A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS),,,,,

[Cherry]

Further clarification to the above post.
This theory also explains orthostatic intolerance, a major symptom of mine. Other research has pointed out that orthostatic intolerance is caused, not by problems in blood pressure as previously assumed, but rather by lack of blood flow to the brain. (If you want the exact reference, I can look it up)

 

[Rufous McKinney]

Great post...very interesting...thanks for sending along background to help us understand.

Treatments?

About two years ago my life long Eppstein Barr type illness seemed to worsen and involved more of these odd symptoms...suggestive of the issues described here.

three months on a visit to a foreign country, despite resting much of the time, and not going on most field trips- I got much worse and developed symptoms like: tachycardia, my heart is flopping around gulping..I'm wearing support hose. I can't process visual stimulus. I can't look at the scenery on the car ride. Very severe brain fog.

I"ve not been able to get far in testing or specialists. My neck is a mess, the inflammation daily is awful. In my case, I get worse if I lie on my back due to something 'in the neck". Ok lying on my stomach. The base of my skull/neck constantly is in a dull pain, which often intensifies. Severe issues with optic nerves, throat- I can lose my voice if I chat at lunch, its very painful.

My right side is much more ill than my left (lymph system, liver).

What is IMHO?

 

[Rufous McKinney]

When I gave birth, my very first contractions were relentless, without any pauses in between. This resulted in record-fast deliveries.

That definately was not the case here- I was far less ill when I had two children decades ago; yet I was ill for most of the pregnancies and had awful ineffective labor- days of it. Swedish vacuums.

 

[Cherry]

I can't process visual stimulus.

This happens to me too!

My neck is a mess

So sorry to hear this

 

[DomSaxum]

I've had batteries of tests over the past 3 years, including 2 weeks at Mayo. Heart pumps, lungs work, blood is carrying oxygen, yet STILL it is as if the cells are crying for O2. The answer HAS to be somewhere in that intercell chemical functioning, but that is my reasoning talking, not any scientific, clinical research.

 

[Alesh]

It is very interesting. About 10 years ago I tried large doses of clenbuterol (I believe it is beta 2 agonist too but stronger than albuterol). And a miracle happened: After more than 10 years in a zombie state I was able to run and drive the bibycle. Unfortunately I wasn't able to replicate this since then. Large doses of clenbuterol are great burden to heart.

 

[bertiedog]

Asthma: My albuterol inhaler (ProAir) seems to have little or no effect: Albuterol is a Beta 2 agonist so if the beta2 receptors are defective, as the theory asserts, then the inhaler would have an attenuated effect at best

I must be different from you in that I take low dose Propananol which always helps me to feel a bit better but of course does nothing if in a PEM state. It stops the adrenaline from getting out of control and helps my OI too which is the adrenergic type.

It's always good to read explanations as to why we suffer like we do.

Pam

 

[bertiedog]

Sorry I forgot to add the explanation of how a beta blocker works is -

Propranolol is a non-selective β-adrenergic receptor antagonist, or beta blocker; that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors.

Pam

 

[Cherry]

It is very interesting. About 10 years ago I tried large doses of clenbuterol (I believe it is beta 2 agonist too but stronger than albuterol). And a miracle happened: After more than 10 years in a zombie state I was able to run and drive the bibycle. Unfortunately I wasn't able to replicate this since then. Large doses of clenbuterol are great burden to heart.

Fascinating!

 

[Cherry]

Sorry I forgot to add the explanation of how a beta blocker works is -

Propranolol is a non-selective β-adrenergic receptor antagonist, or beta blocker; that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors.

Pam

This just goes to show how complex this all is! I think a beta blocker would worsen my condition.

 

[Rufous McKinney]

he answer HAS to be somewhere in that intercell chemical functioning, but that is my reasoning talking, not any scientific, clinical research.

If we have non-deforming red blood cells, seems like that could result in a lack of oxygen in the capillaries and end organs...I always show high levels of DO in my blood- but I"m super air hungry.

 

[MonkeyMan]

@Cherry - this paper is discussed on another thread - https://forums.phoenixrising.me/thr...c-fatigue-syndrome-me-cfs.79681/#post-2273915

@Mary - perhaps these threads should be merged?

 

[Cherry]

One of the two named authors works for a pharma company.
I've looked at more of the paper and understand it to say that in MECFS there is increased sympathetic activity and hence the vasiconstricion.
In response to sustained vasiconstricion, sympatholysis occurs via endogenous vasodilators! That means to counteract the sympathetic effect , the body makes vasodilators.
Vasodilation can result in things like low standing blood pressure and heart issues.
In response to these unhelpful effects of vasodilators, sympathetic tone is increased more.
And on the circle goes !
I read a bit of the paper and think they make it clear that it's only a subset of patients, but unless a person is well practiced with reading ME science , it could be misleading and look like it's about all MECFS.
I for one would like the antibody test.
How do I get one is my next puzzle

I disagree with your interpretation. The sympathetic nervous system includes both vasoconstricting and vaso dialating receptors. The problem is then that only some parts of the body, especially the brain and skeletal muscle, suffer from hypoxia. I didn't see anything about the body compensating with additional vasodilators.

 

[Cherry]

@Cherry - this paper is discussed on another thread - https://forums.phoenixrising.me/thr...c-fatigue-syndrome-me-cfs.79681/#post-2273915

@Mary - perhaps these threads should be merged?

Thank you so much for pointing this out. Merge away! I must admit that I haven't visited this site in ages. I just seem to have more mental energy than usual these past few days.

 

[Mary]

@Cherry - this paper is discussed on another thread - https://forums.phoenixrising.me/thr...c-fatigue-syndrome-me-cfs.79681/#post-2273915

@Mary - perhaps these threads should be merged?

@MonkeyMan - thanks for the heads up! Yes, they should be merged, which I'll do right now -

 

[Cherry]

This theory doesn't take into account this recent finding:

https://forums.phoenixrising.me/thr...d-in-patients-with-me-cfs.79177/#post-2259534

I think both papers agree, Beta 2 receptors are not working or only responding weakly.

 

[Cherry]

To me it sounds like the group is stretching evidence for a small subset of ME to make it sound like it's the majority subset, or even the basis for all ME. It makes me want to ignore it. I'm unaware of having any vascular issues such as they describe.

My guess is that it's written to maximize potential funding, deserved or not.

These are not vascular issues that would be apparent. Redirection of blood flow to some tissues and away from others is a normal bodily function. So when you're resting, more blood flows to the digestive tract and less to skeletal muscle. When a person goes out for a run, less blood flows to the digestive tract, and more flows to the skeletal muscle, that is, if you do not have ME/CFS. With some people with ME/CFS, they are saying that the process that causes contraction of blood vessels works fine, but the part that causes dilation is impaired. In the case of the brain, greater sympathetic stimulation would normally not cause much change to blood flow to the brain, but because of the impairment, greater sympathetic stimulation would cause constriction of the large vessels supplying the brain

 

[Cherry]

I've looked at more of the paper and understand it to say that in MECFS there is increased sympathetic activity and hence the vasiconstricion.

They are not saying that increased sympathetic activity causes vasoconstriction in any general sense. The sympathetic nervous system causes a redirection of blood flow from some organ systems to others. With the dysfunction of the beta 2 receptor, there is a lack of vessel dilation that would supply skeletal muscles with extra blood. In the brain, sympathetic activation does not normally cause reduced blood flow, but it does when the beta 2 receptors are impaired.

 

[Cherry]

I've looked at more of the paper and understand it to say that in MECFS there is increased sympathetic activity and hence the vasiconstricion.
In response to sustained vasiconstricion, sympatholysis occurs via endogenous vasodilators!

Sorry for my last comment on your post. Yes the paper does talk about compensatory vasodilation, but I was viewing this as an afterthought to explain symptoms other than fatigue, brain fog, and orthostatic intolerance. My main interest in the paper was in understanding the core symptoms since they are the symptoms that I find most troubling.
The core problem is with an unbalanced sympathetic activation. Normally sympathetic activation encompasses both vaso constriction and vaso dilation so as to redirect blood flow away from some organ systems and toward others. In their model of ME/CFS, vasodilation is impaired.

 

[Cherry]

For me, I can believe small brain vessels aren't opening up enough,

I was under the impression that the lack of vaso dilation (skeletal muscle) or vaso contriction (brain) was happening in large blood vessels. not small blood vessels. I got this impression from the med school video I referenced above. However, Court's summary mentions small blood vessels, so I could be wrong.