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Infectious agents are among the most frequently studied and biologically plausible putative environmental factors related to multiple sclerosis (MS). The infectious hypothesis, first postulated at the end of the nineteenth century,1 has arisen from epidemiologic studies on incidence pattern and on migrants and from evidence of possible clusters.
While the occurrence of true clusters is still debated, the existence of a temporal trend, both decreasing and increasing, in several countries strongly supports the view that the heterogeneity of the temporal distribution could be linked to the influence of exogenous factors and, moreover, provide clues to the characteristics of the unknown and probably multiple etiologic factors that influence the appearance of MS in genetically prone subjects. These exogenous agents may modify their concentration and aggressiveness over time. Such characteristics are indicative of infectious agents.2,3
Another important etiologic clue in favor of the environmental hypothesis comes from migrant studies. Evaluating the results of this kind of investigation, however, requires taking into account several limitations. For example, the migrants may not be representative of the population origin in social class, age, or general health, and they may not be comparable with the native-born people of the host country. Further, the relatively small sample size of the studies and ambiguous methodologic strategies need to be considered when evaluating migrant studies.4,5 Nevertheless, the results seem to suggest that migration between areas could affect the risk of acquiring MS and indicate the existence of a critical age before puberty for exposure to putative environmental factors; more recent studies have suggested a larger susceptibility age interval with maximal clustering at age 13 to 20.6 On the other hand, the existence of very late onset of the disease is not completely in agreement with the postulated susceptibility age between infancy and adolescence, unless an …
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