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Craniocervical dysfunction, neuroinflammation and infection in ME/CFS ws healthy controls (planned study) Bragée Clinic, Sweden

Discussion in 'Moderated Threads' started by Anna H, Nov 17, 2019.

  1. Anna H

    Anna H Senior Member (Voting Rights)

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    Bragée Clinic in Sweden is planning a study looking at 'Craniocervical dysfunction, neuroinflammation and infection in ME/CFS ws healthy controls' Jonas Bergquist from OMF's research center in Uppsala, among others.

    ETA:
    The study will include 80 patients from the Bragée clinic with an ME/CFS-diagnosis (the Canadian consensus criteria are used) and 40 healthy controls. They will perform blood tests, lumbar punctions, clinical examinations, surveys, MRI examinations etc. Blood and cerebrospinal fluid will be analyzed for signs of infections, inflammation etc.

    The study is awaiting approval, but in the study protocol retrieved from the Swedish Ethical Review Board they state that they will offer 20 randomly chosen ME-patients and 20 controls to fly to London for an upright MRI at Medserena Clinic, since no upright MRI's are available in Sweden.

    For each person the flight to and from London and the upright MRI examination are planned to take place in one single day!
    This is the part of this study that worries me!



    (the application and study protocol in Swedish)

    https://www.dropbox.com/s/t7r15rqibroe45i/Bragee_Bergquiststudie .pdf?dl=0

    Even the Ethical Review Board questions the need to fly severely ill patients to another country, and to fly there and back without an overnight stay planned or anything. PEM isn't even mentioned in the study protocol, which is quite alarming concidering the enormous exertion such an endeavor would be.
    Rather than there being a potential risk of harm, I would say there are guarantees of harm being done.

    And the head author of the study protocol, Bragée himself, is leading one of Sweden's few ME-clinics!!
    I find this extremely scary and disconcerting :sick::(
    Add to that the fact that it's a joint effort with an OMF-financed research center...

    I very much hope they don't get approval to perform this extremely reckless experiment.

    ETA :
    Here's a link to a cleaned up Google translation of the study protocol:

    https://docs.google.com/document/d/111YVl4vxgO_Pwvd5GK2MBfncIHCnZS1wuo2IepyxABM/edit?usp=drivesdk

    And here to the comments from the Swedish Ethical Review Authority, and answers to them by Björn Bragée :

    https://docs.google.com/document/d/111YVl4vxgO_Pwvd5GK2MBfncIHCnZS1wuo2IepyxABM/edit?usp=drivesdk

    (Some medical or anatomical terms may be "lost in translation", and the Swedish language in the study protocol is rather poorly to begin with, but hopefully it's readable at least.)

    Here is a translation of a summary in the application :

    "The overall aim of the project is to describe clinical, radiological and laboratory findings of the disease Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Furthermore, to compare these with findings from healthy test subjects to increase knowledge of possible causes of the disease and thereby improve the care given to ME/CFS patient.

    ME/CFS is also known as chronic fatigue syndrome and is referred to as a neurological diagnosis with ICD code G93.3. The disease is defined as a syndrome based on established criteria (the "Canada criteria") and the absence of other explanations for the often disabling fatigue and exhaustion and worsening of symptoms triggered by exertion is characteristic of the syndrome. The cause of ME/CFS is unknown.

    The number of people in Sweden with ME/CFS is estimated to be more than 40,000, most of which are very debilitated and homebound. Quality of life measured by accepted methods is the lowest among all patient groups, including severe diseases such as cancer and systemic diseases.

    The need for knowledge is great, not only for patients and the Healthcare system, but also for principals, patient representatives, insurance funds, social councils and other authorities.

    Conditions commonly associated with ME/CFS include fibromyalgia, sensitive bowel syndrome (IBS), susceptibility to infection and long-term problems following various traumas. However, psychiatric coexistence is not ascertained. Treatment of ME/CFS is based on symptoms and consists of training and instruction in activity adaptation, pacing.

    In some cases, surgical treatment of the spine has been curative but this lacks scientific support.

    Bragée ME Center is one of only three specialist clinics in Sweden that has been assigned by the county council to meet referred patients with severe problems. The queues to the clinic are long, with referrals mainly from primary care throughout the country. At Bragée ME center, about 80 new assessments are being carried out each month, which results in a uniquely large and unified patient cohort that can be evaluated.

    Based on a review of the current research for ME/CSF and our experience with thorough medical, clinical, radiological and laboratory examination of over 200 patients with established ME/CFS, we have come up with a new scientific hypothesis, and also found other issues that this project aims to clarify.

    The clinical experience at Bragée ME center is that a significant part of patients with ME/CFS have collagenopathy-related motility/weakness in ligamentous structures and many patients have MRI structural changes in the transition brain - cervical spine.

    Our new hypothesis is that a significant proportion of patients with ME/CFS may have problems with constriction in the craniocervical area which can lead to disruption of the cerebrovascular flow and thereby cause neuroinflammation.

    Our study aims to identify to which extent patients with ME/CFS, compared to healthy subjects, have findings related to injury and /or other signs of distress in the lower part of the brain and/or upper part of the spinal cord, i.e. cervical spine.
    We also want to find out if there are signs of neuroinflammation and/or infection in the blood and cerebrospinal fluid and if there are disturbances in the so-called interoceptive signaling system in the central nervous system.

    Our measurement methods (variables) consist of surveys, thorough physical examination, radiological examination of the brain/spine and laboratory tests, including blood and cerebrospinal fluid."

    ETA:
    (Google translated with major errors corrected. I'm not well versed in anatomy and medicine so there might still be some errors)

    " 3.3 What is the scientific purpose of the project? *
    The overall aim of the project is to describe clinical, radiological and laboratory findings in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Furthermore, to compare these with findings from healthy
    test subjects to increase knowledge of possible causes of the disease and thereby achieve improved care for this group of patients, whose quality of life measured by accepted methods is lowest among all patient groups, including severe diseases such as cancer and systemic diseases.

    The knowledge gap regarding ME/CFS refers to its pathophysiology, which means that a cure and/or treatment that provides substantial symptom relief is lacking .
    A research problem in itself is that registers are considerably large cohorts of patients with ME/CFS and their clinical, radiological and laboratory findings are missing.

    Our hypothesis is that the disease ME/CFS in a significant proportion of patients with ME/CFS can be explained by traumatic and/or other changes in the craniocervical area which may cause cervical cranial
    dysfunction and disturbance of the nervous system and cerebrovascular flow, including elevated intracerebral pressure.

    A sub-hypothesis is that there are signs of neuroinflammation and/or infection in the blood and cerebrospinal fluid and that there is interference with the so-called interoceptive signaling. We will therefore, based on clinical examination, assess nerve impacts and on examination of radiological images of brain and spinal cord assess possible constrictions in the craniocervical area.

    We will also measure the width of the optic nerve to get a neuroradiologically correlate to pressure conditions in the brain/spinal cord space measured at spinal puncture. Through analysis of blood samples and samples of cerebrospinal fluid we will look for signs of neuroinflammation and/or infection. "

    3.4 What scientific questions are being raised? *
    Regarding patents having received diagnosis of ME / CFS at Bragée clinic and healthy subjects;

    1. What is the correlation between diagnosed nerve impact, pain and distress and MRI scans of the cervical spine and brain?

    2. In what proportion of patients can we see the following findings ?

    a. Neurological deviations in a clinical examination
    b. Hypermobility in a clinical examination
    c. Elevated intracranial pressure measured with siphon at spinal puncture

    3. What proportion of MR brain and/or cervical spine scans show the following?

    a. Tonsillectomy
    b. Occurrence of construction of the neck
    c. Elevated intracranial pressure measured from the optic nerve diameter

    4. What proportion of patients show evidence of the autonomic nervous system being affected in a clinical examination, measurement of sweating, heart rate, temperature and cardiac activity during rest, stress and position change?

    5. What percentage of patients show signs of neuroinflammation in spinal fluid?

    6. What proportion of patients have specific antibodies in the spinal fluid and serum?"


    " Clinical examinations
    Surveys:
    Questionnaire included in the National Register for Pain Rehabilitation,
    NRS initial background issues,
    RAND 36r,
    EQ-5D (EuroQol 5 dimension),
    MPI, (Multidimensional Pain Inventory),
    HADS, Hospital Anxiety and Depression Scale,
    Canada criteria,
    ME symptoms Questionnaire,
    The clinic's questionnaire Including pain sketch.
    Örebro Musculoskeletal Pain Questionnaire,
    Questionnaire on Autonomic Symptoms,
    MAIA, Multidimensional Assessment of Interoceptive Awareness,
    Fatigue severity scale, Swedish version,
    PIPS Psychological Inflexibility in Pain Scale [13],

    Objection drawing [14, 15]
    Medical history and clinical examination.
    Complete medical history.

    Careful clinical examination including walking test, tilt test (electronic tipping board) quantitative sensory threshold measurements.
    Mobility according to the Beighton model.

    The examinations are harmless, and stimulated cold and heat remain below the thresholds for tissue damage, and
    can also be interrupted by the patient momentarily in case of major discomfort."

    Edit: for clarity and to add links
     
    Last edited: Dec 3, 2019
  2. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    If the scans and any surgery have to be done in another country wouldn’t it make sense to select subjects in that country too?
     
  3. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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    You'd think...
     
  4. Andy

    Andy Committee Member & Outreach

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    It might be thought that the additional challenges of recruiting outside your home country might be more than actually carting your selected patients around between countries? And/or it's easier for them to get ethical approval this way? I have no idea, just guessing.
     
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  5. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    In terms of ethical approval there is generally in the UK a mechanism to get joint health and academic ethical approval in one go, but by recruiting overseas they would presumably need ethical in both the UK and Sweden. However that can not be that difficult given it is not uncommon for clinical drug trials to happen with study cohorts drawn from a number of countries.

    A possible solution would be for this project to work jointly with a UK academic institute.

    I can not imagine myself participating in a research project requiring international travel. It would probably be too much of a challenge to even considering participating in anything more than 25 miles away.
     
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  6. Anna H

    Anna H Senior Member (Voting Rights)

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    Here's the basis for their hypothesis that there is interference with 'interoceptive signaling' in ME.
    Even they seemingly admit to it being far-fetched in a way, with their use of wording: 'may have' and 'if... one might suspect'.

    Is difficulty perceiving hot and cold really part of any diagnostic criteria? I have never heard of this.

    ETA:
    Here with different wording :

     
    Last edited: Nov 19, 2019
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  7. Anna H

    Anna H Senior Member (Voting Rights)

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    Another excerpt from the study protocol, where they argue that the fact patients need to lay down to relieve symptoms is another reason an upright MRI is suitable. What about orthostatic intolerance?

     
    Last edited: Nov 20, 2019
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  8. Wonko

    Wonko Senior Member (Voting Rights)

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    It sounds like they have a hypothesis, that a significant subgroup is caused by trauma, but that they don't believe it, or why would any responsible researcher risk international travel, probably a day that would wipe out a healthy person, and then flying back, and getting home, the same day.

    The only rational conclusion would be that they don't believe their own hypothesis, in which case their motive for proposing this would need to be questioned.

    You do not subject people with suspected 'spinal' trauma to this sort of thing unless it is essential to save their lives. You do not subject bedbound people to this in the name of 'research'.

    So...what's up doc?
     
  9. mango

    mango Senior Member (Voting Rights)

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    Well, we know that Bragée ME Center uses the Canadian criteria. I did a quick search of the Carruthers et al consensus document.

    I didn't find anything about "difficulty perceiving cold and heat in a normal fashion".

    Below are the bits that I found about related words like "temperature", "hot" and "cold".
    A search for "perception" etc in the same document gave the following results:
    In the Overview of the Canadian Consensus Document document I found:
    In the primer:
     
    Last edited: Nov 19, 2019
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  10. Anna H

    Anna H Senior Member (Voting Rights)

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    Here's what's listed under 'Ethical considerations' as potential risks. If one didn't know this was a study that involved ME-patients, you couldn't tell by reading this (except for the mentioning of ME-center) :

    And here are the unmistakable fingerprints of Gunnar Olsson, which gives away some of the psychosocial underpinnings buried within this study:

    "Medicalization" of one's own situation is a potential negative effect for those participating in the study, e.g. 'fear of movement' after getting information about spinal constriction or abnormal blood test response they did not know about earlier.....
    .....In an educational contact with a healthcare provider this can lead to
    increased self-confidence and freedom of action, when you can get an explanation for your problems and knowledge that the condition is harmless."
     
    Last edited: Dec 3, 2019
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  11. Anna H

    Anna H Senior Member (Voting Rights)

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    Thanks for checking up on that@mango!:thumbup:

    There doesn't seem to be anything in there supporting his claim that it's in the diagnostic description of ME. An inability to regulate body temperature and intolerance to heat or cold are quite the opposite to not perceiving heat or cold, I would argue.
    It's of course possible they have met patients with this problem, but maybe that's more an indication that these patients maybe don't have ME, or maybe have some other comorbid condition ?
     
    Last edited: Nov 19, 2019
  12. Anna H

    Anna H Senior Member (Voting Rights)

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    Couldn't agree more!
    Yeah, what's really going on here doc?
     
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  13. mango

    mango Senior Member (Voting Rights)

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    I can't remember ever reading about altered temperature perception in ME before (could be that I simply have forgotten). However, I've seen it mentioned in Jen Brea's posts a few times, for example:

     
  14. JenB

    JenB Senior Member (Voting Rights)

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    I’ve only read about this symptom in Chiari I malformation and in small fiber polyneuropathy (SFN), which Annie Oaklander talked about at the NIH conference. I haven’t read about it in ME or in CCI, either. It lasted either for several days to a couple of weeks until thankfully, going away.
     
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  15. JenB

    JenB Senior Member (Voting Rights)

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    Yeah exactly. I don’t think this is the most important question right now, though. What’s clear is that there are people in our community with treatable neurosurgical conditions and it is important that we find them, because they are our friends and “neighbors.” And they have PEM. So, we can both help them and learn something from them.
     
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  16. JES

    JES Senior Member (Voting Rights)

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    I'm confused by your message. First of all, they already have observations from 200 patients from being examined in their clinic, which has initiated this study, so it can only be assumed they have already seen something in the MRI images. Secondly, the default position is always to not believe your hypothesis unless it is proven correct. And the way to prove a hypothesis correct is to try to falsify it. The only way you can falsify it is by doing more studies and comparing against healthy controls, which is exactly what they are attempting to do with this study.

    Finally, the patients can opt out of the international traveling part. The main study does not include this, it's an extension to the study where 10% take part. I can only assume, but it would make no sense to include severe patients to this part of the study.
     
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  17. Wonko

    Wonko Senior Member (Voting Rights)

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    I think you may be experiencing confusion because you're starting from the position of trusting people who want to put people like me through something I would regard as very similar to torture - and although mostly housebound I am not severe, I just can't undertake journeys that involve more than 1 or 2 stages, or cope with being in crowded or unknown environments, or ones with noise, or ones that are too big or too small, or are too bright, etc..

    I'm moderate, just about capable of functioning independently provided nothing crops up.

    According to what you have just posted I'm an ideal candidate (apart from not being from Sweden).

    The idea that anyone like me, or worse, would even be asked to do something like that, instantly makes me distrust and suspicious.

    I do not read Swedish.
     
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  18. mango

    mango Senior Member (Voting Rights)

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    I've written a bit about this in some of the older threads, for example:
     
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  19. mango

    mango Senior Member (Voting Rights)

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    From an earlier thread:
     
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  20. mango

    mango Senior Member (Voting Rights)

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    About people being free to opt out or decline the invitation to take part in research studies and other experiments. It might not always be so easy for people to say no, even though they have a right to.

    One possible reason, for example, is that the contract Bragée ME Center has with Stockholm County Council only allows the patient a certain number of visits before they are to be sent back to their GP/primary care (who perhaps "doesn't believe in ME" and refuses to continue the medication the ME specialist prescribed for you). However, if you are currently undergoing treatment of some kind or if you're in a research study etc it seems there's less chance that you will be kicked out, you might be allowed to stay a patient at the specialist clinic for a while longer.

    Please note that this is not hard facts, not written in the contract or anything like that -- it's just an observation I've made listening to discussions among patients.
     
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