Pathophysiology of sleep disturbances/unrefreshing sleep in pwME?

[rapidboson]

Hey guys.
I am wondering how much properly addressing sleep disturbances in pwME would help with symptoms. By properly I mean addressing the proposed mechanism that is out of whack in pwME, leading to unrefreshing sleep. From what I can tell from reading this review vertically (Table S3 for outcomes of trials included), the only consistent finding in studies that included MAI, is an increased MAI in pwME.

MAI values allows measurement of sleep fragmentation.

5. Conclusions
In the five studies that investigated MAI, all studies showed an increase in this parameter. SOL and NREM were not significantly different between ME/CFS patients throughout the studies. Slow-wave sleep, AHI, spectral activity, and MSLT were inconsistent across the studies. These results require validation in future well-designed studies. Numerous considerations for future experiments have been recommended including recruitment of participants with more stringent ME/CFS criteria and controlling for first night effects. Effective control of confounding variables of sleep quality including medications, change in time zones or strenuous exercise can also be implemented to improve overall study design. Replication of these studies in larger well-matched populations is also required.

Has anybody stumbled upon studies where they look into this deeper? Try to elucidate the mechanisms behind this seemingly more fragmented sleep?

From own experience, without any medication I have sleep onset and sleep maintenance issues - and surely wake up feeling unrested despite sleeping for 7-9 hours.

As low as 300 mg of gabapentin (or pregabalin 75 mg) taken 1-2 h before sleeping (only 1-2 times a week to keep tolerance low) is the only medication I have tried that actually makes me feel more rested in the mornings and the whole day for that matter.

Other meds knocked me out, but did not subjectively improve my perceived sleep quality or gave me nasty side effects like migraines.

Besides countless supplements from minerals to amino acids to herbal extracts, I have tried H1-antagonists/inverse agonists (promethazine, hydroxyzine), SARI (trazodone - migraine city), benzodiazepines (alprazolam, diazepam) and modified-release melatonin (circadin). Probably more that I don't remember now.

In comparison to benzodiazepines for example, gabapentinoids (gabapentin and pregabalin) seem to increase SWS and reduce sleep fragmentation. Maybe this is why it seems to help me more than other drugs?

In conclusion, this small-scale open-label clinical trial of gabapentin demonstrated the potential of gabapentin to become a supplement treatment of primary insomnia. Its treatment can increase slow-wave sleep along with elevated parasympathetic tone. It can also improve sleep efficiency with decreased spontaneous arousal in sleep maintenance. However, it had no significant influence in sleep initiation or the change of REM sleep. One of the limitations of our study is its small patient group of only 18, which may limit the generalization of the results; in addition, the study did not use a double-blind procedure. Further investigation with a randomized larger-scale double-blind trial would be warranted.

In PSG studies, pregabalin treatment typically improved wake time after sleep onset (DPN, FM and RLS), the number of awakenings (FM and partial seizures) and time spent in slow-wave sleep (FM, RLS and partial seizures). Decreased stage 1 sleep was also commonly found (RLS and partial seizures). Decreased latency to persistent sleep was evident in FM patients but this effect was small relative to the effects on wake time after sleep onset, suggesting that pregabalin predominantly affects sleep maintenance. Findings of fewer awakenings, more time spent in slow-wave sleep and less time spent in stage 1 sleep demonstrate that pregabalin consolidates sleep by increasing “depth of sleep”. These PSG findings may be related to patient reports of improved sleep quality with pregabalin treatment.
Gabapentin, like pregabalin, is an α2δ ligand used to treat seizures and neuropathic pain. A number of RLS studies demonstrate that gabapentin and gabapentin enacarbil (a gabapentin prodrug) have a positive effect on patient-reported measures of sleep [89], [90], [91], [92]. PSG documents that gabapentin improves total sleep time [89], [91], sleep efficiency [89], [91] and wake time after sleep onset [90], [91]. Similar to pregabalin, gabapentin also consistently decreased the amount of stage 1 sleep while enhancing slow-wave sleep [89], [90], [91]. Like pregabalin, gabapentin also enhances slow-wave sleep in patients with epilepsy [63] and in healthy adults [92]. In one small PSG study in patients with primary insomnia, gabapentin increased sleep efficiency and slow-wave sleep, which was accompanied by a decrease in wake time after sleep onset [93]. There are no published studies of pregabalin for the treatment of primary insomnia.

Practice points
The data in this review show that:

• 1)
  patients report improved sleep quality in response to pregabalin across several different clinical conditions;
• 2)
  polysomnography reveals fewer awakenings, more time spent in slow-wave sleep and less time spent in stage 1 sleep, suggesting that pregabalin consolidates fragmented sleep and increases depth of sleep;
• 3)
  evidence suggests that pregabalin has a direct effect on sleep that is distinct from its analgesic, anxiolytic and anticonvulsant effects;
• 4)
  pregabalin and gabapentin exhibit similar effects on sleep, suggesting that these effects are due to their ability to modulate the α2δ subunit of neuronal voltage-gated calcium channels.

Other medication I will try are clonidine and baclofen. Both with different modes of action than gabapentinoids, but modes of action that in my view make sense to try out for pwME. Namely, a2 receptor agonism (clonidine), which could potentially address decreased HRV seen in pwME (at least during PEM) and GABA-B receptor agonism (baclofen).

Orexin antagonists are something I would like to try, unfortunately they are not available where I live.

Does anybody here have more knowledge on how exactly sleep is disturbed in pwME - and whether there have been trials to address exactly this?
I would assume that parts of the fatigue we feel could be alleviated by having some more restful sleep?

Edit: sorry if the post gets worse the longer it gets, my brainfog got worse by the minute.

 

[rapidboson]

I used propranolol for POTS for a while and it definitely maybe me more sleepy, but I don't recall waking up more rested, unfortunately.

I am mild most days, used to be moderate.

Responding to a deleted post about good sleep being helpful.

100% agree. Makes me wonder how (1) how much of the fatigue we experience could be helped by improving sleep architecture longer term (let's say 6+ months of improved sleep architecture) and (2) if more severe people have worse sleep than mild/moderates.

Responding to a comment about fewer bad sleep days.

Which surely is an improvement in quality of life! Happy to hear. What if your "very bad days" is a normal day for a more severe person and we could (at least regarding some symptoms) improve their QoL by regulating their sleep architecture?

I would really like to see a proper study on the mechanisms behind our unrestful sleep and follow up RCTs addressing those mechanisms.

 

[Kitty]

Other meds knocked me out, but did not subjectively improve my perceived sleep quality

I found that too. Gabapentin and melatonin helped me sleep more but not better, and the gabapentin caused weight gain. Sleeping pills made me feel awful and made no difference to sleep quality.

For me the best approach seems to be just living with it, because sleep that isn't naturally induced isn't really sleep. It's just a state of not-awake, and it does nothing to reduce fatigue and general awfulness.

Also, as meds always have some side effects, taking them seems to result a net loss in quality of life.

 

[rapidboson]

I found that too. Gabapentin and melatonin helped me sleep more but not better, and the gabapentin caused weight gain.

Thanks for sharing your experience. Do you remember how much you took, when you took it and for how long?

because sleep that isn't naturally induced isn't really sleep. It's just a state of not-awake, and it does nothing to reduce fatigue and general awfulness.

This is certainly the case with benzodiazepines, they do not improve deep sleep for example.

But I don't think it's necessarily true for all medication - I wouldn't know why it would be. They affect different stages of sleep.

Say a robust study finds out pwME have an altered EEG during a certain sleep stage that affects overall sleep architecture: If that person would take medication targeting that specific thing that makes their sleep unrestful, I would expect them to wake up more rested.

Also, as meds always have some side effects, taking them seems to result a net loss in quality of life.

Sure do - proper dosing to maximize effects and minimize side effects would be imperative.




Orexin antagonists are something I would like to try, unfortunately they are not available where I live.

 

[Kitty]

Do you remember how much you took, when you took it and for how long?

I had two phases on it, the first for pain (didn't work very well) and the second several years later for extreme menopause symptoms (absolute life-saver). I've taken pretty much all the normal doses in trying to find the optimal one, and exceeded it. None of them improved sleep quality, though, I remember that much because it seemed so counterintuitive.

Both phases lasted several years. I took it for drenching sweats for three years; first time round it was longer than that, but probably not more than four years.

 

[Creekside]

My opinion is that ME's "unrefreshing sleep" symptom has nothing to do with duration or quality of sleep. I feel the same level of unrefreshedness regardless of how long or how well I slept, so I consider it a symptom that simply feels similar to lack of sleep.

I haven't noticed any significant correlation between my ME symptoms and sleep duration or quality. Maybe there is a difference, but it's so small that I can't tell. My sleep seemed normal when my ME started, and the increase in wakings and insomnia didn't occur until maybe 10 years into my ME, and my ME symptoms didn't seem to change in response to those changes in sleep.

 

[rapidboson]

I had two phases on it, the first for pain (didn't work very well) and the second several years later for extreme menopause symptoms (absolute life-saver). I've taken pretty much all the normal doses in trying to find the optimal one, and exceeded it. None of them improved sleep quality, though, I remember that much because it seemed so counterintuitive.

Both phases lasted several years. I took it for drenching sweats for three years; first time round it was longer than that, but probably not more than four years.

Great that it at least helped for the menopause symptoms!

My opinion is that ME's "unrefreshing sleep" symptom has nothing to do with duration or quality of sleep. I feel the same level of unrefreshedness regardless of how long or how well I slept, so I consider it a symptom that simply feels similar to lack of sleep.

I haven't noticed any significant correlation between my ME symptoms and sleep duration or quality. Maybe there is a difference, but it's so small that I can't tell. My sleep seemed normal when my ME started, and the increase in wakings and insomnia didn't occur until maybe 10 years into my ME, and my ME symptoms didn't seem to change in response to those changes in sleep.

Interesting, thanks for contributing! How you you measure your "sleep quality"?
Using my smartwatch + Zepp/Notify for Amazfit and also my Polar verity sense armband + Sleep as Android, I can clearly see a stark increase in deep sleep and feeling more rested on mornings after having taken gabapentin at night.
For me (mild/moderate) more deep sleep absolutely translates to feeling more rested the next day. More in the sense of having less awful days though, it's like peeling away one layer of symptom severity - if that makes any sense.

 

[Creekside]

How you you measure your "sleep quality"?

Personal judgement, no fancy devices. Bad quality (frequent wakings, slow to go back to sleep) is far easier to judge than superior quality.

For me, a night of poor sleep, or only a few hours due to insomnia, makes me feel like I didn't get enough sleep, but doesn't noticeably make my ME symptoms worse. It's hard to tell whether a response to a food trigger or whatever is affected by sleep, but there's no obvious correlation.

 

[rapidboson]

Personal judgement, no fancy devices. Bad quality (frequent wakings, slow to go back to sleep) is far easier to judge than superior quality.

Alright. So what if your good quality night baseline (i.e. the nights that are not obviously bad) is full of microarousals that you don't perceive leading to fragmented sleep architecture (as has been shown in several studies for pwME)?

I am trying to dig through the literature, but too brain foggy today.

 

[Arfmeister]

my personal view & experience is :

1) that good sleep will help symptoms (but not cure anything, except when you’re already on an upward spiral)

2) daily benzodiazepine help me sleep
- and help many PwME to relief symptoms, or shield PEM (think Whitney Dafoe)

3) pregabalin helps me better with sleep than benzo and relieves symptoms for the next day
– but may be because I only take it once weekly
- so no tolerance

so I think the effect pregabalin for sleeping is similar to benzo
- possibly specifically because it improves symptoms in general

 

[rapidboson]

Some quotes from this study from 2014:

CDC criteria based CFS patients presenting with clinically significant questionnaire-based fatigue (see below) were selected after exclusion of primary sleep disorders. [...] compared to a healthy control group. [...] All subjects underwent standard physical examination, semi-structured DSM IV based clinical interview and psychometric assessment. [...] CFS = 52 people, HC = 25 people

Psychometric assessment
Self-reporting questionnaires with classical semantic instructions for fatigue and sleepiness were given to all participants on the first day of their stay in our unit at the same daytime (between 5 p.m. and 7 p.m.) before their first night of polysomnographic recording.
The Fatigue Severity Scale (FSS) is a self-reporting tool used to assess symptomatic intensity levels of fatigue and its effect on daily functioning [27]. The FSS was first introduced for individuals with multiple sclerosis and systemic lupus erythematosus [27]. In addition, it has since then been used in many studies investigating fatigue in other chronic conditions like obesity, Parkinson disease, hepatitis C infection, cancer and CFS [13], [28], [29] and in general population samples [4], [30]. The FSS is a 9 item 7-point Likert-type scale. Scores are usually reported as ‘mean scores’ (ranging from 1 to 7) obtained by dividing the total score (ranging from 7 to 63) by 9. For clinically significant pathological daytime fatigue, we used a proposed cut-off > 5 on mean scores [4], [30].
The Epworth Sleepiness Scale (ESS) is the most widely used scale of subjective sleepiness and daytime sleep propensity. The ESS consists of 8 items (described situations) arranged on a 4-point Likert scale ranging from 0 (“never doze”) to 3 (“high chance of dozing” during daytime). The summed scores range from 0 to 24 and scores above 10 are commonly interpreted as clinically relevant increased daytime sleepiness [31]. For clinically significant daytime sleepiness, we here also used a cut-off > 10 on the ESS.
The Pittsburgh Sleep Quality Index (PSQI) assesses subjective sleep quality. The 19 items are grouped into seven component scores, each weighted equally on a scale from 0 to 3. These components are subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medication and daytime dysfunction. The component scores are then summed to yield the global PSQI score. In validation studies, a global PSQI score > 5 indicates that a subject is having severe difficulties in at least two areas, or moderate difficulty in more than three areas [32].
Affective symptoms. The Hospital Anxiety and Depression Rating Scale (HADRS) is a self-report rating scale of 14 items on a 4-point Likert scale (with a range from 0 to 3). It is designed to measure the intensity of anxiety and depression (7 items for each subscale) symptoms [33]. The total score is the sum of the 14 items (ranging from 0 to 42), and for each subscale the score is the sum of the respective seven items (ranging from 0 to 21). The reliability and validity of the HADRS have been tested in a vast number of international clinical and non-clinical studies including CFS [34].

I myself don't know what diagnostic criteria for ME are state of the art currently.

In general, our results show impaired sleep quality, increased fatigue, sleepiness and affective symptoms in patient groups as opposed to healthy controls. With respect to polysomnographic parameters, subject groups mainly differ in sleep efficiency, wake state after sleep onset and duration of NREMS stages, as well as in sleep fragmentation and respiratory disturbance. Regarding power spectra distributions, taking into account the time spent in each NREMS stage, our results suggest a pattern of power exchange in higher frequency bands at the expense of US power in CFS patients at central EEG electrode sites during all stages of NREMS.

Results table:

The amount of SWS (slow-wave sleep) and sleep fragmentation (MAI) seem to be higher in CFS:

Proposed hypotheses about NRS, altered sleep quality and sleep are also often concerned with sleep fragmentation [10], [13], [23]. In our sample, both patient groups presented with higher MAI than control subjects. Although MAI was indeed highest in SAHS patients, significant sleep fragmentation, however, apparently does not systematically present with associated EDS (*) [14], as shown by our results. EDS may therefore only occur if sleep fragmentation is associated to a relative decrease of SWS. Likewise in our study, showing CFS patients having the highest and SAHS patients the lowest SWS duration, the cross-link between fatigue and sleepiness associated conditions within polysomnographically recorded sleep seems indeed to be SWS [11], [14], [18] or SWA [12], [20], [22]. Our findings here corroborate previous reports of chronic daytime fatigue and increased levels of SWS in different chronic fatigue related conditions as CFS [18], [19], [34], HIV [35] or other infectious diseases [36], or increased levels of NREM stage 4 in CFS [37].

*excessive daytime sleepiness

However:

Regarding SWS to LS proportions, NREMS distributions can even show totally opposite ratios between CFS and a PSD like SAHS [18] (Table 2), defying eventual ‘recovery rules’ about SWS/LS proportions in clinical conditions like CFS [18]. In addition to the observed increase of SWS duration, the main differences regarding spectral power analysis within overall SWA, were a systematic deficit of central US power in CFS compared to healthy controls [...] during N1 and N2 and compared to controls alone during SWS. Similarly, lower occipital US in CFS was found [during N1 compared to SAHS patients and] during N2 compared to both groups. Hence, these results extend previous findings of lower central US power in a preliminary study from a different sample of pure CFS patients [22]. In combination with increased SWS duration, the latter might thus reflect a possible homeostatic dysfunction. [...] In turn, the formerly so-called ‘paradoxical’ increase of SWS [38] in chronic fatigue may not be a paradox at all but instead underline a basic difference between sleepiness and fatigue when considering their relationships to sleep. The increased SWS in symptomatic and chronic fatigue might therefore reflect a quantitative attempt to compensate an impaired energy metabolism [39] or at least a qualitatively altered process (potentially reflected by decreased US power during SWS). SWS might indeed even behave or present in an anti-homeostatic manner toward fatigue in CFS. This might also explain the sustained systematic NRS complaints and un-refreshing sensations upon morning arousal independently of SPT over 24 h. [...] CFS patients present with a constantly significant deficit in US power, allowing more rapid frequencies to fill in the gap of total power within a given NREMS stage.

Although the role of US brain waves as a core restorative sleep function remains controversial [42], the CFS patients without PSD in this study show systematically decreased US power during NREMS and SWS in particular; this might nevertheless reflect homeostatic dysfunction. Concurrently, the failure of an adequate homeostatic response of sleep has also been already previously reported in twins discordant for CFS [43].

Interestingly, in this study on gabapentin they find a (non significant?) 13% increase in US delta power (delta-1) and (change of topic) a decrease in LF power and increase in HF power (indicating higher parasympathetic tone) during N3 (SWS).

Table.

Maybe these could be hints for why gabapentin seems to help me in terms of unrestful sleep?

 

[rapidboson]

Seems like this is a follow-up study of the EEG study I quoted in my previous post. Excerpts of the discussion sound interesting:

With respect to standard PSG variables, patients only differed from GSC for SWS duration and MAI. CFS patients showed longest SWS durations while both patient groups showed similar sleep fragmentation (MAI). This is in line with previous reports of chronic daytime fatigue and increased levels of SWS (Kishi et al., 2011, Neu et al., 2009, Le Bon et al., 2007) or increased levels of NREM stage 4 in CFS (Zubieta et al., 1993) on one hand. And likewise in our sample, where patient groups presented with higher MAI than GSC, proposed previous hypotheses about unspecific NRS or altered sleep quality and sleep often concerned the unspecific presence of increased sleep fragmentation (Neu et al., 2007, Le Bon et al., 2012, Punjabi et al., 1999).

In association to significant sleep quality impairment, daytime fatigue without EDS combined to similar TST, normal or even increased SWS durations in patient groups, spectral power showed here systematically lower central US proportions during SWS in both CFS and PI compared to GSC. In addition, absolute spectral power also showed statistically significant lower US power in CFS and PI compared to GSC at the occipital lead. Hence, in association to normal (PI) or increased (CFS) SWS durations, these findings might reflect an impairment in the restorative function of sleep or in sleep homeostasis. Given the related sleep quality impairment, proportions of US activity within SWS, might thus well represent physiological aspects of underlying core restorative functions within sleep.The formerly so-called ‘paradoxical’ increase of SWS (Le Bon et al., 2007) in chronic fatigue may not be a ‘paradox’ at all but instead underline the basic difference between sleepiness and fatigue when considering their relationships to sleep. The increased SWS in symptomatic and chronic fatigue conditions might rather reflect an attempt to compensate an intrinsically impaired process (reflected here by decreased US power proportions during SWS). Hence, SWS might even function in an anti-homeostatic manner towards fatigue in CFS for instance. In turn, this explains the sustained systematic NRS complaints and un-refreshing sensations upon morning arousal independently of SPT over 24 h. Unlike in EDS related conditions, sleep per se is not an efficient counter-measure in chronic fatigue conditions.

Based on this hypothesis of potential sleep homeostasis dysfunction in both CFS and PI and taking into account the time spent in SWS, our results show, at the central derivation, a pattern of power spectra distribution, visually suggesting a proportional exchange towards faster frequencies at the expense of US power in CFS and PI patients. The latter is in line with two previous reports on lower US in CFS (compared to controls and to a PSD, i.e. sleep apnea syndrome) (Neu et al., 2014, Le Bon et al., 2012) and consistent with the findings in a study from Krystal et al. (2002) also reporting diminished low-frequency and elevated higher frequency NREM EEG power in subjective insomnia. Likewise in our study these objective findings were also correlated to subjective sleep complaints in patients.

To these extents, the exploration of pairwise correlations between psychometric variables and SWS-relative spectral power distributions reveals a rather consistent picture here. The general pattern of proportional exchange with respect to power spectra distributions between higher frequencies at the expense of US power at all sites was associated with impaired perceived sleep quality. Regarding affective symptoms, this pattern seems to be associated with depressive symptoms, primarily for frontal and central sites and we find a similar relationship with reported anxiety symptoms, albeit to a lower extent. For the central lead, the contrast between US and more rapid delta was also significantly related to fatigue severity only.

In summary, we found consistent evidence for lower power proportions of slow oscillations in SWS in clinical conditions defined by chronic daytime fatigue which is not EDS or increased sleep propensity. In combination with normal (PI) or even increased SWS durations or proportions (CFS), these findings point towards compensation of a qualitatively altered process within SWS, potentially expressing homeostatic dysregulation. Though, our results imply that lower proportions of US power may indeed be an unspecific sign of sleep related chronic daytime fatigue combined to NRS but do also confirm specific differences between both patient groups with respect to psychometrics on one hand and relative frontal power distribution during SWS on the other. Previous findings and the present results suggest that the evaluation of SWS durations may be considered in chronic fatigue conditions like CFS. The latter might become clinically useful in the future, in particular if confirmatory studies reflect similar findings and if the precision of SWS durations or proportions’ thresholds for given age ranges improves over the next years. Further, we suggest that the assessment of slow oscillation power (<1 Hz) should be considered when conducting research in fatigue related conditions like insomnia and CFS. In chronic fatigue conditions associated to NRS complaints, sleep might indeed, in contrast to EDS related conditions, not present as a relative quantitative loss of SWS or SWA (resulting in higher homeostatic pressure and increased sleep propensity) as in these challenged situations (sleep deprivation e.g.) but rather as a qualitative change or modification of relative spectral power distributions within SWS or slow wave activity itself (i.e. presenting here as relative US power decrease and an implicit power shift towards higher frequency bands).

I like the sound of the idea regarding homeostasis. I wonder whether the increased amount of SWS seen in pwME is due to the body trying to counterbalance the increased microarousals.

Does anybody know if there have been any more studies, specifically looking into the changes in ultra-slow delta power and microarousals in sleep for pwME?

There's a meta-analysis on objective sleep measures in pwME, however they don't really touch upon the US delta and the MAI.

Here, they observed elevated delta power in awake EEG:

Although established in the sleep literature, the functional significance of slow-wave delta, typically predominant during deep restorative sleep, is not well-defined in awake EEG. In ME/CFS, the elevated delta power reported in four of the selected studies could indicate the persistence of sleep EEG features during wakefulness, as proposed by previous studies on insomnia patients (Wu et al., 2013, Zhao et al., 2021). This in conjunction with an increase in theta power may reflect a general state of cortical hypoarousal or EEG slowing that supports the overwhelming feelings of mental fatigue and difficulty in maintaining a fully alert state experienced by ME/CFS patients.

I am wondering if the higher MAI seen is due to increased sympathetic tone at night and if thus nightly clonidine (as mentioned earlier) could improve sleep architecture in ME. This paper seems to go deeper into microarousals. Will dig through when possible.
Will look for more data on gabapentinoids and baclofen or sodium oxybate (GABA-B receptor agonists).

Very interested in hearing more anecdotes!

 

[Creekside]

So what if your good quality night baseline (i.e. the nights that are not obviously bad) is full of microarousals that you don't perceive leading to fragmented sleep architecture (as has been shown in several studies for pwME)?

I'd put that in the category of possibilities to consider if there was some reasonable evidence for it, but to ignore otherwise. I didn't notice any change in dreaming due to ME, or evidence of more movement during sleep, or any other such things. There could be changes in brain function that cause ME symptoms, but which don't register on present scanning technology, but that's the sort of thing that you can't prove or do anything about.

I view "unrefreshing sleep" as similar to the effects of a drug (benzos?). Take a pill and feel like you haven't slept for days. I take that as evidence that the feeling of inadequate sleep doesn't require inadequate sleep.

FWIW, 15-20 years into my ME, I started waking fully every 90 minutes, although able to fall asleep again. That didn't seem to have an effect on my ME symptoms. On the rare nights that I do sleep through some of those cycles, I don't wake feeling significantly more refreshed.

 

[rapidboson]

I'd put that in the category of possibilities to consider if there was some reasonable evidence for it, but to ignore otherwise. I didn't notice any change in dreaming due to ME, or evidence of more movement during sleep, or any other such things. There could be changes in brain function that cause ME symptoms, but which don't register on present scanning technology, but that's the sort of thing that you can't prove or do anything about.

I was under the impression, that I provided several pieces of literature that indeed show evidence for an increased amount of microarousals (and reduced US delta power in SWS) during sleep in pwME. I thus don't fully understand what you are trying to tell me, sorry. Microarousals, as far as I understand, are not felt. I am specifically talking about changes in sleep architecture, not about all ME symptoms.

My previous "what if" question was not meant to speculate about some hypothetical possibility - it was meant to introduce the literature-based notion that your baseline might well not be a "healthy" (sleep architecture wise) baseline. Sorry for being unclear.

 

[poetinsf]

Sleep disturbance and unrefreshing sleep are probably separate things. Some patients suffer sleep disturbance as a part of their symptoms. Some (many?) don't. Unrefreshing sleep, on the other hand, is universal. As for me, sleep and symptoms are inversely correlated. I sleep better while suffering from PEM just as I sleep well when I'm suffering from a flu.

 

[rapidboson]

Sleep disturbance and unrefreshing sleep are probably separate things. Some patients suffer sleep disturbance as a part of their symptoms. Some (many?) don't. Unrefreshing sleep, on the other hand, is universal. As for me, sleep and symptoms are inversely correlated. I sleep better while suffering from PEM just as I sleep well when I'm suffering from a flu.

Interesting, thanks for sharing.

I don't think I perceive my sleep any better or worse when I have PEM or a flu. As in, I don't wake up more often or have any more insomnia. I wake up feeling less rested though.

With regards to separating unrefreshing sleep and sleep disturbances (I guess you mean sleep onset and maintenance insomnia) - I don't know but might well be different etiologies.
The literature I shared is specifically covering altered sleep architecture potentially leading to unrefreshing sleep in pwME and what some studies found is an increase in micro arousal index (unnoticed sleep "disturbances") and a decrease in ultra slow delta power in slow wave sleep (deep sleep).
Big question being "why is this happening?"

 

[poetinsf]

The literature I shared is specifically covering altered sleep architecture leading to unrefreshing sleep in pwME and what some studies found is an increase in micro arousal index (unnoticed sleep "disturbances") and a decrease in ultra slow delta power in slow wave sleep (deep sleep).

I'm questioning the claim that altered sleep pattern is the cause of unrefreshing sleep. Unrefreshing sleep is a hallmark/universal symptom (ME/CFS patients are constantly unrefreshed, after all) whereas altered sleep pattern is not. My take on it would be that it is one of plethora of anomalies in ME/CFS. One still could inquire why that is happening of course, just as one would about any other symptoms. And treating sleep difficulties may help just as it would in healthy people. But I just don't see it leading to refreshing sleep in ME/CFS. If it does, we may have found a solution to ME/CFS.

 

[rapidboson]

I'm questioning the claim that altered sleep pattern is the cause of unrefreshing sleep. Unrefreshing sleep is a hallmark/universal symptom (ME/CFS patients are constantly unrefreshed, after all) whereas altered sleep pattern is not. My take on it would be that it is one of plethora of anomalies in ME/CFS. One still could inquire why that is happening of course, just as one would about any other symptoms. And treating sleep difficulties may help just as it would in healthy people. But I just don't see it leading to refreshing sleep in ME/CFS. If it does, we may have found a solution to ME/CFS.

I don't follow your logic here to be honest, sorry. Hope you can help me understand you!

(1) What makes you believe that different sleep architectures between pwME and healthy controls are not "universal"? All the data I have seen these past days point towards a consistent difference. Moreover, the studies I quoted were able to differentiate clearly between the architecture in different diseases such as sleep apnea, the architecture in ME and healthy controls (three different patterns/groups here). Think "sleep fingerprint". It's not like there's one fingerprint that's healthy and only one other fingerprint that's unhealthy. Even within the group of ME, I'm sure different studies found different fingerprints (different measuring methods, patient stratification etc), but there's always a different fingerprint between ME and healthy from what I have read so far.

(2) Yes, we agree, it's likely one of many anomalies, I am not expecting this to be the main cause of ME symptoms at all. Personally, I (so far) see unrefreshing sleep (likely due to altered sleep architecture) as a symptom that's caused by something upstream.

(3) Which is why normalizing sleep architecture could in my view potentially improve quality of life but not be a solution to ME. It might still make people feel better.

 

[poetinsf]

Moreover, the studies I quoted were able to differentiate clearly between the architecture in different diseases such as sleep apnea, the architecture in ME and healthy controls (three different patterns/groups here). Think "sleep fingerprint".

If there was such a fingerprint, or fingerprints, that uniquely identifies ME/CFS, it would serve as a biomarker. As is, sleep disturbance is not even a requirement for the diagnosis. Will the studies that you quoted change that? Maybe. Sleep disturbance is a common feature of psychiatric conditions, btw. So, I don't think that line of inquiry will be too productive.

As to how universal it is, I guess one way is s4me survey. Maybe someone can point to it if there is one already. If you not, perhaps you can start one?

(3) Which is why normalizing sleep architecture could in my view potentially improve quality of life but not be a solution to ME. It might still make people feel better.

No argument there.

Strangely, I functioned fine with 2-5 hour sleep with occasional nap for 2 weeks when I returned home from abroad 3 weeks ago. Then I overdid with carwash and biking on the same day a few days ago and I've struggling despite 7 hours good sleep according to my fitbit.

 

[bobbler]

I don't follow your logic here to be honest, sorry. Hope you can help me understand you!

(1) What makes you believe that different sleep architectures between pwME and healthy controls are not "universal"? All the data I have seen these past days point towards a consistent difference. Moreover, the studies I quoted were able to differentiate clearly between the architecture in different diseases such as sleep apnea, the architecture in ME and healthy controls (three different patterns/groups here). Think "sleep fingerprint". It's not like there's one fingerprint that's healthy and only one other fingerprint that's unhealthy. Even within the group of ME, I'm sure different studies found different fingerprints (different measuring methods, patient stratification etc), but there's always a different fingerprint between ME and healthy from what I have read so far.

(2) Yes, we agree, it's likely one of many anomalies, I am not expecting this to be the main cause of ME symptoms at all. Personally, I (so far) see unrefreshing sleep (likely due to altered sleep architecture) as a symptom that's caused by something upstream.

(3) Which is why normalizing sleep architecture could in my view potentially improve quality of life but not be a solution to ME. It might still make people feel better.

On point 3 I’m very worried by all of this because I was tortured by sleep hygiene/those obsessed with if you are forced to wake up at set time every day eventually you’ll sleep at the right time. my health made worse and sleep worsened by these presumptions.

I know for sure that I get to choose (but it’s not really a choice as I quickly decline in health far faster than get if I don’t follow my body in sleep and start depriving it so then end up over tired which makes sleep worse) to either have good sleep but be stuck at the behest of my body with only being aware of my energy threshold being the main thing that can help or PEM or over threshold screws it. Or try and do silly things obsessing over ‘being normal’ and make myself much iller much faster.

I have strong views due to strong experience and have been very scientifically-minded from school age so when I say experiment and observation I mean it.

I’ve met enough others who once releasing themselves from the tyranny of what seems to come from values and assumption also realised that napping as needed and following body was eventually the only way for health and therefore ergo sleep. I think this sleep stuff is back to front.

If you try and prioritise sleep wake times you just also end up with not refreshing sleep at all but some I assume prefer that to be half not with it but on the right time zone rather than I lived in a world where I had to be on it too often. So had to if I needed to get x done then wait til I hit good sleep whenever to then function and complete whatever work needed my brain to be on.

there is something very much more than due to routine going on with the sleep thing.

and I know how light weight the research is on sleep because I was shocked at how it summed up to being sleep hygiene and the 4stages 30yrs ago when I did my degree and even more shocked none really moved past that low level still now. And I can’t help but wonder what blind spots get in the way of the area moving to look into it properly


Clearly we know that sleep is where certain key for health and particularly long term health processes take place like the cleansing of certain things out. And other processes must be happening that allow other parts of the brain to then have renewed function after good sleep. But it seems these measures never take place.

so it’s circular (like other have commented FND claims are) in as far as being sure good sleep = about timings and maybe some subjective surveys or tests of certain sleepiness impacted functions , but people just look at these sand things as both the outcomes as the causes rather than thinking other things are impacting both which if you don’t fix those you are just papering over instead of measuring.

but neurology seems to have an issue with wanting to understand other aspects of the body’s systems. Or really understanding how to design experiments to understand causes vs just assume based on association or approx patterns you don’t know if they are cart before horse or both impacted by something else.