Inflammatory demyelination is not central to the pathogenesis of multiple sclerosis

Multiple sclerosis is a disease of the central nervous system that destroys myelin, oligodendrocytes, neurons and axons. Historically considered to be caused by an autoimmune process mainly affecting myelin and oligodendrocytes in the white matter, recent data provide evidence that a generalized, diffuse neurodegenerative process plays an important role in the pathogenesis of MS. There is a high density of axonal transections in active demyelinating lesions, but also persistent low-level axonal damage in inactive plaques and diffuse axonal and neuronal loss throughout the nervous system. Initial axonal injury appears to be closely related to inflammation, but is not restricted to the lesions themselves. Damage may be propagated throughout the nervous system by anterograde Wallerian, retrograde or transynaptic degeneration. Cumulative tissue loss in the grey and white matter, especially of axons, is important and probably the principal determinant of accumulation of irreversible neurological disability and of conversion to a progressive disease course.