The risk of multiple sclerosis on the Orkney islands. A review of the search for distinctively Orcadian risks, with a hypothesis for further investigations.

The most extensive and meticulous epidemiological study yet to be published on the frequency of multiple sclerosis (MS) across the regions of Scotland has confirmed that the high incidence of MS on the Orcadian islands is unique and is most probably the highest in the world. Environmental and genetic studies of Orcadian MS have been carried out over many years but the results have been discouragingly inconclusive; no convincing explanation of the distinctively high Orcadian MS risks has come to light. However, studies of both prevalence and incidence of MS over a time line of approximately five decades, show that Orcadian MS has steadily increased to significantly exceed the neighbouring genetically related populations including North Eastern Scotland and the Shetland islands. Over this period the islands have progressively expanded occupations related to agriculture and have simultaneously acquired the highest concentration of cattle in Europe. Coinciding high and increasing Orcadian MS risk with increasing agricultural activities including bovine density and dairying, points towards a potential but unexpected causal risk. Raised incidence of MS with farming and in particular with dairy farming have been documented in Australia, Denmark, and more recently in Norway, further pointing to a possible MS risk associated with agricultural activities. A clue to the cause of this curious association has unexpectedly emerged from laboratory studies. Using very rarely available tissues from patients coming to autopsy during an MS attack, a toxin known as beta-haemolysin (sphingomyelinase), which is produced by the bacterium Staphylococcus aureus, has been identified in the affected tissues. Staph aureus is a common inhabitant of the mucosal linings of the human nasal sinuses and sinus mucosal inflammations have been shown to be closely associated with attacks of MS and optic neuritis. Irrespective of origin, human or animal, all strains of Staph aureus carry the beta haemolysin gene. However, the toxin is only sporadically expressed by the strains most commonly isolated from human carriers. Strains carried by bovines nearly always express toxin. Has the increasing high risk of MS in Orcadians been promoted by the nasal transmission and subsequent establishment of the high secreting bovine genotypes of Staph aureus in the Orcadian population? To demonstrate that bovine associated strains of Staph aureus are carried more frequently in the Orcadian population (or even specifically in Orcadian MS cases), would not of itself necessarily explain the high prevalence of Orcadian MS. It would however clearly justify an in-depth exploration of the nasal bacterial microbiome of MS cases. This should include the incidence of beta-toxin secreting Staph aureus genotypes. If MS cases are shown to have a distinctive nasal bacterial microbiome, including beta-toxin secretors, this finding would open up an almost entirely new range of investigations and approaches to the understanding of the pathogenesis of MS.