ABSTRACT
The focus of multiple sclerosis (MS) research has been on attempts to identify the
specific pathogenic mechanism responsible for producing the multifocal central nervous
system inflammatory demyelinating lesions. However, extensive in vitro and in vivo
evidence suggests that multiple different immunological mechanisms may produce the
typical demyelinated plaque. A detailed examination of actively demyelinating MS lesions
reveals a profound heterogeneity in the structural and immunopathological patterns
of demyelination and oligodendrocyte pathology between different MS patients, suggesting
multiple pathogenic mechanisms may contribute to oligodendrocyte and myelin injury
in MS. These observations raise the question whether MS may be a neurological syndrome
with different immunopathological mechanisms triggering a common pathway rather than
a single disease with a uniform mechanism of myelin destruction. With the advent of
new tools for neurobiological and immunological research applied to actively demyelinated
MS lesions, an opportunity exists to reevaluate MS neuropathology. This review highlights
the spectrum of the inflammatory demyelinating diseases, the multitude of effector
mechanisms that may produce myelin destruction, and the pathologic heterogeneity observed
in MS lesions. A careful evaluation of MS neuropathology should provide important
clues regarding the induction, target, evolution, and pathogenesis of this complex
disease.
Keywords
Oligodendrocyte - demyelination - immunopathology
