Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. A group of American scientists have previously shown that when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared to healthy controls, despite differences in pain and exertion.

The purpose of the latest study was to examine cardiac and perceptual responses to steady-state, submaximal exercise in CFS patients and healthy controls and found that that CFS and CFS+FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise.

Abstract

Researchers at Bond University have received a landmark grant of over $800,000 from the Mason Foundation to continue their ground-breaking research into identifying the cause and possible treatment of Chronic Fatigue Syndrome (CFS).

They will be looking at the pathology in order to gain insight into the pathway of how CFS develops. Past research has been in line with the Norwegian findings of an abnormal immunological system.

“Ultimately our aim is to develop a clear diagnostic test for CFS and establish a national testing facility here at Bond University, which we believe could happen within the next five years.”

Press release

The Bulletin of the International Association for CFS/ME has published an assesment of the process for ‘Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome’

ABSTRACT:

Across different medical fields, authors have placed a greater emphasis on the reporting of efficacy measures than harms in randomised controlled trials (RCTs), particularly of nonpharmacologic interventions. To rectify this situation, the Consolidated Standards of Reporting Trials (CONSORT) group and other researchers have issued guidance to improve the reporting of harms. Graded Exercise Therapy

(GET) and Cognitive Behavioural Therapy (CBT) based on increasing activity levels are often recommended for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, exercise-related physiological abnormalities have been documented in recent studies and high rates of adverse reactions to exercise have been recorded in a number of patient surveys. Fifty-one percent of survey respondents (range 28-82%, n=4338, 8 surveys) reported that GET worsened their health while 20% of respondents (range 7-38%, n=1808, 5 surveys) reported similar results for CBT.

Using the CONSORT guidelines as a starting point, this paper identifies problems with the reporting of harms in previous RCTs and suggests potential strategies for improvement in the future. Issues involving the heterogeneity of subjects and interventions, tracking of adverse events, trial participants’ compliance to therapies, and measurement of harms using patient-oriented and objective outcome measures are discussed. The recently published PACE (Pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation) trial which explicitly aimed to assess “safety”, as well as effectiveness, is also analysed in detail. Healthcare professionals, researchers and patients need high quality data on harms to appropriately assess the risks versus benefits of CBT and GET.

FROM THE CONCLUSION:

It is hoped that this paper will lead to a greater focus on the reporting of harms in ME/CFS, not just those that might be associated with GET or CBT, but from any posited treatment.

Interventions should not be presumed to be harmless when there exists evidence of potential harm and there have not been well-planned systematic methods to track and assess harms both within and outside trials. Potential strategies to improve reporting of harms are summarized in Table 3.

ME/CFS research should at least conform to standards being recommended for the majority of medical research while taking into account the unique features of the disease, such as its relapsing-remitting nature. Moreover, in the ME/CFS field, comparisons are often not made just within the classes of pharmacologic interventions and non- pharmacologic interventions but also between pharmacologic and non-pharmacologic treatments. False conclusions could be reached that a non-pharmacologic intervention is “safer” than a pharmacologic agent if harms-related data was collected more rigorously for the latter.

Individuals with ME/CFS can face many challenges and have not always been treated as well as they should have been by healthcare professionals. Many feel that their symptoms have been downplayed and their negative experiences of some treatments ignored.

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French researchers questioned whether past experience of high-level physical activity and/or acute infection might affect the response to exercise in people with CFS.

This case-control study compared data from 43 CFS patients to results from a matched control group of 23 healthy sedentary subjects. 18 had practised high-level sport and severe acute infection had been diagnosed in nine patients. A combination of sport practice and infection was noted in 11 patients.

Tests were performed following a maximal cycling exercise test. The presence of stress factors such as acute infection and high-level sport in CFS patients were found to be associated with severe oxidative stress and the suppression of protective HSP27 and HSP70 responses to exercise.

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.

American researchers compared patients meeting the 1994 CFS definition with those meeting the ME/CFS Canadian definition and the Ramsay ME definition. They found that the ME/CFS criteria identified a subset of patients with more functional impairments and physical, mental, and cognitive problems than the subset not meeting these criteria. The ME subset had more functional impairments, and more severe physical and cognitive symptoms than the subset not meeting ME criteria. Both the ME/CFS and ME criteria appear to select a more severe subset of patients than the 1994 CFS case definition.

Abstract

Researchers from Dundee have found evidence that ME/CFS is associated with cardiovascular symptoms including autonomic dysfunction, impaired blood pressure regulation, and loss of beat-to-beat heart rate control. In addition they believe that a number of recent studies that report raised levels of oxidative stress low-grade inflammation and increased arterial stiffness contribute to a picture of increased cardiovascular risk in ME/CFS.

Their findings provide direct evidence of endothelial dysfunction in both the large and small vessels of patients with ME/CFS, which may warrant a large prospective trial of cardiovascular outcomes in the disease.

Abstract

Researchers from the University of Zurich have discovered a mechanism in the brain that triggers a reduction in muscle performance during tiring activities and ensures that one’s own physiological limits are not exceeded. For the first time, the study demonstrates empirically that muscle fatigue and changes in the interaction between neuronal structures are linked.

“The findings are an important step in discovering the role the brain plays in muscle fatigue. Based on these studies, it won’t just be possible to develop strategies to optimize muscular performance, but also specifically investigate reasons for reduced muscular performance in various diseases.’ Prolonged reduced physical performance is a symptom that is frequently observed in daily clinical practice. It can also appear as a side effect of certain medication. However, so-called chronic fatigue syndrome is often diagnosed without any apparent cause.”

Health Canal article

Researchers commissioned by the NIHR Health Technology Assessment programme carried out a systematic review that identified 8 randomised controlled trials on exercise referral schemes.

These studies showed weak evidence for short-term (i.e. up to 12-months’ follow up) increases in physical activity and reductions in the levels of depression, in sedentary individuals after they had taken part in an exercise referral scheme compared to those who received simply advice. There was no demonstrable difference between taking part in an exercise referral scheme or other physical activity promotion intervention such as a walking programme. The review found no consistent evidence in favour of exercise referral schemes in terms of benefits such as physical fitness, psychological well-being, overall health-related quality of life, blood pressure, serum lipid levels, measures of obesity, glycaemic control of respiratory function.

Dr. Toby Pavey, Associate Research Fellow in the Peninsula Technology Assessment Group at PCMD who coordinated the study, said: “Our study does not question the importance of physical activity for good health: what it does do is question the effectiveness of the exercise referral programme as it is delivered at present. It is clear that with increasing pressure on NHS budgets and changes to the way in which services are commissioned as part of current NHS reforms, more work needs to be done to establish how existing referral programmes may be made more effective and who should they be targeted towards.”

Pavey TG et al. Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: Systematic review and meta-analysis. BMJ 2011 Nov 6; 343:d6462. 

Japanese researchers had previously discovered that “small heart” with low cardiac output is prevalent in CFS patients. Colleagues had also reported that patients with postural orthostatic tachycardia, which is often noted in patients with chronic OI (Orthostatic Intolerance), have small hearts coupled with reduced blood volume compared with healthy controls, as determined by magnetic resonance imaging and blood volume measurements.

They concluded that a small size of LV with reduced cardiac function is common in patients with OI and its degree appears to be more pronounced in CFS patients with OI. Chronic fatigue syndrome with OI seems to constitute a well-defined and predominant subgroup of CFS. Small heart with impaired cardiac performance due to decreased preload appears to be an important target for the treatment of CFS and OI.

Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome.