Does the pathology of ME/CFS include brain damage?

[Jonathan Edwards]

Are these simply more "minor, inconsistent, imaging differences"?

Well, if they are not, why have they not been found before. With most neurological diseases that have damage a first year medical student can see what is wrong on scans of most patients.
And why should the right insula atrophy? We have seen dozens of these findings fade out within a year.

...but what kind of documentation do we really have on this? Can we really say with any certainty that they return to the level of cognitive function that they had before?

Yes, in broad medical and real life terms, they do. You might find a statistically significant difference in a huge study but it would probably be die to an artefact. I just see no point in trying to find a hint of a suspicion of something when in robust terms we know people get better.

why does the "fact" of recovery not receive more scrutiny? Or have I simply missed it?

Maybe you have. It has been central to understanding possible mechanisms for many of us on these forums for a decade. I am not sure why you need to 'scrutinise' something as straightforward as that.
Infarction of the right hemisphere, demyelination or Parkinson's disease are not followed by anything like recovery. ME/CFS is.

 

[DHagen]

Well, if they are not, why have they not been found before. With most neurological diseases that have damage a first year medical student can see what is wrong on scans of most patients.
And why should the right insula atrophy? We have seen dozens of these findings fade out within a year.

I don't know why it would atrophy, but that doesn't seem to be a reason in and of itself to dismiss evidence that it does atrophy. Rather, t would be a reason to scrutinize the evidence, which I thought is what we were doing here. If there is atrophy, there must be a reason, which should then be investigated. If there is not atrophy, understanding why some people believe there is would be useful in itself. Isn't that how this is supposed to work?

As for these structural changes not having been found before, the paper specifically references an earlier study with similar findings [S4ME thread].

Neither you nor anyone else is obligated to read the papers, of course, I am simply surprised at the out of hand dismissal.

Maybe you have. It [recovery] has been central to understanding possible mechanisms for many of us on these forums for a decade. I am not sure why you need to 'scrutinise' something as straightforward as that.

I would think that anything "central to understanding possible mechanisms" should absolutely invite scrutiny, particularly when that central something is a. so very difficult to find and b. precisely what we are hoping to effect. It was not my intention to be confrontational, but given the scarcity of recovered persons and the lack of documentation concerning their recovery, it really doesn't seem at all straightforward to me.

 

[Jonathan Edwards]

If there is not atrophy, understanding why some people believe there is would be useful in itself. Isn't that how this is supposed to work?

Yes but understanding that has to include a sense of perspective, which is helped by fifty years experience of reading such reports, reviewing them in journal clubs etc..

90% of what is published now in biomedical research, at least in terms of supposed pathological findings. turns out to be either chance observation or just bad method, finding what you want to find. For ME/CFS that has probably been nearer 95%+.

Researchers are human and the routes to getting duff results are the easy ones.

I have not had time to look at this in detail. But there are some things that make it inherently unlikely to be meaningful. One thing is that the brain has huge recovery powers from small changes and even for very large changes in local cortex. Changes that are subtle enough not to have been reported by routine radiology scans, which will pick up 'shrinkage' are very unlikely to cause the sort of devastating disability seen in ME/CFS. Whatever is causing symptoms in ME/CFS is gross. if it was a structural change it should have been picked up years ago. Which makes it much more likely to be a gross shift in physiology instead.

Selective shrinkage of insula would be very hard to explain on the basis of an immune disorder. It is not as if there are known populations of cells there with chemical differences like Dopamine cells in Substantia Nigra in Parkinson's. Which makes it all the more likely that this is a chance finding.

There is also the worry that it may have been picked out because somebody thought it was what they were looking for. The only thing I can think of that a shrunk insula would do is change mood or motivation and there are too many people looking for those in ME/CFS.

I cannot think of other specific reasons just at present but all I am really saying is that findings in ME/CFS research need to be treated as reliable as reports of UFOs in Wisconsin - because the lack of subsequent confirmation is so low and the same human factors are at work. That is the baseline. A few recent findings have features that make them look more robust, but they are exceptional.

I would think that anything "central to understanding possible mechanisms" should absolutely invite scrutiny,

Sure, but in this business a few observations can refute a type of model pretty well. If a few people recover that is enough to say that severe ME/CFS symptoms can occur without any irreversible damage. And so if some others have symptoms due to such damage you have to make up two explanations - which is always a bad idea. And people who have recovered from being severe are not that rare, particularly if they got ill relatively young. I have a friend who did. All I have to scrutinise there is the bald fact that he is doing a job and living a fairly normal life.

 

[butter.]

Yes but understanding that has to include a sense of perspective, which is helped by fifty years experience of reading such reports, reviewing them in journal clubs etc..

90% of what is published now in biomedical research, at least in terms of supposed pathological findings. turns out to be either chance observation or just bad method, finding what you want to find. For ME/CFS that has probably been nearer 95%+.

Researchers are human and the routes to getting duff results are the easy ones.

I have not had time to look at this in detail. But there are some things that make it inherently unlikely to be meaningful. One thing is that the brain has huge recovery powers from small changes and even for very large changes in local cortex. Changes that are subtle enough not to have been reported by routine radiology scans, which will pick up 'shrinkage' are very unlikely to cause the sort of devastating disability seen in ME/CFS. Whatever is causing symptoms in ME/CFS is gross. if it was a structural change it should have been picked up years ago. Which makes it much more likely to be a gross shift in physiology instead.

Selective shrinkage of insula would be very hard to explain on the basis of an immune disorder. It is not as if there are known populations of cells there with chemical differences like Dopamine cells in Substantia Nigra in Parkinson's. Which makes it all the more likely that this is a chance finding.

There is also the worry that it may have been picked out because somebody thought it was what they were looking for. The only thing I can think of that a shrunk insula would do is change mood or motivation and there are too many people looking for those in ME/CFS.

I cannot think of other specific reasons just at present but all I am really saying is that findings in ME/CFS research need to be treated as reliable as reports of UFOs in Wisconsin - because the lack of subsequent confirmation is so low and the same human factors are at work. That is the baseline. A few recent findings have features that make them look more robust, but they are exceptional.


Sure, but in this business a few observations can refute a type of model pretty well. If a few people recover that is enough to say that severe ME/CFS symptoms can occur without any irreversible damage. And so if some others have symptoms due to such damage you have to make up two explanations - which is always a bad idea. And people who have recovered from being severe are not that rare, particularly if they got ill relatively young. I have a friend who did. All I have to scrutinise there is the bald fact that he is doing a job and living a fairly normal life.

That's fantastic for your friend, but you have no way of knowing if your friend who recovered had the same underlying pathology (causing their ME/CFS) that the vast majority of patients who don't recover have.

 

[Utsikt]

That's fantastic for your friend, but you have no way of knowing if your friend who recovered had the same underlying pathology (causing their ME/CFS) that the vast majority of patients who don't recover have.

No, but that would require that there are at least two vastly different pathologies that cause what appear to be the same disease. That sounds very unlikely to me, and probably crosses into the territory of what you’d call «hypothetical doubt» in law - doubt with no real substance or likelihood that can safely be ignored and would not benefit the defendant.

 

[Peter T]

No, but that would require that there are at least two vastly different pathologies that cause what appear to be the same disease. That sounds very unlikely to me, and probably crosses into the territory of what you’d call «hypothetical doubt» in law - doubt with no real substance or likelihood that can safely be ignored and would not benefit the defendant.

In general the cognitive issues we see in ME/CFS are non specific, relating to things like digit span, memory deficits, information processing load, attention span, word finding difficulties, not necessitating any focal damage involving loss of specific brain cells or white matter. I would argue this is reinforced by the periods of recovery of premorbid cognitive functioning we at times see in between episodes of PEM or in those that experience varying degrees of spontaneous remission. I would argue that particularly in the earlier years and in those not severe, the most likely explanation is something that impacts global brain function, such as reduced blood supply or other biochemical insufficiency or alternatively some toxic effect or even response to viruses, that does not necessitate irreversible loss of either grey matter or demyelination.

However, there were some older autopsy studies that suggested the brains of those with very severe ME do long term show loss of both brain cells and white matter. This to me suggests there may be two processes going, one that we are all aware of during acute illnesses phases or during PEM that is reversible, but a second longer term issue, perhaps occurring over decades, that may possibly be down stream from the ME/CFS disease process that does result in some shrinking of the brain.

 

[butter.]

No, but that would require that there are at least two vastly different pathologies that cause what appear to be the same disease. That sounds very unlikely to me, and probably crosses into the territory of what you’d call «hypothetical doubt» in law - doubt with no real substance or likelihood that can safely be ignored and would not benefit the defendant.

Nothing about this is hypothetical. In the NIH intramural study, roughly (?) 50 percent of ME/CFS-specialist–diagnosed ME/CFS patients were misdiagnosed. And assuming that the remaining 50 percent all share the same underlying pathology is essentially a form of cope.

I have multiple MDs in my family and among my close friends, and they all see several non-hypochondriac patients every day who genuinely believed for a long time that they had a certain disease, but in reality they didn’t. That's not a ME/CFS specific phenomenon, it's just more likely because there are no diagnostic biomarkers.

Anyone who believes that there are no people who think they have ME/CFS while they actually don’t is just as confused as the people who claim it’s psychosomatic.

All of that is without even bringing in the PVFS is potentially ≠ ME/CFS theme.

I know patients who had a ME/CFS diagnosis for 20 years before it turned out to be a mitochondrial disease. They suffer from what they say is PEM.

There are probably like 20 different pathways/routes/pathologies/etc that can lead to all sorts of 'dysautonomias' which play a large part in ME/CFS or can look like it.

 

[forestglip]

In the NIH intramural study, roughly (?) 50 percent of ME/CFS-specialist–diagnosed ME/CFS patients were misdiagnosed.

What's this based on?

 

[butter.]

What's this based on?

It's based on what they (NIH) said. I am sure you will find a source. Pretty sure it's roughly correct, but not 100%. If I am wrong, please post it here. Thank you.

 

[forestglip]

It's based on what they (NIH) said. I am sure you will find a source. Pretty sure it's roughly correct, but not 100%.

Maybe I'm misunderstanding. Do you mean ~50% of the 17 participants in the study were misdiagnosed by the investigators? I don't recall anything in the paper suggesting that.

 

[butter.]

Maybe I'm misunderstanding. Do you mean ~50% of the 17 participants in the study were misdiagnosed by the investigators? I don't recall anything in the paper suggesting that.

Sorry, I can't put more energy into this. I could only find this, atm. Whatever the exact numbers were/are, they were/are high. I think I rember Nath saying something like 'over 40% were essentially misdiagnosed' in a presentation.

What's even more insane about this is that this was already a very rigorously pre-selected group we are speaking about.

So honestly, I have no idea how people seem so confident in what they believe to be true in terms of diagnosis and recovery.

 

[EndME]

Sorry, I can't put more energy into this. I could only find this, atm. Whatever the exact numbers were/are, they were/are high. I think I rember Nath saying something like 'over 40% were essentially misdiagnosed' in a presentation.

What's even more insane about this is that this was already a very rigorously pre-selected group we are speaking about.

So honestly, I have no idea how people seem so confident in what they believe to be true in terms of diagnosis and recovery.

This doesn't not seem quite accurate to me. From the data in the supplementary material of the NIH Intramural study:

The 217 that were selected had undergone one initial telephone screening interview, I wouldn't consider that very rigorous, but it is of course more rigorous than what we see in other studies or other claims of recovery.

Of the 217 that underwent the detailed case review the majority were excluded due to reasons that had to do with the study setup not with them not having ME/CFS. Of the 217, 46 were excluded because a closer review of their medical records showed that the onset was longer than 5 years ago, 26 had no record of infection, 44 were excluded because the pandemic started and 13 were lost to follow up (that is more than 50% of the 217). 37 were excluded due to other conditions with the most common reasons being head injury and inflammatory disorder (in total these people made up less than 25%) but that does not directly mean that they couldn't of had ME/CFS, unfortunately there was no long-term follow-up data (but I agree that there is a high chance of misdiagnosis, in general maybe somewhere around 25% depending on the context and study that may often be higher). Other reasons for exclusion for example included current treatment for Lyme disease or other medication use.

Of course the study also showed that a significant portion of people that other studies include as ME/CFS patients probably don't have ME/CFS (from what I vaguely remember 2 patients even made it through even further workups and were only later excluded due to cancer and MS, and the text talks of 4 people with other conditions that were only discovered later). This has probably had impacts on some study results of other studies, but probably more often than not it means positive results can't be trusted, rather than the opposite (of course there are exceptions). For example it means that if a study claims to have found a 100% accurate biomarker then that cannot be the case!

I think the more prominent detail of the study is rather the opposite: It was the study that probably had the most rigorous selection criteria and yet some participants of the study later recovered. This provides strong evidence that recovery happens even if rare, rather than being evidence of the opposite. And of course there were recoveries in the Rituximab and other studies as well.

Regarding the whole "damage discussion", I see no reason to use terminology if it is not accurate. I can understand that terms such a "brain fog" and other terminologies that downplay the problems and which in many cases are not accurate either are unwanted, but I don't think it is in any way helpful to use scientific terms without a basis for them (and one study here or there with some speculative claims can always be found, that's no different to saying its all psychological because one study claimed this or that).

 

[EndME]

I can see the possibility that ME/CFS is made up of different pathologies, where one may be similar to CTE, in that there is brain damage that is however not detectable by current imagining techniques (and you'd probably need such a subgroup to be somewhat smaller for autopsies to not have picked up such issues just purely out of luck), but in that scenario it seems likely to me that in the long run this condition will at some point anyways not be ME/CFS anymore, whilst the ones with unknown pathology that don't include brain damage will still be falling into the ME/CFS bucket, so I'm not sure how useful "brain damage subgroup" claims are.

More prominently there are other medical conditions where there is no brain damage but where there are severly disabling cognitive problems that are taken seriously. In the absence of evidence it seems most sensible to me to want to push the views on ME/CFS in that direction, rather than anything else.

 

[Jonathan Edwards]

That's fantastic for your friend, but you have no way of knowing if your friend who recovered had the same underlying pathology (causing their ME/CFS) that the vast majority of patients who don't recover have.

The chances of him being an outlier are small. We are in a situation where we have to considr probabilities as important. The model where my friend doesn't have ME/CFS after all is weak. Especially when there are plenty of people who have passed through this forum who have had major improvements.

 

[Jonathan Edwards]

However, there were some older autopsy studies that suggested the brains of those with very severe ME do long term show loss of both brain cells and white matter.

I have not heard of those in the ten years I have been following ME/CFS. Do you have citations - they would be interesting to consider.

 

[Jonathan Edwards]

I think I rember Nath saying something like 'over 40% were essentially misdiagnosed' in a presentation.

That is highly plausible since physicians haven't a clue about ME/CFS, but there are plenty of cases around where we can be confident that they fit the criteria - which is all we have to define ME/CFS. To me the fact that diagnosis in both US and UK and likely everywhere else is grbage is an irrelevance.

 

[Jonathan Edwards]

More prominently there are other medical conditions where there is no brain damage but where there are severly disabling cognitive problems that are taken seriously.

An important argument. Having no brain pathology to show isn't actually the reason why ME/CFS is dismissed. There are plenty of conditions that affect cognition are not dismissed and have no well documented pathology.

 

[Peter T]

I have not heard of those in the ten years I have been following ME/CFS. Do you have citations - they would be interesting to consider.

I knew when I wrote this that some one would ask about references.

Unfortunately my memory for names and dates is pretty non existent. I have started searching, but so far have only come across the various inconsistent scan studies. Am hoping some one else has better memories and record keeping than me.

 

[Peter T]

I knew when I wrote this that some one would ask about references.

Unfortunately my memory for names and dates is pretty non existent. I have started searching, but so far have only come across the various inconsistent scan studies. Am hoping some one else has better memories and record keeping than me.

Struggling to find any references, and the reviews of autopsy studies in ME/CFS that I have so far found don’t make mention of any indications of overall reduced grey or white matter volume. I don’t usually confabulate to fill gaps in my memory, but I do sometimes get the wrong end of the stick.

Wendy Boutilier does offer a useful summary of ME autopsy studies in a recent Facebook post

Autopsy studies in very severe Myalgic Encephalomyelitis (M.E.) patients are rare but provide important pathological insights that support the biological nature of the disease. Although the number of published cases is small, some consistent abnormalities have been reported across different patients. Here is a synthesis of what has been found in the medical literature and case reports:
Neurological Findings
Dorsal Root Ganglia (DRG) Inflammation and Damage
* Dr. Abhijit Chaudhuri (UK) reported neuroinflammation and neuronal degeneration in the dorsal root ganglia of severe M.E. patients, correlating with sensory dysfunction, pain, and autonomic disturbances.
* Findings included perivascular lymphocytic infiltration and signs of chronic inflammation.
Brainstem Abnormalities
* In some autopsies, inflammation of the brainstem has been described. The brainstem is key in autonomic control and arousal systems, both of which are disrupted in M.E.
* Subtle gliosis (scarring of glial cells) and hypoperfusion patterns consistent with premortem imaging studies have been noted.
Enteroviral Persistence
* Dr. John Richardson and Dr. Byron Hyde documented enteroviral proteins in CNS tissue in M.E. cases, supporting the viral persistence hypothesis.
Cardiac and Vascular Findings
Myocarditis and Cardiac Inflammation
* Some autopsies found myocardial inflammation and fibrosis, consistent with patients’ premortem reports of arrhythmias, chest pain, and sudden cardiac death risk.
Small Vessel Disease
* Evidence of microvascular dysfunction and endothelial abnormalities, consistent with reduced cerebral blood flow and orthostatic intolerance seen during life.
Immune and Inflammatory Findings
Activated Microglia and Astrocytes
* Similar to neuroinflammatory diseases, activated microglia have been found in CNS tissue, pointing to ongoing immune activation.
Evidence of Chronic Immune Activation
* Lymphocytic infiltrates in neural and muscular tissue.
Specific Case Reports
1. Sophie Mirza (UK, 2005) – A 32-year-old woman with very severe M.E. who died after years of being bedbound.
* Autopsy showed inflammation of the spinal cord and dorsal root ganglia.
* Coroners concluded death was due to “acute renal failure as a result of dehydration arising from M.E.”
2. Other Documented UK Cases (Chaudhuri, Richardson, Hyde)
* Brain and spinal cord inflammation.
* Enteroviral protein detected in CNS tissue.
* Cardiac inflammation in some cases.
3. Recent Research Autopsies
* Reports shared through the UK ME Association tissue bank indicate abnormalities in immune, nervous, and vascular systems, but many findings remain unpublished or in-progress.
Key Takeaways
* Very severe M.E. is associated with measurable neuropathology—especially dorsal root ganglia and brainstem inflammation.
* Cardiac inflammation and vascular dysfunction are also reported, aligning with patients’ clinical symptoms.
* Findings support viral persistence, chronic immune activation, and neuroinflammation as central processes.
* Autopsy evidence directly refutes the idea that M.E. is a functional or psychosomatic disorder.
Autopsy Findings in Severe M.E. Patients
1980s–1990s
John Richardson (UK, multiple cases)
* Documented autopsies of patients with ME/post-viral fatigue syndromes.
* Findings:
* Evidence of chronic enteroviral persistence in CNS.
* Brain and spinal cord inflammation.
* Vasculitic-type small vessel changes.
* Reference: Richardson J. Enteroviral and Toxin Mediated Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Other Organ Pathologies. The Haworth Medical Press, 2001. https://catalog.nlm.nih.gov/discovery/fulldisplay? also https://2024.sci-hub.se/.../0836c58223d40f.../hooper2006.pdf
2000s
Sophia Mirza (UK, 2005, age 32)
* First officially recorded death from M.E. in the UK.
* Cause of death: Acute renal failure due to dehydration as a result of M.E. (Coroner’s ruling).
* Autopsy Findings (Dr. Abhijit Chaudhuri, Neuropathologist):
* Inflammation of the dorsal root ganglia.
* Spinal cord inflammation consistent with chronic neuroinflammation.
* References:
* Hooper M. What is ME? What is CFS? Information for Clinicians and Lawyers. 2007. http://www.margaretwilliams.me/.../what-is-me-what-is-cfs...
* UK Coroner’s report on Sophia Mirza case. http://www.sophiaandme.org.uk
2009–2010s
Byron Hyde (Canada, Nightingale Research Foundation)
* Reported autopsy results from very severe ME cases.
* Findings:
* Enteroviral protein in CNS tissue, including brainstem and hypothalamus.
* Cardiac inflammation and fibrosis in some cases.
* Widespread signs of viral persistence and immune activation.
* Reference: Hyde B. The Nightingale Definition of Myalgic Encephalomyelitis (M.E.). Ottawa: Nightingale Research Foundation, 2007 (with updates in later case presentations). http://www.investinme.org/.../Byron%20Hyde%20Definition...
2011 – Present
UK ME/CFS Biobank (London School of Hygiene & Tropical Medicine, ongoing)
* Established a structured tissue and blood donation program, including post-mortem studies.
* Reported Findings (summarized in MEA updates):
* Neuroinflammation: activated microglia and astrocytes.
* Immune abnormalities in CNS and peripheral tissues.
* Vascular changes affecting oxygen and nutrient delivery.
* References:
* Nacul LC, Lacerda EM, Kingdon CC, Curran H, Bowman EW. "How have selection bias and disease misclassification undermined ME/CFS research?" Fatigue: Biomedicine, Health & Behavior. 2019. https://core.ac.uk/download/pdf/79657048.pdf
* ME Association: Post-mortem tissue bank updates (2014–2023). https://meassociation.org.uk/.../items/research-post-mortem/
2010s–2020s (Chaudhuri & Colleagues)
* Multiple autopsies on patients with severe ME.
* Findings:
* Chronic dorsal root ganglionitis (lymphocytic infiltration).
* Gliosis in spinal cord and brainstem.
* Subtle vascular inflammation consistent with hypoperfusion.
* Reference:
* Chaudhuri A, Behan PO. "In vivo magnetic resonance spectroscopy in chronic fatigue syndrome." Prostaglandins Leukot Essent Fatty Acids. 2004;71(5):181–183. https://pubmed.ncbi.nlm.nih.gov/15253888/
* (Autopsy findings have been presented in MEA reports and case conferences; some remain unpublished in peer-reviewed literature).
Recent Reports (2020s)
* Nightingale Research Foundation (Hyde, Canada):
* Continued reporting of enteroviral infection in CNS and cardiac tissue in autopsy cases.
* ME Association Tissue Bank:
* Ongoing systematic research on brain, spinal cord, muscle, and vascular tissues of deceased ME patients.
* Early reports confirm neuroinflammatory pathology.
References:
* Hyde B. Nightingale Research Foundation Updates, 2020–2023. https://www.researchgate.net/.../237333246_The...
ME Association, Post-mortem Tissue Bank annual updates (latest 2023).
Summary of Common Autopsy Findings
1. Neurological:
* Dorsal root ganglionitis.
* Spinal cord and brainstem inflammation (gliosis, microglial activation).
* Enteroviral proteins in CNS.
2. Cardiac/Vascular:
* Myocarditis, fibrosis, small vessel vasculopathy.
* Endothelial dysfunction.
3. Immune:
* Lymphocytic infiltrates in CNS and muscle.
* Chronic immune activation.
4. Causes of Death (recorded):
* Renal failure due to dehydration (e.g., Sophia Mirza).
* Possible sudden cardiac death due to myocarditis/arrhythmia in other cases.

See

MEpedia also providers an overview of autopsy studies in ME, see https://me-pedia.org/wiki/Autopsy_in_Myalgic_Encephalomyelitis which also fails to reference any reduction in overall brain volume.

 

[butter.]

I think the more prominent detail of the study is rather the opposite: It was the study that probably had the most rigorous selection criteria and yet some participants of the study later recovered. This provides strong evidence that recovery happens even if rare, rather than being evidence of the opposite. And of course there were recoveries in the Rituximab and other studies as well.

I understand, but that’s just an assumption. Maybe they had what I have, maybe not. There is absolutely no way to tell. It’s unknown, and it’s hard to see how any stronger claim would hold up under scrutiny.

I’m not saying that people can’t recover from ME/CFS. I’m saying I find it likely that there are subgroups with different pathologies and different capacities to recover from insults over time, and also patients who were never true ME/CFS cases in the first place (in the sense that there actually exist people who think they have something when they don't), which is more or less supported by all sorts of direct and indirect evidence.

To work up a syndromic scenario like this, you need very large cohorts and biological data to stratify. You have to analyse tissues and look for real mechanistic clues. It’s no surprise that none of this works with only 17 people (25% with other diagnoses like cancer and 25% recovered? Are these the right numbers?).

If I had to bet, I would bet the people who recovered did not have what I have, but I can't know for sure. The long-term data clearly show the vast majority of people don't recover, that alone should invite some serious thoughts about recovery in a syndrome space.

There are reported and 'real recoveries' from ALS, too. That's according to some people. What does that tell us abot ALS? Did their motor neurons regenerate or have they been misdiagnosed? I can't know. I know what I would bet on, though.

If the Rituximab trials showed anything, it showed that people did not recover due to Rituximab, and for the people that recovered independently of it, the same applies than for the intramural recoveries.

Technically speaking, if you want to speak of actual ME/CFS recovery, it would be good to know what exactly they recovered from biologically first.

PS: With the 'very rigorously pre-selected group' I was referring to the actual patients taking part in the intramural. Whether it's 25, 40 or 50%, and depending on context, it's certainly a high rate of misdiagnosis.