The Pathobiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Case for Neuroglial Failure, 2022, Renz-Polster et al

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking.

Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated.

Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia.

From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features – post exertional malaise and decreased cerebral blood flow – are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

https://www.frontiersin.org/articles/10.3389/fncel.2022.888232/full

 

It fits my thoughts on ME, just with higher detail.

 

But reduced cerebral blood flow is surely something suggested by Campos-Costa thirty years ago and never verified?

 

Twitter thread from one of the authors.

 

They kept finding interesting things in ME studies but there is never any money to do larger trials.

 

The problem in a nutshell. Many interesting initial findings that were never followed up.
Think what could potentially be found with current tech if we could secure funding and decent research protocols

ETA - potentially

 

Well actually I rather think Dr Costa has tried to follow it up and presumably didn't find anything much.

 

It would be good to know.
The negatives are as useful as positives .
Bansal was looking into glucocorticoid receptor resistance , which sounded promising but .... Silence

 

So many unanswered questions, so frustrating considering the advances in our knowledge of other neurological disorders. I often wonder how often they are using the donated brains from pwME/CFS via the USA NIH Brain Bank (and is there a specific brain donation for ME/CFS in UK? UK Biobank? and if they need to get more (despite this sounding unappealing or culturally insensitive to many).

 

What's new is old and what's old is new. That's the history of M.E as it stands.

 

One of the authors talks about his ideas on Cort's blog.
https://www.healthrising.org/blog/2022/06/23/neuroglial-hypothesis-chronic-fatigue-syndrome/

 

Fascinating read. This paper stuck in my head for a long time, until I discovered Jared Younger's research. The more I ponder this, the more low-grade neuroinflammation seems like the most sensible hypothesis given the data currently available. It fits with many aspects of ME that others can't explain:

• The delay of PEM
  
• Both mental and physical activity triggering PEM
• Possibility of worsening with overexertion--maybe the cells "learn" to be more hypersensitive
• Cognitive and autonomic issues

I'm not sure of any other hypothesis that tries to explain PEM rather than handwaving it away. That's what makes neuroinflammation special.

 

Reduced cerebral blood flow has been verified in ME/CFS, although sampling bias (tertiary clinic) may have been an issue:
Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: a quantitative, controlled study using Doppler echography, van Campen et al, 2020

 

Merged thread

Paper supporting hypothesis of ME being neuroglial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124899/

I like the paper because it reflects my beliefs about ME: that glial dysfunction is part of the core dysfunction. It seems to fit better than theories about mitochondria, blood vessels, etc, especially since those other mechanisms depend on proper functioning of the brain, which depends on proper functioning of glial cells.

 

@Creekside I'm getting an error message with that link, is it still working for you?

This link is working for me
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124899/

 

I don't know why the link failed (I've edited it now). Computer glitch?

 

Cerebral hypoperfusion causes vascular dementia. Do we know if VaD and ME/CFS are frequently present together? I haven't encountered it, but the clinical side of things is not where I spend most of my time.