Pathophysiology of sleep disturbances/unrefreshing sleep in pwME?

Jonathan Edwards said:
Sleep seems to be important for forming memories but an important part of that may be forgetting. Sleep may serve the function of erasing useless information from short term store while securing useful memories. In the past I have wondered whether the problem in ME/CFS may be a failure to 'forget' material from yesterday. Hence the interest in complement regulatory proteins since complement is apparently necessary for this forgetting process.
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Interesting angle! As an analogy, would you in that case contribute e.g. impaired working memory with running out of RAM to process/save new information? Though the brain surely is more complex than this analogy would make it sound.

Do you know in which sleep stage this complement-mediated forgetting happens?
 
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There was just a presentation of the "Sleep-Neuro-Path" study in Germany. More info here. Will share some screenshots of disturbances they found in (if I understood correctly) studies done before this new study. Seem to have found a difference in sleep spindles in NREM2 and will now look deeper into it and additionally check brainstem signals (arousals).
Very interesting stuff.
 
Here are the screenshots - I hope it's OK to share them here. Papers in preparation it says.

So they seem to have seen decreased sleep spindles in long COVID patients. Some potential correlations to ACE2-AAbs and serum MDA.
Will be interesting to see the bigger cohort where they will in addition to the thalamo-cortical network also monitor brainstem (HRV, arousals etc).
 

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Jonathan Edwards said:
Sleep seems to be important for forming memories but an important part of that may be forgetting. Sleep may serve the function of erasing useless information from short term store while securing useful memories. In the past I have wondered whether the problem in ME/CFS may be a failure to 'forget' material from yesterday. Hence the interest in complement regulatory proteins since complement is apparently necessary for this forgetting process.
Click to expand...
Is there any broader evidence for the role of complement in sleep-dependent memory pruning in humans? - in mice there is e.g. the Wang et al demonstration of the engulfment of synaptic components by microglia & that boosting CD55 prevented C1q/C3 tagging & protected memories from microglial pruning.

There's some evidence that certain signalling molecules (complement, ephrin) are affected by sleep deprivation (e.g. in Lucey et al (found C1q/C4-pathway proteins upregulated in CSF after one night without sleep) & Reis et al (showed blunted nocturnal C3a after 24 h wakefulness), & some additional evidence from studies of mild TBI. It's an interesting idea - also reminds me a little of the famous REM-dreaming Crick-Mitchison hypothesis (or, if you go well back into medical history, to William James).
 
Has anybody made some pragmatic observations in the meantime?

I've got hold of baclofen, clonidine, and agomelatine and have been trying them out for a little while. No blinding yet.

To me, all of them subjectively improve sleep onset.

Sleep maintenance is drastically increased by baclofen 25 mg and also somewhat by clonidine 75 mcg. Both increased my deep sleep significantly (measured with a polar verity sense and sleep as Android). I wake up significantly more refreshed, and on some days, I dare even say I feel somewhat rested when waking up. This, in my experience, improves the first hours of the day, and as expected, it does not fix all symptoms of my ME.

Agomelatine 25-50 mg has both caused weird nightmares and sleep paralysis, but I'm still waiting and seeing whether these are side effects that subside after a couple of weeks. I have also felt constipated.

None of these has caused drowsiness or anything alike in the mornings.

I will, down the line, decide which of these medications to test for a longer run (~ 3 months) to see if and how the effects change over time.

I am not sure about the combination of these medications; in theory, they all have different modes of action, but who knows?

Wondering if clonidine might negate possible positive effects of agomelatine on fatigue (see other post) due to the reduction of noradrenergic signalling, while agomelatine could maybe enhance it through 5-HT2C antagonism? Interested in hypotheses.

Any other experiences?
 
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