The National Research Council Twin Registry comprises 16,000 pairs of white male twins, both members of which had been in military service, mainly in World War II. All their available military and Veterans Administration records and their responses to a 1965 to 1970 NRC questionnaire have been coded as to disease. Upon review we found 16 cases of multiple sclerosis (MS) among 15 pairs of twins, for an age-specific prevalence rate of 51 per 100,000 veterans aged 43 to 53--about half the expected frequency. Of the 15 sets, three sets refused cooperation and three were unavailable for study. Nine sets were examined and interviewed together with the mother. One of five monozygotic twin pairs was concordant for MS and in another the co-twin of an MS case had had a solitary episode of retrobulbar neuritis; all others were discordant. There were more definable environmental events (as noted below) among the affected twins than among the unaffected co-twins. The greatest excess was within the 20 years before onset. Summing events across the four 5-year periods before onset, among the 10 MS versus the eight not-MS individuals, there were 5:1 instances of trauma, 8:2 or operation, 7:1 of ether anesthesia, 7:1 of allergy, 10:5 of infection, and 9:0 of animal exposure. Summing these same events within each 5-year period, the MS:control ratios were 9:1, 10:2, 12:3, and 15:4, respectively, for 0 to 4, 5 to 9, 10 to 14, and 15 to 19 years before onset.

Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.

Age at onset of multiple sclerosis (MS) symptoms was ascertained for subsets of some 4,400 veterans of World War II who had been adjudged ''service-connected'' for this condition. Average age at onset was 27.0 years for white men, 27.7 for white women, and 27.5 for black men. The unexpectedly older age for women is attributed to their older age at entry into service. When the coterminous United States was divided into three horizontal tiers of states, we found a strong effect of geography on age at onset. By state of residence at entry into active duty (EAD), white men had an average age at onset of 26.4 years in the northern tier, 27.3 years in the middle, and 28.8 years in the south. Trends were similar for white women and black men. Migrants, defined as those whose birth and EAD tiers differed, showed increasing ages at onset with southward moves. A statistical model used to discriminate between the influence of birth and EAD tiers on age at onset confirmed the significant effect of EAD alone. These data are compatible with the theses that the cause of MS is less common (or less efficient) in locations where the clinical disease is less common, and that its acquisition therefore occurs at an older age in those locales.

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