Epilogue: Conclusions and future directions

A large amount of scientific and clinical research has been carried out on MS. This has been aimed at understanding the pathogenesis of the disease and at developing new treatment strategies. We now have a large amount of information concerning MS pathogenesis and the mechanisms are becoming elucidated, both for the disease itself and for EAE and viral models. A main tenet of MS research, first put forward by Dean and colleagues (1), is that MS is triggered by an environmental factor that exerts its effects around adolescence, in genetically susceptible individuals. This general mechanism is still accepted. However, the difficulty comes when these interacting factors are further dissected. Many animal and human diseases are characterised by CNS demyelination, therefore it has been assumed that a likely candidate for the environmental factor postulated in MS is a virus. This has prompted a search for viruses associated with MS. However, this search has led to equivocal results and no one virus has been definitely associated with MS. It may be that several viruses may be responsible, since MS is a disease of varying pathologies (2), each of which may be associated with a different etiology. There may also be an interaction between viruses and other environmental factors, for example activation of herpes viruses caused by vitamin D deficiency (3). The second problem which may be associated with the virus hypothesis is that the virus may not persist in MS tissue, but may be associated with a ‘hit and run’ mechanism, so a later search for the virus may be fruitless (4). Also a problem here is that it is more difficult to publish negative rather than positive claims, so the literature contains many claims for etiological agents associated with MS, not many of which have been refuted or confirmed.