A viral aetiology for multiple sclerosis: In pursuit of Kurtzke's dark horse.

Abstract

Multiple Sclerosis (MS) is a disorder in which autoinflammatory processes contribute significantly to brain and spinal cord pathology. However, the driver of immune dysfunction and the precise pathological mechanisms that result in oligodendrocyte and axonal injury remain incompletely characterised. Following an exhaustive analysis of epidemiological data, John F Kurtzke concluded that an immune process is the "cart" rather than the "horse" and that there is a real possibility of one horse and this horse is a specific, albeit unidentified, infection. A central role for an infectious agent in the aetiology of multiple sclerosis can also be inferred from basic principles of immunology, that are verified in animal models of neuroinflammation, and there are important similarities between multiple sclerosis and proto-typical neuro-inflammatory conditions arising from HTLV-1 and Mycobacterium Leprae infection. Both MS and HTLV-1 associated myelopathy have a discrete geographical distribution and immuno-genetic factors contribute to disease susceptibility, with both disorders occurring three times more commonly in females than males. Leprosy, like MS, has a variable pathological phenotype and heterogeneous patterns of peripheral nerve injury in leprosy reflect the effects of both bacterial determinants and a range of host immune responses. To date an infectious cause of MS has not been established. The requisite characteristics of an infectious agent causing MS will include the ability to infect oligodendrocytes and the presence of antigen(s) reactive with the CSF-specific oligoclonal bands detected in 90-95% of individuals with MS. It is postulated that the heterogeneity of MS pathology will reflect a range of individual immune responses to a single pathogen that meets these stipulated criteria.