Abstract: Dimensional confines of the individual demyelinating plaque in multiple sclerosis indicate a focal or multifocal involvement of the parent axon and also a global progressiveness of the involvement of the blood-brain barrier. A gliopathy affecting viability of the astrocytic foot processes may be re-interpreted within constructs of involvement by a depleted oligodendroglial cell compartment within the demyelinating plaque. It is particularly significant to view dynamics of remyelination within a contextual setting of an afflicted parent axon. Progressiveness is hence compounded by multiple constructs in development of a lesion that is physico-chemically related to new foci of involvement of grey and white matter, beyond the confines of established plaque pathology. In this sense, therefore, a conventional role for a presumed viral etiology would insufficiently account for a multi-focal involvement that mirrors the global dimensions of the blood-brain barrier defects.