Disrupted Glymphatic Function and Its Relationship with Sleep and Cognitive Impairment in ME/CFS Assessed via DTI-ALPS, 2026, Marshall-Gradisnik et al

[richie]

I think the point is when a description resonates with people.“Blocked drains” whilst a cutting remark, is an ideal example. Cutesy headlines and explanations for complex science is the world we live in.

People think there’s something not shifting, something a bit cyclical about their symptoms, a feeling of being poisoned inside.

“Brain not clearing up properly” fits this, and also with the “fragments of virus the body can’t clear” narative that people like.

That’s exactly why “Perrin Technique” is popular- to massage the blocked areas. Get them cleared properly, move the poison/fragments/debris on.

See also the ubiquitous “inflammation” which is bandied around constantl

What you say is understandable but it may be that failure to clear antigens properly is a part of the picture in some patients. It certainly is part of thee orthodox theory of pathogenesis of sarcoidosis. and uncleared bacterial debris may be playing a role in antibiotic refractory post treatment Lyme (some cases may just need more/other antibiotics). I am also a carrier of Pompe's disease and lysosomal inefficiency might affect me. Sarcoid, which I have, is also a condition where lysosomal problems are involved. I was not diagnosed with sarc until 2021 and have had fatigue etc since 1985. It is plausbile in my case that things that the body can't clear have been playing a role incl, before sarc process became apparent. I had no other label but ME.

Perrin made sense to me but I did not feel it was the right fit for me and he seemed to want to "patent" real ME i.e real ME was diagnosable by what responded to his therapy and the rest was sth else.

The problem with inflammation lies in part in competiing usages. If sb says "FM is not inflammatory" using JE's definition, as a far as I know that is correct. If they say "it is not inflammatory" and mean it has nothing to do with the immune system and is all about nervous function and psychology, then they are imo wrong. Not only is the term bandies about, its use is inconsistent.

 

[Creekside]

Do people feel that their inability to sleep restoratively (or at all) is inexplicable, or is it borne of discomfort etc that obviously interferes with good sleeping? That would be the first question I would ask.

An important question before that would be: "Is the feeling of not being restored after sleep related to sleep or due to some other sleep-unrelated mechanism?"

 

[Axel]

An important question before that would be: "Is the feeling of not being restored after sleep related to sleep or due to some other sleep-unrelated mechanism?"

That’s interesting. I get the impression that something is happening whilst I’m asleep. But to what extent is this different from a feeling of unease that builds up during the day? Perhaps the fact that I am unconscious makes it feel like something out of the ordinary, because I move from state A to stage B without being aware of the progression.
In short, it’s quite possible that this is PEM triggered whilst I’m asleep.
Furthermore, my sleep isn’t restorative, but then nothing is. On good days, my sleep is restorative and I also recover as I go along with my daily activities.

 

[DMissa]

Which is what a working scientist is supposed to be. Or at least competent enough in the basics to not get it too wrong, too often.

100%. What I was getting at was that things have become very big and very broad and we are all specialised. I say no to reviewing more papers than I say yes to because I am not confident I’d be a good judge. But having often seen what others toss out as “peer review” they do not have the same reservations. Science has just gotten too big to safely assume that people who actually understand all of the details review most papers. You wouldn’t believe the nonsense I’ve gotten back as comments before.

 

[DMissa]

An important question before that would be: "Is the feeling of not being restored after sleep related to sleep or due to some other sleep-unrelated mechanism?"

I also agree this is interesting

 

[Sean]

An important question before that would be: "Is the feeling of not being restored after sleep related to sleep or due to some other sleep-unrelated mechanism?"

Yes, need to untangle which comes first. One thing is for sure, it does not get fixed by 'better sleep hygiene'. Might help tamp it down a bit, but it is not the underlying primary problem and not even close to being able to resolve it.

 

[DMissa]

Yes, need to untangle which comes first

Yeah I just logged on after having an actual shower thought to ask: do we have any reliable data on whether sleep disturbances typically precede or follow the onset of the other stereotyped symptoms?

 

[Creekside]

Furthermore, my sleep isn’t restorative, but then nothing is. On good days, my sleep is restorative and I also recover as I go along with my daily activities.

That's my point. It's not impossible for there to be some non-sleep-related mechanism that causes the sensation of not having had a good sleep. I expect there are known chemicals that can do that. I think there's something that causes this sensation, and its severity simply has no correlation with sleep duration or quality. It's no different from having pain from a broken toe; it's simply unrelated to sleep quality or duration. The medical system simply made an assumption right at the beginning that it was a sleep problem, and no one has bothered to challenge it.

 

[SugarSquared]

Yeah I just logged on after having an actual shower thought to ask: do we have any reliable data on whether sleep disturbances typically precede or follow the onset of the other stereotyped symptoms?

This is just anecdotal, but sleep disturbances only came in 8 months after my onset. I also still get around 8-11 hours of sleep, but I normally fall asleep between 12-2am. It takes me about 2 hours when it used to take me 30 minutes. It’s like my whole sleep schedule got shifted, and forcing myself to wake up earlier didn’t do much but make me more tired. I also wake up a little more often in the middle of the night.

 

[ScoutB]

do we have any reliable data on whether sleep disturbances typically precede or follow the onset of the other stereotyped symptoms?

I don't think we do, but my sense is trouble sleeping behaves like other symptoms in ME/CFS in that it can come and go, either briefly or in periods (i.e. months or years). Basically being as confusing and hard to interpret as possible.

OTOH, there are two interesting anecdotal patterns that I'm not sure I've see explored much or described clearly in formal places:

• That trouble sleeping is especially common at the start of PEM or after exertion. See this poll for instance, where the leading response to "How does your sleep change on the first night after enough exertion to cause a PEM crash?" was "Increased wired but tired feeling before bed (resembles the effect of a stimulant like caffeine)".
• And my personal favourite unexplored mystery: That a long night's sleep (when we can get it) often seems to leave us feeling worse than before we went to bed. Here's another unscientific poll, where 66% of the responders answered "How do you feel in the morning compared to when you went to bed?" with "worse." In the comments some cite this issue of solid hours of seemingly fine sleep leaving you feeling terrible (as well as the funny result that, in this case, 'disturbed sleep' can leave you feeling better in the morning than a solid night's sleep..)

 

[Creekside]

This is just anecdotal, but sleep disturbances only came in 8 months after my onset.

My sleep deteriorated maybe 10-20 years into my ME. From that, I assume that if sleep problems are caused by ME, it's indirect. There might be multiple mechanisms for an ME-sleep connection, some with a shorter delay, some longer.

 

[Sean]

Yeah I just logged on after having an actual shower thought to ask: do we have any reliable data on whether sleep disturbances typically precede or follow the onset of the other stereotyped symptoms?

In my case it most certainly was not preceding. I was sleeping the best I ever had when I got sick. The kind of sleep where you lay down, close your eyes, then open them 8 hours later and it feels like no time had passed. And the dreams were all good, no bad ones.

Similar story with deconditioning. It cannot possibly be causally relevant to any onset process or conditions for me because I was very fit and active and healthy at the time I got sick, and continued to be more than active enough to avoid at least major deconditioning for at least several years after getting sick. And I still am. I have checked with doctors and physios and general guidelines on that one a few times over the years, so I am very certain of it.

I have also heard that basic story from countless patients. Which is why I am so strongly opposed to deconditioning (and hence rehab for it) having any central role. It may be a secondary issue for the more severe end of the spectrum, the bed-bound, who have been unable to do much at all for long periods. But as a general core underlying feature? Not a shred of good evidence for it, and a lot against it, and treating patients for it in any conventional sense.

 

[SNT Gatchaman]

Ditto to Sean's comment. I slept through the night, very well with no latency or disturbance, and with happy dreams. I was fit. And presumptive asymptomatic Covid means there wasn't even the slightest potential for deconditioning: I continued to be active as symptoms first started. The very first recognisable symptoms were after a six hour sail involving winding winches followed by paddle-boarding and swimming around a bay.

The inability to sleep was a few months in and followed a severe disabling crash, that ended much of my life. It was pathological - a complete physiological inability to sleep for maybe as much as three weeks. Very, very grim. And when sleep became possible, it was dreadful, feeling worse than no sleep and including vivid horrible nightmares. All of this was completely novel.

And I would frequently comment that a worse sleep led to a paradoxically better day.

So yes I also vote that sleep dysfunction is secondary to the disease. Not causing it and "sleep hygiene" ain't gonna help. It feels as if something is wrong with the normal processes of restoration that should be occurring, even inverted. Fortunately 5+ years later it's nowhere near as bad, but still not normal.

 

[Clio]

The inability to sleep was a few months in and followed a severe disabling crash, that ended much of my life. It was pathological - a complete physiological inability to sleep for maybe as much as three weeks. Very, very grim. And when sleep became possible, it was dreadful, feeling worse than no sleep and including vivid horrible nightmares. All of this was completely novel.

Exact same thing happened to me. Was "fine" after a covid infection but my first major crash had this exact course.

 

[NelliePledge]

Obviously with the substantial percentage (30?) who like me have gradual onset it is pretty much impossible to say what is before

For example when I was undiagnosed I self medicated with strong coffee and sugar to up my energy levels and obviously that had a negative effect on my sleep and I got gradually worsening insomnia, but I also had undiagnosed ME so impossible to say what was the cause. However since I stopped caffeine and cut down massively on sugar several years ago I still have had insomnia/sleep delay