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UK Research Collaborative Conference in Newcastle: 13th - 14th October

Sidereal

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This paper by collaborators of Mark Edwards explains how the term functional was chosen i.e. basically one could fool more patients with it

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139034/

BMJ rapid responses here: http://www.bmj.com/content/325/7378/1449/rapid-responses
Right. People need to be careful to not get fooled by this term "functional". It is simply the latest euphemism in a long line of terms used to indicate that you are crazy. Once labels become considered offensive and fall out of favour with patients they are dropped and the next term is adopted. So in the past you had terms like hysteria, Briquet's syndrome, neurasthenia, psychosomatic, psychogenic, somatisation, conversion disorder, MUS, MUPS...

The term "functional" in psychiatry and neurology is NOT used in the conventional English sense of the word functional, as in, indicating a problem with function (as opposed to structure) of the CNS. In the context of "functional neurological symptoms" it means that absolutely nothing is wrong with the patient's brain function except that they have defective/abnormal beliefs, coping skills, emotional conflicts, traumas, personality, learning style etc. which by some nebulous mechanism are said to convert into/generate somatic symptoms. More sophisticated hypotheses such as Edwards' have been proposed but it still boils down to the same thing, only with the added bonus of lots of obfuscating waffle about Bayesian probability. But a polished turd is still a turd.
 
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lansbergen

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The term "functional" in psychiatry and neurology is NOT used in the conventional English sense of the word functional, as in, indicating a problem with function (as opposed to structure) of the CNS.
If he publishes the results of his new research and does that I will put him in the weasel camp. Until then I will give him the benefit of the doubt.
 

Sasha

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It's a pity that Martin Edwards isn't on the forums to answer questions. I think I've been spoiled by having @Jonathan Edwards and @znahle (Zaher Nahle) here because now it seems weird to me that a researcher wouldn't want to discuss his/her work with patients.

Clarity can only be beneficial for science. If Dr Edwards is doing good work, patients will want to sign up to his study and support it. If he's doing something we wouldn't agree with, all parties can only benefit from a discussion of the issues.
 

Research 1st

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Dr Holgate (MRC) introduced Dr Jose Montoya (Stanford medical school, USA). in Video 2.

After requesting a 1 minute silence for Dr Martin Lerner....

Dr Monyota immediately began with some home truths,delivered to the Brits concerning the medical scandal of the consequence of the global psych lobby (MRC funded in UK):

''I have a wish and a dream. I think that that wish and a dream possibly could be fulfilled within our life time, and is that I look forward to the day medical and research societies in the United States (and I hope other countries) will formally apologise to CFS ME patients. They have been ignored, ostracised and humiliated, by the very same establishment that was supposed to help them in the first place. And I think that that may not be that far from reality, given what Dr Holgate mentioned that the Institute of Medicine came up with a formal report earlier this year establishing that ME CFS is not a psychological illness.
Source:
Dr Jose Montoya talking at the UK CFS/M.E. Research Collaborative Science Conference, 2015.
AFME Youtube channel. Video source: Day One, UK CFS/M.E. Research Collaborative Science Conference, Part
Published 13th October, 2015
Time code for quote: 19:10 elapsed


Go Dr Montoya! :thumbsup:
 
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Bob

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A tiny bit more info has now been posted on Sonya's blog... CCC will be used to recruit patients...

CEO's blog: "I have a wish and a dream"
16 October 2015
http://www.actionforme.org.uk/get-informed/news/our-news/ceos-blog-i-have-a-wish-and-a-dream

Extract...
Sonya Chowdhury said:
New MRC-funded research

As mentioned above, Drs Mark Edwards and Neil Harrison announced a new research project at the CMRC conference, with £600,000 funding contributed by the MRC.

"Describing the project is complicated as there are three projects contained within the grant, only one of which is about people with M.E.," explains Dr Edwards. "The other two projects relate to people with functional neurological symptoms (functional motor symptoms in one, and non-epileptic attacks in the other). These are completely separate projects from the one relating to people with M.E., and the total funding for the grant is spread across the three projects.

"In the project looking at people with M.E., we are interested in studying the phenomenon of post-exertional malaise. We plan to include 20 people who fulfil the Canadian criteria for M.E. (as these criteria specifically highlight the presence of post-exertional malaise).

"We are interested in looking at whether patterns of brain activation seen in people with M.E. experiencing post-exertional malaise are similar to, or different from, those we see in people experiencing acute infection or inflammation. In order to do this we will use fMRI to scan the brains of people with M.E. at baseline and 24 hours after exertion, at which time they will have post-exertional malaise.

"By better defining the mechanism at the brain level of post-exertional malaise we think we will be able to understand better how to treat it."
 

Bob

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I might be naive here, but I'm not sure if we should get too hung-up about their usual career focus on functional illnesses. Although it's all rather depressing, we need to judge the trial methodology and the trial outcomes rather their previous history. If they believe that ME is a functional illness from the outset then that might mean that the trial methodology is useless, but if they approach ME as an unknown quantity, with an open mind and an honest attitude, it doesn't matter that they usually deal with functional illnesses. There is a suggestion, from his literature, that Dr Mark Edwards is open-minded to the idea that 'functional' illnesses are as-yet-to-be-explained biomedical illnesses, so let's hope his focus is on that.
 
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Large Donner

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Well the methodology should include objective measures of PEM like the TTT and two day cardio testing etc.

Also they say this...

"We are interested in looking at whether patterns of brain activation seen in people with M.E. experiencing post-exertional malaise are similar to, or different from, those we see in people experiencing acute infection or inflammation.
Are they starting from a basic premise that PWME "are not experiencing infection or inflammation"? Thats crucial too when they have said this...

In order to do this we will use fMRI to scan the brains of people with M.E. at baseline and 24 hours after exertion, at which time they will have post-exertional malaise.
Doesn't all the advice on testing for PEM say it should be done after 48 hours? That was a big issue with the CDC previously, didnt Unger claim the 24 period was good enough?

If they compare us to people with current inflammation and or infection after 24 hours the first problem is they may not measure PEM accurately on the fMRI and secondly it could be claimed that "as we have no active infection or inflammation" our whole illness is now even more subjective.

The CCC being used is a bit more encouraging but I think we need to continue to try to have input into this study and the potential pitfalls just as we had followed the PACE study in advance and all the way up to the present.

I dont want to see "CCC used, no inflammation and no PEM" as a conclusion of this study.
 

Large Donner

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In order to do this we will use fMRI to scan the brains of people with M.E. at baseline and 24 hours after exertion, at which time they will have post-exertional malaise.
Is there a validated method of testing PEM on fMRI after 24 hours?
 

Snowdrop

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But are they aware that not everyone will experience PEM right on cue at the 24 hour mark.
It's just not that simple. I think some people, especially the very ill can be in constant PEM.
I would feel a lot more comfortable with a researcher who had a good grasp of ME and it's subtleties.

Why is he even interested since his focus is generally elsewhere?
 

Scarecrow

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The two-day CPET test is a 24 hour test. I'm not aware of 48 hour testing being used anywhere.
I've never been convinced that the reduced performance on the second day CPET is measuring PEM as such but I accept that it's probably correlated to PEM. Nancy Klimas has stated that immune system is activated almost immediately after an exercise challenge.

For most people, symptoms suggestive of immune activation usually come on anywhere between minutes to a couple of days after exertion. A follow up at 24 hours seems as reasonable for PEM as it does for impaired performance.

I wonder if anyone has yet thought to compare CPETs at 48 hours as well as at 24 hours.
 

Snowdrop

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Ah, well the 2 day CPET requires a second exercise as opposed to exercise the first day then a brain scan. Now if they want to do the CPET that would be great although even with the CPET you are not going to capture to most sick as they cannot do this test.

I know nothing when it comes to science research design and all things around how to do it so I suppose I might seem harsh but I spend my days reading about so much drek in science research and how data is manipulated etc. I am not very trusting here and a lot of money is involved (although not all is for the ME portion) still. . .
 

Aurator

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I'm quietly hopeful amid the understandable scepticism and distrust in which I've shared here that rather than taking the wind out of the researchers' sails our scepticism and distrust will stimulate them all the more to find the sorts of answers that will both vindicate them and help us. If this happens I'll happily be the first to communicate my humble gratitude.
 

Bob

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I wonder if anyone has yet thought to compare CPETs at 48 hours as well as at 24 hours.
I'm not aware of that but I've just looked at a study by the Lights in which they test the blood at various intervals (something like 8, 24 & 48 hours) and the differences between 24 and 48 hours seem minimal. The bulk of the changes seem to occur by 24 hours.

Edited to correct some details.
 
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Large Donner

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But are they aware that not everyone will experience PEM right on cue at the 24 hour mark.
True.

t's just not that simple. I think some people, especially the very ill can be in constant PEM.

Yes. Also the very ill could not take part in an exercise test.
Why is he even interested since his focus is generally elsewhere?
Yes it seems strange. Why also would he be funded for two other projects on "functional disorders and non epileptic seizures" at the very same time, in as it appears??.. one grant. I would like to see those other projects design and purpose and if they are going to be similarly designed to the ME one and if any way the results could be used to claim something in relation to ME or all to each other, even in later literature.

Just because they are not on ME doesn't mean they cannot be used to make claims about "fatigue, mystery illness, MUS" etc.

Also in order to measure PEM at baseline and 24 hours after exertion will the baseline be on arrival at a clinic after the exertion and duress of travel.

There should be a significant rest before baseline measure to compare it with the measure 24 hours after exertion.

One more thing, he says this after mentioning the ME project

The other two projects relate to people with functional neurological symptoms and non epeleptic seizures.....
So what does he consider ME to be if functional is not a spin word for for something else? Is it proven organic to him?

In the minds of the BPS school these 3 labels are the same things, now we have a grant given to one person to study all 3 of them who keeps publishing on psychogenic disorders. This is in a current climate where the DSM is desperately trying to combine all their conversion type disorders under one label.

Does Edwards have any track record on de-discovering something out of the functional, or as he likes to call in often, psychogenic, codes and into the organic disease codes? Or have all of his publications left everything remaining in the spurious functional categories with the same theoretical writings continuously?

This comment is a bit strange too...

Describing the project is complicated as there are three projects contained within the grant,
So it appears to be a single project but its complicated to describe? Why? Did he actually go onto to describe it.... the project.

Does anyone remember how much the original MRC pledge was for bio med research into ME and how much have they attributed so far?
 
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First of my commentaries on the RC Conference.

This is on the new neuroimaging research.

These are a bit delayed because I think it's helpful to think about content of more detailed summaries.

Overall, this was another very enjoyable, stimulating and well attended biomedical research conference. Much of the content was on neurology with plenary sessions on neuropathology and autonomic dysfunction and a two hour workshop on neuropathology - where I have never been with so many colleagues from neurology, neuroradiology, and neuropathology sitting round a table (along with Prof Jose Montoya) discussing the neurobiology of ME/CFS for two hours!

POST-EXERTIONAL MALAISE (PEM) IN ME/CFS: MRC ANNOUNCES NEW NEUROIMAGING RESEARCH
Dr Charles Shepherd comments on post exertional malaise (PEM) and the new Medical Research Council (MRC) funded neuroimaging study that was announced at the Research Collaborative Conference in Newcastle on Tuesday 13th October

WHAT IS PEM?
Post exertional malaise (PEM), or post exertional symptom exacerbation, describes a delayed and significant exacerbation of ME/CFS symptoms that always follows physical activity and often follows cognitive activity
PEM is a highly characteristic clinical and diagnostic feature of ME/CFS
In some respects, PEM is an illness within an illness

WHAT CAUSES PEM?
The cause of PEM remains uncertain. However, clues are starting to emerge. So gaining a better understanding of the underlying pathophysiological mechanisms involved could help to improve at least one aspect of ME/CFS management

EXISTING RESEARCH INTO PEM

The MEA regards PEM as a research priority. Consequently, the MEA Ramsay Research Fund been funding two research studies in this area:

1 Professor Jo Nijs et al in Brussels and Belgium have been looking at the role of autonomic dysfunction in PEM, in particular the parasympathetic response to exercise. Professor Nijs presented some of the unpublished results to this study during the plenary session on autonomic nervous system dysfunction at the RC Conference. The autonomic nervous system - which is not under conscious control, hence the name - has its control centres in the brain. Through a network of sympathetic and parasympathetic nerves it passes messages to heart, blood vessels, bowel and bladder to regulate (by speeding up or slowing down) a wide range of body functions.

2 Dr Amolak Bansal et al at St Helier Hospital, Surrey have been looking at what happens to immune function before and after a cognitive challenge (completed) and an exercise challenge (not yet done).

So we already have some clues from these and other studies to indicate that the immune system and autonomic nervous system are involved in PEM

THE MISSING LINK?

But what might be happening elsewhere in the brain?

There is a growing consensus that ME/CFS may be an illness that is triggered by infection, which then causes the release of cytokines - immune system chemicals that produce flu like feelings, pain and malaise following any infection. This normal acute immune system response, which is unfortunately known as sickness behaviour/response, then continues in the form of low level immune system activity, continued cytokine production, and activation of immune cells in the brain called microglia. This is a model of causation involving on-going low level neuroinflammation which is supported by a recent Japanese PET neuroimaging study by Nakatomi et al:
http://www.ncbi.nlm.nih.gov/pubmed/24665088

And if there is already low level immune system activation, linked to activation of the microglia/low level neuroinflammation, could an exercise challenge with cytokine production, exacerbate the existing microglial activation and cause an increase in symptoms?

From a theoretical point of view, exercise can stimulate cytokine production (ie IL1, IL6 and TNF) and people with ME/CFS show an exaggerated immune response to exercise:
http://www.medizin.uni-tuebingen.de/transfusionsmedizin/institut/eir/content/2014/94/article.pdf

So, in theory, the answer is yes.....

THE NEW RESEARCH:

What has not been done so far in the investigation of PEM is to look at what happens to brain networks before and after an exercise challenge in ME/CFS - which is where this new study fits in

Dr Mark Edwards, a neurologist at the Motor Neurosciences and Movement Disorders Unit, UCL Institute of Neurology,

Dr Neil Harrison from the University of Sussex, who has already shown how acute inflammatory and infective challenges (e.g. following vaccination with typhoid vaccine: http://www.nature.com/npp/journal/v40/n4/full/npp2014222a.html or during interferon treatment for hepatitis) can cause activation in parts of the brain and

Dr James Kilner at University College London, will be carrying out this study.

20 people with ME/CFS and 20 age and sex matched controls will have a baseline functional MRI scan and blood samples (for immune system activation measurements) taken
They will then have a specialised exercise challenge to induce PEM
There will also be a fairly difficult cognitive challenge using what is known as the Stroop test
24 hours later the scans and blood tests will be repeated

In relation to the fMRI scans, they will be looking in particular for evidence of activation in key brain structures such as the dorsal insula

Overall, I believe this is a very sound and welcome piece of research that should help to increase our understanding of what is happening in the brain in PEM.

Thanks are also due to Professor Hugh Perry, a member of the RC Board and Chair of the Neurosciences Board at the MRC, for his determination to see high quality research into the neuropathology of ME/CFS taking place
_______________________________________________________________________________________
Transcript of the presentation from Dr Edwards prepared by Russell Fleming:
https://docs.google.com/document/d/1f3FsqRgzLiah_mbMi1j7nDoUih5auUf8VJv03kjnsUQ/mobilebasic?pli=1

Comments from Professor Jonathan Edwards on the Phoenix Rising Forum discussion on the RC conference:

Now we know what we are talking about. It looks brilliant to me. Neil is superb and he clearly has a big input. It is all about inflammatory and neural pathways and specifically about PEM so all that stuff about Oxford criteria can go in the bin. Presumably they will even correlate findings with the degree of PEM. This is proper science. They have even thought of the confounding problems of what people will be thinking because they are in an experiment - and will control for that be switching around the order of events.

I think this is a seriously important move forward in the science. The right people are focusing in on the most likely place to find some clues. And the cytokines and things will be measured as well it sounds like. It fits with the point made on both sides of the Atlantic that we should be studying people during PEM and looking at the abnormal response to exercise rather than just looking at PWME at any old time.

With this and the people connecting to David Brooks repeating the Japanese PET study I think there is the best chance yet of actually pinning down what is going wrong in the ME brain.I think this is a seriously important move forward in the science. The right people are focusing in on the most likely place to find some clues. And the cytokines and things will be measured as well it sounds like. It fits with the point made on both sides of the Atlantic that we should be studying people during PEM and looking at the abnormal response to exercise rather than just looking at PWME at any old time.With this and the people connecting to David Brooks repeating the Japanese PET study I think there is the best chance yet of actually pinning down what is going wrong in the ME brain.And there is no suggestion that this is money pinched from the ME pot. Edwards and Harrison got this grant through the open application system. There was no special pleading, no internal politics. It would have gone up against applications for MS or Alzheimer's or whatever. ME has actually become a fashionable disease to study I suspect. I would double the £600,000 personally.Full discussion here: http://forums.phoenixrising.me/index.php?threads%2Fuk-research-collaborative-conference-in-newcastle-13th-14th-october.36515%2Fpage-19#post-651365


Dr Charles Shepherd
Hon Medical Adviser, MEABoard member of the UK Research Collaborative
16 October 2015

The MEA funded 4 medical students to attend the RC conference. We also helped to fund the cost of bringing two overseas speakers - Oysten Fluge and Jo Nijs - to the conference.

Ends
 

Research 1st

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The two-day CPET test is a 24 hour test. I'm not aware of 48 hour testing being used by Snell/Stevens. And i think the Lights' research suggests the that differences between 24 hours and 48 hours is minimal.
Bob you appear to have it backwards my friend.

First point:
The American studies on VO2 max that show a big drop not seen in any other disease, are termed 2 days. not 1 day, or 'repeat' VO2 max studies. (On this issue of number of days relating to CFS, Dr Beth Unger @ CDC only agrees to 1 day, because they know this only shows de conditioning, a finding not unique to CFS organic disease). Dr Unger refused to accept 2 day. :grumpy:


Second point:
The two-day CPET test is a 24 hour test.
Well that's a matter of semantics. It is quite correct to say that only 24hrs passes between day 1 and 2. However
to use semantics back, it's not called a 24 hour test. :D

Day 1: Test at 9am.
Day 2: Test at 9am.

Looking above we can see a difference. In a normal VO2 max test 24hrs doesn't pass between tests, as there's only 1 test lasting a short while. A two day V02 max, (takes place on days with 2 seperate names, e.g Monday, Tuesday) has 2 tests. :thumbsup:

Last point:
To my knowledge the 'Lights' are just that, light. They appear to be looking at CFS and not ME. ME is a neurological disease with signs of neurological involvement such as autonomic dysfunction (POTS), seizures, balance disorders and neuropathic pain, heart failure and cancer. CFS does not require this, and so CFS (Light's research CFS criteria is perhaps the more weak Fukuda CFS criteria Vs ME-ICC or Ramsay). I don't know. This is not the Light Teams fault, it's the CDC's fault, for creating CFS in the first place.

In general when reading claims of any researcher in the CFS field who can or cannot find biomedical evidence, make sure we know that ME CFS doesn't exist. Only ME or CFS exists.

CFS in America: Chronic Fatigue + 4 or more symptoms without PEM.
CFS/ME in the UK, this is weaker criteria than America + PEM.

None of the above captures ME. If it does, it's luck.

This is why there is a huge discrepancy amongst the research, be it psychological or biological, because of the curse of heterogeneity the CDC wanted in response to (quoting Straus) a ''failed viral hypothesis''.
 

Large Donner

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First point:
The American studies on VO2 max that show a big drop not seen in any other disease, are termed 2 days. not 1 day, or 'repeat' VO2 max studies. (On this issue of number of days relating to CFS, Dr Beth Unger @ CDC only agrees to 1 day, because they know this only shows de conditioning, a finding not unique to CFS organic disease). Dr Unger refused to accept 2 day. :grumpy:
Yes that sums up the query I had early. Thanks.

I was also thinking, if this new study is three projects one on ME, functional neurological symptoms and non epileptic seizures thats everyone on this forum covered. For some reason they want to cover every area of under the "CFS" banner.

Hmmm!