Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study

Abstract:

PURPOSE: To examine the physiological cost of walking in subjects with chronic fatigue syndrome (CFS) and a matched control group, walking at their preferred and at matched walking speeds.

METHODS: Seventeen people with CFS and 17 matched-controls participated in this observational study of physiological cost during over-ground gait. Each subject walked for 5 min at their preferred walking speed (PWS). Controls then walked for 5 min at the same pace of their matched CFS subject. Gait speed and oxygen uptake, gross and net were measured and oxygen uptake was expressed per unit distance ambulated. CFS subjects completed the CFS-Activities and Participation Questionnaire (CFS-APQ).

RESULTS: At PWS the CFS group walked at a slower velocity of 0.84 +/- 0.21 m s(-1) compared to controls with a velocity of 1.19 +/- 0.13 m s(-1) (p < 0.001). At PWS both gross and net oxygen uptake of CFS subjects was significantly less than controls (p = 0.023 and p = 0.025 respectively). At matched-velocity both gross and net physiological cost of gait was greater for CFS subjects than controls (p = 0.048 and p = 0.001, respectively).

CONCLUSION: The physiological cost of walking was significantly greater for people with CFS compared with healthy subjects. The reasons for these higher energy demands for walking in those with CFS have yet to be fully elucidated.

 

Source: Paul L, Rafferty D, Marshal R. Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study. Disabil Rehabil. 2009;31(19):1598-604. https://www.ncbi.nlm.nih.gov/pubmed/19848558

 

Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing

Nijs and colleagues [1] have found various correlations; however, they have not proven the direction of causation or shown what can be done with the information. As is well known, pain can have a protective effect; conditions involving a lack of sensitivity to pain can cause all sorts of extra complications. Knowledge of why patients with chronic fatigue syndrome (CFS) experience pain following exercise is far from complete. However, studies in recent years such as by Jammes [2] and Sorensen [3] give possible clues that something abnormal biochemically occurs.

The authors found no association between either the current employment rate or the percentage difference between premorbid and current employment rate and either the Pain Catastrophizing Scale, the Beck Depression Inventory score or the SF-36 bodily pain score so none of these can explain the large drop in the employment rate found in the patients in this study and in other studies, suggesting the involvement of an independent variable. The single exercise test methodology used may not find the disease-specific factors associated with the exercise intolerance in CFS; repeat exercise testing such as 24 hours apart “may be necessary to document the atypical recovery response and protracted malaise unique to CFS”[4]. In the world of employment, most jobs do not involve just one intense burst of activity; continuous work, more comparable with repeat exercise testing, is generally required to hold on to a job.

The authors refer to CFS patients supposedly having “personality traits” “involving activity-avoidance.” However studies such as Harvey et al. [5] suggest CFS patients were more active than their contemporaries pre-illness suggesting that if patients avoid activity, it is unlikely to be due to “personality traits.”

You can read the rest of this comment here: http://painmedicine.oxfordjournals.org/content/10/6/1144.long

Comment on: Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. [Pain Med. 2008]

 

Source: Kindlon T. Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. Pain Med. 2009 Sep;10(6):1144; author reply 1145-6. doi: 10.1111/j.1526-4637.2009.00690.x. Epub 2009 Sep 9. http://painmedicine.oxfordjournals.org/content/10/6/1144.long (Full article)

 

Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects

Abstract:

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS.

We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes.

Real-time, quantitative PCR showed that 19 CFS patients had lower expression of beta-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain.

These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.

PERSPECTIVE: Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.

 

Source: Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain. 2009 Oct;10(10):1099-112. doi: 10.1016/j.jpain.2009.06.003. Epub 2009 Jul 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/ (Full article)

 

Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine if self-reported levels of physical activity and fatigue are related to peak oxygen uptake (VO(2peak)) and whether these relationships differ among the patient groups (rheumatoid arthritis [RA], polymyositis [PM], and chronic fatigue syndrome [CFS]).

DESIGN: Correlational investigation.

SETTING: Two ambulatory research clinics at the National Institutes of Health, Clinical Center, Bethesda, MD.

PARTICIPANTS: There were 9 patients with PM, 10 with RA, and 10 with CFS. All patients met case criteria for their respective diagnoses. METHODS/MAIN OUTCOME MEASUREMENTS: VO(2peak) during bicycle ergometry and self-reported fatigability, fatigue, and physical activity. VO(2peak) was used as the criterion measurement of physiological fatigue with which the self-reported variables were compared.

RESULTS: The Pearson r revealed that self-reported physical activity correlated with VO(2peak) (r = 61, P = .01). However, fatigability and fatigue did not correlate with VO(2peak). Linear regression analysis was performed to assess the effects of diagnosis group, self-reported activity level or fatigue, and their interaction. A trend in the data showed a distinctive relationship between fatigue/fatigability within the 3 groups. In addition, when controlling for group status, self-reported activity predicted aerobic capacity as measured by VO(2peak).

CONCLUSIONS: This study confirms that patients with chronic, but stable RA, PM, or CFS are fatigued and have significantly decreased aerobic capacity. Self-reports of physical activity predicted VO(2peak), and may be used as an indicator of activity-based aerobic capacity. Self-reports of fatigue, however, did not correlate with VO(2peak) and hence are assessing something other than an index of aerobic capacity, and provide additional information about patients’ perceptions, which will require further investigation.

 

Source: Weinstein AA, Drinkard BM, Diao G, Furst G, Dale JK, Straus SE, Gerber LH. Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome. PM R. 2009 Jul;1(7):620-8. doi: 10.1016/j.pmrj.2009.04.007. https://www.ncbi.nlm.nih.gov/pubmed/19627955

 

Functional characterization of muscle fibres from patients with chronic fatigue syndrome: case-control study

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Although immunological and psychological aspects are present, symptoms related to skeletal muscles, such as muscle soreness, fatigability and increased lactate accumulation, are prominent in CFS patients.

In this case-control study, the phenotype of the same biopsy samples was analyzed by determining i) fibre-type proportion using myosin isoforms as fibre type molecular marker and gel electrophoresis as a tool to separate and quantify myosin isoforms, and ii) contractile properties of manually dissected, chemically made permeable and calcium-activated single muscle fibres.

The results showed that fibre-type proportion was significantly altered in CSF samples, which showed a shift from the slow- to the fast-twitch phenotype. Cross sectional area, force, maximum shortening velocity and calcium sensitivity were not significantly changed in single muscle fibres from CSF samples. Thus, the contractile properties of muscle fibres were preserved but their proportion was changed, with an increase in the more fatigue-prone, energetically expensive fast fibre type.

Taken together, these results support the view that muscle tissue is directly involved in the pathogenesis of CSF and it might contribute to the early onset of fatigue typical of the skeletal muscles of CFS patients.

 

Source: Pietrangelo T, Toniolo L, Paoli A, Fulle S, Puglielli C, Fanò G, Reggiani C. Functional characterization of muscle fibres from patients with chronic fatigue syndrome: case-control study. Int J Immunopathol Pharmacol. 2009 Apr-Jun;22(2):427-36. https://www.ncbi.nlm.nih.gov/pubmed/19505395

 

Promising outcomes of an adolescent chronic fatigue syndrome inpatient programme

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) is a condition of prolonged and disabling fatigue, which is accompanied by characteristic constitutional and neuropsychiatric symptoms. In children and adolescents, this condition occurring at a developmentally vulnerable time adds to the disability affecting self-concept, autonomy, body image, socialisation, sexuality and academic problems. This case series looks at the effects of a graded exercise programme on physical outcomes, fatigue and mental state in an adolescent population.

METHODS: Data sets from 16 adolescents who completed combined exercise training as part of the 4-week inpatient intensive CFS programme at the Austin Hospital, Melbourne were analysed. All patients completed an exercise assessment and three questionnaires before beginning any training. A paediatrician (LL) confirmed the diagnosis according to the Fukuda criteria in all patients. Exercise was carefully supervised and prescribed daily by an exercise physiologist (BG) according to each individual’s ability and response with the basic aim of increasing exercise tolerance and improving muscle strength and endurance.

RESULTS: There was an 18% improvement in volitional time to fatigue (P= 0.02) and 17% improvement in peak oxygen uptake (VO(2peak)) (P= 0.01). Upper body strength and function improved with a remarkable 70% increase in the number of push-ups. Fatigue severity was reported to improve by 13% (P= 0.01) and depression index improved significantly by 42% (P= 0.02).

CONCLUSIONS: The significance of these improvements cannot be underestimated as an improvement in physical capacity through increased time to fatigue and less severe fatigue allows adolescents to resume school, social and family activities.

Source: Gordon B, Lubitz L. Promising outcomes of an adolescent chronic fatigue syndrome inpatient programme. J Paediatr Child Health. 2009 May;45(5):286-90. doi: 10.1111/j.1440-1754.2009.01493.x. https://www.ncbi.nlm.nih.gov/pubmed/19493121

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

Abstract:

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-alpha) 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-alpha, 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.

 

Source: Jammes Y, Steinberg JG, Delliaux S, Brégeon F.Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med. 2009 Aug;266(2):196-206. doi: 10.1111/j.1365-2796.2009.02079.x. Epub 2009 May 19. https://www.ncbi.nlm.nih.gov/pubmed/19457057

 

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome

Abstract:

The aim of the current study was to investigate the levels of interleukin-6 (IL-6), its soluble receptors (sIL-6R and sgp130) and F(2)-isoprostanes, at rest and during exercise, in patients with chronic fatigue syndrome (CFS).

Six male CFS patients and six healthy controls performed an incremental exercise test to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal test at rest, immediately post-exercise and 24 h post-exercise were analyzed for IL-6, sIL-6R, sgp130 and F(2)-isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood sample for IL-6 and sIL-6R measurement.

During the incremental exercise test only power output at the lactate threshold was lower (P<0.05) in the CFS group. F(2)-isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post-exercise. The exercise study found no differences in IL-6, sIL-6R or sgp130 at any time point between groups. In the larger resting group, there were no differences in IL-6 and sIL-6R between CFS and control groups. This investigation has demonstrated that patients with CFS do not have altered plasma levels of IL-6, sIL-6R or sgp130 either at rest or following exercise. F(2)-isoprostanes, however, were consistently higher in CFS patients.

 

Source: Robinson M, Gray SR, Watson MS, Kennedy G, Hill A, Belch JJ, Nimmo MA. Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome. Scand J Med Sci Sports. 2010 Apr;20(2):282-90. doi: 10.1111/j.1600-0838.2009.00895.x. Epub 2009 Apr 13. https://www.ncbi.nlm.nih.gov/pubmed/19422646

 

Chronic fatigue syndrome

Comment in: Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions. [J Rehabil Med. 2010]

Comment on: Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations. [J Rehabil Med. 2008]

 

Sir, We read with interest the special report by Nijs et al. (1), entitled “Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations”. The paper proposes to provide an integrated model for graded exercise therapy (GET) in patients with chronic fatigue syndrome (CFS).
The authors state that current GET programmes for people with CFS exacerbate symptoms. This is a familiar and mistaken criticism of GET, often quoted from the 2001 Action for myaligic encephalomyelitis (ME) (AfME) survey, which reported that 50% of patients with CFS/ME who received graded exercise felt worse (2). A follow-up survey reported that, in many cases, exercise was being undertaken independently, without the supervision of a therapist trained to deliver GET to patients with CFS (3). In other words, it was not GET.

You can read the rest of this comment here: https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-0261

 

Source: Clark LV, White PD. Chronic fatigue syndrome. J Rehabil Med. 2008 Nov;40(10):882-3; author reply 883-5. doi: 10.2340/16501977-0261. https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-0261

 

Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing

Abstract:

OBJECTIVES: This study aimed to examine the associations between bodily pain, pain catastrophizing, depression, activity limitations/participation restrictions, employment status, and exercise performance in female patients with chronic fatigue syndrome (CFS) who experience widespread pain.

DESIGN: Cross-sectional observational study.

SETTING: A university-based clinic.

PATIENTS: Thirty-six female CFS patients who experienced widespread pain.

OUTCOME MEASURES: Patients filled in the Medical Outcomes Short-Form 36 Health Status Survey, the Chronic Fatigue Syndrome Activities and Participation Questionnaire, the Beck Depression Inventory, and the Pain Catastrophizing Scale, and underwent a maximal exercise stress test with continuous monitoring of electrocardiographic and ventilatory parameters.

RESULTS: Pain catastrophizing was related to bodily pain (r = -0.70), depression (r = 0.55), activity limitations/participation restrictions (r = 0.68), various aspects of quality of life ( r varied between -0.51 and -0.64), and exercise capacity (r varied between -0.41 and -0.61). Based on hierarchical multiple regression analysis, pain catastrophizing accounted for 41% of the variance in bodily pain in female CFS patients who experience chronic widespread musculoskeletal pain. Among the three subscale scores of the Pain Catastrophizing Scale, helplessness and rumination rather than magnification were strongly related to bodily pain. Neither pain catastrophizing nor depression was related to employment status.

CONCLUSIONS: These data provide evidence favoring a significant association between pain catastrophizing, bodily pain, exercise performance, and self-reported disability in female patients with CFS who experience widespread pain. Further prospective longitudinal studying of these variables is required.

Comment in: Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. [Pain Med. 2009]

 

Source: Nijs J, Van de Putte K, Louckx F, Truijen S, De Meirleir K. Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. Pain Med. 2008 Nov;9(8):1164-72. Epub 2007 Oct 3. http://painmedicine.oxfordjournals.org/content/9/8/1164.long (Full article)