Parts of the United Kingdom have the highest incidence, prevalence and mortality rates for multiple sclerosis in the world. Although methods of ascertainment are not standardised, regional differences and changes with time are present for each of these statistics. Mortality has declined, whereas prevalence and hospital discharge rates have increased owing in part to the improved survival but also to better case ascertainment. The gradient in prevalence seen between Southern England (63/10(5)), Northern England and Northern Ireland (76-79/10(5)), Wales (c. 113/10(5)), North-East Scotland (155/10(5)) and the Orkneys (258/10(5)) can in part be attributed to varying methods of ascertainment but correlates with regional differences in the frequency of HLA-DR2 in normal individuals (21-50%). However no HLA-DR2 association is observed in parts of Scotland, where the prevalence is the highest in the United Kingdom, because HLA-DR2 and linked genes occur in up to 50% of the normal population from these areas. If the aetiology of multiple sclerosis is multifactorial the frequency of the disease will increase where susceptibility genes are common because the probability of concurrence of the remaining critical events is high; conversely when each aetiological agent is infrequent the chance of them all occurring in the same individual and therefore incidence of the disease are both lower. The fall in incidence observed in the Orkney Islands, possibly reflecting decline in an exogenous agent interacting with susceptibility factors, is consistent with this multifactorial hypothesis.
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