The putative glymphatic signature of chronic fatigue syndrome: A new view on the disease pathogenesis and therapy, 2018, Wostyn et al

Paywalled at https://www.medical-hypotheses.com/article/S0306-9877(18)30548-6/fulltext

 

When the glymphatic system was first discovered i gave it some serious thought and concluded it was not the cause of ME/CFS. That was a few years ago and i forget how i came to that conclusion (and my cognition was much better then) but i think this is a fishing expedition to be honest, especially given

 

Sorry if this is a silly question: Is toxic build up within the CNS evidenced and is there any evidence of it in pwME?

 

So, we are essentially back to the application of leeches, albeit figurative ones, to drain the bad humors.

Medicine never fails to disappoint me, always goes back to the same old chestnuts when it gets stuck.

 

Not that silly. As far as I know there is no known condition of toxic build up in the CNS. Toxic effects on the CNS, as in hepatic or renal failure, always involve toxins coming in to the CNS from outside, not toxins from the CNS failing to get out.

It is also puzzling that they suggest draining CSF - which is the old way out of the CNS. The lymphatic system is a newly discovered alternative way out - and if it is not working I doubt draining CSF would help. It never made much sense to think of the CSF as the way out from deep brain tissue anyway.

 

@Jonathan Edwards Thank you that helps

 

I wouldn' t dismiss toxic build up. Low glutathione is found in many, compromising detox processes. Should you have a genetic issue ( such as propensity for hemachromatosis, folate/ b12 processing compromising methylation ) then this may become more acute. Too complex for my non science brain, however this seems to be part of the issue for my aunt and daughter, and might also shed light on vaccination onsets.
@mariovitali may be able to shed some light, @JaimeS too.

 

Call this a theory but i think every time something new is discovered many try to pin yet unexplained things to it. The odd time they are correct (narcolepsy being an example).

 

@Amw66

Looking at Liver function as the cause :

The question is whether a Liver insult (EBV, Coxsackie B, Medications) along with chronic Liver Disease (which may not show on any Liver panel but only through Liver Biopsy) could be responsible for this toxic buildup.

Link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803388/

 

Toxic build up due to liver disease is not going to be helped by draining CSF because the toxins are going IN to the brain, not failing to get out.

Toxin build up with liver disease requires serious hepatocyte failure or biliary obstruction. I have seen many people with severe liver disease with liver function tests seriously out of line but no more than a handful with actual symptoms of toxin build up - they are mostly within a few days of death with widespread cancer. None of this is of any relevance to ME to my mind.

 

@Jonathan Edwards

Thank you.

 

Well. 'Toxic buildup' is kind of hand-wavey, ain't it?

There are a series of tiny studies on increased ventricular lactate in ME. When placed together they are more compelling than alone. I sure hope it's not the same patients over and over, though it might be.

These studies compared other diseases considered neuroinflammatory (in some circles). ME patients still have the highest ventricular lactate out of any studied group after four of these studies.

None of this implies a buildup of toxic metabolites due to any kind of blocked glymphatic passages, just a decrease in the flow of oxygen to the brain -- at least, that's the Ockham's razor explanation.

Likewise the T2 hyperintensities they mention. Those are common in other neurological diseases, so it seems strange to posit that they're due to glymphatic blockage when they could very well be due to some minor hypoxia.

I hate to knock someone's theory out of the water, so I'll just say I'd need a heck of a lot more. But then, that's what Medical Hypotheses is for as a journal. If they extract some of what they're written to create a nugget of a rationale and gather a bit of preliminary data, they can use it to apply for a grant and find out more.

That's very tough in neurology, though, where each test used to gather preliminary data is far more expensive than a blood draw.

 

I am curious, can anyone write up a hypothesis and get it published there?
As a forum i bet we could come up with some interesting hypotheses and write them up as a paper.

 

Thanks @JaimeS, that helps too.

 

That would be helpful.

 

Yes, I've been wanting to do that for quite some time actually. There's a serious brain trust here on S4ME.

 

I was hoping it was a serious brain truss, I've certainly been using S4ME to support my brain.

 

I dunno about that, i don't trust my brain anymore, its been faltering
I do know what you mean, we could collectively generate some good material

 

Haven't we all!

Why don't y'all PM me and we can set up a time to discuss? If you're comfortable doing so.