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)

 

Virology. A new virus for old diseases?

There is little consensus in the medical community on whether chronic fatigue syndrome is a distinct disease. As its name implies, the condition is characterized by debilitating fatigue persisting for many years, and it affects as much as 1% of the world’s population. Although chronic inflammation is often found in these patients, no infectious or toxic agent has been clearly implicated in this disease, which is diagnosed largely by excluding other conditions that cause similar symptoms (1). In this week’s Science Express, Lombardi et al. (2) describe the detection of xenotropic murine leukemia virus–related virus (XMRV) in about two-thirds of patients diagnosed with chronic fatigue syndrome. Both laboratory and epidemiological studies are now needed to determine whether this virus has a causative role, not only in this disease, but perhaps in others as well.

Chronic fatigue syndrome is not the first human disease to which XMRV has been linked. The virus first was described about 3 years ago in a few prostate cancer patients (3), and recently detected in nearly a quarter of all prostate cancer biopsies (4). It has been isolated from both prostate cancer and chronic fatigue syndrome patients, and is similar to a group of endogenous murine leukemia viruses (MLVs) found in the genomes of inbred and related wild mice. Although a half century of studies on MLVs and other gammaretroviruses have led to important discoveries on which much of our current understanding of cancer rests, there has been no clear evidence demonstrating human infection with gammaretroviruses, or associating these agents with any human disease.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818280/

Comment on: Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. [Science. 2009]

 

Source: Coffin JM, Stoye JP. Virology. A new virus for old diseases? Science. 2009 Oct 23;326(5952):530-1. doi: 10.1126/science.1181349. Epub 2009 Oct 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818280/ (Full article)

 

The doctor-patient relationship in chronic fatigue syndrome: survey of patient perspectives

Abstract:

BACKGROUND: When confronted with chronic fatigue syndrome (CFS), general practitioners (GPs) need to deal with diverse complaints. This may introduce a sense of powerlessness and frustration in the GP, which could possibly undermine the doctor-patient relationship.

AIM: Our aim was to list the perspectives of patients with CFS regarding the medical encounter.

METHOD: This was a questionnaire study of systematically selected patients presenting to a tertiary clinic specialising in CFS. A questionnaire was presented to every third patient attending the clinic. Statistical computations were performed using the SPSS statistical package.

RESULTS: One hundred and seventy-seven patients completed the questionnaire. A diagnosis of CFS was made by a GP in 8% of the cases. In 31% of the cases the GP had experience with general CFS complaints, and 35% of the GPs showed experience in CFS. Only 23% reported sufficient knowledge to treat the condition. According to the patients surveyed, 35% felt that their GP had experience in dealing with CFS.

CONCLUSIONS: The heterogeneity of CFS and the controversy surrounding this condition seemed to overwhelm GPs and strain the medical encounter. Patients with CFS seemed unsatisfied with the interaction with their doctor. Moreover, the results show that CFS is not addressed well by the medical community, and the failure to diagnose leads to a lack of empathetic care, with consequential loss of the capacity of the doctor to act as a healer.

 

Source: Van Hoof E. The doctor-patient relationship in chronic fatigue syndrome: survey of patient perspectives. Qual Prim Care. 2009;17(4):263-70. https://www.ncbi.nlm.nih.gov/pubmed/19807959

 

Electroencephalographic correlates of Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Unremitting fatigue and unrefreshing sleep, hallmark traits of Chronic Fatigue Syndrome (CFS), are also pathognomonic of sleep disorders. Yet, no reproducible perturbations of sleep architecture, multiple sleep latency times or Epworth Sleepiness Scores are found to be associated consistently with CFS. This led us to hypothesize that sleep homeostasis, rather than sleep architecture, may be perturbed in CFS. To probe this hypothesis, we measured and compared EEG frequencies associated with restorative sleep between persons with CFS and matched controls, both derived from a population-based sample.

METHODS: We evaluated overnight polysomnography (PSG) in 35 CFS and 40 control subjects. PSG records were manually scored and epochs containing artifact removed. Fast Fourier Transformation was utilized to deconstruct individual EEG signals into primary frequency bands of alpha, delta, theta, sigma, and beta frequency domains. The spectral power of each frequency domain for each sleep state was compared between persons with CFS and matched controls.

RESULTS: In persons with CFS, delta power was diminished during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta spectral power during stage 2, Slow Wave Sleep, and REM.

DISCUSSION: Employing quantitative EEG analysis we demonstrate reduced spectral power of cortical delta activity during SWS. We also establish reduced spectral power of cortical alpha activity, with the greatest reduction occurring during REM sleep. Reductions in theta, beta, and sigma spectral power were also apparent.

CONCLUSION: Unremitting fatigue and unrefreshing sleep, the waking manifestations of CFS, may be the consequence of impaired sleep homeostasis rather than a primary sleep disorder.

 

Source: Decker MJ, Tabassum H, Lin JM, Reeves WC. Electroencephalographic correlates of Chronic Fatigue Syndrome. Behav Brain Funct. 2009 Oct 6;5:43. doi: 10.1186/1744-9081-5-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765956/ (Full article)

 

A comparison of classification methods for predicting Chronic Fatigue Syndrome based on genetic data

Abstract:

BACKGROUND: In the studies of genomics, it is essential to select a small number of genes that are more significant than the others for the association studies of disease susceptibility. In this work, our goal was to compare computational tools with and without feature selection for predicting chronic fatigue syndrome (CFS) using genetic factors such as single nucleotide polymorphisms (SNPs).

METHODS: We employed the dataset that was original to the previous study by the CDC Chronic Fatigue Syndrome Research Group. To uncover relationships between CFS and SNPs, we applied three classification algorithms including naive Bayes, the support vector machine algorithm, and the C4.5 decision tree algorithm. Furthermore, we utilized feature selection methods to identify a subset of influential SNPs. One was the hybrid feature selection approach combining the chi-squared and information-gain methods. The other was the wrapper-based feature selection method.

RESULTS: The naive Bayes model with the wrapper-based approach performed maximally among predictive models to infer the disease susceptibility dealing with the complex relationship between CFS and SNPs.

CONCLUSION: We demonstrated that our approach is a promising method to assess the associations between CFS and SNPs.

 

Source: Huang LC, Hsu SY, Lin E. A comparison of classification methods for predicting Chronic Fatigue Syndrome based on genetic data. J Transl Med. 2009 Sep 22;7:81. doi: 10.1186/1479-5876-7-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765429/ (Full article)

 

Functional somatic syndromes from the view of cultural anthropology

Abstract:

The functional somatic syndromes have acquired major socio-cultural and political dimensions. Socio-cultural factors clearly affect symptoms, suffering, and disability perception and reporting. And knowledge of explanatory models of bodily distress for patients from different cultural backgrounds is useful in the establishment of a stable doctor -patient relationship. FSS may be an operational category to bridge between medical explanatory model and patient’s model. According to medical anthropology, sickness has two faces; illness and disease. “Disease” is the problem from the practitioner’s perspective, and “illness” is the human experience of symptoms and suffering. In this paper, the anthropological research on chronic fatigue syndrome as “not real” illness experience was described.

 

Source: Nakagami A, Tsujiuchi T. Functional somatic syndromes from the view of cultural anthropology. Nihon Rinsho. 2009 Sep;67(9):1683-8. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/19768901

 

Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence?

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous syndrome of unknown etiology and physiopathology. CFS patients complain about disabling fatigue, depression, difficulty with memory, and concomitant skeletal and muscular pain. Interestingly enough, there is certain overlap between CFS symptoms, autoimmune rheumatic disease, and infectious diseases.

Certain neuroendocrine-immune abnormalities have also been described, and autoantibodies commonly described in some autoimmune diseases have been found in CFS patients as well. An increasing number of autoantibodies, mainly directed against other nuclear cell components, have been illustrated. Likewise, an association between some infectious agents, antibody production, and later CFS onset has been reported. Similarly, vaccination is depicted as playing an important role in CFS onset.

Recently, a case report pointed toward a causal association between silicone breast linkage, hepatitis B virus vaccination, and CFS onset in a previous healthy woman. Such findings suggest that there is a likely deregulation of the immune system influenced by specific agents (infections, vaccination, and products, such as silicone).

Evidence suggests that CFS is a complex disease in which several risk factors might interact to cause its full expression. Thus, although different alterations have been found in CFS patients, undoubtedly the main feature is central nervous system involvement with immunological alterations. Therefore, a new term neuro-psycho-immunology must be quoted. New studies based on this concept are needed in order to investigate syndromes, such as CFS, in which immunological alterations are thought to be associated with concomitant psychological and health disturbances.

 

Source: Ortega-Hernandez OD, Shoenfeld Y. Infection, vaccination, and autoantibodies in chronic fatigue syndrome, cause or coincidence? Ann N Y Acad Sci. 2009 Sep;1173:600-9. doi: 10.1111/j.1749-6632.2009.04799.x. https://www.ncbi.nlm.nih.gov/pubmed/19758205

 

Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen class II alleles in chronic fatigue syndrome: are they associated with age at onset and specific symptoms?

Abstract:

This study aimed to determine the influence of autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen (HLA) class II genes on age at chronic fatigue syndrome (CFS) onset and symptoms.

Eighty-one CFS patients were enrolled, and clinical data were recorded. Autoantibodies to different components of the central nervous system were tested. Polymorphisms in the promoter of the serotonin transporter gene (l/s) and a single nucleotide polymorphism in the serotonin receptor-2A gene (A/G) as well as HLA class II alleles were determined. Multivariate logistic-regression analyses were carried out.

The mean age at CFS onset +/- SD was 33.5 +/- 12.5 years. An age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor AA genotype and the HLA-DRB1*03 allele. An ACFSO during the fourth decade of life was associated with the HLA-DRB1*07 allele, whereas an ACFSO > or = 43 years was associated with having at least one copy of the serotonin G allele.

Concerning CFS symptoms, the serotonin AG genotype was protective against depressive symptoms. Although having at least one copy of the serotonin A allele and being female were associated with risk for arthralgia, the presence of antineuronal cell antibodies was protective against this. Episodes of unexplained fever were associated with the HLA-DRB1*11 allele. None of the genetic or serological features was associated with myalgia. None of the antibodies determined correlated with any ACFSO or other symptoms.

Our results reveal that in CFS, like other autoimmune diseases, different genetic features are related to age at CFS onset and symptoms.

 

Source: Ortega-Hernandez OD, Cuccia M, Bozzini S, Bassi N, Moscavitch S, Diaz-Gallo LM, Blank M, Agmon-Levin N, Shoenfeld Y. Autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen class II alleles in chronic fatigue syndrome: are they associated with age at onset and specific symptoms? Ann N Y Acad Sci. 2009 Sep;1173:589-99. doi: 10.1111/j.1749-6632.2009.04802.x. https://www.ncbi.nlm.nih.gov/pubmed/19758204

 

When a parent is chronically ill: chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic illness may reshape not only the life of the ill parent but also that of the entire family, but research in this area remains limited. More specifically, little is known about how an ill parent and the family respond to a particularly devastating and controversial chronic illness, chronic fatigue syndrome (CFS).

OBJECTIVES: The objective of this study was to describe the responses of the parent and the ensuing family system responses to the presence of chronic fatigue syndrome as a chronic parental illness.

METHODS: Parents were interviewed individually, and then the ill parent and as many immediate family members as possible were interviewed collectively. After consent or assent, interviews were audiotaped and transcribed. Thematic analyses at the individual, intrafamily, and across-family levels were used to explore these phenomena.

RESULTS: Eight ill parents first described the onset of illness, an ongoing struggle to receive diagnosis and care, and the significance of the illness in transforming present and future roles. Multiple members of the family together with the ill parent described how they struggled with the reality of the illness, the shifting roles and responsibilities, the reduced family income, and the frequent social isolation that could be exacerbated by the controversial nature of the illness. Families described and demonstrated their struggles to maintain normal family life and plans in the face of continuing uncertainty.

DISCUSSION: This study is situated within current scholarship on family responses to chronic parental illness. The value of the family research interview is affirmed. Recommendations are made for future directions in family nursing research exploring responses of families in which a parent is chronically ill.

 

Source: Donalek JG. When a parent is chronically ill: chronic fatigue syndrome. Nurs Res. 2009 Sep-Oct;58(5):332-9. doi: 10.1097/NNR.0b013e3181ac156f. https://www.ncbi.nlm.nih.gov/pubmed/19752673