age (p < 0.001), and sex (p = 0.001) were independently associated with EDSS (R(2) = 0.58). Cord lesion load (p = 0.003), cord area (p = 0.034), and brain parenchymal fraction (p = 0.007) were independently associated with the 9-hole peg test (R(2) = 0.42).
  
  
  CONCLUSIONS
  When quantified on axial MRI with high in-plane resolution, upper cervical cord lesion load is significantly and independently correlated with physical disability and is higher in progressive forms of MS than RRMS.
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK. hugh.kearney.10@ucl.ac.uk.
authors.forename: Hugh
authors.initials: H
authors.lastname: Kearney
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Altmann
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Samson
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK.
authors.forename: Marios C
authors.initials: MC
authors.lastname: Yiannakas
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK.
authors.forename: Claudia A M
authors.initials: CA
authors.lastname: Wheeler-Kingshott
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
authors.affiliation: From the NMR Research Unit (H.K., D.R.A., R.S.S., M.C.Y., C.A.M.W.-K., O.C., D.H.M.), Queen Square MS Centre, UCL Institute of Neurology, London; the Department of Medical Statistics (D.R.A.), London School of Hygiene and Tropical Medicine; and NIHR University College London Hospitals Biomedical Research Centre (C.A.M.W.-K., O.C., D.H.M.), UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D066193:Cervical Cord / Q000473:pathology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology* / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000473:pathology*