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

[JenB]

Patients here in the US do travel identical distances to participate in studies at Harvard and Stanford, and to seek care. It will obviously exclude the severely ill and include those who voluntarily participate. Some people who are moderately affected will choose to undertake this travel, for science, for their own curiosity about their health.

I mean, we also take ME patients and put invasive monitors into their heart and make them exercise and then put them in cold packs and into MRI machines.

Most people should NOT do this but some will. I am grateful to them.

 

[Anna H]

The main study does not include this, it's an extension to the study where 10% take part.

Yes, only 20 patients are offered to fly back and forth to London for an upright MRI during one and the same day.

As I wrote in another thread :

"My main concern, which even the Ethical Review Board agrees with, is the prospect of having all this done in ONE day. Even for patients with mild ME this is a huge ordeal. Had it included several nights stay with the possibility to rest after flights, MRI's etc it would show a completely different understanding of the illness. Add to that the complete omission of PEM in this document, surely flying to another country with all the hassle of getting to the airport, standing in line, waiting and the bombardment of sensory input will cause PEM for anyone with ME, regardless of their severity of illness. And then not be given the chance to rest? The principles of pacing are not being used by someone in charge of an ME clinic which teaches patients pacing and to avoid PEM?"

JES said:
Finally, I reckon there is potential harm associated with almost any kind of studies. Most medical trials will require participants to move from place A to place B.

"Yes, there is. The main problem here as I see it is that they are not mentioned as such, the potential risks mentioned are the possibility of discomfort during and after the lumbar punction, possible bruising after blood tests. Not a single word about PEM or over exertion.
How much of an expert in ME are you, and how ethical is your research, if PEM and risks of deterioration are not even mentioned in a study that includes such great exertions? "

 

[Kalliope]

It seems the date for the protocol is 09.09.2019. I wonder why Jonas Blomberg is listed among contributing researchers as he sadly passed away in February.

Has he contributed with the protocol perhaps? Does this mean that others who are listed as contributing researchers might not be heavily involved?

 

[JenB]

A Norwegian patient helpfully offered a slightly different perspective on the document, which I am pasting here. I obviously can’t read the original document so make no claims as to the accuracy of the comments below. (These comments were in response to a discussion of the study posted on a different thread, not necessarily anything said on this thread):

So, I've read the protocol, and technically the post isn't 100% correct.

1. First. Bo Berthilsson is the main researcher, not Brageé. Brageé and 7 other doctors will be included in the study.

2. They plan on including 80 patients and 40 controls, and put all these through regular brain and cervical MRI. Then 20 of each group will be randomly chosen to go to london to check if the upright MRI will have different results.

3. Jonas Bergquist, which is the one working for OMF is included as a doctor in the study.

4. Bo Berthilson and Brageé have had a theory for years that ME patients have neck issues. This is not new or linked to Jen or CCI in any way. They have been taking cervical MRIs for years, and have stated earlier that 80% of their patients have some kind of compression or blockage of CSF. Mostly Stenosis. I assume this research is to put this obsevation to test. Edit: Berquist has researched inflammation in the CSF.

5. In addition to supine MRI and uMRI, they will take spinal taps and blood tests. The patients will also answer questioners and pain scales

6. It does not say anywhere that they travel back and forth to London in one day. Nor that 20 patients will go at the same time (that's impossible. The uMRI takes an hour). It say that the first patient will go to London in sept 2019, and last inclusion will be feb 2020.

7. The severity of the patients included is not stated in the document. Inclution criteria say patients referred to Brageé institute which satisfy the Canada Criteria, + other general criteria (no pregnancy for instance). So sending 20 severe patients to London is wrong

8. Nowhere does it state they will offer treatment or recommend operation. It sais "to research causes for ME," it also says that surgical treatment have been done in some patients in the past, and they want to check if the science backs this up. It also say "However, the project can be helpful in weighting current issues, identifying relevant diagnosis and providing support regarding future appropriate self-care and treatment" but don't indicate that they mean surgery.​

 

[mango]

I obviously can’t read the original document so make no claims as to the accuracy of the comments below.

Why would you post something if you don't even know if it's true?

A lot of this is very easy to fact check, even if you don't understand Swedish. For example, your text repeatedly says "for years". I'm not sure if that's a helpful reframing of what has been said already. ME Center opened in 2017...

This is not new or linked to Jen or CCI in any way.

What is this statement based on, please? Do you know what recovery stories Björn Bragée was referring to in the slide I shared earlier in this thread?

 

[TiredSam]

A Norwegian patient helpfully offered a slightly different perspective on the document, which I am pasting here.

Why don't they come and post it here? Did they give you permission to paste it here? Is this a source you can cite with a reference at least? I'm not sure gathering hearsay perspectives is that helpful.

 

[mango]

Brageé and 7 other doctors will be included in the study.

As @Kalliope already mentioned, Prof Jonas Blomberg is sadly no longer alive. The application is dated 9 September 2019, which is after he passed. I'm not sure what his contributions would be to this study, maybe the planning of it?

 

[JenB]

Why don't they come and post it here? Did they give you permission to paste it here? Is this a source you can cite with a reference at least? I'm not sure gathering hearsay perspectives is that helpful.

Yup, I have permission.

The person isn’t a member of the forum. Not sure why they didn’t want to create an account or post, they just said they didn’t want to, so I asked them if I could repost.

It’s definitely not true that they are flying everyone in and out in one day, at the same time. That would be impossible. Thought that was at least worth sharing.

My understanding is that this is her reading of the same document (the Dropbox link) that the original poster shared. She just thinks some key points were misinterpreted.

 

[mango]

have stated earlier that 80% of their patients have some kind of compression or blockage of CSF.

Here's a transcription of what Bertilson said about their preliminary finding on Malou efter 10 (morning show on Swedish TV), 13 May 2019.

[...]upwards of 90% have some type of constriction problems in the spine, in the cervical spine.

Etc...

 

[Anna H]

It does not say anywhere that they travel back and forth to London in one day.

Yes it does, and in the lengthy response from the Ethical Review Board they question this:

"5. It seems unreasonable for people suffering from ME / CFS to go to London
over a day to do MRI. How to handle a situation where the research person
due to their illness must remain in a hotel or be hospitalized?

Yes, this objection is reasonable, but it is a very experienced clinic in England, with
established procedures and contacts for any complications, and we cover all costs
for such additional needs. However, we hope to be able to do these surveys in Sweden, when opportunities are open for such an MRI camera located in Stockholm."

 

[MSEsperanza]

Both the opening post and the "slightly different perspective" posted by @JenB seem a bit confusing to me.

1. First. Bo Berthilsson is the main researcher,

I don't understand Swedish but from having a look at the document it seems this correction is right and Bragée isn't the principal investigator, but Bo Bertilson (without ("h) @Anna H , @mango ?

We have threads discussing the Bragée Clinic and Bertilson, but I think it would be good to extend the break we're currently having regarding CCI surgery discussion on spine issues in general.

It’s definitely not true that they are flying everyone in and out in one day, at the same time

Did anyone say this (about the same time)?

(These comments were in response to a discussion of the study posted on a different thread, not necessarily anything said on this thread):

Ah, perhaps on that different thread? On the thread here at least it seems to me a misunderstanding. People seemed concerned that study participants won't stay overnight, not about putting all patients in one plane.

Brain fog is an issue for most of us, and unfortunateIy I also post muddled things too often. I hope all of us try to be very circumspect these days with posting things we know can lead to very heated debates.

Edit: crossposted with @Anna H .
Edit 2: spelling (it IS difficult with brainfog!)

 

[Anna H]

First. Bo Berthilsson is the main researcher, not Brageé

I might have used Bragée both in reference to the Bragée clinic and Bragée himself, sorry for that confusion.
This study is part of Björn Bragées dissertation thesis and he is the author of the study protocol.
Bertilson is Bragées tutor.

 

[Sid]

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.

 

[Anna H]

I'm sorry that the opening post is perceived as muddled . I originally wrote it as a comment in another thread, mainly to point out my concerns with this study, and it seemed to warrant a thread of it's own. I should have rewritten the post to reflect a better summary of the study , which this post never was intended to be.
Again, I'm so sorry for this. I will edit the opening post.

 

[Trish]

Moderator note

This thread was closed for moderation. It has now re-opened as a fully moderated thread. This means all posts will be checked by moderators before appearing on the thread. The aim is to enable productive, respectful and well-focussed discussions.
See the explanation from the committee here.

 

[Anna H]

I have Google translated (major errors corrected) the study protocol in it's enterity.

That way everyone can read it for themselves and there's no need for different "perspectives".

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

I have done the same with the lengthy comment from the Swedish Ethical Review Authority, and the answers to their concerns, signed by Björn Bragée, as I find it rather "interesting" :


https://docs.google.com/document/d/1dX-UU_-Srb6XVnV7zVK3daQRWRLo3z65hevC19lHJ14/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)

 

[JenB]

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.

I think a part of the problem is there have been very few large-scale brain imaging studies on ME patients. Scratch that—have there been any? And no cervical MRI studies as far as I am aware. The work just hasn’t been done.

I know I am just one case but I saw seven ME experts in the US and had a battery of testing, among them two brain MRIs. One MRI report failed to mention the empty sella (which is often considered an incidental finding, but is not if you have symptoms of intracranial hypertension, which I did have), the other reported but misinterpreted it as a “Rathke’s cleft cyst.” I was never referred for a cervical MRI. I also was never given the type of neurological examination that would have revealed clear deficits. The only reason I started down this path was because I was a subject in a film nationally broadcast in the US, and from the film and a TED Talk, a neurosurgeon both saw signs of intracranial hypertension in my MRI and recognized my symptoms as consistent with what he observes in his EDS patient population.

FWIW, there is more work on this in fibromyalgia, where all this has been a “controversial” topic for some time: https://www.me-pedia.org/wiki/Cervical_spinal_stenosis

 

[jpcv]

I think a part of the problem is there have been very few large-scale brain imaging studies on ME patients. Scratch that—have there been any? And no cervical MRI studies as far as I am aware. The work just hasn’t been done.

I know I am just one case but I saw seven ME experts in the US and had a battery of testing, among them two brain MRIs. One MRI report failed to mention the empty sella (which is often considered an incidental finding, but is not if you have symptoms of intracranial hypertension, which I did have), the other reported but misinterpreted it as a “Rathke’s cleft cyst.” I was never referred for a cervical MRI. I also was never given the type of neurological examination that would have revealed clear deficits. The only reason I started down this path was because I was a subject in a film nationally broadcast in the US, and from the film and a TED Talk, a neurosurgeon both saw signs of intracranial hypertension in my MRI and recognized my symptoms as consistent with what he observes in his EDS patient population.

FWIW, there is more work on this in fibromyalgia, where all this has been a “controversial” topic for some time: https://www.me-pedia.org/wiki/Cervical_spinal_stenosis

Very interesting information, in both studies the patients had objective neurological signs and symptoms, my question is, could these findings be generalized to a broader group without these signs and symptoms?

 

[Guest 2176]

Mod note: Copied post. A number of other posts have been moved from the thread about a study completed by the Bragee clinic team.

Iirc Paul Cheney said he found very high pressure on spinal tap in incline village patients. Idk if he published these findings though.

Hes still alive. Does anyone know how to contact him?

Also, re: this study. I am in favor of studying this. I have methodological concerns. Like with the upright MRI, it can be hard to get a clear picture if patients are very symptomatic. So ironically you may either get not clear pictures, or have a less severe patient cohort that you're studying, if you are having people fly out and do it in one day, without medication.
So while its good that they are studying this, I think it's an ex of how researchers should listen to patient input about study design.

 

[Anna H]

Here's a post I wrote regarding this study from another thread. As you can see PEM isn't even mentioned as a risk, but a possible 'fear of movement' following new information about one's health condition is :

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) :

7.1 What are the risks for the participants taking part in this research project? *

Possible risks are assessed as small. The study elements included in the study are all well established in the health care system and at ME-Center where the study is conducted. MRI examination does not involve ionizing radiation and is harmless and common safety practices are used regarding inoperable electronics or
observed metal. Pregnant control persons are not allowed to participate.

The intended blood sampling volumes are small and do not normally affect a person's health condition and constitutes a volume of less than ten percent of blood donor volume. All blood sampling involves the risk of discomfort and some risk of infection, which is however considered to be very small.
Spinal puncture carries the risk of discomfort, and some risk of infection but with the aseptic technique we use it's considered to be very small.

The volume of 10 ml taken is a fraction of what is produced per day and does not entail any risk. The doctors who carry out the examination are anesthesiologists with long experience with the procedure.
The clinical examination follows a structured template with emphasis on detecting nerve impacts and/or instability in the spine, and tests superficial sensation of puncture and touch, reflexes, nerve tension and includes palpation.

The clinical examination does not involve invasive or manipulative procedures. The examination has been done by the participating researchers on thousands of occasions, is accepted and do not pose a risk of injury or discomfort, besides the Sensitivity test, which can be experienced as a pricking sensation in the skin, and during the superficial palpations and the test of the spine there may be a local and transient soreness.

Blood sampling for research subjects in the patient group can cause some discomfort, pain, swelling and bruises at the sampling site. Otherwise, the risk of complications associated with venous blood sampling is considered small when performed in accordance with current medical practice.
Spinal puncture carries a certain risk of subsequent headaches, and discomfort in connection with the examination, but
even in large materials, the risk of complication is stated as small.

MRI examination is done on the basis of accepted principles and limitations, which means that only persons without implanted or otherwise magnetic material can be examined. The MR camera itself can cause feelings of discomfort and of being cramped, which can be reduced by sedatives.

"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. However, the project can be helpful in weighting current issues, identify relevant diagnosis and provide support
regarding appropriate self-care and future treatment. 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. "

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."