Seasonal variation in multiple sclerosis relapse

Abstract

Relapses are a characteristic clinical feature of multiple sclerosis (MS), but an appreciation of factors that cause them remains elusive. In this study, we have examined seasonal variation of relapse in a large population-based MS cohort and correlated observed patterns with age, sex, disease course, and climatic factors. Relapse data were recorded prospectively in 2076 patients between 2005 and 2014. 3902 events were recorded in 1158 patients (range 0–24). There was significant seasonal variation in relapse rates (p < 0.0001) and this was associated with monthly hours of sunshine (odds ratio OR 1.08, p = 0.02). Relapse rates were highest in patients under the age of 30 (OR 1.42, p = 0.0005) and decreased with age. There was no evidence of different relapse rates for males compared to females (OR 0.90, p = 0.19). Identification of potentially modifiable environmental factors associated with temporal variation in relapse rates may allow alteration of risk on a population basis and alteration of outcome of established disease once established. Future epidemiological studies should examine dynamic environmental factors with serial prospective measurements and biological sampling. Significant seasonal differences in relapse rates highlight the importance of environmental factors in disease expression and should be taken into account when planning clinical trials in which relapse frequency is an outcome. In addition, identification of potentially modifiable factors associated with this variation may offer unique opportunities for alteration of risk of relapse and long-term outcome on a population level, and suggest putative biological mechanisms for relapse initiation.

Ozone, NO2 and PM10 are associated with the occurrence of multiple sclerosis relapses. Evidence from seasonal multi-pollutant analyses

“…Seasonal changes in air pollutants concentrations, the type of area (e.g., topography, level of traffic etc.) and the seasonal possible individual air pollutant effect on MS activity could explain mixed results concerning seasonal pattern in relapses rate observed in the literature (Harding et al, 2017). We adjusted on holidays since they may influence industrial activities and road traffic but also and particularly the presence of patients at home.…”

“…Yet, some studies have reported associations between UV level and MS exacerbations (Spelman et al, 2014; Tremlett et al, 2008), suggesting a possible role of erythemal ultraviolet radiation in the production of serum vitamin D production that might influence relapse incidence (Tremlett et al, 2008). However, Harding et al (2017) reported highest risks in early summer when sunshine duration is elevated and lowest risks at the end of summer (Harding et al, 2017), suggesting that vitamin D might not be the only environment factor incriminated in MS relapses (e.g., interactions etc.). Our results seem to corroborate seasonal changes in MS activity, as associations with air pollutants varied across season, so as established or likely confounding variables we accounted in our models (meteorological, infections and allergy variables).…”

“…Therefore, there are expected to spend more time at home with time (Kobelt et al, 2009). We did not adjust for sunlight exposure, which is reported to be related to MS incidence (Harding et al, 2017). …”

“…Seasonal variations occur for both air pollutants concentrations and MS incidence (Harding et al, 2017). Therefore, we fitted regression models separately for “hot” (April 1st to September 30th) and “cold” seasons (October 1st to March 31th).…”

“…Relapses’ incidence varies across seasons (Damasceno et al, 2012; Fonseca et al, 2009; Handel et al, 2011; Harding et al, 2017; Jin et al, 2000; Ogawa et al, 2004; Salvi et al, 2010; Spelman et al, 2014; Tremlett et al, 2008), suggesting a possible role of season-dependent factors such as meteorological variables (Watad et al, 2016) and ambient air pollution (Angelici et al, 2016; Oikonen et al, 2003; Roux et al, 2017). …”