Source: Journal of Neurology, Neurosurgery, and Psychiatry Vol. 69 pages: 302-307 Date: September 2000 URL: http://jnnp.bmjjournals.com (home page) http://jnnp.bmjjournals.com/cgi/content/full/69/3/302 (text) Strength and physiological response to exercise in patients with chronic fatigue syndrome ---------------------------------------------------------------- Kathy Y Fulcher(a), Peter D White(b) (a) National Sports Medicine Institute, St Bartholomew's and the=20 Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK, (b) Department of Psychological Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK Correspondence to: Dr PD White p.d.white@mds.qmw.ac.uk Received 12 January 1999 and in revised form 7 January 2000; Accepted 21 January 2000 Abstract 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. Keywords: chronic fatigue syndrome; exercise; incapacity; muscle strength; fitness=20 Introduction Chronic fatigue syndrome (CFS) is characterised by postexertional or persistent fatigue, with consequent disability.1 2 Until recently no abnormalities of muscle physiology or metabolism that could explain the fatigue had been reported.3 Lane et al found an increased lactic acid response to exercise in 37% of patients with CFS and these patients were particularly likely to have type II muscle fibre predominance.4 Barnes et al also showed increased metabolic acidification with exercise in a smaller minority, but suggested that "detraining" due to inactivity was the likely cause.5 Physical deconditioning may contribute to the fatigue of CFS,6 possibly as a result of a less active lifestyle.7-9 An empirically derived model of fatigue and disability in CFS suggested that the amount of physical activity had an important effect on fatigue and an even stronger effect on disability.10 Both lower exercise capacity and lower peak oxygen consumption have been reported in patients with CFS6 11 and related conditions7 compared with controls. Both higher heart rates6 7 and perceived exertion6 7 11-13 have been reported with submaximal exercise when compared with either healthy active or healthy sedentary controls. All these studies used criteria for CFS that included psychiatric disorders such as major depressive disorder.1 2 There have been no studies of the physiology of CFS in the absence of comorbid psychiatric disorders. The aim of this study was to examine both physiological and symptomatic measures in patients with CFS without psychiatric disorders, and to compare them with both healthy but sedentary subjects and patients with major depressive disorders.=20 Methods Sixty six outpatients fulfilling the Oxford criteria for CFS were recruited through a fatigue clinic at a general hospital department of psychiatry.1 All of these patients had agreed to participate in a trial of graded exercise therapy.14 Seventy seven other potential patients with CFS, who also had a current psychiatric disorder or significant insomnia, were excluded by the structured clinical interview DSM IIIR (SCID),15 because of their separate effects on exercise induced fatigue.16 17 Five potential patients refused to participate and five were judged too incapacitated to participate in the study. We included patients with comorbid phobias, because of evidence that phobias do not exacerbate fatigue.18 Patients with neurasthenia and unspecified somatoform disorder were included as these diagnoses are often synonymous with CFS. Thirty healthy but sedentary controls were recruited through posters and personal referral from staff at St Bartholomew's hospital and its medical and dental school. All volunteers completed an activity questionnaire. This detailed the number of episodes of physical exercise in the previous 3 months and the number of times they took part in strenuous, moderate, or mild activity in the average week. We also assessed their attitude to activity - that is, whether they considered themselves adequately active or sedentary. Only those subjects who took part in no strenuous activity and exercised moderately less than once a week were accepted for entry into the study. Fifteen patients with major depressive disorder (DSM-IIIR criteria)19 were recruited from attendees at the department of psychological medicine. Ethical approval was obtained from the district research ethics committee and all subjects gave valid and informed consent before entering the study. SYMPTOMATIC ASSESSMENTS All questionnaires were completed by subjects before the physiological assessments. Fatigue was measured with self rated visual analogue scales measuring physical, mental, and total fatigue,18 and a self rated 14 item fatigue questionnaire.20 The hospital anxiety and depression scale was used to assess anxiety and depression.21 The Pittsburgh sleep quality index measured quality and quantity of sleep.22 The 36 item short form health survey self rated questionnaire measured general health, physical, mental and social capacity.23 The five item Barsky self rated somatic amplification scale assessed the tendency to amplify specific body sensations.24 PHYSIOLOGICAL ASSESSMENT Skinfold measurements were taken at four sites to give a total score in millimetres as an indication of body fat composition. Forced vital capacity (FVC) and forced expired volume in 1 second (FEV1) were measured with a Vitalograph spirometer. Normal ranges were taken from Vitalograph Ltd spirometric tables.25 Maximum voluntary isometric contraction of the quadriceps muscle of the dominant leg was measured, with percutaneous twitch interpolation to ensure maximal activation and to override central inhibition.26 Subjects were seated in a specially adapted rigid, straight backed chair, and asked to push against a strap placed around their ankle. The best of five repetitions was recorded and we noted whether it was with or without stimulation. All subjects were thoroughly familiarised with the treadmill before the walking test, carried out at a constant speed of 5 kph and a gradient increase of 2.5% every 2 minutes. Expired air was collected through a lightweight mouthpiece and analysed for oxygen, carbon dioxide, and minute ventilation. Heart rate was monitored using a three lead ECG. Ratings of perceived exertion (RPEs) were recorded with the Borg 15 point scale in the last 30 seconds of each treadmill stage.27 The capillary blood lactate concentration was measured at a Borg RPE rating of 14 (between "somewhat hard" and "hard") and 3 minutes after completion of the test. The test was terminated at volitional fatigue whereby subjects were encouraged to continue to their maximum. Peak levels for all variables were recorded at this point. Age predicted maximum heart rates were calculated from the formula 210 - (age=D70.65).28 Because patients with CFS were about to be entered into a therapeutic trial, it was not possible to assess them blindly, but care was taken to ensure that the same explanation and encouragement were given to all subjects. ANALYSIS Analysis of variance (ANOVA) or a Kruskal-Wallis analysis were used to compare the means or medians between the three groups. When either test indicated a significant difference between the three groups, either Student's t tests or Mann-Whitney U tests were used to compare the means or medians between two groups of interest. We compared the submaximal responses to exercise between groups by comparing the area under the curve of between 6 and 12 minutes inclusively on the treadmill by Kruskal-Wallis one way ANOVA. We examined the possibly confounding effects of taking antidepressant medications in the CFS group. Forward stepwise multiple regression models were calculated on patients with CFS alone, to explore the relation between the dependent variable of exercise capacity and the independent variables of mood, sleep, body mass ratio, strength, and physiological responses to exercise.=20 Results There were no significant differences between the three groups in age, height, weight, sex, or body mass index (table 1). The median (range) duration of illness for the patients with CFS was 2.7 (0.6-19.0) years which was significantly longer than the depressed patients (1.2 (0.25-12.0) years (p<0.05)). Thirty two (48%) of the patients with CFS were taking medication at the time of assessment; 20 patients were taking normal doses of antidepressants (having previously been treated for a depressive illness), 10 were taking antidepressants at low (hypnotic) doses, and two were on other medication. Thirteen (87%) patients in the depressed group were on normal doses of antidepressant medication, which was significantly more than the proportion of patients with CFS taking medication (chi^2=3D8.4, df=3D2, p<0.05). Table 1: Characteristics of patients and controls -------------------------------------------------------------------------- - Variable CFS patients Depressed patients Sedentary controls ANOVA n=3D66 n=3D15 n=3D30 p= value -------------------------------------------------------------------------- - Age (y) 37.2 (10.7) 35.3 (10) 36.8 (11.1) 0.31 Height (cm) 169.5 (163-176) 169 (162-173) 163 (159-168) 0.07 Weight (kg) 67.2 (13) 70.1 (12.1) 67.9 (14.2) 0.27 Body mass 22.7 (20.0-25.4) 23.7 (20.7-26.8) 23.4 (20.8-26.0) 0.38 index Total 53 (34-71) 42 (30-54) 51 (39-63) 0.23 skinfold (mm) Female:male 49/17 (74) 10/5 (66) 22/8 (73) 0.09