Now, this is interesting. I'm not sure if this has been posted here in detail before or not, but I believe we've all at one time or another speculated about it.
It is regarding demyelination occurring from totally different originations and pathogenesis, which would require totally different types of therapy. I think most of us believed that, but here is some actual detail!
Here is an excerpt from an article written by Drs. Claudia Lucchinetti and Moses Rodriguez from the Mayo Clinic. I found it at: http://fedem.org/revista/n7/patogeniaing.html
I would like to focus your attention right away, though, to what they found regarding the EAE model of MS and T-cell mediated inflammation (I'll highlight it in red). Uh oh, is all I can say!
....Experimental Models of Inflammatory Demyelination: Clues to MS Pathogenesis
Current experimental models of MS indicate that fundamentally different immunological mechanisms may lead to demyelination in the CNS.
T cell-mediated Inflammation: Experimental Autoimmune Encephalomyelitis (EAE) Model
The consequences of T-cell mediated brain inflammation can best be studied in the model of experimental autoimmune encephalomyelitis (EAE). Intravenous transfer of activated autoreactive T-cells leads to brain inflammation, that mimics the inflammatory pattern found in multiple sclerosis (54). Many different brain antigens (including myelin and non-myelin antigens) can serve as a target for such encephalitogenic T-lymphocytes (55). In most animal species, however, such a T-cell mediated encephalomyelitis is a monophasic disease, which is not associated with destruction of myelin sheaths. In humans, T cell mediated inflammation results in acute disseminated encephalomyelitis (ADEM) with only minimal demyelination. This is in contradistinction with MS in which demyelination is the primary feature. These data indicate, that the formation of an "MS-like" inflammatory demyelinating plaque requires the presence of additional demyelinating amplification factors.
Antibody mediated Demyelination: Myelin-Oligodendrocyte Glycoprotein (MOG)-Induced EAE Model
Up to now, only few models are available, that unequivocally define pathways of myelin and oligodendrocyte destruction in vivo. The best characterized pathogenic pathway involves a T-cell mediated autoimmune reaction, that is responsible for inflammation, in cooperation with a specific antibody reaction against myelin oligodendroglia glycoprotein (MOG), a myelin surface antigen (56-58 ). MOG is a minor myelin protein which is expressed on the surface of mature myelin and oligodendrocytes but is absent from oligodendrocyte progenitor cells. It contains epitopes that can be recognized by autoimmune T cells (59). In addition, anti-MOG antibodies can induce selective demyelination in vitro and in vivo following injection into the CSF. In the course of T-cell mediated autoimmune encephalomyelitis circulating anti-MOG antibodies augment disease and lead to the formation of large demyelinated plaques (58 ). Active sensitization of animals with MOG induces an inflammatory demyelinating disease with focal plaques of demyelination (59).
TNF-alpha mediated Demyelination: TNF-alpha Transgenic Model
TNF-alpha can induce demyelination and oligodendrocyte apoptosis in vitro. In vivo transgenic models that over express TNF-alpha in the CNS have been generated (60) The lesions in this model demonstrate focal demyelination associated with T cell inflammation, microglial activation, oligodendrocyte apoptosis, and astroglial scar formation. The neuropathology of this model reveals that in spite of the very similar final outcome of the demyelinating lesion in comparison to MOG-induced EAE, the pattern of active demyelination is profoundly different.
Demyelination induced by cytotoxic T-cells
Oligodendrocytes can also be destroyed in vitro directly by activated CD4-+ lymphocytes independent of TNF-alpha (61,62). This may involve the interaction if Fas antigen with Fas ligand. Fas expression has been observed in oligodendrocytes within MS lesions whereas Fas ligand was found on activated T cells (62,63). Although the target antigen for cytotoxic T cell reactions in MS is unknown, there is some data that suggests stress proteins may be one such target. A colocalization of gamma-delta T cells and stress protein reactive oligodendrocytes has been observed in MS lesions (64). Furthermore, gamma-delta T cells preferentially lyse oligodendrocytes in vitro (65). It is possible that in the course of demyelination, oligodendrocytes upregulate stress protein expression and as a consequence are rendered more susceptible to injury during demyelination.
Demyelination induced by direct oligodendrocyte injury: Viral-Induced Demyelinating Models
Inflammatory demyelinating lesions resembling those found in MS can also be induced by certain neurotrophic viruses (66). Although no specific virus has been implicated in the cause of MS, several case reports document brain virus infections leading to a pathology mimicking MS (67,68 ). The experimental viral models best characterized include Theiler's virus induced encephalomyelitis and coronavirus induced subacute demyelinating encephalomyelitis. Although the demyelinating lesions in these models in many respects resemble those found in multiple sclerosis, the problem of these models resides in their pathogenic complexity. Theiler's virus is a naturally occurring pathogen in mice. The Daniels (DA) and the BeAn strains produce a chronic persistent CNS infection resulting in inflammatory demyelination similar pathologically and clinically to the chronic progressive form of MS (69). The mechanism of demyelination has not been fully elucidated in this model, and both direct viral, and bystander or autoimmune mediated mechanisms affecting the oligodendrocytes and/or myelin sheath have been proposed (70-74). This model has been well characterized in our laboratory. Although the mechanism by which this virus causes demyelination is controversial, we have proposed that early oligodendrocyte injury is a key event (73, 75-77). TMEV infection initially results in metabolic injury to the oligodendrocyte which precedes demyelination. In TMEV, the earliest pathological changes occurred in the inner cytoplasmic tongues of oligodendrocytes, the most distal extension of these cells, resulting in a dying-back oligodendrogliopathy whereby the cell body could no longer support the metabolic demands necessary to maintain the distal axon (77).
Evidence for Pathogenetic Heterogeneity in MS Lesions
The experimental models discussed above indicate that multiple different CNS antigens as well as multiple immune effector pathways may lead to inflammatory demyelinating lesions in the CNS. Pathological analysis of actively demyelinating MS lesions, which previously had been performed on very small numbers of cases, have revealed many different structural and immunological features, suggesting multiple possible mechanisms may be involved in the evolution of the MS lesion. These include the involvement of activated macrophages and/or microglia, cytotoxic cytokines, reactive oxygen or nitrogen species, or specific demyelinating antibodies and activated complement components. In other cases, signs of oligodendrocyte dystrophy were noted, reflected by impaired expression of certain myelin proteins, such as myelin associated glycoprotein or dystrophic changes in the most distal oligodendrocyte processes (5).
A recent study based on 51 biopsies and 32 autopsies, which contained actively demyelinating lesions consistent with MS supports the concept that the mechanisms leading to demyelination in MS may be heterogenous in different subgroups of MS patients (23). Lesions were analyzed using a broad spectrum of immunological and neurobiological markers. The majority of active MS plaques were characterized by the precipitation of immunoglobulins and complement components at sites of active myelin breakdown. These lesions resembled the model of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis (21) However not all cases of MS followed this pathway. The other cases demonstrated signs suggestive of a primary oligodendrocyte dystrophy. This was reflected either by a disproportionate loss of myelin-associated glycoprotein, and oligodendrocyte apoptosis, or degeneration of oligodendrocytes in a small rim of periplaque white matter adjacent to active sites of demyelination (78 ). These lesions were reminiscent of virus or toxin induced demyelination rather than autoimmunity. At a given time point of the disease – as reflected in autopsy cases - the patterns of demyelination were heterogenous between patients, but homogenous within multiple active lesions from the same patient. It therefore appears that different mechanisms of demyelination may operate in different subgroups of MS patients. This pathogenetic heterogeneity of plaques from different MS patients may have fundamental implications for the diagnosis and therapy of this disease. ....
The rest of this particular article is worth reading, also, (in my opinion).