Stressful Life Events and Multiple Sclerosis: A Call for Re-Evaluation

Background: The case of Sir Augustus d’Este (1794 – 1848) is the earliest documented and detailed account of MS. In his Diary he wrote “In the month of December 1822 I travelled from Ramsgate to the highlands of Scotland for the purpose of passing some days with a Relation for whom I had the affection of a Son. On my arrival I found him dead…… Shortly after the funeral I was obliged to have my letters read to me, and their answers written for me………..” and he continued to describe what appeared as the onset of his illness. Later, Dr. JM Charcot stated that "Grief and adverse social circumstances might be causally linked to MS onset". This was followed by few studies reporting the association between significant stressful life events and MS. However, the evidence is still limited despite all available clues.

Objectives: The current study was designed to: 1. reexamine the association between major stressful life event(s) and MS development in two different patient populations; 2: propose a theoritcal model linking MS development and chemical changes in the brain in response to major stressful life events.

Methods: First, a questionnaire was designed and administered to 30 MS patients enrolled in the Jordanian MS society. The main question addressed was: “What do you think is the cause of your illness?". All responses were collected and analyzed. in addition, detailed review of published bibliographies of 32 “famous” people with MS was done. Specific search for reported major stressful events that occurred before the date of either diagnosis or documented initial symptoms was implemented. Results were compared with those obtained from 31 matched controls (date of birth, sex, occupation). Major adult onset stressful life events were defined as in Brown and Harris, 1978. Percentages were compared using the Fisher Exact test. Significance was set at p<0.05.

Results: Remarkably, 24 out of 30 MS patients (80%) linked their disease to a well identified major stressful event that happened before the onset of their symptoms. Furthermore, major adult onset stressful life events were identified in 87.5% of famous people with MS compared to 22.5% of matched controls (P<0.00001). Finally, a theoretical model linking major stressful event(s) to initial blood brain barrier impairment, MS onset, and disease progression together with identifying possible pharmacological targets is proposed.

Conclusions: An interesting association that was first described two centuries ago still exists and further research is needed to unravel its exact contribution to MS development and progression.