Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by tiredness, difficulty in concentration and memory, and concomitant skeletal and muscular pain, thus affecting both mental and physical domains. The pathogenesis of chronic fatigue syndrome is multifactorial and involves increased oxido-nitrosative stress along with generation of pro-inflammatory cytokines such as TNF-α.

In the present study chronic fatigue was produced in rats by plunging a load of 10 ± 2% body weight and subjecting them to forced swim inside a rectangular jar daily for 28 days. Endurance capacity and post-swim fatigue were assessed on 1st, 7th, 14th, 21st and 28th days. EGCG was administered daily by oral gavage 30 min before forced swim session. On the 29th day, after assessment of various behavioral parameters, blood was collected through tail vein, and animals were sacrificed to harvest the brains, spleens and thymus.

Chronic fatigue group exhibited significant behavioral alterations along with enhanced oxido-nitrosative stress and serum TNF-α level as compared to naive group. Chronic treatment with EGCG restored all the behavioral and biochemical alterations associated with chronic fatigue syndrome. The present study signifies the therapeutic potential of EGCG for the treatment of chronic fatigue syndrome.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Sachdeva AK, Kuhad A, Chopra K. Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull. 2011 Oct 10;86(3-4):165-72. doi: 10.1016/j.brainresbull.2011.06.007. Epub 2011 Jul 28. https://www.ncbi.nlm.nih.gov/pubmed/21821105

 

Autonomic symptoms at baseline and following infectious mononucleosis in a prospective cohort of adolescents

Chronic fatigue syndrome (CFS) is a complex condition involving fatigue and musculoskeletal and cognitive symptoms. Six, 12, and 24 months following monospot-positive acute infectious mononucleosis (IM), 13%, 7%, and 4%, respectively, of adolescents met criteria for CFS.1 As part of their evaluation at baseline and 6, 12, and 24 months following IM, adolescents diagnosed with CFS and recovered controls completed questionnaires regarding autonomic symptoms.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896070/

 

Source: Katz BZ, Stewart JM, Shiraishi Y, Mears CJ, Taylor R. Autonomic symptoms at baseline and following infectious mononucleosis in a prospective cohort of adolescents. Arch Pediatr Adolesc Med. 2011 Aug;165(8):765-6. doi: 10.1001/archpediatrics.2011.124. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896070/ (Full article)

 

Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Jerome KR, Diem K, Huang ML, Selke S, Corey L, Buchwald D.Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome. Diagn Microbiol Infect Dis. 2011 Sep;71(1):66-71. doi: 10.1016/j.diagmicrobio.2011.06.003. Epub 2011 Jul 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158821/ (Full article)

 

Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units

Abstract:

BACKGROUND AND OBJECTIVE: The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units.

PATIENTS AND METHODS: We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment.

RESULTS: A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment.

CONCLUSIONS: CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity.

Copyright © 2011 Elsevier España, S.L. All rights reserved.

Comment in: Chronic fatigue syndrome: current situation. [Rev Clin Esp. 2011]

 

Source: Ruiz E, Alegre J, García Quintana AM, Aliste L, Blázquez A, Fernández de Sevilla T. Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units. Rev Clin Esp. 2011 Sep;211(8):385-90. doi: 10.1016/j.rce.2011.02.013. Epub 2011 Jul 27. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21794854

 

Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or chronic fatigue syndrome (CFS) has been used to name a range of chronic conditions characterized by extreme fatigue and other disabling symptoms. Attempts to estimate the burden of disease have been limited by selection bias, and by lack of diagnostic biomarkers and of agreed reproducible case definitions. We estimated the prevalence and incidence of ME/CFS in three regions in England, and discussed the implications of frequency statistics and the use of different case definitions for health and social care planning and for research.

METHODS: We compared the clinical presentation, prevalence and incidence of ME/CFS based on a sample of 143,000 individuals aged 18 to 64 years, covered by primary care services in three regions of England. Case ascertainment involved: 1) electronic search for chronic fatigue cases; 2) direct questioning of general practitioners (GPs) on cases not previously identified by the search; and 3) clinical review of identified cases according to CDC-1994, Canadian and Epidemiological Case (ECD) Definitions. This enabled the identification of cases with high validity.

RESULTS: The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD. The overall estimated minimal yearly incidence was 0.015%. The highest rates were found in London and the lowest in East Yorkshire. All but one of the cases conforming to the Canadian criteria also met the CDC-1994 criteria, however presented higher prevalence and severity of symptoms.

CONCLUSIONS: ME/CFS is not uncommon in England and represents a significant burden to patients and society. The number of people with chronic fatigue who do not meet specific criteria for ME/CFS is higher still. Both groups have high levels of need for service provision, including health and social care. We suggest combining the use of both the CDC-1994 and Canadian criteria for ascertainment of ME/CFS cases, alongside careful clinical phenotyping of study participants. This combination if used systematically will enable international comparisons, minimization of bias, and the identification and investigation of distinct sub-groups of patients with possibly distinct aetiologies and pathophysiologies, standing a better chance of translation into effective specific treatments.

 

Source: Nacul LC, Lacerda EM, Pheby D, Campion P, Molokhia M, Fayyaz S, Leite JC, Poland F, Howe A, Drachler ML. Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care. BMC Med. 2011 Jul 28;9:91. doi: 10.1186/1741-7015-9-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170215/ (Full article)

 

Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging

Abstract:

OBJECTIVES: Impaired cardiac function has been confirmed in patients with chronic fatigue syndrome (CFS). Magnetic resonance cardiac tagging is a novel technique that assesses myocardial wall function in vivo. We hypothesized that patients with CFS may have impaired development and release of myocardial torsion and strain.

METHODS: Cardiac morphology and function were assessed using magnetic resonance imaging and cardiac tagging methodology in 12 CFS patients (Fukuda) and 10 matched controls.

RESULTS: Compared to controls, the CFS group had substantially reduced left ventricular mass (reduced by 23%), end-diastolic volume (30%), stroke volume (29%) and cardiac output (25%). Residual torsion at 150% of the end-systolic time was found to be significantly higher in the patients with CFS (5.3 ± 1.6°) compared to the control group (1.7 ± 0.7°, P = 0.0001). End-diastolic volume index correlated negatively with both torsion-to-endocardial-strain ratio (TSR) (r = -0.65, P = 0.02) and the residual torsion at 150% end-systolic time (r = -0.76, P = 0.004), so decreased end-diastolic volume is associated with raised TSR and torsion persisting longer into diastole. Reduced end-diastolic volume index also correlated significantly with increased radial thickening (r = -0.65, P = 0.03) and impaired diastolic function represented by the ratio of early to late ventricular filling velocity (E/A ratio, r = 0.71, P = 0.009) and early filling percentage (r = 0.73, P = 0.008).

CONCLUSION: Patients with CFS have markedly reduced cardiac mass and blood pool volumes, particularly end-diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls. The CFS group appeared to have a delay in the release of torsion.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Hollingsworth KG, Hodgson T, Macgowan GA, Blamire AM, Newton JL. Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging. J Intern Med. 2012 Mar;271(3):264-70. doi: 10.1111/j.1365-2796.2011.02429.x. Epub 2011 Aug 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627316/ (Full article)

 

In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome

Abstract:

BACKGROUND: Central sensitisation entails several top-down and bottom-up mechanisms, all contributing to the hyperresponsiveness of the central nervous system to a variety of inputs. In the late nineties, it was first hypothesised that chronic fatigue syndrome (CFS) is characterised by hypersensitivity of the central nervous system (i.e. central sensitisation). Since then, several studies have examined central sensitisation in patients with CFS. This study provides an overview of such studies.

MATERIALS AND METHODS: Narrative review.

RESULTS: Various studies showed generalised hyperalgesia in CFS for a variety of sensory stimuli, including electrical stimulation, mechanical pressure, heat and histamine. Various tissues are affected by generalised hyperalgesia: the skin, muscle tissue and the lungs. Generalised hyperalgesia in CFS is augmented, rather than decreased, following various types of stressors like exercise and noxious heat pain. Endogenous inhibition is not activated in response to exercise and activation of diffuse noxious inhibitory controls following noxious heat application to the skin is delayed.

CONCLUSIONS: The observation of central sensitisation in CFS is in line with our current understanding of CFS. The presence of central sensitisation in CFS corroborates with the presence of several psychological influences on the illness, the presence of infectious agents and immune dysfunctions and the dysfunctional hypothalamus-pituitary-adrenal axis as seen in these severely debilitated patients.

© 2011 The Authors. European Journal of Clinical Investigation

© 2011 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Nijs J, Meeus M, Van Oosterwijck J, Ickmans K, Moorkens G, Hans G, De Clerck LS. In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome. Eur J Clin Invest. 2012 Feb;42(2):203-12. doi: 10.1111/j.1365-2362.2011.02575.x. Epub 2011 Jul 27. https://www.ncbi.nlm.nih.gov/pubmed/21793823

 

Chronic fatigue syndrome: understanding a complex illness

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating illness that affects many people. It has been marred by controversy, from initial scepticism in the medical community about the existence of the condition itself to continuing disagreements–mainly between some patient advocacy groups on one side, and researchers and physicians on the other–about the name for the illness, its aetiology, its pathophysiology and the effectiveness of the few currently available treatments. The role of the CNS in the disease is central in many of these discussions. Nature Reviews Neuroscience asked four scientists involved in CFS research about their views on the condition, its causes and the future of research aimed at improving our understanding of this chronic illness.

 

Source: Holgate ST, Komaroff AL, Mangan D, Wessely S. Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci. 2011 Jul 27;12(9):539-44. doi: 10.1038/nrn3087. https://www.ncbi.nlm.nih.gov/pubmed/21792218

 

Myalgic encephalomyelitis: International Consensus Criteria

Abstract:

The label ‘chronic fatigue syndrome’ (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term ‘myalgic encephalomyelitis’ (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization’s International Classification of Diseases (ICD G93.3).

Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions.

The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

Comment in: A controversial consensus–comment on article by Broderick et al. [J Intern Med. 2012]

 

Source: Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles AC, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011 Oct;270(4):327-38. doi: 10.1111/j.1365-2796.2011.02428.x. Epub 2011 Aug 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427890/ (Full article)

 

The effect of homework compliance on treatment outcomes for participants with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

PURPOSE: This study examined the relationship between level of treatment engagement through completion of homework on treatment outcomes within nonpharmacological interventions for participants with ME/CFS.

METHOD: A sample of 82 participants with ME/CFS was randomly assigned to one of four nonpharmacological interventions. Each intervention involved 13 sessions over the course of 6 months. Change scores were computed for self-report measures taken at baseline and 12-month follow-up. Homework compliance was calculated as the percentage of completed assignments across the total number of sessions and grouped into three categories: minimum (0-25%), moderate (25.1-75%), or maximum (75.1-100%).

RESULTS: Findings revealed that after controlling for treatment condition, those who completed a maximum amount of homework had greater improvement on a number of self-report outcome measures involving role, social, and mental health functioning. There were no differential improvements in physical and fatigue functioning based on level of homework compliance.

IMPLICATIONS: Findings from this study suggest homework compliance can have a positive influence on some aspects of physical, social, and mental health functioning in participants with ME/CFS. It should be emphasized that these interventions do not cure this illness. The lack of significant changes in physical functioning and fatigue levels suggests a need for more multidisciplinary treatment approaches that can elicit improvement in these areas.

 

Source: Hlavaty LE, Brown MM, Jason LA. The effect of homework compliance on treatment outcomes for participants with myalgic encephalomyelitis/chronic fatigue syndrome. Rehabil Psychol. 2011 Aug;56(3):212-8. doi: 10.1037/a0024118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166212/ (Full article)