Article: Light on ME/CFS II: The Dorsal Ganglia - Ground Zero for ME?

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And hence the need for specialized autopsy studies with a well defined CCC cohort. We've needed this desperately for years.

Plenty of ME/CFS patients have been willing to donate there bodies to science for decades. Where are the researchers willing to undertake this endeavor?

 

Basically what we're missing is infrastructure. With CFS 210th of 215 disorders in funding there's precious little money or infrastructure built up around it and alot of that stuff is private. The WPI and CAA both have biobanks but I don't know if they are collecting autopsy samples.

I'm pretty sure that there are reserachers who would love to do this - if they had the money and resources.

You wouldn't want just a CCC cohort by the way I don't think - you'd want the whole range of CFS patients and then see if the CCC cohort popped out with more abnormalities. In science they always want a control group.

 

THe control group would be healthy volunteers to start. This is what most control groups are in initial studies. And you would not want them to be contacts of the patient either for fear of common environmental exposures.

What other cohort would you use? According to Jason Fukuda includes a high percentage of MDD. You would not want a high percentage of Psychological disorders mixed in with your cohort. That is what has weekened the CDC studies for years.

An outbreak cohort would be real nice and clean. Unless someone subscribes to them being hysteria as the Reeves led CDC program has in the past.

I would like to see an autopsy studay that had inline Village and Lyndonville patients. At least a nice chunk of them in that study so to speak.

 

This is interesting research although I think its a long bow to connect this the Light's work to the Shapiro work. Gradual onset - as occurs in many patients - doesnt really fit with an infectious pathophysiology.
Secondly, the POTS finding seems strange given there are already proven distinct subsets found in POTS and the Low Flow subset explains the increased oxidisive stress and increased inflammation through increased angiotensin II / Low neuronal nitrix oxide mechanism. The majority of POTS patients dont have pooling in their legs as an example and only a small subset have faulty musclepump activity and this was related to excessive peripheral vasoconstriction and vasomotor failure. There is a subset that have peripheral neuropathy and its only this group that have reduced peripheral expression of sympathetic a1 adrenoceptors.
What I did find particularly interesting is the overstimulation side of things - something that isnt really explained in any of the current POTS theories and in many of the CFS theories. By overstim I mean both mental overstim, and substance sensitivities.
Secondly here is another take on the relevance of the COMP gene:

There was a theory a few years back that CFS and POTS were caused by hypermethylation of the Norepinephrine transporter gene causing a hypervigilent state of perpetual increased sympathetic drive and paradoxical orthostatic blood flow disregulation. Cardiac MIBG reuptake has been found consistently to be low in POTS.

An argument was made that increased activation of an adrenogenic (sympathetic ganglia) methyltransferase was potentially causing this hypermethylation. They were looking at a different one but I wonder whether this could be a culprit? I might ask...

My angle with CFS/POTs has always been different. I developed it with Ankylosing Spondylitis slowly at the same time. For me it has to be related to autoimmune/inflammation. Exactly how I dont know...

 

This is interesting research although I think its a long bow to connect this the Light's work to the Shapiro work. Gradual onset - as occurs in many patients - doesnt really fit with an infectious pathophysiology.

Actually Dr. Light agreed that a herpesvirus, such as Shapiro suggested, was a ready possibility.

Secondly, the POTS finding seems strange given there are already proven distinct subsets found in POTS and the Low Flow subset explains the increased oxidisive stress and increased inflammation through increased angiotensin II / Low neuronal nitrix oxide mechanism. The majority of POTS patients dont have pooling in their legs as an example and only a small subset have faulty musclepump activity and this was related to excessive peripheral vasoconstriction and vasomotor failure. There is a subset that have peripheral neuropathy and its only this group that have reduced peripheral expression of sympathetic a1 adrenoceptors.

I agree that there seem to be several POTS subsets. I wonder if just the alpha2 group showed up here as there were some POTS patients left in the general group.

What I did find particularly interesting is the overstimulation side of things - something that isnt really explained in any of the current POTS theories and in many of the CFS theories. By overstim I mean both mental overstim, and substance sensitivities.
Secondly here is another take on the relevance of the COMP gene:

There was a theory a few years back that CFS and POTS were caused by hypermethylation of the Norepinephrine transporter gene causing a hypervigilent state of perpetual increased sympathetic drive and paradoxical orthostatic blood flow disregulation. Cardiac MIBG reuptake has been found consistently to be low in POTS.

An argument was made that increased activation of an adrenogenic (sympathetic ganglia) methyltransferase was potentially causing this hypermethylation. They were looking at a different one but I wonder whether this could be a culprit? I might ask...

Interesting....
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From my angle it still feels like overstimulation/inflammation as well, esp. the reaction to exercise. FWIW, I will have my VZV titers checked (blood only though) next week.

 

From my angle it still feels like overstimulation/inflammation as well, esp. the reaction to exercise. FWIW, I will have my VZV titers checked (blood only though) next week.

From my angle it feels like overstimulation as well. That titer check will be interesting. Shapiro does warn about the virus being sequestered in the ganglia and not showing up well in the blood - but it could and a high titer level would be interesting.

 

Dr Montoya seemed to be having success with anti-herpes drugs - could this be tied to these theories of herpes in the dorsal???

 

Sorry for bumping an old thread but it won't let me comment on the main site article, I just wanted to ask: I've read a lot about the gene expression changes, but I'm yet to see anyone speculate as to what could trigger these abnormalities or cause them to persist.