Weinshenker and colleagues (1989), on the basis of observations in 1,099 MS patients over a 12-year period, have identified a number of features of the early clinical course that were predictive, in a general way, of the outcome of the illness. Perhaps not surprisingly, they found that a high degree of disability, as measured by the Kurtzke Disability Status Scale, was reached earlier in patients with a higher number of attacks, a shorter first interattack interval, and a shorter time to reach a state of moderate disability. Kurtzke had earlier reported that the feature most predictive of long-term disability was the degree of disability at 5 years from the first symptom. Confavreux and colleagues (2000) analyzed a cohort of 1,844 patients with multiple sclerosis and found, somewhat surprisingly, that relapses did not significantly influence the progression of irreversible disability. Furthermore, large population studies (Pittock et al, 2004; Tremlett et al) have shown that many patients develop only mild disability after long follow-up (so-called benign MS). Regardless of the age of onset, approximately 20 percent of patients do not become disabled, even after many decades of illness. These data should inform the use of the long-term disease-modifying therapies discussed in a later section but, as pointed out by Sayao and colleagues, reliable criteria for identifying patients who are destined to accumulate minimal or no disability are not available but are being sought.
After a number of years there is an increasing tendency for the patient to enter a phase of slow, steady, or fluctuating deterioration of neurologic function, attributable to the cumulative effect of increasing numbers of lesions (secondary progressive MS as described in the introductory section). However, in approximately 10 percent of cases, the clinical course lacks periodic relapses and is almost evenly progressive from the beginning (primary progressive MS; see Thompson et al). In these latter cases, the disease usually takes the form of a chronic asymmetrical spastic paraparesis and probably represents the most frequent type of difficult to diagnose as MS. In Thompson’s review of primary progressive MS, there was little change over time in the MRI findings, a negligible response to therapy, and a poor outcome. The frequency with which acute MS blends into the progressive variety has already been emphasized. (See earlier comments regarding the pathologic distinctions between types of MS.)
Pregnancy in MS is typically associated with clinical stability or even with improvement (as it is in a number of autoimmune diseases). The average relapse rate in established cases declines in each trimester, reaching a level less than one-third of the expected rate by the third trimester. However, there appears to be an increased risk of exacerbations, up to twofold, in the first few months postpartum (Birk and Rudick). An extensive study of 269 pregnancies by Confavreux and colleagues (1998) established a rate of relapse of 0.7 per woman per year before pregnancy and rates of 0.5 in the first, 0.6 in the second, and 0.2 in the third trimester, the rate then increasing substantially to 1.2 in the first 3 months postpartum.
The duration of the disease before death is exceedingly variable. A small number of patients die within several months or years of the onset, but the average duration of the illness is in excess of 30 years. A 60-year appraisal of the resident population of Rochester, Minnesota, disclosed that 74 percent of patients with MS survived 25 years, as compared with 86 percent of the general population. At the end of 25 years, one-third of the surviving patients were still working and two-thirds were still ambulatory (Percy et al). Other statistical analyses have given a less optimistic prognosis; these were reviewed by Matthews. Patients with mild and quiescent forms of the disease are, of course, less likely to be included in such surveys. Although exceptional, one of our patients relapsed and developed massive brainstem demyelination and coma after 30 years (confirmed by postmortem examination) and cases of an aggressive myelopathy that appears after years are well known.