News from Germany

I emailed the three researchers with the message above, and Claudia Schilling responded:

"Thank you for your mail. Your comment that sleep can be influenced by previous exercise is certainly correct and important.

Disturbed sleep after exercise also corresponds to what is known from overtraining syndrome in competitive sports, whose immunological and hormonal mechanisms presumably have similarities with PEM in ME/CFS, but at a pathologically shifted level of exertion.

We use the Canadian criteria for the diagnosis of ME/CFS, and we assess PEM with a questionnaire that quantifies it.

Your email now gives us the valuable tip that in addition to recording the general presence of PEM, we should also record how things looked in terms of PEM in the days immediately before the study examination.

As far as I know, there is no standardized instrument for this. In my opinion, it makes little sense to record the activity level directly before participation in the study, as PEM is triggered individually at very different activity levels. Nor do I know of any instrument that measures the current (rather than general) level of post-exertional malaise. Are you aware of such an instrument?

Otherwise it would be an option to record this in a free question.

Many thanks for your advice and best regards

Claudia Schilling"

Any ideas for how I can respond with the best way to record PEM? Is there a good questionnaire for "Am I currently in a crash?" or "How does today compare to my baseline?"

 

The thing is, I'm not sure that what she's asking for would add much value. It may be that the sleep of someone who is moderate and in a crash is the same level of "disturbed" as someone who is severe but at baseline. I'm mainly wondering how exertion specifically changes sleep within a single person.

I think the signal would be best found by comparing the same person at two different points where they are at baseline and in a crash. Maybe if they did two sleep studies and asked how they compare to baseline at each visit so they could see how change in sleep compares to change in symptoms within each person. I'm guessing adding another sleep study would require substantially more funding though.

 

@MelbME I know you are tracking symptom severity over time in your studies. Do you have ideas for how best to quantify how bad PEM is on a given day?

Edit: If you have an answer, please reply to the thread created for this topic: Assessing current PEM severity (whether one is in a crash)

 

I wrote up a draft of something to email back:

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Thank you very much for responding, and I’m pleased to hear that you might incorporate PEM severity on the study day into the analysis.

I also am not aware of a standardized instrument for measuring this, but maybe PEM severity could be assessed with a question like:

“On a 1 to 10 scale, where 1 means you are at baseline and not at all in a PEM crash, and 10 is the most your symptoms have ever increased after exertion compared to your baseline, how would you rate your PEM level today?”

My main concern with this, and I’m not sure if your study would be able to address it, is that I think it is very possible that in a person with mild ME/CFS who is in a crash, their sleep is exactly as “disturbed” as someone who has severe ME/CFS but is at baseline. So comparing them would show no difference, even though one is experiencing PEM.

For example, in a study of severely ill ME/CFS patients, the majority had poor sleep (1). While, for example, in myself, where I have ME/CFS, but am not severe enough to be bedbound or housebound, I can sleep a full night if I am not in PEM, but if I am in PEM, I have substantial insomnia.

It is possible, though, that all of these severe patients in the study were in PEM, especially as they had to undertake the effort of doing the sleep study. But it is something to keep in mind.

Mainly, what I was hoping to convey in my first email was that there may be signals in the sleep that explain why exertion causes PEM, since in myself and others, sleep is affected even on the first night, often before PEM has begun. I think it is possible that problems with sleep caused by exertion may be a factor in why PEM happens at all.

I think the best way to test this would be an exercise test with two sleep studies per patient, like the 2010 and 2013 studies I mentioned in my last email (which both used the same set of 33 participants). Though there is risk of long term worsening from performing exercise tests, so this may not be an appropriate study to do without substantial justification.

But both studies did find that exercise caused decreased sleep latency in controls, but sleep latency did not change in ME/CFS. The direction of the between group effect agrees with my and others’ personal experiences of exertion causing increased sleep latency.

Another interesting finding from the 2013 study (2) that I hope you can follow up on was that REM to wake transition probability correlated with the change in fatigue from the evening after the exercise to the following morning after the exercise. And interestingly, this correlation only existed in ME/CFS, not controls. The fatigue change metric may be a marker of ME/CFS severity, showing the delayed effect of exercise.

The paper suggested this finding may be useful for understanding pathophysiology or finding treatments for ME/CFS:

“Our additional analyses showing positive and significant relations between transition probability from REM to wake and an increase in fatigue as well as pain and sleepiness over night suggest that the abnormality in REM in CFS may reflect an underlying pathophysiologic mechanism. […] The specific sleep finding in CFS, increased transitions from REM to wake, could be a target of the treatment to improve the symptoms of fatigue, sleepiness, and pain in CFS.”


1. Chang, C., Hung, L., Kogelnik, A. M., Kaufman, D., Aiyar, R. S., Chu, A. M., Wilhelmy, J., Li, P., Tannenbaum, L., Xiao, W., & Davis, R. W. (2021). A comprehensive examination of severely ill ME/CFS patients. Healthcare, 9(10), 1290. https://doi.org/10.3390/healthcare9101290

2. Kishi, A., Togo, F., Cook, D. B., Klapholz, M., Yamamoto, Y., Rapoport, D. M., & Natelson, B. H. (2013). The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome. Physiological Reports, 1(6), e00152. https://doi.org/10.1002/phy2.152

 

Good on Claudia for engaging and thinking about this

I'm not aware of any validated standardised instrument, or any really, for this. So an open question might be the best way to go for now. Maybe two questions:

1. In the last x number days, were you more active than usual?
2. Are you currently experiencing PEM?

The first question could theoretically be supported by actigraphy for, say, a month before the study day itself, funding and time permitting

@forestglip, maybe make a separate thread for this, for better visibility?

Many studies don't take pre-visit PEM into account so it's worth drawing attention to, beyond this present study. In any particular study PEM or non-PEM may turn out to not be relevant but we won't know until we can look back with the benefit of hindsight. Until then participants' PEM-state on the day of any tests would seem an important data point to record. Question is how best to do this

 

Good idea, thread created: Assessing current PEM severity (whether one is in a crash)

 

People with post-Covid: “Two-thirds of the condition does not improve”

Four university hospitals in Baden-Wuttemberg have systematically examined people who suffer from the long-term consequence of a corona infection. Study leader Winfried Kern explains what can be deduced from this about the disease mechanisms- and why those affected are often examined incorrectly in doctor's offices.

For the study called EPILOC (Epidemiology of Long Covid), health authorities in Baden-Württemberg sent questionnaires in late summer 2021 to adults up to 65 years of age who were infected with Corona between October 2020 and March 2021. They were able to provide information about their health status six to twelve months after the infection and again up to 14 months later.
LINK

 

Study on Post-COVID Syndrome: Evaluation of Antiviral Therapy in Patients with Post-COVID Syndrome" Dresden, Berlin, Kiel, Detmold, Göttingen, Frankfurt, Cologne, Freiburg, Munich, Würzburg are now recruiting

Study on post-Covid syndrome

Evaluation of antiviral therapy in patients with post-COVID syndrome

Randomized Adaptive Assessment of post COVID syndrome treatments_Reducing Inflammatory Activity in patients with post COVID syndrome (RAPID_REVIVE)

The RAPID_REVIVE study investigates whether drug treatment with a previously unapproved drug has a positive influence on the development of post-COVID syndrome.

LINK

 

The Vice Chancellor of Germany raising awareness for ME

Stell dir vor, du bist permanent erschöpft. Dein Körper spielt nicht mehr mit, der Kreislauf schwankt, die Konzentration bricht weg, Schmerzen und Überempfindlichkeit begleiten jeden Tag. Jede Anstrengung macht es schlimmer. Arbeiten? Unmöglich. Schule? Keine Chance. Dein Leben ändert sich von jetzt auf gleich. Behandlungsmöglichkeiten gibt es kaum.

So ließe sich das Leben mit #MECFS beschreiben – einer Krankheit, die viel zu oft als "Müdigkeit" abgetan wird. Dabei betrifft sie weltweit über 40 Millionen Menschen, darunter auch Kinder. Eine Krankheit, die Aufmerksamkeit, Forschung und eine besseren Gesundheitsversorgung braucht.

Betroffene haben deshalb mit der #LemonChallengeMECFS eine Initiative ins Leben gerufen, die ins Bewusstsein rufen soll, was sonst oft gar nicht sichtbar ist. Dabei unterstütze ich gern. Denn solche Aktionen erinnern uns daran: Es geht nicht nur um Zahlen oder Diagnosen. Es geht um Menschen.

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Imagine you are constantly exhausted. Your body is no longer working, your circulation is fluctuating, you can't concentrate, you are in pain and hypersensitivity every day. Any exertion makes it worse. Working? Impossible. School? No chance. Your life changes from one moment to the next. There are hardly any treatment options.

This is how one could describe life with #MECFS - a disease that is far too often dismissed as "fatigue". It affects over 40 million people worldwide, including children. A disease that needs attention, research and better healthcare.

Those affected have therefore launched an initiative called #LemonChallengeMECFS to raise awareness of what is otherwise often not visible. I am happy to support this, because such campaigns remind us that it is not just about numbers or diagnoses. It is about people.

 

Here's the website for the lemon challenge:

https://mecfs-research.org/lemonchallengemecfs/

 

Website in English:
https://mecfs-research.org/en/lemonchallengemecfs/