title: Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis.
abstract: Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years.
  
  
  
  Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1-10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated.
  
  
  
  While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS.
  
  
  
  While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that 1 route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted.
authors.affiliation: Mellen Center for Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Lael Anne
authors.initials: LA
authors.lastname: Stone
authors.affiliation: Department of Biostatistics, UAB School of Public Health, Birmingham, AL.
authors.forename: Gary Raymond
authors.initials: GR
authors.lastname: Cutter
authors.affiliation: Biogen Inc, Cambridge, MA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fisher
authors.affiliation: Biogen Inc, Cambridge, MA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Richert
authors.affiliation: Neuroimmunology Branch of the National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McCartin
authors.affiliation: Neuroimmunology Branch of the National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Joan
authors.initials: J
authors.lastname: Ohayon
authors.affiliation: Department of Neuroradiology, Uniformed Services School of Medicine, Bethesda, MD.
authors.forename: Craig
authors.initials: C
authors.lastname: Bash
authors.affiliation: Cumming Foundation, Salt Lake City, UT.
authors.forename: Henry
authors.initials: H
authors.lastname: McFarland
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007089:Image Enhancement; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000000981:diagnostic imaging*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging*; D009460:Neurologic Examination; D013223:Statistics as Topic
keywords: Contrast-enhancing lesions; MRI; disability; mediator variable; multiple sclerosis; relapses