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

Here's a link to the first film in the series:
The role of CCI, Chiari and Tethered Cord in Long Covid | With Dr Jen Curtin
This is the blurb about it on YouTube:

I'll watch it and post my notes in my next post.

 

First film:

Gez introduces it by referring to Dr Curtin as an expert in 'ME/CFS and associated structural disorders'. He then introduces the film as providing information on these disorders 'How common are they in ME/CFS and does the same apply to Long Covid? And just how might a Covid infection bring on conditions like these?'

First introducing the doctor - she's an internal medicine physician. Had ME/CFS herself - says part of her reason for doing medicine was trying to figure out what was wrong with her. Figured out her own problems were POTS and hypermobility. Started treating patients with complex chronic medical conditions like ME/CFS and then started having Long Covid patients coming to her and saw some similarities.
Co-founded a tele health company to try to help deal with diagnositic delay.

Question: Asks for indication of how common anatomical problems are in diseases like ME/CFS and LC.

She replies by quoting from memory 'a paper' that showed over 50%. She misremembers it as from the karolinska institute, but I think she's probably referring to the highly problematic Bragee paper discussed here. She says she has seen it in 'quite a few patients'. She concludes with 'I don't think we have numbers yet for LC'

4 minutes:
Question: Can you describe the differences between some of the structural issues and what the primary ones are you see in your practice?

She then goes into an attempt at a lay description of Chiari using confusing diagrams and analogies to try to explain cerebrospinal fluid. She gives scary sounding simplistic explanations of intracranial pressure and what might cause it

5.30 min. On to craniosacral instability. She shows a scan image and tries to expain why the diagnosis from it. Uses scary descriptions demonstrating with her hands 'the brain stem is smashed into the skull and kinked over it'.

6.33min. On to tethered cord. She says there are lots of other structural problems but these are 'the big 3 that I tend to see'. She attempts a lay description of tethered cord using a diagram of the lower spine. She says this can cause not being able to walk and some neurological signs 'some quite subtle'. You need a physician to diagnose them.

Question: In ME/CFS, of these 3 which is most common, and does it look like the same pattern you're seeing with Long Covid patients?

8.40 min. Can't tell in LC yet. 'It takes a while to do the work up process'.
In her patients with Chiari or CCI, 'tend to see tethered cord as well'. Probably more CCI than Chiari, some have all 3.

Question: if someone has a bit of Chiari or a bit of CCI, and has mild symptoms, then they catch Covid, and the develop Long Covid, and now it becomes a problem. And even the same thing for virally or bacterially triggered ME/CFS, do we know, are there any decent theories about what physically changes there with that infection that suddenly creates a problem that wasn't there before. Apart from, as you say, deconditioning from lying down, is there something to do with inflammation or with the way the body fights infection that can lead to these conditions getting worse. Or, I don't know if there's been much talk about this...

Answer:
Short version: She throws out lots of theories, mostly posed as questions, and concludes there are lots of possible explanations, but none established.

Long version:
There is theory around this, but none of it is confirmed yet. Some surgeons are taking a small piece of ligaments when they do surgery to 'do pathology on it', 'to look at it under a microscope to try to figure out what looks different and why. Looking at ? mast cells in and around the ligament becoming activated and releasing compounds that actually degrade collagen - is that may be part of what's going on? Is it actually translocation of 'bad bacteria from the throat', the other thing is that ligaments don't actually have the greatest blood flow, so is the blood flow to the area somehow compromised so the ligament can't repair itself so it becomes weaker and thinner. The other possiblity is that Grisel syndrome ? infection in the back of the throat is transmitted back and the veins that drain that area ' there have been accounts of infections draining back and established in the bones'. 'If there's not something we can detect it doesn't mean it's not happening.
Also you can imagine there's lots of cytokines and inflammatory molecules, you know, enzymes released from mast cells at the back of the throat, all kinds of things that would also be transmitted back to those veins, the impact of those on the ligaments at the back.
She then goes on to speculate wildly that because Covid is detected in the throat, the stuff she's speculating about could happen in Covid too. So for her the next challenge it 'getting that data'.

 

So my summary of what all this boils down to:

There are a few people like doctor Curtin (who is not a neurologist or spinal surgeon), speculating about a connection between ME/CFS, and now also Long Covid, and spinal problems, and attracting patients as a result.

The only data on prevalence is the problematic Bragee paper we have discussed elsewhere, and she didn't even bother to check it and quote it accurately.

Her only other 'evidence' is her own clinic, which I gather hasn't been running for long, and has presumably picked up some of the patients alerted to the spinal ideas via some individuals with ME/CFS and some with hypermobility who have picked up and run with this, so she is seeing a very skewed sample.

The only explanations she has for speculation of a connection between infections triggering post infection syndromes and structural issues are highly speculative.

She gave no information on outcomes for her patients or for any other pwME who have had any spinal surgery.

So it's all speculation. And I think highly irresponsible, given the reach Gez has with his videos.

 

I haven't yet been able to catch up on the 75 pages of posts in this thread (!), as well as the related threads. Obviously a contentious area with little evidence, and as noted we're talking fairly major and life-committed surgery with risks and likely very limited benefit to a patient group as a whole.

Despite poor evidence, I try to keep an open mind and recognise that our knowledge is growing, including for things we thought we understood pretty well over a long time. If there were to be a link with impaired CSF flow, perhaps that might be in the form of a last straw on top of an immunological pathology, that tips the patient out of homeostatic recoverability; where conceivably its correction could allow return back to the physiologically happy zone (or at least its subclinical, essentially symptom-free part). But that's just conjecture. There are lots of people with impaired CSF physiology for many reasons and they don't appear to have the cardinal symptoms of ME/CFS.

As far as ME is concerned, I would prefer to see research focus (and funding) on the presumed foundational immuno-metabolic pathology, rather than any potentially contributory mechanical aspect.

But, I've recently posted a few papers on some of the newer thinking around CSF physiology generally, as well as new findings and identified knowledge gaps regarding the spinal cord and canal in particular. So, posting in this thread for reference —

A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases (2022)
Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases (2021)
Spinal CSF flow in response to forced thoracic and abdominal respiration (2019)

 

The problem is not close mindedness on the part of critics, and never has been. The problem is the lack of good evidence about the reality and relevance of the diagnosis, and the efficacy and safety of the potentially very risky and dangerous proposed treatments, combined with the almost evangelical attitude of some of its advocates.

And that is a huge problem.

You can mess with a lot of the body's systems and structures without running too much risk of serious long term damage. But the central nervous system and related structures are certainly not among them. It is very easy to get that very wrong, and leave the patient in very very deep shit, with no way out.

Advocating for good quality research into this possibility is okay. Advocating for clinical application, at this stage, is not okay.

There are very good reasons why medicine should be conservative on this kind of stuff. Those lessons have been hard earned over the centuries. Safety rules are written in blood and destroyed lives.

 

Circulating miRNAs as diagnostic biomarkers for adolescent idiopathic scoliosis (2018, Nature Scientific Reports)

 

For those of us getting confused by all the 'm's' in front of RNA and DNA:

messenger RNA (mRNA) - a single strand of RNA. Gene > transcript of the gene is the mRNA > the mRNA is read by a ribosome to make a protein
(transfer RNA (tRNA) bring the Amino acids to make the proteins)

microRNA (miRNA) - as in the post above - are involved in gene silencing. They are little snippets of RNA that attach on to messenger RNA; they stop the messenger RNA being read, and lead to the messenger RNA breaking down.
Wikipedia has a nice diagram that helps to visualise at least part of what is going on.
There's also small interfering RNA's (siRNA) which, as far as I can see do much the same thing, but differently.

mDNA or mtDNA is mitochondrial DNA.



miRNA's are potentially important as biomarkers of disease; there's at least a few thousand of them coded in the human genome and they are thought to target around 60% of the human genes They are present in cells and as extracellular circulating miRNAs.
The first human disease associated with deregulation of miRNAs was chronic lymphocytic leukemia.

Aside from the fact that the code for the miRNA's is often on bits of the gene that might not have been paid much attention (introns and exons), the DNA code doesn't necessarily produce a consistent product. So, that's a reason why a GWAS won't tell us everything.

 

I just started having a look at later cited-bys and a 2022 paper made reference to finding a decrease in miR-30e in a 2019 paper. That paper is Incidence of scoliosis among junior high school students in Zhongshan city, Guangdong and the possible importance of decreased miR-30e expression (2019). Not prospective but reasonably large numbers showing a significant difference.

This caught my eye as the Prusty 2022 Nature paper identifies the mechanism of herpesvirus-induced down-regulation of the miR-30 family, so while we wait for his ME biomarker announcement, I have been wondering about some of the potential overlap disorders. (I've noticed in my practice a seemingly increasingly busy "EDS pathway" needing bone age x-rays for evaluation of adolescent eating disorders, that seems to have more than its share of scoliosis, so was wondering about possible links beyond simply an association with low BMI, hormonal imbalance etc.)

---
The team that published the paper on AIS in comment #1491 also published Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies (2022, Orphanet Journal of Rare Diseases). I'll cross-post in the relevant thread.

 

Fatigue is a common symptom seen in adolescent idiopathic scoliosis. It's usually attributed to "the body having to work harder to compensate for the abnormal biomechanics." I think that's simplistic, similar to a cardiologist looking at a POTS patient and saying "yes you'll feel tired because your heart is beating faster and working harder."

Hence the field of chiropractics, which gives you —

What else is seen in scoliosis? Breathing disturbance. Sleep disturbance. Again, attributed to the scoliosis and abnormal mechanics, chest wall deformity. No doubt a factor once a significant curve has developed, but what about in early scoliosis? See trial reg: Idiopathic Scoliosis Progression and Sleep-disordered Breathing in Children

There are unanswered aspects in relation to pain too, see eg review Back pain in adolescent idiopathic scoliosis: A comprehensive review (2023) although caution, the review of articles leads to inclusion of some of our favourite words: "biopsychosocial factors" and "catastrophizing".

 

So do I! Except I had no noticeable effects and didn't realise until my mid 20s. I had a pre-employment TB chest x-ray before starting as a house officer that showed an incidental trivial thoracic curve. At the same time I bought some new trousers ready to look tidy on the ward. I must have skimped on costs, as when they did the measurements to adjust the legs, they only pinned one side (the short one as it turned out). On arrival my new trousers had the other leg way too short. Hilarious - but the penny dropped.

But yes, in regard to your question on whether this is a) at all sensible b) relevant to pwME: absolutely, I am being highly speculative in referencing these papers. Certainly not about to put out a hypothesis paper!, but I thought it was of potential interest for this thread on possible connections between spine and ME/CFS. At 75 pages already, and it being contentious enough with CCI and tethered cord etc, perhaps I should leave this thread alone