Are Infections Just a Trigger of ME/CFS, or an Ongoing Cause of ME/CFS?

[Sidereal]

@Sidereal The kind Dr. Hyde sees on SPECT scans. I'm sure it's more complicated than that but I don't know the details.

Dr Goldstein has shown with repeated (pre- vs. post-treatment) testing that you can change the CFS SPECT pattern with successful treatment. Dr Hyde doesn't believe in treatment so perhaps what he interprets as irreversible brain damage from a viral or immune assault is just a functional problem with blood vessel regulation or a metabolic abnormality. Given the fluctuating, waxing-waning nature of the encephalopathy in most patients (and the relapsing-remitting pattern in some), I think it's unlikely (though not impossible) that there is structural brain damage in ME.

 

[alex3619]

Note: This thread was split from this point in the thread: I need help--just left hospital with a deadly drug--hence no proper opening post.

I do not believe that ME is an infectious illness. I believe it often begins with an infectious (or other) trigger but I do not believe ME is a persistent infectious state.

I think patients tend to believe that because they felt good, got a virus, and didn't recover - but that doesn't mean that there is ongoing infection.

I tend to agree with this but with one caveat. There is a suspicion that the early stage disease is infectious, and this goes back to the animal testing in 1955 after the Adelaide, Australia outbreaks. The trigger is infectious and might be for some time. Whether there is an ongoing infectious agent involved is unknown, but does not seem likely.

However if you look at ME as a conglomeration of many similar diseases, this argument might change. In any one individual there might be one or more perpetuating agents, even if as a population you cannot find anything.

So this debate is about two things. Is ME caused by a pathogen generally, or is it caused by a pathogen in specific individuals?

There is no question that many pathogens seem to be able to trigger ME. The question is about the mechanisms.

 

[alex3619]

Given the fluctuating, waxing-waning nature of the encephalopathy in most patients (and the relapsing-remitting pattern in some), I think it's unlikely (though not impossible) that there is structural brain damage in ME.

I am not convinced there is no damage. Not all the evidence is SPECT related. However it is unclear just how much is permanent, temporary, or irrelevant. If the Stanford MRI data from last year is replicable then there may be permanent changes to the brain, but its unclear how important this is. Not all evidence of brain changes is about permanent damage.

My suspicion though is that most of the SPECT data is showing metabolic issues, not structural damage, and this may not even be about blood flow all the time.

I think that a recovered ME patient, when that happens, might be better considered like a fully recovered (mild) stroke patient. Yes there might be issues, and maybe they will show up in old age, but barring a recurrence then for the most part they do not matter.

 

[alex3619]

want at least the first 2 of Koch's postulates fulfilled - these are the basis of infectious disease. The 3rd is important too but impractical (if you look it up you'll see why...) =P

Here they are, from Wikipedia:

1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.
2. The microorganism must be isolated from a diseased organism and grown in pure culture.
3. The cultured microorganism should cause disease when introduced into a healthy organism.
4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

http://en.wikipedia.org/wiki/Koch's_postulates

With respect to a heterogeneous disease pretty well all these things have been shown by Chia to some extent The enterovirus has been shown, but I do not know if this has been properly published, to be infectious in animals after removal from the stomach lining of patients. So it can cause some disease, but ME? That is the part that is very hard to test.

All of this is probably moot though unless we can use a validated diagnostic blood test to be sure of the problem. How do we even diagnose ME in mice, and can they even get sick? From the 1955 animal study we know Monkeys get similar nerve damage to what we see sometimes in ME patients, but this was something like 4 monkeys.

Modern virological research, and indeed general pathogen research, has to go way beyond Koch's postulates. They were for another age.

What I want to see is verifiable molecular mechanisms that are induced by a pathogen. I want to see that resolution of those mechanisms correlates closely with recovery. I want to see that worsening of those mechanisms correlates with increased symptomology.

 

[alex3619]

In other words, it is not inconceivable that there may be both an initial trigger action, as well as an ongoing causal action from a chronic infection.

Yes, and only further research can resolve this issue.

 

[alex3619]

What about viral or bacterial meningitis, which only lasts for a few hours or days, but which can lead to permanent loss of mental faculties and permanent personalities changes.

Which in my case was measles encephalitis. Measles used to be very common in children, but if any virus gets into the brain it can induce immunological damage even if the virus itself is not doing much damage.

 

[heapsreal]

@heapsreal - Yep - I'm not a doctor but that sure sounds like it. VZV, unlike HSV1/2, is often not symmetrical and affects only one side. It usually follows a dermatome (the area of skin innervated by one nerve).

They don't test CD8 function - too hard to do - but NK function is a near-perfect proxy for the ability of the cells to lyse targets (but not to recognize them - that mechanism is different - but the former seems to be more relevant).

You would have good humoral immunity - not surprising. When cell-mediated immunity is impaired, viruses replicate more, antigen presentation increases, and titers go up. So that all makes sense. The vax may help but it will mostly just stimulate more antibodies. You might do well with a th1 shifter like imunovir if your doc agrees to prescribe it (in addition to the antivirals you are already getting).

Also take a look at Jay Goldstein's work on cimetidine in treating mono - the mechanism would likely apply to shingles as well, although not sure if he has tried it. Cimetidine is very cheap and OTC (it's an H2 blocker / acid reducer). Some of the newer ones have fewer side effects (like zantac / ranitidine) and I believe studies showed they worked just as well - so I'd try that if doc thinks it's reasonable / harmless (even maybe if he doesn't think it would help - few are aware of Goldstein's very interesting work on this).

I don't think it's your innate immune system that is the issue - I think it's the adaptive cellular response that is impaired. If you don't mind my asking, what is your age? Shingles is uncommon in younger people but gets more common by the 50's. Not unheard of in 40's, pretty rare before then.

I'm not sure how often headaches accompany shingles. While possible that it's a low grade meningitis, there are some reasons to doubt this. First, VZV travels along a given nerve. It doesn't generally travel through the blood stream - although oddly you have it in 2 very different locations. I believe that is not the norm - it's usually on 1 dermatome or 2 closely related ones, suggesting the VZV worked its way back to the intersection of the 2. There's also the BBB which offers some protection to the brain and CNS, but that's obviously not perfect since VZV meningitis can occur.

I'm not sure what the penetration of various drugs through the BBB is - that might be worth looking at (e.g. valaciclovir, famciclovir, ranitidine, cimetidine, etc.)

@Eeyore im 44 so not really in the bracket for shingles supposedly but then again one isnt suppose to get chickenpox twice either, once as a kid and the other at 31, but probably due to the fact i was in a post cmv mono state when i got chickenpox the second time, which was quite severe. Shortly after had ebv mono. So my body got a belting by infections for several months.

The immune testing i had done in a cfs research study done by NCNED at bond university and now being done by griffith university. Its the aussie team that has connection with Dr Peterson. CD8 function was low in the general findings of the cfs group i was in that they studied, so a good chance i was one of them. The testing they do isnt standard testing any doctor can do or get here, but research only.

My thoughts are that its probably PHN but because it seems to have triggered hypertension 190/130, probably some type of meningitis. Bp is now controlled, headaches have eased some but still ongoing.

I will continue famvir for a few reasons but mostly because i think i had 2 more outbreaks on my legs after the head. Plus famvir has been helpful for cfs symptoms which return 2-4 weeks after stopping it.

Interesting u mention immunovir, i was on it when i got the first lot of shingles but not on avs. SO due to cost and not preventing shingles i have given up on immunovir for now. I started ahcc shortly after the first episode and this also didnt seem to help, recent blood work showed i still had neutropenia which ahcc is suppose to be good at correcting. Im still on it and will finish a total of 3 months worth but i dont think i will spend my money on it either. I guess add neutropenia to the list with low nk function and cd8. Lymphocyte subsets are always elevated but are lower than pre antiviral levels several years ago now.

As for adaptive immune response, not sure i agree as previous tests said i had good immunity to vzv. I had this test 9 months ago to see if it was worth me having shingles vaccine and going by this test i didnt need it. obviously the little bugger still got in which is because my innate immune system ie nk and neutrophils are low.

Hopefully i will see my dr today or tomorrow and go on some extended sick leave. In a state where i cant concentrate enough for work and memory is a shocker too. Also on pain meds which isnt good for my job. Im stressing more out about financial stuff at the moment as i have no sick leave and its 2 weeks with no income before income protection will kick in. Plus trying to understand the paperwork etc my brain wont absorb much. Its taken me alot longer to type this then it normally would???

thanks for your answers,
cheers

 

[alex3619]

If we could do this, you would start to piece together a universal theory of ME/CFS, where different causes each activate the same central pathological mechanism of chronic sickness behavior.

Presuming its a single disease. It might not be. Its too early to be sure. So far its a syndrome, and may not be the same disease. I suspect from the way things have been moving in the research the last ten years that ME might be two different but similar diseases. In which case we might need two models of the disease.

 

[Hip]

I don't think the vagus nerve infection theory is correct.

What about the sickness behavior theory of ME/CFS?

If you look at this post which describes the four known pathways of activation of sickness behavior (the vagus is one of the four), do you think that certain autoimmune processes could be chronically activating sickness behavior, and thus causing the symptoms of ME/CFS?

If you come up with any suggestions on how autoimmune processes might chronically activate sickness behavior through one or more of these four pathways, I'd love to hear your ideas.

A better explanation is that organophosphates are cholinergics - they inhibit acetylcholinesterase irreversibly. The cholinergic pathways can be permanently damaged from organophosphate exposure.

One way in which the body regulates immune activity and keeps inflammation localized is the cholinergic anti-inflammatory pathway. If you had damage from organophosphates, your body's natural ability to regulate runaway inflammation would have been severely impaired. Thus you could have had a runaway inflammatory process that caused longer term damage.

I take you point about cholinergic pathways being permanently damaged from organophosphate exposure.

But this brings us into tricky territory, because the researchers who study the ME/CFS-like illness that can follow organophosphate exposure do not believe it is a good idea to think of this organophosphate illness as a version of ME/CFS, even though it has very similar symptoms. They think the etiology is basically different.

Now, I recovered fully after my organophosphate exposure, which suggests there was no permanent damage; but then some months after this full recovery, I got hit with a nasty enterovirus.

This virus spread to around 30 friends and family, and caused very mild (and sometimes not so mild) ME/CFS symptoms in all these 30 people. I am talking about classic ME/CFS symptoms like fatigue, sounds sensitivity and “tip-of-the-tongue” phenomena (the inability to retrieve a word or name from memory during conversation) — these symptoms all suddenly appeared in these 30 people after they cause the virus. These symptoms have persisted in all 30 people for over 10 years now. Four people got heart attacks from the virus, and in two cases, this was proven to be chronic myocarditis-related (enteroviruses are very common causes of myocarditis).

And incidentally, this is surely evidence that some viruses can produce ME/CFS symptoms in everyone; it's just that in most people the symptoms are subclinical.

Anyway, it was only me who developed full ME/CFS from this virus. So it's possible that somehow, the organophosphates predisposed me to getting ME/CFS from this enterovirus.

 

[Eeyore]

Autoimmune disease certainly causes inflammatory problems and alterations in cytokine production and immune polarization, and yes, this could cause a feeling of being sick. This isn't unique to autoimmune disease or even specific for it, but it certainly can happen. I think it's possible that autoimmunity plays a role in ME. I'm not sure how big a role. There have been studies that have found increased prevalence of some autoantibodies in ME. The APS antibodies are the best replicated although the studies aren't too big - but the studies do all reach similar conclusions. Also found in POTS. There are also some studies suggesting autoantibodies to the HSP's - which is very interesting. It may simply reflect an upregulation of the UPR though (physiological or pathological, it's not clear yet which that would be). So they might be more a result than a cause, but might then contribute in their own way to symptoms. I think a subset of patients probably have antibodies to the alpha-3 subunit of the the nicotinic acetylcholine receptor - and possibly the alpha-7 subunit as well. This is most likely to be present in patients with prominent autonomic dysfunction. It is found in POTS frequently. I have not yet found any positive antibodies in my testing.

I suspect you had a weakened cholinergic system and an impaired cholinergic response - resulting in the inability to control CNS inflmmation via the cholinergic anti-inflammatory pathway. Your dysfunction may have been subclinical but I doubt you were at premorbid functioning after the OP exposure. You may not have a genetic predisposition - you may have been entirely induced by environment and bad luck.

Much of the damage in stroke is actually inflammatory. I think ME may be similar - highly virulent viruses that impact the CNS cause runaway inflammation, and if the body has an impaired ability to reduce that inflammation, ME results. It's not the same as a stroke as stroke patients do not develop ME, but both are CNS.

Another interesting point here is that Dr. Klimas believes that GWI and ME are the same thing. We don't really know the cause of GWI, but many have suspected cholinergic toxins or even the antidotes to them that were given to the soldiers (pyridostimine - which is used to treat POTS). Another suspicion is that it's linked to many vaccines they received which upregulated and overstimulated the immune system, so that the body was unable to bring the inflammation back down.

Dr. Klimas gets a lot of her research money from the DoD for GWI - she says it doesn't matter which group she studies because they are exactly the same immunologically.

 

[SOC]

Another interesting point here is that Dr. Klimas believes that GWI and ME are the same thing. We don't really know the cause of GWI, but many have suspected cholinergic toxins or even the antidotes to them that were given to the soldiers (pyridostimine - which is used to treat POTS). Another suspicion is that it's linked to many vaccines they received which upregulated and overstimulated the immune system, so that the body was unable to bring the inflammation back down.

Dr. Klimas gets a lot of her research money from the DoD for GWI - she says it doesn't matter which group she studies because they are exactly the same immunologically.

That's not what she said to me personally, although that was several years ago and she may have changed her position since then.

What I recall her saying was that GWI and ME are very similar, but show clear differences that suggest they are two different causal paths to similar (but not identical) conditions.

 

[Eeyore]

Maybe I misinterpreted - or maybe it was just that it was identical in the context of the talk she gave at the conference that I saw her at.

 

[Hip]

I suspect you had a weakened cholinergic system and an impaired cholinergic response - resulting in the inability to control CNS inflmmation via the cholinergic anti-inflammatory pathway. Your dysfunction may have been subclinical but I doubt you were at premorbid functioning after the OP exposure.

On the assumption that my cholinergic anti-inflammatory pathway may be under par due to prior organophosphate exposure and damage, I have been looking for drugs or supplements that might ramp up this pathway. There does not seem to be that much.

Dietary fat seems to boost the cholinergic anti-inflammatory pathway, as does nicotine.

This study says that the nicotinic acetylcholine alpha7 receptor is an essential component of the cholinergic anti-inflammatory pathway, because activation of this receptor prevents cytokine release. So that seems like a good receptor to agonize. Alpha7 agonists include nicotine, anabasine, and the drug tropisetron, plus a number of compounds in development.

Perhaps I will take up smoking e-cigarettes...

 

[Eeyore]

@Hip - I actually have considered trying the e-cigs too. I haven't - and wouldn't recommend it to anyone - as it does have a lot of side effects (although much less than real cigarettes, which are likely very bad for us or anyone). I've never smoked in my life and have never had any desire to, but I wonder if nicotine might help.

I think the connection to organophosphates does argue for a role of the cholinergic anti-inflammatory pathway. Not a certainty by any means, but very interesting as a possibility.

 

[lansbergen]

Alpha7 agonists include nicotine, anabasine, and the drug tropisetron, plus a number of compounds in development.

You forget the immune modulator I use.

 

[Eeyore]

@Hip - My mom had an ME-like illness when she was 15-17ish, but it resolved and she has been well since. She smoked from her late teens through her late 20's, but quit after that. I wonder if it actually helped her recovery...

I wonder if anyone has ever done a study on smoking habits in ME patients - that could be quite interesting. Also, if mothers smoked while pregnant with the kids (my mom did).

 

[lansbergen]

I wonder if anyone has ever done a study on smoking habits in ME patients - that could be quite interesting.

I smoke like a chimney. I need it together with the immunemodulator I use.

 

[Hip]

You forget the immune modulator I use.

That is a taciturn post!

 

[Sidereal]

My mother has had an ME-type illness and dysautonomia since teens. She is mildly affected compared to me. She has smoked like 50 a day for decades. She says with the cigs she feels like she has the flu all the time - fatigue, pain everywhere etc. Sounds familiar.

The brain craves what the body needs.

 

[Eeyore]

@Sidereal - Interesting, similar story with our moms, although mine quit smoking when I was a kid.

Any unusual or interesting health issues with your dad?