Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Chu et al., 2019)

Pyrrhus

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Not new, but an important epidemiological paper:

Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Chu et al., 2019)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370741/
Lily Chu, Ian J. Valencia, Donn W. Garvert, and Jose G. Montoya

Excerpt:
Chu et al 2019 said:
Background:
Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together.

Objective:
Describe ME/CFS onset and course in one United States-based cohort.

Methods:
One hundred and fifty subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics.

Results:
The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20–25%).

Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course.

Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included.

Conclusions:
This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g., the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition.
 

Pyrrhus

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So it looks like roughly:
  • 64% of patients said that their ME started with an infection.
  • Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms.
  • 47% of patients were unable to work.
  • 59% of patients said their disease had a fluctuating course- neither improving nor declining.
  • 97% suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions.
  • 13% of patients had a family member with ME.
 

nerd

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All of these diagnoses and symptoms are associated with each other in one way or another. Stress can trigger viral reactivations and viral reactivations can cause stress. Maybe stress contributes to viral reactivations and this causes the whole vicious cycle, just one theory of many. I don't think that the high representation of infection episodes is just a perception and reporting bias, especially since viral reactivations might not happen symptomatically and there is also the possibility that this is underreported. The difference is just too large.

Psychiatrists might look at this and point out the depression, as if it could explain all of the issues and was the causality. My point is, this will be a chicken and egg situation as long as research looks at symptoms and diagnoses. Pathophysiological findings might describe correlating factors as well, and not necessarily the causality.


I'd hope for more research on children, their pathology when healthy and their pathology during infection, after infection and when developing ME, vs. controls. There are a few studies on this, but not much on the pathological side. I think that children might be the best candidates to minimize the risk of a "sleeping" condition that just takes an infection as trigger while this infection might not necessarily be responsible for the underlying pathology and just trigger it. For example, just as SARS-CoV-2 triggers viral reactivations so that it becomes difficult to distinguish SARS pathology from herpes pathology. They would really have to look at the whole latent/sleeping reservoir, and quantify it regularly. Something might stick out at one point. Even if it's not statistically significant at first. It might give them a clue what pathogen is really responsible from a causal side, and what pathogens can trigger a sleeping pathogen. It also allows to exclude some theories that have never been reproduced or confirmed.

There is also the possibility of predisposition, that a virus just triggers autoimmunity even if it's completely eliminated. But I'm beginning to have doubts that autoimmunity can be an completely self-sufficient disease, just triggered like that, and not be resolved. I have the notion that many autoimmune diseases have some sleeping/hidden component that has nothing to do with serology and that the serology is just a vicious cycle that keeps getting fed by something else. This reminds me of SLE, which is still not very clear in my view, despite the complete pathway that has been researched on how EBV can cause antibody formation eventually. They often put it like there's first EBV, and then there's SLE, ME, MS, lymphoma, or whatever, just because EBV isn't acute anymore. I'm not trying to imply that EBV treatment alone could reverse these vicious antibody cycles and their havoc, but maybe there's something to it that allows the conditions to eventually recur and maybe there's something to the treatments of the diseases (such as HCQ for SLE) that also helps from a causal perspective, which then serves the confirmation that the suspected mechanism of action is the only responsible mechanism of action and that this implies that the hypothesized pathophysiology is complete even if it isn't complete in reality.
 
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godlovesatrier

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Your new avatar is really cool @Pyrrhus !!!

Is something going around, or in the water or whatever? Everyone seems to be sprouting new avatars .... OK, not everyone, but at least a few ..... OK, not a few, but at least 2. Or maybe 3 .....
Your responses are the best :_

Someone's messed with the coolaid! As you'd say in the states.

So it looks like roughly:
  • 64% of patients said that their ME started with an infection.
  • Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms.
  • 47% of patients were unable to work.
  • 59% of patients said their disease had a fluctuating course- neither improving nor declining.
  • 97% suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions.
  • 13% of patients had a family member with ME.
This is really interesting. I wonder what proportion of the 53% were able to work full and part time. My god I am in the 13% with a family member who has ME, that's incredibly low really.
 
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Second star to the right ...
Your responses are the best :_
Thank you !!! Personally, I really like yours, above :D:D:D :rolleyes::rolleyes: .....
Someone's messed with the coolaid! As you'd say in the states.
Someone's always messing with the KoolAid over here, which is probably why we insist on spelling it incorrectly :xeyes::xeyes::xeyes: ....
My god I am in the 13% with a family member who has ME, that's incredibly low really.
I'm right there with you. We certainly belong to a sad little droopy, exclusive club, eh?


My dad had to give up his travel jones, as well as his happy life in Rome, because of some viral infection that no one could really figure out and that landed him in a hospital in Spain, delirious and running a frighteningly high fever, as he and my stepmother (who I adored ..... a truly lovely, lovely woman) were on their way home to the US for an annual visit. He was in quarantine for a couple of months while they ran tests and poked and probed, before they let him and my stepmother close out their apartment and life in Rome, settle any other affairs, and return to the US. The best the Drs in teh Spanish hospital could come up with was a viral infection that caused severe inflammation of the brain, and damage to the myelin sheathing around his nerves, which is a damn sight better than we get today, diagnosis-wise.

Many years later it was diagnosed as infectious encephalomyelitis. He never saw Europe again, and while he gradually recovered and was only moderately affected, he never regained his previous vigorously rude health.


EDIT .... for my undefeatable ability to either commit endless typos or, alternately, leave out entire words ....
 
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All of these diagnoses and symptoms are associated with each other in one way or another. Stress can trigger viral reactivations and viral reactivations can cause stress. Maybe stress contributes to viral reactivations and this causes the whole vicious cycle, just one theory of many. I don't think that the high representation of infection episodes is just a perception and reporting bias, especially since viral reactivations might not happen symptomatically and there is also the possibility that this is underreported. The difference is just too large.
some of us, at this too long, may never figure it out.

I had 40 years of mild CHRONIC EPPSTEIN BARR I called it. I worked full time, I could hike all day, and I did not get PEM in any classic sense. Just 10 years ago I was leaping off giant boulders and running thru creekbeds.

I'd wipe out from an overdoing- and have to recover, but that wasn't frequent.

Once stresses with too many lawyers and menopause hit, it got much harder to cope.

My mom clearly had IBS-d type issues, and was severely depressed at 48, hospitalized. (I can't blame her, frankly, youd' be depresssed too)....but had lots of energy (later). My brother claims he never had mono. I had it FOUR times at least, with big bummers of complications with each bout.

Unsolved Mysteries its called and yes, I totally agree looking at young children right when this stuff is happening makes alot of sense.
 

mariovitali

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definitely had energy issues prior to age 29 when I got ME. I reckon it was probably something metabolic or viral sapping my energy, I was always the child with low energy and less energy than other kids. Can't have been a coincidence. I trained just as hard, but never got there.
Yes, counting me in at this one.


Also, i find it extremely interesting that there are many more causes of ME apart from viral infections.
 

nerd

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I definitely had energy issues prior to age 29 when I got ME. I reckon it was probably something metabolic or viral sapping my energy, I was always the child with low energy and less energy than other kids. Can't have been a coincidence. I trained just as hard, but never got there.
Same story. The first time I noticed it was around the age of 17 when doing sports and when my incapable aerobe metabolism and the low-level neuromuscular issues affected my athletic performance. And my first seizure happened when I was even younger. I could never have imagined that this was something pathological. I thought that I just didn't do enough for my fitness/stamina.

Also, i find it extremely interesting that there are many more causes of ME apart from viral infections.
Just as stress and traumatic events, I'd call them "triggers" and not "causes" until everything is properly ruled out. Because any of these triggers can affect latent/abortive viral pathology, can't they? So they just might trigger viral pathology, or some other sleeping/hidden pathogen, and contribute to a synergistic pathology. Do you have any trigger in mind that is inconsistent with the hypotheses of viral pathology?
 

godlovesatrier

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I was regularly lethargic from age 12 to age 18/19 and then I had about ten years where I managed to get pretty fit although I am not always sure my body was firing on all cylinders like everyone elses. Even so life was good, no health issues to speak of really apart from depression. Until I found the holy grail and started taking fish oil capsules I honestly had no control over the depression. But that was it. I did have PVFS twice in my twenties though, low white blood cell count one time and post viral fatigue the second time, but both lasted 6 months and both classed as PVFS.

So yes very frustrating for us both.

I think you can go into remission with various treatments and an event can bring you right out of that remission. That's the feeling I get based on some of the more long term remissions I've heard of. But it's impossible to know if this is true for everyone or not.
 

mariovitali

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Just as stress and traumatic events, I'd call them "triggers" and not "causes" until everything is properly ruled out.
Well said.

Do you have any trigger in mind that is inconsistent with the hypotheses of viral pathology?
Well, i would call "Liver Injury" as a hypothesis and the common factor. Seen triggers under this perspective then we could say that Viruses, Chemical toxins and chronic stress can all potentially injure the Liver.

Regarding chronic stress :

From the experimental data described above, we can summarize the underlying mechanisms for stress‐induced liver injury as follows. Stress conditions can induce hepatic hypoxia and reperfusion, the over‐influx of gut LPS, and an increase in the release of stress hormones, including corticosteroids and catecholamines. This systemic alteration of the hepato‐intestinal blood flow first causes the partial necrosis of hepatocytes, which can leak intracellular substances. The leakage of unwanted antigens, called DAMPs, initiates the inflammatory reaction surrounding the hypoxic region and consequently activates NK cells to produce IFN‐γ, leading to M1 polarization of Kupffer cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422711/


Its seems that Traumatic Brain Injury may also affect the Liver :

https://academic.oup.com/bja/article/112/2/298/284708
 

nerd

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Well, i would call "Liver Injury" as a hypothesis and the common factor. Seen triggers under this perspective then we could say that Viruses, Chemical toxins and chronic stress can all potentially injure the Liver.
I would say that liver pathology is one hypothesis for causality, but not necessarily inconsistent with the viral pathology hypothesis in that a latent viral reservoir can exist in the liver and thrive during liver pathology. Your referenced paragraph already mentions one potential mechanism that links the pathology, namely NK activation and M1 polarization.
 

Pyrrhus

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There is also the possibility of predisposition, that a virus just triggers autoimmunity even if it's completely eliminated. But I'm beginning to have doubts that autoimmunity can be an completely self-sufficient disease, just triggered like that, and not be resolved. I have the notion that many autoimmune diseases have some sleeping/hidden component that has nothing to do with serology and that the serology is just a vicious cycle that keeps getting fed by something else.
You're not alone here, many other people say the same thing.

The problem is that there is a double standard for evidence:
  • In order to diagnose an infection, hard evidence of a pathogen is required. (To say that the infection is the cause of a disease requires satisfaction of Koch's postulates, which is an even higher level of evidence.)
  • However, in order to diagnose an autoimmune condition, all you need is a lack of evidence of infection. The easiest way to achieve a lack of evidence of infection is to simply not perform any diagnostic testing for infections. (This may sound absurd, but this is how autoimmune diseases are often diagnosed in the clinical setting.)

Obviously, this double standard needs to be fixed, and the way to fix it is to require hard evidence of autoreactive phenomena, either autoreactive antibodies or autoreactive T cells, in order to be able to diagnose an autoimmune condition.

Additionally, one must concede that diagnosis of an autoimmune condition does NOT preclude the diagnosis of an infection. In fact, the two often occur together and there is plenty of evidence that infections can cause autoimmunity, through multiple mechanisms.