Do MEs cause CFS?

[Forbin]

I think the sensitivity to mould would come under my ME3, along with sensitivity to other sensory stimuli like light and sound. I do not think what you describe could be explained in terms of an immunological or allergic reaction. The only explanation that I can think of is that the sensitivity is within the brain sensory pathways, perhaps in the basal ganglia. Sense of smell can have very powerful effects on us, even in the normal situation. That could fit with the popular theory of microglial changes perhaps.

The light and sound sensitivity part of ME makes me think of migraine headaches. I developed terrible headaches a few months after coming down with ME. Due to their character, I assumed they were migraines, but they had no aura. I'd never had migraines before. Years later, I experienced episodes of classic, visual migraine aura without any headache. I still occasionally get such episodes. They leave me feeling kind of "out of it" in an odd sort of way.

Dr. James N Baraniuk of the Division of Rheumatology, Immunology and Allergy at Georgetown University, Washington, DC, authored a paper in 2011 that concluded:

"CFS subjects had higher prevalences of MO [migraine without aura] and MA [migraine with aura] than HC [healthy controls], suggesting that mechanisms of migraine pathogenesis such as central sensitization may contribute to CFS pathophysiology."

Migraine headaches in Chronic Fatigue Syndrome (CFS):
Comparison of two prospective cross-sectional studies
http://www.biomedcentral.com/1471-2377/11/30

 

[knackers323]

I am very tempted to think that where people have speckled ANA at that sort of level and fatigue that the antinuclear antibodies are involved in the cause of the fatigue - what I called ME1. The situation may be clearer if a specific antigen screen has been done to see what the speckled pattern is due to - anti-Sm, anti-RNP, anti-Ro etc etc. Labs tend to call this an ENA screen although ENA is not an ideal term for these antigens. If the speckling is due to anti-Ro then it would be fairly clear that this was a Sjögren's type fatigue.

The same might apply at 1:40 but it is just that there is no clear limit to the 'normal range' for the test so it becomes a matter of probability.

Ok. No Dr I have seen looked any further into the ANA result.
What other symptoms do you suggest would be in this ME1 group? Do you know of any potential treatments for the fatigue? Thanks

 

[MeSci]

The light and sound sensitivity part of ME makes me think of migraine headaches. I developed terrible headaches a few months after coming down with ME. Due to their character, I assumed they were migraines, but they had no aura. I'd never had migraines before. Years later, I experienced episodes of classic, visual migraine aura without any headache. I still occasionally get such episodes. They leave me feeling kind of "out of it" in an odd sort of way.

Were the effects purely visual? I ask because I have had two episodes of what could have been thought of as 'aura without migraine' but they were purely visual - there was no strange feeling at all. The first lasted about 15 minutes and the second about 30 minutes. They were months apart, perhaps longer.

After a lot of searching I came to a tentative self-diagnosis of scintillating scotoma.

 

[Jonathan Edwards]

Ok. No Dr I have seen looked any further into the ANA result.
What other symptoms do you suggest would be in this ME1 group? Do you know of any potential treatments for the fatigue? Thanks

I am not sure the symptoms would be different from the other groups necessarily. There are no specific treatments for fatigue associated with ANA even in the well recognised situations like Sjögren's. One day we may be able to target the antibodies themselves. ANA antibodies are not as easily dealt with by rituximab as some other types of autoantibody but it may be that over the next year or two people will make progress on that.

 

[Forbin]

Were the effects purely visual? I ask because I have had two episodes of what could have been thought of as 'aura without migraine' but they were purely visual - there was no strange feeling at all. The first lasted about 15 minutes and the second about 30 minutes. They were months apart, perhaps longer.

After a lot of searching I came to a tentative self-diagnosis of scintillating scotoma.

Yes, that's it. The odd feeling comes afterward. I just feel sort of "drained." The episodes started about 3 years after I got ME/CFS. They became less frequent, but I still get a couple a year, at least. There is also a degree of light sensitivity that I have noticed both preceding and following these episodes.

Here's a pretty good video of what they look like. The progression seen in this 60 second video actually takes about 30 minutes or more before the "aura" gradually exits the visual field. Also, in my case at least, there is a more distinct triangular geometry to the flickering edge - like seeing a lot flickering triangle facets shaped in a broad curve. The colors look pretty "unreal."

 

[aimossy]

@Jonathan Edwards
Hi,
I would fit into your proposed ME1 I think. I have 1:640 ANA homogenous that went ticking up as I got really ill and I was screened at Rheumatology. It has been like this for years now but last year it shifted from homogenous to speckled. Is it a good idea to get rechecked if the pattern changes?

 

[Jonathan Edwards]

@Jonathan Edwards
I would fit into your proposed ME1 I think. I have 1:640 ANA homogenous that went ticking up as I got really ill and I was screened at Rheumatology. It has been like this for years now but last year it shifted from homogenous to speckled. Is it a good idea to get rechecked if the pattern changes?

The pattern report may depend on the lab technician. Homogeneous and speckled are subjective gradings so there may not be any real change in the antibody specificity. However, patterns do change for some people. Even so, I am not sure how relevant that is to clinical issues. What I think may be useful is to have the specific antigen (ENA) screen done. If ANAs are relevant to MEs then at least it would be worth knowing which antigens are targeted. The ENA screen only looks at a standard range of common antigens though. Many people will come up with nothing specific. To find out what their antigen specificity is one needs to do a Western blot in a research lab and then identify the antigen. That can be a mini-research project in itself just for one serum, costing thousands of dollars, so it is not often done. However, it is something that maybe someone should look into in more detail for ME in general.

 

[knackers323]

I am not sure the symptoms would be different from the other groups necessarily. There are no specific treatments for fatigue associated with ANA even in the well recognised situations like Sjögren's. One day we may be able to target the antibodies themselves. ANA antibodies are not as easily dealt with by rituximab as some other types of autoantibody but it may be that over the next year or two people will make progress on that.

My ANA levels have fluctuated throughout my illness. Is this normal in the known autoimmune diseases?

 

[aimossy]

Thanks @Jonathan Edwards, so I think that means clinically for me it would not really matter that much getting any further testing done. But it would be interesting to know if the ENA screen shows anything from a scientific perspective?

 

[Jonathan Edwards]

My ANA levels have fluctuated throughout my illness. Is this normal in the known autoimmune diseases?

Yes ANA in particular often goes up and down.

 

[Jonathan Edwards]

Thanks @Jonathan Edwards, so I think that means clinically for me it would not really matter that much getting any further testing done. But it would be interesting to know if the ENA screen shows anything from a scientific perspective?

Right.

 

[MeSci]

Yes, that's it. The odd feeling comes afterward. I just feel sort of "drained." The episodes started about 3 years after I got ME/CFS. They became less frequent, but I still get a couple a year, at least. There is also a degree of light sensitivity that I have noticed both preceding and following these episodes.

Here's a pretty good video of what they look like. The progression seen in this 60 second video actually takes about 30 minutes or more before the "aura" gradually exits the visual field. Also, in my case at least, there is a more distinct triangular geometry to the flickering edge - like seeing a lot flickering triangle facets shaped in a broad curve. The colors look pretty "unreal."

Mine isn't like that. Mine is quite symmetrical shimmering at the periphery, and it doesn't make me feel dazed, disoriented or tired. I fell completely normal except that I just can't see properly and instead have to settle for looking at the pretty pattern until it goes away! Your 'triangle facets' perhaps describes the zigzag pattern of scintillating scotoma though.

Mine was more like the street image on this page. No colour - just pale zigzags on a darker background.

The first thing I did was self-test for stroke, and when I passed that I was not so worried!

EDIT - sorry about the duplication, now removed. Must have pasted instead of copying!

 

[Helen]

@Jonathan Edwards , I hope you don´t mind that I am back with questions about your opinion on B12- and folate supplementation and decreased methylation among people with ME. Just now I wish English had been my first language .

It´s obvious that quite a few people with ME improve, many rather dramatically, from taking MeCbl and the kind of folate that works for him/her. This protocol has been used for decades by some clinicians in my country for people with ME/CFS, people with health problems from mold, people with health problems from amalgam fillings and for people with health problems from certain chemical products as organic phosphates a.o. Often the sensitivities are mixed among these people (and on top of everything they are more prone to get autoimmune thyroiditis that you are looking at).

The question bothering me, that so far isn´t answered by research, is "why do so many improve significantly by taking MeCbl and for them proper folate?" The genetics that have been discussed here for long time doesn´t seem to give the full answer as these mutations are rather common in a healthy population too, and there are people with ME who don´t have the SNP´s that are focused on, and they still improve on (Me)Cbl+folate.

Is there any other group of patients that you have studied that is helped by high and frequent doses of B12 and folate? I haven´t heard of any. Or could it be that this need is typical to ME? Maybe even the cause to ME as proposed by Rich Van Konynenburg?

@eve789 highlights the fact that pregnancy could elicit ME. One reason could be that the mothers got nitrous oxide while giving birth that have depleted their storage of B12 and therefore decreased the total reduced glutathione. I have interviewed about ten women in my country where this was the case. Later they all had their amalgam fillings removed and they got much better after that , which could be from a lower demand on glutathione too.

Getting completely well by living in a desert, when sick from mold exposure, could be that the glutathione restores when the demand on gluthatione is lowered by zero exposure and there isn´t any longer a need to detoxify with the help of glutathione.

(To new friends at this forum, the possible connection and maybe causation is presented by Rich Van Konynenburg in this seminar and on the slides http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/ .

Rich was hoping that someone would look at the level of reduced glutathione and other parameters in the methionine and folate cycles (and the outcome of reduced glutathione ) before and after Rituximab treatment. I wish this could be done as the need for B12 and folates seems to be so crucial for most people with ME. As far as I have got it, people that get well from Rituximab have no need of other treatments, not even B12 and folate supplementation. How could that be? Why did this need disappear?

I would be very happy to get your opinion on this @Jonathan Edwards. I might be out biking as we say in Swedish -(which means be wide of the mark) .

 

[Jonathan Edwards]

@Jonathan Edwards , I hope you don´t mind that I am back with questions about your opinion on B12- and folate supplementation and decreased methylation among people with ME.

The question bothering me, that so far isn´t answered by research, is "why do so many improve significantly by taking MeCbl and for them proper folate?"

Is there any other group of patients that you have studied that is helped by high and frequent doses of B12 and folate?

@eve789 highlights the fact that pregnancy could elicit ME. One reason could be that the mothers got nitrous oxide while giving birth that have depleted their storage of B12 and therefore decreased the total reduced glutathione. I have interviewed about ten women in my country where this was the case. Later they all had their amalgam fillings removed and they got much better after that , which could be from a lower demand on glutathione too.

Getting completely well by living in a desert, when sick from mold exposure, could be that the glutathione restores when the demand on gluthatione is lowered by zero exposure and there isn´t any longer a need to detoxify with the help of glutathione.

I would be very happy to get your opinion on this @Jonathan Edwards. I might be out biking as we say in Swedish -(which means be wide of the mark) .

I am afraid to say that I am sceptical about this sort of biochemical discussion. Do we have data from blinded trials of B12 and folate in ME? I think not. Without that my instinct is to think that PWME feel better after taking vitamins for the same reason that millions of other people feel better after taking vitamins - probably nothing to do with needing vitamins. And the various changes you suggest might relate to glutathione I cannot think will actually make any significant difference to basic metabolic pathways, except pregnancy which changes everything so we could blame anything else just as much.

I fear all the talk of B12 sounds like using scientific language without any true grasp of what would actually happen in reality. Long ago I learnt only to believe an effect where you had a quantitative 'dose-response' type relation. A theory that predicts something goes up is pretty useless. A theory that predicts something will go up somewhere between 0.35 and 0.45 units with a dose of 60mg and 0.75-0.85 units with 90mg is worth testing. Show me a glutathione dose response curve in a blinded trial of vitamins in ME patients and I will take note.

I hate to sound a spoilsport in regard to suggestions from patients, particularly as so many insightful comments come up on PR. But I have to stick to Spock mode and be dispassionate about all the theories around. We want the right answer. Methylation does not add up to me, at least so far.

 

[Jonathan Edwards]

Out biking in Sweden doesn't sound too bad to me - especially as the bit I know is quite flat.

 

[Hip]

Thanks Hip. The problem with 'models of autoimmunity' in mice is that they are not in fact models of human autoimmunity. For nearly all human autoimmune diseases there is no evidence for an infective trigger. People confuse autoimmunity with post-infective hypersensitivity responses as in rheumatic fever, Reiter's syndrome, coxsackie infections etc. In none of these do you get any evidence of persistent reaction against self antigens. Unfortunately, for decades lab scientists have worked on these self-fulfilling model systems that don't really tell us anything. Coxsackie sensitivity in mice may tell us about coxsackie sensitivity in humans but that is not related to autoimmune disease as far as we know. 'Autoimmune' gets used just to mean 'excessive inflammation'. Back in the 1950s all the infectious disease doctors looking after rheumatic fever had to find a new job because of penicillin. They all became 'immunologists' and as a result it became fashionable to think that autoimmune diseases were like rheumatic fever, but there is nothing in common as far as I can see. Everybody came to believe in the theory of 'molecular mimicry' but virtually nothing has been found to support that idea.

That is not to say that post-infective hypersensitivity may not be one sort of ME. I am suggesting that in ME2. But ME2 is not intended to be autoimmune.

Looking back I see that Dr Bateman cites potential environmental triggers in autoimmunity as:
virus, bacteria, stress, food, pollutants, hormones
but the list for which we have any evidence is actually very limited. Smoking makes RA more likely. Drugs can induce SLE. Bone marrow transplantation can trigger several autoimmune diseases. That's about it. No viruses or bacteria with the possible excpetion of Guillain Barre neuropathy and that is rather an odd monophasic disease that may turn out to be a post-infective hypersensitivity after all.

That's very interesting about the confusion of autoimmunity with post-infective hypersensitivity responses. I take it you mean allergy when you are referring to hypersensitivity here. Increase or modulations in allergies and sensitivities is of course a common phenomenon in ME/CFS.


But regarding evidence for an an infective trigger of autoimmunity: wouldn't the associations between autoimmune conditions and certain pathogens represent suggestive evidence? For example, there seems to be an association between type 1 diabetes and coxsackievirus B and echovirus:

"Diabetes mellitus type 1 is associated with viral species from the enterovirus genus,[89][90] specifically echovirus4[91] and Coxsackie B virus (the latter it is thought may infect and destroy the insulin producing beta-cells in the pancreas and also damage these cells via indirect autoimmune mechanisms).[92][93] One study found Coxsackie B1 virus associated with a higher risk of the beta cell autoimmunity that portends type 1 diabetes; though Coxsackie B3 and B6 viruses were found to be associated with a reduced risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus).[94] In boys, human parechovirus infection has been linked to a subsequent appearance of diabetes-associated autoantibodies.[95]"

Source: List of human diseases associated with infectious pathogens - Wikipedia

What I find intriguing about pathogens is the many immune evasion tactics they employ in the body. Immune evasion of course being the process of "hacking" into the immune system, and deliberately disrupting it or altering its function, in order to thwart the immune attack. For example, coxsackievirus B3 down-regulates MHC I from the cells it infects, and Epstein-Barr virus has genes to make a fake version of IL-10.

If a pathogen is actually altering the function of the immune system in this way, might this set the stage for autoimmunity to appear? I haven't seen any studies on this, but I am curious as to whether anyone has looked at the possibility of a link between immune evasion and autoimmunity.

 

[Jonathan Edwards]

That's very interesting about the confusion of autoimmunity with post-infective hypersensitivity responses. I take it you mean allergy when you are referring to hypersensitivity here.

But regarding evidence for an an infective trigger of autoimmunity: wouldn't the associations between autoimmune conditions and certain pathogens represent suggestive evidence? For example, there seems to be an association between type 1 diabetes and coxsackievirus B and echovirus:

What I find intriguing about pathogens is the many immune evasion tactics they employ in the body. Immune evasion of course being the process of "hacking" into the immune system, and deliberately disrupting it or altering its function, in order to thwart the immune attack. For example, coxsackievirus B3 down-regulates MHC I from the cells it infects, and Epstein-Barr virus has genes to make a fake version of IL-10.

If a pathogen is actually altering the function of the immune system in this way, might this set the stage for autoimmunity to appear? I haven't seen any studies on this, but I am curious as to whether anyone has looked at the possibility of a link between immune evasion and autoimmunity.

Post-infective hypersensitivity responses are not allergies in fact. They come in a variety of forms but do not involve the IgE-related processes of allergy.

I am not sure about the link between type I diabetes and viral infection. I would not put too much weight on a Wikipedia entry on that. People are always wanting to make this sort of connection but for the great majority of autoimmune diseases the evidence simply is not there - and as I indicated the epidemiological evidence is very much against. Type I diabetes is hard to fit into a category and is not obviously a true autoimmune process. Autoantibodies do occur but usually only transiently. Unlike most true autoimmune states it often occurs in children.

Again, everyone would like to think that pathogens 'hacking' the immune system could 'trigger' autoimmunity because they think in terms of the two component model of genes and environment. But the evidence, as far as I know, simply does not bear that out. Moreover, nobody has actually come up with a way it would work - or with a reason why 99% of people do not get autoimmunity with these infections. With the alternative model of an intrinsically metastable regulatory system making use of stochastic events the mechanisms are quite easy to define. There is one for rheumatoid factor, one for anti-DNA, one for antiAChR etc etc.

 

[Hip]

Again, everyone would like to think that pathogens 'hacking' the immune system could 'trigger' autoimmunity because they think in terms of the two component model of genes and environment. But the evidence, as far as I know, simply does not bear that out. Moreover, nobody has actually come up with a way it would work - or with a reason why 99% of people do not get autoimmunity with these infections.

I did come across this interesting finding by Dr Art Ayres, which I posted here:

Enterovirus VP1 protein contains an allergen that causes autoimmunity?

Basically Ayers says he found an amino acid sequence in the VP1 protein of enteroviruses that he also found in all allergens (such as peanut, ragweed, dust mite, bee venom) as well as in the autoantigens of autoimmune diseases like lupus and multiple sclerosis.

It sounds intriguing, but I don't have the knowledge to even begin to judge whether this is a viable idea.

 

[knackers323]

Yes ANA in particular often goes up and down.

So are there any other tests that can be run to show that the ANA is due to an autoimmune illness?

Is there anything else that can cause these ANA readings?

Are there no immune regulators that are used in other autoimmune conditions that may have an effect? Like immuran that my brother uses for his crohns.

 

[Jonathan Edwards]

I did come across this interesting finding by Dr Art Ayres, which I posted here:

Enterovirus VP1 protein contains an allergen that causes autoimmunity?

Basically Ayers says he found an amino acid sequence in the VP1 protein of enteroviruses that he also found in all allergens (such as peanut, ragweed, dust mite, bee venom) as well as in the autoantigens of autoimmune diseases like lupus and multiple sclerosis.

It sounds intriguing, but I don't have the knowledge to even begin to judge whether this is a viable idea.

This is the old 'molecular mimicry' idea that if you think about it hard enough makes no sense. Something in a pathogen that looks like self is more likely to be ignored. It is things that look like something different that are likely to trigger reactions. There are literally tens of thousands of papers like this. People have been looking for this peptide overlap for forty years, apparently unaware that they are looking for something that would explain nothing. But unfortunately that is the way mainstream science often goes.

The one environmental antigen we do know gets caught up in autoimmunity is gluten in coeliac disease and it looks nothing like anything self. It drives an autoantibody response because it binds to the autoantigen, not because it looks like the autoantigen. I suspect that is true for virtually all molecules that drive autoimmune loops.