The World Risk of Relapse under the control of the Environment

Spelman T, Gray O, Trojano M, Petersen T, Izquierdo G, Lugaresi A, Hupperts R, Bergamaschi R, Duquette P, Grammond P, Giuliani G, Boz C, Verheul F, Oreja-Guevara C, Barnett M, Grand’Maison F, Rio ME, Lechner-Scott J, Van Pesch V, Bolanos RF, Flechter S, Den Braber-Moerland L, Iuliano G, Amato MP, Slee M, Cristiano E, Saladino ML, Paine M, Vella N, Kasa K, Deri N, Herbert J, Moore F, Petkovska-Boskova T, Alroughani R, Savino A, Shaw C, Vucic S, Santiago V, Bacile EA, Skromne E, Poehlau D, Cabrera-Gomez JA, Lucas R, Butzkueven H. Seasonal variation of relapse rate in multiple sclerosis is latitude-dependent. Anal Neurol. 2014 Oct. doi: 10.1002/ana.24287. [Epub ahead of print]

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 if there is a temporal variation in onset of relapses in both hemispheres and to determine if seasonal peak relapse probability varies with latitude. Methods: The MSBase international 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 ultra-violet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak. 

Results: 32,762 relapses from 9811 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 degrees of latitude away from the equator was associated with a mean decrease in ultra-violet radiation trough to subsequent relapse peak lag of 28 .5 days (95 % CI 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.

Maybe this is the post that ProfG should have made because it will get his juices going as it speaks to an environmental factor are the the core of the disease driving forward. 

This study looks at the effect of relapses in people with MS across 30 countries and links this to latitude or distance from the equator and season. What this study suggests is that there is are a seasonal risks of MS relapse that peak and trough and are more common spring and less common in winter. This may be consistent with the hypothesis that vitamin D which is produced in response to sunlight may have some role in determining disease activity or may be seasonal infections, not forgetting that it could be related to ice cream consumption which is higher in summer and lower in winter:-).

Importantly this trend is found in the Southern Hemisphere as well as the Northern Hemisphere therefore indicating it is no simply a time issue but a time issue in relation to day length. Interestingly as you move from the equator there is a lag of about a month for every 10 degress North or South.

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  • My doc said they got two peaks: autumn and spring. And the same I see there, there is nobody in summer and the clinic is full during the spring/autumn with huuuuge queues everywhere. I think clinicians are noticing this obvious patterns everywhere?

  • This is a trend I'm bucking, my first relapse was in September 15 years ago. Since then it's mainly been August and December. I live in the mainly unsunny city of London. This year it was late August again (and it had been unseasonably sunny for months). I don't get heat intolerance either. So I'm reasonably confident that my relapses have nothing to do with the season and a lot to do with stress – a particular type at that. Because every relapse I've had has followed a period of chronic emotional stress.

    • It's interesting stress as a relapse trigger keeps coming up. Its not a few hours of stress, it's stress over days or weeks that seem to be a problem.

  • Always had my relapses in Spring or Autumn, If I told my friends I didn't feel well, they'd tell me to look at the calendar. I seemed to be in hospital in May and October. I thought it was only me.

  • The lag in the peak with latitude, if real, points to it not being absolute level of anything (say UV or vitamin d) that is the trigger, but something sensing the change in level and the timing is to match the lowest point. My money is on Epstein Barr.

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