title: Seasonal variation of relapse rate in multiple sclerosis is latitude dependent.
abstract: OBJECTIVE
  Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude.
  
  
  METHODS
  The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak.
  
  
  RESULTS
  A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29-53.71, p = 0.028).
  
  
  CONCLUSIONS
  We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere.
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.forename: Orla
authors.initials: O
authors.lastname: Gray
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giuliani
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.forename: Freek
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authors.lastname: Verheul
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.forename: Francois
authors.initials: F
authors.lastname: Grand'Maison
authors.forename: Maria
authors.initials: M
authors.lastname: Edite Rio
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez Bolanos
authors.forename: Shlomo
authors.initials: S
authors.lastname: Flechter
authors.forename: Leontien
authors.initials: L
authors.lastname: Den Braber-Moerland
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.forename: Edgardo
authors.initials: E
authors.lastname: Cristiano
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Saladino
authors.forename: Mark
authors.initials: M
authors.lastname: Paine
authors.forename: Norbert
authors.initials: N
authors.lastname: Vella
authors.forename: Krisztian
authors.initials: K
authors.lastname: Kasa
authors.forename: Norma
authors.initials: N
authors.lastname: Deri
authors.forename: Joseph
authors.initials: J
authors.lastname: Herbert
authors.forename: Fraser
authors.initials: F
authors.lastname: Moore
authors.forename: Tatjana
authors.initials: T
authors.lastname: Petkovska-Boskova
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.forename: Aldo
authors.initials: A
authors.lastname: Savino
authors.forename: Cameron
authors.initials: C
authors.lastname: Shaw
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.forename: Vetere
authors.initials: V
authors.lastname: Santiago
authors.forename: Elizabeth Alejandra
authors.initials: EA
authors.lastname: Bacile
authors.forename: Eli
authors.initials: E
authors.lastname: Skromne
authors.forename: Dieter
authors.initials: D
authors.lastname: Poehlau
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Cabrera-Gomez
authors.forename: Robyn
authors.initials: R
authors.lastname: Lucas
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D016208:Databases, Factual / Q000639:trends; D005260:Female; D006801:Humans; D038622:Internationality; D008137:Longitudinal Studies; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000453:epidemiology*; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D012621:Seasons; D013472:Sunlight; D014466:Ultraviolet Rays; D055815:Young Adult