Was there a gap between trigger and onset of your ME/CFS?

[Evergreen]

Because we don’t know how many of us looking at this don’t recognise a specific trigger or how many with gradual onset if the longer the gap between any possible trigger event and the ME onset makes any possible link more tenuous, it is difficult to know how meaningful these figures are.

Objectively I can not conclude my glandular fever was the trigger of my ME, though I feel confident in assuming it was because there was no gap between the acute infection and the chronic condition. However the longer any gap the harder it is to make that assumption.

Yep, I know what you mean. People with no gap are, by definition, going to be the ones filling out the poll most because they're the ones who are most confident that their ME/CFS was triggered by an infection or vaccination. People who got ill within a few weeks of the onset of a substantial infection are also usually pretty confident that there's a link. If the latter group is less confident, then yes, the poll may not yield useful info. From the timeframes in the poll, I suspect JE is not interested in the gradual onset group for this particular question.

I think JE might be trying to figure out if something specific is happening here, like a biological/immunological process Y that would be expected to kick in at a certain timepoint e.g. 2 weeks after the onset of symptoms because that would be 2 weeks after immunological process X which happens at onset. So I'm not sure if the details we think might matter, matter. I'm sure he'll explain soon!

 

[Jonathan Edwards]

It's all fine. I will explain when we have a hundred entries!

 

[hotblack]

I didn’t want to let looking at the results impact my decision so decided to just vote and went for ‘more than two weeks’ as what I would now call ME happened later and ‘more than’ is a very vague definition (which could include more than 2 months!)

It is interesting seeing the skew towards no.

 

[Nightsong]

My own story is.. rather more complex. There was an infection (a specific one) from which I used to date my onset, but I have a suspicion that that was more something that brought an ongoing process to the surface (one that might perhaps have developed into ME/CFS over a longer period of time in a more gradual way). In the two or three years prior to that apparent trigger there were a small number of anomalies, often where I felt unusually weak or fatigued or had orthostatic symptoms, sometimes after periods of more intense physical activity, and they seemed to be very slowly increasing in frequency - something that I only worked out after working through all my journals and emails and everything from the period. At the time I didn't think much of any of them but in retrospect they seem to make more sense.. or alternatively they could be completely coincidental.

So, not knowing for sure if I'm really a slow-onsetter or a classical post-viral case, I guess I'd better not vote. I'm a little surprised, actually, seeing so many "no"s, which has some implications as to what kind of pathophysiological processes are not likely to be involved.

 

[hotblack]

I think JE might be trying to figure out if something specific is happening here, like a biological/immunological process Y that would be expected to kick in at a certain timepoint

Or perhaps how people who think there was a clear trigger think about or describe that?

It's all fine. I will explain when we have a hundred entries

Or just how quickly he can get 100 of us to answer a question!

We’re GuinME pigs

 

[Evergreen]

It's all fine. I will explain when we have a hundred entries!

It's as if you don't want to influence our responses. Don't you know how ME/CFS research works?!

 

[AliceLily]

I think I might have been too quick to answer this poll. I can't remember back to 1995 and the first weeks after my ME onset. ME has always felt to me that once I got it, it has never left me. I feel it there. I know how subtle ME can be as well at times. But that is not accurate enough for a poll.

*Please can you minus my vote of 'No' from the tally. I shouldn't have voted at all.

 

[Jonathan Edwards]

I think JE might be trying to figure out if something specific is happening here

Yes, I should spill the beans now, although I wasn't quite sure which hypotheses would stand or fall with all the possible results. I think I should have said three weeks rather than two but never mind.

What the results seem to show is that ME/CFS inset is probably not like rheumatic fever or Reiter's syndrome in which an immune response evolves, starting at the point of infection and taking about 10-20 days. The two situations are probably different in that rheumatic fever stops evolving if you kill the bacteria, Reiter's does not.

I think this tends to scotch the 'molecular mimicry' autoimmune response theory. It does not necessarily go against autoimmunity though, since autoantibody evolution can occur over periods of years, but importantly it does not usually seem to have anything to do with triggers at all!

The results look to me to suggest what some others have suggested. Maybe viral malaise provides one side of a vicious cycle that can trip you into ME/CFS if you already have a disturbance of regulation of that cycle hiding away. It might also prime whatever the disturbance can be but for 'later use' so that ME/CFS does not itself appear until 3 months later. This would explain why the relation to infection seems inconsistent. In rheumatic fever and Reiter's the infective episode is always there as far as we know and nearly always traceable.

 

[Ash]

Yes, I should spill the beans now, although I wasn't quite sure which hypotheses would stand or fall with all the possible results. I think I should have said three weeks rather than two but never mind.

What the results seem to show is that ME/CFS inset is probably not like rheumatic fever or Reiter's syndrome in which an immune response evolves, starting at the point of infection and taking about 10-20 days. The two situations are probably different in that rheumatic fever stops evolving if you kill the bacteria, Reiter's does not.

I think this tends to scotch the 'molecular mimicry' autoimmune response theory. It does not necessarily go against autoimmunity though, since autoantibody evolution can occur over periods of years, but importantly it does not usually seem to have anything to do with triggers at all!

The results look to me to suggest what some others have suggested. Maybe viral malaise provides one side of a vicious cycle that can trip you into ME/CFS if you already have a disturbance of regulation of that cycle hiding away. It might also prime whatever the disturbance can be but for 'later use' so that ME/CFS does not itself appear until 3 months later. This would explain why the relation to infection seems inconsistent. In rheumatic fever and Reiter's the infective episode is always there as far as we know and nearly always traceable.

Your hypothesis could be correct based upon lots of other information you have on autoimmunity, that being your expertise. Plus your observations from here and elsewhere re pwME and their illness course.

But for this poll I am unsure.
People on here who respond most often, are long time ill people. Maybe we can’t remember back that far. Especially if we were very sick right at the relevant time point, or teenagers or children, as to the transition from one type of feeling terrible, infection, to another, ME.

I was very ill for three weeks plus. I’ll never forget that. I remember the really intense part and I remember the aftermath very clearly. But there is a blank in my mind between the two. So what if it did change at around ten days or so? I couldn’t say.


If there was a change at 10-20 days for some, would you suspect something non ME as the illness?

 

[Jonathan Edwards]

So what if it did change at around ten days or so? I couldn’t say.

Yes, I appreciate that this is a very rough and ready survey. What has actually surprised me is the complete lack of report of a short window. For the 'reactive' arthritis that short window sticks out like a sore thumb. It is the norm.

 

[EndME]

Yes, I appreciate that this is a very rough and ready survey. What has actually surprised me is the complete lack of report of a short window. For the 'reactive' arthritis that short window sticks out like a sore thumb. It is the norm.

I'm wandering whether this might not be somewhat trigger specific rather than something to do with signals in regards of ME/CFS.

Avi Nath has certainly spoken about the "recovery window" and it is certainly a topic amongst Long-Covid patients.

When I try to remember my time with glandular fever and the following episode of post-viral fatigue I am unable to recall a "recovery window" it was more so an extremely slow and somewhat continuous process. But I suspect that has more to do with glandular fever/EBV than it does with post-viral fatigue or even ME/CFS. If for a large part of people the trigger was to be gladular fever it might be hard to recall a "recovery window" or they might not even exist if recovery from gladular fever generally tends to be slow in which case a "recovery window"/"development of ME/CFS" would overlap with slow recovery times from glandular fever.

For Covid the situation could be quite different (at least for reinfections/amongst people with some form of pre-existing immunity) where the acute illness phase might tend to be behave more like one is used to with a shorter acute illness duration and a more sudden recovery (at least in the general population).

I wonder whether the rough results would not look quite different if one where to poll onset of ME/CFS and a "recovery window" according to different triggers. Would the results be similar or does the slow recovery process for example after glandular fever hide a recovery window/the onset of ME/CFS?

I'm guessing for Reiters the characteristic symptoms of the acute infection are different to that of Reiters, which is the same for ME/CFS (patients with ME/CFS don't have a fever, swollen lymph nodes, a cough etc), but if I'm guessing right the problem in the comparison might be that the symptoms of Reiters also don't overlap much with the symptoms of an acute infection which is different to ME/CFS where many symptoms of ME/CFS do overlap with that of an acute infections as well (for instance fatigue, muscle pain or brain fog), possibly making the identification of a "recovery window" harder even if very similar immunolgical processes would be occuring across conditions. It could be interesting if for ME/CFS a well established trigger or at least somewhat common trigger would be known whose symptoms don't overlap with ME/CFS, but I'm not aware of one...

 

[Jonathan Edwards]

Avi Nath has certainly spoken about the "recovery window" and it is certainly a topic amongst Long-Covid patients.

Thanks for several interesting thoughts. Is there a citation for this recovery window talk? It would be interesting to know how consistent its length is thought to be.

 

[Ash]

I'm wandering whether this might not be somewhat trigger specific rather than something to do with signals in regards of ME/CFS.

Avi Nath has certainly spoken about the "recovery window" and it is certainly a topic amongst Long-Covid patients.

When I try to remember my time with glandular fever and the following episode of post-viral fatigue I am unable to recall a "recovery window" it was more so an extremely slow and somewhat continuous process. But I suspect that has more to do with glandular fever/EBV than it does with post-viral fatigue or even ME/CFS. If for a large part of people the trigger was to be gladular fever it might be hard to recall a "recovery window" or they might not even exist if recovery from gladular fever generally tends to be slow in which case a "recovery window"/"development of ME/CFS" would overlap with slow recovery times from glandular fever.

For Covid the situation could be quite different (at least for reinfections/amongst people with some form of pre-existing immunity) where the acute illness phase might tend to be behave more like one is used to with a shorter acute illness duration and a more sudden recovery (at least in the general population).

I wonder whether the rough results would not look quite different if one where to poll onset of ME/CFS and a "recovery window" according to different triggers. Would the results be similar or does the slow recovery process for example after glandular fever hide a recovery window/the onset of ME/CFS?

I'm guessing for Reiters the characteristic symptoms of the acute infection are different to that of Reiters, which is the same for ME/CFS (patients with ME/CFS don't have a fever, swollen lymph nodes, a cough etc), but if I'm guessing right the problem in the comparison might be that the symptoms of Reiters also don't overlap much with the symptoms of an acute infection which is different to ME/CFS where many symptoms of ME/CFS do overlap with that of an acute infections as well (for instance fatigue, muscle pain or brain fog), possibly making the identification of a "recovery window" harder even if very similar immunolgical processes would be occuring across conditions. It could be interesting if for ME/CFS a well established trigger or at least somewhat common trigger would be known whose symptoms don't overlap with ME/CFS, but I'm not aware of one...

Yeah. I also wondered about a trigger difference. EBV to ME than for SARS-2 to long Covid.


But when I had EBV, this came with massive lymph swellings and a high temperature. I thought this was characteristic?

 

[Evergreen]

Yes, I should spill the beans now, although I wasn't quite sure which hypotheses would stand or fall with all the possible results...Maybe viral malaise provides one side of a vicious cycle that can trip you into ME/CFS if you already have a disturbance of regulation of that cycle hiding away. It might also prime whatever the disturbance can be but for 'later use' so that ME/CFS does not itself appear until 3 months later. This would explain why the relation to infection seems inconsistent. In rheumatic fever and Reiter's the infective episode is always there as far as we know and nearly always traceable.

Thank you for spilling! When you say "Maybe viral malaise provides one side of a vicious cycle", does that relate to "stay-at-home" in this previous post of yours?

When I first started thinking about ME I wondered if perhaps it might be the post-infective result of over-enthusiasm in a fifth domain - which we might call stay-at-home. There might be CD8 T cells that express none of the domain specific adhesion molecules and rather than police specific peripheral tissues police lymphoid tissue itself. Policing lymphoid tissue is a major job of its own, because CD8 cells are used there to refine clonal selection for B cells and very likely CD4 T cells.

You could then have an illness with systemic symptoms similar to Crohn's or Reiter's, including 'fatigue' but with no local inflammation. Symptoms would be mediated by non-inflammatory danger signals, possibly through T cell/neural interaction through muscarinic receptors etc. I don't know if I buy that as at all likely but it remains in my view a sort of model for how a theory could fall into place for ME.

And then would you expect this group to have had a little gap between infection and ME/CFS?

It does look as if there is something different about people who report improvement after cyclo. IgG is lower but IgM is higher. Both IgG1 and IgG4 are lower and have completely different functional roles so if anything I suspect this is telling us about some feedback effect on Ig production, possibly due to a shift in T cell behaviour. That would fit with the idea that some ME/CFS is a bit like Reiter's with an ongoing shift in T cells. I don't think it points to autoimmunity.

 

[Sean]

Was immediate for me, and started with a violent medical event.

I woke up fine on a Saturday, and played squash. Went home had a shower, and then did some shopping and had lunch. Came back home and started feeling unwell, which deteriorated seriously over the next hour or so. Had to be taken to the emergency department. Symptoms superficially resembling kidney stone or pancreatitis. Had bloods, x-rays, etc. Nothing obvious. (Keep in mind that this was in the mid 1980s, so most medical tech was not as advanced or available as now. Didn't get a CAT scan, for example, just basic x-rays.)

They were about to start prepping me for exploratory bowel surgery, when I started throwing up a lot of bright green muck. Nothing out of the other end, only the mouth. Started improving afterwards. After a bit they shot me full of pethidine. Lights out for a few hours. Woke up, and they sent me home, feeling very sore and exhausted and sorry for myself.

But a bunch of symptoms started that day that have stayed with me ever since. Took some time for me to start discerning the patterns and features, of course. But the basic symptom profile was clearly there and causing serious trouble from day one.

About two years after onset I got a very nasty flu, which made it permanently worse. Forty years after onset it has never even looked like going away.

From a healthy active 20 yo man, with no significant medical history, to unrelenting serious ME took less than 12 hours.

 

[EndME]

Yeah. I also wondered about a trigger difference. EBV to ME than for SARS-2 to long Covid.

But when I had EBV, this came with massive lymph swellings and a high temperature. I thought this was characteristic?

Yes that is my understanding as well. A high temperature, lymph swellings etc are all the main characteristics of glandular fever, but they are not the main characteristics of ME/CFS.

I think I expressed myself badly above. What I was trying to say is that the main characteristics of the acute illness (fever, cough, high temperature, discoloured mucus, massive lymph swellings etc), i.e. the trigger, are not the main characteristics of ME/CFS. This holds for both Reiters and ME/CFS and the respective illnesses/triggers that cause them (at least that is my understanding). The problem however on the opposite side is that the main symptoms of Reiters are also not part of the acute illness (at least if I'm assuming correctly), whilst the main symptoms of ME/CFS are often tend to be part of the trigger as well (fatigue, cognitive problems, muscle pain etc).

So identifying a "recovery period" similar to Reiters might not be possible in ME/CFS simply because there is a larger symptom overlap in ME/CFS with the trigger rather than having something to do with a time duration of an immunological response.

I'm wandering whether such problems could possibly be dismanteled by approaching the problem slightly differently, which might however require rather smart and careful investigators. For instance one could only look at a specific symptom that is believed to be a central part of ME/CFS but doesn't appear very often in certain ME/CFS triggers. I was for instance specifically thinking about onset brain fog/cognitive problems in ME/CFS after Covid because my understanding is that the current Covid variants don't cause brain fog in the same way the initial variants did in a population with less immunity. The problem here is of course that ME/CFS after Covid isn't well characterised and additionally that ME/CFS after Covid appears to be becoming less common. Additionally doing it retrospectively could also introduce bias.

But if you'd have a study that showed people with ME/CFS and cognitive problems develop brain fog after a period of recovery or even don't report it as part of the acute illness than that could be signal for this specific symptom to underly a certain dynamic. Alternatively you might find out that only people that also have brain fog as part of their acute illness also develop ME/CFS with brain fog and that there is a "recovery period" from brain fog or that there is no "recovery period" from brain fog and that it is rather constant which would point at different dynamics. I would expect the results to be somewhat heterogeneous, but someone smart might still get good data if such a study was carefully conducted.

I don't know whether something similar could be done with EBV/glandular fever because my impression is simply that the glandular fever episode appears to be longer lived so that it all becomes rather muddy, but maybe someone smarter can work something out. I believe Scheibenbogen is part of a study that follows teenagers in Germany that have glandular fever and studies the relationship to the development of ME/CFS. I thought brain fog might be the better symptom to study rather than PEM in this instance because PEM as part of ME/CFS and fatigue as part of acute illness triggers might be too similar but I could be wrong about that. A rather obvious hurdle here could be that no one has characterised the cognitive problems reported by pwME...

 

[Jonathan Edwards]

Yes, I am thinking that the stay at home T cell story may not be on target quite. There is no HLA genetic link as far as we know, which is also a negative. The more I look at it the more it seems to me that the immune side of a cycle would need to be something not usually involved in other chronic diseases.

 

[Creekside]

The more I look at it the more it seems to me that the immune side of a cycle would need to be something not usually involved in other chronic diseases.

This link appeared on PR this morning: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awae215/7811070

It's a 7-T MRI study about long covid, and it found long-term changes in cells in the brainstem. One change seems to involve iron accumulation. My mental image of this is the cells building up some extra tools and workbenches to deal with the virus (or maybe the immune response to it), and there's no clean-up squad to completely remove the changes afterwards. We know what happens when we allow our workspaces to become cluttered. Another thought is that this might be an anti-viral response from very early in life's evolution; a way to improve protection from later infections of that sort. It then got superceded by our modern immune system, but hasn't been completely removed. This change is showing up in the primitive part of our brains; maybe it's harder to shut old genetic pathways down there.

ME might not show that specific change in brainstem cells, but there could be some other holdover primitive antiviral response hiding somewhere, somehow activating to cause ME.

Another thought on how ME could be hiding: perspective. It could involve multi-system interaction, such as a small change in one cell's parameters and a different small change in another's, and you won't notice it just looking at cell parameters individually; you need a wider perspective.

 

[Robert 1973]

I think I’ve said this before but maybe worth repeating. What I consider to be me ME/CFS symptoms started suddenly when I had an accurate infection – tonsillitis and suspected glandular fever. In fact I had had bad tonsillitis for a few weeks and the ME/CFS seemed to come on when I was prescribed a second course of stronger antibiotics. However, looking back I hadn’t been particularly well for 3-4 years. I had had to cut back on sports because of unexplained joint problems, I seemed to keep getting infections, I was unusually tired, and I used to get what felt like some sort of circulatory pain which again was never explained. In retrospect I wonder if I had very mild ME/CFS, or some sort of pre-ME/CFS state. But the transition from leading a normal life – studying, socialising, drinking alcohol exercising – to being severely incapacitated by ME/CFS was sudden and came as described above.

Important to emphasise that the ME/CFS symptoms came on quite suddenly (I remember exactly where I was) and very different from the tonsillitis/EBV symptoms. It didn’t feel like a continuation or a worsening of those symptoms. It felt like something new and very different.

The other thing I’ve found is that the experience I’ve described does not usually fit well with questionnaires that I’ve filled in over the years, where the choice is normally sudden onset or gradual, and post acute infection or not. My history doesn’t really fit into those boxes and I wonder how many other people may have similar histories that are not identified because of the way histories are recorded.

I also remember that I was reluctant to tell doctors that I thought I had had something wrong for me for 3-4 years because a) I wanted to emphasise the sudden onset of the new debilitating symptoms and b) I didn’t want to be perceived as being a hypochondriac or someone who has been depressed for a long time (which wasn’t and hadn’t been).

[Edit: typos]

 

[Sly Saint]

It didn’t feel like a continuation or a worsening of those symptoms. It felt like something new and very different.

Similar to me. I had had very bad flu a year before and a string of minor health problems before and after that.

I too felt that the new symptoms, when I had officially 'recovered' from the pneumonia (IE chest x-ray was clear), were not the same.

Yes, I did still have chest pains which I put down to costochondritis, sore throat and headaches, but there were others like loss of balance ( which were more like when I had labyrynthitis) but also the cognitive symptoms which were scary. (egSpeech, stammer, not able to think straight or do basic problem solving. I was an analyst/programmer).