Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with ME/CFS: results of the retrospective CoLGEM study, 2022, Retornaz et al

Andy

Retired committee member
Abstract

Background
Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS.

Methods
This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests.

Results
The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured.

Conclusions
These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms.

Open access, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03638-7
 
It has already been shown that a large proportion (around 70%) of patients with ME/CFS have neuromuscular disorders characterized by exercise-induced alterations of muscle excitability, assessed by decreased amplitude and lengthening of M-waves [14,15,16,17].

14 Jammes Y, Steinberg JG, Delliaux S. Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med. 2012;272:74–84.

15 Jammes Y, Steinberg JG, Mambrini O, Brégeon F, Delliaux S. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med. 2005;257:299–310.

16 Jammes Y, Adjriou N, Kipson N, Criado C, Charpin C, Rebaudet S, et al. Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome. J Transl Med. 2020;18:173.
Science for ME discussion, with an explanation of M-waves from @Snow Leopard
 
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Science for ME discussion, with an explanation of M-waves from @Snow Leopard

See also:
The Hoffmann Reflex: Methodologic Considerations and Applications for Use in Sports Medicine and Athletic Training Research
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC522151/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC522151/figure/F1/



Electric stimulation to elicit the H-reflex measures the efficacy of synaptic transmission5 as the stimulus travels in afferent (Ia sensory) fibers through the MN pool of the corresponding muscle to the efferent (motor) fibers.5 The afferent (sensory) portion of the H-reflex begins at the point of electric stimulation and results in action potentials traveling along afferent fibers until they reach and synapse on αMNs. The efferent portion of the H-reflex pathway results from action potentials, generated by the αMNs, traveling along efferent fibers until they reach the neuromuscular junction and produce a twitch response in the electromyograph (EMG) (the H-reflex). When the action potentials in the αMNs reach a neuromuscular junction, a synchronized twitch is produced in the muscle. This twitch is a synchronized contraction. The H-reflex is a compound action potential or a group of almost simultaneous action potentials from several muscle fibers in the same area. In addition to the afferent and efferent pathways that contribute to the H-reflex, electric stimulation of the peripheral nerve causes direct activation of the efferent fibers, sending action potentials directly from the point of stimulation to the neuromuscular junction. This efferent arc produces a response in the EMG known as the muscle response (M-wave) (Figure (Figure11)

(type 1a sensory fibres are part of muscle spindles which measure muscle stretch - these spindles are effectively in parallel with the main alpha muscle fibres and note that they have their own separate drive from the brain (gamma motor neurons), the purpose of which is to keep the muscle spindles taught)

ELICITING THE M-WAVE

Continuing to increase the stimulus intensity beyond that required for an H-reflex results in direct stimulation of the motor axons and the presence of an M-wave. The threshold of the motor axons is higher (a higher-intensity stimulus is required to activate these fibers) than that for the Ia sensory neurons due to the latter's smaller size. In general, the larger the axon, the easier it is to stimulate that neuron. In almost all cases, it is possible to preferentially stimulate the Ia sensory neurons before the motor axons are activated. When the stimulus intensity reaches the depolarization threshold for the efferent fibers, action potentials are generated and fired toward the neuromuscular junction. This volley of activity also causes a muscle contraction, but because it did not pass through the spinal cord, it is not referred to as a reflex. It is simply called a muscle response and is termed the M-wave. Due to the relatively short path the action potentials must travel for a muscle response to occur, the M-wave tracing appears on the EMG at a shorter latency than the H-reflex (ie, shows up first in the tracing). In the soleus, for example, the M-wave appears at approximately 6 to 9 milliseconds; as mentioned previously, the H-reflex appears at approximately 30 milliseconds.
 
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