The role of axonal pathology in MS disability

It is well recognized that in end-stage multiple sclerosis (MS) pathology there is axon loss. Since the axons of central nervous system fibre tracts regenerate very poorly (if at all), it is axon loss that is likely to be responsible for the permanent clinical deficits of MS. Thus, the key question is not whether there is axon degeneration in MS, but when it occurs during the course of the disease. If it develops early in the disease, and is not just a consequence of long-standing demyelination, this would suggest that therapies directed at preventing the pathology early in the disease should be implemented. This article reviews the recent evidence that axonal damage does indeed occur early in MS and considers the mechanisms by which an inflammatory response might damage the axons acutely