Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome

OBJECTIVES—To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy andhypertrophy in patients with chronic fatigue syndrome in relation tolactate responses to exercise, and to determine to what extent anyabnormalities found might be due to inactivity.
METHODS—Quadriceps needle muscle biopsies wereobtained from 105 patients with chronic fatigue syndrome and theproportions of type 1 and 2 fibres and fibre atrophy and hypertrophyfactors were determined from histochemical preparations, using asemiautomated image analysis system. Forty one randomly selectedbiopsies were also examined by electron microscopy. Lactate responsesto exercise were measured in the subanaerobic threshold exercise test (SATET).
RESULTS—Inactivity would be expected to result ina shift to type 2 fibre predominance and fibre atrophy, but type 1 predominance (23%) was more common than type 2 predominance (3%), andfibre atrophy was found in only 10.4% of cases. Patients withincreased lactate responses to exercise did have significantly fewertype 1 muscle fibres (p<0.043 males, p<0.0003 females), but there was no evidence that this group was less active than the patients withnormal lactate responses. No significant ultrastructural abnormalitieswere found.
CONCLUSION—Muscle histometry in patients withchronic fatigue syndrome generally did not show the changes expected asa result of inactivity. However, patients with abnormal lactateresponses to exercise had a significantly lower proportion ofmitochondria rich type 1 muscle fibres.

     

Strength and physiological response to exercise in patients with chronic fatigue syndrome

OBJECTIVE: To measure strength, aerobic exercise capacity and efficiency, and functional incapacity in patients with chronic fatigue syndrome (CFS) who do not have a current psychiatric disorder. METHODS: Sixty six patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder were recruited into the study. Exercise capacity and efficiency were assessed by monitoring peak and submaximal oxygen uptake, heart rate, blood lactate, duration of exercise, and perceived exertion during a treadmill walking test. Strength was measured using twitch interpolated voluntary isometric quadriceps contractions. Symptomatic measures included physical and mental fatigue, mood, sleep, somatic amplification, and functional incapacity. RESULTS: Compared with sedentary controls, patients with CFS were physically weaker, had a significantly reduced exercise capacity, and perceived greater effort during exercise, but were equally unfit. Compared with depressed controls, patients with CFS had significantly higher submaximal oxygen uptakes during exercise, were weaker, and perceived greater physical fatigue and incapacity. Multiple regression models suggested that exercise incapacity in CFS was related to quadriceps muscle weakness, increased cardiovascular response to exercise, and body mass index. The best model of the increased exercise capacity found after graded exercise therapy consisted of a reduction in submaximal heart rate response to exercise. CONCLUSIONS: Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function.     

Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome

Background: Data on the prevalence of orthostatic intolerance (OI) in patients with chronic fatigue syndrome (CFS) are limited and controversial. We tested the hypothesis that a majority of CFS patients exhibit OI during head-up tilt. Methods: Hemodynamic and neurohumoral responses to 40 minutes of head-up tilt were studied in 36 CFS patients and 36 healthy controls. Changes in stroke volume, cardiac output and peripheral vascular resistance were estimated from finger arterial pressure waveform analysis (Modelflow). Blood samples were drawn before and at the end of head-up tilt for measurement of plasma catecholamines. Results: At baseline, supine heart rate was higher in CFS patients (CFS: 66.4 ± 8.4 bpm; controls: 57.4 ± 6.6 bpm; p < 0.001) as was the plasma epinephrine level (CFS: 0.11 ± 0.07 nmol/l; controls: 0.08 ± 0.07 nmol/l: p = 0.015). An abnormal blood pressure and/or heart rate response to head-up tilt was seen in 10 (27.8 %) CFS patients (6 presyncope, 2 postural tachycardia, 2 tachycardia and presyncope) and 6 (16.7 %, p = 0.26) controls (5 presyncope, 1 tachycardia, 2 tachycardia and presyncope). Head-up tilt-negative CFS patients showed a larger decrease in stroke volume during tilt (−46.9 ± 10.6) than head-up tilt-negative controls (−40.3 ± 13.6 %, p = 0.008). Plasma catecholamine responses to head-up tilt did not differ between these groups. Conclusion: Head-up tilt evokes postural tachycardia or (pre)syncope in a minority of CFS patients. The observations in head-up tilt-negative CFS patients of a higher heart rate at baseline together with a marked decrease in stroke volume in response to head-up tilt may point to deconditioning. Received: 20 July 2001, Accepted: 19 February 2002     

Blunted adrenocorticotropin and Cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome

Hyperfunctioning of the pituitary-adrenal axis has been suggested as the pathophysiological basis for chronic fatigue syndrome (CFS). Blunted adrenocorticotropin (ACTH) responses but normal Cortisol responses to exogenous corticotropin-releasing hormone (CRH), the main regulator of this axis, have been previously demonstrated in CFS patients, some of whom had a comorbid psychiatric disorder. We wished to re-examine CRH activation of this axis in CFS patients free from concurrent psychiatric illness. A sample of 14 patients with CDC-diagnosed CFS were compared with 14 healthy volunteers. ACTH and Cortisol responses were measured following the administration of 100 μg ovine CRH. Basal ACTH and Cortisol values did not differ between the two groups. The release of ACTH was significantly attenuated in the CFS group (P<0.005), as was the release of Cortisol (P<0.05). The blunted response of ACTH to exogenous CRH stimulation may be due to an abnormality in CRH levels with a resultant alteration in pituitary CRH receptor sensitivity, or it may reflect a dysregulation of vasopressin or other factors involved in HPA regulation. A diminished output of neurotrophic ACTH, causing a reduced adrenocortical secretory reserve, inadequately compensated for by adrenoceptor upregulation, may explain the reduced Cortisol production demonstrated in this study.     

Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome

Patients with the chronic fatigue syndrome (CFS) complain consistently of delay in recovery of peripheral muscle function after exercise. The purpose of this study was to try to confirm this observation. A fatiguing exercise test was carried out on the quadriceps muscle group of ten patients and ten control subjects. The test consisted of 18 maximum voluntary contractions (MVCs) with a 50% duty cycle (10 s contraction, 10 s rest), and the force generated by each contraction was recorded using a KinCom dynamometer. This was followed by a recovery phase lasting 200 min in which quadriceps strength was evaluated at increasing intervals, and a follow-up session at 24 h post-exercise involving three 10 s MVCs. Throughout the exercise period, the MVCs obtained from the control group were significantly higher than those of the patient group (P = 0.006), but both groups showed a parallel decline in force over the 18 contractions, in keeping with a similar endurance capacity. Recovery was prolonged in the patient group, however, with a significant difference compared to initial MVCs being evident during the recovery phase after exercise (P = 0.001) and also at 24 h (P < 0.001). In contrast, the control group achieved MVCs which were not significantly different from initial values during the recovery phase, and maintained these at 24 h. These findings support the clinical complaint of delayed recovery after exercise in patients with CFS.     

Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome

OBJECTIVE: Subtle dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as an underlying pathophysiological mechanism in chronic fatigue syndrome (CFS). This study attempted to assess the relationship between patient characteristics and HPA axis functioning using a neuroendocrine challenge test. METHOD: A test battery designed to assess different dimensions of CFS was given to 18 CFS patients and 17 controls. To evaluate the integrity of the HPA axis, the Insulin Tolerance Test (ITT), a centrally acting neuroendocrine challenge test, was performed on patients and controls. ACTH, salivary free cortisol and total plasma cortisol levels were assessed as a measure of the HPA axis stress response. Correlations of patient characteristics were calculated with integrated responses for all endocrine parameters. RESULTS: CFS patients had a significantly reduced area under the ACTH response curve (AUC) in the ITT. The AUC was significantly associated with the duration of CFS symptoms (r = -.592, P = .005) and the severity of fatigue symptomatology (r = -.41, P = .045). In addition, duration of CFS was correlated with the severity of fatigue symptoms (r = .38, P = .045). Similar associations were not observed for cortisol parameters. CONCLUSION: It has been postulated that neuroendocrine dysregulations observed in CFS are of an acquired nature. The results of a strong association between the integrated ACTH response and the duration of CFS emphasizes the need to consider factors known to be risk factors for the chronicity of CFS symptoms, such as profound inactivity, deconditioning and sleep abnormalities, as possible candidates for secondary causes of neuroendocrine dysregulations in CFS.     

Coping strategies in twins with chronic fatigue and chronic fatigue syndrome

Objectives: Individuals with chronic fatigue and chronic fatigue syndrome (CFS) face debilitating symptoms as well as stressful life situations that may result from their condition. The goal of this study was to examine the coping strategies used by fatigue-discordant twin pairs. Methods: We utilized a co-twin design to assess how twin pairs discordant for chronic fatigue and CFS cope with stress. All twin pairs were administered the Revised Ways of Coping Checklist. Results: Overall, the pattern of coping strategies was similar for fatigued and non-fatigued twins. However, twins with chronic fatigue or CFS utilized more avoidance strategies than their non-fatigued counterparts; those with chronic fatigue also used more avoidance relative to problem-focused coping than their co-twins. Conclusions: These results suggest that while fatigue-discordant twins generally exhibit similar behavior patterns in order to cope with stress, there may be an association between fatigue and avoidance coping. Future research should focus on the role of avoidance and its relationship to fatiguing illnesses.     

Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression

OBJECTIVES—Patients with chronic fatigue syndromecomplain of physical and mental fatigue that is worsened by exertion.It was predicted that the cognitive and motor responses to vigorousexercise in patients with chronic fatigue syndrome would differ fromthose in depressed and healthy controls.
METHODS—Ten patients with chronic fatiguesyndrome, 10 with depressive illness, and 10 healthy controls completedcognitive and muscle strength testing before and after a treadmillexercise test. Measures of cardiovascular functioning and perceivedeffort, fatigue, and mood were taken during each stage of testing.
RESULTS—Depressed patients performed worst oncognitive tests at baseline. During the treadmill test, patients withchronic fatigue syndrome had higher ratings of perceived effort andfatigue than both control groups, whereas patients with depressionreported lower mood. After exertion, patients with chronic fatiguesyndrome showed a greater decrease than healthy controls on everydaytests of focused (p=0.02) and sustained (p=0.001) attention, as well asgreater deterioration than depressed patients on the focused attentiontask (p=0.03). No between group differences were found incardiovascular or symptom measures taken during the cognitive testing.
CONCLUSIONS—Patients with chronic fatigue syndromeshow a specific sensitivity to the effects of exertion on effortfulcognitive functioning. This occurs despite subjective and objectiveevidence of effort allocation in chronic fatigue syndrome, suggestingthat patients have reduced working memory capacity, or a greater demandto monitor cognitive processes, or both. Further insight into thepathophysiology of the core complaints in chronic fatigue syndrome islikely to be realised by studying the effects of exercise on otheraspects of everyday functioning.

     

Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome

OBJECTIVE: This study examined the effects of exercise on symptoms and activity in chronic fatigue syndrome (CFS). METHODS: Twenty CFS patients and 20 neighborhood controls performed an incremental exercise test until exhaustion. Fatigue, muscle pain, minutes spent resting, and the level of physical activity were assessed with a self-observation list. Physical activity was assessed with an actometer as well. Data were obtained 3 days before the maximal exercise test (MET) up to 5 days thereafter. RESULTS: For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h. Both CFS patients and controls spent more minutes resting on the day before and on the day after the MET. For CFS patients, self-observed minutes resting increased on the day of the exercise test. For neither group, a decrease of actometer recorded or self-observed physical activity after exercise was found. CONCLUSION: Fatigue in CFS patients increased after exercise, but the level of actual physical activity remained unchanged.     

Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome

OBJECTIVE: Enhancement of negative feedback control of the HPA axis in patients with chronic fatigue syndrome (CFS) has been reported using the low dose dexamethasone suppression test. We have developed the use of prednisolone (5mg) as a more physiologically appropriate alternative to dexamethasone in the investigation of mild degrees of glucocorticoid resistance or supersensitivity. The objective of the study was to use this test to look for alterations in negative feedback control of the HPA axis in CFS patients. METHODS: Fifteen patients with CFS were recruited after fulfilling strict criteria including the absence of comorbid psychiatric diagnosis. They collected urine between 0900 and 1800h and saliva at 0900h pre-prednisolone. At midnight, they took prednisolone (5mg) orally and then collected urine and saliva at the same intervals the following day. RESULTS: Salivary cortisol was lower in CFS subjects pre-prednisolone than controls. Urinary cortisol metabolites were lower in CFS subjects pre-prednisolone, but did not reach significance. Both measures were significantly lower in CFS subjects post-dose. Mean percentage suppression of both salivary cortisol and urinary cortisol metabolites was significantly higher in CFS compared to controls. CONCLUSION: There is enhanced sensitivity of the HPA axis to negative feedback in CFS as demonstrated using the prednisolone suppression test. This provides further evidence of alterations in the control of the HPA axis in patients with established CFS.     

Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome

Background: An association between chronic fatigue syndrome (CFS) and abnormalities of the hypothalamo-pituitary-adrenal axis has been described, and other adrenal steroid abnormalities have been suggested. Dehydroepiandrostenedione (DHEA) and its sulphate (DHEA-S), apart from being a precursor of sex steroids, have other functions associated with memory, depression and sleep. It has been suggested that CFS may be associated with a state of relative DHEA(-S) deficiency. Therefore we investigated basal levels of DHEA(-S), the cortisol/DHEA molar ratio and the responsiveness of DHEA to stimulation by corticotrophin-releasing hormone (CRH). Recent studies have also suggested that low dose hydrocortisone may be effective at reducing fatigue in CFS. We therefore also assessed these parameters prior to and following treatment with low dose oral hydrocortisone. Methods: Basal levels of serum DHEA, DHEAS and cortisol were measured in 16 patients with CFS without depression and in 16 controls matched for age, gender, weight, body mass index and menstrual history. CRH tests (1 g/kg i.v.) were carried out on all subjects and DHEA measured at 0, +30 and +90 min. In the patient group, CRH tests were repeated on two further occasions following treatment with hydrocortisone (5 or 10 mg, p.o.) or placebo for 1 month each in a double-blind cross over study protocol. Results: Basal levels of DHEA were higher in the patient, compared to the control, group (14.1+/-2.2 vs. 9.0+/-0.90 ng/ml, P=0.04), while levels of DHEAS in patients (288.7+/-35.4 microg/dl) were not different from controls (293.7+/-53.8, P=NS). Higher DHEA levels were correlated with higher disability scores. Basal cortisol levels were higher in patients, and consequently the cortisol/DHEA molar ratio did not differ between patients and controls. Levels of DHEA (8.9+/-0.97 ng/ml, P=0.015) and DHEAS (233.4+/-41.6 microg/dl, P=0.03) were lower in patients following treatment with hydrocortisone. There was a rise in DHEA responsiveness to CRH in the patients after treatment but this did not attain significance (AUCc: 2.5+/-1.7 ng/ml h pre-treatment vs. 6.4+/-1.2 ng/ml h post-hydrocortisone, P=0.053). However, those patients who responded fully to hydrocortisone in terms of reduced fatigue scores did show a significantly increased DHEA responsiveness to CRH (AUCc: -1.4+/-2.5 ng/ml h at baseline, 5.0+/-1.2 ng/ml h after active treatment, P=0.029). Conclusions: DHEA levels are raised in CFS and correlate with the degree of self-reported disability. Hydrocortisone therapy leads to a reduction in these levels towards normal, and an increased DHEA response to CRH, most marked in those who show a clinical response to this therapy.     

Underlying self-esteem in chronic fatigue syndrome

OBJECTIVE: It has been suggested that people with chronic fatigue syndrome (CFS) have low self-esteem; however, this is not necessarily apparent when self-esteem is measured overtly. This study is the first to investigate underlying self-esteem using information-processing measures and overtly administered measures of self-esteem with this population. METHODS: The study comprised 68 participants (24 CFS, 24 healthy volunteers, and 20 chronic illness volunteers). A Self-Statements Questionnaire (SSQ) and an Emotional Stroop Test (EST) using neutral, positive, and negative trait words were administered. RESULTS: Participants with CFS reported lower self-esteem than the two comparison groups on overt measures. Overt responses, however, did not fully account for the full extent of the interference effect from the negative word Stroop compared to the positive word Stroop. CONCLUSION: In contrast to previous studies, participants with CFS reported lower levels of self-esteem on overt measures than two comparison groups. It is suggested, however, that the extent to which participants reported low self-esteem did not fully reflect their underlying low self-esteem and that this may result from the use of rigidly held defence mechanisms. Further use of information-processing measures, in contrast to relying only on self-report measures, is advocated for future research.     

Alcohol use in chronic fatigue syndrome

OBJECTIVE: To examine the anecdotal observation that patients with chronic fatigue syndrome develop alcohol intolerance. METHODS: A consecutive case series of 114 patients fulfilling UK criteria for chronic fatigue syndrome referred to a specialist clinic. Self-reported alcohol use pre- and postdiagnosis, fatigue symptoms and comorbidity measures were collected. RESULTS: Two-thirds reduced alcohol intake. The most common reasons were increased tiredness after drinking (67%), increased nausea (33%), exacerbated hangovers (23%) and sleep disturbance (24%). One-third of the subjects also stopped drinking because "it seemed sensible." Some had been advised to avoid alcohol, but the majority (66%) did so on the basis of personal experience. CONCLUSION: Our data supports the anecdotal belief that chronic fatigue syndrome patients reduce or cease alcohol intake. This is associated with greater impairment in employment, leisure and social domains of function, and may hint at psycho-pathophysiological processes in common with other conditions that result in alcohol intolerance.