The buspirone challenge test clearly distinguishes ME/CFS patients from healthy controls: why is it not being developed and deployed?

[SugarSquared]

But mainly we need curious, capable researchers to run new studies.

That is proving to be the most difficult part. I really hope we can get someone soon, like the end of this year. I literally asked my dentist today if he knew someone doing medical research. (Unfortunately no.) I’m not giving up until we get someone.

 

[forestglip]

I literally asked my dentist today if he knew someone doing medical research.

That's amazing.

I emailed around ten ME/CFS researchers about this a month ago. I don't want to name the person, but only one responded to say that the study would require funds which they don't have.

 

[wigglethemouse]

I'm as frustrated and have as much urgency as you. I'm using the very limited bits of energy I have trying to figure this out by reading prolactin response papers and learning basic neuroscience. But mainly we need curious, capable researchers to run new studies.

I really appreciate and admire the effort you have put into this to consolidate the research findings and move those forward.

What I didn't mention before and what doesn't come across in this thread it that it is a challenge test in that you have to give the patient a drug they may react very badly too. There is a risk with a challenge test that could affect a small minority of patients badly, perhaps long term.

 

[wigglethemouse]

I emailed around ten ME/CFS researchers about this a month ago. I don't want to name the person, but only one responded to say that the study would require funds which they don't have.

Thank you for trying. I'm hearing the same thing that there are promising leads to follow up on but they need funding.

The other problem I hear from researchers is they need to work with doctors to get access to patients and then to follow up with those doctors about their patients. Without a specialist medical entity for ME/CFS it's a real road block.

A BCT test is a challenge test and requires a doctor to be on hand to monitor the patient from an IRB perspective when a researcher runs the test. In the US it is also a $$$ problem as adding clinical help greatly adds to cost of the research study and many doctors don't want the liability as they are not ME/CFS specialist doctors, a specialty that doesn't really exist except in a handful of places. ME/CFS needs a specialty home.

 

[Jonathan Edwards]

And yes, some researchers have been pondering this test for years. Don't just think s4me are the only ones that have noticed this test. Much happens behind closed doors that we never hear about.

I don't get this. What is the point of pondering a test if you do noting about it? People pondering behind closed doors is of no use to the science community, and no use to people with ME/CFS.

"what's the point testing when we know they have ME/CFS anyway" was the feedback I heard.

And if that is the extent of pondering they seem to have missed the point. We don't "know they have ME/CFS" in any useful biological sense if we don't have any account of this ME/CFS.

Sorry, but who are these great ponderers? Why do we hear nothing from them? Are they more interested in cultivating their academic reputations than contributing to useful knowledge?

Chris Ponting's group's most recent data show that you cannot assume that you will get the same biological results from two different 'ME/CFS' cohorts. There are huge issues of bias in subject selection and at present we cannot be sure of diagnostic ascertainment to within a factor of about 5. So we don't actually know "they have ME/CFS" at all.

 

[Chandelier]

I saw a paper yesterday that seemed worth looking at with a similar finding: Brainstem perfusion is impaired in chronic fatigue syndrome (Costa et al. 1995) [Edit: That paper shares an author with this one.]

From Bluesky by Lucibee:

One of the interesting things about this documentary, that I hadn't noticed before, is that she talks to Dr Durval Costa, who was doing a SPECT study in patients with ME/CFS.

So I did a bit of searching to see if I could find out whether the study had been published...

Lucibee@lucibee.bsky.social
The full documentary is available here: www.youtube.com/watch?v=lINk...

Dr Anne MacIntyre's Frontline programme about ME/CFS. It actually aired in July 1993.

I also found a transcript here: www.blogistan.co.uk/blog/article...

Dr. Ann McIntire's Frontline Program about ME/CFS (Vintage VHS)​

YouTube video by hoofbags

www.youtube.com/watch?v=lINkStCj3rs


And it was - in 1995 in QJM: pubmed.ncbi.nlm.nih.gov/8542261/

But why was it seemingly overlooked at the time?
The authors seemed fairly convinced that they had found a useable "biomarker" (brain perfusion dysfunction) for identifying ME/CFS, but few seem to have followed it up.

Brainstem perfusion is impaired in chronic fatigue syndrome - PubMed​

We looked for brain perfusion abnormalities in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An initial pilot study revealed widespread reduction of regional brain perfusi...

pubmed.ncbi.nlm.nih.gov/8542261/


This study has an interesting history. Not least because it seems to have been caught up in one of the mega correspondence spats in medical journals that I have been following over the past few years.
I also realise that I've seen reference to this study before, and by Costa et al. themselves.



The early results from Costa's study were actually published in a letter in BMJ in 1992. pmc.ncbi.nlm.nih.gov/articles/PMC...

It was then dismissed by Tony Delamothe in his "Look at ME" review (March 1994 - www.bmj.com/content/308/...) because it was only a letter.

Postviral fatigue syndrome​

pmc.ncbi.nlm.nih.gov/articles/PMC1882397/


The reason Costa published it as a letter, in response to another study by Behan's group, was because they were early results of a pilot study, and they intended to publish the full study once it was complete, as they explain here: pubmed.ncbi.nlm.nih.gov/8205029/

But the damage was done.

Chronic fatigue syndrome. Preliminary report misrepresented - PubMed​

Chronic fatigue syndrome. Preliminary report misrepresented

pubmed.ncbi.nlm.nih.gov/8205029/


This BMJ issue (19 March 1994) was a particularly contentious one as it also included a nasty editorial by Lawrie & Pelosi, and 2 epi studies by the psych brigade - Pawlikowska et al. (Wessely) prevalence study (which I've discussed elsewhere as it contains a nasty flaw), and Wilson et al.'s study.



My blogs about Pawlikowska are here: lucibee.wordpress.com/2023/08/08/i...

and here: lucibee.wordpress.com/2023/08/08/p...

Is science self-correcting? How flawed stats and false assumptions plague the medical literature​

“Read the evidence!” we are told, when we question long-held views. However, the historic structure of scientific literature often makes it very difficult to track the evolution of evidence through…

lucibee.wordpress.com/2023/08/08/is-science-self-correcting-how-flawed-stats-and-false-assumptions-plague-the-medical-literature/


For how many decades will this finding now be ignored in Long Covid too, I wonder...?

The BPS machine is already talking this one down, I see.

Brain blood flow linked to fatigue after COVID-19

Fatigue is one of the most common and disabling symptoms of post-COVID-19 condition (PCC), often referred to as long COVID. Although the condition has been studied extensively since the pandemic, the biological mechanisms behind persistent symptoms are still not fully understood.

medicalxpress.com

 

[V.R.T.]

From Bluesky by Lucibee:

So that's three possible leads abandoned on the table - buspirone, the drg autopsy findings and this. It's enough to make you weep.

 

[Andy]

Why do we need yet another buspirone challenge test and waste yet more years with no treatment, no closer to understanding the illness. Have some urgency.

To understand the illness.

I strongly urge researchers and others to look into the pathology and how those results observed could happen. Lets not waste yet more years of our lives repeating research that is already very clear. Lets dig into the why.

Very clear how? This whole thread is about wanting to explore the why, which isn't very clear.

 

[Jonathan Edwards]

I would not put too much weight on the study on brainstem perfusion. I was working alongside Durval Campos-Costa in the 1990s. We shared a project on radioactive Samarium treatment. At the time the observation seemed interesting but it was not clear how reproducible it would prove. The SPECT technology was relatively new then. Durval moved on,I think to Lisbon, and has been working on radiolabel imaging ever since.

And I think a finding of reduced blood flow on a single test without time course is hard to build much of a story out of that would explain clinical features of ME/CFS. It might relate to OI, but I am not sure wha else.

We have analysed this study in the past.

 

[justlxsa]

At the Amsterdam PAIS Conference a person announced they would probably have a diagnostic marker for ME/CFS in a year and have been working on it for a time- but I don’t know more than that. The person who I heard this from was very secretive so it seemed pretty secret still.

 

[V.R.T.]

At the Amsterdam PAIS Conference a person announced they would probably have a diagnostic marker for ME/CFS in a year and have been working on it for a time- but I don’t know more than that. The person who I heard this from was very secretive so it seemed pretty secret still.

Was this to you personally in conversation or in a talk?

 

[justlxsa]

At the Amsterdam PAIS Conference a person announced they would probably have a diagnostic marker for ME/CFS in a year and have been working on it for a time- but I don’t know more than that. The person who I heard this from was very secretive so it seemed pretty secret still.

I don’t know how good it will be though and what kind of marker we‘re talking about.
But the source is valid.

 

[justlxsa]

Was this to you personally in conversation or in a talk?

not in a talk (i guess), i haven’t heard the talks.

 

[V.R.T.]

I don’t know how good it will be though and what kind of marker we‘re talking about.
But the source is valid.

So a researcher at the conference said this to you directly or said this to someone who then told you?

Either way, I hope your source is correct. I'd really like to believe this but I've been burnt before.

 

[EndME]

I don’t know how good it will be though and what kind of marker we‘re talking about.
But the source is valid.

I'm not sure who you are talking about, but Jeroen den Dunnen (based on antibodies) has said something similar for some years. Until now that has remained an empty promise. We've discussed this on the forum.

 

[hotblack]

What I didn't mention before and what doesn't come across in this thread it that it is a challenge test in that you have to give the patient a drug they may react very badly too

The risk of negative reactions, particularly for severe patients is a problem that’s been mentioned multiple times.

 

[hotblack]

Thank you for trying. I'm hearing the same thing that there are promising leads to follow up on but they need funding.

Exactly. The problems are the usuals of funding, needing the right people and that me/cfs as a condition needs a good home.

I think we all share your frustration that we don’t have answers, we don’t have better and at the situation we find ourselves in. It’s incredibly tough.

I am enormously grateful for the huge efforts in this thread and looking forward to what may come from it. What is happening here should have been done years ago by others but at least people here are trying to piece things together and do something about it now. That is unreservedly a good thing.

 

[justlxsa]

So a researcher at the conference said this to you directly or said this to someone who then told you?

Either way, I hope your source is correct. I'd really like to believe this but I've been burnt before.

A researcher at the conference said this to someone who then told me.

We‘ll see in a year I guess.

And I agree- we need to follow different leads for a biomarker, this test should be one of them.

 

[Hutan]

We have moved some posts to a new thread 'A role for neurology and neurologists in finding answers about ME/CFS'

 

[forestglip]

I made a few minor changes in a new version of the review (GitHub link).

A few little style and grammar improvements, thanks to some proofreading from a family member.

I also realized that the control group for Behan's organophosphate CFS-like buspirone study was the same exact data as the control group in Majeed's 1996 thesis, so I noted that.

Updated some citations for depression-related findings.

Made my description more accurate about Duval et al's claims for why they think neuroendocrine challenge testing became less popular in psychiatry.

I noted that fenfluramine was withdrawn from the market in 1997, which might have some role in the research slowing down.

I added some speculation about how estrogen levels increase after brain damage, based on the paper jnmaciuch previously shared, and how something similar might lead to increased prolactin response in ME/CFS.

I re-calculated all the prolactin response values in the tables using higher resolution plot images to get more accurate data. A few values changed by a small amount of 0.1 or 0.2, and I also realized for Sharpe et al., 1996, I accidentally used the the -30 minute timepoint for baseline instead of 0, so I corrected that one.

Edit: Replaced file after just a couple more extremely minor typo/style fixes.