The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Abstract:

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms.

More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

 

Source: Morris G, Berk M, Walder K, Maes M. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol. 2016 May;53(4):2550-71. doi: 10.1007/s12035-015-9262-7. Epub 2015 Jun 17. https://www.ncbi.nlm.nih.gov/pubmed/26081141

 

Distinct plasma immune signatures in ME/CFS are present early in the course of illness

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness.

Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246).

Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

 

Source: Hornig M, Montoya JG, Klimas NG, Levine S, Felsenstein D, Bateman L, Peterson DL, Gottschalk CG, Schultz AF, Che X, Eddy ML, Komaroff AL, Lipkin WI. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Sci Adv. 2015 Feb;1(1). pii: e1400121. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465185/ (Full article)

 

National Institutes of Health Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

The National Institutes of Health (NIH) Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome was cosponsored by the NIH Office of Disease Prevention and the Trans-NIH Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Research Working Group. A multidisciplinary working group developed the agenda, and an Evidence-based Practice Center prepared an evidence report through a contract with the Agency for Healthcare Research and Quality to facilitate the discussion. During the 1.5-day workshop, invited experts discussed the body of evidence and attendees had the opportunity to comment during open discussions. After weighing evidence from the evidence report, expert presentations, and public comments, an unbiased, independent panel prepared a draft report that identified research gaps and future research priorities. The report was posted on the NIH Office of Disease Prevention Web site for 4 weeks for public comment.

 

Source: Green CR, Cowan P, Elk R, O’Neil KM, Rasmussen AL. National Institutes of Health Pathways to Prevention Workshop: Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ann Intern Med. 2015 Jun 16;162(12):860-5. doi: 10.7326/M15-0338. http://annals.org/aim/article/2322804/national-institutes-health-pathways-prevention-workshop-advancing-research-myalgic-encephalomyelitis (Full article)

 

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States.

PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs.

DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information.

STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments.

DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus.

DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence).

LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality.

CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

Comment in

 

Source: Smith ME, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, Fu R, Nelson HD. Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16;162(12):841-50. doi: 10.7326/M15-0114. http://annals.org/aim/article/2322801/treatment-myalgic-encephalomyelitis-chronic-fatigue-syndrome-systematic-review-national-institutes (Full article)

 

Comments

  • Ellen M Goudsmit 2016 Feb 12 05:56 a.m.

    Postscript 2016. The errors noted were rejected as inaccuracies by the editors and thus my comment (under Haney et al) was not published as a letter or correction. Example, they refused to accept that a trial discussed used two sets of criteria, not just the one listed. And if they had checked the reference given for the London criteria, they would have known that it does not give a list of authors. I was not named, so the citation is factually incorrect. I submit that this attitude to factual errors is inconsistent with good science.

  • Ellen M Goudsmit 2015 Jun 24 10:14 a.m.

    I’ve already noted some of the factual errors and misleading comments in this review online: http://annals.org/article.aspx?articleid=2322800

    Due to the word limit, I could not add that Haney et al named four individuals as authors of the London criteria for ME, despite the fact that their reference, the Westcare Report, did not [1]. The people listed in the review did not write the version published in the Westcare Report and this information has been in the public domain since 1994.

    I was also unable to point out that that Haney et al refer to clinical criteria (e.g., p. 834), when most of the case definitions they discussed were formulated for research.

    The omission of the new research criteria for classic ME is baffling as they have already been cited in the literature, most recently by Jason et al [2]. If people are going to make decisions about ME, or ME/CFS, they need to know what ME is. I suggest readers look online or access the original paper from 2009 [3].

    [1]. The UK Patient Organisations. “London Criteria”. In: Report from The National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Bristol: Westcare; 1994. Appendix B, Names, Definitions and Descriptions: p. 96-8. Available from: http://www.actionforme.org.uk/Resources/Action for ME/Documents/get-informed/national task force.pdf

    [2]. Jason, LA., Sunnquist, M., Brown, A and Reed, J. Defining essential features of myalgic encephalomyelitis and chronic fatigue syndrome. Journal of Human Behavior in the Social Environment, 2015, 25, 6, 657-674. Online 6th May. doi:10.1080/10911359.2015.1011256

    [3]. Goudsmit E, Shepherd C, Dancy CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33. Available from: http://shop.bps.org.uk/publications/publications-by-subject/health/health-psychology-update-vol-18-no-1-2009.html

    Alternatively see: http://www.foodsmatter.com/me_and_cfs/cfs_me_causes_general/articles/goudsmit-me-clinical entity-10-12.html

    Revised article (2014): http://www.axfordsabode.org.uk/me/mecrit2014.htm

  • This article was mentioned in a comment by Ellen M Goudsmit 2015 Jul 17 1:24 p.m.

    See:Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. [Ann Intern Med. 2015.]

  • Lily Chu 2016 Aug 24 04:39 a.m.

    In response to public comments, Dr. Smith and her colleagues have conducted sensitivity analyses on the data, assessing the impact of CBT and GET on various outcomes when only subjects fitting Oxford criteria are considered versus when subjects fitting non-Oxford case definitions (i.e. 1994 Fukuda) are considered. They concluded in an Addendum to the original report that:

    “Our sensitivity analysis would result in a downgrading of our strength of evidence on several outcomes which can be attributed to the decrease in power, dominance of one large trial, or lack of trials using criteria other than the Oxford (Sharpe, 1991) case definition for inclusion. Blatantly missing from this body of literature are trials evaluating effectiveness of interventions in the treatment of individuals meeting case definitions for ME or ME/CFS.”

    Almost all patients are diagnosed in the United States and most countries using the Fukuda criteria. The United Kingdom is the only region that uses the Oxford criteria on a regular basis. This means that clinicians need to be aware of low strength of evidence or the lack of evidence behind CBT and GET when considering this treatment for their ME/CFS patients.

    The full revised report may be read at: https://effectivehealthcare.ahrq.gov/ehc/products/586/2004/chronic-fatigue-report-160728.pdf

Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Abstract:

BACKGROUND: The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm.

PURPOSE: To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research.

DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists.

STUDY SELECTION: English-language studies describing methods of diagnosis of ME/CFS and their accuracy.

DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus.

DATA SYNTHESIS: Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability.

LIMITATIONS: Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations.

CONCLUSION: Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.

 

Source: Haney E, Smith ME, McDonagh M, Pappas M, Daeges M, Wasson N, Nelson HD. Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Jun 16;162(12):834-40. doi: 10.7326/M15-0443. http://annals.org/aim/article/2322800/diagnostic-methods-myalgic-encephalomyelitis-chronic-fatigue-syndrome-systematic-review-national (Full article)

Comments

  • Ellen M Goudsmit 2015 Dec 02

    Sad to note today that the journal chose to publish letters, favouring opinion above the correction of factual errors. How can science progress if editors collude in the perpetuation of inaccuracies and myths? Who will know that there ARE research criteria for ME as described by Ramsay? That there are helpful alternatives to CBT and GET?

    Postscript 2016. The editors decided not to publish the comment as a letter in the journal as they rejected the view that there were factual errors. Thus while I was not a co-author of the criteria cited in the article, and I’m not named in the reference given, listing me as a co-author is not a ‘factual error’ in their eyes. Nor is the claim that a trial I discussed selected patients using two sets of criteria, not just the one referred to in the article. In my view, this failure to correct errors and misleading information is inconsistent with good science.

  • Ellen M Goudsmit 2015 Jul 17

    As someone who has studied myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) since the 1980s, I appreciate the work completed by The National Institutes of Health Pathways to Prevention Workshops on what is now known as ME/CFS. Unfortunately, some of the information in the two reviews is inaccurate, incomplete and misleading (1,2). For example, in the report on diagnostic methods, the reviewers included the London criteria for ME but gave details in the table based on a version written by a layperson, rather than the four individuals cited in their reference (3). Moreover, they did not consider the updated criteria for ME (4), although one of the authors had emailed the panel on two separate occasions during the consultation phase to alert them to their existence.

    The second review (2) encourages further research on subgroups and outcomes other than fatigue and function but did not identify one of the few controlled studies which had employed such a design (5). For instance, in the Appendix, Table 1 lists the programme evaluated by Goudsmit and colleagues under ‘counseling and behavioural therapies’, and describes the treatment as ‘counseling’. It also states that patients were selected using the Oxford criteria, that the duration of follow-up was six months and that the outcomes were function and fatigue.

    In fact, the trial evaluated a physician-led multi-component programme comprising medical care, information on the illness, diet and relaxation, as well as advice on activity management and some counselling (5). It was conducted in the naturalistic setting of an NHS hospital clinic, patients were diagnosed using criteria for post-viral fatigue syndrome as well as the Oxford criteria, and data were available for a number of symptoms including cognitive impairment, as well as other variables. Fatigue improved as noted in the review but the latter did not convey that 82% of the patients rated themselves as ‘better’, that 23% were well enough to be discharged at six months and that the improvements were maintained at 1 year. Given the missing details, the study’s rating as ‘poor’ is understandable.

    The reviewers concluded that “more definitive studies comparing participants meeting different case definitions, including ME… are needed to fill research gaps”. It was therefore disappointing that they did not recognise the positive aspects of a study that used a different case definition and assessed a range of symptoms, not just fatigue.

    1. Haney E, Smith MEB, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Diagnostic methods for myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162: 834-40. [PMID: 26075754] doi:10.7326/M15-0443
    2. Smith MEB, Haney E, McDonagh M, Pappas M, Daeges M, Wasson N, et al. Treatment of myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162:841-
    3. [PMID: 26075755] doi:10.7326/M15-0114
    4. Dowsett E, Goudsmit E, Macintyre A, Shepherd C. London Criteria for myalgic encephalomyelitis. In: Report from The National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Westcare. 1994. 96-98. Available from: http://www.actionforme.org.uk/Resources/Action for ME/Documents/get-informed/national task force.pdf
    5. Goudsmit E, Shepherd C, Dancy CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33. Available from: http://shop.bps.org.uk/publications/publications-by-subject/health/health-psychology-update-vol-18-no-1-2009.html
    6. Goudsmit EM, Ho-Yen DO, Dancey CP. Learning to cope with chronic illness. Efficacy of a multi-component treatment for people with chronic fatigue syndrome. Patient Educ Couns. 2009;77:231–6. [PMID: 19576714 ] doi:10.1016/j.pec.2009.05.015

    Ellen M Goudsmit PhD FBPsS

    Comment also on Annals of Internal Medicine website under Haney et al.

 

Prediction of complex human diseases from pathway-focused candidate markers by joint estimation of marker effects: case of chronic fatigue syndrome

Abstract:

BACKGROUND: The current practice of using only a few strongly associated genetic markers in regression models results in generally low power in prediction or accounting for heritability of complex human traits.

PURPOSE: We illustrate here a Bayesian joint estimation of single nucleotide polymorphism (SNP) effects principle to improve prediction of phenotype status from pathway-focused sets of SNPs. Chronic fatigue syndrome (CFS), a complex disease of unknown etiology with no laboratory methods for diagnosis, was chosen to demonstrate the power of this Bayesian method. For CFS, such a genetic predictive model in combination with clinical evidence might lead to an earlier diagnosis than one based solely on clinical findings.

METHODS: One of our goals is to model disease status using Bayesian statistics which perform variable selection and parameter estimation simultaneously and which can induce the sparseness and smoothness of the SNP effects. Smoothness of the SNP effects is obtained by explicit modeling of the covariance structure of the SNP effects.

RESULTS: The Bayesian model achieved perfect goodness of fit when tested within the sampled data. Tenfold cross-validation resulted in 80% accuracy, one of the best so far for CFS in comparison to previous prediction models. Model reduction aspects were investigated in a computationally feasible manner. Additionally, genetic variation estimates provided by the model identified specific genetic markers for their biological role in the disease pathophysiology.

CONCLUSIONS: This proof-of-principle study provides a powerful approach combining Bayesian methods, SNPs representing multiple pathways and rigorous case ascertainment for accurate genetic risk prediction modeling of complex diseases like CFS and other chronic diseases.

 

Source: Bhattacharjee M, Rajeevan MS, Sillanpää MJ. Prediction of complex human diseases from pathway-focused candidate markers by joint estimation of marker effects: case of chronic fatigue syndrome. Hum Genomics. 2015 Jun 11;9:8. doi: 10.1186/s40246-015-0030-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479222/ (Full article)

 

The theoretical basis for chronic fatigue syndrome from bladder meridian of foot-taiyang

Abstract:

The bladder meridian of foot-taiyang is considered as key of six meridians and the yang of the yang, which is the pivot of transportation for qi and blood in the meridians and zang-fu. The running route and treatment characteristic of bladder meridian is closely related with chronic fatigue syndrome (CFS). The bladder meridian belongs to brain and connects with governor vessel, which has a close relationship with zang-fu function, quality of sleep and fatigue. Besides, the running route of bladder meridian is highly consistent with the surface projections of important anatomical structures such as muscle, nerve and sympathetic trunk, etc. Therefore, regulating the meridian-qi of bladder meridian can harmonize five-zang and calm the mind, but also effectively relieve physical and mental fatigue in CFS.

 

Source: Yao F, Zhao Y, Jiang S, Fang M. The theorotical basis for chronic fatigue syndrome from bladder meridian of foot-taiyang. Zhongguo Zhen Jiu. 2015 Mar;35(3):295-8. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/26062210

 

Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study

Abstract:

OBJECTIVE: Patients with myalgic encephalomyelitis/chronic fatigue syndrome experience cognitive difficulties. The aim of this study was to evaluate the effect of computerized training on working memory in this syndrome.

DESIGN: Non-randomized (quasi-experimental) study with no-treatment control group and non-equivalent dependent variable design in a myalgic encephalomyelitis/chronic fatigue syndrome-cohort.

SUBJECTS: Patients with myalgic encephalomyelitis/chronic fatigue syndrome who participated in a 6-month outpatient rehabilitation programme were included in the study. Eleven patients who showed signs of working memory deficit were recruited for additional memory training and 12 patients with no working memory deficit served as controls.

METHODS: Cognitive training with computerized working memory tasks of increasing difficulty was performed 30-45 min/day, 5 days/week over a 5-week period. Short-term and working memory tests (Digit Span – forward, backward, total) were used as primary outcome measures. Nine of the 11 patients were able to complete the training.

RESULTS: Cognitive training increased working memory (p = 0.003) and general attention (p = 0.004) to the mean level. Short-term memory was also improved, but the difference was not statistically significant (p = 0.052) vs prior training. The control group did not show any significant improvement in primary outcome measures.

CONCLUSION: Cognitive training may be a new treatment for patients with myalgic encephalomyelitis/chronic fatigue syndrome.

 

Source: Maroti D, Westerberg AF, Saury JM, Bileviciute-Ljungar I. Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study. J Rehabil Med. 2015 Aug 18;47(7):665-8. doi: 10.2340/16501977-1976. https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-1976 (Full article)

 

Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Abstract:

BACKGROUND: Abnormal immune function is often an underlying component of illness pathophysiology and symptom presentation. Functional and phenotypic immune-related alterations may play a role in the obscure pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The objective of this study was to investigate the functional ability of innate and adaptive immune cells in moderate and severe CFS/ME patients. The 1994 Fukuda criteria for CFS/ME were used to define CFS/ME patients. CFS/ME participants were grouped based on illness severity with 15 moderately affected (moderate) and 12 severely affected (severe) CFS/ME patients who were age and sex matched with 18 healthy controls. Flow cytometric protocols were used for immunological analysis of dendritic cells, monocytes and neutrophil function as well as measures of lytic proteins and T, natural killer (NK) and B cell receptors.

RESULTS: CFS/ME patients exhibited alterations in NK receptors and adhesion markers and receptors on CD4(+)T and CD8(+)T cells. Moderate CFS/ME patients had increased CD8(+) CD45RA effector memory T cells, SLAM expression on NK cells, KIR2DL5(+) on CD4(+)T cells and BTLA4(+) on CD4(+)T central memory cells. Moderate CFS/ME patients also had reduced CD8(+)T central memory LFA-1, total CD8(+)T KLRG1, naïve CD4(+)T KLRG1 and CD56(dim)CD16(-) NK cell CD2(+) and CD18(+)CD2(+). Severe CFS/ME patients had increased CD18(+)CD11c(-) in the CD56(dim)CD16(-) NK cell phenotype and reduced NKp46 in CD56(bright)CD16(dim) NK cells.

CONCLUSIONS: This research accentuated the presence of immunological abnormalities in CFS/ME and highlighted the importance of assessing functional parameters of both innate and adaptive immune systems in the illness.

 

Source: Hardcastle SL, Brenu EW, Johnston S, Nguyen T, Huth T, Wong N, Ramos S, Staines D, Marshall-Gradisnik S. Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). BMC Immunol. 2015 Jun 2;16:35. doi: 10.1186/s12865-015-0101-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450981/ (Full article)

 

Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Toward An Empirical Case Definition

Abstract:

Current case definitions of Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS) have been based on consensus methods, but empirical methods could be used to identify core symptoms and thereby improve the reliability. In the present study, several methods (i.e., continuous scores of symptoms, theoretically and empirically derived cut off scores of symptoms) were used to identify core symptoms best differentiating patients from controls. In addition, data mining with decision trees was conducted. Our study found a small number of core symptoms that have good sensitivity and specificity, and these included fatigue, post-exertional malaise, a neurocognitive symptom, and unrefreshing sleep. Outcomes from these analyses suggest that using empirically selected symptoms can help guide the creation of a more reliable case definition.

 

Source: Jason LA, Kot B, Sunnquist M, Brown A, Evans M, Jantke R, Williams Y, Furst J, Vernon SD. Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Toward An Empirical Case Definition. Health Psychol Behav Med. 2015;3(1):82-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443921/ (Full article)