Multiple Sclerosis Research Repository

1. “Multiple sclerosis: Enigmatic factors and new controversies”: Annabel Vila et al

-MS: principally mediated by thymus-derived lymphocytes 

-some cases of MS are due to primary oligodendrocyte pathology rather than to a chronic inflammatory process.  For example, one study described four distinct patterns of demyelination, two of which were highly suggestive of a primary oligodendrocyte apoptosis is the initial event in the formation of an MS plaque

-only HLA B*44 has been shown to influence disease

-highly suggestive of a primary oligodendrocyte dystrophy or apoptosis, reminiscent of virus or toxin-induced demyelination rather than autoimmunity

-prominent nuclear expression of hypoxia-inducible factor-1a (HIF-1a)

-finding significantly more gray matter affected in SPMS than in RRMS patients; this pattern is related to Inside-Out model which suggests high amount of antigen released from primary cytodegeneration from axon’s oligodendroctyes (inside) to myelin (outside)

-meningeal inflammation was present in all the disease stages

-the ultimate cause initiating the disease remains ambiguous

-the purpose of activated microglia as an initial pathogenic event in MS must be considered

-it is even possible that oligodendrocyte apoptosis is the initial event in the formation of an MS plaque

-even as early as 9 months into the disease, a 22% loss has been reported in the descending tracts distal to a brainstem lesion, with preservation of other tracts

-an actual neuro-axonal degeneration and synaptic pathology 

-here it is seen that the lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model)

-within a few years, a large number of these patients (RRMS) with or without treatment with immunomodulatory agents enter in another phase of disease known as SPMS

-antiphospholipids antibodies (APLA)

-aPL occur at high frequency in many disorders including MS

-the reported frequencies of positive APLA in MS have ranged from 10% to 44% and 88%; a high correlation of several APLA-IgM associated with exacerbations in MS comparing with remission

-in 2000, our collaborative investigation demonstrated elevated endothelial microparticles (EMP) during exacerbations in MS; the hypothesis that aPL might be involved in endothelial activation in MS

-Another theory regarding MS that is basically in a degenerative disorder, similar to Parkinson’s and Alzheimer’s diseases and other progressive degenerative CNS disorders of unknown etiology.  As with many of these conditions, the degenerative process probably began many years or possibly decades before the initial symptoms of disease presented.  Kerbrat et al supports this claim by saying that the adolescents with MS have a significantly reduced brain volume as well as reduced head size [117], implying that the inception of the disease was many years ago while the skull was still in the development phase [86]”

-Louapre et al claim that neurodegeneration in MS is an event independent of inflammation and that it occurs early in the disease making it a significant predictor of clinical disability

-making neurodegeneration an independent event as a possible explanation

-that the predictive value of relapses becomes becomes mostly or completely obsolete after the first 2 to 5 years

– -It is also interesting to note the discussion of another set of auto antibodies, the antibodies against the axon, as these antibodies have been detected in high quantities in the CFS of multiple sclerosis patients and were also present in the autopsy tissue of diseased individuals, these antibodies could be a possible explanations for the axonal pathology seen in MS, as it was seen that these antibodies were not only seen in the active lesions but had infiltrated the white matter without any apparently demyelination and axonal damage was independent of oligdendrocyte pathology

-contribution of PTX3 to antiinflammatory effects in MS and its animal model EAE