The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome

OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome (CFS), accounting for comorbid fibromyalgia (FM) and controlling for aerobic fitness. METHODS: Twenty-nine patients with CFS only, 23 patients with CFS plus FM, and 32 controls completed an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual responses were measured. Results were determined for the entire sample and for 18 subjects from each group matched for peak oxygen consumption. RESULTS: In the overall sample, there were no significant differences in cardiorespiratory parameters between the CFS only group and the controls. However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO2, and higher ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS plus FM group rated exercise as more effortful than did controls. Patients with CFS plus FM rated exercise as significantly more painful than did patients with CFS only or controls. In the subgroups matched for aerobic fitness, there were no significant differences among the groups for any measured cardiorespiratory response, but perceptual differences in the CFS plus FM group remained. CONCLUSION: With matching for aerobic fitness, cardiorespiratory responses to exercise in patients with CFS only and CFS plus FM are not different from those in sedentary healthy subjects. While CFS patients with comorbid FM perceive exercise as more effortful and painful than do controls, those with CFS alone do not. These results suggest that aerobic fitness and a concurrent diagnosis of FM are likely explanations for currently conflicting data and challenge ideas implicating metabolic disease in the pathogenesis of CFS.     

Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase,complement C4a and interleukin‐1β

Abstract. Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L (Vrije Universiteit Brussel, Brussels; University College Antwerp, Antwerp; University Hospital Brussels, Brussels; Private Practice for Internal Medicine, Gent/Aalst; and RED Laboratories N.V., Zellik; Belgium, and University of Glasgow, Glasgow, UK). Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin‐1β. J Intern Med 2010; 267 : 418–435. Objectives. Too vigorous exercise or activity increase frequently triggers postexertional malaise in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a primary characteristic evident in up to 95% of people with ME/CFS. The present study aimed at examining whether two different types of exercise results in changes in health status, circulating elastase activity, interleukin (IL)‐1β and complement C4a levels. Design. Comparative experimental design. Setting. University. Subjects. Twenty‐two women with ME/CFS and 22 healthy sedentary controls Interventions: participants were subjected to a submaximal exercise (day 8) and a self‐paced, physiologically limited exercise (day 16). Each bout of exercise was preceded and followed by blood sampling, actigraphy and assessment of their health status. Results. Both submaximal exercise and self‐paced, physiologically limited exercise resulted in postexertional malaise in people with ME/CFS. However, neither exercise bout altered elastase activity, IL‐1β or complement C4a split product levels in people with ME/CFS or healthy sedentary control subjects (P > 0.05). Postexercise complement C4a level was identified as a clinically important biomarker for postexertional malaise in people with ME/CFS. Conclusions. Submaximal exercise as well as self‐paced, physiologically limited exercise triggers postexertional malaise in people with ME/CFS, but neither types of exercise alter acute circulating levels of IL‐1β, complement C4a split product or elastase activity. Further studying of immune alterations in relation to postexertional malaise in people with ME/CFS using multiple measurement points postexercise is required.     

Chronic fatigue syndrome combines increased exercise‐induced oxidative stress and reduced cytokine and Hsp responses

Objectives. As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic fatigue syndrome (CFS) who present an accentuated exercise‐induced oxidative stress. Design. This case–control study compared nine CFS patients to a gender‐, age‐ and weight‐matched control group of nine healthy sedentary subjects. Interventions. All subjects performed an incremental cycling exercise continued until exhaustion. We measured ventilation and respiratory gas exchange and evoked compound muscle potential (M‐wave) recorded from vastus lateralis. Repetitive venous blood sampling allowed measurements of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)], two cytokines (IL‐6 and TNF‐α) and two Hsp (Hsp27 and Hsp70) at rest, during maximal exercise and the 60‐min recovery period. Results. Compared with controls, resting CFS patients had low baseline levels of RAA and Hsp70. Their response to maximal exercise associated (i) M‐wave alterations indicating reduced muscle membrane excitability, (ii) early and accentuated TBARS increase accompanying reduced changes in RAA level, (iii) absence of significant increase in IL‐6 and TNF‐α, and (iv) delayed and marked reduction of Hsp27 and Hsp70 variations. The post‐exercise increase in TBARS was accentuated in individuals having the lowest variations of Hsp27 and Hsp70. Conclusions. The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress, which might result from delayed and insufficient Hsp production.     

Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome

Abstract. Jones DEJ, Hollingsworth KG, Taylor R, Blamire AM, Newton JL (From the Institute of Cellular Medicine, Newcastle Magnetic Resonance Centre, and Institute for Ageing and Health, Newcastle University, UK). Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome. J Intern Med 2010; 267 : 394–401. Objectives. To examine muscle acid handling following exercise in chronic fatigue syndrome (CFS/ME) and the relationship with autonomic dysfunction. Design. Observational study. Setting. Regional fatigue service. Subjects & interventions. Chronic fatigue syndrome (n = 16) and age and sex matched normal controls (n = 8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load maximum voluntary contraction. Heart rate variability was performed during 10 min supine rest using digital photophlethysmography as a measure of autonomic function. Results. Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately postexercise (CFS: 1.1 ± 0.5 mmol L^?1 min^?1 vs. normal: 3.6 ± 1.5 mmol L^?1 min^?1, P < 0.001) and maximally (CFS: 2.7 ± 3.4 mmol L^?1 min^?1 vs. control: 3.8 ± 1.6 mmol L^?1 min^?1, P < 0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6 ± 36.1 s vs. normal: 3.8 ± 5.2 s, P < 0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r² = 0.6; P < 0.01). In CFS patients, in contrast, this significant normal relationship was lost (r² = 0.003; P = ns). In normal individuals, the maximum proton efflux following exercise were closely correlated with total heart rate variability (r² = 0.7; P = 0.007) this relationship was lost in CFS/ME patients (r² < 0.001; P = ns). Conclusion. Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.     

Effect of pulmonary rehabilitation on quadriceps fatiguability during exercise

We have recently shown that patients with chronic obstructive pulmonary disease (COPD) develop contractile fatigue of their quadriceps muscle following endurance exercise. Pulmonary rehabilitation can produce physiological adaptations in patients with COPD. We hypothesized that if pulmonary rehabilitation induces physiological adaptations in the exercising muscle, it should become more fatigue resistant. Twenty one patients with COPD, mean age 69.9 +/- 1.9 yr, FEV(1) 45 +/- 4% predicted, participated in an 8-wk outpatient, supervised pulmonary rehabilitation exercise program. Quadriceps contractile fatigue was detected by a fall in quadriceps twitch force postexercise. Twitch force was measured during magnetic stimulation of the femoral nerve. Because potentiated twitches may be more sensitive at detecting fatigue, both unpotentiated (TwQu) and potentiated (TwQp) twitches were obtained before and 10, 30, and 60 min after constant load cycle exercise. Prerehabilitation, during constant load exercise, patients exercised at 37 +/- 4 W for 11.2 +/- 1.8 min. Prerehabilitation, TwQu fell significantly postexercise down to a minimum value of 82.5 +/- 3.1% of the baseline preexercise value (p < 0.001). Similarly, prerehabilitation, TwQp fell significantly postexercise down to a minimum value of 73.9 +/- 3.9% of baseline (p < 0.001). Postrehabilitation, for the same intensity and duration of exercise, TwQu was not significantly different from baseline at any time postexercise. Postrehabilitation, TwQp fell significantly postexercise but the fall in TwQp with exercise was significantly less postrehabilitation compared with prerehabilitation (p < 0.001). In conclusion, pulmonary rehabilitation resulted in increased fatigue resistance of the quadriceps muscle in patients with COPD.     

Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc. Mira Meeus is financially supported by a Ph.D. grant (“Chronic pain in chronic fatigue syndrome: a biopsychosocial approach”) supplied by the Higher Institute of Physiotherapy, Department of Health Sciences, Hogeschool Antwerpen, Antwerp, Belgium and co-financed by Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Brussels, Belgium (OZR project OZ.R. 1234/MFYS Wer2).     

Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: An experimental study

Abstract. Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L (Vrije Universiteit Brussel, Brussels; Artesis University College Antwerp, Antwerp; University Hospital Brussels, Brussels; Private Practice For Internal Medicine, Ghent/Aalst; CVS Contactgroep, Bruges; Belgium; and University of Glasgow, Glasgow, UK). Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome. J Intern Med 2010; 268 : 265–278. Objectives. To examine the efficacy of the pain inhibitory systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) during two different types of exercise and to examine whether the (mal)functioning of pain inhibitory systems is associated with symptom increases following exercise. Design. A controlled experimental study. Setting and subjects. Twenty‐two women with ME/CFS and 22 healthy sedentary controls were studied at the Department of Human Physiology, Vrije Universiteit Brussel. Interventions. All subjects performed a submaximal exercise test and a self‐paced, physiologically limited exercise test on a cycle ergometer. The exercise tests were undertaken with continuous cardiorespiratory monitoring. Before and after the exercise bouts, subjects filled out questionnaires to assess health status, and underwent pressure pain threshold measurements. Throughout the study, subjects’ activity levels were assessed using accelerometry. Results. In patients with ME/CFS, pain thresholds decreased following both types of exercise, whereas they increased in healthy subjects. This was accompanied by a worsening of the ME/CFS symptom complex post‐exercise. Decreased pressure thresholds during submaximal exercise were associated with postexertional fatigue in the ME/CFS group (r = 0.454; P = 0.034). Conclusions. These observations indicate the presence of abnormal central pain processing during exercise in patients with ME/CFS and demonstrate that both submaximal exercise and self‐paced, physiologically limited exercise trigger postexertional malaise in these patients. Further study is required to identify specific modes and intensity of exercise that can be performed in people with ME/CFS without exacerbating symptoms.     

Fibromyalgia and chronic fatigue syndrome

Fibromyalgia (FM) is a common disorder that affects 3% of the general population. Chronic fatigue syndrome (CFS) is less common, with about 1% of adults in the US meeting the current CDC criteria for case definition. Both conditions are controversial because they do not fit either a strictly physical or psychological concept of disease. Their symptoms overlap and they share many clinical features with irritable bowel syndrome, atypical migraine and muscle tension headaches, multiple chemical sensitivities, interstitial cystitis and multiple allergies syndrome, all poorly understood entities. This review provides an historical perspective on both disorders and presents the clinical features and differential diagnoses. The relative success of current classification criteria is discussed. Pathogenic mechanisms are presented, including the relationship of FM and CFS to depression and other psychiatric diseases and the possibility that they may be ‘diseases constructs’ called ‘memes’ that are invented by physicians. A cognitive‐behavioral approach to treatment is presented that emphasizes the roles of education, stress reduction, improvement of sleep, exercise and the effective use of analgesics, antidepressants and other psychoactive medications.     

Depression, attribution style and self-esteem in chronic fatigue syndrome and fibromyalgia patients: is there a link?

The aims of the present study were to compare a single diagnosis (chronic fatigue syndrome, CFS) and a double diagnosis (CFS + fibromyalgia, CFS+FM) group regarding depression, attribution style and self-esteem as well as to examine whether attribution style is a mediator in the relationship between self-esteem and depression. Eighty-five patients (CFS: 47, CFS+FM: 38) completed questionnaires on attribution style, self-esteem and depression. The single and double diagnosis groups tended to differ slightly, but the differences were never statistically significant. In addition, only one condition was met of the four conditions mentioned by Baron and Kenny to establish that mediation exists between two variables. In conclusion, an external attribution style does not protect the CFS or CFS+FM patients with a low self-esteem from depression. The prevalence rate of depression was high in both patient samples, of which clinicians should be aware.     

Fear of movement and avoidance behaviour toward physical activity in chronic-fatigue syndrome and fibromyalgia: state of the art and implications for clinical practice

Severe exacerbation of symptoms following physical activity is characteristic for chronic-fatigue syndrome (CFS) and fibromyalgia (FM). These exacerbations make it understandable for people with CFS and FM to develop fear of performing body movement or physical activity and consequently avoidance behaviour toward physical activity. The aims of this article were to review what measures are available for measuring fear of movement and avoidance behaviour, the prevalence fear of movement and avoidance behaviour toward physical activity and the therapeutic options with fear of movement and avoidance behaviour toward physical activity in patients with CFS and FM. The review revealed that fear of movement and avoidance behaviour toward physical activity is highly prevalent in both the CFS and FM population, and it is related to various clinical characteristics of CFS and FM, including symptom severity and self-reported quality of life and disability. It appears to be crucial for treatment (success) to identify CFS and FM patients displaying fear of movement and avoidance behaviour toward physical activity. Individually tailored cognitive behavioural therapy plus exercise training, depending on the patient’s classification as avoiding or persisting, appears to be the most promising strategy for treating fear of movement and avoidance behaviour toward physical activity in patients with CFS and FM.     

Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome.

OBJECTIVE: To compare the cardiovascular response during postural challenge of patients with fibromyalgia (FM) to those with chronic fatigue syndrome (CFS). METHODS: Age and sex matched patients were studied, 38 with FM, 30 with CFS, and 37 healthy subjects. Blood pressure (BP) and heart rate (HR) were recorded during 10 min of recumbence and 30 min of head-up tilt. Differences between successive BP values and the last recumbent BP, their average, and standard deviation (SD) were calculated. Time curves of BP differences were analyzed by computer and their outline ratios (OR) and fractal dimensions (FD) were measured. HR differences were determined similarly. Based on the latter measurements, each subject's discriminant score (DS) was computed. RESULTS: For patients and controls average DS values were: FM: -3.68 (SD 2.7), CFS: 3.72 (SD 5.02), and healthy controls: -4.62 (SD 2.24). DS values differed significantly between FM and CFS (p < 0.0001). Subgroups of FM patients with and without fatigue had comparable DS values. CONCLUSION: The DS confers numerical expression to the cardiovascular response during postural challenge. DS values in FM were significantly different from DS in CFS, suggesting that homeostatic responses in FM and CFS are dissimilar. This observation challenges the hypothesis that FM and CFS share a common derangement of the stress-response system.     

Financial,occupational, and personal consequences of disability in patients with chronic fatigue syndrome and fibromyalgia compared to other fatiguing conditions

OBJECTIVE: To examine the nature and degree of self-reported disability in patients with chronic fatigue syndrome (CFS) and its associated conditions, fibromyalgia (FM) and subsyndromal fatigue (CF), compared with a chronically fatiguing but unrelated medical condition (MED). METHODS: Six hundred and thirty patients evaluated at the University of Washington Chronic Fatigue Clinic were sent questionnaires asking them to identify the financial, occupational, and personal consequences of their fatiguing illness. Thorough medical evaluations had previously applied accepted criteria for defining CFS, FM, and CF. RESULTS: The FM groups (those with and without CFS) were among the least employed. Likewise, the FM and CFS groups, more frequently than the other groups, endorsed loss of material possessions (such as car), loss of job, and loss of support by friends and family, as well as recreational activities as a result of their fatiguing illness. There were no reliable differences between groups in use of disability benefits. CONCLUSION: There is substantial illness-related disability among those evaluated at a specialized chronic fatigue clinic. Those reporting the most pervasive disability met criteria for FM either alone or in conjunction with CFS. Employers and personal relations of patients with chronic fatigue should make a greater effort to accommodate the illness-related limitations of these conditions, especially for those with FM and CFS.     

Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study

Abstract. Jones DEJ, Gray J, Frith J, Newton JL (UK NIHR Biomedical Centre in Ageing, Institute of Cellular Medicine, Institute for Ageing and Health, Newcastle University, Newcastle, UK) Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study. J Intern Med 2011; 269 : 182–188. Objectives: To examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability. Design: Longitudinal cohort study of patients with CFS (Fukuda criteria). Setting: Specialist CFS clinical service. Subjects: Phase 1: 100 patients who participated in a study of CFS symptoms in 2005 were revisited in 2009. Phase 2: 25 patients completed fatigue diaries to address intra‐ and inter‐day variability in perceived fatigue. Main outcome measures: Phase 1: subjects completed fatigue impact scale (FIS), Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS). Changes in variables represented the differences between 2005 and 2009. Phase 2: subjects rated fatigue on a scale of 0 (no fatigue) to 10 (severe fatigue) four times a day for 5 weeks. Results: Symptom assessment tools were available in both 2005 and 2009 for 74% of patients. FIS and HADS depression (HAD‐D) and anxiety (HAD‐A) scores significantly improved during follow‐up whereas ESS and OGS remained stable. FIS improved in 29/74 (39%) subjects, and by ≥10 points in 19 (26%). FIS worsened by ≥10 points in 33/74 (45%) subjects. On multivariate analysis, independent predictors of current fatigue (FIS in 2009) were FIS in 2005, HAD‐D in 2009, OGS in 2009 and change in HAD‐A. Reported fatigue was stable from week to week and from day to day. Patients reported higher fatigue in the morning (mean ± SD; 6.4 ± 2), becoming significantly lower at lunchtime (6.2 ± 2; P < 0.05) and increasing again to 7 ± 2 at bedtime. Conclusions: Current fatigue is independently associated with current autonomic symptom burden, current depression and change in anxiety during follow‐up. These findings have implications for targeted symptom management in CFS.     

The effects of traditional Chinese manual therapy (Tuina) for chronic fatigue syndrome: A protocol for systematic review and meta-analysis

Background:Chronic fatigue syndrome (CFS) is a common disease and characterized by fatigue, exhaustion, heavy limbs, and dizziness. Tuina, as a traditional Chinese manual therapy, is usually used for CFS in China. Several studies have reported that Tuina can improve fatigue exhaustion, and dizziness of patients with CFS. However, the effects of Tuina for CFS still remain controversial. Therefore, the current systematic review and meta-analysis will be conducted to investigate the effects of Tuina in the management of CFS.Methods:The comprehensive electronic search of PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, Embase, Cochrane Library, Chinese Science Citation Database, Technology Periodical Database from their inception to October 2021 will be conducted. Randomized controlled trials of Tuina for CFS will be included in the review. Two independent reviewers will complete the study selection, data extraction, and the risk of bias. The meta-analysis will be conducted using the Review Manager Version 5.3 software. The heterogeneity will be assessed using the I² statistic and Q statistic. The standardized mean difference and 95% confidence intervals will be calculated based on different heterogeneity. The subgroup analysis will be conducted based on the duration of treatment, age, gender, duration of CFS. Quality of evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation.Results:The current systematic review and meta-analysis will be to investigate the effects of Tuina in the management of CFS.Conclusion:The conclusion of this study will provide the evidence for the treatment of CFS in the future. It is expected that the conclusions drawn from this review will benefit patients, clinical practitioners and policy makers.     

Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) are at a mechanical disadvantage and should be predisposed to the development of diaphragmatic fatigue when the ventilatory system is stressed by exercise. The purpose of this study was to determine whether patients with moderately severe COPD develop contractile fatigue of the diaphragm after cycle exercise to the limits of tolerance. Twelve male patients with COPD, age 61.4 +/- 3.0 yr, participated. Their forced expiratory volume in 1 s (FEV(1)) was 1.79 +/- 0.14 L, 49.6 +/- 3.4% of predicted. Patients cycled at 60-70% of their predetermined maximal work capacity until they had to stop because of intolerable symptoms. Twitch transdiaphragmatic pressure (Pdi,tw) was measured during cervical magnetic stimulation before and 10, 30, and 60 min after exercise. A persistent fall in Pdi,tw postexercise of >/= 10% was considered potentially indicative of contractile fatigue of the diaphragm. Patients cycled for 10.2 +/- 2.0 min at a workload of 59.9 +/- 4.3 W. Patients exercised maximally relative to their capacity reaching a peak oxygen consumption (V O(2)) of 108.1 +/- 2.8% of the peak V O(2) obtained during a preliminary maximal incremental exercise test. Pdi,tw was not significantly different from baseline at any time postexercise. Pdi,tw was 19.9 +/- 1.6 cm H(2)O at baseline, 19.6 +/- 2.0 cm H(2)O at 10 min postexercise, 18. 6 +/- 2.0 cm H(2)O at 30 min postexercise, and 19.5 +/- 1.7 cm H(2)O at 60 min postexercise. In the individual patients, two of the patients had a persistent >/= 10% fall in Pdi,tw postexercise, potentially indicative of contractile fatigue of the diaphragm. In conclusion, the majority of patients with moderately severe COPD do not develop contractile fatigue of the diaphragm after high-intensity constant workload cycle exercise to the limits of tolerance.     

Association of fibromyalgia with altered skeletal muscle characteristics which may contribute to postexertional fatigue in postmenopausal women

Objective

To identify muscle physiologic properties that may contribute to postexertional fatigue and malaise in women with fibromyalgia (FM).

Methods

Healthy postmenopausal women with (n = 11) and without (n = 11) FM, ages 51–70 years, participated in this study. Physical characteristics and responses to self‐reported questionnaires were evaluated. Strength loss and tissue oxygenation in response to a fatiguing exercise protocol were used to quantify fatigability and the local muscle hemodynamic profile. Muscle biopsies were performed to assess between‐group differences in baseline muscle properties using histochemical, immunohistochemical, and electron microscopic analyses.

Results

There was no significant difference between healthy controls and FM patients in muscle fatigue in response to exercise. However, self‐reported fatigue and pain were correlated with prolonged loss of strength following 12 minutes of recovery in patients with FM. Although there was no difference in percent succinate dehydrogenase (SDH)–positive (type I) and SDH‐negative (type II) fibers or in mean fiber cross‐sectional area between groups, FM patients exhibited greater variability in fiber size and altered fiber size distribution. In healthy controls only, fatigue resistance was strongly correlated with the size of SDH‐positive fibers and hemoglobin oxygenation. In contrast, FM patients with the highest percentage of SDH‐positive fibers recovered strength most effectively, and this was correlated with capillary density. However, overall, capillary density was lower in the FM group.

Conclusion

Peripheral mechanisms, i.e., altered muscle fiber size distribution and decreased capillary density, may contribute to postexertional fatigue in FM. Understanding of these defects in fibromyalgic muscle may provide valuable insight with regard to treatment.

     

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

Abstract. Jammes Y, Steinberg JG, Delliaux S (Aix‐Marseille University, Marseille, France). 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. Objectives. A history of high‐level physical activity and/or acute infection might constitute stress factors affecting the plasma oxidant–antioxidant status and levels of heat shock proteins (HSPs) in patients with chronic fatigue syndrome (CFS). Design. This case–control study compared data from 43 CFS patients to results from a matched control group of 23 healthy sedentary subjects. Setting and subjects. Five patients had no relevant previous history (group I). Eighteen had practised high‐level sport (group II), and severe acute infection had been diagnosed in nine patients (group III). A combination of sport practice and infection was noted in 11 patients (group IV). Interventions. After examination at rest, all subjects performed a maximal cycling exercise test. Plasma levels of two markers of oxidative stress [thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA)] and both HSP27 and HSP70 were measured. Results. At rest, compared with the control group, the TBARS level was higher in groups II, III and IV patients, and the RAA level was lower in groups III and IV. In addition, HSP70 levels were significantly lower in all CFS groups, compared with controls, but negative correlations were found between resting HSP27 and HSP70 levels and the history of physical activity. After exercise, the peak level of TBARS significantly increased in groups II, III and IV, and the variations in HSP27 and HSP70 were attenuated or suppressed, with the greatest effects in groups III and IV. Conclusion. The presence of stress factors in the history of CFS patients is associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.     

Melatonin levels in women with fibromyalgia and chronic fatigue syndrome

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are stress associated disorders mainly affecting women. FM is characterized primarily by widespread musculoskeletal pain, and CFS by profound debilitating fatigue, but there is considerable overlap of clinical symptoms between these 2 syndromes. Neuroendocrine abnormalities have been noted in both FM and CFS and desynchronization of circadian systems has been postulated in their etiology. The pineal hormone melatonin is involved in synchronizing circadian systems and the use of exogenous melatonin has become widespread in patients with FM and CFS. METHODS: We examined the characteristics and relationship of melatonin and cortisol levels in premenopausal women with FM (n = 9) or CFS (n = 8), compared to age and menstrual cycle phase matched controls. Blood was collected from an indwelling intravenous catheter every 10 min over 24 h, and plasma melatonin and cortisol were determined by radioimmunoassay at 60 and 10 min intervals, respectively. RESULTS: Night time (23:00-06:50) plasma melatonin levels were significantly higher in FM patients compared to controls (p<0.05), but there was no significant difference in melatonin levels between CFS patients and controls. No differences in the timing of cortisol and melatonin secretory patterns and no internal desynchronization of the 2 rhythms were found in either patient group, compared to controls. CONCLUSION: Raised plasma melatonin concentrations have been documented in several other conditions that are associated with dysregulation of neuroendocrine axes. Increased melatonin levels may represent a marker of increased susceptibility to stress induced hypothalamic disruptions. These data indicate that there is no rationale for melatonin replacement therapy in patients with FM and CFS.     

Electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome

BACKGROUND: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) frequently overlap clinically and have been considered variants of one common disorder. We have recently shown that CFS is associated with a short corrected electrocardiographic QT interval (QTc). In the present study, we evaluated whether FM and CFS can be distinguished by QTc. METHODS: The study groups were comprised of women with FM (n=30) and with CFS (n=28). The patients were evaluated with a 10 min supine-30 min head-up tilt test. The electrocardiographic QT interval was corrected for heart rate (HR) according to Fridericia's equation (QTc). In addition, cardiovascular reactivity was assessed based on blood pressure and HR changes and was expressed as the 'hemodynamic instability score' (HIS). RESULTS: The average supine QTc in FM was 417 ms (SD 25) versus 372 ms (SD 22) in CFS (p<0.0001); the supine QTc cut-off <385.7 ms was 79% sensitive and 87% specific for CFS vs. FM. The average QTc at the 10th minute of tilt was 409 ms (SD 18) in FM versus 367 ms (SD 21) in CFS (p<0.0001); the tilt QTc cut-off <383.3 ms was 71% sensitive and 91% specific for CFS vs. FM. The average HIS in FM patients was -3.52 (SD 1.96) versus +3.21 (SD 2.43) in CFS (p<0.0001). CONCLUSION: A relatively short QTc and positive HIS characterize CFS patients and distinguish them from FM patients. These data may support the contention that FM and CFS are separate disorders.     

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

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.