Reduced oxidative muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15).

CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14).

In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Comment in: Chronic fatigue syndrome and skeletal muscle mitochondrial function. [Muscle Nerve. 1997]

 

Source: McCully KK, Natelson BH, Iotti S, Sisto S, Leigh JS Jr. Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. 1996 May;19(5):621-5. http://www.ncbi.nlm.nih.gov/pubmed/8618560

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Patients’ beliefs about their illness were probably not a major factor

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Michael Sharpe and colleagues’ study confirms that the best medical advice for patients with the chronic fatigue syndrome is not “nothing can be done” or that “the disease will burn itself out.”‘ The study produced improvement in 73% of the patients, which is comparable to the 80% improvement produced by my management techniques.2 3 Interestingly, my approach seems to be fundamentally different from that of Sharpe and colleagues.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350897/pdf/bmj00539-0053d.pdf

 

Source: Ho-Yen DO. Cognitive behaviour therapy for the chronic fatigue syndrome. Patients’ beliefs about their illness were probably not a major factor. BMJ. 1996 Apr 27;312(7038):1097-8. http://www.ncbi.nlm.nih.gov/pubmed/8616430

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Essential elements of the treatment must be identified

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-We have several practical and theoretical concerns about Michael Sharpe and colleagues’ study of cognitive behaviour therapy in the chronic fatigue syndrome.’ The authors managed to obtain almost 100% uptake of treatment and compliance among patients who were attending an infectious diseases clinic and were strongly convinced that their chronic fatigue had a physical cause. We would struggle to engage our patients similarly, even with two hours for an initial appointment, and we could not offer them anything approaching an hour of treatment a week for four months. The difference between what was provided in the study and what clinicians can routinely offer their patients makes it important to identify the essential elements of the treatment.

The package given included cognitive techniques such as “question[ing] a simple disease explanation,” “strategies to reduce excessive perfectionism and self criticism,” and a problem solving approach of “gradual and consistent increases in activity.” The continuing improvement after the end oftreatment is unusual for the cognitive psychotherapies and suggests that the behavioural component was most effective. We find it puzzling, therefore, that the authors attribute the beneficial effects of treatment to “a specific effect on illness perpetuating beliefs and coping behaviour,” particularly as these attitudes did not change substantially. The patients would inevitably report less avoidance of exercise if they were complying with the study. After treatment at least half of the patients still believed that the illness was physical (from tables 2 and 5), and the vast majority still applied the damaging label of “myalgic encephalomyelitis”2 to their condition.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350875/pdf/bmj00539-0053b.pdf

 

Source: Lawrie SM. Cognitive behaviour therapy for the chronic fatigue syndrome. Cognitive behavior therapy. Essential elements of the treatment must be identified. BMJ. 1996 Apr 27;312(7038):1097; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350875/

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Cognitive behavior therapy should be compared with placebo treatments

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Lest Michael Sharpe and colleagues’ paper lends respectability to the notion that the chronic fatigue syndrome is a diagnostic entity or suggests that cognitive behaviour therapy has any value specific to the condition,1 I wish to make three points.

Firstly, the disorder that the authors treated is heterogeneous, the only defining criteria used being fatigue, impaired daily activities, and the absence of signs of physical disease or “severe depression.” Claims for a specific effect in any diffuse symptom complex are dangerous. Quinine is effective in many cases of cramp, but neither the symptom nor the benefit is specific.

Secondly, cognitive behaviour therapy and any comparable substitute were denied the control patients, who were therefore matched only on pretreatment criteria regarding their clinical state and not controlled in respect of a comparable treatment. Despite the authors’ claim for a “specificity of treatment effect” the benefits shown are consistent with the provision of much attention, encouragement, and a positive attitude to the nature of the illness and the strategies to counter it.’

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350872/pdf/bmj00539-0053c.pdf

 

Source: Pearce J. Cognitive behaviour therapy for the chronic fatigue syndrome. Cognitive behavior therapy should be compared with placebo treatments. BMJ. 1996 Apr 27; 312(7038): 1097–1098. http://www.ncbi.nlm.nih.gov/pubmed/8616428

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Use an interdisciplinary approach

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-From their randomised trial in the chronic fatigue syndrome Michael Sharpe and colleagues conclude that cognitive behaviour therapy is more effective than “medical care” in improving day to day function.1 It is not clear that the data presented justify this conclusion. Firstly, the authors do not compare like with like: the group given cognitive behaviour therapy received 16 hours of therapy while the “medical” group received no intervention. Secondly, the “medical” group of patients were “advised to increase their level of activity by as much as they felt able,” which may have had adverse effects if the activity was unsupervised and inappropriate.2 This could have affected the results by making the group given cognitive behaviour therapy seem to improve by more than they did. Thirdly, all patients, and particularly those with the chronic fatigue syndrome, need detailed discussion of their problems. Many doctors will not have been aware that in providing such discussion-surely the duty of all doctors-they were in part providing cognitive behaviour therapy.

You can read the full comment here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350862/pdf/bmj00539-0053a.pdf

 

Source: Eaton KK. Cognitive behaviour therapy for the chronic fatigue syndrome. Use an interdisciplinary approach. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350862/

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Patients were not representative of all patients with the syndrome.

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Michael Sharpe and colleagues conclude that cognitive behaviour therapy leads to a sustained reduction in functional impairment for patients with the chronic fatigue syndrome.1 The levels of disability of the 60 patients who took part in the study suggest, however, that these patients do not represent a comprehensive cross section of patients with the syndrome. The 60 patients scored 60-78 on the Karnofsky scale assessing disability and so represent a different population from the 143 patients reported on by Case History Research on ME (myalgic encephalomyelitis), who would have scored 30-60 (R Gibbons et al, first world congress on chronic fatigue syndrome and related disorders, Brussels, Nov 1995). Fifty nine of these 143 patients reported functional deterioration after sustained, incrementally increased physical exertion.

The authors did not assess other symptoms common in the chronic fatigue syndrome, such as pain, nausea, muscle weakness, or balance problems-a measure of the reduction of which was taken as a standard for “success” in an earlier trial.2 The lack of evidence of significant changes in other measures besides “the principal complaint of severe fatigue” in the authors’ study tends to diminish the validity of their conclusions.

You can read the full comment here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350876/pdf/bmj00539-0052c.pdf

 

Source: Gibbons R, Macintyre A, Richards C. Cognitive behaviour therapy for the chronic fatigue syndrome. Patients were not representative of all patients with the syndrome. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350876/

Cognitive behaviour therapy for the chronic fatigue syndrome. Good general care may offer as much benefit as cognitive behaviour therapy

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Successful outcomes have been reported from controlled clinical trials of an eclectic range of treatments-from immunotherapy to magnesium supplementation-for the chronic fatigue syndrome.’ Unpublished data suggest that equal success can be achieved with some forms of alternative therapy (for example, homoeopathy) when patients believe strongly in the approach. Most physicians, however, continue to view all such results with healthy scepticism. An equally cautious view needs to be taken when assessing Michael Sharpe and colleagues’ study of cognitive behaviour therapy.2 In a disorder that is almost certainly heterogeneous in nature, two important questions need to be answered before we can conclude that cognitive behaviour therapy is of value.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350899/pdf/bmj00539-0052b.pdf

 

Source: Shepherd C. Cognitive behaviour therapy for the chronic fatigue syndrome. Good general care may offer as much benefit as cognitive behaviour therapy. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350899/

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective

EDITOR,-In their paper on cognitive behaviour therapy for the chronic fatigue syndrome Michael Sharpe and colleagues state that many pharmacological treatments have been suggested but none are of proved value.1 Last year Lewith stated that the only two treatments that had been properly evaluated were evening primrose oil and magnesium by injection.2 Intramuscular magnesium supplements have been given to patients with low red cell magnesium in a double blind placebo controlled trial; myalgia and fatigue improved in about 70% of subjects.3 Evening primrose oil has been used to treat myalgic encephalomyelitis and is the only other treatment that has been adequately tested in a controlled trial. High doses in randomised controlled trials have been shown to have a significant effect in 70-80% of patients with myalgic encephalomyelitis or the chronic fatigue syndrome.4 I would be interested to hear Sharpe and colleagues’ comments about these papers.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350915/pdf/bmj00539-0052a.pdf

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

Source: Chilton SA. Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pubmed/8616424

 

Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects.

Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values.

By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripheral mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis.

 

Source: Vecchiet L, Montanari G, Pizzigallo E, Iezzi S, de Bigontina P, Dragani L, Vecchiet J, Giamberardino MA. Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome. Neurosci Lett. 1996 Apr 19;208(2):117-20. http://www.ncbi.nlm.nih.gov/pubmed/8859904

 

Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome

Abstract:

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism.

2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio.

3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase).

4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.

 

Source: McArdle A, McArdle F, Jackson MJ, Page SF, Fahal I, Edwards RH. Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. Clin Sci (Lond). 1996 Apr;90(4):295-300. http://www.ncbi.nlm.nih.gov/pubmed/8777836