Do MEs cause CFS?

[MeSci]

I thought your response seemed odd! It followed the earlier thread of conversation relating to ME research.

I am guessing that Prof Edwards had in mind your earlier statement:

The MRC is entirely populated by Doctors, not a single biochemist on the panel.

 

[user9876]

I am guessing that Prof Edwards had in mind your earlier statement:

The MRC is entirely populated by Doctors, not a single biochemist on the panel.

There is the Biotechnology & Biological Sciences Research Council (BBSRC) which I assume funds biochemistry research.

 

[Jonathan Edwards]

I understand that many medics have some interest in biochemistry localized around their special interest (e.g. Immunology in your case). Compared with a biochemist such as Alex though, that would warrant the term 'working knowlege' rather than 'expert'.

Is the precise nature of my objection to the current panel clearer now?

I don't think real life is like that Leopardtail. Many of us retrain during a career in much more detail than the primary training in our BSc or PhD discipline. In a University Department of Medicine we are all expected to understand detailed presentations on everything from biochemical pathways to MRI to population genetics on a weekly basis. I probably know a lot more about the properties of uridine diphosphoglucose dehydrogenase than most 'biochemists' because I spent five years studying hyaluronic acid synthesis (before I moved on to immunology, which is not my original discipline either).

You have every reason to query the efficiency of the grant awarding system but knocking doctors just because they are doctors seems to me something to get out of one's hair. There are a lot of bogeymen in this story but they cannot just be identified by the letters after their names.

I admit to not being up to speed on the methylation story but my impression is that it will not have been considered for funding simply because nothing has even come on the general scientific radar screen that would make a plausible story - and I guess nobody has applied anyway.

 

[Jonathan Edwards]

@Jonathan Edwards
I'd like to know whether autoimmune diseases are affected by exposure to allergens.

My particular reason for asking is I have an unusual (even for ME) and strong seasonal pattern to my disease: best in spring worst in summer. Its hard to tell whether autumn and winter are almost the same as summer and its just the contrast to spring that makes summer feel so bad.This applies to both northern and southern hemisphere: so in the UK mid April to Mid June are great. I get a sort of remission, my energy levels go way up, I can do loads more without PEM, think more clearly and then suddenly comes the summer and its back to very limited again.

Allergy is in general quite a separate thing from autoimmunity and autoimmune diseases are not much affected by allergens. However, if there was an autoimmune disease that targeted a self antigen involved in allergic responses one could imagine the symptoms might be seasonal. That would be pure speculation though.

 

[Jonathan Edwards]

Professor Edwards:
(i.) Does Chia's research look credible?
(ii.) If an ME patient records strong positive results in multiple of these tests, would you consider that convincing evidence of enteroviral infection?
(iii.) If "yes" to qu-(ii), and if those results were reproduced over an extended period of time, then would it be reasonable to postulate that persistent EV infection might be the cause of that patient's ME?

(1) J Clin Pathol. 2008 Jan;61(1):43-8.
(2) J Clin Pathol. Nov 2005; 58(11): 1126–1132.

I have not looked at this in detail yet and I should. I think the general idea is credible. Persistent presence of enteroviruses would not be at all surprising and they do seem to produce a lot of the right sorts of symptoms. How much one can interpret antibody titres I am not sure. I tend to think that we need to find some reason why the antibody levels are high but symptoms are persistent. There also has to be some reason why an ME illness is not simply like having a persistent virus - there are other features, like the sleep changes, that seem to be on top of that. I think it would be very plausible if some regulatory change in antibody production was constantly egged on by low levels of viruses of this sort.

So I guess that I am not sure one should say that persistent EV infection was the cause of the ME. It may be a necessary ingredient, and one that is not particularly unique to that form of ME. But if it is a necessary ingredient that in itself would be very important.

 

[Snow Leopard]

I have not looked at this in detail yet and I should. I think the general idea is credible. Persistent presence of enteroviruses would not be at all surprising and they do seem to produce a lot of the right sorts of symptoms.

My opinion is that enteroviruses are just one of of the short list of triggers of a post-infection chronic fatigue syndrome. I think that they are even more likely to trigger CFS than EBV, but tends to be less common hence less people actually have their illness triggered by an enterovirus rather than EBV. But I also think they are a potential trigger for the many of the outbreaks observed around the world.

 

[Kati]

Enterovirus D-68 is hitting the US and Canada right now. 4 children if not more have died and quite a few are stricken by paralysis of some sort. Very likely we will see post EV fatigue syndrome in at least so,e of the cases. You'd think the CDC would be ready in recognizing the signs and the illness by now, perhaps monitoring all cases for more than a year afterwards. . In my opinion, it is not likely to occur.

 

[Jonathan Edwards]

Enterovirus D-68 is hitting the US and Canada right now. 4 children if not more have died and quite a few are stricken by paralysis of some sort. Very likely we will see post EV fatigue syndrome in at least so,e of the cases. You'd think the CDC would be ready in recognizing the signs and the illness by now, perhaps monitoring all cases for more than a year afterwards. . In my opinion, it is not likely to occur.

Yup, I think I just had it, at least it felt pretty much like a dose of ME and at least 68 worth and I would definitely give it a grade D in class. Knocked me for six. Fortunately, I ran up the stairs in the underground/subway today without too much ill effect.

 

[Scarecrow]

He insisted that diabetes insipidus (which a number of us here appear to have) was something that was absolute (no grey areas) and that you had to be born with it, both of which are incorrect.

I think he also forgot to tell my dog that you have to be born with it.

 

[Leopardtail]

@Jonathan Edwards
I'd like to know whether autoimmune diseases are affected by exposure to allergens.

My particular reason for asking is I have an unusual (even for ME) and strong seasonal pattern to my disease: best in spring worst in summer. Its hard to tell whether autumn and winter are almost the same as summer and its just the contrast to spring that makes summer feel so bad.This applies to both northern and southern hemisphere: so in the UK mid April to Mid June are great. I get a sort of remission, my energy levels go way up, I can do loads more without PEM, think more clearly and then suddenly comes the summer and its back to very limited again.

Any thoughts?
Thankyou

OTH

I am guessing that Prof Edwards had in mind your earlier statement:

The panel bit was the key thing there, but point taken...

 

[Leopardtail]

I don't think real life is like that Leopardtail. Many of us retrain during a career in much more detail than the primary training in our BSc or PhD discipline. In a University Department of Medicine we are all expected to understand detailed presentations on everything from biochemical pathways to MRI to population genetics on a weekly basis. I probably know a lot more about the properties of uridine diphosphoglucose dehydrogenase than most 'biochemists' because I spent five years studying hyaluronic acid synthesis (before I moved on to immunology, which is not my original discipline either).

You have every reason to query the efficiency of the grant awarding system but knocking doctors just because they are doctors seems to me something to get out of one's hair. There are a lot of bogeymen in this story but they cannot just be identified by the letters after their names.

I admit to not being up to speed on the methylation story but my impression is that it will not have been considered for funding simply because nothing has even come on the general scientific radar screen that would make a plausible story - and I guess nobody has applied anyway.

My point isn't and never was knocking doctors, what I am knocking is the make up the panel - entire and relevant fields of science are missing as are relevant fields of medicine. I know my concerns are shared by at least two of the national charities. What I am saying is that the panel needs to have doctors playing well with others who understand that other vital dimension much better and we need members of that discipline directly on the panel and building up their knowledge of ME - their presence and mutual discussion of applications would create synergy.

In similar fashion to you I know a great deal more about the regulation of hormones in the limbic system that most professional endocrinologists. I also know vastly more about ATP synthesis and B-Vitamin metabolism than many (but far from all) biochemists. That however would prepare neither of us to judge the quality of a project that examined the interaction of some aspect of arcane biochemistry with endocrine hormones. @alex3619 or any other biochemist would likely spot risk and opportunities that you and I would not.

Fatigue is a sensation generate by the brain to facilitate rest - fatigued parents can still care for their children. The body's energy management system is endocrine and complex. The bodies energy generation system is within the cell. The disease for a good proportion of us is about fundamental lack of energy generation - not about fatigue. The severe energy deficit (aka exhaustion) with severe ME is much closer to severe hypoglycaemia moments before going comatose when legs turn to jelly and one cannot choose to function or override the sensation. Both those detailed areas of knowledge are missing from the panel. This is analogous to Stevie Wonder choosing the Turner prize.

We are never likely to have good quality endocrine or intracellular research while the panel must work from the kind of impressions you expressed about methylation. This is why we are stuck in a situation where we have very small scale investigation, small numbers of medics with very detailed knowledge but a paucity of cold hard published (and repeated) science.

If we had a very large population of dedicated researchers itching to get into the field then this would concern me less. What we have though is a paucity of both researchers and funding sources. Were I a newly qualified researcher with special interest in ME, with a fellow student interested in Biochemistry would I come into this field or diabetes when both fields were missing from the panel? The make up of such panels creates practical issues at 'first filtering' of applications it also sends messages.

Somebody with your gravitas for example might well be able to get funding for the thyroid investigation you discussed despite the lack of expertise on the panel, I question however whether others would even feel it was worth trying. More so given the history of the panel and the sheer amount of effort such applications take.

Trying doing a pub-med search for anything (ME related) to do with energy generation, endocrine hormones etc and the reason why these disciplines need direct presence becomes all too obvious. What many of us know has not been investigated by science.

 

[Leopardtail]

This is not necessarily the case. Some of us have found endos specialising in diabetes to be astonishingly ignorant about other aspects of endocrinology.

For example, I saw a highly-regarded endo who has appeared in the media a number of times, about my polyuria. He specialises in diabetes, but presumably his expertise is limited to the mellitus variety.

He insisted that diabetes insipidus (which a number of us here appear to have) was something that was absolute (no grey areas) and that you had to be born with it, both of which are incorrect.

Type II diabetes in research is a different ball game, a great deal revolves around intracellular biochemstry and ATP. I was not referring to a practicising doctor here, but a medic of the scientific persuasion with a research background. Researcher rather than medic would likely have been clearer wording though I thought that would be assumed in the context.

Most endos do spend the vast majority of their time dealing with the various forms of diabetes mellitus and have rather more limited understanding of other endocrinology (including inpsidus). I share your view re insipidus and have my own concerns about the way it's diagnosed (at both stages) and handled in the NHS.

I would obviously hope that at the level of the MRC they would choose a reasonably well rounded endo with a wider knowledge of the field and extensive interaction with researchers across the field.

 

[Kati]

Yup, I think I just had it, at least it felt pretty much like a dose of ME and at least 68 worth and I would definitely give it a grade D in class. Knocked me for six. Fortunately, I ran up the stairs in the underground/subway today without too much ill effect.

@Jonathan Edwards I am not entirely sure you are being serious, sarcastic, or joking right now.

My point was that viral illness keep happening, H1N1, swine flu, and else, many with high profile in the media and we know that a fraction of the recovered will end up with ME, and yet as a patient population we are ignored and left behind.

 

[Jonathan Edwards]

@Jonathan Edwards I am not entirely sure you are being serious, sarcastic, or joking right now.

My point was that viral illness keep happening, H1N1, swine flu, and else, many with high profile in the media and we know that a fraction of the recovered will end up with ME, and yet as a patient population we are ignored and left behind.

Sorry, not being sarcastic at all. I had gone off at a tangent to your important point. I was doing a bit of introspective research on myself.

I had a really nasty dose of enterovirus and I found it useful to think to myself 'what if Monday and Tuesday were like having ME and the previous Sunday and subsequent Thursday were like not having ME any more'? And on Monday I thought ' what would it be like to be like this for years on end'? And I could sense that the whole thing was my own body (and especially parts of my nervous system) telling 'me' to go and sit in my bedroom while the grown - ups dealt with the man who was saying that dad was bankrupt and that we could not live in our house any more (so to speak). And then on Thursday I thought 'it wasn't 'me' that switched all that stuff off, I couldn't switch it on again even if I tried, it just went.' And I do have a memory of a time after mono when it didn't just go like that despite me being jealous of all my pals playing in boats. So I was just trying to think what could be happening when it doesn't switch off.

 

[Jonathan Edwards]

OK Leopardtail, I know what you are saying and there is a lot of justification for it.

But let's turn this into an exercise. We need a proposal of intent for a grant application to investigate methylation in ME and applicants are allowed 500 words to convince some intelligent funders to invite a formal proposal. I am the intelligent funders' advisor, who looks at the proposals of intent. (You may realise that this is not so very far away from reality.) If the case for studying methylation is solid enough then anyone with familiarity in the field should be able to put the case. When some new avenue opens up in research it is usual for every Tom Dick and Harry on the planet to put in a proposal to work on it. The case needs to relate the problem seen at the widest angle to something very specific and testable through a tight series of argued steps. Could you persuade me in 500 words?

 

[Bob]

@Jonathan Edwards , I appreciate your mental exercise of putting yourself in the mind/body of an ME patient.
It seems to me that such an exercise of empathy is a very basic human ability, and not particularly difficult to do, if minded to do so.
And nearly everyone on the planet has had a bad bout of flu, or similar illness, where they've been severely incapacitated for a short period, barely able to walk to the toilet.
So it doesn't seem unreasonable to expect all physicians and researchers to carry out such a mental exercise as you've done above, in order to understand more about their patients and the illness.
As you say, you could no more switch your symptoms off than you could switch them on, through force of will, or any mental exercise.

 

[MeSci]

Type II diabetes in research is a different ball game, a great deal revolves around intracellular biochemstry and ATP. I was not referring to a practicising doctor here, but a medic of the scientific persuasion with a research background. Researcher rather than medic would likely have been clearer wording though I thought that would be assumed in the context.

Most endos do spend the vast majority of their time dealing with the various forms of diabetes mellitus and have rather more limited understanding of other endocrinology (including inpsidus). I share your view re insipidus and have my own concerns about the way it's diagnosed (at both stages) and handled in the NHS.

I would obviously hope that at the level of the MRC they would choose a reasonably well rounded endo with a wider knowledge of the field and extensive interaction with researchers across the field.

The top endo I was talking about is a professor of endocrinology and metabolism at a research institute as a well as a hospital consultant. His research interests include autoimmunity.

 

[JalapenoLuv]

Methylation fails as a theory to account for CFS. It is merely treating a dysfunctional system by trying to palliate the broken pathways. However by ignoring the bacteria and viruses causing the disease it can't remove the cause of the problem so its effectiveness is limited. That's why it is a dead end.

 

[Jonathan Edwards]

Methylation fails as a theory to account for CFS. It is merely treating a dysfunctional system by trying to palliate the broken pathways. However by ignoring the bacteria and viruses causing the disease it can't remove the cause of the problem so its effectiveness is limited. That's why it is a dead end.

So insulin would be a dead end for diabetes, JalapenoLuv? I think I am prepared to give methylation a bit more consideration than that. And since we do not understand the role of bacteria and viruses, if any, I don't think I am persuaded any more in that direction.

 

[lansbergen]

However by ignoring the bacteria and viruses causing the disease it can't remove the cause of the problem so its effectiveness is limited. That's why it is a dead end.

I do not do that protocol but I do not see why treating a disfunctional system can not help the immune system to fight intracellulair infections.