Trial Report Blood Flow To The Head Is Reduced in a Patient With Myalgic Encephalomyelitis With Confirmed Post-Exertional Malaise, 2024, Lee

It's always a valid point but there is no way around it. What's unethical is that people suffering from PEM get zero support, but research is not going to make progress without doing exertion challenges, PEM being the main problem.

I've long believed and said that the only way to truly solve this will involve research facilities with live-in patients long-term, so they can be monitored almost 24/7. I would volunteer for that in a heartbeat if it was truly made safe and comfortable, although the odds of that happening seem almost comical. Even though there technically are such facilities, but they're clinical, don't seem to do any research. Which is such a damn waste.

It would be expensive, but it's far more expensive to not do what's necessary and never make any progress.

 

I fully understand your position and, as I said earlier in the week, I Amy sometimes sound a bit hard hearted or abrupt about these things but my intention is just to ensure we are not fooling ourselves about anything. My criticisms are quite often shown to be off target but I don't have the energy to sift through everything to be absolutely sure in the way that some others do brilliantly.

 

Yes, I think it would have to wouldn't it? I haven't looked for any papers on this but will try find some to read. As you said earlier the important thing would be to measure as close to directly as possible blood flow in the brain itself. However many of those techniques (CT, PET, current MR) require the patient to be supine, so as far as I know only ultrasound (transcranial or four-vessel extracranial) can look with the patient sitting/standing.

Your other point about measuring jugular outflow (which must match inflow) is important too. I wonder whether there's more variation because of moment-moment jugular distensibility that might affect accuracy though.

As an aside, most people are quite asymmetric with jugular outflow - usually right-dominant. Absent carotid plaques etc I think carotid inflow is usually symmetric. I'll see if I can dig up anything useful later this morning.

 

Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study - PMC (nih.gov)

No idea of value or relevance of this. I link to it as Gingko enjoys some reputation for sarcoid fatigue. On the other hand active sarcoid cohorts have not shown 2day CPET worsening - though post granulomatous fatigued sarcoid might. No one tests them.

 

Proof of concept study is typically using low number of patients, use seed grants to fund the experiment and if the experiment is successful then the authors can apply for a larger grant to test their concept/experiment on a much larger number of patient and controls.

 

Yes, ethics can pose inconvenient dilemmas. Goodness knows as a human being I have made enough mistakes myself, which is why I conclude one has to make it a rule to face up to ethical issues and respond constructively rather than ignore them. To which end it helps to discuss and debate and listen to other peoples' opinions. So here is mine.

I once did a stint briefly employed in ethical vetting of sponsorship partners for a charity. It was salutory to learn what people working for companies can do following simple motivations, like a fiduciary responsibility for the pursuit of profit, if ethical oversight is absent.

Profit is not the only motivation which can lead to unethical behaviour, science can too. We see increasing instances where desire for personal career success distorts science and replaces truth with plausible fiction, also the use of scientific publications for influencing.

Considering knowledge as power, the desire in ME's case is for scientific revolution, for PWME to be recognised after decades of being treated as abjects. We should be very careful where that takes us, as ends justifying means arguments, regarding experimentation on PWME, risk backfiring and justifying the cruelty of the mistaken psychologists we decry.

Conversely both money and knowledge can help a lot if used wisely. The devil is in the detail.

Experimental investigation can be ethical if designers can be sufficiently inventive to get around ethical obstructions via experimental design, in vitro methods would be very helpful for this.

I agree it might be ethical to monitor PWME in their daily activity for example and study self induced occurrences of PEM and compare these with healthy controls. It might even be more informative.

To my mind exercise challenge for PWME is like asking a diabetic to do without insulin to see what happens, it just ain't right. We already know this and bravado doesn't help any. You end up with a scenario comparable to lining up "brave" servicemen in a nuclear detonation zone to see what effect it has, hindsight proves they shouldn't have done that but they did.

If we learn anything from that, it should be not to repeat the error of unethical treatment of human beings. If you know something is harmful, the ethical choice is not to deliberately inflict it on others, whether part of an experiment or not. Experimentalists ought to face and rise to that challenge IMHO.

 

Going from the usual outpatient "exercise challenge" approach to an inpatient model changes everything. Right now we are stuck at doing exercise challenges because it depends on borrowed time, patients are invited and will utilize equipment for 2-3 hours, then go back home, with all the additional load that this involves on them, and context-switching for the staff, who are always part-time, juggling between various projects, the equipment and rooms are also on a tight schedule, are utilized for other purposes.

There is no need to do exercise challenges to induce PEM, it often takes little exertion and it would actually allow to finally study it as a cumulative problem. There is also no need to go with the too-soft approach like Moreau's cuff. When you have inpatients who can do light exertion without everyone being pressed with time, the risk of going too hard on a single have-to-go-hard-enough test is much less significant.

Problem is that this means fully dedicated staff and facilities. Which already exist, there are several inpatient rehabilitation programs that do all of this except for actual science and an actionable goal, and only for a limited time. So it's quite doable, the problem is finding the budgets and authorization. This is exactly what the NIH intramural study should have done, and in fact partially did, but they botched too many aspects for it to work out. In part by being lead by someone who openly dismisses the very existence of the illness, among many problems.

That could all have been done over 5 decades ago, and in a continuous process since. We could have so much data, and instead we basically have nothing. Compared to the trillions this illness has cost since, it's a tiny blip.

 

Some of the questions raised in this thread are addressed in this video from the company:

https://www.youtube.com/watch?v=1pHiJRR0yFM

Sorry, it is a long video, and it was my daughter who watched it, so I can’t provide time stamps for every point.

The bit about the external carotid artery is at 17 minutes in.

The segments from Dr Amanda Miller address comparison to TCD and some other scientific points.

The segments from Shivani Ugrin are patient experiences.

A proper comparison study with TCD is in the pipeline, by the sound of it.