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Chronic Fatigue Syndrome is Associated with Chronic Enterovirus Infection of the Stomach
John K S Chia, Andrew Y Chia
J Clin Pathol 2007;0:1–6. doi: 10.1136/jcp.2007.050054

The cause of Chronic Fatigue Syndrome (CFS) is still unknown although persistent or intermittent gastrointestinal (GI) symptoms and the presence of viruses in the stomach biopsy specimens of patients with CFS was evaluated for this study.
165 consecutive patients with CFS had upper GI endoscopies and biopsies. 82% of the patients’ biopsies were positive for Viral Capsid Protein whereas only 20% of the controls were positive.    
Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2–8 years later showed positive. Enterovirus RNA was detected in 37% in biopsy samples; 1 out of 21 controls had detectable Enterovirus RNA; 1 out of 3 patients had detectable Enterovirus RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic (causing cell damage) enteroviruses.
The results showed that Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.
The researchers stated, “Although finding a chronic infection of the stomach may not directly prove a similar infection in the brain, muscle or heart, it opens up a new direction in the research for this elusive disease. By inference, a significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which can lead to diffuse symptomatology without true organ damage. If confirmed, stomach biopsies could be used as a test to document viral persistence, and serve as an objective means to follow the response to antiviral therapy, in addition to quantitation (measure the quantity) of subjective complaints.


 Specially-formulated dark chocolate may help cut CFS symptoms

Patients in a pilot study, run by researchers from Hull York Medical School, found they had less fatigue when eating dark chocolate with a high cocoa content than with white chocolate dyed brown.

The researchers said that the results were surprising but dark chocolate may be having an effect on the brain chemical serotonin.
Professor Steve Atkin, study leader and an expert in endocrinology, said the idea for the study came from a patient who reported feeling much better after eating dark chocolate with a high cocoa solid content.  He carried out a trial of 10 patients who received a daily dose of 45g of dark chocolate or white chocolate dyed to look like dark chocolate for two months.

The patients had a month off before taking the other type of chocolate for two months.

Those taking dark chocolate reported significantly less fatigue and reported feeling more fatigue when they stopped eating it.

Professor Atkin was very surprised at the strength of the results and said, "Although it was a small study, two patients went back to work after being off for six months."
He explained: "Dark chocolate is high in polyphenols, which have been associated with health benefits such as a reduction in blood pressure. "Also high polyphenols appear to improve levels of serotonin in the brain, which has been linked with chronic fatigue syndrome and that may be a mechanism."

He stated that although more research was needed, patients would not do themselves any harm by eating small amounts of dark chocolate. 

Heather Walker, Communications Manager, Action for ME, said: "If it were that easy, there would not be 250,000 people in the UK today whose lives are being devastated by ME."

The researchers stressed the chocolate formulation used in the study was not currently available to the public.


Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study. Scott LV, Teh J, Reznek R, Martin A, Sohaib A, Dinan TG. Psychoneuroendocrinology. 1999 Oct;24(7):759-68.
Department of Psychiatry, Trinity College Dublin Medical School, St. James's, Hospital, Ireland.

No inclusive or satisfactory biomedical explanation for chronic fatigue syndrome (CFS) has as yet been forwarded. Recent research suggests that a dysregulated hypothalamic-pituitary-adrenal axis (HPA) may be contributory, and in particular that there may be diminished forward drive and adrenal under-stimulation. In this preliminary study we wished to examine a cohort of CFS patients in whom evidence for such hypofunctioning was found. Our aim was to establish whether these patients had altered adrenal gland size. Patients were recruited from a fatigue clinic. Those who fulfilled the Centre for Disease Control and Prevention (CDC) criteria underwent a 1 microgram adrenocorticotropin (ACTH) stimulation test, a test of adrenal gland functioning. Eight subjects (five females, three males) with a subnormal response to this test underwent a computer tomography (CT) adrenal gland assessment. Measurements were compared with those from a group of 55 healthy subjects. The right and left adrenal gland bodies were reduced by over 50% in the CFS subjects indicative of significant adrenal atrophy in a group of CFS patients with abnormal endocrine parameters. This is the first study to use imaging methods to measure adrenal gland size in CFS. It is a limitation of this study that a selected CFS sample was employed. A future larger study would optimally employ an unselected cohort of CFS patients. This study has implications not only for the elucidation of CFS pathophysiology, but also for possible therapeutic strategies.

PMID: 10451910 [PubMed - indexed for MEDLINE]


Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome

N Kaushik, D Fear, S C M Richards, C R McDermott, E F Nuwaysir, P Kellam, T J Harrison, R J Wilkinson, D A J Tyrell, S T Holgate, J R Kerr  J Clin Pathol 2005:58:826-832.

Aims: To test the hypothesis that there are reproducible abnormalities of gene expression in patients with CFS compared with normal healthy persons.
The peripheral blood mononuclear cells from 25 patients with CFS and 25 normal blood donors matched for age, sex, and geographical location were tested. The data revealed differential expression of 35 genes. 

Conclusion: These results suggest that patients with CFS have reproducible alterations in gene regulation.

This study is being repeated at the moment by Dr Jonathan Kerr, looking at 1000 patients, and so far that study is backing up the results of this one.
Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study

 Daniel Blockmans, Philippe Persoons , Boudewijn Van Houdenhove , Marina Lejeune and Herman Bobbaers
American Journal of Medicine - 15 June 2003, Volume 114, Issue 9 Pages 736-741


Purpose - Chronic fatigue syndrome has been associated with decreased function of the hypothalamic-pituitary-adrenal axis. Although neurally mediated hypotension occurs more frequently in patients with chronic fatigue syndrome than in controls, attempts to alleviate symptoms by administration of hydrocortisone or fludrocortisone have not been successful. The purpose of this study was to investigate the effect of combination therapy (5 mg/d of hydrocortisone and 50 μg/d of 9-alfa-fludrocortisone) on fatigue and well-being in chronic fatigue syndrome.

We performed a 6-month, randomized, placebo-controlled, double-blind, crossover study in 100 patients who fulfilled the 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome. Between-group differences (placebo minus treatment) were calculated on a 10-point visual analog scale.

Results - Eighty patients completed the 3 months of placebo and 3 months of active treatment in a double-blind fashion. There were no differences between treatment and placebo in patient-reported fatigue (mean difference, 0.1; 95% confidence interval [CI]: −0.3 to 0.6) or well-being (mean difference, −0.4; 95% CI: −1.0 to 0.1). There were also no between-group differences in fatigue measured with the Abbreviated Fatigue Questionnaire, the Short Form-36 Mental or Physical Factor scores, or in the Hospital Anxiety and Depression Scale.

Conclusion - Low-dose combination therapy of hydrocortisone and fludrocortisone was not effective in patients with chronic fatigue syndrome.


Fine-needle aspiration cytology of the thyroid in chronic fatigue

Sir--Armando Bartolazzi and Alessandra Gasbarri (Dec 9, p 2010)1 and D N Poller and colleagues (Dec 9, p 2010)2 discuss the use of fine-needle aspiration (FNA) cytology of the thyroid. In this context, the technique is used for the classification of lesions according to degree of suspicion of malignancy.
FNA cytology of the thyroid has other applications. Inflammatory dis-orders, especially chronic lymphocytic (autoimmune) thyroiditis, can be clearly ascertained by this technique. In non-iodine-deficient areas, lymphocytic thyroiditis is the most common cause of hypothyroidism.3

In the investigation of patients complaining of chronic (>1 year) fatigue, FNA cytologic assessment of the thyroid has been tested in addition to conventional first-line biochemical thyroid function tests. Of 219 patients (90% women), 87 (40%) were diagnosed with definite cytological lymphocytic thyroiditis.
The distribution of thyrotropin ([thyroid stimulating hormone] reference range 0·1-5 mU/L) among the 87 with lymphocytic thyroiditis is shown in the figure. In patients with chronic fatigue and lymphocytic thyroiditis, thyrotropin values were scattered (median 3·8 mU/L). Clinical response to thyroxine was equally favourable among patients with lymphocytic thyroiditis, irrespective of initial thyrotropin concentration.
We strongly advocate FNA cytologic assessment of the thyroid in the investigation of chronic fatigue. TL died before this letter was published.

*Bo Wikland, Torsten Löwhagen, P 0 Sandberg

*Hötorget Medical Centre, PO 1417, SE-11184 Stockholm, Sweden; and Department of Clinical Cytology, Medilab, PO Box 1550, Täby, Sweden (e-mail:bo.wikland@telia.com)

1 Bartolazzi A, Gasbarri A. Thyroid disease classification. Lancet 2000; 356: 2010.
2 Poller DN, Yiangou C, Cummings ME, Boote D. Thyroid disease classification. Lancet 2000; 356: 2010-11.
3 Braverman LE, Utiger RD, eds. Werner and Ingbar's the thyroid, 7th edn. Philadelphia: Lippincott-Raven, 1996.

NB: Dr Peatfield feels that diagnosis should be perfectly clear clinically without the necessity of sticking needles into peoples necks; and that the diagnosis can then be confirmed by a trial of treatment.This article just goes to show that  if we did use fine-needle aspiration cytology, many more people would be diagnosed!


Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome?

Roberts AD, Charler ML, Papadopoulos A, Wessely S, Chalder T, Cleare AJ.
King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK
Psychol Med. 2010 Mar;40(3):515-22. Epub 2009 Jul 17.

Some studies have shown that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism but researchers are not sure of the clinical significance of this.

The researchers of this study wanted to find out whether hypocortisolism had any effect on the response of CFS to cognitive behavioural therapy (CBT).
84 patients with CFS defined by the Centers for Disease Control and Prevention (CDC) of whom 64 were free from psychotropic medication were measured for 24-h urinary free cortisol (UFC).  These patients then received CBT in a specialist, out-patient clinic as part of their usual clinical care.

Salivary cortisol output from 8am to 10pm was also measured in a subsample of 56 patients not on psychiatric treatment.

Overall, 39% of patients responded to CBT after 6 months of treatment. Lower 24-h UFC output was associated with a poorer response to CBT but only in psychotropic medication-free patients. A flattened diurnal (daily variation) profile of salivary cortisol was also associated with a poor response to CBT.

The researchers concluded that “Low cortisol is of clinical relevance in CFS, as it is associated with a poorer response to CBT.
Hypocortisolism could be one of several maintaining factors that interact in the persistence of CFS.”