Clinical, radiological and immunological findings in ME/CFS, other pain conditions or fatigue; Bertilson

There’s been some discussion in other threads about some very bold claims made by Bo Christer Bertilson and Björn Bragée at Bragée ME-center in Stockholm, Sweden.

For example, in an interview on Swedish TV (Malou efter 10, 13 May 2019), Bertilson claimed that close to 90% of the patients at ME-center have some kind of stricture issues in the spine, in the cervical spine. When asked why, he replied “We can’t say. But many have had some kind of trauma, like fallen down or traffic accident or has been horse back riding,…"

They are planning a research study, or maybe it is already happening. At the time of posting I don’t know if the application for ethical approval has been processed yet.

I haven’t been able to find any public info about this study online yet, but I’ve read the ethical approval application — gotten through a FOI request — and I’ll share some parts of it below (translated with the help of Google Translate, sorry about the low quality). The original document is in Swedish, 65 pages.

Clinical, radiological and immunological findings in ME/CFS, other pain conditions or fatigue

Bo Bertilson and Björn Bragée
Bragee Medect AB / Bragée ME-center Stockholm, Sweden

“3.2 Purpose
The project aims at retrospectively mapping anamnestic, clinical, laboratory and radiological findings to the disease Myalgic Encephalomyelitis/Chronic Fatigue syndrome (ME/CFS) and to compare these findings with findings from patients with the diagnosis of fibromyalgia or burnout in order to increase knowledge of possible underlying disease cause and thereby laying the groundwork for improved care.

The mapping will be done through compilation of findings from surveys, clinical body examinations, laboratory samples and cervical spine and brain MRI of over 200 patients who visited the specialist clinic and were diagnosed with ME/CFS and one, as well as a corresponding number of patients diagnosed with fibromyalgia and burnout respectively, who also visited the specialist clinic.

Radiological findings on magnetic camera (MRI) of the cervical spine and brain will be evaluated in particular. This is because our experience and several published studies have shown that ME/CFS and similar conditions such as fibromyalgia may be connected to restricted space in the central nervous system. Space reduction that can lead to neurological symptoms that are not only common, but part of the diagnostic criteria for the condition."

“3.3 Scientific purpose
The main hypothesis is that ME/CFS in a significant proportion of patients can be explained by post-traumatic or other dysfunction in the craniocervical area, which can lead to disturbed flow of cerebrospinal fluid with concomitant elevation intracranial pressure and immunological response in the central nervous system.

The project aims to retrospectively identify anamnestic, clinical, laboratory and radiological findings in the disease Myalgic Encephalomyelitis/Chronic Fatigue syndrome (ME/CFS) and to compare these findings with findings from patients with the diagnosis of fibromyalgia or burnout, in order to increase knowledge of possible underlying disease cause and thereby laying the groundwork for improved care.

In particular, we want to test the hypothesis that patients with ME/CFS have findings suggesting neuropathic or nociplastic (formerly referred to as sensitized) pain that can be traced back to space restriction in the central nervous system which can cause interference with the cerebrospinal flow. Radiological findings on magnetic camera (MRI) of cervical spine and the brain should therefore be specifically evaluated. If the hypothesis is substantiated by the mapping, the investigation and treatment recommendations need to be revised and supplemented."

“3.4 What are the scientific issues? *
Regarding patients that have been diagnosed with ME/CFS or fibromyalgia or burnout at Bragée clinics.

1. What percentage of cervical spine and/or brain MRI has the following?
1a. Tonsillecti
1b. Presence of narrowing of the cervical spine
1c. Increased intracranial pressure measured by the diameter of the optic nerve
2. Are there differences in the incidence of findings in question 1 between patients with and without H-EDS/EDS respectively?
3. What inter-judgment reliability exists when assessing the existence of findings in question 1.
4. What is the correspondence between the diagnosis of nerve impact on the symptom sketch and during magnetic camera examination of the cervical spine and brain?
5. Are there signs of the influence of the autonomic nervous system on body examination, measurement of sweating, pulse rate, temperature and heart activity at rest, stress and change of position?”

“4. Method
Data that has already been collected is reviewed and evaluated. The material consists of radiological examinations, primarily cervical spine and brain MRI, answers to questionnaires, and exam findings and laboratory results documented in the journal.

As regards the assessment of MRI findings, these are made by three independent assessors, a trained specialist in radiology, an experienced ST doctor and a medical student, following an established protocol where we through MRI measure the diameter of the eyeball, the diameter of the eye nerve, the position of the cerebellum in relation to the so-called McRae line, i.e. at the exit of the spinal cord through the foramen magnum. Cervical spine conditions are categorized according to narrowings and their levels. Presence of cysts, spondylolistes, misshapen discs and osteophytes are reported, as well as medullary impact and space restrictions.

This is a study of findings from clinical exams made for diagnostic purposes, and no exams are added or made especially for research purposes, but is determined from clinical and anamnestic findings during normal business.”

“5.1 Expected start date for the project *
2019-02-15

5.2 Expected end date of the project *
2019-12-31”

“8.1 How is the selection of the subject population done? *
The study includes patients enrolled at Bragée clinics. All patients diagnosed with ME/CFS will be included in the study, providing they have given consent to participate in the study, which takes place before and during new visits to the clinic. To create a representative material, patients are studied in randomized order, but if resources allow, as many as possible of those who visited the clinic or visit it during the course of the study will be included in the material. Regarding patients with fibromyalgia and burnout, a selection of patients who have completed rehabilitation and one-year follow-up, meet the criteria below and have given written consent will be studied.”

“8.2 How many subjects will be included in the research project? *
200-500 patients with ME/CFS and 40 patients with fibromyalgia and burnout, respectively.”

“8.3 Which selection criteria will be used for inclusion? *
Patients with ME/CFS must meet the so-called Canadian criteria and have been assessed and referred by a doctor. The patients will be studied in randomized order, i.e. the whole population gets one particular number that is generated randomly and determine the order in which they will be included in the study. Patients with Fibromyalgia should meet the AC R criteria for the diagnosis but not have PostExertional Malaise, the distinguishing symptom for ME/CFS. Patients with burnout should be exhausted without
pain estimate more than 30 in VAS and have at least 4.47 p at performed Shirom Melamed Burned Out Questionnaire. 40 subjects with fibromyalgia and 40 with burnout can be included, and if the number of patients who meet the inclusion criteria are larger, a sample of the patients of the last two years is randomized.”

“13.3 How and when are the results planned to be published? *
Results will be compiled and submitted to scientific journals in 2019, and at medical congresses in 2019 and 2020. Popular science compilation can take place during the same period.”

“14.1 Report any financial agreements with contributors or other financiers
(name and amount)
The research is funded by the principal investigator, no other contributors have been asked or shown any interest.”

 

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

Available to watch online here (In Swedish. Geoblocked outside of Sweden).
https://www.tv4play.se/program/malou-efter-tio/11795690

Google Translate:

"Among other things, we look at pictures of the spine and the brain. [...]
What we have found in a large part of our patients is that they often have constrictions in the spinal canal or in the transition between brain and spinal canal, the so-called large hole, the foramen magnum. [...]

What can be seen in our population is that about half of the patients have a part of the cerebellum that penetrates into this hole, more or less. [...]

[The flow of the spinal fluid is disturbed], the flow is not as free. And these freedom depriving strictures can be found at the top of this large hole or they can be further down in many patients. [...]

One can hypothetically say that, now if one assumes that some of these patients have constrictions, which we see very often, in the group of patients we have at ME centers in any case, so upwards of 90% have some type of constriction problems in the spine, in the cervical spine. [..]

[Why?] We can't say that. But many have been involved in some type of trauma, ie fallen or traffic accident or riding, or ... "

 

Here's an earlier thread about one of Bertilson's other studies:

https://www.s4me.info/threads/the-med-study-bo-christer-bertilson-sweden.8443/

 

Here's a link to another tv programme where Bertilson talks about ME and his hypotheses.

It's in Swedish, was recorded 12 April 2019 during a seminar arranged by Bragée ME-center.

https://urplay.se/serie/212286-ur-samtiden-kronisk-utmattning

(I'm in a bad relapse, haven't had a chance to watch it yet so I can't comment on it.)

 

This is going to be conducted in the same country where I am residing. Very exciting. I have even seen that Jonas Bergquist was there giving a speech regarding "Internationell Forskning" (which stands for internationall research), which is very intressting. Thank you @mango .

 

Is this a private clinic?

The material presented looks shaky.

I am trying to remember my CSF physiology but as far as I remember narrowing of the cervical canal is not a cause of raised intracranial pressure - CSF is normally absorbed through arachnoid granulations above the foramen magnum. If I am remembering rightly they have got the mechanism back to front.

 

Ok so half the patients that’s a lot ...is that the ones with burnout as well?

It begs the question that if half of pwme have this ..what about the other half and what about general population controls?

Really? I must be in the half that didn’t have a trauma then?

This looks decidedly dodgy ..almost like they are picking something relatively common (90%?) and making a non proven connection to encourage very expensive treatments? Perhaps I’m being cynical?

 

Yes, a private clinic. Opened in February 2017. Both Bo Christer Bertilson and Björn Bragée are new to ME.

ETA: They do have a contract with Stockholms Läns Landsting, the regional public health authority, which means that patients don't pay more than at public health providers/centers. I don't know the terms in English, sorry...

 

No, not including the ones with burnout. He was talking about ME patients only.

 

Interesting that when the clinic opened Dr Bragee claimed that:

The etiology of ME/CFS is unknown, but in 90% of cases an infection has precipitated the onset of the condition.

Now it seems that trauma is responsible for 90%.

That seems like 180%.

Although my analysis might be too simple!

 

This is from an earlier thread:

 

The video shows typical woolly pseudoscience. Nothing actually hangs together.

It all seems to stem from this paper by Rowe. But from there it goes in all directions in a completely random way. I have listened to talks like this for years. PWME need something better than this.

 

Thanks for the info @mango, very helpful.

This seems interesting, let's hope this will be research of high quality. It can be a good thing to have a researcher from outside the field who presents with new ideas but the 90% figure makes me a bit suspicious, to be honest.

Also a bit weird that they are aiming for a sample size of 200-500! That doesn't seem necessary, other methodological factors seem more important. If I remember correctly there was a study by Heffez et al. that used a large sample size of more than 200 patients and that reported high rates of Chiari malformation and spinal stenosis in fibromyalgia patients. But the trial was unblinded and there was no control group (to test if the researcher weren't simply overdiagnosing). Other studies couldn't confirm these findings. So I really hope that the trial of Bertilson will be blinded.
https://twitter.com/user/status/1067829911807803392


It also seems that they are mostly looking at increased intracranial pressure. There's a Belgian research team at the University of Leuven that's also looking into this in patients with fibromyalgia and ME/CFS (Hulens et al. 2018). But they have only published preliminary studies. for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292399/

 

You are diligent in the literature searching @Michiel Tack. But the more I hear of this the less it looks real. If rates of Chiari vary widely then I suspect the whole thing is a house of cards.

 

A - how shall I put this? - 'surprising' hypothesis. Here's hoping they use sound methodology and make it a good study that gives us some solid, interpretable data. With all the current fuss around ME and various neck/brain stem/spinal problems it would be good to get some better data on this even if it ends up showing, as I suspect it will, that the hypothesis is wrong.

What I can't figure out is how PEM is supposed to fit in with this hypothesis. They clearly are aware of PEM since it's a major criteria for participant selection so must have thought about it. But if you have an old traumatic injury causing your symptoms, wouldn't you feel equally awful all the time? Or alternatively only feel awful when you twist your head a certain way that aggravates your old injury? Why would exertion that doesn't affect the site of the old injury cause a worsening of symptoms?

But I did fall off a horse once...

 

I must say ..the historical injury thing sounds a bit like the leading suggestions put out by fortune tellers ....you will meet someone in the future, did you mother have brown hair etc.

I’m sure if we all cast our minds back we could pick an event to confirm this hypothesis ...I’ve been in several shunts in a car, fallen over (not always drunk) got an egg on the forehead from walking into a lamp post (I was definitely drunk that time). These were all a long time before I got ill though, but I guess they can say I perhaps didn’t realise which would be neatly self fulfilling.

I’m not getting a good feeling that the design of this work has any intention of finding the truth.

So far they haven’t used proper controls from what I can see, and as others have pointed out ..90% seems a bit unlikely.

There seems to be a lot of confirmation bias going on here.

 

Amen.

 

Did you, by any chance, have a look at the questionnaires they are using? Unfortunately the questionnaires they have chosen don't capture PEM in a meaningful way (or at all?), and I'd say that's definitely a problem.

 

Here's one of Bragée's slides from Ur Samtiden, about recovery in ME. The title is "But certainly one can be cured", and the last bullet point says "More reports about recoveries after neck surgery". Would be very interesting to know what source(s) that statement is based on?

 

No, I didn't look at their questionnaires, only at the statement under point 8.3 "Patients with ME/CFS must meet the so-called Canadian criteria and have been assessed and referred by a doctor."

CCC require PEM to be present, so far so good - in theory anyway. Trouble is there are a lot of doctors, even some ME experts, who seem to confound PEM and ordinary post-exertional fatigue. Unfortunately these days everyone throws the term PEM about without defining it so there's no way of knowing what they mean by it. Consequently there is also no way of knowing what their study results mean and which patient groups they may apply to.