Is PEM a disturbance in the transmission of sensory information?

[Hoopoe]

PEM could be described as an overload problem. If too much of something yet to be identified happens, then we crash and recover slowly.

But what is being overloaded? Is it the energy production systems due to excessive demand? Is it the waste clearing systems? Is it the repair and maintenance systems? Is it the nervous system that can't process all the activity? Is it the systems that transmit electrical and chemical signals between the nervous system and the rest of the body?

I'm being diagnosed with autism and that got me thinking about possible connections between sensory overload and PEM. It does feel like activity that occurs in non-stressful, familiar, low stimulation environments is better tolerated and more of it can be done before entering PEM territory. That could explain some of the unexpected variance in how well activity is tolerated, because we don't usually pay attention to these things but rather focus on the activity per se.

Maybe orthostatic stress can trigger PEM not because it is so stressful per se, but because it results in an increase in signals reaching the brain that must be processed.

Intuition tells me that a brain that can't process all information properly might wake up feeling unrefreshed and not ready for another day of activity.

@Jonathan Edwards also recently commented about PEM being maybe a sensitivity to internal stimuli (and not just sensitivity to external stimuli like light, sound, touch).

There were also these autopsies of ME patients that found anomalies in the dorsal root ganglions which seems like it might be relevant. If this part of the nervous system has problems transmitting signals, what would happen?

Does this idea seem interesting and get us anywhere?

 

[Haveyoutriedyoga]

Are you taking about both the cause and the crash/experience after the cause?

 

[Hoopoe]

To answer my own question:

Currently we study PEM almost exclusively by collecting information from self-reported symptoms and by doing 2-day CPET studies.

It could be useful to study other potential triggers of PEM: processing conversations, spending time in stimulus rich environments, touch, orthostatic stress, heat and cold exposure, metabolic stress, and so on. Maybe useful information could be gained in this way.

We could discover that physical activity is the most obvious trigger but not the only important one. That in turn might make it easier to figure out where things are going wrong in the body. If PEM can be triggered without stress on muscles or the vascular system, that would suggest the problem is not limited to those systems or is elsewhere.

 

[Haveyoutriedyoga]

I feel it is central to my experience, I am neurodivergent and was primarily very sensory seeking and under registering* had migraine which involve light sensitivity (during migraine) for years, since getting CFS my window of tolerance in the first place is much smaller, and then being in a crash makes my window even smaller (which many of us report).

I have learned a lot more about proprioception interception and vestibular senses since becoming ill with CFS and learning about my neurodivergence, it has helped me understand what invisible things might be overloading me at any given time.


A model of sensory processing here which explains what I mean by under registering
https://www.researchgate.net/figure/Model-of-Sensory-Processing-Patterns-Dunn-1997_fig4_360082452

 

[ukxmrv]

I am sensitive to noise, smells, heat,
visual stimulation but these don't cause the same PEM that physical exercise does in the same way.

As an example even if I get the 'brain overloaded' sensation it doesn't result in a delayed inability to walk etc that occurs after exceeding my physical limits.

It doesn't build up over days in the same way or take weeks to recover from. It doesn't cause pain or the weakness or viral symptoms

For me it is different but I appreciate we are not all the same

 

[Jonathan Edwards]

One thing that interests me at the moment is that people with ME/CFS may be partly misinterpreting the cause and effect relations of symptoms, not because of any unhelpful preconceived ideas but because the disease plays tricks on our natural way of understanding symptoms.

My analogy would be a band of musicians getting ready for a concert on stage, one of whom is carrying a microphone around absentmindedly while another is setting up the mike stand. Others are tuning up and kicking chairs around. Every now and then the microphone howls a high pitched whistle ('microphony') because it is close enough both to a noise and to a speaker to generate a signal loud enough to produce a positive feedback loop with the speaker. The noise may not be that unusual. It may simply be that the musician has walked between a guitarist and a speaker a bit close.

The point being that a complex regulatory system can generate responses to stimuli in very unpredictable ways. We see this in lupus, where major flares can be triggered by all sorts of events or no identifiable event.

I wouldn't be surprised if long term studies of activity and crashes, if they get done, do not show a very consistent relation, not because there is no relation but because the cause and effect link is complicated. The sort of complexity I am thinking of probably implicates neural mechanisms but that does not exclude the final generation of symptoms being mediated through immune mechanisms such as local cytokines. Longer term immune mechanisms might also determine the instability of the neural responses.

The net effect on health may then look more like snakes and ladders than a classical allergy to a seasonal pollen or Bradley Wiggins's exercise-induced asthma.

 

[hotblack]

That’s a really interesting analogy. My knowledge of biology is poor but I used to deal with problems in large complex software systems, so that’s often one way I look at things. And often there a problem we’d see would take ages to track down because of a complex interaction of different bits of code and other factors like hardware it was being run on or timing. Here may be an input which was triggering things but that wouldn’t always lead us directly to the root cause, and sometimes the input would be something unexpected but others it would be benign or not always cause the problem.

 

[Haveyoutriedyoga]

One thing that interests me at the moment is that people with ME/CFS may be partly misinterpreting the cause and effect relations of symptoms, not because of any unhelpful preconceived ideas but because the disease plays tricks on our natural way of understanding symptoms.

My analogy would be a band of musicians getting ready for a concert on stage, one of whom is carrying a microphone around absentmindedly while another is setting up the mike stand. Others are tuning up and kicking chairs around. Every now and then the microphone howls a high pitched whistle ('microphony') because it is close enough both to a noise and to a speaker to generate a signal loud enough to produce a positive feedback loop with the speaker. The noise may not be that unusual. It may simply be that the musician has walked between a guitarist and a speaker a bit close.

The point being that a complex regulatory system can generate responses to stimuli in very unpredictable ways. We see this in lupus, where major flares can be triggered by all sorts of events or no identifiable event.

I wouldn't be surprised if long term studies of activity and crashes, if they get done, do not show a very consistent relation, not because there is no relation but because the cause and effect link is complicated. The sort of complexity I am thinking of probably implicates neural mechanisms but that does not exclude the final generation of symptoms being mediated through immune mechanisms such as local cytokines. Longer term immune mechanisms might also determine the instability of the neural responses.

The net effect on health may then look more like snakes and ladders than a classical allergy to a seasonal pollen or Bradley Wiggins's exercise-induced asthma.

I guess some assumptions on this thread and in my thinking on this matter include that
1. processing sensory input takes energy...or 'capacity' or 'ability' (attention being something that uses energy?)
1.1 That certain sensory input or combinations of sensory input uses more energy
2. that we have less of this energy or capacity or ability (overall? Specifically for processing internal and external sensory input?), that we have an envelope
3. That when we use more than our envelope it causes a reduction in our envelope
4. That when we use more than our envelope then it causes PEM - delayed onset multiple sympoms
5. That the PEM physiological state causes the symptoms that happen at that time

What else are we assuming with this?

I find that a top up dose of my ADHD stimulant can help me cope with going to an environment that is busy (as in, visually busy and bright, lots of different sounds and sources of sounds) and make the experience itself easier and I don't crash as much after, the psychiatrist was not surprised at all about this, I know it's something to do with regulation of attention to, or away from stimuli, regulation of emotion to do with that process/outcome, and my neurodivergent AND ME/CFS brain benefits from whatever the stimulant does - when we say stimulants give energy we still don't know what that really means, does that mean it gives energy to the thing that produces the chemical that causes a chain reaction that makes us able to regulate our attention consciously and subconsciously with less 'effort'?

Energy, capacity, ability, effort, stimulate, attention, regulate, conscious, subconscious and envelope...all muddy terms with muddy connections.

 

[Creekside]

Is it the energy production systems due to excessive demand?

I think that's a false trail. The "energy" hypotheses are popular because we feel like we're lacking in energy, but so far there's no reliable evidence to support it. There are other possibilities for that feeling, such as neurological dysfunction.

My cognitive triggers for PEM are inconsistent with level of neural processing. I expect that riding a bike involves about the same amount of neural processing as driving a vehicle, but the latter triggers my PEM while the former doesn't. Driving is more stressful (crashing at 100 km/h is far worse than at 10 km/h. driving at night on icy roads in a snowstorm triggers much worse PEM than driving under good conditions. Stress hormones? However, a pleasant friendly chat for a few minutes is hardly stressful, yet results in the same level of PEM as driving in somewhat stressful conditions. Stressful driving conditions do require more focus, but I'm not sure what that means in terms of neural processing.

It's possible that the region of the brain involved in an activity is important. ME's effects on neural function might vary regionally. Some regions might have longer synapses, a different density of glia, or different blood or glymph vessel properties (are you next to the main line, or at the end of a long narrow branch), and that would vary with the individual. Thus some people would have more severe muscle symptoms, or gut symptoms (or sensitivities), or be overly sensitive to signals (light, sound, etc).

For me, foods can cause the same symptoms as PEM, so it seems likely that the ratios of certain chemicals can produce the same results. I think physically-induced PEM is due to changes in ratios of chemicals, such as IFN-g, that result from muscle exertion. The immune system has consistent delays, so that would explain the consistency of physically-induced PEM delay. Cognitive exertion affects the brain cells directly, thus a shorter and less consistent delay.

 

[Kitty]

The "energy" hypotheses are popular because we feel like we're lacking in energy, but so far there's no reliable evidence to support it.

Specially as the fatigue+ill feeling can come and go within the same day in milder ME. I get up feeling like death, my limbs are barely working, but on a better day a good part of it will evaporate within a couple of hours like a spring haar. I haven't done anything except get out of bed and sit on a sofa; some of the time I haven't even eaten.

It's hard to explain it by saying there must have been excessive energy demands when I was lying down, but I recovered by sitting up.

As for the steep reduction in sensory tolerance in PEM: I can't differentiate it from the same effect when feeling really unwell with an infection. It seems at least possible that it's part of the normal illness phenomenon.

 

[hibiscuswahine]

I think there are central mechanisms involved but there is not enough evidence.

I don't think it is a problem with the structure and function of the peripheral nervous system. Neurology has not been able to delineate it. The dorsal ganglion finding is interesting and I do recall this from a few years ago (or decades as I can often not trust my recall), but I would expect this sort of disruption to be testable (either by examination or with some sort of electrophysiological technique on the dorsal ganglion. (If I had the cognition I would check out a few papers but alas I am not up to it today)... I think postmortem examination of more ME brains and the nervous system would be useful but there haven't been enough brains donated and examined to properly show anything. We have only had biobanks developed over the last few years.

There is a lot of research into brain diseases like Alzheimers, MS, Parkinson's etc but not much into our illness. It may not show up at postmortem because it is due to brain function rather than a structural problem. For instance, in psychiatry, not much turns up as a structural problem in brains of people with Schizophrenia, Bipolar Affective Disorder, Major Depressive Disorder, ADHD, but imaging can show dysfunction and is usually pretty clear after a thorough psychiatric assessment.

For ME, imaging is definitely showing differences in functioning and last year, or the year before, some preliminary scanning work in Australia showed enlargement of the brain stem but for all of these studies they need to be performed on larger groups of pwME and be replicated to really understand what is going on. Neuropsychological testing can show the deficits in cognition but I don't think they have ever been done longtidunally, eg looking at times in PEM and times when not in PEM. I think that would be very useful to document scientifically but would not tell us the cause but perhaps some of the pathways. The science is still in the very early phases of researching structural and functional pathways in ME eg the default mode network.

I am not neurodivergent but I do understand why medication would help ADHD and help cope with ME due to improved cognitive function. I often reflect on how poor my cognitive function is compared to when I was able practising medicine a decade ago and how different my cognition is when in a crash and when recovered from it. And then there is age related decline and any other comorbid illness effects on it.

 

[SNT Gatchaman]

It may not show up at postmortem because it is due to brain function rather than a structural problem. For instance, in psychiatry, not much turns up as a structural problem in brains of people with Schizophrenia, Bipolar Affective Disorder, Major Depressive Disorder, ADHD, but imaging can show dysfunction and is usually pretty clear after a thorough psychiatric assessment.

Though the structural problem underlying dysfunction may have been very difficult to delineate ex vivo. Eg this recent paper —

Glycocalyx shedding patterns identifies antipsychotic-naïve patients with first-episode psychosis (Sep 2024)
Andersen; DellaValle; Bøgehave; Mogensen; Hahn; Goth; Sørensen; Sigvard; Tangmose; Bojesen; Nielsen; Tonetto; Jørgensen; Hempel; Rungby; Glenthøj; Ambrosen; Ebdrup

ABSTRACT
Psychotic disorders have been linked to immune-system abnormalities, increased inflammatory markers, and subtle neuroinflammation. Studies further suggest a dysfunctional blood brain barrier (BBB). The endothelial Glycocalyx (GLX) functions as a protective layer in the BBB, and GLX shedding leads to BBB dysfunction.

This study aimed to investigate whether a panel of 11 GLX molecules derived from peripheral blood could differentiate antipsychotic-naïve first-episode psychosis patients (n=47) from healthy controls (HC, n=49) and whether GLX shedding correlated with symptom severity. Blood samples were collected at baseline and serum was isolated for GLX marker detection. Machine learning models were applied to test whether patterns in GLX markers could classify patient groups. Associations between GLX markers and symptom severity were explored.

Patients showed significantly increased levels of three GLX markers compared to HC. Based on the panel of 11 GLX markers, machine learning models achieved a significant mean classification accuracy of 81%. Post hoc analysis revealed associations between increased GLX markers and symptom severity.

This study demonstrates the potential of GLX molecules as immuno-neuropsychiatric biomarkers for early diagnosis of psychosis, as well as indicate a compromised BBB. Further research is warranted to explore the role of GLX in the early detection of psychotic disorders.

Link (Psychiatry Research)

While Structure and Response to Flow of the Glycocalyx Layer (2014, Biophysical Journal) said —

the glycocalyx plays two critical functions for the endothelium: as an interface between chemical signals in the blood and biochemical pathways inside cells; and as a barrier against chemical or mechanical damage.

In early studies of the endothelium, the glycocalyx had remained unnoticed because it was dificult to visualize: the tiny sugar coat was washed out by the preparation procedures involved in conventional light and electron microscopy.

 

[hibiscuswahine]

@SNT Gatchaman Though the structural problem underlying dysfunction may have been very difficult to delineate ex vivo.

Yes good point. Nice study.

(Translation: Ex vivo - out of the body, post mortem study, that stirred a few brain cells on a rainy afternoon )

 

[Haveyoutriedyoga]

I am not neurodivergent but I do understand why medication would help ADHD and help cope with ME due to improved cognitive function.

By "cognitive function" do you include the functions involved in being comfortable and alert in busy noisy environments, as well as thinking deciding and planning etc?

One thing that interests me at the moment is that people with ME/CFS may be partly misinterpreting the cause and effect relations of symptoms, not because of any unhelpful preconceived ideas but because the disease plays tricks on our natural way of understanding symptoms.

I think what I'm hearing from some of the replies is that the sensory processing issues and other symptoms we get in crashes, while worth understanding from a management point of view, may be less helpful (and possibly distracting?) for working out what is causing a. the disease and b. the experience of the disease.

Does it 'interest you' or are you politely pointing it out?

 

[hibiscuswahine]

@Haveyoutriedyoga yes, part of the neuropsychological examination is distractibility, the ability to maintain attention (sort of like alertness, preparedness) when asked to do a cognitive task. If the clinical psychologist (or psychiatrist who does more simpler tests for cognition), understands ME takes a history and talks about social interactions etc, they will be trying to work out what environments you can manage comfortably vs the one's that are stressful. Eg I like being on my own as it is quiet and I can then concentrate on the things I want to do, but add noise, I can easily become distracted (and irritable, sometimes). I don't mind busy environments as long as there is no expectation that I have to take part in them, but I have to be able to leave them if they become overwhelming with noise. Of course, things could be different with neurodivergent people. I know some people with ADHD who like busy environs, it calms them.

 

[EndME]

It does feel like activity that occurs in non-stressful, familiar, low stimulation environments is better tolerated and more of it can be done before entering PEM territory. That could explain some of the unexpected variance in how well activity is tolerated, because we don't usually pay attention to these things but rather focus on the activity per se.

I think if one leaves away the term "PEM", you would have described something that would apply to most of the rest of the world. Students prefer to do study in libraries rather than in subway stations, seminars tend to take place in classrooms rather than at raves, athletes tend to perform better if they aren't stressed about transfer rumours, some people are able to work from home better than at the office and for some it is the exact opposite, high performance athletes tend to have routines etc. Yet all of these people will be able to handle more "workload" on some days and less on others. There will always be a tremendous amount of variance I think inferring anything from that about ME/CFS might be difficult and if something such as described by @Jonathan Edwards would be occuring it might be entirely pointless. It that case it could be like inferring that a broken leg has something to do with ME/CFS, simply because people feel worse when they have a broken leg.

To answer my own question:

Currently we study PEM almost exclusively by collecting information from self-reported symptoms and by doing 2-day CPET studies.

It could be useful to study other potential triggers of PEM: processing conversations, spending time in stimulus rich environments, touch, orthostatic stress, heat and cold exposure, metabolic stress, and so on. Maybe useful information could be gained in this way.

We could discover that physical activity is the most obvious trigger but not the only important one. That in turn might make it easier to figure out where things are going wrong in the body. If PEM can be triggered without stress on muscles or the vascular system, that would suggest the problem is not limited to those systems or is elsewhere.

I agree!

Additionally I think the first thing that would have to be done is to begin to try to understand the cognitive problems pwME are reporting. From what I've seen most studies use examinations used for other illnesses and then either obtain a null result or not, but I'm not sure if anyone has tried to capture what is going on. From my, possibly extremely biased view, a group of people report some from of "neurological PEM". Many describe it to be similar to "physical PEM" but many descriptions also seem to support it being slightly different (from what I've seen less delayed and maybe with a shorter lasting duration). I don't know if you'd even have to start of with an in person study. A well conceived questionnaire, possibly in combination with some "exercises" that can be done on the computer, could serve as a beginning, just to understand what patients are even describing and at what frequency.

I think instead of starting by doing a in person study you'd probably want to understand what impacts actually what symptoms, in which populations and at which rates. I don't know if anybody has actually done that.

Energy, capacity, ability, effort, stimulate, attention, regulate, conscious, subconscious and envelope...all muddy terms with muddy connections.

I agree! I think if we're speaking colloquially many, or at least some people, will understand what is meant, but if this language is being used to untangle physiological phenomena it seems to be an additional hurdle more than anything (what I've written below is not a criticism but should rather highlight the fact that I have no idea which words are sensible).

I guess some assumptions on this thread and in my thinking on this matter include that
1. processing sensory input takes energy...or 'capacity' or 'ability' (attention being something that uses energy?)
1.1 That certain sensory input or combinations of sensory input uses more energy
2. that we have less of this energy or capacity or ability (overall? Specifically for processing internal and external sensory input?), that we have an envelope
3. That when we use more than our envelope it causes a reduction in our envelope
4. That when we use more than our envelope then it causes PEM - delayed onset multiple sympoms
5. That the PEM physiological state causes the symptoms that happen at that time
What else are we assuming with this?

I might be wrong but I don't think any of these things would have much to do with "energy" or at least not in the way it is defined in physics and possibly also not with the other things we often consider to be related, such as ATP.

At least I'm not aware of any evidence suggesting "thinking hard about something" would require more energy than not doing so, i.e. does a quantum physicist sitting at his desk use more "energy" than someone sitting at their desk watching a Netflix series inattentively/ reading a children's book (or whatever analogy may be more fitting in regards to a similar activity that is less vigorous)?

Nor do I think that point 2 would really match the description @Jonathan Edwards described. If there is a feedback loop that occurs than there wouldn't have to be less capacity, rather than some events, some of which might be entirely random, occuring that lead to a symptomatic worsening. It may be that certain things are more likely to amplify this feedback loop or increase the chance of it occuring, but I think that would be a different assumption.

Ability seems to have other problematic connotations and seems unwise to be used as such.

Similarly whilst I think the term envelope is easy for patients, carers and clinicans to understand in the everyday context and lives, if there is a complex system as in the hypothetical description above with different feedback loops there might be no envelope at all, at least not in the classical sense typically referred to by patients, i.e. in the sense that this is controllable as the words "when we use more than our envelope" would suggest. Something similar might be true for a term such as capacity or a term such as threshold, which could be more accurate description of there simply being some complex dynamics which sometimes lead to a passing of the threshold with the dynamics below, at and above threshold possibly being very different and sometimes possibly completely out of control of the person being affected.

So what words should one use?

 

[Creekside]

So what words should one use?

A very good question, since it affects how we are treated by physicians and society. No obvious answer pops up though.

To me, ME involves "some factors or combinations of factors result in a combination of symptoms". Detailing what those factors are is difficult, since it varies so much between patients, they can be hard to identify (Was it something I ate an hour ago, or something I did 3 days ago?), and there are enough factors to make a lot of different combinations. Furthermore, the symptoms are generally unmeasurable and hard to consistently describe. I'm not sure there is any good way to communicate that to people who don't have the same condition.

Microbial infections are much more consistent in symptoms and responses to various factors. What words were used to communicate that in pre-scientific times? Did they solve that problem before science came up with microbial theory?

 

[Haveyoutriedyoga]

Microbial infections are much more consistent in symptoms and responses to various factors. What words were used to communicate that in pre-scientific times? Did they solve that problem before science came up with microbial theory?

Theory wise - myth, superstition, supernatural forces like evil spirits demons and wrath, punishments for moral failings and sins, religious theory. Balance of bodily fluids/humours (phlegm, bile etc). Miasmas/bad air. Symbolism for moral decay of society (e.g. in Shakespeare) - interesting parallel with the concept of yuppie flu.

Descriptive - plague smallpox and TB described symptoms of boils, fever, wasting

In pre-scientific method literature about MS, vision problems such as blurred or double vision, optic neuritis, and temporary blindness have been described as "dimness" or "darkness" falling over the eyes and been said to be divine punishment or a temporary affliction brought on by stress/ excessive emotions, humoral imbalance (fluids/bile/phlegm).

Eta: the issue is it's so hard to describe some of the sensations of an ME crash. That also feels supportive of the idea that we need a whole new paradigm to understand it.

Eta.2: I have tried a number of times to capture what I'm feeling while I'm in PEM, but it's so hard, I think I sort of disassociate when in that state, which might be a symptom of the physiological change or a mental reaction to the symptoms of PEM. It's really hard to describe the physical feelings in tangible words and not metaphors. Ok - twitching eyes, or a sharp pain in my forehead is easy but that overall unwell feeling is hard. But... we don't need to justify that unwell feeling when we obviously have covid or have had concussion.

 

[EndME]

To me, ME involves "some factors or combinations of factors result in a combination of symptoms". Detailing what those factors are is difficult, since it varies so much between patients, they can be hard to identify (Was it something I ate an hour ago, or something I did 3 days ago?), and there are enough factors to make a lot of different combinations. Furthermore, the symptoms are generally unmeasurable and hard to consistently describe.

I'm not entirely sure. I think there is a large difference between vague and meaningless descriptions of "chronic fatigue" vs ME/CFS as defined for example by the CCC and similarly other descriptions of delayed PEM appear to be rather specific. Of course there are still various problems, but specificity seems to be highly advantageous when describing symptoms.

A lot of these points will probably be applicable too many different illnesses, diseases or syndromes. For many of which diagnoses will also be difficult, require several years of training and will sometimes also just be "a patient has to fulfil a certain number of symptoms from a list of symptoms". For others they might simply have been untangled because someone found a clue inside the symptom description that had been ignored until then.

In that case I don’t really see ME/CFS being too different, but I also don’t have any medical knowledge.

One difference to most other illnesses, diseases or syndromes will be that nobody has been able to find any really valuable clues that lead to untangling parts of the pathology yet. But that will probably have more to do with the approach of seeing it as “chronic fatigue” rather than being more specific and going after specific clues. In that scenario words such as “energy” could be inappropriate and misdirect research into wrong directions, but I don’t there is any advantage too using a highly unspecific language. "some factors or combinations of factors result in a combination of symptoms" doesn’t describe anything but a chain of events, which applies to an infinite amount of different things in the world.

It seems advantageous to tear down the walls certain words such as “energy” have created for a moment, but that is only for a moment. One does so to gain a deeper understanding of certain things, a more specific understanding that can help build better walls build on top of a more solid foundation, rather than the goal being to end up with an ominous and vague description.

I'm not sure there is any good way to communicate that to people who don't have the same condition.

I think there are clinicians who have listened and understood the symptoms that are being described. For researchers it might be more important to find relevant and vital clues that can be examined, that has partially been done in terms of studying physical activity provoking PEM in 2-day CPET studies, but at the end of the day it has been done far too little in far too few directions (for example I don’t think anybody has even tried to understand to which degree “cognitive PEM” is a thing and what that thing entails). But I don’t think one can blame that entirely on issues of communication either, when ingenuity seems to have been such a massive hurdle.

Communication with care takers, families and the general society is an entirely different issue, but I think if a patient was to describe Graves disease to the general public they would also just hear "this person is tired”.

infections are much more consistent in symptoms and responses to various factors.

Are they? If anything the response to "too much activity" in ME/CFS patients seems to be more consistent than the response different humans have to a Covid infection (I'm wrongly replacing bacterial with viral, but i think the point will still stand similarly for bacterial infections, at least the PTLDS community would probably argue as such).

Eta: the issue is it's so hard to describe some of the sensations of an ME crash. That also feels supportive of the idea that we need a whole new paradigm to understand it.

Would that be important at all for research? Are patients with MS better able to describe what MS feels like or patients with Alzheimers better able to describe what Alzheimers feels like than ME/CFS patients are able to describe ME/CFS? For a study focused on something specific, I think you'd need a description that is somewhat consistent in a sufficiently large subset of patients and that is able to give specific clues towards a very specific pathology that you can try to entangle, rather then being able to accurately describe everything that is occuring in everyone. To recruit patients you'll need to recruit according to some criteria, but at least until now the sensations of an ME crash have been of rather little importance in those.

 

[Haveyoutriedyoga]

Would that be important at all for research? Are patients with MS better able to describe what MS feels like or patients with Alzheimers better able to describe what Alzheimers feels like than ME/CFS patients are able to describe ME/CFS? For a study focused on something specific, I think you'd need a description that is somewhat consistent in a sufficiently large subset of patients and that is able to give specific clues towards a very specific pathology that you can try to entangle, rather then being able to accurately describe everything that is occuring in everyone. To recruit patients you'll need to recruit according to some criteria, but at least until now the sensations of an ME crash have been of rather little importance in those.

If this were to happen, would one apply an existing theoretical model or framework to the questions and the interpretation of the responses? Are there any existing frameworks that work?