2010 – Page 4 – American ME and CFS Society

The search for pain relief in people with chronic fatigue syndrome: a descriptive study

Abstract:

The purpose of this study was to investigate the use and perceived benefit of complimentary and alternative medicine (CAM) and physiotherapy treatments tried by people with chronic fatigue syndrome (CFS) to ease painful symptoms. This study used a descriptive, cross-sectional design.

People with CFS who experienced pain were recruited to this study. Participants were asked during a semistructured interview about the treatments they had tried to relieve their pain. Each interview was conducted in the home of the participant. Fifty participants were recruited, of which, 10 participants were severely disabled by CFS. Eighteen participants were trying different forms of CAM treatment for pain relief at the time of assessment. Three participants were currently receiving physiotherapy.

Throughout the duration of their illness 45 participants reported trying 19 different CAM treatments in the search for pain relief. Acupuncture was reported to provide the most pain relief (n=16). Twenty-seven participants reported a total of 16 different interventions prescribed by their physiotherapist. The results of this study suggest some physiotherapy and CAM treatments may help people manage painful CFS symptoms. Future research should be directed to evaluating the effectiveness of interventions such as acupuncture or gentle soft tissue therapies to reduce pain in people with CFS.

Source: Marshall R, Paul L, Wood L. The search for pain relief in people with chronic fatigue syndrome: a descriptive study. Physiother Theory Pract. 2011 Jul;27(5):373-83. doi: 10.3109/09593985.2010.502554. Epub 2010 Nov 1. https://www.ncbi.nlm.nih.gov/pubmed/21039301

A review of the definitional criteria for chronic fatigue syndrome

Abstract:

RATIONALE, AIMS AND OBJECTIVES: The research community has for more than three decades tried to unravel the diagnostic mystery that is Chronic Fatigue Syndrome (CFS). This has resulted in considerable amounts of time and money being invested in attempts aimed at establishing the aetiology and pathogenesis of CFS. All of this investment has produced evidence of an interesting variety of endocrine, immune, infectious, muscular and neurological abnormalities in CFS; however, the cause remains elusive. The absence of a known causative agent or diagnostic test for CFS has resulted in the development of a number of CFS case definitions. As such, the main objectives of this paper are to provide a critical review of the similarities and differences between the varying approaches to CFS case definition. The conflicts and controversies that have emerged as a result of the differing definitional criterion for CFS are highlighted and the potential impact on future research is identified.

METHODS, RESULTS AND CONCLUSIONS: This paper presents a critical review of the most frequently used case definitions in CFS. There are currently five case definitions of CFS; however, the most prominent and widely used of these definitions is the 1994 Centre for Disease Control and Prevention Case Definitions. However, the pre-eminence of this definition over the others has never been substantiated and it has been widely criticized for its lack of specificity. Furthermore, none of the above case definitions have produced evidence to demonstrate their accuracy or precision at defining cases of CFS. A summary description of the symptom profile included in each of the case definitions is provided. The inconsistencies that have emerged in CFS research as a consequence of differing approaches to case definition are also highlighted and discussed.

Source: Christley Y, Duffy T, Martin CR. A review of the definitional criteria for chronic fatigue syndrome. J Eval Clin Pract. 2012 Feb;18(1):25-31. doi: 10.1111/j.1365-2753.2010.01512.x. Epub 2010 Oct 4. https://www.ncbi.nlm.nih.gov/pubmed/21029269

Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue?

Abstract:

Chronic NF-κB activation has been supposed as a key event in chronic fatigue syndrome (CFS) and many other better-defined pro-inflammatory diseases. Knowledge about the impact of deficiency vitamin D on chronic NF-κB activation could open a new disease approach. Whereas NF-κB activation leads at first to a pro-inflammatory immune response, later on a vitamin D-dependent anti-inflammatory response ensues. Binding of the active vitamin D metabolite 1,25(OH)(2)D(3) to vitamin D receptor (VDR) yields a transcription factor which represses NF-κB activation, and additionally modulates and down-regulates adaptive, but enhances innate immune responses, and improves redox balance, thus counterbalancing inflammation on multiple levels. However, this built-in late counterbalance against inflammation works only when stores of calcium and 25(OH)D(3) are abundant. Therefore a connection between lowered vitamin D-metabolism and persistent NF-κB activation, augmented nitrosative-oxidative stress, redox imbalance, chronic inflammation, and concomitant fatigue can be postulated. In order to confirm this hypothesis, randomized controlled clinical studies about the clinical effects of supplementation of calcium and vitamin D(3) would be necessary in diseases characterized by persistent NF-κB activation and chronic inflammation and fatigue.

Source: Hoeck AD, Pall ML. Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue? Med Hypotheses. 2011 Feb;76(2):208-13. doi: 10.1016/j.mehy.2010.09.032. Epub 2010 Oct 25. https://www.ncbi.nlm.nih.gov/pubmed/20980105

Unraveling the role of perfectionism in chronic fatigue syndrome: is there a distinction between adaptive and maladaptive perfectionism?

Abstract:

In the current study, we investigated whether the distinction between adaptive (i.e. high personal standards) and maladaptive (i.e. concern over mistakes and doubt about actions) perfectionism that has been found in the literature, is also valid in patients with chronic fatigue syndrome (CFS). We hypothesized that maladaptive, but not adaptive, perfectionism would be significantly and positively related to severity of fatigue and depression in CFS. We examined this hypothesis in a sample of 192 CFS patients using structural equation modelling (SEM).

Although the two perfectionism dimensions were related to each other, results supported a model in which only maladaptive perfectionism was positively related to severity of fatigue and depression. Further, we found that depression fully mediated the effect of maladaptive perfectionism on fatigue. The results suggest that adaptive and maladaptive perfectionism are two distinct, albeit related, dimensions in CFS. Findings of this study have important implications for theory and treatment of CFS, particularly for cognitive-behavioral treatment.

Source: Unraveling the role of perfectionism in chronic fatigue syndrome: is there a distinction between adaptive and maladaptive perfectionism? Psychiatry Res. 2011 Apr 30;186(2-3):373-7. doi: 10.1016/j.psychres.2010.09.016. Epub 2010 Oct 18. https://www.ncbi.nlm.nih.gov/pubmed/20961622

The HPA axis in the pathogenesis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a clinical syndrome characterized by profound disabling chronic fatigue associated with a wide array of other physical symptoms. Its etiology is currently unknown. Among the various hypotheses, considerable interest has been placed in the hypothalamus-pituitary-adrenal axis as a possible target of the pathogenesis of CFS. This article reviews the available scientific evidence about a role of hypothalamic-pituitary-adrenal axis in the pathogenesis of chronic fatigue syndrome.

Source: Ursini F, Succurro E, Grembiale A, Gagliardi DA, Arturi F. The HPA axis in the pathogenesis of chronic fatigue syndrome. Clin Ter. 2010;161(5):461-4. [Article in Italian] https://www.ncbi.nlm.nih.gov/pubmed/20949245

Daily physical activity of patients with the chronic fatigue syndrome: a systematic review

Abstract:

OBJECTIVE: To give an overview of the physical activity level of patients with chronic fatigue syndrome in comparison with asymptomatic controls.

DATA SOURCES: MEDLINE, Web of Science, EMBASE, PsycINFO, Picarta, the Cochrane Controlled Trial Register that is included in the Cochrane Library and reference tracking.

REVIEW METHODS: A systematic literature search was conducted focusing on studies concerning physical activity levels of patients with chronic fatigue syndrome compared to controls. A meta-analysis was performed to pool data of the studies.

RESULTS: Seventeen studies were included with 22 different comparisons between patients with chronic fatigue syndrome and controls. Fourteen studies, including 18 comparisons, showed lower physical activity levels in patients with chronic fatigue syndrome as compared to controls. Four studies, including four comparisons, showed no differences between both groups. The meta-analysis included seven studies and showed a daily physical activity level in patients with chronic fatigue syndrome of only 68% of the physical activity level observed in control subjects. The pooled mean coefficient of variation in patients with chronic fatigue syndrome was higher as compared to control subjects (34.3% versus 31.5%), but this difference did not reach significance.

CONCLUSION: Patients with chronic fatigue syndrome appear to be less physically active compared with asymptomatic controls. There is no difference in variation of physical activity levels between patients with chronic fatigue syndrome and healthy control subjects, but the validity and reliability of some methods of measuring physical activity is questionable or unknown.

Source: Evering RM, van Weering MG, Groothuis-Oudshoorn KC, Vollenbroek-Hutten MM. Daily physical activity of patients with the chronic fatigue syndrome: a systematic review. Clin Rehabil. 2011 Feb;25(2):112-33. doi: 10.1177/0269215510380831. Epub 2010 Oct 13. https://www.ncbi.nlm.nih.gov/pubmed/20943713

Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association

Abstract:

Serotonergic neurotransmission plays a key role in the pathophysiology of neuropsychiatric illnesses. The functional significance of a promoter polymorphism, -1438G/A (rs6311), in one of the major genes of this system (serotonin receptor 2A, HTR2A) remains poorly understood in the context of epigenetic factors, transcription factors and endocrine influences. We used functional and structural equation modeling (SEM) approaches to assess the contributions of the polymorphism (rs6311), DNA methylation and clinical variables to HTR2A expression in chronic fatigue syndrome (CFS) subjects from a population-based study. HTR2A was up-regulated in CFS through allele-specific expression modulated by transcription factors at critical sites in its promoter: an E47 binding site at position -1,438, (created by the A-allele of rs6311 polymorphism), a glucocorticoid receptor (GR) binding site encompassing a CpG at position -1,420, and Sp1 binding at CpG methylation site -1,224. Methylation at -1,420 was strongly correlated with methylation at -1,439, a CpG site that is dependent upon the G-allele of rs6311 at position -1,438. SEM revealed a strong negative interaction between E47 and GR binding (in conjunction with cortisol level) on HTR2A expression. This study suggests that the promoter polymorphism (rs6311) can affect both transcription factor binding and promoter methylation, and this along with an individual’s stress response can impact the rate of HTR2A transcription in a genotype and methylation-dependent manner. This study can serve as an example for deciphering the molecular determinants of transcriptional regulation of major genes of medical importance by integrating functional genomics and SEM approaches. Confirmation in an independent study population is required.

Source: Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS. Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association. Neuromolecular Med. 2011 Mar;13(1):66-76. doi: 10.1007/s12017-010-8138-2. Epub 2010 Oct 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044825/ (Full article)

Gut inflammation in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms the pathology of which is incompletely understood.

Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS-related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder’s pathogenesis.

Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease.

In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut. If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder.

For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.

Source: Lakhan SE, Kirchgessner A. Gut inflammation in chronic fatigue syndrome. Nutr Metab (Lond). 2010 Oct 12;7:79. doi: 10.1186/1743-7075-7-79. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964729/ (Full article)

Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity

Abstract:

BACKGROUND: The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).

METHODS: Female patients (n = 15) and controls (n = 15) performed a cardiopulmonary exercise test (CPET) by cycling at a continuously increased work rate till maximal exertion. The CPET was repeated 24 h later. Before the tests, blood was taken for the isolation of peripheral blood mononuclear cells (PBMC), which were processed in a special way to preserve their oxidative phosphorylation, which was tested later in the presence of ADP and phosphate in permeabilized cells with glutamate, malate and malonate plus or minus the complex I inhibitor rotenone, and succinate with rotenone plus or minus the complex II inhibitor malonate in order to measure the ATP production via Complex I and II, respectively. Plasma CK was determined as a surrogate measure of a decreased oxidative phosphorylation in muscle, since the previous finding that in a group of patients with external ophthalmoplegia the oxygen consumption by isolated muscle mitochondria correlated negatively with plasma creatine kinase, 24 h after exercise.

RESULTS: At both exercise tests the patients reached the anaerobic threshold and the maximal exercise at a much lower oxygen consumption than the controls and this worsened in the second test. This implies an increase of lactate, the product of anaerobic glycolysis, and a decrease of the mitochondrial ATP production in the patients. In the past this was also found in patients with defects in the mitochondrial oxidative phosphorylation. However the oxidative phosphorylation in PBMC was similar in CFS/ME patients and controls. The plasma creatine kinase levels before and 24 h after exercise were low in patients and controls, suggesting normality of the muscular mitochondrial oxidative phosphorylation.

CONCLUSION: The decrease in mitochondrial ATP synthesis in the CFS/ME patients is not caused by a defect in the enzyme complexes catalyzing oxidative phosphorylation, but in another factor.

TRIAL REGISTRATION: CLINICAL TRIALS REGISTRATION NUMBER: NL16031.040.07.

Source: Vermeulen RC, Kurk RM, Visser FC, Sluiter W, Scholte HR. Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med. 2010 Oct 11;8:93. doi: 10.1186/1479-5876-8-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964609/ (Full article)

Current status of xenotropic murine leukemia virus-related retrovirus in chronic fatigue syndrome and prostate cancer: reach for a scorecard, not a prescription pad

Xenotropic murine leukemia virus-related retrovirus (XMRV) is a newly discovered member of the gammaretrovirus genus of retroviruses, which has been recently associated with 2 human disorders, prostate cancer and chronic fatigue syndrome [1]. Since it was first reported in 2006, XMRV has been intensely investigated, but no clear picture of prevalence, geographic distribution, or disease association has emerged. In this issue of the Journal, 3 studies shed new light on the presence of XMRV in human populations.

You can read the rest of this comment here: http://jid.oxfordjournals.org/content/202/10/1463.long

Comment on:

Detection of xenotropic murine leukemia virus-related virus in normal and tumor tissue of patients from the southern United States with prostate cancer is dependent on specific polymerase chain reaction conditions. [J Infect Dis. 2010]

Failure to detect xenotropic murine leukemia virus-related virus in blood of individuals at high risk of blood-borne viral infections. [J Infect Dis. 2010]

Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions. [J Infect Dis. 2010]

Source: Kearney M, Maldarelli F. Current status of xenotropic murine leukemia virus-related retrovirus in chronic fatigue syndrome and prostate cancer: reach for a scorecard, not a prescription pad. J Infect Dis. 2010 Nov 15;202(10):1463-6. doi: 10.1086/657169. Epub 2010 Oct 11. http://jid.oxfordjournals.org/content/202/10/1463.long (Full article)