The science of craniocervical instability and other spinal issues and their possible connection with ME/CFS - discussion thread

quite. Not to mention the fact that it will all play beautifully into the hypochondriasis/aberrant illness beliefs/unconscious desire to be seen as having a serious illness/etc etc etc nonsense of the BPS narrative.
I'm appalled that she can't see the harm she is doing. Jen isn't just another patient, she has a huge platform and won quite a few in the medical/political community over with her advocacy after Unrest. She is ruining her credibility in the scientific & medical communities & how long before those who were won over by her initially, revert to their previous thinking after seeing some of this. Reddit will have a ruddy field day!
It's all very well but this is going to have real negative effects on all of us, if things continue & our GPs see it. You wont be able to go to the GP with neck pain & get it properly investigated because the BPS lot will end up spreading the word that we all think we have CCI or want to have it. ... "I suppose you think you've got CCI" will be the jibe. We've got enough trouble... I wish she & the rest of the CCI fan club would just shut up if they cant be responsible about it.

 

I feel a bit bad for saying that now, perhaps I was being harsh my patience is thin today. I know she means well & the dramatic relief of her symptoms must be hard not to extrapolate from & enthuse about. But I don't think it's doing the rest of us much good.

 

"Michaela [sic] has severe ME due to CCI..."
"My ME symptoms were most certainly a function of CCI and tethered cord"

 

A position statement from the Board of Directors of MEAction is long overdue.

 

Followers of this thread might also want to keep an eye on this new thread:

https://www.s4me.info/threads/mediu...al-strain-jennifer-brea-september-2019.11138/

Medium Blog: 'Could PEM be a symptom of neural strain?' Jennifer Brea, September 2019

Extract:

"In my view, there is ample suggestive evidence that craniocervical junction abnormalities, in particular those associated with Ehlers-Danlos Syndrome (e.g., Chiari malformation, craniocervical instability, atlanto-axial instability, cervical stenosis, and possibly tethered cord syndrome), are among those diagnoses that could cause PEM and many of the other symptoms of ME. This hypothesis should be formally tested..."

 

Very interesting thread!

I have severe ME/CFS and EDS, being completely bedbound since 2017.

I have a translational BAI of 6 mm, that is a measurement that has been recorded via uMRI before (!) I became bedridden.

People seem to be quite adamant that uMRI is an unnecessary tool, I ask very specifically @Jonathan Edwards what he thinks about this measurement and whether he believes that this is within the normal range, and if not if it could be related to ongoing neural damage with every extension or flexion of my neck.

This measurement can not be done with a normal supine MRI.

What says the actual science about that?

And if it says nothing about it, does that mean it is not relevant, and if so how would you know?

Thank you.

 

As I understand it BAI is basion-axis-interval. As far as I am aware the best way to measure this would be on plain x-rays of the sort we have had for fifty years - and specifically with a view taken with the head bent forward, which is when the BAI tends to increase.

The BAI is a measurement of bone positions and x-rays are more accurate for imaging bone than MRI or CT. The most accurate pictures come from x-ray tomography.

It would make sense to do an MRI these days to look at the way the bone relates to brain steam and spinal cord but that would be different from the BAI measurement itself. So an assessment for craniocervical mobility should include an MRI. I do not see why there should be any advantage in a standing MRI, although it is likely to be useful to have an MRI with the head bowed forward, which is not possible in a standard machine. From what research I have done the general agreement from government run centres is that standing MRI has no advantage but I have no personal experience of the practicalities.

I am not an expert on this imaging but my clinical understanding has always been that what matters is actual compression of the brain stem or cord - which you can see on MRI. A BAI figure does not necessarily mean anything as far as I know. I am not even sure why it is measured by the people who do.

To a large extent my feeling is that all this is largely irrelevant to clinical care. There would only be a reason to investigate and treat cervical hypermobility if there were neurological symptoms and signs specifically related to brain stem or cord compression. ME does not include such features and I would be surprised if they occurred in EDS except in a very few cases with Chiari malformations. Generalised pain and fatigue would not be in this category, nor PEM.

 

I might add that so far in all these discussions I have not yet seen an MRI image on someone with ME or EDS with actual brain stem or cord compression. Maybe such images exist but I have not seen them.

 

I have done a PubMed search on Ehlers Danlos and cord compression.

There are 5 papers in all.

1. Case report of cervical vertebral anomaly (not instability) in 16 yr old.

2. Case report of cervical vertebral anomaly (not instability) in 15 month old.

3. An Ontario Health Technology assessment that failed to find any literature indicating that standing MRI was of value.

4. A review of complications of connective tissue diseases. Abstract as follows makes no mention of neurological problems in EDS from instability.

Inherited disorders of connective tissue are single gene disorders affecting structure or function of the connective tissue. Neurological manifestations are classic and potentially severe complications of many such disorders. The most common neurological manifestations are cerebrovascular. Ischemic stroke is a classic complication of vascular Ehlers-Danlos syndrome (type IV), homocystinuria, and arterial tortuosity syndrome, and may occasionally be seen in Marfan syndrome and pseudoxanthoma elasticum with distinct underlying mechanisms for each disease. Vascular Ehlers-Danlos syndrome can also lead to cervical artery dissection (with or without ischemic stroke), carotid-cavernous fistula, intracranial dissections and aneurysms potentially causing subarachnoid or intracerebral hemorrhage, and arterial rupture. Other neurological manifestations include nerve root compression and intracranial hypotension due to dural ectasia in Marfan and Loeys-Dietz syndrome, spinal cord compression in osteogenesis imperfecta, and mucopolysaccharidosis type I and VI, carpal tunnel syndrome in mucopolysaccharidosis type I, II, and VI. Impaired mental development can be observed in homocystinuria, mucopolysaccharidosis type II, and the severe form of mucopolysaccharidosis type I. For the neurologist, being aware of these complications and of the diagnostic criteria for inherited connective tissue disorders is important since neurological complications can be the first manifestation of the disease and because caution may be warranted for the management of these patients.

5. A single case of EDS with Atlanto-axial dislocation (not CCI). The case did not fit any of the nine classes of EDS.

If this is the sum of reports of problems from CCI in hEDS over the last 50 years (i.e. nil reports) then it seems hard to argue that people with EDS are at risk of sudden death or neurological damage from CCI.

 

A PubMed search of EDS and brain stem returns no papers dealing with CCI.

 

A search of Ehlers Danlos and cervical (without compression) brings up the Brodbelt review and the Henderson review of Chiari cases. Nothing else of significance as far as I can see.

 

Thank you for your reply Dr. Edwards!

I will come back with a reply when I feel a bit better, hopefully in the next days.

To completely understand your stance please let me ask you the following:

1.)

Do you still believe that EDS has no connection whatsoever to what is known as ME/CFS? Meaning EDS has the same prevalance rate in HC and ME/CFS?

(you can chose criteria, it does not really matter)


2.)

Could you please define exactly what is PEM, and how it differs from fatigue (that has been triggered by exertion) in other diseases?

What is this PEM that so many seem to bet their horses on? And if you can not explain it to me in scientific terms and or studies to proof how it differs between ME/CFS and lets say primary mitochondrial disease why would you use it as an exclusion criteria for other diseases that might be causing the very symptom?

3.)

Would you say that POTS and other dysautonomia symptoms are part of what is known as ME/CFS?

Would you say that symptoms of dysautonomia are more prevalent in EDS and ME/CFS than in healthy control?

4.)

How would you define the set of symptoms that are related to brain stem and cord compression?

Would you not think that there is a difference between chronic compression (bone structure issues causing vertical instability i.e) and non chronic (in that it is non constant in nature) repetitive shear and tear that is caused by hypermobility of ligamentous structures?

5.)

Who are the experts that you are stating? Can you name them?

6.)

How would you diagnose a cervical instability that is caused by ligamentous instability if not by comparison of flexion and extension of the neck (the chance that this (being lax ligaments in the neck) is not happening to people is 0%)

Further, how would such knowledge be established (that there is cci and aai that can only be diagnosed with uNRI) if there are no ways (do you know the number of uMRI in the world) to test the hypotheses? What is the chance that diseases that have close to zero research (being ME/CFS and or/EDS) would be deemed necessary to look into when a decision is made whether or not uMRI is needed for the general population?

To take „there is no research“ as an argument in (a) disease(s) that are notouriously neglected seems not very wise at best.


Thank you.

 

I have every reason to think this is the case. The suggestions of an association look to me highly unreliable.

PEM involves a worsening of symptoms over a time frame that does not fit with simple exhaustion of energy supply at the time or even with the normal fatiguing that occurs after a period of hard exertion (having had enough of hiking by tea time). It is characteristically delayed (i.e. it hits the person later after a period of being OK) and prolonged - going on for days, weeks or more. There is no other illness where I have reason to think this occurs, with the possible exception of the fatigue associated with autoantibodies like Ro, where it is hard to be sure PEM is not a feature. In conditions like mitochondrial disease where we have some understanding of mechanism PEM would not be expected from the mechanism (and as far asI know does not occur).

People with ME have orthostatic intolerance but whether this is related to postural tachycardia or dysautonomia I am very uncertain.

I think that can be a misleading question. A lot of symptoms crop up in many conditions. The diagnostician makes use of combinations of symptoms and their patterns to make a diagnosis. So symptom overlap is everywhere, but that does not tell us much.

Weakness and numbness in the arms, stiffness in the legs and unsteadiness, sometimes problems with swallowing or facial sensation, problems with bladder control of a specific type. There are many but the combination of features should be reasonably easy to interpret.

I do not know what you mean by vertical instability - things do not move up and down where neck meets skull, only back and forth.

I don't think we are talking about shear and tear. If you actually tear the spinal cord you are likely to die immediately.

I agree that there are different situations though and these tend to be reflected in the symptoms. Intermittent compression can produce blackouts. Chronic compression produces gradually worsening numbness and weakness.

I think I have mentioned names where specific I have quoted specific points. Otherwise I am going on the basis of what I have read and heard at presentations and from colleagues I worked with over years.

As indicated in the review from Liverpool we are not interested in 'instability' so much as movement that is sufficient to cause compression. So a clear diagnosis is based on showing compression, not just movement. Excessive range of movement on x-ray or scan might make one suspect compression could be occurring and one might monitor clinical signs and scans. But the detail of how one would manage the case would be very dependent on all sorts of other factors including the underlying cause and I would decide in discussion with a neurosurgeon if necessary. I am no longer practicing so there is no particular neurosurgeon I am thinking of. I think both of us would be aware that the literature on benefit from surgery is very sparse and inconclusive so a sensible judgment would be made on each case hopefully.

That is simple. The neurosurgeons should have been doing organised prospective studies over the last forty odd years recruiting all their cases if possible to trials. That is what the oncologists have always done with their patients and that is why treatment of cancer has advanced so much. It requires a degree of humility on the part of surgeons to accept that they might not know best and also taking the time to do long term follow up.

It is not an 'argument'. It is, as you clearly agree, a fact. And if past experience is that a significant proportion of people receiving a treatment die on the operating table or within a week or suffer complications in the long term then it seems unwise to consider it for a condition that shows no signs of being likely to benefit, having no similarity in clinical picture.

 

Thank you for your answers, many of my questions do not seem to be answered, of course you do not have to answer them and I think maybe this exchange is the necessary seed for further discussions into this topic.

Things are not as clear cut as presented here mostly, nor are they as presented on the other side of the aisle of patients that believe cci is me/cfs.

All the best to everyone!

 

If a large number of cases of ME are caused by viruses then CCI can't be a cause. It could well be a secondary disease having ME does not make you immune to anything. For intance, many of us have type 2 diabetes which I believe I was more vulnerable to because of the ME but it is not caused by the ME, it is caused by a defect in my pancreas and it is treated and researched by diabetes specialists.

If someone is tragic enough to have ME and EDS with CCI then it is specialists in EDS and CCI who will have the answers.

Mixing them all up together won't help anyone, our ME doctors, what few there are, will not be qualified to help with CCI.

The worry within the community is that people are claiming the operation is a cure for ME. When my blood sugars are under control my ME feels better because ME makes us very sensitive to outside conditions, even things like temperature, but glycazides do not cure ME.

People with ME/CFS are held in such contempt that we fight to be taken seriously so anything that threatens to confirm we are the equivalent of antivaxxers and climate change deniers is a threat to us all and, more importantly, a threat to the things we really want to fight for such as energy production defects.

People with other diseases get an increase in their symptoms following over exertion but this is different from ME. We get fatigued and achy but we also get swollen glands, sore throats, all sorts of things which other people do not get. Cardiopulmonary testing (on a bike or treadmill) has been used in heart and lung disease for years but people have only been tested on one day as their results are the same the next even if they are low. When they did this with ME patients they could not match their first day results. Other physiologists found this so hard to accept they thought the machine must have been broken.

Dr Lily Chu has stated that the distinction between post exertional fatigue and post exertional malaise is not being made properly. Only ME/CFS patients have PEM.

My own belief is that we do not get POTS and dysautonomia exactly, not the way they exist as a primary disease. It has always been known that in ME there is a problem with homeostasis so we could be said to have symptoms similar to POTS and dysautonomia as a secondary result of ME.

 

If I understand correctly the argument being made is that a virus is causing me and cci by causing damage to the connective tissue.

My question with that argument is why the connective tissue in the rest of the body isn’t damaged?

I know there’s a lot of skepticism about hEDS, but I have that diagnosis and have problems both with joint dislocation and organ prolapses throughout my body (including severe visceroptosis).

 

I think the answer is that by and large virus infections do not cause structural damage to tissues, except sometimes epithelia like skin vesicles. I do not think there is evidence for viruses causing structural change to ligaments.

 

So just to clarify do you mean that virus would not or could not affect the connective tissue in the neck either ?

 

Speaking at the community symposium at Stanford today Ron Davis mentioned a possible cause of collagen degradation in me/cfs.

It went by too fast for me to keep up. I’m waiting for the video to be posted so I can watch it again.

I read somebody else’s notes on the talk which stated that there were two metabolites that were significantly different in severe MSCSF patients.

One of those was high hydroxyproline levels, which was what was noted as a possible cause of collagen degradation and cci.

Thoughts?

 

I believe that there is a rare syndrome reported in young children where pharyngitis appears to be followed by cervical instability problems. I know very little about it and I doubt anyone does much. Whether it is anything to do with viruses or not I do not know. The pharynx is very close to the craniocervical junction.

But apart from that I think it is reasonable to say that we have no evidence whatever to suggest that viruses might affect ligaments. It is the wrong sort of inflammation. Viral inflammation almost never produces the sort of phagocytic cell infiltrate and cytokine environment that leads to connective tissue destruction. I spent my doctoral years working on the pathology of inflammation. I think the idea that viral infection in adolescence or adulthood can lead to cervical ligament laxity is totally implausible. If such a thing was possible we would have clear documentation and museum specimens and accounts in textbooks. Nothing of that sort exists.

I think people are connecting bits of medical knowledge that have nothing to do with each other.