After trying to skim read this article I was forced to diagnose myself with an acute allergy to the word 'stress'. This really ought to be added to the list of possible ME symptoms. Like for ME, there's currently no cure for this allergy but symptom reduction may be achieved by placing heavy weights on one's knees to suppress the worst knee jerk reflexes. Keeping the broad dictionary definition of 'stress' on hand helps, too.
Anyway, I reread the article more carefully and noticed that the word 'stress' was in quotation marks throughout. Are the authors co-suffers of my allergy? Mind you, other words are consistently in quotation marks, too, so not sure what the intention with that is.
Next thing that struck me was the relative weight given to discussing fatigue and PEM. Compared to most other papers fatigue is less prominent and PEM gets more consideration. This is a welcome change. It's probably explained by this at the end of the article (bolding mine):
Declaration of conflicting interests
The authors have no conflict of interest or financial benefit from the ideas expressed, but direct (AM) and indirect (WT) in-depth experience of ME/CFS has inspired this contribution.
Digging deeper, as far as I can make out the key idea of the paper is that ME is primarily a neuroinflammatory condition of the CNS. That neuroinflammation just happens to hit a specific part within the hypothalamus, the hypothalamic paraventricular nucleus (PVN).
And the PVN has a central position in the brain. 'Stress' messages arrive there via different pathways. Psychological 'stress' signals come in from one path, viral infection 'stress' signals come in from a different path and so on.
These incoming signals cause and/or perpetuate and/or exacerbate inflammation in the PVN in (genetically?) susceptible individuals.
The inflammation then messes with outgoing signals, causing all sorts of symptoms. Areas located close to the PVN may also be affected so symptoms can differ depending on where exactly the inflammation in bad in an individual patient at a given time.
The above would explain why there are patients who believe their trigger was psychological stress and other patients who believe psychological stress had nothing whatsoever to do with it but that it was all due to a virus or some toxin. It would also explain why some patients suffer psychological symptoms and others do not.
Not saying that the proposed mechanisms are correct - I've no idea TBH, I'm not equipped to judge how strong the evidence is for the different dysfunctional processes referred to in the article - but there does seem to be some internal logic at least.
Where the paper really challenges my limited understanding of biology is where it discusses possible disease mechanism similarities between ME and some other major diseases.
An initial ‘neuroinflammatory’ response, due to persistently activated microglia and astrocytes, is reported to occur across ‘early-stage’ neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Intriguingly, what appears to differentiate their pathological outcomes are the presence of disease and (CNS) location-specific ‘endogenous factors’ that help stimulate and sustain each of these uncontrolled ‘inflammatory’ responses: ‘amyloid-beta’ for AD, ‘α-synuclein’ for PD, ‘mutant SOD1’ for ALS and ‘myelin-peptide-mimetic’ for MS.
Different triggers and predisposing factors, in combination with a disease-specific ‘endogenous factor’, for ME/CFS, inducing a similar type of initial ‘neuroinflammatory’ response, but at different locations within the CNS and with different pathological outcomes, seems plausible.
Is somebody able to explain, in
very simple terms, when and how this unidentified 'endogenous' factor enters the picture, and its exact role?
If either of the authors is reading this, maybe you could respond? Correct any of our probably many misunderstandings? And it would be great to discuss your ideas further.
