The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology

Abstract:

Patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are bedridden and suffer from hypersensitivities to light and noise, severe orthostatic intolerance reducing cerebral blood flow, and skeletal muscle symptoms, including loss of force, fatigue, pain, fasciculations, and cramps. Because neurological investigations exclude neuronal causes of myasthenia, we hypothesize a muscular pathomechanism.

In previous articles, we considered insufficient activity of the Na+/K+-ATPase to be the main cause of mitochondrial damage via high intracellular sodium that reverses the transport mode of the sodium-calcium-exchanger to import calcium, causing calcium overload. Low Na+/K+-ATPase activity also causes sarcolemmal depolarization, leading to less effective action potential propagation and loss of force. Depolarization brings the membrane potential closer to the threshold potential, causing hyperexcitability that explains fasciculations and cramps. These increase sodium influx during excitation to further increase the workload of Na+/K+-ATPase. Thereby, depolarization causes further depolarization.

Higher intracellular sodium favors calcium overload and mitochondrial damage, which lowers the energy supply of Na+/K+-ATPase and increases the reactive oxygen species, further inhibiting Na+/K+-ATPase. The muscle is in a state of depolarization even at rest. Depolarization and mitochondrial damage reinforce each other. Thus, dysfunction of Na+/K+-ATPase as a single mechanism can explain the different skeletal muscle symptoms of severely ill ME/CFS patients, comprising loss of force, fatigue, and fasciculations.

Source: Wirth KJ, Steinacker JM. The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology. Front Physiol. 2026 Feb 2;16:1693589. doi: 10.3389/fphys.2025.1693589. PMID: 41705124; PMCID: PMC12907180. https://pmc.ncbi.nlm.nih.gov/articles/PMC12907180/ (Full text)

Physical activity levels respiratory and peripheral muscle strength and pulmonary function in young post-COVID-19 patients : A cross-sectional study

Abstract:

Objective: Coronavirus disease 2019 (COVID-19) causes permanent problems, even mild severity. The long-term consequences of COVID-19 are still unknown. This study aimed to investigate physical activity levels, respiratory and peripheral muscle strength, and pulmonary function in the long term in young adult COVID-19 patients who recovered from mild disease.

Methods: This cross-sectional study was carried out at least 6 months after the COVID-19 diagnosis, 54 patients with COVID-19 (median age: 20 years) and 46 controls (median age: 21 years) were compared. Functional status (post-COVID-19 functional status scale), respiratory (maximum inspiratory and expiratory pressures (MIP, MEP)) and peripheral muscle strength (dynamometer), pulmonary function (Spirometry), dyspnea and fatigue (modified Borg scale), and physical activity levels (International Physical Activity Questionnaire) were evaluated.

Clinicaltrial number: NCT05381714.

Results: Patients with COVID-19 measured and percent predicted MIP and MEP were statistically decreased compared with the controls (p < 0.05). Shoulder abductors muscle strength (p < 0.001) and the number of individuals with low physical activity levels were significantly higher in patients compared with controls (p = 0.048). Pulmonary function, quadriceps muscle strength, exertional dyspnea, and fatigue scores were similar in groups (p > 0.05).

Conclusion: Respiratory and peripheral muscle strength and physical activity levels are adversely affected in patients with COVID-19, even though the patients were mildly affected in the long term. Also, symptoms such as dyspnea and fatigue may persist. Therefore, these parameters should be evaluated in the long term, even in young adults who are mildly affected by COVID-19.

Source: Güneş M, Yana M, Güçlü MB. Physical activity levels respiratory and peripheral muscle strength and pulmonary function in young post-COVID-19 patients : A cross-sectional study. Wien Klin Wochenschr. 2023 May;135(9-10):251-259. doi: 10.1007/s00508-023-02204-5. Epub 2023 Apr 28. PMID: 37115337; PMCID: PMC10141881. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141881/ (Full text)

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study

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. Trial registration Registered retrospectively.

Source: Retornaz F, Rebaudet S, Stavris C, Jammes Y. Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study. J Transl Med. 2022 Sep 24;20(1):429. doi: 10.1186/s12967-022-03638-7. PMID: 36153556. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03638-7 (Full text)

A four-year follow-up study in fibromyalgia. Relationship to chronic fatigue syndrome

Abstract:

The primary objectives of this study were to examine to what extent fibromyalgia patients later on developed presumpted causative somatic diseases and to examine symptoms and muscle strength some years after the diagnosis of fibromyalgia was established. A secondary objective was to describe the overlap between fibromyalgia and chronic fatigue syndrome.

Only in two of 91 the muscle pain was found to be caused by another somatic disease during the median 4 year follow-up period. In one of the 83 attending subjects a somatic disease associated with muscle symptoms was established at the follow-up visit. 60 out of 83 reported increased pain, 8 reported improvement of pain. The 83 subjects showed no significant fall in muscle strength during the follow-up period. The majority reported severe fatigue but only one fifth fulfilled the proposed chronic fatigue syndrome criteria.

 

Source: Nørregaard J, Bülow PM, Prescott E, Jacobsen S, Danneskiold-Samsøe B. A four-year follow-up study in fibromyalgia. Relationship to chronic fatigue syndrome. Scand J Rheumatol. 1993;22(1):35-8. http://www.ncbi.nlm.nih.gov/pubmed/8434245