The Pathology of Multiple Sclerosis and Its Variants

of illnesses with varied etiology. They range from clearly infectious diseases such as progressive multifocal leucoencephalopathy to hereditary metabolic disorders such as adrenoleucodystrophy and metachromatic leucodystrophy to a group of disorders of unknown etiology (Table 14.1). Whether multiple sclerosis (MS) and its variants comprise a single disease with a highly varied course or a group of syndromes of diverse etiology remains controversial, although recent evidence suggests that it actually involves at least four different pathologic variants (1). Numerous clinical demyelinating disorders may be part of the MS spectrum or may represent different diseases with similar clinical and pathologic features. For years, many clinicians have felt that primary progressive MS and Devic syndrome (neuromyelitis optica) were distinct from relapsing remitting and secondary progressive MS. Balo concentric sclerosis was felt to be a different disease, but recent evidence has suggested that it is a variant of relapsing remitting MS. Whether the Marburg variant and acute disseminated encephalomyelitis (ADEM) are part of the MS spectrum or represent different disease entities remains a matter of debate. Recent immunopathologic studies are beginning to clarify these issues, but, ultimately, clarification of the relationship of the variants to each other will have to await determination of the etiology of these conditions. Recent developments in immunopathology have suggested that MS is several different diseases with a common clinical presentation (1). These immunopathologically different disorders are likely to have different etiologies. Guillian-Barre syndrome has been shown to have several variants caused by different agents including Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumonia, swine flu vaccine, and probably several others (2–4). Typical relapsing remitting MS now appears to have several variants, and these are likely to have different etiologies. The inflammatory demyelination in different cases has immunologic features that are sufficiently different from each other to suggest that this is really a group of diseases (1). These demyelinating disorders appear to have central myelin and the cells that form central myelin, the oligodendrocytes, as the target of attack. MS usually does not affect peripheral myelin, although there are cases of a disease clinically and pathologically indistinguishable from MS in which there is also peripheral demyelination in a pattern indistinguishable from chronic inflammatory demyelinating polyneuropathy (5–7). Because there is good evidence that molecular mimicry is involved in Guillian-Barre syndrome (3), molecular mimicry of a shared epitope could cause this rare combination of cen-