The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome, 2013, Kishi et al

[forestglip]

The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome

Akifumi Kishi, Fumiharu Togo, Dane B Cook, Marc Klapholz, Yoshiharu Yamamoto, David M Rapoport, Benjamin H Natelson

Published: 2013

(Line breaks added)

Abstract
Effects of exercise on dynamic aspects of sleep have not been studied. We hypothesized exercise altered dynamic sleep morphology differently for healthy controls relative to chronic fatigue syndrome (CFS) patients.

Sixteen controls (38 ± 9 years) and 17 CFS patients (41 ± 8 years) underwent polysomnography on baseline nights and nights after maximal exercise testing. We calculated transition probabilities and rates (as a measure of relative and temporal transition frequency, respectively) between sleep stages and cumulative duration distributions (as a measure of continuity) of each sleep stage and sleep as a whole.

After exercise, controls showed a significantly greater probability of transition from N1 to N2 and a lower rate of transition from N1 to wake than at baseline; CFS showed a significantly greater probability of transition from N2 to N3 and a lower rate of transition from N2 to N1. These findings suggest improved quality of sleep after exercise.

After exercise, controls had improved sleep continuity, whereas CFS had less continuous N1 and more continuous rapid eye movement (REM) sleep. However, CFS had a significantly greater probability and rate of transition from REM to wake than controls. Probability of transition from REM to wake correlated significantly with increases in subjective fatigue, pain, and sleepiness overnight in CFS – suggesting these transitions may relate to patient complaints of unrefreshing sleep.

Thus, exercise promoted transitions to deeper sleep stages and inhibited transitions to lighter sleep stages for controls and CFS, but CFS also reported increased fatigue and continued to have REM sleep disruption. This dissociation suggests possible mechanistic pathways for the underlying pathology of CFS.

Link | PDF (Physiological Reports) [Open Access]

 

[forestglip]

I could only find two studies that monitored sleep quality after an exercise test. The other one is:

Sleep is not disrupted by exercise in patients with chronic fatigue syndrome, 2010, Togo et al (thread)

Most of the authors are the same, including Benjamin Natelson.

Still haven't read these. But I feel like there should be more studies on this.

Insomnia after exercise or heavy cognitive activity is maybe my most objective symptom. If I do a lot of activity, I can be almost certain that that night I'll feel far more "wired" at my usual bedtime, like I just drank caffeine, and it'll take at least an hour or two longer than normal to fall asleep.

I've seen this mentioned by others a lot as well. Maybe we should do a poll thread about how many people experience this?

 

[forestglip]

I could only find two studies that monitored sleep quality after an exercise test.

Both studies used Fukuda. So basically this has never really been tested in ME/CFS.

 

[Peter T]

Interesting, but waking from sleep or disrupted sleep cycles once sleep has been initiated is only one aspect of ME/CFS sleep issues, others include trouble initiating sleep (as mentioned by others here), shifting in the internal clock, excessive sleeping and unrefreshing sleep can be more than implied in the abstract, for example following a ‘good night’s’ sleep I can wake feeling significantly iller than when I went to sleep requiring several hours rest before I can begin any activity.

It is good to have a putative mechanism that would not necessarily be amenable to treatment by sleep hygiene measures, certainly I think it is also interest that at least some of us find trying to impose a presumed normal sleep pattern can make the situation much worse.

Then of course there is those of us who experience night sweats, currently apposite for me as I lie debating which will be more disruptive to my sleep remaining in damp clothing or getting up to change into dry clothing.

 

[Yan]

CFS had less continuous N1 and more continuous rapid eye movement (REM) sleep. However, CFS had a significantly greater probability and rate of transition from REM to wake than controls.

I've noticed this kind of pattern from my wearable sleep data. REM sleep very often initiated every 1.5h and after that waking up. Few days ago it happened 5 times in a row. Sure, the data might be somewhat unreliable but I do remember seeing lots of different dreams and waking up often.

Then of course there is those of us who experience night sweats, currently apposite for me as I lie debating which will be more disruptive to my sleep remaining in damp clothing or getting up to change into dry clothing.

I've had same kind of problems and at least on winters I've got a life hack for it. My problem has been that normal blanket gets too hot for me and thin blanket too cold for me. I then realized that I could lower my room temperature! Got it down to 18℃ from 22℃ and now I can sleep and sweat less with the normal blanket.

 

[Utsikt]

A poll sounds like a good idea. Cognitive efforts reduce my sleep quality and duration.

 

[Mij]

Then of course there is those of us who experience night sweats, currently apposite for me as I lie debating which will be more disruptive to my sleep remaining in damp clothing or getting up to change into dry clothing.

This is brutal for me during the cold winter months when I don't heat my room for sleeping. I feel chilled and frozen. So now I keep dry shirts warmed up under the covers so I don't have to get up at all. My sleep is disrupted, but once I get into dry warmer clothing I am able to fall back asleep for the most part of the night.

 

[Yann04]

REM sleep disruption

Totally spitballing but could this by why people often report weirdness around dreams. “ie. vivid dreams, constantly wake up after dreaming, fever dreams etc”

 

[forestglip]

I've made a poll about sleep changes due to exertion:

[Poll] How does exertion affect sleep?

 

[forestglip]

So this study looked at the same 33 participants as the other 2010 study linked above.

The subjects were 33 women, 17 with CFS (age: 41 ± 8 years; mean ± SD) and 16 healthy controls (38 ± 9 years), whose traditional sleep variables have previously been reported (Togo et al. 2010). [...] all were negative for sleep disorders in the form of restless leg syndrome or obstructive sleep apnea. [...] The patients all fulfilled the 1994 case definition for CFS (Fukuda et al. 1994) [...] To further reduce variability, menstrual subjects were all studied in the follicular phase of their menstruating cycles.

I'm not sure it's good to exclude those with restless leg syndrome, since that may be an effect of ME/CFS.

For the below "traditional" sleep variables, the most significant effect seems to be sleep latency (how long it takes to fall asleep). Healthy controls fell asleep significantly faster after exercise (about 15 minutes, p<0.01), while sleep latency change was not significant in ME/CFS (about 3 minutes faster).


And it looks like ME/CFS there might be an effect of more REM sleep and less non-REM sleep in ME/CFS after exercise compared to controls.

There were a few other findings, but the other main one that is interesting to me is that they found that in ME/CFS, the higher a person's probability of transitioning from REM to wake (I think this is the night after exercise), the more their fatigue, sleepiness, and pain worsened the morning after exercise compared to the evening after exercise but before sleep. In controls, there was no such correlation. (After removing an outlier, sleepiness and fatigue were still significant, but not pain.)

Since this study used Fukuda, it's unclear if everyone had PEM. But asking about how much fatigue, sleepiness, or pain worsened the morning after exercise may be a useful indicator of PEM. So using a correlation may be showing that this variable is actually associated with PEM severity, or only high in those patients who have PEM, if not all do.

We found positive and significant correlations among the transition probability from REM to wake and an increase in subjective fatigue, pain, and sleepiness overnight for patients with CFS. The change of fatigue and sleepiness in CFS, however, did not correlate significantly with the transition rate from REM to wake. A fundamental difference between transition probability and transition rate lies in whether the metric takes account of other patterns of transition (from the same stage). Transition probability represents relative frequency of transitions with focus on the direction of the transition, while transition rate simply quantifies the degree of the fragmentation of the stage due to the specific transition (i.e., transition frequency per unit time spent in the stage). Transition probability therefore could better reflect some element like a “pressure” to produce the transition than transition rate, and the “pressure” indicated by transition probability could reflect a relative difference among wake, REM, and non-REM (or N1, N2, and N3) sleep pressures. Therefore, overall, CFS patients could have less sleep pressure during REM sleep than controls, and this interpretation may relate to the common complaint of “unrefreshing sleep” in CFS; we have seen this reduction in REM sleep in the baseline condition (Kishi et al. 2008), and it remained reduced after exercise. While a literature exists showing evidence of the relationship between selective REM sleep disruption and daytime sleepiness in normal subjects (Glovinsky et al. 1990), such a relationship was not confirmed in patients with REM-predominant SDB (Chami et al. 2010), who have similar daytime manifestations to CFS patients such as fatigue, sleepiness, and cognitive impairment. This emphasizes the notion that disruption in REM may be a unique marker of the underlying pathophysiology of CFS.

[...]

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.

---

Edit: I'm not totally sure what night the correlation stats are based on, or if they averaged the two nights, or something else.

Relationships between transition probability from REM to wake and change of the subjective fatigue, pain, and sleepiness over night in healthy controls and patients with CFS. Open circles (○) represent data for the baseline night and closed circles (●) represent data for the postexercise night.

Edit 2: Okay, I think they used both nights, but controlled for which night it was. I was worried they treated different nights from a single person as independent samples.

Relationships between the specific transitions (probability and rate) and change of the subjective feelings over night (before and after sleep) were examined using partial correlation analyses controlling for conditions for each group;

 

[Sean]

I'm not sure it's good to exclude those with restless leg syndrome, since that may be an effect of ME/CFS.

I have had that at various times. Especially early on, not so much any more. Might be in part because of getting old (early 60s).

 

[Trish]

I have had that at various times. Especially early on, not so much any more. Might be in part because of getting old (early 60s).

I get it sometimes still (age 75). Worst instance recently on trying a newly prescribed medication that set of bad restless legs lasting 8 hours.
My mother who didn't have ME/CFS had it quite badly.

 

[DigitalDrifter]

Both studies used CDC 1994. So basically this has never really been tested in ME/CFS.

What do you class as genuine ME then? Also which pre-Covid prevalence figures do you believe because the 250,000 figure often cited is derived from the criteria you disqualified? https://meassociation.org.uk/2024/05/how-many-people-have-me-cfs-in-the-uk/

 

[forestglip]

What do you class as genuine ME then?

I don't know if there's a "genuine" ME/CFS since all the criteria are mostly just arbitrary groups of symptoms that happen together often. I'm interested in these studies because I think whatever is harmful about exercise in people with PEM might show up on before/after exercise tests. There's not as obvious a reason to include people without PEM and I think it's likely to just dilute the effect, if there is one.

Also which pre-Covid prevalence figures do you believe because the 250,000 figure often cited is derived from the criteria you disqualified? https://meassociation.org.uk/2024/05/how-many-people-have-me-cfs-in-the-uk/

I don't know much and am not overly concerned about prevalence. If 250,000 is based on Fukuda, it's based on Fukuda.

 

[forestglip]

If people who previously would have fulfilled Fukuda, but are not considered ME/CFS any longer because they don't fulfill newer criteria with PEM, feel like the science is moving on without them and they're stuck with something like "idiopathic chronic fatigue" that doesn't have the momentum of "ME/CFS", well, that's a tragedy. And I'm sure there are very, very many of those people.

With long COVID, what is it 50% have PEM, and the rest are chronically ill in other ways? I have little doubt there are similar percentages for triggers of similar pre-COVID illnesses. But the non-PEM people don't have the massive COVID pandemic everyone else is experiencing as their trigger to unite them, and they don't fit ME/CFS criteria. They might not even know if there was a viral trigger so can't say they have post-viral fatigue. They're just sick and don't know who's going to help, and that's awful.

It may be a bit insensitive of me to say some people have no reason to be in a study when not many others are including them in studies either. It's definitely something for me to think about.

 

[Utsikt]

It may be a bit insensitive of me to say some people have no reason to be in a study when not many others are including them in studies either. It's definitely something for me to think about.

Wide definitions lead to more heterogenity in the studied population. This added noise makes it more difficult to find patterns and results.

When we have limited resources, it makes sense to study only the strictest definitions first, and then expand the inclusion criteria once we have something specific to target.

I understand that «being studied» might have some value for the patients, but I don’t think that warrants the cost.

 

[forestglip]

it makes sense to study only the strictest definitions first, and then expand the inclusion criteria once we have something specific to target.

Would you want to hear "we need to study the people with IBS but without PEM first and once we figure something out, we'll include the ones with PEM as well"?

While the best solution probably isn't to spend $100 of available research funds on a study that globs everyone together, I don't think it's fair to use all $100 on PEM and tell everyone else to be patient.

There are 8500 papers on PubMed that mention "chronic fatigue syndrome". For "post viral fatigue" (or similar terms)...344. "Idiopathic chronic fatigue"...84.

 

[Yann04]

Would you want to hear "we need to study the people with IBS but without PEM first and once we figure something out, we'll include the ones with PEM as well"?

While the best solution probably isn't to spend $100 of available research funds on a study that globs everyone together, I don't think it's fair to use all $100 on PEM and tell everyone else to be patient.

There are 8500 papers on PubMed that mention "chronic fatigue syndrome". For "post viral fatigue" (or similar terms)...344. "Idiopathic chronic fatigue"...84.

It makes sense to seperate into subgroups and prioritise the more disabling ones. It also makes sense to study strict definitions and see if anything can be found there, then see if it holds in less strict definitions.

It obviously does not make sense to only study one subgroup or definition. Because in that case people are left behind.

 

[Utsikt]

Would you want to hear "we need to study the people with IBS but without PEM first and once we figure something out, we'll include the ones with PEM as well"?

If the objective is to figure out IBS, then yes.

I have had IBS for over ten years. It changed after I got Covid and PEM as a result of that.

If the objective is to figure out ME/CFS, being strict about having PEM makes sense. The effort preference NIH study did not make sense because they excluded all co-morbidities, even POTS. So it depends on the specifics.

 

[EndME]

The effort preference NIH study did not make sense because they excluded all co-morbidities, even POTS.

As far as I've seen, I don't think this is the case. Most people that applied for the study didn't get in because they failed had been ill for longer than 5 years or didn't have an infectious onset (or one that couldn't be documented). Of course the sickest are never going to be able to participate in the first place. Diseases such autoimmune diseases, cancers, Lyme diagnosis etc were an exlusion criteria but I think it can be argued that, that is very sensible given the scope of the study. We shouldn't forget that even after people had passed screening and medical records reviewed, in person evualations still revealed things such as cancer, Parkinson etc. I haven't seen POTS mentioned as exclusion criteria, where did you see that?

I'm afraid we cannot have it both ways. We can't criticise the intramural study, that is one of the only studies to have ever rigorously recruited patients, whilst accepting other studies that pay little attention to recruitment and yet at the same time criticise the BPS lobby for being too little attention to recruitment criteria.

IMO recruitment is one of the few things they got right!