title: Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon beta-1a (Rebif) treatment trial.
abstract: BACKGROUND
  Pathology in the cervical spinal cord is considered an important cause of disability in multiple sclerosis. However, the majority of serial studies have failed to find a correlation between spinal cord atrophy and disability.
  
  
  OBJECTIVE
  To use a highly reproducible and accurate method to quantify spinal cord area change on three dimensional magnetic resonance imaging and relate this to disability change in patients with multiple sclerosis.
  
  
  METHODS
  38 patients with multiple sclerosis (20 with the relapsing-remitting (RRMS) form and 18 with the secondary progressive (SPMS) form) were imaged at baseline and at months 6, 12, 18, and 48 during two treatment trials of the high dose subcutaneous thrice weekly interferon beta-1a (IFNbeta, Rebif). Thirty one healthy subjects were also imaged at baseline. Upper cervical cord area (UCCA) was measured using Sobel edge detection.
  
  
  RESULTS
  The intraobserver coefficient of variation of the method was 0.42%. A significant reduction in UCCA was detected at month 6 in the placebo group (p = 0.04) and at month 12 for INFbeta (p = 0.03). The mean reduction of UCCA at month 48 was 5.7% for patients initially on placebo who received treatment at 24 months (RRMS) or at 36 months (SPMS), and 4.5% for those on IFNbeta throughout the study (p = 0.35). The change in UCCA was significantly correlated with change in the expanded disability status scale at month 12 (r = 0.4, p = 0.016), month 18 (r = 0.32, p = 0.05), and month 48 (r = 0.4, p = 0.016) in the total cohort.
  
  
  CONCLUSIONS
  Despite the small number of patients studied and the possible confounding effects of interferon treatment, this study showed that edge detection is reproducible and sensitive to changes in spinal cord area, and that this change is related to changes in clinical disability. This suggests a role for measurement of spinal cord atrophy in monitoring disease progression and possible treatment effects in clinical trails.
authors.affiliation: Division of Clinical Neurology, Faculty of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: C R
authors.initials: CR
authors.lastname: Tench
authors.forename: B
authors.initials: B
authors.lastname: Turner
authors.forename: L D
authors.initials: LD
authors.lastname: Blumhardt
authors.forename: C S
authors.initials: CS
authors.lastname: Constantinescu
mesh_terms: D000328:Adult; D001284:Atrophy; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy; D015588:Observer Variation; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D016899:Interferon-beta; D000068556:Interferon beta-1a