Open Cervicocranial dysfunction, neuroinflammation and infection in ME/CFS compared to healthy subjects, Bragée & Bertilson [MEPRO study]

[JES]

I think it's a good thing that they are doing biomedical studies in Sweden, especially since Denmark, Finland to some degree and also Norway with the Lightning Process meme are not progressing much at all on the biomedical front. I hope they don't become over-invested in the craniocervical/structural hypothesis as I don't think we have much reason to believe it's the root cause of ME/CFS, but there's always a chance that by doing all these proposed lab tests they are able to discover something new.

 

[mango]

The hypothesis is that the disease in a significant proportion of patients can be explained by [...] a disturbance of so-called interoceptive signaling.

I think it's a good thing that they are doing biomedical studies in Sweden

Do we know for sure that these are truly biomedical hypotheses, though? (Genuine question, I'd really like to know.)

I'm asking in part because we know this ME center was (is?) also running an ACT study (according to the research plan aiming to correct so called fear avoidance behaviour through "education"/talk therapy and gradually increased activity).

And there's the neurosomatic approach.

And the talk about the brain's "threat defence", the reptilian brain, sensitisation, and so on.

Also, I feel there are still many unknowns regarding their view on interoception in this context:

mango said: ↑
Bragée mentioned a study that has validated the results of his already published study. This new one isn't published yet but is available in preprint. It's by a research group in Sussex, England. He thinks it will get a lot of attention in the media.

I've been trying to find this preprint, but no luck so far. Does anyone have a link to share?

If the info I have [something Jen Brea tweeted] is correct, it's by a researcher called Jessica Eccles.

https://www.researchgate.net/profile/Jessica_Eccles

"Areas of expertise: Brain-Body Interactions, Joint hypermobility, Liaison Psychiatry

Research areas: Neuroscience, Psychiatric manifestations of connective tissue disorders, Mechanisms of chronic pain and fatigue"

https://www.bsms.ac.uk/about/contact-us/staff/dr-jessica-eccles.aspx

Here's one of her papers that is currently in preprint, but I doubt this is the one Bragée referred to in his talk.

Beyond Bones - The Relevance of Variants of Connective Tissue (Hypermobility) To Fibromyalgia, ME/CFS and Controveries Surrounding Diagnostic Classification: An Observational Study
https://www.medrxiv.org/content/10.1101/2020.02.21.20025072v1

...which is related to this:

HYPERMOBILITY AND AUTONOMIC DYSFUNCTION: INSIGHTS FROM BENCH TO BEDSIDE (2019) with lead researcher Jessica Eccles with a BA in History and Philosophy of Science, in Sussex and Brighton (Crawley is medical advisor for the Kent and Sussex "ME" charity), which concluded...
A data- driven theoretical model linking joint hypermobility to psychiatric disorder is proposed, characterised by aberrant autonomic control and central representation, grounded in current theoretical models that seek to frame emotion as interoceptive inference, using leading-edge predictive coding approaches.

Sorry if I'm repeating myself. These are very important questions to me, and I'd really like to find out.

 

[JES]

Do we know for sure that these are truly biomedical hypotheses, though? (Genuine question, I'd really like to know.)

I'm asking in part because we know this ME center was (is?) also running an ACT study (according to the research plan aiming to correct so called fear avoidance behaviour through "education"/talk therapy and gradually increased activity).

And there's the neurosomatic approach.

And the talk about the brain's "threat defence", the reptilian brain, sensitisation, and so on.

Also, I feel there are still many unknowns regarding their view on interoception in this context:


...which is related to this:

Sorry if I'm repeating myself. These are very important questions to me, and I'd really like to find out.

I guess you pointed out the main risk and most damaging one, i.e. that they would turn into using behavioral therapies, either already, or later if they fail to find anything in their MRI studies. I don't have much knowledge of Swedish clinics, but I do remember the Gottfries clinic used to not include any BPS nonsense (not sure if it's running anymore?), so I have a bit more hope in them than what I heard from Denmark or the so called treatment I have encountered here in Finland.

Actually I just yesterday happened to find a new interview here with Bragée and a recovered patient discussing rituximab and other treatments, I think it was quite good in general (only in Swedish).

 

[Anna H]

Actually I just yesterday happened to find a new interview here with Bragée and a recovered patient discussing rituximab and other treatments, I think it was quite good in general (only in Swedish).

The link goes to another segment from the same show. One where longcovid and ME are discussed.

Below is a link to the interview you mentioned, with Björn Eklund and Dr Björn Bragée:

 

[Jonathan Edwards]

I think it's a good thing that they are doing biomedical studies in Sweden

It is only good if the study is competent and does not produce a bogus answer. Collecting data from a 'non-probability' sample looks to me like a non-starter here. And remember that it was the BPS people who pushed this spine story as much as any.

 

[FMMM1]

The claim that 80% or 90% have abnormal neck MRI is an astonishing one. You'd expect such a finding to have appeared in the peer-reviewed literature by now. As far as I know, our patient population has been having structural MRI scans since the 1980s and no consistent abnormalities have been found.

Some thoughts -

• what is the abnormality [present at 80% or 90%]?
• have the looked at controls i.e. to establish what "normal" is?
• if you sent them a set of MRIs could they identify ME from healthy controls?

Like you, I'd expect that a lot of people with ME would have had an MRI; therefore, a consistent problem [80% or 90%] should have been identified by now.

 

[JemPD]

Like you, I'd expect that a lot of people with ME would have had an MRI; therefore, a consistent problem [80% or 90%] should have been identified by now.

I'm not pro structural abnormality theory by any means, but just to say that in UK from my experience of listening to other patients, very few people with ME/CFS will have had an brain MRI, much less the neck. Not saying they should have had a neck MRI, just that i'd be astonished to discover any more than a tiny minority of PWME have had one

 

[Wyva]

I'm not pro structural abnormality theory by any means, but just to say that in UK from my experience of listening to other patients, very few people with ME/CFS will have had an brain MRI, much less the neck. Not saying they should have had a neck MRI, just that i'd be astonished to discover any more than a tiny minority of PWME have had one

It's probably similar everywhere. I'm currently in the process of being officially diagnosed, which has been going on for several months now, since my GP has referred me to different kinds of specialists to rule everything else out (not really a PwME-friendly process). But he has never even mentioned sending me to a neurologist or having MRI or anything similar, so I expect to be diagnosed without any of that in the end. I would be thrilled to have some brain scans performed on me but I guess you can't have everything. :sighs:

 

[FMMM1]

I'm not pro structural abnormality theory by any means, but just to say that in UK from my experience of listening to other patients, very few people with ME/CFS will have had an brain MRI, much less the neck. Not saying they should have had a neck MRI, just that i'd be astonished to discover any more than a tiny minority of PWME have had one

Probably true i.e. the % of people who've had an MRI is probably quite low.

My wife has syringomyelia and my impression is that an increasing number of people are having MRIs and being told they have an abnormality - often they are not symptomatic - generally wait and see I guess i.e. no symptoms then no problem.

It might be interesting to see what the normal range of MRI findings is i.e. to see if this study has in fact identified "abnormal"/pathology?

I'd find even a small % of people with ME who have a spinal cord/cerebro-spinal fluid/CCI problem interesting.

 

[Ariel]

And remember that it was the BPS people who pushed this spine story as much as any.

Can someone explain some of the context here? I would appreciate it; I am unaware of it. I did not know that! I have been sick for well over a decade and haven't always followed what is happening online; recently I came back after a while and all I saw was spine/structural causes content. I don't know the details of how it started other than JB and other patient advocates.

 

[Jonathan Edwards]

Can someone explain some of the context here? I would appreciate it; I am unaware of it. I did not know that! I have been sick for well over a decade and haven't always followed what is happening online; recently I came back after a while and all I saw was spine/structural causes content. I don't know the details of how it started other than JB and other patient advocates.

The spine story goes back to Peter Rowe in the US around 1990 at least. It is muddled in with the EDS and Chiari stories which go back further. It was picked up by Hans Knoop, the Dutch BPS guy who has published with White. I suspect Knoop's paper is chiefly responsible for the continued momentum meme. Peter White liked to talk about the hypermobility aspect as the 'bio-' part of BPS. Basically, the BPS people are happy to weave whatever speculation is available into their story so that you can never pin it down. We now have bendiness and psychology in Brighton with Jessica Eccles.

A key common feature of both the spine ideas and the BPS ideas is that they do not add up when looked at in total. All you have is a scattershot speculations that might sound plausible at first but do not fit together. Theymight seem opposites at first but in reality they are both much the same - muddled thinking.

 

[Anna H]

It's probably similar everywhere. I'm currently in the process of being officially diagnosed, which has been going on for several months now, since my GP has referred me to different kinds of specialists to rule everything else out (not really a PwME-friendly process). But he has never even mentioned sending me to a neurologist or having MRI or anything similar, so I expect to be diagnosed without any of that in the end. I would be thrilled to have some brain scans performed on me but I guess you can't have everything. :sighs:

I managed to get a referral to a neurologist, before I got diagnosed. But he was very dismissive, especially after asking about my PTSD diagnosis. He only agreed to do a lumbar punction and some blood tests after I broke down and cried. So I agree, there's probably a small percentage who get an MR.

 

[mango]

Re: interoceptive signalling. I dug up some old notes of mine, from back when I first heard about Bragée's hypothesis, some years ago. In case anyone is interested, the following is some of what Google told me.

The very first thing I noticed was that "interoceptive signalling" returns lots of pop-science links about behaviour, the fight or flight response, perceived threats, anxiety, experiencing extreme emotionality, emotional instability, health anxiety (hypochondria), anxiety attacks, panic attacks, depression, mood disorders, etc.

I took a closer look at the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire used in this study:

1. Noticing: Awareness of uncomfortable, comfortable, and neutral body sensations
2. Not-Distracting: Tendency not to ignore or distract oneself from sensations of pain or discomfort
3. Not-Worrying: Tendency not to worry or experience emotional distress with sensations of pain or discomfort
4. Attention Regulation: Ability to sustain and control attention to body sensations
5. Emotional Awareness: Awareness of the connection between body sensations and emotional states
6. Self-Regulation: Ability to regulate distress by attention to body sensations
7. Body Listening: Active listening to the body for insight
8. Trusting: Experience of one’s body as safe and trustworthy

1. When I am tense I notice where the tension is located in my body.
2. I notice when I am uncomfortable in my body.
3. I notice where in my body I am comfortable.
4. I notice changes in my breathing, such as whether it slows down or speeds up.
5. I do not notice (I ignore) physical tension or discomfort until they become more severe.
6. I distract myself from sensations of discomfort.
7. When I feel pain or discomfort, I try to power through it.
8. When I feel physical pain, I become upset.
9. I start to worry that something is wrong if I feel any discomfort.
10. I can notice an unpleasant body sensation without worrying about it.
11. I can pay attention to my breath without being distracted by things happening around me.
12. I can maintain awareness of my inner bodily sensations even when there is a lot going on around me.
13. When I am in conversation with someone, I can pay attention to my posture.
14. I can return awareness to my body if I am distracted.
15. I can refocus my attention from thinking to sensing my body.
16. I can maintain awareness of my whole body even when a part of me is in pain or discomfort.
17. I am able to consciously focus on my body as a whole.
18. I notice how my body changes when I am angry.
19. When something is wrong in my life I can feel it in my body.
20. I notice that my body feels different after a peaceful experience.
21. I notice that my breathing becomes free and easy when I feel comfortable.
22. I notice how my body changes when I feel happy / joyful.
23. When I feel overwhelmed I can find a calm place inside.
24. When I bring awareness to my body I feel a sense of calm.
25. I can use my breath to reduce tension.
26. When I am caught up in thoughts, I can calm my mind by focusing on my body/breathing.
27. I listen for information from my body about my emotional state.
28. When I am upset, I take time to explore how my body feels.
29. I listen to my body to inform me about what to do.
30. I am at home in my body.
31. I feel my body is a safe place.
32. I trust my body sensations.

Wikipedia's page on interoception says:

Interoceptive signals are projected to the brain via a diversity of neural pathways that allow for the sensory processing and prediction of internal bodily states.

Misrepresentations of internal states, or a disconnect between the body’s signals and the brain’s interpretation and prediction of those signals, have been suggested to underlie some mental disorders such as anxiety,[6] depression, panic disorder, anorexia nervosa, bulimia nervosa, posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), autism spectrum disorders, somatic symptom disorder, and illness anxiety disorder.

ME-pedia's page on Brian Walitt says:

Dr. Walitt's research interests include "pain and related interoceptive disorders (i.e. fibromyalgia, chronic fatigue)" and "social construction of illness and disease."

He is interested in studying "perceptual illness" which he defines as follows:

"In these disorders, a person experiences a range of different bodily sensations, such as pain and fatigue, without any clear external cause. In some, these sensations can be bothersome while in others they can be disabling. The perceptual illnesses that interest me change their names with every generation, with current disorders being called fibromyalgia, chronic fatigue syndrome, and post-Lyme syndrome."

A blog article by Cort Johnson on a POTS study says:

They assessed the role of the autonomic nervous system in producing anxiety like states by the participants interoceptive awareness as they did exercise and stress tests. They proposed that their enhanced awareness of their heartbeat and other symptoms was making them more anxious.[...]

Plus, they proposed that the autonomic hypervigilance present in POTS and the array of symptoms it produces was necessarily anxiety-provoking. The anxiety in POTS was not due, they felt, to neurosis or trauma as in anxiety, but to a disconnect in the brain between the symptoms an environment should evoke and the cascade of symptoms often present in POTS.

The authors hypothesized that the anxiety type symptoms POTS patients experience were due to an over-awareness of their physical symptoms (i.e. an interoceptive problem). This didn’t suggest that people with POTS focused more on their symptoms but that their symptoms were so present that they were difficult to ignore.

Interoceptive Awareness Skills for Emotion Regulation: Theory and Approach of Mindful Awareness in Body-Oriented Therapy (MABT):

Emotion regulation involves a coherent relationship with the self, specifically effective communication between body, mind, and feelings. Effective emotion regulation involves the ability to accurately detect and evaluate cues related to physiological reactions to stressful events, accompanied by appropriate regulation strategies that temper and influence the emotional response.

(Edited to correct spelling mistakes, sorry.)

 

[Milo]

Re: interceptive signalling. I dug up some old notes of mine, from back when I first heard about Bragée's hypothesis, some years ago. In case anyone is interested, the following is some of what Google told me.

The very first thing I noticed was that "interoceptive signalling" returns lots of pop-science links about behaviour, the fight or flight response, perceived threats, anxiety, experiencing extreme emotionality, emotional instability, health anxiety (hypochondria), anxiety attacks, panic attacks, depression, mood disorders, etc.

I took a closer look at the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire used in this study:


Wikipedia's page on interoception says:


ME-pedia's page on Brian Walitt says:


A blog article by Cort Johnson on a POTS study says:


Interoceptive Awareness Skills for Emotion Regulation: Theory and Approach of Mindful Awareness in Body-Oriented Therapy (MABT):

So tired of this s@#t

 

[mango]

I guess you pointed out the main risk and most damaging one, i.e. that they would turn into using behavioral therapies, either already, or later if they fail to find anything in their MRI studies. I don't have much knowledge of Swedish clinics, but I do remember the Gottfries clinic used to not include any BPS nonsense (not sure if it's running anymore?), so I have a bit more hope in them than what I heard from Denmark or the so called treatment I have encountered here in Finland.

Actually I just yesterday happened to find a new interview here with Bragée and a recovered patient discussing rituximab and other treatments, I think it was quite good in general (only in Swedish).

Yes, you're right, both Gottfries and Stora Sköndal had a biomedical approach, Gotahälsan too. Gotahälsan closed down their ME clinic years ago, Gottfries sadly had to close down last year, and Stora Sköndal is closing down 31 May 2021

Thanks, yes I shared links to the most recent Bragée tv interview in the News From Scandinavia Thread here, and Anna H shared her thoughts about it in the same thread here.

I agree with you that there were some good bits in the interview, but I found the main message hugely problematic and I'm feeling very very disappointed I agree with Anna H's comments in the other thread.

Björn Bragée seemed happy to let them portray experimental treatment with Rituximab as something extraordinarily "hopeful", worth trying, and worth doing more research into. They completely glossed over the fact that proper Rituximab studies have in fact already been done, didn't even take a moment to explain what the results mean. Didn't mention Fluge & Mella or that they have been consistently sending a very strong and clear message: this is a very risky treatment, do not try it (unless it's a proper clinical trial).

They didn't mention that many of the pwME who tried Rituximab at the private clinic in Norway or elsewhere deteriorated very badly, nor the fact that some of them died or chose to end their own life not long after. I don't think Bragée or Malou's team understand how harmful false hope can be. This concerns me greatly.

They didn't make it clear that the private clinic in Norway no longer offers Rituximab treatments to pwME. Didn't mention that the doctor in question was reported and temporarily(?) but repeatedly got his medical licence suspended because of him offering this and other non-evidence-based treatments.

Since the interview was broadcast, I've seen so many new posts in Swedish ME groups on social media, desperate people asking about Rituximab: where to get it, for how long you should "eat it" etc... It absolutely breaks my heart, on so many levels.

How many pwME in Sweden have struggled to find the right words when replying to excited emails and messages from hopeful friends and family telling them about this "really amazing cure" they saw on TV the other day?

I'm disappointed that such a great opportunity to raise awareness about the really important issues pwME are facing was, in my opinion, wasted.

I can't see how this kind of framing/focus on "hope" based on a "miraculous recovery" associated with wild experimentation with non-evidence-based treatments will help get us better treatments, better care or support. Can't imagine it will help fight stigma, discrimination, prejudice or medical gaslighting. Can't imagine it will improve patient safety. If this is what the viewers now think matters to us, won't it undermine our demands for proper evidence-based treatments and high-quality research?

I'm well aware that TV interviews can be heavily edited, but still... The impression I got was not of a doctor/researcher that values the scientific process, understands the importance of patient safety or respects the patients enough to give it to them straight. It doesn't fill me with hope, nor confidence. But that's just my personal opinion/impression, others might of course see it differently.

(Edited to correct spelling mistakes, sorry.)

 

[mango]

Will it be a representative sample? I don't know enough to comment on the finer details of the methodology etc, but I really hope they have somehow found a way to make sure to compensate for the fact that pwME in Sweden are aware of the general differences between the two ME specialist clinics in Stockholm: Bragée and Stora Sköndal. They have different approaches, different focus, they are known for doing different kinds of tests, different kinds of research, offer different treatments, and so on, and this is openly discussed among pwME on social media and other places.

PwME with neck or spinal problems, from all over the country, for sure know where to have their referral sent if they are hoping for MRIs and a chance to see a well-known and respected neck/spine specialist, have a chance to participate in a certain kind of research projects, get a certain kind of referral, and so on.

(Edited to correct spelling mistakes, sorry.)

 

[Jonathan Edwards]

Will it be a representative sample? I don't know enough to comment on the finer details of the methodology etc, but I really hope they have somehow found a way to make sure to compensate

No, it is clearly not a representative sample. There will be bias. And if the result is a 'statistically significant' difference between ME and control there will be no way of interpreting it. This is why I suggested that the recent paper was withdrawn. It is highly damaging to produce statistically bogus results that reinforce popular myths.

This is what I mean by 'mass hysteria' being as much fantasies spread by doctors or politicians as anything to do with suggestibility of the subjects. The false beliefs in the ME field are largely spread by doctors.

 

[Milo]

I really hope they have somehow found a way to make sure to compensate for the fact that pwME in Sweden are aware of the general differences between the two ME specialist clinics in Stockholm: Bragée and Stora Sköndal

Hey @mango, what is the other clinic all about?

 

[mango]

No, it is clearly not a representative sample. There will be bias.

I've just read the cover letter/invitation that has now been sent out to potential study participants (ETA: ie people who have heard about the study, for example read about it on Bragée's website or on social media, and contacted the clinic for more info).

This bit caught my attention:

The interest in participating in this study has been overwhelming with hundreds of positive responses. For natural reasons, not everyone can participate at this stage so a selection will be made on medical grounds.

 

[Jonathan Edwards]

This bit caught my attention:

It would be fair to select on the grounds of diagnostic criteria but...