title: Progression of disability in multiple sclerosis: A study of factors influencing median time to reach an EDSS value.
abstract: BACKGROUND
  The extended disability severity scale (EDSS) is clinically useful in assessing disability in multiple sclerosis (MS) patients. It is also being used in studies to determine how genes and environment influence disability. However, since it has a complex relationship with functional scores and mobility and is strongly determined by disease duration its use can be limiting.
  
  
  OBJECTIVE
  Study associations of variables with progression described by time from disease onset until EDSS.
  
  
  METHODS
  We used a variable based on below/above median time from MS onset to reach a single EDSS value to define slow or fast progression. We compared patient categorization using this variable and MSSS, and in 533 patients (EDSS 1-8) and 242 of these patients with EDSS1-4, studied associations with skin type, gender, ultraviolet radiation and MC1R Asp294His.
  
  
  RESULTS
  Classifying patients into quartiles of slow/fast progression showed mean MSSS increased with faster progression (p<0.001). For EDSS 1-8: MSSS, late onset age and childhood sunburning were associated with fast and MC1R CG/GG(294) with slow progression. Combinations of skin type (1/2 or 3/4) with childhood weekend exposure (< or ≥median) or sunburning (yes/no) were not associated with progression. However, in patients with EDSS1-4, relative to other combinations, those with no sunburning history and types 1/2 demonstrated slow progression (odds ratio=0.15, 95% CI=0.04, 0.57).
  
  
  CONCLUSIONS
  This method, though a pilot, allows study of associations of variables with EDSS. It is based on local patients and could substitute for MSSS. In patients with EDSS1-4 but not 1-8, skin type 1/2 with no history of childhood sunburning was associated with slow progression. This is compatible with the view that disability develops through a first stage dependent on inflammation.
authors: Keele Multiple Sclerosis Research Group, Department of Neurology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7LN, England, United Kingdom; Department of Biochemistry, Good Hope Hospital, Heart of England Foundation Trust, Sutton Coldfield B75 7RR, England, United Kingdom.
authors: Sudarshan
authors: S
authors: Ramachandran
authors: Keele Multiple Sclerosis Research Group, Department of Neurology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7LN, England, United Kingdom; Institute for Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, Stoke-on-Trent, ST4 7QB, England, United Kingdom.
authors: Richard C
authors: RC
authors: Strange
authors: Keele Multiple Sclerosis Research Group, Department of Neurology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7LN, England, United Kingdom; Institute for Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, Stoke-on-Trent, ST4 7QB, England, United Kingdom.
authors: Seema
authors: S
authors: Kalra
authors: Keele Multiple Sclerosis Research Group, Department of Neurology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7LN, England, United Kingdom; Institute for Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, Stoke-on-Trent, ST4 7QB, England, United Kingdom.
authors: Devaki
authors: D
authors: Nayak
authors: Unit of Urologic and Genetic Epidemiology, School of Health & Populations Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England, United Kingdom.
authors: Maurice P
authors: MP
authors: Zeegers
authors: Keele Multiple Sclerosis Research Group, Department of Neurology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7LN, England, United Kingdom; Institute for Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, Stoke-on-Trent, ST4 7QB, England, United Kingdom.
authors: Janice
authors: J
authors: Gilford
authors: Keele Multiple Sclerosis Research Group, Department of Neurology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire ST4 7LN, England, United Kingdom; Institute for Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, Stoke-on-Trent, ST4 7QB, England, United Kingdom. Electronic address: c.p.hawkins@pmed.keele.ac.uk.
authors: Clive P
authors: CP
authors: Hawkins
keywords: Disability evaluation; EDSS; MC1R; Multiple sclerosis; Ultraviolet radiation