Hunt for the missing link

Scientists continue to look for a connection between stress and MS. Some say they're wasting their time

By Katherine Addleman

"The only time I'm troubled by MS tingling these days is after a nice relaxing bath!" says Montrealer Ellen Presner, who was diagnosed with MS seven years ago.

Ms Presner's story doesn't exactly back up the controversial idea of a link between stress and exacerbations of multiple sclerosis (MS), which has been raging among scientists for years. Some researchers insist that symptoms flare up as a result of stress, but many neurologists remain sceptical. What's a doctor � and MS patient � to believe?

BEYOND A REASONABLE DOUBT?
A new review article in the March 27 issue of the British Medical Journal by Dr David C Mohr, a psychiatrist at the University of California at San Francisco, supports the hypothesis that stress is a potential trigger of MS. He and his colleagues analysed the outcomes of 14 studies, all of which had in their opinion reliable quantitative measures of stress and MS symptoms. Their data revealed a consistent "modest but significant" association between stress and new onset of symptoms.

Other researchers are coming up with similar evidence. Working out of the University of Lethbridge's Canadian Centre for Behavioural Neuroscience, Dr Gerlinde Metz's particular area of study is the impact of stress on Parkinson's disease, which, like MS, affects the central nervous system. Her research suggests that exposure to a variety of environmental stressors, including pesticides or other chemicals, as well as the daily grind, can play a role in symptom flare-ups in these diseases.

This ties in with research by Duke University pharmacologist, Dr Mohamed Abou Donia, which has shown that stress can intensify the effects of certain chemicals. Dr Donia discovered that when animal models were put under moderate stress � a few minutes of restraint in a holding pen � and exposed to commonly used insect repellents like DEET and other compounds, "the effects of the chemicals were intensified dramatically." In MS, disruption of the blood-brain barrier precedes clinical symptoms. Dr Donia's research demonstrates that the combination of stress and low-level, short-term chemical contact can kill brain cells and impact the blood-brain barrier.

There's a possible, though partial, explanation for this effect on the blood-brain barrier. The stress hormone, corticotropin-releasing factor, triggers the release of two other stress hormones, adrenocorticotropic hormone and cortisol. When stress hormones are chronically elevated, they can suppress the immune system, predisposing people to autoimmune disorders and inflammatory disease. High cortisol levels have been found in the cerebrospinal fluid of MS patients. Damage to myelin in the neuronal sheath occurs when destructive immune system lymphocytes somehow manage to cross the blood-brain barrier and enter the brain.

THEORETICAL HOLES SINK THE 'EVIDENCE'
Research presenting a MS/stress link is only half the story. There are lots of potential holes in the assumption that stress can be accurately measured. It's difficult to gauge something so subjective and there's no consistent or widely accepted measure for it. How life events affect different people and how individuals deal with different types of stress (ie, divorce, loss of employment) can vary greatly. Also, asking people after the event to remember how it affected them isn't always reliable and can lead to significant bias. Aside from that, even if a link between stress and MS does exist, it still wouldn't explain certain characteristics of the disease, such as the higher prevalence in women or the typical geographical distribution of cases.

In an added twist, a number of studies have appeared showing that stress may in fact be beneficial in MS. For example, a study of MS patients in Israel who were subjected to missile bombardments for a month during the first Gulf war actually found that their symptoms had improved during this time of acutely traumatic, life-threatening stress.

"The idea that stress plays a role in MS has been around for decades, but there's still a lack of good published evidence one way or the other," explains Dr Yves LaPierre, director of the MS Clinic at the Montreal Neurological Institute. "Assessments are difficult to make and they're very subjective. Until the relationship between stress and exacerbations are proven, most neurologists consider this issue still up in the air."