Chronic Fatigue Syndrome

INTRODUCTION Chronic fatigue syndrome (CFS) is a relatively poorly recognized clinical entity in medi- cal practice, although everyday experience teaches us that there are many patients who have CFS symptoms. The unwritten rule is that the syndrome is associated with viral infections as triggers or with a protracted subfebrile condi- tion, so that they are mostly managed by infec- tious disease specialists, despite requiring most serious multidisciplinary approach.

Chronic fatigue syndrome (CFS), also referred to as myalgic encephalomyelitis, is a disabling condition. 1,2 In addition to fatigue for more than 6 months that is not relieved by sleep and interferes with activities of daily life, patients suffer other symptoms such as cognitive impairment, muscle and joint pains and sore throat. 3 The diagnostic criteria for CFS are outlined in Table 1.

Introduction Chronic Fatigue Syndrome (CFS), also called Chronic Fatigue Immune Deficiency Syndrome (CFIDS), is a group of disorders characterized by chronic fatigue and multiple symptoms. There are probably many causes of CFS/CFIDS, although doctors do not have a good understanding of what those causes may be or the correct treatment. The symptom of fatigue is quite common and may be extremely debilitating, forcing the patient to have altered lifestyle, work and personal patterns. The complaint of fatigue is a source of frustration and confusion for any physician. Part of the difficulty of obtaining proper diagnosis and treatment is the lack of blood tests or imaging studies to correctly characterize the patient as having CFS/CFIDS. Thus, the diagnosis is based on symptoms, unlike most diseases where blood tests and studies are used to define the diagnosis.

Received 24 November 2011; revised 27 December 2011; accepted 8 January 2012 ABSTRACT Chronic fatigue syndrome (CFS) is a poorly under- stood condition primarily characterized by debilitate- ing, persistent or recurrent fatigue, increased physi- cal and mental fatigability, cognitive impairment and widespread musculoskeletal pain. During the past two decades, there have been heated debates about CFS among researchers, practitioners and patients. The existence of the disorder has been questioned, its underlying pathophysiology debated and an effective treatment opposed (such as antidepressants, stimu- lants or antibiotics). A lot of multidisciplinary litera- ture is found about CFS, but to date, many psychia- trists seem to unknown the existence of this illness or think that it is a purely psychological disorder. How- ever, CFS is sitting on the border between medicine and psychiatry. The aim of this review is to make psychiatrists aware of the existence of CFS and that they will, one day, be confronted with the manage- ment of this illness. Thus, this update allows under- standing what is CFS, the diversity of physiopatho- logy underlined and its management.

Orthostatic symptoms were not explained by POTS in our participants. Exercise induced transient, postural tachycardia in both control and CFS subjects (START), but the occurrence of START did not account for ortho- static symptoms. These findings suggest that postural tachycardia and orthostatic symptoms may be separate co-morbidities of CFS. ROC analysis established thresh- olds of 2 on the Gracely Box Scale for significant Diz- ziness and Lightheadedness in CFS. These thresholds stratified our participants into three groups: (i) No OI group with no significant Dizziness and Lightheaded- ness, (ii) Postural OI with symptoms only after standing, and (iii) Persistent OI with significant recumbent and standing complaints. Persistent OI had greater lability and higher OI complaints than other CFS subjects. Dizzi- ness and Lightheadedness while recumbent is an impor- tant finding in chronic fatigue syndrome and should be measured when doing a clinical evaluation to diagnose orthostatic intolerance.

3. DISCUSSION Ms A’s previous history of anti-depressant use and failure to diagnose her cluster of symptoms prompted a referral to psychiatry. However a clear absence of a mood component and anhedonia rules out a major depressive disorder. Ms A’s symptoms are of a sudden onset and unresolving fatigue seems to be predominant. It is masked by neurological and gastrointestinal symptoms. Foggy memory, muscle pain, arthralgias, sore throat with occipital lymph nodal swelling and unrefreshing sleep of more than six months durationsatisfy the CDC criteria for chronic fatigue syndrome. Circumstantial evidence of preceding tropical travel further corroborates the diagnosis. Cytomegalovirus and Epstein- Barr virus as a cause for chronic fatigue syndrome in tropical travelers has been well documented [3]. In addition she also exhibits word finding difficulties, blurred vision, hair loss, new sensitivity to noise, smell and alcohol and poor fine motor coordination which are associated with chronic fatigue syndrome. Essentially Ms A suffers from chronic fatigue syndrome and has fibromyalgia, irritable bowel syndrome and panic disorder as the commonly described comorbidities. She does have symptoms suggestive of obstructive sleep apnoea that can contribute to unrefreshing sleep and fatigue thereby clouding the picture and mimicking depression. The findings of endometriosis and Arnold Chiari malformation are coincidental. Fatigue and neurological symptomsoverlap with chronic fatigue syndrome. The endometriosis led to anemia which could have contributed to fatigue.

8. Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome. QJM 1995;88:767–773 9. Schwartz RB, Garada BM, Komaroff AL, et al. Detection of intracra- nial abnormalities in patients with chronic fatigue: comparison of MR imaging and SPECT. AJR Am J Roentgenol 1994;162:935–941 10. Daugherty SA, Henry BE, Peterson DL, et al. Chronic fatigue

The website of the HHS Chronic Fatigue Syndrome Advisory Committee includes the following comment about the IOM committee report: “With their recommendation of a streamlined, yet evidence-based set of diagnostic criteria, the IOM committee has taken a critical step toward assisting medical providers in making a diagnosis for those with this serious and debilitating illness.” The website also states that the HHS agencies are committed to working with partners, stakeholders, experts in the field, and CFSAC to review the report’s recommendations and appropriate next steps.

Medical Center, East Orange, New Jersey 2 ; and Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 3 Received 6 July 1998/Returned for modification 23 October 1998/Accepted 10 November 1998 We have conducted a double-blind study to assess the possible involvement of the human herpesviruses (HHVs) HHV6, HHV7, Epstein-Barr virus (EBV), and cytomegalovirus in chronic fatigue syndrome (CFS) pa- tients compared to age-, race-, and gender-matched controls. The CFS patient population was composed of rigorously screened civilian and Persian Gulf War veterans meeting the Centers for Disease Control and Pre- vention’s CFS case definition criteria. Healthy control civilian and veteran populations had no evidence of CFS or any other exclusionary medical or psychiatric condition. Patient peripheral blood mononuclear cells were analyzed by PCR for the presence of these HHVs. Using two-tailed Fisher’s exact test analyses, we were unable to ascertain any statistically significant differences between the CFS patient and control populations in terms of the detection of one or more of these viruses. This observation was upheld when the CFS populations were further stratified with regard to the presence or absence of major axis I psychopathology and patient self-re- ported gradual versus acute onset of disease. In tandem, we performed serological analyses of serum anti-EBV and anti-HHV6 antibody titers and found no significant differences between the CFS and control patients.

SUZANNE D. VERNON, PhD, earned her doctorate in virology at the University of Wisconsin at Madison and worked in public health research on infectious diseases at the US Centers for Disease Control and Prevention for 17 years before joining the CFIDS Association of America’s staff as scientific director in 2007. She has more than 70 peer-reviewed scientific publications on topics including human immunodeficiency virus, human papillomavirus, cervical cancer, and chronic fatigue syndrome.

A recent study (M Vera, MA Fletcher, C Cuba, L Garcia, N Klimas, presented to the International Association for Chronic Fatigue Syndrome/Myalgic Encephalitis, Reno, NV, March, 2009) reported that the anti-viral and immuno-modulatory drug, inosine pranobex, led to sig- nificant improvement in the clinical scores of 61 patients treated for 6 months. Immune activation was decreased, NK cell activity was improved and titers of anti-Epstein Barr Virus Viral Capsid Antigen IgG were significant decreased. Antibody titers to Human Herpes Virus 6 were unchanged. A larger randomized trial would seem appro- priate.

Discussion The primary objective of this study was to determine immunological and rheological characteristics of fatigue related conditions such as Chronic Fatigue Syndrome (CFS). This is the first study to confirm significant changes in NK phenotypes in CFS particularly decreases in CD56 bright CD16 - NK cells from preferentially isola- tion of NK cells from whole blood. Similar to other findings NK cytotoxic activity was also decreased. This study has illustrated for the first time significant reduc- tions in neutrophil respiratory burst in CFS patients.

http://creativecommons.org/licenses/by/4.0/ Abstract There is no agreement on the etiology of chronic fatigue syndrome (CFS), and the main theories (behavioural and viral/immune) do not satisfactorily explain the condition. A growing body of evidence suggests that CFS may be caused by a dysfunction of the stress system—and the hypo- thalamic-pituitary-adrenal (HPA) axis in particular—as a result of chronic stress. CFS shares many similarities to occupational burnout, including similar symptoms, physiological abnormalities and triggers. After a brief review of the science of stress, burnout, central fatigue and CFS, I propose a model of CFS based on a state of persistent burnout that remains after the initial stressors have been removed. This persistence may be due to a combination of a dysregulation of the HPA axis, and behavioural factors. A novel treatment approach based on self-efficacy and positive goals is proposed.

Javier Rivera Redondo - jriveraredondo@telefonica.net; José Ramón Ramón Giménez - jramon@isciii.es * Corresponding author Abstract Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post- traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities.

Fries et al. hypothesize that the hypocortisolism seen in stress-related disorders is a protective mechanism which has evolved to conserve energy during threats that are beyond the organism's ability to cope. 12 Persistent burnout theory of chronic fatigue syndrome Burnout and CFS share similar symptoms, as well as both being triggered by stress. 28 The main difference between burnout and CFS appears to be illness attribution: psychological for burnout, and physical for CFS. 28,29 Both CFS and burnout show a hypofunction of the HPA axis, which appears to resolve in burnout after taking time off work, but persists in CFS.

ABSTRACT: The cause of Chronic Fatigue Syndrome (CFS) is as yet undeter- mined; therefore, precise definitions for diagnosis and research have been developed. The most accepted diagnostic criteria are detailed below. It has been suggested that there are 150 000 cases of CFS in the UK, with a 2:1 predominance of females to males, and that prognosis without treatment is poor. The patterns of illness seen in CFS are identified and the development of an occupational therapy programme for the management of CFS is described.

Introduction Chronic fatigue syndrome (CFS), postviral fatigue syndrome and myalgic encephalomyelitis (ME) are names that have been used to describe the same syndrome1. The consensus is that chronic fatigue syndrome is the most appropriate title,2 as it does not presuppose a specific cause and identifies the most prominent feature - fatigue. Information concerning prevalence and the natural history of the syndrome is relatively scarce. It has been suggested that the overall prevalence in the UK is 150 000 cases with a 2:11 predominance of females compared to males.3 The main complaint is persistent fatigue, which differs from normal tiredness as it is usually severe and disabling, affecting physical and mental functioning, and follows minimal effort.1,4,5 The advice given to patients can be misleading. Patients are often told to rest until symptoms subside or to learn to live within their limits and modify their

Amplifying on Streeten’s observations, Low et al 14,21,22 noted similar orthostatic symptoms in pa- tients with tachycardia when upright who, on ortho- static challenge, were not always hypotensive but had many symptoms similar to hypotensive and tachycardic patients. POTS may occur much more frequently than autonomic failure and may represent an attenuated form of dysautonomia. In support of this we have obtained preliminary data using tech- niques of heart rate variability which indicate that there is very little variability in many children with CFS at rest and during tilt (Stewart J, Weldon A, Arlievsky N, Li K, Munoz J. Neurally mediated hy- potension and autonomic dysfunction measured by heart rate. Variability during head-up tilt testing in children with chronic fatigue syndrome. Clin Auton Res. 1998;8:221–230). These data may be interpreted as showing that both sympathetic and parasympa- thetic modulation of autonomic activity are severely compromised in children with CFS. Alternatively, they may interpreted as showing combined barore- ceptor and parasympathetic dysfunction that is con- sistent with the resting tachycardia observed in CFS patients. Often symptoms have their onset soon after a viral syndrome or other inflammatory process.

Chronic fatigue syndrome (CFS) in children and young people is a debilitating disease that has a major impact on the lives of children and their families. 1–3 CFS, also known as myalgic encephalomyelitis (ME) or, more recently, systemic exertion intolerance disease, 4 has been defined by using various diagnostic criteria. 5 Guidelines from the UK National Institute for Health and Care Excellence state that the diagnosis of CFS should be made after 3 months of persistent or recurrent fatigue that is not the result of ongoing exertion, not substantially alleviated by rest, has resulted in a substantial reduction in activities, and has no other known cause. 6 The diagnostic criteria of the Centers for Disease Control and Prevention require 6 months’

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