Epidemiology in multiple sclerosis: a pilgrim's progress

There was more neurology taught under Harold G. Wolff at Cornell University Medical College in New York than perhaps anywhere else in the country when I attended from 1948 to 1952. I took my residency at the Veterans Administration Hospital in the Bronx, New York, a teaching hospital of Cornell, with Wolff as my Director of Training. While a resident, we thought we had found a treatment for multiple sclerosis. To test our conclusion, the first Class 1 treatment trial ever conducted for multiple sclerosis was performed. This showed no effect, but the participants began investigating multiple sclerosis among the 16 million persons at prime age for symptom onset who had served in the military in World War II. This led me to study its epidemiology worldwide, beginning with a detailed review of all published population-based estimates of frequency. Among these were nationwide surveys from Sweden, Denmark, Switzerland and later Norway and Finland, which showed in each country a concentration of the significantly high regions into contiguous areas forming a single 'focus' in each land, maximal in Denmark under the age of 15 years. The primary locus of high frequency multiple sclerosis seemed to be in the south-central inland lake region of Sweden, with spread to its contiguous neighbours. These concentrations in time and space indicated that multiple sclerosis was a disease probably acquired in early adolescence. Migration studies supported this: moves from high to low showed retention of birthplace risk only for those aged >15 years, whereas opposite moves indicated susceptibility limited to some 11-45 year olds. Epidemics of multiple sclerosis would suggest the disease is not only acquired but also infectious. If an infectious origin were true, transmission would have to occur before clinical onset, and would have to involve a much greater number of subjects than clinically involved. I believe there have been epidemics in Iceland, Shetland-Orkney and the Faroe Islands. On the Faroes there were no cases of multiple sclerosis among native-born resident Faroese from 1900 until 1943, when the first of 21 cases had clinical onset, heralding a type 1 epidemic with peak incidence rates >10 per 100,000 for 1945-46. British troops who occupied the islands from April 1940 to September 1945 we believe brought a widespread (because of the scatter of Faroese cases), asymptomatic (because they were healthy troops), persistent infection we called the primary multiple sclerosis affection that involved a large proportion of Faroese, with clinical multiple sclerosis ensuing in a very small proportion. Primary multiple sclerosis affection itself may have been manifest there as a newly introduced cause of acute infectious gastroenteritis and is possibly the underlying cause of multiple sclerosis in general.