A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS

Abstract:

Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations and medical professionals to legitimize the combination of Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing deconditioning, respectively.

In this review we invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration.

Moreover, this review shows that exertion and thus GET most likely have a negative impact on many ME/CFS patients. Exertion induces post-exertional malaise with a decreased physical performance/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, “fatigue”, and weakness, and a long lasting “recovery” time.

This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis.

We conclude that it is unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful “rehabilitation therapies”, such as CBT/GET.

 

Source: Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99. https://www.ncbi.nlm.nih.gov/pubmed/19855350

 

Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study

Abstract:

PURPOSE: To examine the physiological cost of walking in subjects with chronic fatigue syndrome (CFS) and a matched control group, walking at their preferred and at matched walking speeds.

METHODS: Seventeen people with CFS and 17 matched-controls participated in this observational study of physiological cost during over-ground gait. Each subject walked for 5 min at their preferred walking speed (PWS). Controls then walked for 5 min at the same pace of their matched CFS subject. Gait speed and oxygen uptake, gross and net were measured and oxygen uptake was expressed per unit distance ambulated. CFS subjects completed the CFS-Activities and Participation Questionnaire (CFS-APQ).

RESULTS: At PWS the CFS group walked at a slower velocity of 0.84 +/- 0.21 m s(-1) compared to controls with a velocity of 1.19 +/- 0.13 m s(-1) (p < 0.001). At PWS both gross and net oxygen uptake of CFS subjects was significantly less than controls (p = 0.023 and p = 0.025 respectively). At matched-velocity both gross and net physiological cost of gait was greater for CFS subjects than controls (p = 0.048 and p = 0.001, respectively).

CONCLUSION: The physiological cost of walking was significantly greater for people with CFS compared with healthy subjects. The reasons for these higher energy demands for walking in those with CFS have yet to be fully elucidated.

 

Source: Paul L, Rafferty D, Marshal R. Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study. Disabil Rehabil. 2009;31(19):1598-604. https://www.ncbi.nlm.nih.gov/pubmed/19848558

 

Phenotypes of chronic fatigue syndrome in children and young people

Abstract:

OBJECTIVE: To investigate the heterogeneity of chronic fatigue syndrome (CFS/ME) in children and young people.

SETTING: Regional specialist CFS/ME service Patients Children and young people aged <19 years old.

METHODS: Exploratory factor analysis was performed on symptoms present at assessment in 333 children and young people with CFS/ME. Linear and logistic regression analysis of data from self-completed assessment forms was used to explore the associations between the retained factors and sex, age, length of illness, depression, anxiety and markers of severity (fatigue, physical function, pain and school attendance).

RESULTS: Three phenotypes were identified using factor analysis: muscoloskeletal (factor 1) had loadings on muscle and joint pain and hypersensitivity to touch, and was associated with worse fatigue (regression coefficient 0.47, 95% CI 0.25 to 0.68, p<0.001), physical function (regression coefficient -0.52, 95% CI -0.83 to -0.22, p=0.001) and pain. Factor 2 (migraine) loaded on noise and light hypersensitivity, headaches, nausea, abdominal pain and dizziness and was most strongly associated with physical function and pain. Sore throat phenotype (factor 3) had loadings on sore throat and tender lymph nodes and was not associated with fatigue or pain. There was no evidence that phenotypes were associated with age, length of illness or symptoms of depression (regression coefficient for association of depression with musculoskeletal pain -0.02, 95% CI -0.27 to 0.23, p=0.87). The migraine phenotype was associated with anxiety (0.40, 95% CI 0.06 to 0.74, p=0.02).

IMPLICATIONS: CFS/ME is heterogeneous in children with three phenotypes at presentation that are differentially associated with severity and are unlikely to be due to age or length of illness.

 

Source: May M, Emond A, Crawley E. Phenotypes of chronic fatigue syndrome in children and young people. Arch Dis Child. 2010 Apr;95(4):245-9. doi: 10.1136/adc.2009.158162. Epub 2009 Oct 19. https://www.ncbi.nlm.nih.gov/pubmed/19843509

 

Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS) and viral persistence

Abstract:

AIMS: Enteroviruses are well-known causes of acute respiratory and/or gastrointestinal infections and non-specific flu-like illness. Although enterovirus protein, RNA and non-cytopathic viruses have been demonstrated in the stomach biopsies of patients with myalgia encephalomyelitis/chronic fatigue syndrome (ME/CFS), causality for chronic diseases is difficult to establish without having well-documented cases of acute enterovirus infections. The aim of this study was to link acute enteroviral infection to viral persistence in patients with ME/CFS.

METHOD: Patients admitted to the hospital with acute febrile illnesses were screened for enteroviral infections. Acutely infected patients were followed longitudinally, and those who developed symptoms of ME/CFS underwent oesophagogastroduodenoscopy and biopsies of the antrum to document viral persistence by immunoperoxidase staining for viral protein and viral RNA assay.

RESULTS: Three representative patients with different manifestations of acute enterovirus infections progressed to have chronic symptoms of ME/CFS. Persistent viral infection was demonstrated in the antrum years later.

CONCLUSION: After acute infections, enteroviruses can persist in patients resulting in manifestation of ME/CFS. Chronic enterovirus infection in an immunocompetent host may be an example of a stalemate between attenuated, intracellular viruses and an ineffective immune response.

 

Source: Chia J, Chia A, Voeller M, Lee T, Chang R. Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS) and viral persistence. J Clin Pathol. 2010 Feb;63(2):165-8. doi: 10.1136/jcp.2009.070466. Epub 2009 Oct 14. https://www.ncbi.nlm.nih.gov/pubmed/19828908

 

Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients.

In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in the vastus lateralis muscle of female and male CFS patients.

We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission. We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.

Source: Pietrangelo T, Mancinelli R, Toniolo L, Montanari G, Vecchiet J, Fanò G, Fulle S. Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):795-807. https://www.ncbi.nlm.nih.gov/pubmed/19822097

 

Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome

Abstract:

The receptor for advanced glycation end product (RAGE) is thought to play an important role in inflammation. Chronic fatigue syndrome (CFS) is a long-lasting fatigue that compromises at least 50% of a subject’s daily activities without other known cause. Immune dysfunction has been implicated and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory response of inflammatory nature, was found.

The aim of this study is to analyse RAGE polymorphisms and HLA-DRB1 alleles in seventy-five Italian CFS patients and 141 controls matched for age, sex and ethnicity. These two groups underwent genomic study for RAGE 374T/A and 429C/T promoter polymorphisms; moreover, 46 patients and 186 controls were typed for HLA-DRB1 at low resolution molecular level. Of these, 31 patients and 99 controls also underwent high resolution analysis to define the HLA-DRB1*11 and DRB1*13 alleles.

The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism.

The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLADRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem to be involved in CFS, probably including a subregion of major interest.

 

Source: Carlo-Stella N, Bozzini S, De Silvestri A, Sbarsi I, Pizzochero C, Lorusso L, Martinetti M, Cuccia M. Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):745-54. https://www.ncbi.nlm.nih.gov/pubmed/19822091

 

Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue is increasingly common. Conventional medical care is limited in treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies, including herbal medicine.

OBJECTIVES: To assess the effectiveness of traditional Chinese medicine herbal products in treating idiopathic chronic fatigue and chronic fatigue syndrome.

SEARCH STRATEGY: The following databases were searched for terms related to traditional Chinese medicine, chronic fatigue, and clinical trials: CCDAN Controlled Trials Register (July 2009), MEDLINE (1966-2008), EMBASE (1980-2008), AMED (1985-2008), CINAHL (1982-2008), PSYCHINFO (1985-2008), CENTRAL (Issue 2 2008), the Chalmers Research Group PedCAM Database (2004), VIP Information (1989-2008), CNKI (1976-2008), OCLC Proceedings First (1992-2008), Conference Papers Index (1982-2008), and Dissertation Abstracts (1980-2008). Reference lists of included studies and review articles were examined and experts in the field were contacted for knowledge of additional studies.

SELECTION CRITERIA: Selection criteria included published or unpublished randomized controlled trials (RCTs) of participants diagnosed with idiopathic chronic fatigue or chronic fatigue syndrome comparing traditional Chinese medicinal herbs with placebo, conventional standard of care (SOC), or no treatment/wait lists. The outcome of interest was fatigue.

DATA COLLECTION AND ANALYSIS: 13 databases were searched for RCTs investigating TCM herbal products for the treatment of chronic fatigue. Over 2400 references were located. Studies were screened and assessed for inclusion criteria by two authors.

MAIN RESULTS: No studies that met all inclusion criteria were identified.

AUTHORS’ CONCLUSIONS: Although studies examining the use of TCM herbal products for chronic fatigue were located, methodologic limitations resulted in the exclusion of all studies. Of note, many of the studies labelled as RCTs and conducted in China did not utilize rigorous randomization procedures. Improvements in methodology in future studies is required for meaningful synthesis of data.

 

Source:Adams D, Wu T, Yang X, Tai S, Vohra S. Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006348. doi: 10.1002/14651858.CD006348.pub2. https://www.ncbi.nlm.nih.gov/pubmed/19821361 

 

An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome

Abstract:

BACKGROUND: The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.

METHODS: We used a population-based telephone survey of randomly selected individuals, followed by a clinical evaluation in the study metropolitan, urban, and rural counties of Georgia, USA. The medical and psychiatric histories of the subjects were examined and they underwent physical and psychiatric examinations and laboratory screening. We also employed the multidimensional fatigue inventory (MFI), the medical outcomes survey short form-36 (SF-36) and the US Centres for Disease Control and Prevention symptom inventory (SI).

RESULTS: Twenty-nine percent (1,609) of the 5623 subjects who completed the detailed telephone interview reported exclusionary diagnoses and we diagnosed an exclusionary condition in 36% of 781 clinically evaluated subjects. Both medical and psychiatric exclusionary conditions were more common in women, blacks and participants from rural areas. Subjects with and without exclusions had similar levels of fatigue and impairment as measured by the MFI and SF-36; those with CFS-like illness (not meeting the formal CFS definition) were more likely to have an exclusionary diagnosis. After adjusting for demographics, body mass index, fatigue subscales, SF-36 subscales and CFS symptoms, CFS-like illness did not remain significantly associated with having an exclusionary diagnosis.

CONCLUSION: Medical and psychiatric illnesses associated with fatigue are common among the unwell. Those who fulfill CFS-like criteria need to be evaluated for potentially treatable conditions. Those with exclusionary conditions are equally impaired as those without exclusions.

Comment in: Chronic fatigue syndrome: identifying zebras amongst the horses. [BMC Med. 2009]

 

Source: Jones JF, Lin JM, Maloney EM, Boneva RS, Nater UM, Unger ER, Reeves WC. An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome. BMC Med. 2009 Oct 12;7:57. doi: 10.1186/1741-7015-7-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768736/ (Full article)

 

Chronic fatigue syndrome: identifying zebras amongst the horses

Abstract:

There are currently no investigative tools or physical signs that can confirm or refute the presence of chronic fatigue syndrome(CFS). As a result, clinicians must decide how long to keep looking for alternative explanations for fatigue before settling on a diagnosis of CFS. Too little investigation risks serious or easily treatable causes of fatigue being overlooked, whilst too many increases the risk of iatrogenic harm and reduces the opportunity for early focused treatment.

A paper by Jones et al published this month in BMC Medicine may help clinicians in deciding how to undertake such investigations. Their results suggest that if clinicians look for common psychiatric and medical conditions in those complaining of prolonged fatigue, the rate of detection will be higher than previously estimated. The most common co-morbid condition identified was depression, suggesting a simple mental state examination remains the most productive single investigation in any new person presenting with unexplained fatigue. Currently, most diagnostic criteria advice CFS should not be diagnosed when an active medical or psychiatric condition which may explain the fatigue is identified.

We discuss a number of recent prospective studies that have provided valuable insights into the aetiology of chronic fatigue and describe a model for understanding chronic fatigue which may be equally relevant regardless of whether or not an apparent medical cause for fatigue can be identified. See the associated research paper by Jones et al: http://www.biomedcentral.com/1741-7015/7/57.

Comment on: An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome. [BMC Med. 2009]

 

Source: Harvey SB, Wessely S. Chronic fatigue syndrome: identifying zebras amongst the horses. BMC Med. 2009 Oct 12;7:58. doi: 10.1186/1741-7015-7-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766380/ (Full article)

 

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.

Comment in:

Erratum in: Partial retraction. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2011]

Retraction in: Retraction. [Science. 2011]

 

Source: Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science. 2009 Oct 23;326(5952):585-9. doi: 10.1126/science.1179052. Epub 2009 Oct 8. http://science.sciencemag.org/content/326/5952/585.long (Full article)