Purpose of review: Is multiple sclerosis (MS) a generalized disease of the central nervous system? Or put another way, is MS pathology primarily focal with global consequences or global with focal consequences? Consideration of this question depends on how you view it both spatially and temporally. In this review, we address some of the main themes underlying this issue, drawing on evidence especially from MRI, but also from histopathological studies.
Recent findings: Pathology in MS is not confined only to white matter lesions; apparently normal appearing tissues, including the grey matter, are also affected. Within what is classified as normal-appearing tissue, there may be variable degrees of demyelination, particularly in the grey matter, along with regions that will eventually become overtly lesion containing and areas of remyelination. It remains uncertain whether changes within the normal-appearing tissues are immediately associated with, or a direct consequence of, lesion formation.
Summary: At present, it is not possible to determine whether lesion formation, or a more diffuse process, is the principal pathological event in MS.