Clinical Briefs

With Comments from Russell H. Greenfield, MD

Stress and Multiple Sclerosis

Source: Mohr DC, et al. Association between stressful life events and exacerbation in multiple sclerosis: A meta-analysis. BMJ 2004;328:731-740.

Goal: To further assess the association between exacerbations of multiple sclerosis (MS) and stressful life events.

Design: Systematic review and quantitative meta-analysis.

Studies: Culled from PubMed, PsychInfo, and Psychological Abstracts from 1965 to 2003.

Methods: Three investigators independently reviewed papers, coding studies based on a variety of factors including study design, outcome, type of patients (relapsing-remitting or progressive), and use of validated/unvalidated measures of stress.

Results: A total of 20 studies were identified, of which 14 met inclusion criteria (seven case control, seven longitudinal prospective studies). A significant increased risk of MS exacerbation after stressful life events was identified, with a weighted average effect size of d = 0.53.

Conclusion: A modest, but consistent, association exists between non-traumatic stressful life events and subsequent exacerbation of MS.

Study strengths: Inclusion of longitudinal prospective trials.

Study weaknesses: The unique response of an individual to stress is difficult to control for; weaknesses inherent to meta-analyses including the varying quality of studies; unmeasured factors likely played a role in some of the documented exacerbations.

Of note: Charcot first put forth the notion that "grief, vexation, and adverse changes in social circumstance" were related to the onset of MS more than 100 years ago; included studies were statistically homogenous (effect sizes were not impacted significantly by either sampling or study design); the researchers emphatically state that results of this study should in no way suggest that patients are responsible for their exacerbations.

We knew that: The majority of people with MS have relapsing-remitting disease, and most of them believe that stress can cause or contribute to exacerbations; the role of stress as a trigger for exacerbation of MS is controversial among health care providers; at least one other study suggests that traumatic, life-threatening stress may actually reduce the risk of MS exacerbation as compared to more moderate life stresses that can increase exacerbation risk (strongly suggesting that different types of stress create varying physiological responses); no biological mechanism linking stress and inflammation in MS has yet been tested.

Clinical import: The authors of this interesting study refer to a recent meta-analysis of the use of interferon beta for people with MS that showed an overall effect size of d = 0.36 in reducing exacerbations in the first year of treatment, and d = 0.30 over the initial two years of therapy (this compared with an effect size of d = 0.53 associated with stressful life events in this study). While the authors are careful to point out they are not disparaging the use of interferon, they do suggest that the negative effects of stress may be equivalent to the posi- tive effects of one of the mainstays of treatment of MS, at least as relates to exacerbations.

Although everyone experiences stress, few people can truthfully state that they possess adequate tools with which to manage stress. Health care providers need not wait for additional research to guide people with MS to explore the wide range of stress management techniques readily available to them.

What to do with this article: Keep a copy of the abstract on your computer.