Seasonal variation of relapse rate in multiple sclerosis is latitude dependent

Tim Spelman*, Orla Gray, Maria Trojano, Thor Petersen, Guillermo Izquierdo, Alessandra Lugaresi, Raymond Hupperts, Roberto Bergamaschi, Pierre Duquette, Pierre Grammond, Giorgio Giuliani, Cavit Boz, Freek Verheul, Celia Oreja-Guevara, Michael Barnett, Francois Grand'Maison, Maria Edite Rio, Jeannette Lechner-Scott, Vincent Van Pesch, Ricardo Fernandez BolanosShlomo Flechter, Leontien Den Braber-Moerland, Gerardo Iuliano, Maria Pia Amato, Mark Slee, Edgardo Cristiano, Maria Laura Saladino, Mark Paine, Norbert Vella, Krisztian Kasa, Norma Deri, Joseph Herbert, Fraser Moore, Tatjana Petkovska-Boskova, Raed Alroughani, Aldo Savino, Cameron Shaw, Steve Vucic, Vetere Santiago, Elizabeth Alejandra Bacile, Eli Skromne, Dieter Poehlau, Jose Antonio Cabrera-Gomez, Robyn Lucas, Helmut Butzkueven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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).

INTERPRETATION: 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.

Original languageEnglish
Pages (from-to)880-90
Number of pages11
JournalAnnals of Neurology
Issue number6
Publication statusPublished - Dec 2014


  • Adult
  • Databases, Factual
  • Female
  • Humans
  • Internationality
  • Longitudinal Studies
  • Male
  • Multiple Sclerosis, Relapsing-Remitting
  • Prospective Studies
  • Recurrence
  • Registries
  • Seasons
  • Sunlight
  • Ultraviolet Rays
  • Young Adult

Cite this