A function of myelin is to protect axons from subsequent injury: implications for deficits in multiple sclerosis

Once it was thought that the mechanism for development of permanent neurological deficits in multiple sclerosis was understood. Demyelination, the pathological hallmark of the multiple sclerosis lesion, was the culprit. Elegant physiological studies demonstrated that demyelination results in conduction slowing and, in particular, conduction block (McDonald and Sears, 1969). These observations appeared sufficient to explain the majority of deficits in multiple sclerosis. However, clinical observations began to challenge this hypothesis. With the development of MRI, clinicians saw patients with extensive white matter lesion load with minimal or no neurological deficits. Pathological studies demonstrated that lesions observed by MRI were indeed demyelinated and frequently involved eloquent areas of CNS that should have resulted in neurological deficits. Autopsy series made it clear that substantial demyelination, sufficient to make the pathological diagnosis of multiple sclerosis, can be observed in individuals who during life remained normal in neurological function (Mews et al ., 1998). Patients with essentially normal vision have been documented in which the optic nerve and its tracts were completely demyelinated.The hypothesis that I favour is that demyelination is necessary, but not sufficient, for development of permanent deficits in multiple sclerosis. Demyelination predisposes axons to subsequent secondary injury. …