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The natural history of multiple sclerosis (MS) should be considered in the context of better understood disorders where the problems of definition, ascertainment, and outcomes can be more easily appreciated.
DEFINITION OF NATURAL HISTORY
The definition of the natural history of acute illnesses has been difficult to establish. Imagine, however, the degree of uncertainty in an earlier age when fever itself was considered to be a disease. The appearance of fever could represent a banal upper respiratory disease or underlying untreatable infection or malignancy. Good outcomes offered unlimited opportunities for unwarranted claims for credit. Bad outcomes were blamed on “sin”, and the physician's contribution would be one of either commission or omission. When evaluation consisted largely of taking the pulse and measuring the temperature, the study of physical findings was exhaustive. Text books of thermometry described undoubtedly accurate vagaries of fever long forgotten in diseases still commonly seen today.1 Fever became rationally dissected into a large number of specific entities with the development of microbiology changing the focus of diagnosis and prognosis to the specific clinical features characterising each causal organism. It must have been both surprising and disappointing to find that a large variability in outcome remained, even when the microbiological cause was pinpointed. The spectrum of outcome for many disorders ranged from self limited nuisance to fatality (for example, pulmonary tuberculosis infection) and was hardly narrower than for the “diagnosis” of fever. The failure of outcome to define disease entity had to be repeatedly demonstrated. Only recently has attention shifted significantly to the study of host factors and in the last generation have tools become available to investigate this with any power.
The problems of defining outcome seen in the infectious disorders are compounded in the more chronic diseases where, in most, survival is excellent in the short term. The dearth …