Heterogeneity: New Ways of “Seeing” the mechanistic MS

[frodo]

New Ways of “Seeing” the Mechanistic Heterogeneity of Multiple Sclerosis Plaque Pathogenesis

https://insights.ovid.com/crossref?an=0 ... 3000-00021

Background: Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments.

Evidence Acquisition: A constellation of inflammation, ion channel derangements, bioenergetic supply: demand mismatches within the intra-axonal compartment, and alterations in the dynamics and oximetry of blood flow in CNS tissue compartments are observed in MS. These findings have raised questions regarding how histopathologic heterogeneity may influence the diverse clinical spectrum of MS; and, accordingly, how individual treatment needs vary from 1 patient to the next.

Results: We are now on new scaffolding in MS; one that promises to translate key clinical and laboratory observations to the application of emerging patient-centered therapies.

Conclusions: This review highlights our current knowledge of the underlying disease mechanisms in MS, explores the inflammatory and neurodegenerative consequences of tissue damage, and examines physiologic factors that contribute to bioenergetic homeostasis within the CNS of affected patients.

[vesta]

New Ways of “Seeing” the Mechanistic Heterogeneity of Multiple Sclerosis Plaque Pathogenesis

https://insights.ovid.com/crossref?an=0 ... 3000-00021

Background: Over the past few decades, we have witnessed a transformation with respect to the principles and pathobiological underpinnings of multiple sclerosis (MS). From the traditional rubric of MS as an inflammatory and demyelinating disorder restricted to central nervous system (CNS) white matter, our contemporary view has evolved to encompass a broader understanding of the variable mechanisms that contribute to tissue injury, in a disorder now recognized to affect white and grey matter compartments.

Evidence Acquisition: A constellation of inflammation, ion channel derangements, bioenergetic supply: demand mismatches within the intra-axonal compartment, and alterations in the dynamics and oximetry of blood flow in CNS tissue compartments are observed in MS. These findings have raised questions regarding how histopathologic heterogeneity may influence the diverse clinical spectrum of MS; and, accordingly, how individual treatment needs vary from 1 patient to the next.

Results: We are now on new scaffolding in MS; one that promises to translate key clinical and laboratory observations to the application of emerging patient-centered therapies.

Conclusions: This review highlights our current knowledge of the underlying disease mechanisms in MS, explores the inflammatory and neurodegenerative consequences of tissue damage, and examines physiologic factors that contribute to bioenergetic homeostasis within the CNS of affected patients.

Translation: It looks like we need to take Prof Zamboni's CCSVI theory seriously.

Regards, Vesta

[frodo]

Translation: It looks like we need to take Prof Zamboni's CCSVI theory seriously.

Regards, Vesta

Yes vesta. I would say that some cases could be of vascular origin. The problem is that Zamboni didn't make any difference in his studies.

[vesta]

Translation: It looks like we need to take Prof Zamboni's CCSVI theory seriously.

Regards, Vesta

Yes vesta. I would say that some cases could be of vascular origin. The problem is that Zamboni didn't make any difference in his studies.

Greetings:

Dr. Zamboni’s work was the starting point for me in understanding that neurological damage in MS begins with obstructed CSF and/or blood flow through the Central Nervous System. That the issue is more complicated than Zamboni’s initial hypothesis in no way invalidates it. Rather, it’s time to expand upon it.

An issue overlooked at the outset was the skeletal factor, that pressure ON the vein by a bone, muscle or artery may be obstructing blood flow rather than a  problem IN the vein. Chiropractor Dr. Michael Flanagan, author of The Downside of Upright Posture – The Anatomical Causes of Alzheimer’s, Parkinson’s and Multiple Sclerosis estimated that up to 25% of MS cases fall into this category. In this case venoplasty is ill advised since the treatment will not overcome the obstruction and may well damage a healthy vein.

So consider the factors. Is blood flow from the brain impeded by a venous obstruction? Or does a dysregulated autonomic nervous system cause the smooth muscles of the vein to go into spasm, thus sending refluxed blood into the CNS? Will simple body tension cause the veins to seize up and impede blood flow, tension caused by emotional stress, the flu, toxins, poor food? Has stress re-activated a dormant EBV Herpes virus lodged in the autonomic nervous system causing the veins to seize up in spasm? Is there a bone pressing on the otherwise healthy vein? Does cerebro-spinal fluid flow obstruction damage the axons, the spinal cord?  Where is the principle obstruction to the free flow of  central nervous system fluids? How should it be treated? 

The ferocious opposition of the MS drug/Neurologist lobby has nothing to do with Science and everything to do with protecting territory (and profits). Slowly the Science will seep in to undermine the « politics », but how long will it take to free MSers from the clutch of these « respectable » vested interests?

Thanks for all your research posts.

Regards, Vesta