Chronic fatigue syndrome from vagus nerve infection: psychoneuroimmunological hypothesis

halcyon

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It just hit me last night that the pathogen involvement might have started in the gut, spread to the vagus nerve, but now is in the brain, maybe the hypothalamus. Oh gee, how does one get to a virus in the brain? That's a little bit more difficult.
If you watch Dr. Chia's talk from Invest in ME this year, this is his hypothesis with enteroviruses.
 

Hutan

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But presumably if you took probiotics when you are on antibiotics (which I have always done), this would prevent this problem.
The gut has thousands of different kinds of bacteria. Who knows what a particular antibiotic is doing to the gut flora in a particular individual? Taking a probiotic with just a few different kinds of bacteria may help, but it almost certainly won't correct all of the impacts of the antibiotic. So, presuming a probiotic prevents problems caused by an antibiotic is a bit of a leap.

Anyway, this thread is going off track.
Yep, sorry.
 
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so....if we all have bacteria in the gut....and the gut leaks....it has lots of places to leak into. Like lyme, bacteria could leak into the lymph system where the lymph system is a storage (like your computer running in limp mode or your car transmission) until the gut gets back to working properly. Could this be why nothing is detectable...there is really no disease found because its just a leaky gut spilling into other areas and causing the body to go into distress. Could this be why some of us miraculissly pull out of this because the immune system finally corrects itself and begins to work agian.
 

unto

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Hello,
I do not think the virus (?) steps before the n. vague and then to the brain because in my experience before I heard the v. in the throat, then into the head (headaches type meningitico) and then came the digestive problems (a few months after the start) ........

nor do I believe that it may be more virus to cause ME, because people (young and old, family members / relatives, friends, partners) have had symptoms of the disease only after attending my house ......., surely already with antibodies for dozens of viruses including ..... (I think) EBV and herpes viruses.

I am convinced that it must be a family of unknown viruses.
good night
 

Violeta

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Hello,
I do not think the virus (?) steps before the n. vague and then to the brain because in my experience before I heard the v. in the throat, then into the head (headaches type meningitico) and then came the digestive problems (a few months after the start) ........


nor do I believe that it may be more virus to cause ME, because people (young and old, family members / relatives, friends, partners) have had symptoms of the disease only after attending my house ......., surely already with antibodies for dozens of viruses including ..... (I think) EBV and herpes viruses.

I am convinced that it must be a family of unknown viruses.
good night
Do you think the virus might have entered through the nose?

http://www.livescience.com/15453-nose-gateway-virus-brain-disorders.html
 

Hip

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It just hit me last night that the pathogen involvement might have started in the gut, spread to the vagus nerve, but now is in the brain, maybe the hypothalamus. Oh gee, how does one get to a virus in the brain? That's a little bit more difficult.
Dr Chia mentioned that an enteroviral infection in the gut can travel to the brain along the vagus nerve itself in matter of just 3 days. The vagus nerve runs from the gut to the brain, and so enterovirus can just hitch a ride along this nerve route.

The vagus nerve terminates in the brainstem area of the brain, an area involved in the control of heart rate, blood pressure, autonomic functions — all things that tend to go out of whack in ME/CFS. Might an enteroviral infection entering into the brainstem from the vagus be the cause? Certainly brainstem dysfunction has been found in ME/CFS. (1)

Enterovirus travels along the vagus by a mechanism called retrograde axonal transport, which viruses make use of to travel along nerves. Enterovirus 71 travels along nerves by this retrograde axonal transport mechanism, (1) as does poliovirus. (1)

Tetanus toxin incidentally can also travel along nerves by means of retrograde axonal transport.
 
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Stretched

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<<Tetanus toxin incidentally can also travel along nerves by means of retrograde axonal transport.>>

All clear until last sentence... . Whoa! Is the Tetanus anti-serum (vaccine) considered a
'toxin', i.e. capable of axonal transport?

If yes, then perhaps I have two 'hard' connections to the current mass outbreak of ME:
a week's visit at Lake Tahoe (+ Incline Village) circa my own CFS onset AND, now,
possibly, a Tetanus vaccination in that same time framework!

From your perspective would these two events conjure up any scientific synthesis (or deduction), sic as to what to look for, if anything?

(I hate to even mention the squirrel found with 'the plague!', but hey, we're looking
under rocks these days.):wide-eyed:
 
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unto

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@Violeta,said
Do you think the virus might have entered through the nose?

no, I think rather by mouth ..... in those days I was young 1984/5
was often in the company, he often exchanged: cigarettes glasses and bottles.......,
he changedgirl...... I think it's like the EBV in saliva, then also in body fluids including blood naturally.

@Stretched,
if it was the vaccine tetanus the "culprit" I think that doctors who studied
those outbreaks would find the connection.

@Hip
I agree that this virus (as many virus) is hungry for nerves .....
and that the hypothesis retrograde axonal transport is very interesting
 

Violeta

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@Violeta,said
Do you think the virus might have entered through the nose?

no, I think rather by mouth ..... in those days I was young 1984/5
was often in the company, he often exchanged: cigarettes glasses and bottles.......,
he changedgirl...... I think it's like the EBV in saliva, then also in body fluids including blood naturally.
So then would it very easily proceed to the brain, too, the way it does when it enters the nasal cavity?

Surely would explain frequent sore throats.
 

Hip

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From your perspective would these two events conjure up any scientific synthesis (or deduction), sic as to what to look for, if anything?
I was toying with an idea a few years ago that if enterovirus enters the brain by traveling along the vagus nerve using retrograde axonal transport (RAT), then possibly anything that promotes the speed of the RAT process might conceivably make it easier for this virus to get to and enter the brain.

So a RAT-promoting factor might explain why some people develop ME/CFS from an enterovirus infection, but other's don't: my idea was that if you were exposed to any toxins or drugs that speed up RAT, and then simultaneously you caught an enterovirus infection, that combination of events might lead to the enterovirus getting into your brain, and thereby causing ME/CFS.

That was a hypothesis I was toying with.


Various factors do speed up or slow down (or even block) RAT. For example, organophosphate pesticides (which have been linked to ME/CFS) slow down RAT. 1

But I wasn't really able to join the dots on this hypothesis.
 
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Bob

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Just highlighting this again in case anyone missed it. Nothing new but an interesting read if the subject interests you. Available as a long-read or podcast.

He makes an interesting hypothetical disease link between ME & chronic Lyme. He also explores his hypothesis in relation to why various pathogens have been associated with ME, but none pinned down as the cause.

Interview with Dr VAN ELZAKKER.

HARVARD NEUROSCIENTIST DR. MICHAEL VAN ELZAKKER: CHRONIC FATIGUE VAGUS NERVE LINK
8th Dec 2015
http://thelowhistaminechef.com/harv...an-elzakker-chronic-fatigue-vagus-nerve-link/


 

Stretched

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Just a comment or two and a question re: the hypothetical… .

Great, the attention and the focus on specific neurology research related to CFS! However, I think it’s way early to get excited about this; AND the research is on rats with broad presumptions about human CFS (when only ~50%-? of 'rat findings' apply to humans). Also, by his own admission, there are so many ancillary neuronal areas (receptors) that could simulate similar conditions to CFS… . And isn't he really drawing a line between auto-immune and
anti-inflammatory affects; this part seems unclear to his focus?

As a PWC +/- 30 years, trying a whole bunch of related medical this and that, and studying more research than I would wish on an enemy, and still declining, my own resultant opinion as a cause leans towards over-stress inducing processes not unlike the mechanisms described in the discussion but with differences in biochemistry… . To wit,

From the interview: Even mast cells have these receptors that basically look for things that look kind of like a virus or look kind of like a bacteria and they become activated when they discover something that seems sort of foreign. They start pumping out these immune modulators, which then are detected by the vagus nerve and cause a sickness response... .

So, I would pose the question if he thinks over productions of adrenaline/norephinephrin might fit his research model and could possible look kind of like a virus or look kind of like a bacteria... and cause similar results…?

If so, this kind of research might be appended towards satisfying the bifurcating schools of pathogen mediated CFS vs stress induced immune dysfunction (ala HPA up-regulation affecting this doc's referenced mast or glia affects).
 
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Marco

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As a PWC +/- 30 years, trying a whole bunch of related medical this and that, and studying more research than I would wish on an enemy, and still declining, my own resultant opinion as a cause leans towards over-stress inducing processes not unlike the mechanisms described in the discussion but with differences in biochemistry… . To wit,

From the interview: Even mast cells have these receptors that basically look for things that look kind of like a virus or look kind of like a bacteria and they become activated when they discover something that seems sort of foreign. They start pumping out these immune modulators, which then are detected by the vagus nerve and cause a sickness response... .

So, I would pose the question if he thinks over productions of adrenaline/norephinephrin might fit his research model and could possible look kind of like a virus or look kind of like a bacteria... and cause similar results…?

If so, this kind of research might be appended towards satisfying the bifurcating schools of pathogen mediated CFS vs stress induced immune dysfunction (ala HPA up-regulation affecting this doc's referenced mast or glia affects).
You might be interested in this abstract which discusses how stress (potentially via glucocorticoids) can prime microglia in advance of an 'immune challenge'. This may have implications for a two (or multi) hit scenario and may also help explain why a range of stressors knock us off our feet.

Worth accessing the full paper if you can.

Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming

http://www.sciencedirect.com/science/article/pii/S0889159115000811
 

unto

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I do not think that the various viruses or bacteria known or stress or chemicals can trigger ME / CFS according to this hypothesis, because:1) if the cause are the "germs known" there should have been news around the world of symptoms before 1950 or 1934, and there is no clear trace;2) if the fault is stress or chemicals should detect higher percentage of patients in the conditions (stress) and concentrations (chemical) more, but the epidemiology does not seem to be affectedby these factors;the perception (of us sick) stress or to feel immersed in a polluted environment I think is due to the increased sensitivity caused by inflammation of the nerves and of course from the fact that (being so vulnerable and tired) any action or commitment there threadbare .The stroria ME instead of us that is epidemic-infectious (many local outbreaks and more than one case in the same environment), now, after 60 years, it has becomea clear global epidemic .........Of course the majority of virus prefers the nerve tissue and the virus (?) Which causes the ME , jus the samet we do not even know it ......
 
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Stretched

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@Marco. I believe I see the direction from the abstract (and will add the full text near term to my collection).

@unto. While not exactly a validation of causation this report suggests some predisposition and correlation of stress and CFS, though admittedly the small n begs significance.

Journal Transl Med. 2015 Aug 14;13(1):264. doi: 10.1186/s12967-015-0628-4. Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome.


BACKGROUND:
Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI.

METHODS:
We analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA.

RESULTS:
Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI.

CONCLUSION:
Our results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS.
 

Marco

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@Stretched

The met/met COMT polymorphism certainly isn't a smoking gun for ME/CFS but it's presence does suggest a number of things including a greater susceptibility to stress under pressure.

Coincidentally I was reading up on related things today and apparently (and speaking loosely - I need to tie down and confirm the details) :

It appears that chronic stress activates microglia via TLR4 including those in the paraventricular nucleus which may lead to an increase in sympathetic nervous system activity which is immunosuppressive (possibly with a corresponding down regulation of the parasympathetic arm including the cholinergic anti-inflammatory pathway).

I was quite surprised to learn that one of the leading causes of death following ischemic stroke (which of course also results in gliosis) is respiratory infection.
 

MeSci

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@Stretched

The met/met COMT polymorphism certainly isn't a smoking gun for ME/CFS but it's presence does suggest a number of things including a greater susceptibility to stress under pressure.

Coincidentally I was reading up on related things today and apparently (and speaking loosely - I need to tie down and confirm the details) :

It appears that chronic stress activates microglia via TLR4 including those in the paraventricular nucleus which may lead to an increase in sympathetic nervous system activity which is immunosuppressive (possibly with a corresponding down regulation of the parasympathetic arm including the cholinergic anti-inflammatory pathway).

I was quite surprised to learn that one of the leading causes of death following ischemic stroke (which of course also results in gliosis) is respiratory infection.
Can I just check, @Marco, that your penultimate paragraph doesn't relate to non-human studies, as these tend to have at least two major confounding factors (species differences and physical exertion, not to mention unnatural situations).