A Comprehensive Examination of Severely Ill ME/CFS Patients, 2021, Chang et al

[Sly Saint]

Abstract
One in four myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients are estimated to be severely affected by the disease, and these house-bound or bedbound patients are currently understudied. Here, we report a comprehensive examination of the symptoms and clinical laboratory tests of a cohort of severely ill patients and healthy controls.

The greatly reduced quality of life of the patients was negatively correlated with clinical depression. The most troublesome symptoms included fatigue (85%), pain (65%), cognitive impairment (50%), orthostatic intolerance (45%), sleep disturbance (35%), post-exertional malaise (30%), and neurosensory disturbance (30%).

Sleep profiles and cognitive tests revealed distinctive impairments. Lower morning cortisol level and alterations in its diurnal rhythm were observed in the patients, and antibody and antigen measurements showed no evidence for acute infections by common viral or bacterial pathogens.

These results highlight the urgent need of developing molecular diagnostic tests for ME/CFS. In addition, there was a striking similarity in symptoms between long COVID and ME/CFS, suggesting that studies on the mechanism and treatment of ME/CFS may help prevent and treat long COVID and vice versa.

https://www.mdpi.com/2227-9032/9/10/1290

 

[Andy]

Twitter thread by @Michiel Tack

 

[Grigor]

It's look like they didn't find much. Sadly...

 

[DigitalDrifter]

The most troublesome symptoms included fatigue (85%), pain (65%), cognitive impairment (50%), orthostatic intolerance (45%), sleep disturbance (35%), post-exertional malaise (30%), and neurosensory disturbance (30%).

Only 30% had PEM, that's a huge red flag for bad research.

Edit: Just reading the full paper, and it says they used the ICC "Must carry a diagnosis of ME/CFS as defined by the ICC criteria" so I'm confused. I wish all research would mention the criteria in the abstract, it should be mandatory.

 

[Grigor]

Only 30% had PEM, that's a huge red flag for bad research.

I don't think that's what they meant. I think this refers to the symptoms that bothered them the most. They all had PEM as it was based on the ICC criteria.

 

[5vforest]

This paper struck me as being very surface level. Some questionnaires and basic labwork but not enough to uncover anything that wouldn't be obvious already.

 

[Milo]

This seems to me a first of many papers. Not terribly exciting but it is simply meant to establish the obvious.

 

[Denise]

I am not clear as to why Figure 1 in this article uses both ME/CFS and CFS?

 

[dreampop]

I'm afraid the cortisol finding may be a reflection of the high frequency of sleep disturbance noted in this study.

Cortisol after awakening was significantly decreased in primary insomnia. Salivary cortisol at the time of awakening correlated negatively with the subjective estimation of sleep quality, i.e. a low salivary cortisol level directly after awakening correlated with a higher frequency of nightly awakenings (r=−0.50), a diminished sleep quality (r=−0.34) and a decreased feeling of recovery after awakening (r=−0.35; all p<0.05).

https://www.sciencedirect.com/science/article/abs/pii/S0306453004000125

I was unable to find data on total patient sleep time and delayed phased sleep, but I assume that impacts cortisol as well and may explain the slightly higher levels later on in the day.

 

[Perrier]

I don't think that's what they meant. I think this refers to the symptoms that bothered them the most. They all had PEM as it was based on the ICC criteria.

Yes, you are correct. But I am really stunned that PEM interfered only 30%. Watching our family member, I would say that PEM is the worst and primary symptom. She can walk, and do virtually anything, intellectual labour, but if she does, if she dares do this--this results in severe PEM or a crash from hell, which lasts and lasts. The second symptom she suffers from is low BP, and then when there is a crash, cognitive trouble. Fatigue comes later, during a bad crash. That is why I rather liked Dr Davis' name: systemic exertion intolerance disease. SEID. For that is what I have seen exactly here at home. I guess without a diagnostic test, we are still in a bit of a fog.

 

[Milo]

Yes, you are correct. But I am really stunned that PEM interfered only 30%. Watching our family member, I would say that PEM is the worst and primary symptom. She can walk, and do virtually anything, intellectual labour, but if she does, if she dares do this--this results in severe PEM or a crash from hell, which lasts and lasts. The second symptom she suffers from is low BP, and then when there is a crash, cognitive trouble. Fatigue comes later, during a bad crash. That is why I rather liked Dr Davis' name: systemic exertion intolerance disease. SEID. For that is what I have seen exactly here at home. I guess without a diagnostic test, we are still in a bit of a fog.

Perhaps the participants felt that it wasn’t their worst symptom because they are so used to pace themselves that they very seldom go beyond the boundaries that will lead to PEM?

 

[Remain in Light]

As severe myself, pem is ironically not as severe as it used to be. Nobody wants pem but I had a sense that I was circling the drain and terrified that over exertion would push me into it. An abundance of caution became the norm and my activity infringements are minor and so is my PEM..
I don't feel like testing this.
I also wonder whether those with severe ME are more likely to be years in and in the chronic phase of the illness where the body seems to have accommodated the illness somewhat, softened it's extremes.
As a further speculation, I hardly have any muscles left , Does this affect the feed back loop of the activity/pem cycle?

 

[Trish]

There is also the problem in making such comparisons that PEM is not so much a symptom but a worsening of lots of symptoms, so, for example someone's OI and pain and fatiguability may be much worse during PEM, though they are present all the time as well. They might therefore list OI and pain and fatiguability among their most troubling symptoms, rather than choosing PEM.

 

[Solstice]

There is also the problem in making such comparisons that PEM is not so much a symptom but a worsening of lots of symptoms, so, for example someone's OI and pain and fatiguability may be much worse during PEM, though they are present all the time as well. They might therefore list OI and pain and fatiguability among their most troubling symptoms, rather than choosing PEM.

Yeah, this whole transforming to PESE is a bit worrying to me. I can't speak for other patients, but when I do get PEM I get extra symptoms on top of a worsening of existing symptoms. I'm a far cry from being depressed normally speaking for example, but if I crash from eating certain foods it triggers something in my mood. Physical overexertion triggers other symptoms like an aching body. Mental overexertion again triggers other symptoms such as trouble sleeping.

 

[Milo]

There is also the problem in making such comparisons that PEM is not so much a symptom but a worsening of lots of symptoms, so, for example someone's OI and pain and fatiguability may be much worse during PEM, though they are present all the time as well. They might therefore list OI and pain and fatiguability among their most troubling symptoms, rather than choosing PEM.

OI can be quite disabling if you are trying to perform your activities of daily living, such as going to the washroom, brushing your teeth or fixing a simple meal. By understanding pacing and resting between tasks, some (but not all) can go by and do these tasks with minimal or no payback.

Same goes with muscle fatiguability and cognitive fog.

 

[Perrier]

Then there are those who just wake up with PEM (and all the symptoms Trish underlines), day after day after, and they lie in bed like Egyptian mummies and the PEM still comes and they still wake with it (going to the WC, brushing teeth, I guess brings it on).

 

[cfsandmore]

I think this a is very poor study for our community. I'm not a scientist so there is a lot beyond my understanding. To this lay person, it sounds like SIPS is putting Fatigue back into Chronic Fatigue Syndrome.

The last thing on earth people with ME/CFS need is for Fatigue to become the number one symptom again.

I gave money for this study. They said, no one was studying the most severely affected, what was going to be learned would change our ME/CFS world. I bought into that hype. Finally the study has been published. I can see why the loud talk became a whisper.

The biggest shocker for me was, we were told the participants of SIPS were so severely ill the scientists were driving to their homes to conduct the study, and yet I meet the Inclusion Criteria. In fact, I'm worse than the median in all of the categories except steps.

We were told this was going to be a study of severely ill people who live in darkness. It's promoted inside our community that these are the most depressed members. 20% of people with MECFS commit suicide but this study would lead one to believe few of them are in the severe category.

20 participants are in no way conclusive of the severely ill ME/CFS community. I will not bother printing this out for my physician. She would just circle the 20 participants and shake her head. She will get out her pen and say, how many Americans have MECFS? Lets say a million, and 25% are severe. She would say, does 0.008% represent your severe community? So I would be setting there looking like a fool in front of my physician.

If your severe MECFS doesn't fit into SIPS findings don't feel alone. You are part of the 99.99% of the severe community not studied.

From my understanding the spit cortisol levels was their biggest molecular find. However, it's so close to the control subjects they aren't promoting additional study. So molecularly this is a bust. No biomarkers found.

Walter Koroshetz who holds the purse strings at NIH refuses to fund much research into ME/CFS. He said, the money is there for research, but he can't find good studies to fund. Walter's correct, we need better research.

I gave money to the nanoneedle which turned out to be mostly hype. OMF and Davis talked about it being a test in the doctor's clinic but it turned out to be false hope. When asked about it, they have version 2.0 of the nanoneedle that is just gangbusters in the lab. Or so they say.

After it became clear the nanoneedle was going to sit on a shelf, I asked my therapist about this. She said some organizations must put out something new because they can't deliver on what was promised. The new claim distracts from the failure. She said they jingle the keys for the baby and when the baby reaches for the keys they take the money out of the baby's hands.

It takes a lot of me to write, so I'm going to be resting for a bit. I'm horribly disappointed. False hope is painful.

edit: spelling

 

[Ariel]

I don't think that's what they meant. I think this refers to the symptoms that bothered them the most. They all had PEM as it was based on the ICC criteria.

Bothered in what sense? This question concerned me. As in, it upset them emotionally? Or limited their functioning? Why bother asking this question and highlighting it so much as the top line item?

I frankly thought this study was a waste of money. What were they trying to establish or discover? Yes, severe ME/CFS exists. The CDC has said so.

 

[Trish]

Only 30% had PEM, that's a huge red flag for bad research.

Edit: Just reading the full paper, and it says they used the ICC "Must carry a diagnosis of ME/CFS as defined by the ICC criteria" so I'm confused. I wish all research would mention the criteria in the abstract, it should be mandatory.

Yes, you are correct. But I am really stunned that PEM interfered only 30%.

As shown in Figure 2a, all the patients had fatigue, sleep disturbance, and post-exertional malaise, and had either cognitive impairment (19/19 or 100%) or orthostatic intolerance (15/19 or 79%), or both. Therefore, all the patients met the IOM ME/CFS diagnosis criteria. Additional symptoms include pain, neurosensory disturbance, flu-like symptoms and/or susceptibility to viral infections, gastrointestinal tract impairments, Genitourinary impairment, and Respiratory impairment. Notably, 100% of the patients (19/19) suffer from the presence of significant pain and 89% (17/19) had sensitivity to light, noise, vibration, odor, taste, and touch (Figure S2a).

So the 30% figure for PEM is only in relation to their list of their 3 most troublesome symptoms. It's very hard to pick just 3 when people with severe ME have so many symptoms all the time.

Also, as others have said, this is just a preliminary paper with results of questionnaires and standard lab tests. We already know that most of us have no abnormalities shown on standard blood tests, so I'm not surprised they found nothing at this stage. The important bit, from the hype during the data collection a few years ago, was that they were going to do lots of more sophisticated tests using various -omics, and expect to find more. It appears that hasn't been done yet.

 

[dreampop]

So the 30% figure for PEM is only in relation to their list of their 3 most troublesome symptoms. It's very hard to pick just 3 when people with severe ME have so many symptoms all the time.

Also, as others have said, this is just a preliminary paper with results of questionnaires and standard lab tests. We already know that most of us have no abnormalities shown on standard blood tests, so I'm not surprised they found nothing at this stage. The important bit, from the hype during the data collection a few years ago, was that they were going to do lots of more sophisticated tests using various -omics, and expect to find more. It appears that hasn't been done yet.

You are correct. The follow-up is called the "Extended Big Data Study in Families"

The rationale of this study is that by using the unaffected family members as a control, the differences observed in the ME/CFS patients will be more specific to the disease and less related to differences in genetics, environment, and diet.

Almost as extensive as the SIPS study, blood from each patient is being used to examine the following:

• Genome
• Gene expression
• Metabolomics
• Proteomics
• Cytokines

By comparing patients to healthy blood relatives, we are more likely to understand what genes cause or contribute to the development of ME/CFS. This data will also be integrated with the SIPS data.

And in addition, the OMF website says the SIPS study should include the following, unless they were dropped.

• Genome
• Gene expression on individual immune cell types
• Metabolomics
• Microbiome
• Cell-free DNA sequencing and quantitation
• Cytokines
• Clinical tests

I'm also untroubled by the subjective account of most troublesome symptoms. The average fatigue scores were 17ish, disturbingly low. I'm confident in the cohort selection. And as a severe but not very severe patient, my most troublesome symptoms match up fairly well. Everyone is different though, but I don't think that not having PEM at the top is a red flag.