Exercise a health risk for chronic fatigue [syndrome] sufferers
Adelaide scientists have found evidence that exercise programs commonly undertaken by patients with chronic fatigue syndrome (CFS), may actually make the condition worse.
Exercise Capacity in Chronic Fatigue Syndrome.
RESULTS: The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed.
CONCLUSIONS: When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances.
Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome.
The authors attempted to confirm the consistent report by patients with the CFS of delay in recovery of peripheral muscle function after exercise. They tested the quadriceps muscle group of 10 patients and 10 controls. Recovery was prolonged in the patient group, with a significant difference between the two groups after exercise and after 24 hours. These findings support the clinical complaint of delayed recovery after exercise in patients with CFS.
Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression.
The authors theorized that cognitive and motor responses to vigorous exercise in patients with chronic fatigue syndrome would differ from those in depressed and healthy control, and following their study they made the following conclusions: "patients with CFS show a specific sensitivity to the effects of exertion on effortful cognitive functioning. This occurs despite subjective and objective evidence of effort allocation in chronic fatigue syndrome, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both."
Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome.
We interpret this increase in circadian rest-activity period seen in CFS patients following exercise to indicate that exhaustive exercise interferes with normal entrainment to 24-h zeitgeber(s). This effect may be associated in part with the common patient complaint of symptom worsening following exertion.
Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response.
Second, the activation of the protein kinase R enzyme, a characteristic feature in at least subsets of CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with CFS. Elevated NO is known to induce vasidilation, which may limit CFS patients to increase blood flow during exercise, and may even cause and enhance postexercise hypotension.
Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise.
Plus a discussion of the text.
Thus, as in inherited muscular dystrophy in which a variety of cellular abnormalities can be accounted for by free radical-mediated damages including abnormal functions of the sarcolemma and an altered activity of membrane-bound enzymes involved in excitation-contraction coupling, an increased level of free radical damage in CFS may be a contributor to the underlying functional defects and symptom presentation. This should promote further researches towards the goal of an effective treatment of CFS-suffering patients.
On the pathophysiology of ME/CFS by Les Simpson, MD
The significance of the concept of 'mean capillary diameter' is that it explains why individuals with similar values for altered red cell shapes do or do not evince symptoms. While the effects on red cell shape of a change in the environment is the same, only those with small capillaries will develop symptoms. As overexertion changes red cell shape in an additive fashion, there will be an accompanying exacerbation of symptoms. It is worth noting that in a CFS patient with SPECT-demonstrated reduced cerebral blood flow in a pre-exercise sample, the cerebral blood flow was further reduced in a post-exercise SPECT scan.
Medical Neurobiology of CFS & FM: May May 7-9, 1993 by Jay Goldstein
It is widely documented that exercise is an exacerbator of CFIDS symptoms. Drs. Mena and Goldstein presented a series of SPECT scans which showed extreme hypoperfusion (reduced blood flow) in the brain following exercise. There appeared to be "holes" where blood would normally be flowing -- the degree of hypoperfusion was astonishing. Even 24 hours later, cerebral blood flow was severely reduced.
Cerebral hypoperfusion is not the only result of exercise intolerance. Drs. Lapp and Goldstein referenced irregular tidal volume rates common in PWCs. Hyperventilation and shallow breathing are frequent results of exertion. Normal controls breathe irregularly at the start of exercise, but respiration becomes regular over time. Dr. Lapp reported that PWCs breathed more regularly than controls at the outset, but during exercise their breathing was more variable. Dr. Goldstein concurred, "This phenomenon has never been described before in any population and, as of now anyway, we think that it's a diagnostic marker for CFS."
Neuroendocrine responses were often reversed or blunted in the Cheney-Lapp study. Cortisol, epinephrine, norepinephrine, DHEA levels and body temperature normally rise with exercise, but PWCs were found to have lower than expected measures of all of the above. Dr. Goldstein related this phenomenon to limbic dysfunction, as altered levels of interleukins and nitric oxide (NO) can result in altered neuroendocrine responses to exercise.
Dr. Lapp and Dr. Kathy Sietsema reported that PWCs reached anaerobic threshold much sooner than predicted. Anaerobic threshold (AT) is the point at which a healthy person becomes completely fatigued and cannot exercise any longer (commonly called "hitting the wall"). In the Cheney-Lapp study, PWCs continued exercising beyond the point of AT. Dr. Cheney has hypothesized that PWCs normally perform above AT in everyday activity due to a metabolic injury, and therefore are more accustomed to performing at this level than controls.
Dr. Les Simpson – Rethinking the Pathogenesis of CFIDS By Craig Maupin at http:///www.cfidsreport.com
Simpson continues, "I found that ME blood filtered poorly - implying that they had a problem with blood flow, particularly at capillary level. In a paper published by New Jersey Medicine, I suggested that ME people might have the anatomical feature of smaller than usual capillary diameters. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people."
Other models for the illness have struggled to fit the distinct features of CFIDS, such as exertion intolerance and circulatory dysfunction. Simpson feels impaired blood flow offers a unifying thesis that can explain many of these distinct symptoms. He vividly recalls the unique response to exercise of a patient referred to him. "Two scans were done [SPECT scans] -- pre and post exercise. While the pre-exercise scan showed reduced cerebral blood flow, this was much worse in the post-exercise scan. At that time, the effects of physical activity on red cell shape had not been reported. This shows the extent of ignoring blood rheology factors as determinants of blood flow."
*O* CRITICAL CONSIDERATIONS by Margaret Williams
Since as long ago as 1996 it has been known that those with ME / CFS have abnormal lung function tests, with a significant reduction in all lung function parameters tested (see "Lung function test findings in patients with chronic fatigue syndrome" De Lorenzo et al. Australia and New Zealand Journal of Medicine 1996:26:4:563-564), and Jo Nijs from Belgium presented evidence at the Wisconsin international conference of underlying lung damage in ME / CFS through intracellular immune dysregulation with impairment of cardiopulmonary function.
How can forced aerobic exercise regimes be guaranteed to be harmless where there is existing underlying lung damage?
Montague/Hooper paper by Sally Montague, Malcolm Hooper
Tests of exercise capacity
Investigation of exercise capacity (VO2 max) ie. measurement of maximal oxygen uptake and investigation of oxygen delivery to muscle are essential in patients with ME/CFS; oxidative metabolism is known to be reduced in ME/CFS. (78) This could affect patients’ physical abilities to a severe degree. ME/CFS patients have recovery rates for oxygen saturation that are 60% lower than normal controls. (79) It is imperative to ascertain oxygen delivery status before insisting on inappropriate interventions eg. CBT / graded exercise.
Exercise limits in chronic fatigue syndrome [Letter]. Lapp CW. American Journal of Medicine 1997; 103(1): 83-84.
Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome - left ventricular dysfunction in a cohort. Lerner AM, Lawrie C, Dworkin HS. Chest 1993; 104(5): 1417-21.
Abstract:
This study surveys the occurrence of repetitively negative to flat T waves, alternating with normal upright T waves in 24-h electrocardiographic recordings from a subspecialty infectious diseases outpatient practice during the years 1982 to 1990. Patients with normal resting electrocardiogram in the assayed leads, but with repetitively inverted to isoelectric abnormal T waves at Holter monitors, were considered to have abnormal readings. A total of 300 patients had undergone a 24-h Holter monitor. This group included 24 individuals with chronic fatigue syndrome (CFS). This population was restricted to individuals 50 years old or younger, and the patients with CFS are compared with the patients without CFS. One of the more striking differences between the two groups was the difference in abnormal Holter readings. The patients with CFS all had abnormal Holter readings, while 22.4 percent patients without CFS had abnormal readings (p < 0.01). We further report the occurrence of mild left ventricular dysfunction in 8 of 60 patients in continuing studies of this population with CFS, younger than 50 years old, and with no risk factors for coronary artery disease. All 60 patients with CFS showed repetitively flat to inverted T waves alternating with normal T waves. Stress multiple gated acquisitions (MUGAs) (labeled erythrocytes with stannous pyrophosphate) were abnormal in eight patients with CFS. Although resting ejection fractions (EFs) were normal (mean, 60 percent), with increasing work loads (Kilopon meters [Kpms]), gross left ventricular dysfunction occurred. The fatigue of patients with CFS may be related to subtle cardiac dysfunction occurring at work loads common to ordinary living.
The relationship between neurally mediated hypotension and the chronic fatigue syndrome. Bou-Holaigah I, Rowe PC, Kan J, Calkins H. Journal of the American Medical Association 1995; 274(12): 961-7.
Abstract: OBJECTIVE-To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome. DESIGN-Case-comparison study with mean (SD) follow-up of 24 (5) weeks. SETTING-Tertiary care hospital. PATIENTS AND OTHER PARTICIPANTS-A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators' clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years). INTERVENTIONS-Each subject completed a symptom questionnaire and underwent a three-stage upright tilt-table test (stage 1, 45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension. MAIN OUTCOME MEASURES-Response to upright tilt and scores on symptom questionnaires prior to and during follow-up. RESULTS-An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension. CONCLUSIONS-We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.
Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome. De Lorenzo F, Hargreaves J, Kakkar VV. Clinical Autonomic Research 1997; 7(4): 185-90.
Abstract: The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.
Possible relationship between chronic fatigue and postural tachycardia syndromes. De Lorenzo F, Hargreaves J, Kakkar VV. Clinical Autonomic Research 1996; 6: 263-264.
Abstract: Postural tachycardia syndrome refers to the development of symptoms such as light-headedness, visual blurring, palpitations and weakness on assuming an upright posture; these symptoms are relieved by resuming a supine posture. This syndrome is occasionally associated with idiopathic hypovolemia, impaired vasomotor tone, deconditioning and autonomic neuropathy, but has not been reported in association with chronic fatigue syndrome (CFS). We describe five patients who satisfied the CFS criteria of the Centres for Disease Control and Prevention. Upright tilt-table testing induced significant hypotension and increased heart rate in all five patients, consistent with clinical and autonomic manifestation of postural tachycardia syndrome.
Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Bazelmans E, Bleijenberg G, Van Der Meer JW, Folgering H. Department of Medical Psychology, University of Nijmegen, The Netherlands.
BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that physical exertion produces an increase of complaints, leading to a greater need for rest and more time spent in bed. It has been suggested that this is due to a bad physical fitness and that physical deconditioning is a perpetuating factor in CFS. Until now, studies on physical deconditioning in CFS have shown inconsistent results. METHODS: Twenty CFS patients and 20 matched neighbourhood controls performed a maximal exercise test with incremental load. Heart rate, blood pressure, respiratory tidal volume, O2 saturation, O2 consumption, CO2 production, and blood-gas values of arterialized capillary blood were measured. Physical fitness was quantified as the difference between the actual and predicted ratios of maximal workload versus increase of heart rate. Fatigue, impairment and physical activity were assessed to study its relationship with physical fitness. RESULTS: There were no statistically significant differences in physical fitness between CFS patients and their controls. Nine CFS patients had a better fitness than their control. A negative relationship between physical fitness and fatigue was found in both groups. For CFS patients a negative correlation between fitness and impairment and a positive correlation between fitness and physical activity was found as well. Finally, it was found that more CFS patients than controls did not achieve a physiological limitation at maximal exercise. CONCLUSIONS: Physical deconditioning does not seem a perpetuating factor in CFS.
Complement activation in a model of chronic fatigue syndrome. Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, Jones JF. Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA.
BACKGROUND: A need exists to identify biological markers in chronic fatigue syndrome (CFS). OBJECTIVE: To use an exercise and/or allergen challenge to induce the symptoms of CFS and to identify a biological marker that correlates with these symptoms. METHODS: Patients with CFS (n = 32) and age-matched, normal control patients (n = 29) exercised for 20 minutes on a stationary bike at 70% of their predicted max work load (Watts). Patients from each group with positive skin test results were also challenged with intranasally administered relevant allergens. Symptoms were recorded for 2 weeks before and 1 week after each challenge, using 3 different instruments. Blood samples were taken before, and 0, 1, 6, and 24 hours after challenges. Levels of complement split products, cell-associated cytokines, and eosinophilic cationic protein were measured. Mean preexercise and postexercise symptom scores were evaluated for each group. RESULTS: Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P <.01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P <.03) and a weekly diary (P <.01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories "reduced activity" and "mental fatigue" were significantly increased in the CFS group only (P <.04 and P <.02, respectively). CONCLUSIONS: Exercise challenge may be a valuable tool in the development of diagnostic criteria and tests for CFS. Establishment of a role for complement activation products as markers or participants in production of illness require further study.
Exercise lowers pain threshold in chronic fatigue syndrome. Whiteside A, Hansen S, Chaudhuri A. Departments of Clinical Physics, Institute of Neurological Sciences, South Glasgow University Hospitals NHS Trust, Glasgow, UK.
Post-exertional muscle pain is an important reason for disability in patients who are diagnosed to have Chronic Fatigue Syndrome (CFS). We compared changes in pain threshold in five CFS patients with five age and sex matched controls following graded exercise. Pain thresholds, measured in the skin web between thumb and index finger, increased in control subjects with exercise while it decreased in the CFS subjects. Increased perception of pain and/or fatigue after exercise may be indicative of a dysfunction of the central anti-nociceptive mechanism in CFS patients.
Altered central nervous system signal during motor performance in chronic fatigue syndrome. Siemionow V, Fang Y, Calabrese L, Sahgal V, Yue GH. Department of Biomedical Engineering, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
OBJECTIVE: The purpose of this study was to determine whether brain activity of chronic fatigue syndrome (CFS) patients during voluntary motor actions differs from that of healthy individuals. METHODS: Eight CFS patients and 8 age- and gender-matched healthy volunteers performed isometric handgrip contractions at 50% maximal voluntary contraction level. They first performed 50 contractions with a 10 s rest between adjacent trials--'Non-Fatigue' (NFT) task. Subsequently, the same number of contractions was performed with only a 5 s rest between trials--'Fatigue' (FT) task. Fifty-eight channels of surface EEG were recorded simultaneously from the scalp. Spectrum analysis was performed to estimate power of EEG frequency in different tasks. Motor activity-related cortical potential (MRCP) was derived by triggered averaging of EEG signals associated with the muscle contractions. RESULTS: Major findings include: (i) Motor performance of the CFS patients was poorer than the controls. (ii) Relative power of EEG theta frequency band (4-8 Hz) during performing the NFT and FT tasks was significantly greater in the CFS than control group (P < 0.05). (iii) The amplitude of MRCP negative potential (NP) for the combined NFT and FT tasks was higher in the CFS than control group (P < 0.05) (iv) Within the CFS group, the NP was greater for the FT than NFT task (P<0.01), whereas no such difference between the two tasks was found in the control group. CONCLUSIONS: These results clearly show that CFS involves altered central nervous system signals in controlling voluntary muscle activities, especially when the activities induce fatigue. SIGNIFICANCE: Physical activity-induced EEG signal changes may serve as physiological markers for more objective diagnosis of CFS.
