There are inconsistent reports of significant improvement following a Stellate Ganglion nerve block - would that fit with what you are saying here?
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Preprint A Proposed Mechanism for ME/CFS Invoking Macrophage Fc-gamma-RI and Interferon Gamma, 2025, Edwards, Cambridge and Cliff
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There are inconsistent reports of significant improvement following a Stellate Ganglion nerve block - would that fit with what you are saying here?
Is this last part true? I mean in real terms of course it is, and maybe my mind has been warped by the slow pace of medical research, but surely existing drugs could go straight to a phase 3 trial if we gain from DecodeME etc evidence that they are likely to work? And if that were to happen it could be a case of a few years if it did turn out to work.
Of course there would probably be a pilot study first, but if pharma get involved and see dollar signs who knows what they're likely to do.
You might even end up with a large platform trial with several candidates...
Jonathan Edwards
Senior Member (Voting Rights)
I don't have much faith in the significance of those reports. They mostly come from practitioners who make a living from such treatments and I cannot see how that approach would make much sense in any model - other than as a very frightening experience causing a massive cortisol surge maybe.
Kitty
Senior Member (Voting Rights)
I guess if there is a drug already that will help, there's no reason for a 10-year wait. Small proof of concept studies could be followed by a much bigger trial if the results are good enough.
If there isn't a drug, hopefully there's enough potential profit out there for a pharmaceutical company to be interested. Even more so if it appears new immune mechanisms have been shown that could have implications for other diseases.
Jonathan Edwards
Senior Member (Voting Rights)
I have been reading through the paper again and got to about page five. I think some wording could be tightened up but the one thing that hit me as maybe out of place was the term 'neuro-immune hypervigilance' in the summary.
This term arose from wider discussion of 'immune hypervigilance states' towards the end of the paper, which I think are valid but re-reading made me wonder two things. One is that this might not fit into a brief summary and the other is that the term is problematic, partly in style and partly in implications.
My main worries are that it is not plain English and also teleologic (it implies a purpose, which I always think is bad)(and no, teleologic isn't plain English either), but I can see that it can also lead to misinterpretation later on. I am thinking that 'Neuro-immune' is OK here because this is an adjective to describe something involving neural and immune signalling. I wouldn't want to talk of a neuroimmune disease but that is a bit different. Hyper is Greek or something and sniffs of jargon. Vigilance is too loaded.
I wonder whether 'Neuro-immune over-responsiveness' would do better. It could be over-signalling but that is not easy to parse. It could be over-sensitivity or over-sensitisation but that isn't good to me. I would need to check with the other authors but they might agree. Some of the later discussion could be changed in line but I think the 'vigilance' metaphor may be helpful in one or two places to indicate that this is an error in a system seen as having 'adaptive function'. In general though, we are talking about over-responsiveness I think.
What do people think?
This term arose from wider discussion of 'immune hypervigilance states' towards the end of the paper, which I think are valid but re-reading made me wonder two things. One is that this might not fit into a brief summary and the other is that the term is problematic, partly in style and partly in implications.
My main worries are that it is not plain English and also teleologic (it implies a purpose, which I always think is bad)(and no, teleologic isn't plain English either), but I can see that it can also lead to misinterpretation later on. I am thinking that 'Neuro-immune' is OK here because this is an adjective to describe something involving neural and immune signalling. I wouldn't want to talk of a neuroimmune disease but that is a bit different. Hyper is Greek or something and sniffs of jargon. Vigilance is too loaded.
I wonder whether 'Neuro-immune over-responsiveness' would do better. It could be over-signalling but that is not easy to parse. It could be over-sensitivity or over-sensitisation but that isn't good to me. I would need to check with the other authors but they might agree. Some of the later discussion could be changed in line but I think the 'vigilance' metaphor may be helpful in one or two places to indicate that this is an error in a system seen as having 'adaptive function'. In general though, we are talking about over-responsiveness I think.
What do people think?
Sasha
Senior Member (Voting Rights)
As I posted some time back:
I'd try this now but I'm much older and would be scared about having a heart attack, plus I'm too feeble to get out of a bath now...Back in the 90s (?), after years in bed and having to have my food cut up for me, I had a spectacular improvement after several weeks of a cold-water therapy that consisted of immersing yourself in an increasingly cold bath for longer and longer. I'd read about it in the Daily Mail- a Professor Kakkar (this guy, I think) had published a protocol for readers with ME to follow and IIRC was claiming to have got results and was promising a clinical trial (which never appeared, AFAIK).
Jonathan Edwards
Senior Member (Voting Rights)
Yes, I think that was what triggered my example!
Peter T
Senior Member (Voting Rights)
In this context are you talking about a reduced threshold for triggering a response or an increased magnitude of responses or both?
Is there a less emotive term to describe the mechanism(s) rather than ‘hypervigilance’ which is open to wilful misinterpretation? As with Dawkins phrase the ‘selfish gene’, when people can misinterpret a phrase to mean some form of conscious agency, many will.
Sasha
Senior Member (Voting Rights)
It was a real shame that Prof. Kakkar never did the clinical trial he promised. We hear of PwME doing cryotherapy, with anecdotal success IIRC. Do we have trials of cryotherapy?
Is there anything similar we could do without the heart-attack risk for those of us now knocking on a bit?
We have several threads about a Polish group testing this, including this latest one:
Effects of whole-body cryotherapy and static stretching are maintained 4 weeks after treatment in most patients with CFS 2023 Kujawski et al
I tried the cold baths treatment many years ago and had no effect, though I didn't follow the protocol exactly. I recall thinking it had helped, doing more and crashing.
I agree hyper-vigilance is problematic and can be misused by others. Those interested in brain retraining may choose to assume that the vigilance refers to thoughts, not biological processes, and is something that can be influenced by changing thinking.
Over-responsiveness of neuro-immune signalling?
Is the signalling two separate sorts, one neurological and one immune, or do you mean signalling between nerves and the immune system and vice versa? I find the term neuro-immune confusing, but that may just be my ignorance about how they work together.
Kitty
Senior Member (Voting Rights)
If it's just for that first instance, 'immune and neural over-responsiveness'?
Many options are going to equate to "central sensitisation". Maybe consider de-emphasising the over/hyper-responsiveness aspect and keep it more general, as in "neuro-immune dysregulation".
(Edit: fix tautology)
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From my layperson perspective (and basic level of understanding) I prefer ‘Neuro-immune over-responsiveness’ for the additional reason that it could imply both an inappropriate signal AND the generation of PEM symptoms for which there is no actual justification (no infection).
Utsikt
Senior Member (Voting Rights)
As a non-native speaker, I take «vigilance» to mean being more alert or more on the look out for something. So it’s about what happens before something has been detected. «Responsiveness» is more about what happens after something has been detected.
Although I can see on google that responsiveness means different things in different fields. So it might be useful to include a definition in the paper.
Hoopoe
Senior Member (Voting Rights)
Re. eicosanoids and pain without inflammation.
I remember that when the illness began as adolescent, one noticable change was less tolerance of certain foods like pizza. Eating too much fatty meat or dairy products in particular seemed to cause reactions. Typically I would feel unwell in the digestive period, and in the following days it seemed to affect my sleep and sometimes cause visible reactions on the skin in the form of acne. These were subtle changes but I remember that there was a clearly a change in my tolerance of foods, with a subsequent change in eating habits.
I don't remember any significant pain early on in my illness. There was however another noticable change, that walking for an hour would cause muscle pain that seemed out of proportion to the intensity and duration of the activity (but not in a way that was concerning). I understand that muscle pain is normal after intense and/or long activity or unaccustomed activity, but this muscle pain was the result of ordinary daily activities I did nearly every day and it seemed a bit odd.
I remember that when the illness began as adolescent, one noticable change was less tolerance of certain foods like pizza. Eating too much fatty meat or dairy products in particular seemed to cause reactions. Typically I would feel unwell in the digestive period, and in the following days it seemed to affect my sleep and sometimes cause visible reactions on the skin in the form of acne. These were subtle changes but I remember that there was a clearly a change in my tolerance of foods, with a subsequent change in eating habits.
I don't remember any significant pain early on in my illness. There was however another noticable change, that walking for an hour would cause muscle pain that seemed out of proportion to the intensity and duration of the activity (but not in a way that was concerning). I understand that muscle pain is normal after intense and/or long activity or unaccustomed activity, but this muscle pain was the result of ordinary daily activities I did nearly every day and it seemed a bit odd.
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Jonathan Edwards
Senior Member (Voting Rights)
It's annoying that immuno-neural would make more sense than Neuro-immune but it sounds daft.
I am struggling to find a better term but my sense is that over-responsiveness may at least be better than hypervigilance?
Maybe an option would be 'immune over-responsiveness, targeting the nervous system and mediated...'
hotblack
Senior Member (Voting Rights)
For me it’s been absolutely fine with flu but terrible with the covid ones. So I assumed it’s more complex and related to specifics of antigen rather than just severity or anything which stimulates immune activity.
But there’s also a question of systemic versus localised. Does the antigen need to get to the right place in the body? Get to wherever these localised interactions are happening to have an impact? Maybe in those cases a systemic reaction to a vaccine is more likely to trigger than a response more localised to say virus in your nose? And maybe nasal vaccines will help here?
hotblack
Senior Member (Voting Rights)
Treatment, an area I’ve avoided thinking too much about, but since the paper mentions it…. it looks like what we’d be hoping to do here is find something to stop the feedback loop? We’d then be back to our pre illness state (yey) but still presumably have a potential susceptibility for future triggering events?
Intravenous immunoglobulin therapy is mentioned as being expensive but if it helped, even at a couple of grand a go, it would be cheaper than say care costs which can easily be that or more per month. So seems maybe worth investigating while other avenues are being looked at.
Talk of anti CD52 is interesting too, I know some people who’ve had Alemtuzumab for MS talk of various short term impacts, some not insignificant, but it seems to help reduce deterioration longer term. It could be worth understanding how people with ME/CFS, especially those already struggling, can tolerate these sort of drugs and short term side effects if there are gains to be had.
Intravenous immunoglobulin therapy is mentioned as being expensive but if it helped, even at a couple of grand a go, it would be cheaper than say care costs which can easily be that or more per month. So seems maybe worth investigating while other avenues are being looked at.
Talk of anti CD52 is interesting too, I know some people who’ve had Alemtuzumab for MS talk of various short term impacts, some not insignificant, but it seems to help reduce deterioration longer term. It could be worth understanding how people with ME/CFS, especially those already struggling, can tolerate these sort of drugs and short term side effects if there are gains to be had.