Pre-active lesions hold clues to stop MS

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Pre-active lesions hold clues to stop MS

Post by frodo » Wed Jan 23, 2019 6:25 am

Preactive lesions in multiple sclerosis ... sis.4.aspx

Compelling evidence is accumulating for pathological changes in normal-appearing white matter of MS patients, which occur before the actual development of the active demyelinating lesion.

Focal disorder has been documented in normal-appearing white matter of MS months to years before the appearance of gadolinium-enhancing lesions. In these foci, clusters of activated microglia are found in the absence of demyelination and clear leukocyte infiltration, distinguishing them from the traditional demyelinating active and chronic active lesions.

Although the events that give rise to preactive lesions are still to be identified, oligodendrocyte abnormalities appear to be crucially involved. Importantly, preactive lesions do not always develop into demyelinating lesions but often appear to resolve without subsequent disorder.


Preactive lesions in MS represent early stages in the formation of destructive MS lesions. As many of them spontaneously resolve, they are expected to hold important clues to stop the inflammatory process in MS.

More about this subject

Preactive Multiple Sclerosis Lesions Offer Novel Clues for Neuroprotective Therapeutic Strategies ... 1/art00007

During MS, small clusters of activated microglia frequently emerge throughout normal appearing white matter. Several lines of evidence suggest that these clusters, which are referred to as preactive MS lesions, represent a reversible first stage in the development of inflammatory, demyelinating MS lesions. Progression onto this final destructive stage may occur but, importantly, does not seem to be inevitable. Instead, resolution of preactive lesions is probably the rule rather than the exception.

For as long as preactive lesions remain non-infiltrated by peripheral lymphocytes, they reflect a local neuroprotective and reparative response. A critical factor in the emergence of preactive lesions is oligodendrocyte stress, which leads to accumulation of factors such as small heat shock proteins. At least some of these can induce an immune-regulatory response in neighboring microglia. A closer understanding of the molecular make-up of preactive MS lesions, of the signals which cause microglial activation, and of the protective mediators produced by microglia in this context, will help uncover novel clues for neuroprotective therapeutic strategies with relevance for clinical applications well beyond the field of MS alone.

And, ( ... 5/art00005)

More recently, re-examination of the neuropathology has led to a resurgence of interest in the neurodegenerative aspects of the disease, the involvement of cortical damage as well as the role of innate immunity in MS. These ideas have led to paradigm shifts from MS being the result of autoimmunity to myelin due to initial adaptive immune responses, to that of a neurodegenerative disease in which, besides T and B cells, innate immunity may play a major role in the disease process.

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