Research in progress: A Unified Mechanism for Functional Neurological Symptoms, 2015 to 2018, Edwards et al

Andy

Senior Member (Voting rights)
My brain fogged brain isn't sure whether this should be in Biomed Research or here in Psychosocial, happy for it to be moved if better minds than mine decide it should be.
Abstract

From the earliest medical records to the present day, doctors have separated out a group of patients from those with a typical "organic" cause for their physical symptoms. These patients have had many labels: "hysteria","conversion", "medically unexplained", "functional". Patients with functional symptoms are seen across primary care and all medical specialities, but are particularly common in neurological practice. Here they make up about 16% of those seen in neurology outpatient clinics, making functional neurological symptoms (FNS) one of the commonest diagnosis of neurology outpatients. People with these symptoms are, as a group, as disabled and experience as poor a quality of life as patients with Parkinson's disease or multiple sclerosis. Despite this, clinical services for such patients are poorly developed, research into causes of symptoms and treatment is very limited, and attitudes in society and within medicine to patients with functional symptoms are often poor.

With this work, we want to test a new theory for how functional symptoms can arise from the brain. One of the difficulties in understanding functional symptoms is that the brain and the rest of the nervous system appears to be intact, despite severe symptoms. Indeed in patients with some types of symptoms, for example people with limb weakness, it is possible to demonstrate on examination that the apparently weak limb can generate normal power, even though the patient cannot get this to happen him or herself. We believe it is vitally important for research and development of better diagnosis and treatment for us to understand how functional symptoms are produced by the brain. We have previously developed a theory that we believe provides a reasonable mechanism for how symptoms are produced. We have already gathered evidence that supports this theory in patients who have functional symptoms affecting movement (e.g. weakness, tremor) and sensation (e.g. numbness). We now want to move forward and test if this theory can also account for symptoms experienced by people with chronic fatigue syndrome and non-epileptic attack disorder.

Chronic fatigue syndrome is a disabling condition characterised by persistent fatigue in the absence of a clear medical cause. We believe that fatigue in chronic fatigue syndrome may occur because of abnormal activation of a network of structures in the brain that are usually involved in signalling the presence of infection and inflammation in the body and which give rise to a common set of symptoms experienced by everyone (and indeed across species) when infection or inflammation occur (known as the "sickness response"). This sickness response is usually short-lived, but we believe that the system could be abnormally activated in people with chronic fatigue syndrome in the absence of any ongoing infection or inflammation in the body.

Non-epileptic attack disorder is a common cause of fit-like episodes which can be prolonged and very frequent. We know that these attacks are different from epilepsy, as there is no epileptic activity on brainwave (EEG) recordings performed during such attacks, but it is not known what is happening in the brain prior to and during attacks that could be responsible for the symptoms. We believe that changes in the brain's focus of attention in an abnormal way towards the body is an important part of triggering the attacks, and we will test this in our study.

If our theory is correct, then when people get better with treatment then we should see corresponding changes in the way the brain is working. We will therefore test if particular aspects of brain function which our theory predicts are involved in generating functional symptoms become more normal when people with functional symptoms go through successful treatment. This would be a key step in proving or disproving our theory for how functional symptoms can be produced by the brain, and will help with future treatment development.
http://gtr.rcuk.ac.uk/projects?ref=MR/M02363X/1
 
What I was unable to discern from the write-up was the methods they will employ to examine these 'sickness response' mechanisms in the brain (assuming they find them). I read all the blurb but there didn't seem to be anything relating to recruitment, assessment, testing, etc. But after the PACE Trial debate and press stuff, my brain is mush.

N.b. Thanks Andy for finding those details. I'd forgotten all about this study and didn't realise it ends this year.
 
Well if CFS was just chronic fatigue....

I'm not going to say the study will find nothing useful or is bad but I'm not convinced the researchers get ME at least, but they don't need to do they CFS can become fatigue and ME systemic disease can be ignored. The brain may be key though so at least Its sonething and PEM is part of the study.

However, It's just ridiculous that's the uk minister in parliament in all seriousness referred to this single piece of state funded fatigue research as her attempt to reassure the sick, suffering, wailing, abandoned ME community that uk was taking biological CFS research seriously, along with MRC and NIH welcoming research proposals which dont happen . contrast americas effort
 
Oh dear, I thought I'd look at where this is coming from and have fallen down the FND rabbit hole. The write up relating to CFS which states...

Chronic fatigue syndrome is a disabling condition characterised by persistent fatigue in the absence of a clear medical cause. We believe that fatigue in chronic fatigue syndrome may occur because of abnormal activation of a network of structures in the brain that are usually involved in signalling the presence of infection and inflammation in the body and which give rise to a common set of symptoms experienced by everyone (and indeed across species) when infection or inflammation occur (known as the "sickness response"). This sickness response is usually short-lived, but we believe that the system could be abnormally activated in people with chronic fatigue syndrome in the absence of any ongoing infection or inflammation in the body.

...would seem to indicate that the study will be looking at inflammation or neuroimmune factors*. But the PI seems to mainly be interested in using imaging to look at conversion disorders and seems to be lumping ME/CFS in with that. I might be wrong, but this would appear to be a study that will be looking at which bits of the brain light up more in patients suffering from 'false illness beliefs'. I can't see otherwise why one would view the cause of ME/CFS and NEAD as being related. For 'neurobiologic' read 'biopsychosocial' - and if this is the study the government is trumpeting as reflecting a change in the UK's attitude to ME/CFS then I'm more than a little underwhelmed.
 
The Sussex CFS service is involved in this study, which is warmly welcomed by the unaccountable BPS supporting Sussex and kent cfs Society. Sussex and Brighton medical school is involved via Dr Neil Harrison.


Edit. Here the chairman of the Sussex cfs society writes that his charity is "assisting" with research by the sussex and brighton medical school. Charity supporter Martine McCutcheon says we can recover and patron actress Jenny Seagrove welcomes research on brain plasticity.
https://www.gscene.com/news/sussex-m-e-society-marks-30th-anniversary/



I cant bear to read that nonsense.
 
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If our theory is correct, then when people get better with treatment then we should see corresponding changes in the way the brain is working. We will therefore test if particular aspects of brain function which our theory predicts are involved in generating functional symptoms become more normal when people with functional symptoms go through successful treatment.

Just one little problem there: There are no treatments that make people get better, so they are chasing a chimera.

'Successful treatment'? Lead me to it...

Looks like horrible BPS stuff to me. No proper definition of ME, just fatigue, and no mention of how they will measure successful treatment.
 
Basically another central sensitization theory - definitely psychosocial. And combined with an apparent determination to keep using Oxford criteria while the researchers happily rot in their remote little cave, cut off from the rest of society :rolleyes:

No, it isn't characterized by fatigue:
Chronic fatigue syndrome is a disabling condition characterised by persistent fatigue in the absence of a clear medical cause.

Even if two factors were ruled out, it wouldn't prove a faulty sickness behavior is to blame:
This sickness response is usually short-lived, but we believe that the system could be abnormally activated in people with chronic fatigue syndrome in the absence of any ongoing infection or inflammation in the body.

It's not even a fault with the brain, but with the attention of the brain which supposedly creates epileptic and CFS symptoms:
We believe that changes in the brain's focus of attention in an abnormal way towards the body is an important part of triggering the attacks, and we will test this in our study.

It sounds like they're only doing brain scans, and not checking for inflammation or infection:
If our theory is correct, then when people get better with treatment then we should see corresponding changes in the way the brain is working. We will therefore test if particular aspects of brain function which our theory predicts are involved in generating functional symptoms become more normal when people with functional symptoms go through successful treatment.

This is pretty bizarre in general, since they're purporting to discover the mechanism by which "treatment" cures psychosomatic disorders, while lacking evidence that treatment is a cure at all, or that psychosomatic disorders even exist :confused:

Yeah right :rofl::
1. In the longer term, the key beneficiary of this work will be patients with functional neurological symptoms.

Ah yes, it's the presumed insanity causing the symptoms, not the known disease:
3. This work will benefit patients with other neurological and general medical disorders. About 12% of patients with neurological illness also have functional symptoms.
 
What I was unable to discern from the write-up was the methods they will employ to examine these 'sickness response' mechanisms in the brain (assuming they find them)
Perhaps they will dismantle a VO2 max machine and put patients on a treadmill to induce the sickness behaviors, whilst shouting at them and using a cattle prod.

Can just imagine them commandeering the treadmill and throwing that stupid tubey thing attached to a box in the bin.

Do we know how much this is costing and who exactly funded it?
 
This is what St Georges website has to say:

Professor Mark Edwards is a neurologist who studies how the brain controls movement and how abnormalities of movement occur in people with neurological illness

He leads the Motor Control and Movement Disorder Group which is comprised of neurologists, psychiatrists, physiotherapists and basic scientists. As a group they use psychophysical and neurophysiological techniques to study motor control and how it is disrupted in common movement disorders such as Parkinson’s disease, dystonia, functional movement disorders, and Tourette’s syndrome
.

It is unclear how these interests relate to ME. It looks like £661,000 to look at something outwith one's area of claimed expertise.
 
Yes, I think he was. That makes a lot of sense now.

At least one person has told me that he suspects NICE wants to lump ME under functional neurological symptoms. Russell has been contacted by the same person, I believe, as has Jane at TYMES Trust. Whether that's an accurate assessment or not . . . this study doesn't fill me with hope. I hope it's not true.
 
Mark Edwards is now quite a big player in the CMRC.

I can't remember much about the study, discussed months ago, but I do know @Jonathon Edwards on PR was actually very impressed with it. The PR thread went into depth on it. Neil Harrison is one of its authors who has done talks, quite possibly at the last CMRC conference if anyone wants to look it up on YouTube, JE was very impressed with him too. I guess he might have been talking about this stuff at CMRC. I'm not up to engaging in heavy science over my head but perhaps using FND terminology is off putting to us for an otherwise useful brain study ?

For anyone who's been in the scene for years, you might share my suspicion that the MRC is now only currently funding CFS as part of functional brain disorders. As I said, the study might have merit but in bad days after Colin blakemore was saying just fund behaviour stuff for CFS at MRC he was saying it's a brain disorder (I don't know where he gets any expertise on this subject) and Wessely I think has said similar - it's central fatigue etc. There's affiliation with FNS king Jon stone and chalder etc. Whilst the brain might well be key, Keeping it as a functional brain disorder is a "bearable shift" for the MRC in the way that funding research proving its a cellular energy issue, CNS infection etc might not be, Remember they've turned other CFS research down apparently.
 
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Do we know if this definitely is the research she was referring to? (I'm trying to go thro what the Minister said and come up with info related to it).
Not definitely but it seems to be the only trial that fits the criteria of being funded by the MRC, researching the brain and finishes this year.

To find it I used this site, http://gtr.rcuk.ac.uk/, and searched for all studies matching "chronic+fatigue+syndrome" which gave me this list, which I sorted by end date.
 
At least one person has told me that he suspects NICE wants to lump ME under functional neurological symptoms.
This development was commented on by Invest in ME Research in their response to the NICE surveillance review last year.
"It seems as though NICE is now complicit in the attempt in the UK to steer an increasing acceptance of CFS/ME in to the umbrella of functional (nothing wrong pathophysiologically) neurological disorders (FND)." http://www.investinme.org/IIMER-Newslet-17-07-04.shtml

The relevant response starts on page 8 of the comment form:

10. NICE states “ The experts also gave their thoughts on the current status of diagnostic criteria in NICE guideline CG53 and elsewhere, in light of these reports. Their comments included: The HHS Chronic Fatigue Syndrome Advisory Committee state: ‘A priority should be placed on developing biomarkers and diagnostic tests... research has neglected many of the biological factors underlying ME/CFS’. Whereas in the UK there may be increasing acceptance of CFS/ME in the umbrella of functional neurological disorders.”
http://www.investinme.org/Documents/NICE/comments-form-2 - from INVEST in ME 23-7-2017.pdf


Also, in September 2017, the Forward-ME Group submitted comments on a new draft NICE guideline for suspected neurological conditions: http://www.forward-me.org.uk/comments-form-2 Neuro doc for submission.pdf
The draft guideline made specific references to ME and CFS: https://www.nice.org.uk/guidance/gid-cgwave0800/documents/draft-guideline

The writing for this development has been on the wall for a few years; red flags included that the BPS lobby seemed to be conceding to describing ME as neurological and were making noises about the need to end the distinction between mental and neurological illnesses, such as this article by PDW: http://www.bmj.com/content/344/bmj.e3454
 
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