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Self reported stressful life events and exacerbations in multiple sclerosis:prospective study

BMJ 2003; 327 doi: (Published 18 September 2003) Cite this as: BMJ 2003;327:646
  1. D Buljevac, medical doctor1,
  2. W C J Hop, biostatistician2,
  3. W Reedeker, medical student1,
  4. A C J W Janssens, psychologist3,
  5. F G A van der Meché, neurologist1,
  6. P A van Doorn, neurologist1,
  7. R Q Hintzen, neurologist (rhintzen{at}
  1. 1Department of Neurology, Erasmus MC, Postbox 2040, 3000 CA Rotterdam, Netherlands
  2. 2Department of Epidemiology and Biostatistics, Erasmus MC
  3. 3Department of Medical Psychology and Psychotherapy, Erasmus MC
  1. Correspondence to: R Q Hintzen
  • Accepted 17 July 2003


Objective To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis.

Design Longitudinal, prospective cohort study.

Setting Outpatient clinic of department of neurology in the Netherlands.

Participants Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded.

Main outcome measure The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events.

Results Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress.

Conclusion Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis.


  • Funding Stichting Vrienden MS Research, the Preventiefonds, and Erasmus MC Rotterdam.

  • Competing interests None declared.

  • Ethical approval The medical ethical committee of Erasmus MC approved the study

  • Accepted 17 July 2003
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