Does the pathology of ME/CFS include brain damage?

[Utsikt]

A bruise is damage and it isn't typically permanent.

Damage as in «brain damage» that you are proposing to use as a description, not damage in general. I should have been clearer about that.

Sure, but cognitive impairment is downstream to brain damage.

It doesn’t have to be, which I think will be clear to most laypeople because most people have experienced some kind of temporary cognitive impairment.

Some of us suffer them to a greater degree than others within our own ME/CFS community - and certainly some endure intellectual deficits.

You seem highly intellectual to me, even though I have no doubt that it requires much more effort and comes at a much higher cost than before you got ME/CFS.

I’m not able to solve the same equations as I could before getting ME/CFS, but that’s not because I don’t understand them anymore, I just don’t have the stamina to do it and I loose track of trails long before I’m done. Sometimes I forget part of the equations. Does that make me less intellectual? I don’t think so.

These are problems that extend well beyond clarity and processing speed. They can include deficits across cognitive domains

«Thinking» refers to all cognitive processes, it’s as general as you can get it.
Clearly = doing what you’re supposed to.
Quickly = doing it at speed.

Are there other ways for thinking to be impaired?

 

[duncan]

Are there other ways for thinking to be impaired?

Certainly. Logic. Judgement. Recall. There are others.

You seem highly intellectual to me, even though I have no doubt that it requires much more effort and comes at a much higher cost than before you got ME/CFS.

My IQ tests would challenge that: They've dropped by almost 20 pts since I first started getting sick a quarter century ago.

I’m not able to solve the same equations as I could before getting ME/CFS, but that’s not because I don’t understand them anymore, I just don’t have the stamina to do it and I loose track of trails long before I’m done. Sometimes I forget part of the equations. Does that make me less intellectual? I don’t think so.

I frequently don't understand instructions. Each time I've traveled to the NIH to participate in a study, I've had to ask a random passerby to aid me in figuring out the metro ticket machine. There's a range of deficits in pwME. Some of us are screwed brain-wise, and brain damage is the only word tandem I can think of that approaches those deficits accurately or in a way that conveys the breadth of that range,

It doesn’t have to be, which I think will be clear to most laypeople because most people have experienced some kind of temporary cognitive impairment.

Nods.

 

[Creekside]

I would suggest that something like this or aberrant signaling would qualify as damage. It implies a change in a patient's normal brain make-up/functioning characterized by negative consequences.

The original word was "injury", (online definition: Injury is physiological damage to the living tissue of any organism). Something like aberrant signalling or a change in feedback loop variables wouldn't be damage, but rather a change in function. You can't intentionally plan a vacation or solve a complex mathematical equation if you fall asleep, but that doesn't mean that a sleeping brain is damaged or injured. Windows computers often lock up or enter the blue screen of death without injury to the hardware. ME dysfunction could be the equivalent of a software error or even correct but unwanted function (the computer doesn't respond because it's doing a software upgrade at that time). ME symptoms are similar to sickness behaviour, which is an intentional function with a valid purpose, when it is activated in the appropriate circumstances. It could be inappropriately activated by means other than injury.

 

[duncan]

The original word was "injury", (online definition: Injury is physiological damage

"Damage" is in your own definition.

Something like aberrant signalling or a change in feedback loop variables wouldn't be damage, but rather a change in function.

I'm not sure I agree. Besides, change in function likely doesn't happen in a vacuum. At the very least, damage of some sort has caused the change in functioning.

ME symptoms are similar to sickness behaviour, which is an intentional function with a valid purpose, when it is activated in the appropriate circumstances. It

Sickness behaviour is a spectator concept. It's for animals that cannot communicate with words. Makes sense since it was proposed by a veterinarian.

 

[Utsikt]

My IQ tests would challenge that: They've dropped by almost 20 pts since I first started getting sick a quarter century ago.

That could be confounded by e.g. speed being involved in the measurements and some tasks being too complex for you to solve with your current limitations, even though you’d understand them if they were adapted to you. I don’t think IQ tests are vey good at measuring intelligence.

Certainly. Logic. Judgement. Recall. There are others.

That sounds like things relying on thoughts working like they are supposed to.

I have no doubt that people experience that their minds don’t work like they used to. Mine certainly doesn’t and I know many that are much more impaired than me even though I’m severe.

It just doesn’t look to me like the impairments that you see in people with permanent brain damage (like stroke, MS, AD, HD, etc.) that I’ve seen up close.

And when people that have the same kinds of impairments as me have recovered and regained their cognitive functioning, it demonstrates that my impairments can be caused by something that can resolve naturally if the ME/CFS resolves.

Which gives me little reason to think that ME/CFS has to involved permanent brain damage. Not that pwME/CFS would be immune to brain damage from other sources (even just something indirectly caused by living with ME/CFS like prolonged sleep issues), but that’s a different question.

 

[DHagen]

You seem highly intellectual to me, even though I have no doubt that it requires much more effort and comes at a much higher cost than before you got ME/CFS.

My IQ tests would challenge that: They've dropped by almost 20 pts since I first started getting sick a quarter century ago.

I feel I am in much the same boat as @duncan here - there are a whole host of ways in which my brain no longer functions properly, and lots of ways in which information is processed incorrectly or even not at all, no matter how much time is allowed. Yes, there are some tasks I can still perform that "merely" require additional effort or come at additional cost, and sometimes it is a matter of not being able deal with the quantity of information involved in a complex task, but at others, even the first step simply isn't possible. The closest parallels to my experience that I have found in my own life are with those who are suffering from dementia, a brain tumor, or concussion/CTE.

I understand the resistance to "brain damage" and the reluctance to assign permanence, but both of those seem accurate to my experience. There are many people here who obviously are in better shape cognitively than I am, even when many of those same people are worse-off in other ways, and I am happy for each of you, if also angry and jealous (as I suspect we all are in our own ways and according to our own particular circumstances).

It just doesn’t look to me like the impairments that you see in people with permanent brain damage (like stroke, MS, AD, HD, etc.) that I’ve seen up close.

For myself, I do (sadly) see quite a few similarities - not identical in all cases, but pretty close in some.

And when people that have the same kinds of impairments as me have recovered and regained their cognitive functioning, it demonstrates that my impairments can be caused by something that can resolve naturally if the ME/CFS resolves.

I hope this is the case. I don't have any experience of it myself, nor have I witnessed it, but that doesn't mean it isn't possible for some.

Which gives me little reason to think that ME/CFS has to involved permanent brain damage. Not that pwME/CFS would be immune to brain damage from other sources (even just something indirectly caused by living with ME/CFS like prolonged sleep issues), but that’s a different question

I don't know that the claim has been made that ME/CFS or LC necessitates brain damage, merely that in at least some cases it is observable and that it correlates with the degree of cognitive impairment. Sleep disruption could be causing this or a consequence of it, or both (feedback loops and all that). If the damage is from sleep problems, I don't know that that's any cause for optimism regarding recovery.

I recognize that we all speak from unique positions with regard to our respective afflictions and that these, along with our hopes and fears, naturally affect our interpretations of the studies shared here and inform the terminology that we employ. I certainly do not mean to invalidate anyone else's experience - and, while I am quite pessimistic myself, I do hope that you are right concerning the possibility of recovery, @Utsikt.

 

[Utsikt]

For myself, I do (sadly) see quite a few similarities - not identical in all cases, but pretty close in some.

Could you describe them? I’m genuinely curious.

Examples of things I haven’t seen in pwME/CFS are personality changes, thinking you’re in a different time period, lower insight into your own health (many with Huntington’s disease refuse to acknowledge their level of impairment and have completely unrealistic expectations about what they are able to do), thinking you’re somewhere you’re not (so going to the bathroom in your closet).

Lots of pwME/CFS struggle to do things, forget where they are or what they are doing, and so on. But I don’t have the impression that they are confused in the same way that you see with neurodegenerative diseases.

I don't know that the claim has been made that ME/CFS or LC necessitates brain damage, merely that in at least some cases it is observable and that it correlates with the degree of cognitive impairment.

Then the question is if brain damage is part of the pathophysiology of ME/CFS or LC, or of it’s a secondary effect, or if it’s just a co-morbidity, perhaps with a higher prevalence than in the general population. I’m sure there are some pwME/CFS with regular or early onset dementia, as an example.

 

[duncan]

That could be confounded by e.g. speed being involved in the measurements and some tasks being too complex for you to solve with your current limitations, even though you’d understand them if they were adapted to you. I don’t think IQ tests are vey good at measuring intelligence.

Intelligence Quotient? How would you gage intelligence? I've also taken the MOCA and did poorly on that, too.

Listen: After a certain undefinable threshold, you know when your intelligence has taken a hit. You know.

That sounds like things relying on thoughts working like they are supposed to.

I think you are misunderstanding me. I'm suggesting these are all cognitive aspects already impaired or at risk or in decline. At least in some pwME.

It just doesn’t look to me like the impairments that you see in people with permanent brain damage (like stroke, MS, AD, HD, etc.) that I’ve seen up close.

We are unique I think. But I see similarities in other conditions. And we are different amongst each other in many more regards than simply cognitive.

And when people that have the same kinds of impairments as me have recovered and regained their cognitive functioning, it demonstrates that my impairments can be caused by something that can resolve naturally if the ME/CFS resolves.

Maybe. That's not a lottery I would bank on.

Which gives me little reason to think that ME/CFS has to involved permanent brain damage.

As I alluded to earlier, brain damage doesn't have to be permanent. But I surely don't like our odds.

 

[duncan]

But I don’t have the impression that they are confused in the same way that you see with neurodegenerative diseases.

Personally, I absolutely believe ME/CFS can be neurodegenerative, but I don't think it needs be an endless spiral downward. It's like we drop so far, and then plateau; the distance we fall varies. This is true for all aspects of ME/CFS. Degrees of ME/CFS symptom impairment never stop surprising me.

 

[DHagen]

Could you describe them? I’m genuinely curious.

Being able to absorb but not process information (e.g. repeating each word in a sentence upon hearing it, but being unable to establish the connection between the words such that it would produce meaning, essentially the loss of the ability to process syntax), dyslexia-like issue with ordering information (text and images), difficulties in processing spatial relationships, losing track of one's own limbs, temporarily regaining access (and sometimes vivid recall) of events long past but inability to remember what happened an hour ago, emotional disregulation (sometimes extreme), varied forms of paresthesia, near complete loss of a skill set (e.g. playing guitar, speaking a language, even reading), among others. Some of these are constant and seemingly permanent, others fluctuate drastically - just as I have witnessed in friends and relatives suffering from CTE, repeated TIA, and MS. There also seems to be a lot of overlap with CTE and concussion with regard to sensory sensitivities. Others that I know and have known with Parkinson's related dementia have had some similar issues, including fluctuation, but with the notable distinction that the impairments are more obviously progressive (in one case continuing to worsen until complete obliteration occurred several months prior to death, in the other, appearing to stabilize after a few years).

 

[Utsikt]

Intelligence Quotient? How would you gage intelligence? I've also taken the MOCA and did poorly on that, too.

I don’t think there exists good ways of measuring intelligence because all of the measurements will depend on functions that have little to do with intelligence.

I have less access to my intelligence. But I don’t think I’m less intelligent.

Our difference in opinion might be caused by us meaning different things.

Personally, I absolutely believe ME/CFS can be neurodegenerative, but I don't think it needs be an endless spiral downward. It's like we drop so far, and then plateau; the distance we fall varies. This is true for all aspects of ME. Degrees of ME symptom impairment never stop surprising me.

Are there any other neurodegenerative diseases that work that way? That just stop after a while?

 

[Utsikt]

Being able to absorb but not process information (e.g. repeating each word in a sentence upon hearing it, but being unable to establish the connection between the words such that it would produce meaning, essentially the loss of the ability to process syntax), dyslexia-like issue with ordering information (text and images), difficulties in processing spatial relationships, losing track of one's own limbs, temporarily regaining access (and sometimes vivid recall) of events long past but inability to remember what happened an hour ago, emotional disregulation (sometimes extreme), varied forms of paresthesia, near complete loss of a skill set (e.g. playing guitar, speaking a language, even reading), among others. Some of these are constant and seemingly permanent, others fluctuate drastically - just as I have witnessed in friends and relatives suffering from CTE, repeated TIA, and MS. There also seems to be a lot of overlap with CTE and concussion with regard to sensory sensitivities. Others that I know and have known with Parkinson's related dementia have had some similar issues, including fluctuation, but with the notable distinction that the impairments are more obviously progressive (in one case continuing to worsen until complete obliteration occurred several months prior to death, in the other, appearing to stabilize after a few years).

Thank you.

Those sound a lot like what you’d observe in people on drugs or during a heavy infection of some kind. They seem to be more universal to the brain or body being sick. In ME/CFS it’s just turned up some notches. And it gets temporarily worse during PEM.

When you look at the things not observed in those situations but that are present in neurodegenerative diseases, like the things I mentioned above, I don’t see much overlap with ME/CFS. And I don’t think those aspects tend to improve much during fluctuations, but I don’t know that for sure.

 

[Turtle]

Maybe it ain't broke but sometimes certainly not working in an intelligent way.

I had to start injecting insuline for diabetes. So I collected the insuline from the pharmacy, already halfway to the supermarket, got me some groceries, too much again (intruduction). This time I decided to hide one bag and picked that up later.
Already in PEM, I "used" my first dose. For two days I injected myself without a needle. That ain't'working.

I'm always in trouble with user guides. I had not picked up that I had to check my insuline inventory myself. So for several days I injected "nothing." Untill my intelligence took over again and found out the numbers didn't add up.

That's what 34 years of bad brainfog add up to.

This time I got away with it. Now it's routine so don't worry.

 

[duncan]

Are there any other neurodegenerative diseases that work that way? That just stop after a while?

I don't know. Maybe it doesn't just stop. Maybe the decline continues but at what amounts to an almost imperceptible crawl. I think I'm at my worst now. Not sure, though.

Admittedly, my primary template is me. And what I've been reading about and from fellow patients in many forums over the last couple of decades.. Not to mention a host of inadequate studies.

 

[ScoutB]

I relate very strongly to what you're saying @DHagen, the cognitive decline is the worst problem for me as well.

I'm waiting for more data to answer the question of damage. It doesn't seem like we know enough about how the brain works to even know which issues (whether they are called damage or not) cause which problems. People can have 'silent' strokes with damage but without obvious outward symptoms (or at least not the usual symptoms we associate with strokes). On the other hand, temporarily illnesses can cause severe cognitive problems.

In the meantime I'll just complain that the standard tests/signs we look for with impaired cognition don't do a great job at capturing the problems we deal with in "brain fog". We're pretty good at catching cognitive impairment when the person is too unaware to mask it (such as in the examples @Utsikt gave of personality changes, delusions etc.) -- bluntly, when someone's difficulties are more likely to become problems for people around them, we notice. But other kinds of cognitive impairment might not be as correlated with that lack of self awareness.

To give an example for me personally -- this was my process the other day *immediately* after my partner asked for a screenshot of the main page of a health app:
Step 1. Pick up phone and completely forget what I was supposed to be doing.
Step 2. Scroll randomly through apps hoping it'll jog my memory.
Step 3. Find the app but don't remember what I wanted to do with it.
Step 4. Click randomly around the pages of the app, hoping it'll come back to me.
Step 5. Stare at main page of app for a while.
Step 6. (Penny drops) Realize I wanted to screenshot the very page I am looking at.
Sometimes I'll see imaging studies say they found patients with ME/CFS "recruited additional brain regions" for a task, and I kind of wonder if these weird compensation tactics are what that looks like in real life...

 

[Creekside]

I'm not sure I agree. Besides, change in function likely doesn't happen in a vacuum. At the very least, damage of some sort has caused the change in functioning.

We undergo changes in brain function daily: sleep, hunger/satiation, exercise, etc. Even without functional changes, try solving a complex problem while your bladder is distracting you. Nutrients or other chemicals can change cellular functions without causing damage. Neural pathways change all the time too. Memorizing a new phone number is a change of function of cells, but isn't damage. Our myelin sheaths are constantly undergoing removal/replacement, with changes to meet a purpose. It's possible for this sort of structural change to alter a feedback loop which causes more structural changes that strengthen those feedback variables, which cause more changes that strengthen them. Not damage, just undesirable changes.

Sickness behaviour is a spectator concept. It's for animals that cannot communicate with words.

When I get the flu, I certainly want to hide in bed until I feel better. There are some non-damage changes going on that affect my behaviour.

 

[poetinsf]

To give an example for me personally -- this was my process the other day *immediately* after my partner asked for a screenshot of the main page of a health app:
Step 1. Pick up phone and completely forget what I was supposed to be doing.
...

This sure sounds like a working memory problem all too common with brain fog, allegedly caused by inflammation in the hippocampus area.

I think the importance of working memory in intelligence and other mental functioning is underestimated. Even the most brilliant brain can't function without enough registers to hold and juggle data, to the point that it looks like a brain damage.

 

[Yann04]

To give an example for me personally -- this was my process the other day *immediately* after my partner asked for a screenshot of the main page of a health app:
Step 1. Pick up phone and completely forget what I was supposed to be doing.
Step 2. Scroll randomly through apps hoping it'll jog my memory.
Step 3. Find the app but don't remember what I wanted to do with it.
Step 4. Click randomly around the pages of the app, hoping it'll come back to me.
Step 5. Stare at main page of app for a while.
Step 6. (Penny drops) Realize I wanted to screenshot the very page I am looking at.
Sometimes I'll see imaging studies say they found patients with ME/CFS "recruited additional brain regions" for a task, and I kind of wonder if these weird compensation tactics are what that looks like in real life...

Very much relate

 

[Jonathan Edwards]

I haven't followed this thread much but the simple answer is that in any reasonable usage, either medical or lay, there is no brain damage in ME/CFS in the way that there clearly is in MS or Parkinson's. The minor, inconsistent, imaging differences reported for ME/CFS against controls are trivial in comparison to those seen in other disorders with similar disability.

And as has been said, people improve, and not in the usual time scale of CNS recovery but in unpredictable time frames, sometimes very rapid.

Beyond this, to my understanding, you just get into quibbling over words for no benefit. And all that is really of interest is whether or not the problems are reversible. Everything we know suggests that they probably are, even if we have no idea t present how to induce reversal.

 

[DHagen]

I haven't followed this thread much but the simple answer is that in any reasonable usage, either medical or lay, there is no brain damage in ME/CFS in the way that there clearly is in MS or Parkinson's. The minor, inconsistent, imaging differences reported for ME/CFS against controls are trivial in comparison to those seen in other disorders with similar disability.

Understanding, of course, that these are LC rather than ME/CFS focused studies, would you be willing to comment on the atrophy and "alterations" observed in the recent studies under discussion (when/if you've the time)? Are these simply more "minor, inconsistent, imaging differences"?

https://www.s4me.info/threads/a-reg...-brain-fog-2025-yang-et-al.47326/#post-656956
https://www.s4me.info/threads/disti...te-sequelae-of-covid-19-2025-seo-et-al.47370/


I certainly hope that it is true that

people improve, and not in the usual time scale of CNS recovery but in unpredictable time frames, sometimes very rapid

...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? There are a lot of unevidenced claims that are (rightfully) criticized on S4ME, even if some of them are ultimately accepted as likely true, why does the "fact" of recovery not receive more scrutiny? Or have I simply missed it?