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

Andy

Andy

Retired committee member
Abstract
The underlying pathophysiology of chronic fatigue syndrome remains incompletely understood and there are no curative treatments for this disorder at present. However, increasing neuroimaging evidence indicates that functional and structural abnormalities exist in the brains of chronic fatigue syndrome patients, suggesting that the central nervous system is involved in this disorder and that at least some chronic fatigue syndrome patients may have an underlying neurological basis for their illness.

In the present paper, we speculate that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome. We further postulate that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain. Although recent evidence indicates that at least some chronic fatigue syndrome patients may benefit from cerebrospinal fluid drainage, further studies are needed to confirm this finding and to determine whether this can be attributed to enhancement of glymphatic fluid flow and interstitial fluid clearance. If confirmed, this could offer promising avenues for the future treatment of chronic fatigue syndrome.

Clearly, given the relative invasive nature of cerebrospinal fluid diversion, such procedures should be reserved for chronic fatigue syndrome patients who are severely debilitated, or for those with severe headaches. Anyhow, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given that there are currently no effective treatments for this condition.
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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
Anyhow, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given that there are currently no effective treatments for this condition.
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Skycloud said:
Sorry if this is a silly question: Is toxic build up within the CNS evidenced and is there any evidence of it in pwME?
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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.
 
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.
 
I wonder whether this has any relevance:
A lymphatic waste-disposal system implicated in Alzheimer’s disease
The discovery that a set of lymphatic vessels interacts with blood vessels to remove toxic waste products from the brain has implications for cognition, ageing and disorders such as Alzheimer’s disease.
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Published 25/7/18

https://www.nature.com/articles/d41586-018-05763-0
 
@Amw66

Looking at Liver function as the cause :


Glymphatic convective flow is responsible for the drainage of ISF and its constituent solutes, at least in part, to the subarachnoid CSF via perivenous spaces. These solutes can then be cleared to the peripheral venous blood, ultimately to be eliminated in the liver or kidney, by a number of post-glymphatic clearance sites. CSF and waste can pass directly into the venous blood via arachnoid granulations protruding into dural sinuses, such as the superior sagittal sinus (lower left inset). Additionally, macromolecules contained within the CSF can exit the cranium via lymphatic vessels aligning the dural venous sinuses, or alongside olfactory nerves as they traverse the cribiform plate. Both meningeal lymphatics and those positioned within the olfactory mucosa drain to the deep cervical lymph nodes before returning to the venous blood.
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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.
 
Skycloud said:
Sorry if this is a silly question: Is toxic build up within the CNS evidenced and is there any evidence of it in pwME?
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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.
 
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