Pathophysiology
The pathology of the different stages of MS plaque is characterized more than the pathology of the ADEM. This is because most patients recover completely with ADEM and without apparent pathological consequences. A few biopsies were obtained and forensic analysis was done. MS plaques show organization characteristics, especially at the active plaque boundaries which is not the case with ADEM. On the other hand, the similarities in pathologies suggests but not confirm the possibility that ADEM is a crude form of MS and is in some way effectively and continuously kept in check after one, or maybe a few, episodes of demyelination.
Patients with large tumor-like demyelinating lesions can show a combination of pathological features consistent with MS and ADEM. The possible link between these disorders is supported by the similarity of clinical manifestations in these diseases and by the development of MS during adolescence in a small minority of patients who had typical ADEM episodes in the first decade of life.
The pathophysiological similarities of these diseases suggest that immunological constitution of susceptible individuals is in a way permissive of ADEM, MS or both. The threshold for initial episode of demyelination can be determined by the combination of this constitution and immunological nature of a specific antigenic stimulus.
Cases with features that lead them to be classified in this indeterminate area of continuum such as those that repeatedly have ADEM, pose a significant challenge for accurate classification. The mechanisms of these demyelinating diseases remains incompletely understood, despite the extraordinary richness and complexity of the immunological abnormalities that have been identified after more than a century of clinical, pathological and laboratory examinations. Fundamental studies have shown that in the early stages of inflammation in both MS and ADEM are probably mediated by stimulated clones of T-helper cell sensitized to autoantigens such as myelin proteins. Pathogenic differences between MS and ADEM are probably partly caused by differences in the details of pro-inflammatory cytokines and anti-inflammatory cytokines and chemokines.
Disruption of the blood-brain barrier may be an important event. Recent data in studies of the brains of MS patient show that the degeneration of gray matter (more of the descending subcortical fibers) can participate in the progression of MS. The involvement of gray matter also occurs in ADEM.
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