Review [ME/CFS] from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances, 2024, Pietrangelo et al.

[SNT Gatchaman]

Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances
Tiziana Pietrangelo; Stefano Cagnin; Danilo Bondi; Carmen Santangelo; Lorenzo Marramiero; Cristina Purcaro; Raphael Severino Bonadio; Ester Sara Di Filippo; Rosa Mancinelli; Stefania Fulle; Vittore Verratti; Xuanhong Cheng

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a demanding medical condition for patients and society. It has raised much more public awareness after the COVID-19 pandemic since ME/CFS and long-COVID patients share many clinical symptoms such as debilitating chronic fatigue. However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research.

This review moves from pathophysiology of ME/CFS through the compelling evidence and most interesting hypotheses. It focuses on the pathophysiology of skeletal muscle by proposing the hypothesis that skeletal muscle tissue offers novel opportunities for diagnosis and treatment of this syndrome and that new evidence can help resolve the long-standing debate on terminology.

Link | Paywall (Acta Physiologica)

 

[Hoopoe]

What do they say? Can anyone give me a copy?

 

[Dolphin]

I remember some of these Italian researchers did some interesting ME/CFS muscle research in the 2000s.
It's good to know they are still interested.

 

[wabi-sabi]

However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research.

How can people keep claiming this?!

Sure, we don't know everything (or even enough), but this constant refrain of can't find the patho despite decades of research is a back handed way of hinting that there is no patho, because you know, it's all in our heads. Why can't they just say it's historically underresearched so we know very little about it, but this paper starts to rectify that situation?

 

[Hutan]

And, that sentence rings alarm bells for me for the opposite reason. We don't know the etiopathology of Longcovid. We know what appears to be the inciting illness, sure, but we know that for a whole range of ME/CFS cases e.g. EBV infection.

Still, perhaps their discussion about muscles will be interesting.

 

[SNT Gatchaman]

@Hoopoe I've DM'ed.

 

[SNT Gatchaman]

Sure, we don't know everything (or even enough), but this constant refrain of can't find the patho despite decades of research is a back handed way of hinting that there is no patho, because you know, it's all in our heads.

This review is quite comprehensive. There is a little reference to psychosocial factors in parts of the paper, but this is a firmly biological review.

 

[dave30th]

this constant refrain of can't find the patho despite decades of research is a back handed way of hinting that there is no patho,

The argument obviously is used in this way by certain people, but that's on them--it's not inherent in the point or statement itself. I read it here as a neutral statement. Sure, they could have added that it's been historically under-researched but I don't see any problem with it as is.

 

[SNT Gatchaman]

A few quotes to frame the review.

Fatigue And Muscle Fatigue In ME/CFS

ME/CFS is marked by both central and peripheral fatigue. Central fatigue is represented by decreased recruitment of motor neurons which leads to highly fatiguing motor units. Peripheral fatigue, on the other hand, is caused by muscle fibres' inability to contract as a result of several altered metabolic processes, such as oxygen imbalance and modified flux of calcium or potassium. In patients both conditions can be measured: central fatigue is assessed by measuring the restoration of a contractile response during fatiguing attempts, while peripheral fatigue can be observed when the contractile response under direct electrical muscle stimulation is reduced. Both conditions finally cause muscle fatigue (MF), a condition characterized by decreased power production and incapability to generate the necessary amount of force to maintain muscle contraction.

When MF is caused by accumulation of byproducts of intermediary energy metabolism or depletion of energy-rich compounds related to demanding physical activity, it is defined as temporary muscle fatigue. Otherwise, when MF is caused by muscle atrophy, which also occurs due to sarcopenia, muscle disuse or neurogenic impairment, it is defined as chronic muscle fatigue.

MF is one of the main symptoms of ME/CFS reported by patients after moderate physical activity. In fact, difficulty in maintaining muscle activity is broadly described and it seems to be caused by lack of energy or muscle pain, with the latter underlying the neurological involvement. In order to evaluate muscular strength and to obtain information regarding patient's state of health and physical function, measurement of hand grip strength (HGS) and recovery time from fatiguing exercise are used. Several studies highlighted the decrease in HGS and impaired recovery in people affected by ME/CFS, suggesting the clinical relevance of the HGS evaluation in this illness.

With regard to the impairment of recovery, the work rate of ME/CFS patients at anaerobic threshold is reduced in the second out of two VO2 peak tests separated by 24 h compared to healthy controls, with a minimal clinically important difference of 10 W. Ample evidence shows that ME/CFS patients have reduced functional capacity in repeated cardiopulmonary exercise tests compared with healthy controls, 24–26 supporting systemic exertion intolerance as a cornerstone of ME/CFS.

 

[SNT Gatchaman]

Oxidative stress in fatigue and ME/CFS

Some oxidative molecular damages have been found in skeletal muscle of ME/CFS, specifically increased membrane rigidity and cytosolic [Ca2+] elevation and decreased antioxidant enzyme activity. Fluidity and fatty acid composition in ME/CFS muscle membranes are significantly different from those of the controls. The typical symptoms of muscle weakness and fatigability in the presence of non-atrophic contractile muscle suggest a very complicated framework in which skeletal muscle is able to reveal the biological origin of the syndrome.

Skeletal muscle of ME/CFS patients shows no sign of atrophy along with significant downregulation of FOXO, the master gene involved in atrophy

The physiological consequences of a shortage of ATP-bearing energy and excessive lactate production are in agreement with the debilitating exercise intolerance found in patients with ME/CFS.

 

[wabi-sabi]

The argument obviously is used in this way by certain people, but that's on them--it's not inherent in the point or statement itself.

Well, I did just read the abstract and not the whole paper. I may have leapt to some conclusions!