Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study

Abstract:

PURPOSE: To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24-h repeated exercise test.

METHODS: Ten CFS, seven MS and 17 age- and gender-matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR).

RESULTS: On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml  kg  min-1 ). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC.

CONCLUSION: These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions.

© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Source: Hodges LD, Nielsen T, Baken D. Clin Physiol Funct Imaging. Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study. 2017 Aug 7. doi: 10.1111/cpf.12460. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28782878

Evidence for sensitized fatigue pathways in patients with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently demonstrate intolerance to physical exertion that is often reported as increased and long-lasting fatigue. Because no specific metabolic alterations have been identified in CFS patients, we hypothesized that sensitized fatigue pathways become activated during exercise corresponding with increased fatigue.

After exhausting handgrip exercise, muscle metabolites were trapped in the forearm tissues of 39 CFS patients and 29 normal control (NC) by sudden occlusion for up to 5 minutes. A nonocclusive condition of similar duration was used as control. Repeated fatigue and pain ratings were obtained before and after exercise. Mechanical and heat hyperalgesia were assessed by quantitative sensory testing. All subjects fulfilled the 1994 Fukuda Criteria for CFS.

Normal control and CFS subjects exercised for 6.6 (2.4) and 7.0 (2.7) minutes (P > 0.05). Forearm occlusion lasted for 4.7 (1.3) and 4.9 (1.8) minutes in NC and CFS subjects, respectively (P > 0.05). Although fatigue ratings of CFS subjects increased from 4.8 (2.0) to 5.6 (2.1) visual analogue scale (VAS) units during forearm occlusion, they decreased from 5.0 (1.8) to 4.8 (2.0) VAS units during the control condition without occlusion (P = 0.04). A similar time course of fatigue ratings was observed in NC (P > 0.05), although their ratings were significantly lower than those of CFS subjects (P < 0.001). Quantitative sensory testing demonstrated heat and mechanical hyperalgesia in CFS subjects.

Our findings provide indirect evidence for significant contributions of peripheral tissues to the increased exercise-related fatigue in CFS patients consistent with sensitization of fatigue pathways. Future interventions that reduce sensitization of fatigue pathways in CFS patients may be of therapeutic benefit.

 

Source: Staud R, Mokthech M, Price DD, Robinson ME. Evidence for sensitized fatigue pathways in patients with chronic fatigue syndrome. Pain. 2015 Apr;156(4):750-9. doi: 10.1097/j.pain.0000000000000110. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366335/ (Full article)

 

Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) subjects would produce greater force production in their matching limb during a fatiguing contralateral limb-matching task of the elbow flexors, compared with healthy, matched controls.

Eight CFS subjects and 8 healthy, matched control subjects participated in a fatiguing task that consisted of intermittent submaximal contractions (30% maximal voluntary contraction) of the nondominant arm performed over a 45 min duration. Each minute, the subject attempted to match the force of the nondominant arm with their dominant arm (without visual feedback for the dominant arm).

Results showed that average matching force and ratings of perceived effort values were significantly higher in the CFS group during the fatiguing task (P = 0.04, P = 0.02, respectively). This study demonstrated objectively that CFS subjects experienced a greater sense of effort in the elbow flexors while performing a fatiguing task.

 

Source: Wallman KE, Sacco P. Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome. Res Sports Med. 2007 Jan-Mar;15(1):47-59. https://www.ncbi.nlm.nih.gov/pubmed/17365951

 

Exercise testing in children and adolescents with chronic fatigue syndrome

Abstract:

The objective of this study was to evaluate exercise capacity in children and adolescents diagnosed with Chronic Fatigue Syndrome (CFS). We examined 20 patients (12 girls and 8 boys; mean age 14.9 +/- 3.7 years) diagnosed with CFS.

Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Fatigue was assessed using a questionnaire and a daily activity diary was used to describe activities for three days. Z-scores were calculated using age- and sex-matched reference values. Z-scores in children and adolescents with CFS were – 0.33 +/- 1.0 (p = 0.17) for peak oxygen uptake, – 1.13 +/- 1.41 (p = 0.002) for relative peak oxygen uptake [ml/kg/min] and – 0.93 +/- 1.29 (p = 0.07) for maximal work load. Both heart rate and blood pressure at peak performance were significantly reduced compared to reference values.

Fatigue levels were significantly positively associated with age and negatively with blood pressure at peak exercise (p < 0.05). In conclusion maximum exercise testing was feasible in young people with CFS. Maximal exercise capacity was only reduced in a minority of the patients and was related to current physical activity levels.

 

Source: Takken T, Henneken T, van de Putte E, Helders P, Engelbert R. Exercise testing in children and adolescents with chronic fatigue syndrome. Int J Sports Med. 2007 Jul;28(7):580-4. Epub 2007 Mar 15. https://www.ncbi.nlm.nih.gov/pubmed/17357961

 

Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions

Abstract:

OBJECTIVE: In an attempt to examine whether impairments in cardiorespiratory fitness are associated with daily functioning in patients with chronic fatigue syndrome (CFS), this study addresses the correlations between exercise capacity and activity limitations/participation restrictions.

DESIGN: Prospective observational study.

SETTING: An outpatient tertiary care, chronic fatigue clinic at the Vrije Universiteit Brussel (VUB), Belgium.

SUBJECTS: Seventy-seven patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) case definition for CFS.

INTERVENTIONS: All patients filled in the Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ) and performed a maximal exercise stress test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Metabolic and ventilatory parameters were measured through spirometry.

RESULTS: A statistically significant correlation between the score obtained with the CFS-APQ and the body weight-adjusted peak oxygen uptake (Spearman rho = -0.32; p = 0.005), functional aerobic impairment (rho = 0.33; p = 0.004), workload/body weight (rho = -0.30; p = 0.009), exercise duration (rho = -0.30; p = 0.008), and the percentage of target heart rate achieved (rho = -0.33; p = 0.004) was observed. The correlations between the remaining exercise capacity parameters and the scores obtained with the CFS-APQ all indicated a trend towards association (0.01 <p<0.05).

CONCLUSIONS: These results suggest a moderate association between exercise capacity and activity limitations/participation restrictions in patients with CFS. The observed correlations lack strength to predict activity limitations/ participation restriction based on exercise capacity parameters. Disability evaluation in CFS should therefore encompass both exercise capacity testing and measurements at the activity/participation dimension.

 

Source: Nijs J, De Meirleir K, Wolfs S, Duquet W. Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions. Clin Rehabil. 2004 Mar;18(2):139-48. http://www.ncbi.nlm.nih.gov/pubmed/15053122

 

Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy

Abstract:

BACKGROUND: Previous study of patients with chronic fatigue syndrome (CFS) has demonstrated a markedly reduced dynamic exercise capacity, not limited by cardiac performance and in the absence of clinical neuromuscular dysfunction, suggesting the possibility of a subclinical defect of skeletal muscle.

METHODS: The in vivo metabolism of the gastrocnemius muscles of 22 CFS patients and 21 normal control subjects was compared during rest, graded dynamic exercise to exhaustion and recovery, using 31P nuclear magnetic resonance (NMR) spectroscopy to reflect minute-to-minute intracellular high-energy phosphate metabolism.

RESULTS: Duration of exercise was markedly shorter in the CFS patients (8.1 +/- 2.8 min) compared with the normal subjects (11.3 +/- 4.3 min) (p = 0.005). There were large changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH from rest to clinical fatigue in all subjects, reflecting the high intensity of the exercise. The temporal metabolic patterns were qualitatively similar in the CFS patients and normal subjects. There were early and continuous changes in PCr and Pi that peaked at the point of fatigue and rapidly reversed after exercise. In contrast, pH was relatively static in early exercise, not declining noticeably until 50 percent of total exercise duration was achieved, and reaching a nadir at 2 min postexercise, before rapidly reversing. There were no differences in pH at rest (7.08 +/- 0.04 vs 7.10 +/- 0.04), exhaustion (6.85 +/- 0.17 vs 6.76 +/- 0.17) or early (6.64 +/- 0.25 vs 6.56 +/- 0.24) or late recovery (7.09 +/- 0.04 vs 7.10 +/- 0.05), CFS patients vs normal subjects, respectively (NS). Neither were there intergroup differences (NS) in PCr or Pi. Although, quantitatively, the changes in PCr, Pi, and pH were marked and similar in both groups from rest to exhaustion, the changes all occurred much more rapidly in the CFS patients. Moreover, adenosine triphosphate (ATP) was significantly (p = 0.007) less at exhaustion in the CFS group.

CONCLUSIONS: Patients with CFS and normal control subjects have similar skeletal muscle metabolic patterns during dynamic exercise and reach similar clinical and metabolic end points. However, CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients. This metabolic defect may contribute to the reduced physical endurance of CFS patients. Its etiology is unknown. Whether CFS patients’ overwhelming tiredness at rest has a similar metabolic pathophysiology or etiology also remains unknown.

 

Source: Wong R1, Lopaschuk G, Zhu G, Walker D, Catellier D, Burton D, Teo K, Collins-Nakai R, Montague T. Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest. 1992 Dec;102(6):1716-22. http://www.ncbi.nlm.nih.gov/pubmed/1446478

 

Physiologic measurement of exercise and fatigue with special reference to chronic fatigue syndrome

Abstract:

Oxidative metabolism is the major source of energy for muscle activity, and maximal oxygen uptake (VO2max), the product of maximal cardiac output and maximal arteriovenous oxygen difference, indicates individual capacity for oxidative metabolism and performance of exercise by the large muscles.

Strength, a function of muscle cross-sectional area, motor-unit recruitment, and neuromuscular coordination, is the ability to develop force in a single, brief, maximal-effort voluntary contraction of rested muscle. Weakness is a diminished ability of rested muscle to exert maximal force. Fatigue is a loss of maximal force-generating capacity that develops during muscular activity, likely originates within muscle itself, and persists until muscle is fully recovered. Individual perception of motor effort can be determined with standardized rating scales.

These concepts are discussed in detail, their relevance to the pathophysiology of exercise in chronic fatigue syndrome is analyzed, and a general strategy of exercise evaluation pertinent to chronic fatigue syndrome is presented.

 

Source: Lewis SF, Haller RG. Physiologic measurement of exercise and fatigue with special reference to chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S98-108. http://www.ncbi.nlm.nih.gov/pubmed/2020810