Chronic fatigue syndrome

Comment on: Phosphate diabetes in patients with chronic fatigue syndrome. [Postgrad Med J. 1998]

 

Sir, De Lorenzo and colleagues’ report a previously undefined relationship between chronic fatigue syndrome (CFS) and phosphate diabetes. They also report that mean serum phosphate concentration was found to be significantly lower in CFS patients than in control subjects. They explain their findings by the hypothesis that CFS patients have a metabolic defect that is secondary to their chronic underutilisation of skeletal muscle. Another hypothesis can, however, be proposed.

Hypophosphataemia in sepsis has been recently reported to be associated with high levels of tumour necrosis factor-a and interleukin-6.’ However, these inflammatory cytokines are also produced to excess in both CFS patients 3 and hypocortisolaemic subjects.4 De Lorenzo and colleagues’ findings,’ therefore, may simply reflect the hypocortisolism of CFS patients, 5 which is one of the 20 features that CFS shares with Addison’s disease.5

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431605/pdf/postmedj00143-0063a.pdf

 

Source: Baschetti R. Chronic fatigue syndrome. Postgrad Med J. 1998 Nov;74(877):701. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431605/ (Full article)

 

Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome

Abstract:

Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) is a disorder characterized by debilitating fatigue associated with immunological abnormalities and cognitive impairments. The recently cloned RNase L Inhibitor (RLI) gene encodes a specific protein which is believed to regulate 2-5A synthetase and RNase L activity via the formation of a latent heterodimeric protein complex.

In the present study, we investigated the levels of 2-5A synthetase, RNase L and RLI in patients with CFIDS as compared to healthy controls. Quantitative Competitive PCR (Q/C PCR) analysis showed a statistically significant decrease in RLI mRNA present in the peripheral blood lymphocytes (PBL) of patients with CFIDS (n = 25, mean = 569, S.E = 154) as compared to RLI mRNA level present in peripheral blood lymphocytes (PBL) of healthy controls (n = 15, mean = 2296, S.E = 506; p < 0.0001).

The decrease in RLI mRNA in CFIDS individuals correlated directly with RLI and RLI: RNase L protein ratio while showing an inverse relationship to the 2-5A synthetase and RNase L activity. This RLI mRNA and protein deficiency in CFIDS patients may explain the increase in activity of RNase L found in CFIDS patients.

The unidirectional decrease in RLI message and protein levels in CFIDS individuals may contribute to the destabilization of the latent RLI:RNase L heterodimeric protein complex, resulting in the excessive activation of RNase L shown in this study.

The increased activation of RNase L may result in an increased cellular RNA turnover and subsequent inhibition of protein synthesis; thus resulting in general fatigue, myalgia muscle weakness and other symptomatologies shown in CFIDS patients.

Furthermore, this data supports the hypothesis that the antiviral 2-5 oligoadenylate synthetase (2-5OAS) overexpression in individuals with CFIDS correlates with an increase in RNase L activity and with a decrease in RNase L inhibitor.

 

Source: Vojdani A, Choppa PC, Lapp CW. Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome. J Clin Lab Immunol. 1998;50(1):1-16. http://www.ncbi.nlm.nih.gov/pubmed/10189612

 

Orthostatic intolerance in the chronic fatigue syndrome

Abstract:

This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS).

Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical suspicion as to the likelihood of observing laboratory evidence of OI was assigned. Laboratory investigation consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing (6 breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched healthy controls who had no history of OI were used to define the range of normal responses to these three maneuvers.

Forty percent of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva maneuver and to deep breathing were similar in controls and patients. On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in patients with OI than in those without OI.

We conclude that there exists a clinically identifiable subgroup of patients with CFS and OI that differs from control subjects and from those with CFS without OI for whom treatment specifically aimed at improving orthostatic tolerance may be indicated.

 

Source: Schondorf R, Benoit J, Wein T, Phaneuf D. Orthostatic intolerance in the chronic fatigue syndrome. J Auton Nerv Syst. 1999 Feb 15;75(2-3):192-201. http://www.ncbi.nlm.nih.gov/pubmed/10189122

 

What causes chronic fatigue?

Comment on:

Chronic fatigue syndrome comes out of the closet. [CMAJ. 1998]

Chronic fatigue syndrome or just plain tired? [CMAJ. 1998]

Chronic fatigue syndrome get court’s nod of approval as legitimate disorder. [CMAJ. 1998]

 

The 3 excellent articles on chronic fatigue syndrome 1–3 reminded me of the desperate need for a discussion of the ethics — or lack thereof — related to independent medical examinations of patients with this condition.

A recent 21-page report from an independent medical examination of one of my patients with chronic fatigue syndrome included 2 pages of error-riddled history and the results of only a cursory physical exam, along with a bold admission that a full physical examination had not been done. The other 19 pages, clearly based on a word-processor template, were peppered with such clichés as “illness-seeking behaviour,” “somatization syndromes” and “preconscious motives.” The fee assessed for this report was $1200.

I used to be asked by insurance companies to perform independent medical examinations (for the standard fee suggested by the Alberta Medical Association), requests that I always accepted. However, when it became known that, in appropriate circumstances, I might support a diagnosis of chronic fatigue syndrome, such requests ceased abruptly.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230108/pdf/cmaj_160_5_638.pdf

 

Source: Voth A. What causes chronic fatigue? CMAJ. 1999 Mar 9;160(5):638. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230108/pdf/cmaj_160_5_638.pdf (Full article)

 

What causes chronic fatigue?

Comment on:

Chronic fatigue syndrome comes out of the closet. [CMAJ. 1998]

Chronic fatigue syndrome or just plain tired? [CMAJ. 1998]

Chronic fatigue syndrome get court’s nod of approval as legitimate disorder. [CMAJ. 1998]

 

Even though the 3 articles on chronic fatigue syndrome 1–3 in the Sept. 8 issue commendably demolish the obsolete claim that chronic fatigue syndrome is a psychiatric illness, they also offer outdated biological explanations for the syndrome, namely, either a chronic viral infection or a weakened immune system. Although the first of these explanations seemed convincing until a few years ago, it is hardly tenable now, because no specific virus has been identified in these patients.4

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230107/pdf/cmaj_160_5_636.pdf

 

Source: Baschetti R. What causes chronic fatigue? CMAJ. 1999 Mar 9;160(5):636, 638. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1230107/pdf/cmaj_160_5_636.pdf (Full article)

 

A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently associate the disease onset with a period of high physical and/or emotional stress. Alterations in hypothalamic-pituitary adrenal axis (HPA) function have been demonstrated. Although Cortisol production in patients with CFS has proven to be low, Dehydroepiandrosterone (DHEA) production has not been measured. DHEA output may be altered in this population.

The purpose of this uncontrolled, prospective, 6 month study of 23 white women, ages 35-55 was to identify CFS patients with suboptimal serum levels of DHEA-sulphate (DHEA-S), defined as DHEA-S <2.0 microg/mL, and to treat those patients with oral DHEA.

DHEA-S levels were re-measured after 4-6 weeks of oral DHEA therapy (25 mg). If DHEA-S remained <2.0 microg/ mL, or if no clinical response was achieved after 4-6 weeks of therapy, then an increased dose of DHEA was given. Physical and psychological impairment and disability status were measured by the MHAQII before DHEA intervention and at 3-month intervals. Of initially screened patients with CFS, 76% (116 of 153) were ages 35-55, and 89% (103 of 116) had suboptimal (<2.0 microg/mL) production of DHEA-S.

Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p < 0.01), thinking (improved by 26%, p < 0.01), memory (improved by 17%, p < 0.05), and sexual problems (improved by 22%, p = 0.06) over the period of the trial.

Further study is necessary to determine the safety and efficacy of supplementation of DHEA to this population in a controlled setting.

 

Source: Himmel PB, Seligman TM. A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. J Clin Rheumatol. 1999 Apr;5(2):56-9. http://www.ncbi.nlm.nih.gov/pubmed/19078357

 

Chronic fatigue syndrome, chronic fatigue, and psychiatric disorders: predictors of functional status in a national nursing sample

Abstract:

Members of 2 nurses’ associations (N = 71) were assessed using 2 mail questionnaires, a telephone questionnaire, the Diagnostic Interview Schedule, and medical records. Physicians reviewed participants to determine whether they met current criteria for chronic fatigue syndrome(CFS). Stepwise multivariate regression analyses were conducted to identify predictors of functional status scores.

Impairments in physical, role, and social functioning increased as fatigue severity increased. Bodily pain increased as fatigue severity increased, and ratings of overall health increased as severity of fatigue decreased. Nurses with a current psychiatric diagnosis reported more impairments in emotional functioning than nurses with a lifetime diagnosis or no psychiatric diagnosis.

Quality of life decreased as fatigue severity increased. Nurses with fatigue not meeting CFS criteria reported better quality of life than those with CFS or medical exclusions.

 

Source: Wagner-Raphael LI, Jason LA, Ferrari JR. Chronic fatigue syndrome, chronic fatigue, and psychiatric disorders: predictors of functional status in a national nursing sample. J Occup Health Psychol. 1999 Jan;4(1):63-71. http://www.ncbi.nlm.nih.gov/pubmed/10100114

 

Fibromyalgia syndrome

Abstract:

Fibromyalgia syndrome (FMS) is recognizable syndrome characterized by chronic, diffuse pain, an absence of inflammatory or structural muscloskeletal abnormalities, and a range of symptoms that include fatigue, and sleep and mood disturbances. Physical examination and laboratory testing are unrevealing, except for the presence of pain on palpation of characteristic soft-tissue sites, the tender points.

Despite the recognition of FMS by the World Health Organization, it remains a controversial condition and its existence as a distinct entity remains uncertain. However, the concept of FMS is a useful one, allowing many investigations to be avoided and appropriate advice on treatment to be given. FMS may overlap with symptoms of, and the patient further impaired by, anxiety and depression. The term FMS dose not imply causation and merely describes the most common symptoms.

Many patients with chronic fatigue syndrome(CFS) fulfill the criteria of FMS and represent one end of a spectrum of presentation. Evidence for triggering viral infection and the lower level of serum acylcarnitine, observed in CFS patients, is lacking in the majority of patients with FMS. These findings are suggestive to be distinctively another disorders between FMS and CFS.

 

Source: Matsumoto Y. Fibromyalgia syndrome. Nihon Rinsho. 1999 Feb;57(2):364-9. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/10078006

 

Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome

Abstract:

Previous studies have demonstrated concentrating neuroendocrinological disturbances in chronic fatigue syndrome (CFS) patients, concentrating in particular on low cortisol levels and a hypothalamic deficiency.

In order to investigate the dynamic response of the adrenal glands, we measured dehydroepiandrosterone (DHEA) in serum after adreno-corticotropic hormone (ACTH) stimulation during 60 minutes in 22 CFS-patients and 14 healthy controls.

We found normal basal DHEA levels, but a blunted serum DHEA response curve to i.v. ACTH injection. This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS, and could explain some of the immunological disturbances observed in this syndrome.

Comment in: Overlap of chronic fatigue syndrome with primary adrenocortical insufficiency. [Horm Metab Res. 1999]

 

Source: De Becker P, De Meirleir K, Joos E, Campine I, Van Steenberge E, Smitz J, Velkeniers B. Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Horm Metab Res. 1999 Jan;31(1):18-21. http://www.ncbi.nlm.nih.gov/pubmed/10077344

 

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known.

OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects.

METHODS: Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study. Medical history, physical examination, laboratory studies, and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period.

RESULTS: No severe adverse effects were observed related to the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients.

CONCLUSION: Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.

Comment in: Is NADH effective in the treatment of chronic fatigue syndrome? [Ann Allergy Asthma Immunol. 2000]

 

Source: Forsyth LM, Preuss HG, MacDowell AL, Chiazze L Jr, Birkmayer GD, Bellanti JA. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1999 Feb;82(2):185-91. http://www.ncbi.nlm.nih.gov/pubmed/10071523