title: Temporal trends in the incidence of multiple sclerosis: a systematic review.
abstract: BACKGROUND
  Multiple sclerosis (MS) has been traditionally considered to be more frequent in women and in regions more distant from the equator. However, recent reports suggest that the latitude gradient could be disappearing and that the female-to-male ratio among patients with MS has increased in the last decades. We have conducted a systematic review of incidence studies of MS to assess the overall incidence of MS and explore possible changes in the latitude gradient and the female-to-male ratio over time.
  
  
  METHODS
  Systematic review of incidence studies of MS published in Medline between 1966 and February 2007. Age- and sex-specific incidence rates were collected from eligible publications. We computed age-adjusted rates using the world population as standard, and assessed differences in rates according to latitude and period of case ascertainment. Additionally, we evaluated the association between period of case ascertainment and the female-to-male ratio.
  
  
  RESULTS
  The overall incidence rate of MS was 3.6 cases per 100,000 person-years (95% CI 3.0, 4.2) in women and 2.0 (95% CI 1.5, 2.4) in men. Higher latitude was associated with higher MS incidence, though this latitude gradient was attenuated after 1980, apparently due to increased incidence of MS in lower latitudes. The female-to-male ratio in MS incidence increased over time, from an estimated 1.4 in 1955 to 2.3 in 2000.
  
  
  CONCLUSIONS
  The latitude gradient present in older incidence studies of multiple sclerosis (MS) is decreasing. The female-to-male MS ratio has increased in the last five decades.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, West Bank Office Building, 1300 S 2nd St, Suite 300, Minneapolis, MN 55454, USA. aalogut@alumni.unav.es
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D014943:Global Health; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology*; D012307:Risk Factors; D017678:Sex Distribution