Multiple sclerosis plaques constitute distinctive lesions of disease involvement evolving largely as extension of margins and also as new foci in other regions of the white matter. It appears that a vascular basis for progression would also implicate a series of axonal lesions that incorporate demyelination as aggregate phenomena affecting both oligodendrocytes and neurons. A strict neuronopathy and an axonal participation in the loss of myelin sheaths in multiple sclerosis might evolve as immunologically mediated processes arising on vessels and endothelium within plaques that enlarge and subsequently mature. In terms of such demyelination of multiple plaques there would subsequently evolve a process of repeated remyelination of the axonal segments largely based on a phenomenon of aggregate involvement of multiple oligodendrocytes supplying multiple segments of different axons on a regional basis of progression.