Multiple sclerosis: a two-stage process?

The concept that the pathogenesis of multiple sclerosis (MS) is dependent on both an environmental factor and host factors associated with the puberty period was tested using the data for the Faroe Islands "outbreak." Although this "outbreak" affected only 25 individuals, its value may be unique since it is the only virgin outbreak described. The population affected demonstrated an age-associated bimodality. Incubation period for the older group, using 1942 (midpoint of British troop occupation) as onset time, was 5 years, while for the younger group, using puberty as onset time, a similar 5.7-year incubation period was demonstrated. Male and female incubation periods for both groups were similar, demonstrating an internal validity check. Although 10 cases were below the age of puberty at the time of the occupation, none of these developed disease prior to reaching puberty. The data suggest that onset of pathogensis of MS is dependent on passing or having passed through the puberty period. This would explain why MS is rarely seen below age 10, is unusual below age 15, why age 15 has been a "critical time" in migration studies and why females have an earlier onset than males. The data further indicate that susceptibility to MS may be acquired over a wide range of ages. The fact that many aging curves such as those for estrogen, testosterone or 17-hydroxycorticosteroid show striking similarity to the MS incidence curves raises the question whether infection is the entire explanation for the age distribution.