There is growing body of evidence that support an association between stressful life events (SLEs) and an increase risk for Multiple Sclerosis (MS) exacerbations. The aims of this study were: first, to examine the relationship between SLEs and MS exacerbations; second, to investigate how SLEs frequency influence MS disease activity.

Twenty six ambulating women (Expanded Disability Status Score, EDSS ≤3) with relapsing-remitting Multiple Sclerosis were followed-up for one year or more. Patients documented SLEs weekly in self report diaries which were then collected at regular clinic visits every 4 weeks. Neurological examination was performed, at baseline and at every regular and additional visit after a suspect exacerbation.

A Cox univariate regression analysis showed that 1 or 2 SLEs had no effect on risk for relapses. In the opposite 3 and ≥ 4 SLEs were associated with 5.3 (95% CI 1.7 to 16.4, p=0.003) and 16.7 (95% CI 4.6 to 60.5, p<0.001) times respectively the rate of relapsing during the following four weeks. The number of the reported SLEs was not correlated with the EDSS score [r(26)=-0.10, p>0.05], the system involved [r(26)=0.01, p>0.05], or the duration of the relapse [r(26)=0.02, p>0.05].

This data provide prospective evidence that SLEs may trigger MS exacerbations. The effect of stress on relapse risk in MS is cumulative. A higher density of stress is not related with a mayor inflammation process.