Tag: muscles

Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles.

Methods: Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement.

Results: The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6-86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3-55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period.

Conclusions: There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles.

Source: Matsui T, Hara K, Iwata M, Hojo S, Shitara N, Endo Y, Fukuoka H, Matsui M, Kawaguchi H. Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). BMC Musculoskelet Disord. 2021 May 5;22(1):419. doi: 10.1186/s12891-021-04293-7. PMID: 33952227. https://pubmed.ncbi.nlm.nih.gov/33952227/

The role of IP-10 in Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a severely debilitating and complex illness of uncertain cause, characterised by prolonged, fatigue triggered by minimal activity. There is evidence that CFS is associated with chronic inflammation. Studies have shown that plasma levels of cytokines are chronically modified in patients with CFS.

This study examined physiological, subjective and cognitive factors associated with plasma cytokine concentrations in a cohort of 92 patients compared with age and sex matched healthy controls. A sub-group of patients and healthy controls (HCs) also underwent more detailed analyses of muscle function, cytokine production and cognitive function. Patients were diagnosed with CFS if they met the Oxford criteria for Chronic Fatigue Syndrome and recommended NICE guidelines. Patients completed a number of validated questionnaires including the Chalder Fatigue Questionnaire (CFQ) which is considered a valid and reliable measure of fatigue in patients with CFS.

Patients with CFS demonstrated a characteristic significant reduction in Maximal Voluntary Contraction Force compared with HCs. Data on plasma concentrations of 27 pro- and anti-inflammatory cytokines were analysed using multiple or logistic regression with age and sex which were significant covariates included in each model. CFS was strongly associated with a limited number of cytokines. Diagnosis of CFS was associated with increased plasma contents of MIP-1a, MIP-1b and RANTES (p<0.05) and marginally with Eotaxin (p=0.07) when modelled individually. MVC and self-reported fatigue both showed particularly strong associations with plasma IP-10 concentrations.

Muscle content of IP-10 mRNA was significantly elevated, suggesting that, at least in part, muscle was a source of this IP-10 but not the other cytokines. Pairwise associations between MVC and cytokines demonstrated that the reduced MVC seen in patients with CFS was strongly associated with plasma levels of IP-10, TNF-α and IL-5. Further analyses revealed strong correlations between plasma RANTES and eotaxin levels and poorer verbal recall and RTs of patients with CFS. The consistent association of IP-10 with the physiological features and of RANTES and eotaxin with the cognitive features of CFS provides compelling evidence for a role of these cytokine/chemokines in the physiological and cognitive pathology of CFS.

This work was funded by the Medical Research Council.

Source: Anne McArdle, Arief Gusnanto, Kate Earl, George Sakellariou, Clare Lawton, Daniel Owens, Graeme Close, Michael Beadsworth and Louise Dye. The role of IP-10 in Chronic Fatigue Syndrome. April 2017, The FASEB Journal, vol. 31 no. 1 Supplement lb789. http://www.fasebj.org/content/31/1_Supplement/lb789.short

 

Effects of tuina on the mechanical properties of skeletal muscles of four limbs in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To study the effects of tuina on the mechanical properties of skeletal muscles of four limbs in patients with chronic fatigue syndrome (CFS).

METHODS: Thirty CFS patients were recruited as the test group, while another 30 healthy volunteers were recruited as the healthy control group. Patients in the test group received tuina therapy, 30 min each time, once every other day, for totally 10 times. Isokinetic testing technology was used to compare peak torque (PT), total watt (TW), average power (AP), and flexor/extensor (F/E) ratio in the elbow and knee muscles of CFS patients before and after treatment. The Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale was used to evaluate the fatigue degree before and after treatment, and compared with the healthy control group.

RESULTS: After treatment the FACIT fatigue scale score decreased significantly in the test group when compared with before treatment (27.5 +/- 9.1 vs 42.5 +/- 11.2), showing statistical difference (P < 0.05). The pre-treatment PT, TW, AP, and F/E ratio in the skeletal muscle were all lower in the test group than in the healthy control group. Compared with before treatment in the test group, patients’ elbow 60 degrees/s angular velocity values during exercise extensor PT and TW, knee 60 degrees/s and 180 degrees/s angular velocity values during exercise flexor PT and TW increased significantly; elbow extensor and knee extensor, flexor AP was significantly elevated; knee in 180 degrees/s angular velocity of movement F/E ratio significantly increased, and all the differences were statistically significant (P < 0.05). The improvement of the fatigue degree in CFS patients and elbow in 60 degrees/s angular velocity values under the flexor and extensor TW, and flexor AP value of the degree of improvement were negatively correlated (r = -0.282, -0.482, -0.285, P < 0.05, P < 0.01). Meanwhile, the muscles with the knee in 180 degrees/s angular velocity was negatively correlated with the F/E ratio of the degree of improvement (r = -0. 330, P < 0.05).

CONCLUSIONS: CFS patients have lowered mechanical properties of four limbs. Tuina therapy can improve the biomechanical properties of limb skeletal muscle and reduce the overall degree of fatigue in patients. The changes of limb skeletal muscle and mechanical properties can provide objective reference for the clinical diagnosis and assessment of CFS.

 

Source: Liu KP, Fang M, Jiang SY. Effects of tuina on the mechanical properties of skeletal muscles of four limbs in patients with chronic fatigue syndrome. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 May;32(5):599-602. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/22679716

 

Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients.

In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in the vastus lateralis muscle of female and male CFS patients.

We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission. We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.

Source: Pietrangelo T, Mancinelli R, Toniolo L, Montanari G, Vecchiet J, Fanò G, Fulle S. Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):795-807. https://www.ncbi.nlm.nih.gov/pubmed/19822097

 

Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients

Abstract:

In a previous study we evaluated muscle blood flow and muscle metabolism in patients diagnosed with chronic fatigue syndrome (CFS). To better understand muscle metabolism in CFS, we re-evaluated our data to calculate free Magnesium levels in skeletal muscle. Magnesium is an essential cofactor in a number of cell processes. A total of 20 CFS patients and 11 controls were evaluated.

Phosphorus magnetic resonance spectroscopy from the medial gastrocnemius muscle was used to calculate free Mg2+ from the concentrations and chemical shifts of Pi, PCr, and beta ATP peaks. CFS patients had higher magnesium levels in their muscles relative to controls (0.47 + 0.07 vs 0.36 + 0.06 mM, P < 0.01), although there was no difference in the rate of phosphocreatine recovery in these subjects, as reported earlier. This finding was not associated with abnormal oxidative metabolism as measured by the rate of recovery of phosphocreatine after exercise. In summary, calculation of free Mg2+ levels from previous data showed CFS patients had higher resting free Mg2+ levels compared to sedentary controls.

 

Source: McCully KK, Malucelli E, Iotti S. Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients. Dyn Med. 2006 Jan 11;5:1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360067/ (Full article)

 

Urinary and plasma organic acids and amino acids in chronic fatigue syndrome

Abstract:

Previous work by others have suggested the occurrence of one or more chemical or metabolic ‘markers’ for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups.

Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed.

Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.

 

Source: Jones MG, Cooper E, Amjad S, Goodwin CS, Barron JL, Chalmers RA. Urinary and plasma organic acids and amino acids in chronic fatigue syndrome. Clin Chim Acta. 2005 Nov;361(1-2):150-8. http://www.ncbi.nlm.nih.gov/pubmed/15992788

 

Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome

Abstract:

OBJECTIVE: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS).

METHODS: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered.

RESULTS: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction.

CONCLUSIONS: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue.

SIGNIFICANCE: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.

 

Source: Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwarts MJ. Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol. 2004 Nov;115(11):2518-24. http://www.ncbi.nlm.nih.gov/pubmed/15465441

 

Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response

Abstract:

The exacerbation of symptoms after exercise differentiates Chronic fatigue syndrome (CFS) from several other fatigue-associated disorders. Research data point to an abnormal response to exercise in patients with CFS compared to healthy sedentary controls, and to an increasing amount of evidence pointing to severe intracellular immune deregulations in CFS patients. This manuscript explores the hypothetical interactions between these two separately reported observations.

First, it is explained that the deregulation of the 2-5A synthetase/RNase L pathway may be related to a channelopathy, capable of initiating both intracellular hypomagnesaemia in skeletal muscles and transient hypoglycemia. This might explain muscle weakness and the reduction of maximal oxygen uptake, as typically seen in CFS patients.

Second, the activation of the protein kinase R enzyme, a characteristic feature in at least subsets of CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with CFS. Elevated NO is known to induce vasodilation, which may limit CFS patients to increase blood flow during exercise, and may even cause and enhanced postexercise hypotension.

Finally, it is explored how several types of infections, frequently identified in CFS patients, fit into these hypothetical pathophysiological interactions.

 

Source: Nijs J, De Meirleir K, Meeus M, McGregor NR, Englebienne P. Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response. Med Hypotheses. 2004;62(5):759-65. http://www.ncbi.nlm.nih.gov/pubmed/15082102

 

Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome

Abstract:

In chronic fatigue syndrome, several reported alterations may be related to specific oxidative modifications in muscle. Since sarcoplasmic reticulum membranes are the basic structures involved in excitation-contraction coupling and the thiol groups of Ca(2+) channels of SR terminal cisternae are specific targets for reactive oxygen species, it is possible that excitation-contraction coupling is involved in this pathology.

We investigated the possibility that abnormalities in this compartment are involved in the pathogenesis of chronic fatigue syndrome and consequently responsible for characteristic fatigue. The data presented here support this hypothesis and indicate that the sarcolemmal conduction system and some aspects of Ca(2+) transport are negatively influenced in chronic fatigue syndrome.

In fact, both deregulation of pump activities (Na(+)/K(+) and Ca(2+)-ATPase) and alteration in the opening status of ryanodine channels may result from increased membrane fluidity involving sarcoplasmic reticulum membranes.

 

Source: Fulle S, Belia S, Vecchiet J, Morabito C, Vecchiet L, Fanò G. Modification of the functional capacity of sarcoplasmic reticulum membranes in patients suffering from chronic fatigue syndrome. Neuromuscul Disord. 2003 Aug;13(6):479-84. http://www.ncbi.nlm.nih.gov/pubmed/12899875

 

Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle

Abstract:

It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET).

This cannot be explained satisfactorily by the effects of ‘inactivity’ or ‘deconditioning’, and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers.

There were no differences in resting spectra between these groups but at the end of exercise, intracellular pH in the SATET +ve patients was significantly lower than in both the SATET -ve cases and controls (P < 0.03), and the SATET +ve patients also showed a significantly lower ATP synthesis rate during recovery (P < 0.01), indicating impaired mitochondrial oxidative phosphorylation.

These observations support other evidence which indicates that chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that some chronic fatigue syndrome patients have a peripheral component to their fatigue.

 

Source: Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R. Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord. 1998 May;8(3-4):204-9. http://www.ncbi.nlm.nih.gov/pubmed/9631403