Does the pathology of ME/CFS include brain damage?

[EndME]

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.

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?).

There was no rate of misdiagnosis in the 17 people that took part. They did not have any alternative diagnoses, they were selected on the basis of having ME/CFS (which is defined by the presence of certain symptoms) and ruling out alternative diagnoses. It's certainly possible that someone still has a condition that is missed as part of that whole process but for obvious reasons we have no numbers for that and of course these were more rigorously selected patients than we've seen elsewhere and it would seem that chances are if something is missed then those people will have been less likely to recover, rather than the opposite, because no treatment was reported for those people.

I've said it before, but I think it is worth mentioning again: Something that could be a possible quick "S4ME project" is request data from the NIH to decipher which of the people later recovered (25% of the group) to see if these people differed in any way from the cohort in their biological measurements. This will introduce issues surrounding p-hacking and the sample size will diminish once more and since the study didn't yield any leads the whole project probably isn't worth much, but it should be fairly straightforward. Moreover, people in the intramural study have gone on to be part of further studies (for example the WASF3 study), so it might be worth a look.

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.

Yes and we'd also like to speak of ME/CFS knowing what the biology entails but we have no idea about that because there have been no biological findings that have been positive. The only thing we have are negative results. Including brain autopsys and neuroimaging studies.

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.

From my understanding, in that case it then becomes a discussion of "there is something that causes symptoms that appear to be identical to ME/CFS, that goes on for many years, but that can be recovered from" which again gives the presence of recovery value in trying to understand the then existing differing illnesses. As I see it the high recovery rate (25%) in the intramural study can be explained by 3 things: Rigorous workout to rule out other conditions that would otherwise go untreated (for example seen as part of the study: cancer, Parkinson, Atypical myositis, Primary biliary cholangitis had all been missed previously), low sample sizes inflating effects, short term illness giving higher chances of recovery (which is what we've seen in other studies and in the study patients had been sick for shorter than 5 years).

 

[duncan]

there is no brain damage in ME/CFS in the way that there clearly is in MS or Parkinson's.

Our keys aren't necessarily under that light.

And as has been said, people improve,

Rarely, and even then, any number of theories could explain them away.

With most neurological diseases that have damage a first year medical student can see what is wrong on scans of most patients.

Clearly that is not relevant to our damage.

Infarction of the right hemisphere, demyelination or Parkinson's disease are not followed by anything like recovery. ME/CFS is.

Maybe. We do have epic diagnostic issues. But if recovery does happen, it seems to have been vanishingly rare.

If a few people recover that is enough to say that severe ME/CFS symptoms can occur without any irreversible damage.

But not necessarily "will".

No, but that would require that there are at least two vastly different pathologies that cause what appear to be the same disease.

I can think of a few just off the top of my head. Any of the channelopathies, late stage Lyme - both of which are beset by inadequate diagnostics. There are more.

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).

Damage is damage, whether it's employed colloquially or medically. And just because the bruise on my arm is no longer discolored, that doesn't mean the pain that impedes its movement has gone.

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.

Surely it has a utility if its accurate, if only for accuracy for accuracy's sake.

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.

Why? Because of stigma? I'm curious.

To me the fact that diagnosis in both US and UK and likely everywhere else is grbage is an irrelevance.

Crappy diagnostics are a primary reason pwME have been kicked to the curb. But there are certainly other reasons, like the CBT cult - who could be dismissed summarily if we had proper diagnostics.

They did not have any alternative diagnoses, they were selected on the basis of having ME/CFS (which is defined by the presence of certain symptoms) and ruling out alternative diagnoses.

Yeah, ruling out alternative diagnosis is a joke.

 

[Mij]

Dr. Hyde referred to ME as a vascular disturbance of the brain, or cerebrovascular disease. Wouldn't that fit more with what we are experiencing concerning blood flow and cognitive issues?

 

[duncan]

Dr. Hyde referred to ME as a vascular disturbance of the brain, or cerebrovascular disease. Wouldn't that fit more with what we are experiencing concerning blood flow and cognitive issues?

I seem to recall a couple studies suggesting low VEGF in pwME.

 

[OrganicChilli]

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

Wouldn't this potentially happen to anyone who was stuck in a dark room without stimulation for years on end? Along the lines of use it or lose it?

 

[Creekside]

Crappy diagnostics are a primary reason pwME have been kicked to the curb.

I don't think it's because the available diagnostic techniques are "crappy". It's that no one knows what to look for yet. People in the 1200's didn't have "crappy technology" just because they hadn't discovered or invented everything we know and use today.

I think we're dismissed more because doctors don't like admitting inability to help with a disease. I've only had a few doctors brave enough to admit that medical science isn't capable of diagnosing and treating a large number of diseases.

 

[Nightsong]

Re the post-mortem studies - if you search PubMed for post-mortem/autopsy in ME/CFS most of the results you find are where specific viruses have been looked for. There is a paucity of serious neuropathological evaluations. In my collection of research publications I did find that at an Australian conference in 2010 a British neuropathologist presented post-mortem results on four cases. I have not been able to find any publication by him but there is this report by a doctor who attended the conference (attached, p6-7). I don't see any consistent pattern in the reported results. (There is also the published Sophia Mirza neuropathology report which I believe may have been conducted by the same pathologist).