No detectable XMRV in subjects with chronic fatigue syndrome from Quebec

Abstract:

We investigated the presence of XMRV in a cohort of Quebec patients with chronic fatigue syndrome (CFS). DNA was purified from activated peripheral blood mononuclear cells (PBMCs) and PCR was used to detect XMRV gag and env in 72 patients. Anti-XMRV antibodies were searched in sera of 62 patients by Western blot analysis. Attempts to detect XMRV antigens was made, using immunofluorescence with Gag anti-p30 antiserum on activated PBMC from 50 patients. Plasma viremia was measured by RT-PCR on 9 subjects. Finally, detection of infectious virus in 113 CFS subjects was made by co-culture of PHA+IL-2 activated PBMC with human LNCaP carcinoma cells, and by infecting the same susceptible cells with plasma, using a reverse transcriptase (RT) assay as a readout in both experiments. No detection of XMRV footprints nor infectious virus was detected with any of the approaches, in any of the tested individuals.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Cool M, Bouchard N, Massé G, Laganière B, Dumont A, Hanna Z, Phaneuf D, Morisset R, Jolicoeur P. No detectable XMRV in subjects with chronic fatigue syndrome from Quebec. Virology. 2011 Nov 10;420(1):66-72. doi: 10.1016/j.virol.2011.08.018. Epub 2011 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/21925693

 

The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database

Abstract:

BACKGROUND: Few studies have investigated factors associated with discontinuation of employment in patients with CFS/ME or quantified its impact on productivity.

METHODS: We used patient-level data from five NHS CFS/ME services during the period 01/04/2006-31/03/2010 collated in the UK CFS/ME National Outcomes Database. We used logistic regression to identify factors associated with discontinuation of employment. We estimated UK-wide productivity costs using patient-level data on duration of illness before assessment by a CFS/ME service, duration of unemployment, age, sex and numbers of patients, in conjunction with Office for National Statistics income and population data.

RESULTS: Data were available for 2,170 patients, of whom 1,669 (76.9%) were women. Current employment status was recorded for 1,991 patients (91.8%), of whom 811 patients (40.7%) were currently employed and 998 (50.1%) had discontinued their employment “because of fatigue-related symptoms”. Older age, male sex, disability, fatigue, pain, and duration of illness were associated with cessation of employment. In a multivariable model, age, male sex, and disability remained as independent predictors. Total productivity costs among the 2,170 patients due to discontinuation of employment in the years preceding assessment by a specialist CFS/ME service (median duration of illness=36 months) were £49.2 million. Our sample was equivalent to 4,424 UK adults accessing specialist services each year, representing productivity costs to the UK economy of £102.2 million. Sensitivity analyses suggested a range between £75.5-£128.9 million.

CONCLUSIONS: CFS/ME incurs huge productivity costs amongst the small fraction of adults with CFS/ME who access specialist services.

 

Source: Collin SM, Crawley E, May MT, Sterne JA, Hollingworth W; UK CFS/ME National Outcomes Database. Collaborators (8) The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database. BMC Health Serv Res. 2011 Sep 15;11:217. doi: 10.1186/1472-6963-11-217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184626/ (Full article)

 

Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome

Abstract:

BACKGROUND: There is no consistent evidence of specific gene(s) or molecular pathways that contribute to the pathogenesis, therapeutic intervention or diagnosis of chronic fatigue syndrome (CFS). While multiple studies support a role for genetic variation in CFS, genome-wide efforts to identify associated loci remain unexplored. We employed a novel convergent functional genomics approach that incorporates the findings from single-nucleotide polymorphism (SNP) and mRNA expression studies to identify associations between CFS and novel candidate genes for further investigation.

METHODS: We evaluated 116,204 SNPs in 40 CFS and 40 nonfatigued control subjects along with mRNA expression of 20,160 genes in a subset of these subjects (35 CFS subjects and 27 controls) derived from a population-based study.

RESULTS: Sixty-five SNPs were nominally associated with CFS (p<0.001), and 165 genes were differentially expressed (≥4-fold; p≤0.05) in peripheral blood mononuclear cells of CFS subjects. Two genes, glutamate receptor, ionotropic, kinase 2 (GRIK2) and neuronal PAS domain protein 2 (NPAS2), were identified by both SNP and gene expression analyses. Subjects with the G allele of rs2247215 (GRIK2) were more likely to have CFS (p=0.0005), and CFS subjects showed decreased GRIK2 expression (10-fold; p=0.015). Subjects with the T allele of rs356653 (NPAS2) were more likely to have CFS (p=0.0007), and NPAS2 expression was increased (10-fold; p=0.027) in those with CFS.

CONCLUSION: Using an integrated genomic strategy, this study suggests a possible role for genes involved in glutamatergic neurotransmission and circadian rhythm in CFS and supports further study of novel candidate genes in independent populations of CFS subjects.

Copyright © 2011 S. Karger AG, Basel.

 

Source: Smith AK, Fang H, Whistler T, Unger ER, Rajeevan MS. Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome. Neuropsychobiology. 2011;64(4):183-94. doi: 10.1159/000326692. Epub 2011 Sep 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701888/ (Full article)

 

Long-term sickness absence among patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is associated with high levels of occupational disability. Consecutive out-patients at a chronic fatigue syndrome treatment service were studied for associations between occupational status, symptom severity and cognitive and behavioural responses to symptoms. All patients had high symptom levels; however, those on long-term sickness absence had significantly more physical fatigue (β = 0.098, P<0.05) and worse sleep (β = 0.075, P<0.05). Patients with long-term sickness absence also demonstrated more embarrassment avoidance cognitions (β = 0.086, P<0.05) and avoidance resting behavioural responses (β = 0.078, P<0.05). Identifying and addressing avoidance behaviours and cognitions regarding embarrassment in interventions may enhance the chances of individuals returning to work.

 

Source: Knudsen AK, Henderson M, Harvey SB, Chalder T. Long-term sickness absence among patients with chronic fatigue syndrome. Br J Psychiatry. 2011 Nov;199(5):430-1. doi: 10.1192/bjp.bp.110.082974. Epub 2011 Sep 8. http://bjp.rcpsych.org/content/199/5/430.long (Full article)

 

An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Kindling might represent a heuristic model for understanding the etiology of Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Kindling occurs when an organism is exposed repeatedly to an initially sub-threshold stimulus resulting in hypersensitivity and spontaneous seizure-like activity. Among patients with ME/CFS, chronically repeated low-intensity stimulation due to an infectious illness might cause kindling of the limbic-hypothalamic-pituitary axis. Kindling might also occur by high-intensity stimulation (e.g., brain trauma) of the limbic-hypothalamic-pituitary axis. Once this system is charged or kindled, it can sustain a high level of arousal with little or no external stimulus and eventually this could lead to hypocortisolism. Seizure activity may spread to adjacent structures of the limbic-hypothalamic-pituitary axis in the brain, which might be responsible for the varied symptoms that occur among patients with ME/CFS. In addition, kindling may also be responsible for high levels of oxidative stress, which has been found in patients with ME/CFS.

 

Source: Jason LA, Sorenson M, Porter N, Belkairous N. An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Neurosci Med. 2011 Mar 1;2(1):14-27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166239/ (Full article)

 

Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running

Abstract:

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, Kai Xin San (KXS), composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart.

AIM OF THE STUDY: The present study investigated the effect of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running.

MATERIALS AND METHODS: Seventy two healthy adult male Kunming mice were randomly divided into six groups: home cage control group, CFS group, CFS group with Modafinil treatment at 13 mg/kg/d doge, KXS treatment at 175 mg/kg/d, 350 mg/kg/d and 700 mg/kg/d doge. CFS mice were induced by forced wheel running with higher speed for 4 weeks and then taken an exhausted exercise. The biochemical parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and muscle lactic acid (MLA) were determined by using commercially available kits. The splenocytes proliferation from mice was examined by MTT method. The levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were determined by ELISA.

RESULTS: CFS mice with KXS administration exhibited less electric shock time when compared with CFS group without drug treatment. The effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an increase in T, LG and MG levels. CFS mice with KXS could improve the proliferation of splenocytes compared with CFS group without drug treatment. The cultured splenocytes from CFS mice without KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage control mice. The cultured splenocytes of CFS mice with KXS supplementation produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with CFS group without drug treatment.

CONCLUSIONS: The results of this preliminary study provide evidence that KXS could ameliorate CFS by affecting the physiological markers for fatigue. This study also supported the use of KXS against CFS by improving the proliferation of splenocytes from CFS mice and modulating the disturbance of cytokines induced by CFS.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

 

Source: Cao Y, Hu Y, Liu P, Zhao HX, Zhou XJ, Wei YM. Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue syndrome mice induced by forced wheel running. J Ethnopharmacol. 2012 Jan 6;139(1):19-25. doi: 10.1016/j.jep.2011.08.030. Epub 2011 Aug 22. https://www.ncbi.nlm.nih.gov/pubmed/21884774

 

Myalgia and Fatigue: Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes

Excerpt:

Muscle fatigue and pain are among the most common complaints at emergency rooms and clinics across the country. Fatigue and pain are often acute, remitting spontaneously or appearing to be attenuated by a variety of drugs and treatment modalities.

In spite of these remissions, popular magazines (e.g., Time) estimate that each year Americans spend over $30 billion on herbal remedies and $50 billion on alternative therapies to treat symptoms that include muscle pain and fatigue. These statistics indicate that even acute muscle pain and fatigue are serious health problems that are not adequately addressed by current medical practice. Occasionally, muscle pain and fatigue take on a chronic nature, leading to syndromes including chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS)—devastating conditions characterized by continuing, debilitating fatigue, which is made worse by even mild exercise in the case of CFS and by chronic widespread pain (CWP) with a particular emphasis in the muscles, which can prevent most or all activities in the case of FMS.

Both of these conditions are frequently associated with each other and with a variety of other illnesses, such as temporomandibular disorder (TMD), irritable bowel syndrome (IBS), and multiple chemical sensitivity. These syndromes destroy lives, respond poorly to current treatment strategies, and can lead to exhaustion of the financial resources of afflicted patients. Together, these disorders affect 7 to 20 million people in the United States each year, as reported by various authorities (Reeves et al. 2007). Clearly, patients with these syndromes deserve a concerted research effort to understand, treat, and eventually cure these illnesses. In contrast to cutaneous pain, which has been thoroughly studied and is comparatively well understood, the molecular mechanisms for muscle pain are still unknown.

Even more enigmatic is the symptom of debilitating fatigue. Mosso, in his compendious volume on the subject a century ago, remarked that all cultures seem to have just one word for fatigue (Mosso 1904). Yet fatigue describes many conditions, including failure of muscle fibers to shorten normally, deficient motor command signals, feelings of tiredness, heaviness, pressure, and weakness from muscles, and a feeling of mental fatigue that impedes concentration and performance of conceptual tasks.

The subject of most physiological investigations of fatigue has been voluntary muscle contraction. Decreased function causing failure of voluntary muscle contraction can occur at all levels of the neuromuscular system, including the motor cortex, signaling to motoneurons, motoneuron signals to the muscle, excitation-contraction coupling in the muscle, and actin-myosin filament interactions. However, the most common failure is a decrease in the motor command signal from the motor cortex (see recent reports and reviews by Bellinger et al. 2008; Gibson et al. 2003; Noakes et al. 2005; St Clair and Noakes 2004).

A recent review suggests that failures in voluntary muscle contraction are most often caused by a central comparator that integrates homeostatic inputs from many physiological systems and shuts down motor commands when energy resources are threatened (Noakes 2007). One of the homeostatic inputs is suggested to “originate from a difference between subconscious representations of baseline physiological homeostatic state and the state of physiological activity induced by physical activity, which creates a second order representation which is perceived by consciousnessproducing structures as the sensation of fatigue” (Gibson et al. 2003, page 174).

We suggest that there is a simpler sensation of fatigue that is triggered by inputs from specific receptors that are sensitive to metabolites produced by muscle contraction. We further propose that this elementary sensation is transduced, conducted, and perceived within a unique sensory system with properties analogous to other sensory modalities such as pain. We call it the “sensation of muscle fatigue.”

Copyright © 2010 by Taylor and Francis Group, LLC.

 

Source: Light AR, Vierck CJ, Light KC. Myalgia and Fatigue: Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes. In: Kruger L, Light AR, editors. Translational Pain Research: From Mouse to Man. Boca Raton, FL: CRC Press/Taylor & Francis; 2010. Chapter 11. Frontiers in Neuroscience. https://www.ncbi.nlm.nih.gov/books/NBK57253/ (Full chapter)

 

The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME)

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and children can be severely affected attending little or no school for extended periods. There are no studies quantifying the financial impact of having a child with CFS/ME and there is little information of the impact on parental mood.

METHODS: Forty mothers of children with CFS/ME from a regional specialist CFS/ME service completed inventories to assess their psychological well-being (Hospital Anxiety and Depression Scale, General Health Questionnaire-12) loss of earnings and increased expenditure. In addition, eight mothers took part in a semi-structured qualitative interview.

RESULTS: Most parents of children with CFS/ME experience loss of monthly income (mean = £247) and increase in monthly expenditure (mean = £206). Twenty-eight (72%) mothers were above the cut-off for the General Health Questionnaire-12 compared with 20% in the healthy population (95% CI 55, 85, P < 0.001) suggesting they probably have a mental health problem. This may be explained by the qualitative interviews where mothers described five areas contributing to poor parental health: lack of understanding from others; marital tension; concern about their child’s distress; concern about the impact on siblings and emotional distress causing physical symptoms.

CONCLUSIONS: The majority of families of children with CFS/ME experience decreased income and increased expenditure with a marked impact on maternal psychological health. Clinicians need to be aware of this to provide appropriate support to families who care for children with CFS/ME.

© 2011 Blackwell Publishing Ltd.

 

Source: Missen A, Hollingworth W, Eaton N, Crawley E. The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME). Child Care Health Dev. 2012 Jul;38(4):505-12. doi: 10.1111/j.1365-2214.2011.01298.x. Epub 2011 Sep 1. https://www.ncbi.nlm.nih.gov/pubmed/21880054

 

Small wins matter in advocacy movements: giving voice to patients

Abstract:

In this article, the various players are delineated in a story of a contested illness and patient advocacy, played out within the corridors of federal power. It is suggested that the mistreatment and negative attitudes that health care providers and others have towards those with chronic fatigue syndrome (CFS) is possibly due to the social construction of this illness as being a “Yuppie flu” disease. Institutional factors are identified that created these norms and attributions, as well as the multiple stakeholders and constituent groups invested in exerting pressure on policy makers to effect systemic change. This article also provides examples of how the field of Community Psychology, which is fundamentally committed to/based on listening to and giving voice to patients, is broadly relevant to patient activism communities. This approach focused, over time, on epidemiological studies, the name, the case definition, and ultimately the change in CFS leadership at the Centers for Disease Control and Prevention. Keys to this “small wins” approach were coalition building, use of “oppositional experts” (professionals in the scientific community who support patient advocacy goals) to challenge federal research, and taking advantage of developing events/shifts in power. Ultimately, this approach can result in significant scientific and policy gains, and changes in medical and public perception of an illness.

 

Source: Jason LA. Small wins matter in advocacy movements: giving voice to patients. Am J Community Psychol. 2012 Jun;49(3-4):307-16. doi: 10.1007/s10464-011-9457-7. https://www.ncbi.nlm.nih.gov/pubmed/21858612

 

Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort

Abstract:

BACKGROUND: Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.

AIMS: To examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.

METHOD: Data were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.

RESULTS: Adjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16-3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00-2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09-2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.

CONCLUSIONS: This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.

Comment in: Childhood sexual abuse and chronic fatigue syndrome. [Br J Psychiatry. 2012]

 

Source: Clark C, Goodwin L, Stansfeld SA, Hotopf M, White PD. Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort. Br J Psychiatry. 2011 Oct;199(4):323-9. doi: 10.1192/bjp.bp.110.083956. Epub 2011 Aug 18. http://bjp.rcpsych.org/content/199/4/323.long (Full article)