Exacerbation rates in MS patients vary greatly but tend to diminish with increasing duration of illness [13, 14, 18, 33]. When a patient has established disability, exacerbations do not appear to correlate with increasing disability [13]. Pregnancy has long been thought to decrease the risk of relapse in the third trimester, as shown in a large prospective study [34]. This is thought, at least in part, to be secondary to high concentrations of estrogen and progesterone, and phase II clinical trials have shown a potential role for estriol in treatment of MS [35]. The risk of relapse in the first trimester, however, is increased. The French study also confirmed a long recognized phenomenon that the risk of exacerbation of MS is markedly increased for 3 months postpartum. This study also showed this risk continued at a somewhat lower level for the 33 months of follow-up in the study. The importance of infection as a precipitating factor for exacerbations has long been recognized [36].

Emotional stress and its impact on MS has been the subject of a number of excellent studies [37-40]. All of these studies have consistently shown a correlation between major life stress and a significantly increased risk of exacerbation of MS. In a remarkable more recent study, Mohr et al. have demonstrated a correlation between stress, including “hassles” and the appearance of new active gadolinium-enhancing brain lesions [40]. The perception of stress, rather than a particular life event, is related to an increased risk of exacerbation [37-40]. While other factors are thought to influence prognosis in MS patients, no similar studies of risk factors has addressed them adequately.

A large number of neurologists at academic centers in the United States and elsewhere have concluded that the majority of MS patients develop secondary progressive disease and then progress rapidly to disability. Confavreux et al. have published their studies of the natural history of a large population of French patients [13]. The French workers have concluded that there is no relationship between relapses and progression, once disability is established. They have further concluded that only 30% of their relapsing-remitting patients had secondary progressive MS. Pittock et al. at the Mayo clinic published important observations of a 10-year follow-up of their MS population from Olmsted County, Minnesota [14]. They too found that disability in the majority of their patients did not progress measurably during the 10-year period of observation. Only 30% of their patients progressed to needing a cane or a wheel chair, but most patients remained stable despite the fact that only 15% had received immunomodulatory therapy. It is obvious that the perception that the vast majority of MS patients develop secondary progressive disease with rapid progression to serious disability is incorrect. The group in Lyon, France, has also found that longer periods of follow-up show that patients thought to have “benign MS” do develop some neurological impairment over 20-30 years of follow-up. Please see Table 2.3 for a list of proposed prognostic indicators.

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