Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome, Norcliffe-Kaufmann et al, 2022

Other questions I have on this paper —

1. Authors make little acknowledgement of the anticipatory tachycardia seen in HCs. That HC tachycardia could be to the same level as pats. And that some pats had an anticipatory bradycardia.
2. No discussion of lack of hyperventilation in the supine anticipatory phase.
3. No mention that I could see of the time course of end-tidal CO2 and reduced MCA velocity. Their conjecture is that fear -> hyperventilation -> dec. CO2 -> cerebral vasoconstriction -> inc. cerebral vascular resistance -> dec. cerebral blood flow. If the drop in MCA velocity occurs immediately on standing rather than following the slower onset of respiratory alkalosis - that knocks down their theory.

 

It seems to me that most anybody in that situation would be wondering over the 30 seconds if something had gone wrong with the mechanism, am I about to be jerked upright to catch up because it's supposed to be immediate? etc etc.

 

Isit possible to experience fear without being afraid? There seems to be far too much reification in these "studies".

 

They measured MCA velocity at 10 minutes. I expect cerebral blood flow actually drops on orthostatic challenge in association with decreased cardiac output and that this occurs quickly. But, I can't find information about expected timeline for MCA velocity drop in experimentally hyperventilating normals or in patient evaluations (eg. van Campen/Visser/Rowe).

However, as a first approximation to cerebral blood flow, last year I recorded my frontal lobe SpO2 dropping by 10% within 10-20 seconds of standing — to the surprise and lack of delight of my intensivist colleague. I think we both would have noticed if I was hyperventilating sufficient to blow off the required amount of CO2 to achieve that...

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Hyperventilation is used in neuro-ICU to try and reduce cerebral blood flow and thereby intracranial pressure. See Hyperventilation in Adult TBI Patients: How to Approach It? (2021). Also pCO2 and pH regulation of cerebral blood flow (2012) is probably worth referencing for this part of the discussion. The overview for respiratory alkalosis is here.

 

This idea was quite popular in the 1980s/1990s in the UK. There were some studies showing hyperventilation on exercise challenge or tilt table but ultimately it did not pan out and even BPSers don’t really talk about it these days.

 

One of my favorite "Far Side" cartoons. I will avoid the obvious joke about research going to the dogs. (Ooops!)

 

We already know that isn't true (hyperventilation is not the cause of the cerebral vasoconstriction). But I think the hypothesis is the fear leads to sympathetic activation that leads to increased cerebral vasoconstriction in parallel with the hyperventilation.

But in POTS the increased vasoconstriction is a central/body-wide symathetic response to increased venous blood pooling. Their study is meaningless unless they measure the kinetics of this pooling.

 

Is it just me or has this been an experiment in taking 2 unrelated things and putting them in the same sentence, or on this occasion experiment, in the hope that some people will fall for the fallacy that means the two are connected?

I just can't understand the ethics of how they got POTS patients onto a tilt test that is known to make them really ill and be very challenging to even get through (ends with passing out) if they did not hide the reason for this being to do this. It clearly offers no medical benefit to those with POTS so there must have been industrial-sized lies as far as I would believe ethics goes.

They could easily have done such an experiment without the actually setting off the table part - because neither design would mean anything. It has no connection to POTS and the next part whatsoever from what I can see. They maybe had some call for those who didn't have POTS ie HCs to put them on the table and set it off in order to check they weren't in the group and show that in normal people scaring them vs tilting them has a x proportionate effect but I don't get the point..

But for this design, with POTS patients... it's just comparing those who knew what was coming, are objectively made more ill by it, and had been through the same thing before where there was no pause would be more puzzled by it - as they knew that delay was abnormal - than those to whom a tilt test was novel. And to be fair they might at that point, some of them, realised they'd been tricked into something they would never have signed up to and now strapped in to something that will damage their health to no good avail.

Why doesn't someone report that? This is just into the realms of someone signing off toying with subjects for the sake of it. Given there would surely be room for 'other ways of obtaining this information' to be achieved how on earth did someone sign this off?

Or am I missing something

 

Nope. Biopsychosocial is not serious, a return to old style pre-science medicine where someone tries a bunch of stuff and says "good enough for me", explicitly set out with a conclusion to prove and do the rest around it.

It turns out that trying to solve a problem without bothering to understand it leads to very silly and incompetent nonsense. Who knew?!

 

Indeed.

What is strange is that someone with responsibility for ethics and patient safety - and with that the risks being 'worthwhile' is signing these things off.

I find it impossible to see how this was sold to anyone from an ethics perspective as justifiable, and who on earth as a POTS patient would voluntarily put themselves on a tilt table without having been led to believe there was some serious medical help/progress/good to come from it. Only bad answers come to my mind for that second one

What does: (31 ± 12 years old, 25 women) mean in the POTS sample? what is the + above the - and what does it mean in relation to the 12 years old after it?

 

Average age is 31, range is 19 to 43 (i.e. 31+12yrs and 31-12yrs). 28 POTS patients, 25 female, 3 male.

 

ha! thank you, I'll blame cognitive fatigue - I just couldn't put the bits together for some reason

 

Wouldn't that actually be average is 31 and standard deviation is 12? It would be rare in a distribution for the difference between minimum and average and between average and maximum to be the same.

 

Yes I think you're right, that makes more sense. It's an odd way of writing it that I haven't seen before. I had presumed they did not have patients under the age of 19. Now I look back, I see they've used the "±" in all their tabulated data too, so yes: it must be mean / standard deviation. Thanks for clarifying.

 

Trial By Error: Brain Publishes Letter About Flawed Study from NYU on ‘Psychogenic POTS’

https://www.virology.ws/2022/09/24/...ut-flawed-study-from-nyu-on-psychogenic-pots/

 

Link to another letter about the study to the journal, Lambrechts and Jacobs, claims to be open access but seems to be paywalled, https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awac346/6713528

Link to reply from the authors, claims to be open access but also seems to be paywalled, https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awac349/6713532