Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: Results of supervised learning techniques applied on clinical and inflammatory data

Maes Clinics @ TRIA, Piyavate Hospital, 998 Rimklongsamsen Road, Bangkok 10310, Thailand.
Psychiatry Research (Impact Factor: 2.47). 04/2012; 200(2-3). DOI: 10.1016/j.psychres.2012.03.031
Source: PubMed


There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM).

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Available from: Frank N.M. Twisk, Jun 12, 2015
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    • "Especially the expression of CD38 was highly increased on CD8+ T cells of patients with ME/CFS. Our findings in part replicate the findings byLanday et al. (1991)findings show that CD8+, but not CD4+, cells are activated in ME/CFS, but not CF, findings which support our view that both groups are immunologically different (Maes et al. 2012b). Nevertheless, no significant associations could be found between the increased expression of CD38 and HLA-DR on CD8+ T cells and activation of other immune-inflammatory and O&NS pathways. "
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    ABSTRACT: Background: There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS. Methods: Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40). Results: The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin. Conclusions: The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.
    Full-text · Article · Jan 2016 · Neuro endocrinology letters
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    • "In contrast to the CDC, ICC and SEID criteria (Fukuda et al. 1994; Carruthers et al. 2011; IOM 2015), which proposed criteria based on " clinical expertise " or " consensus among clinicians and scientists " we have constructed our algorithms based on multivariate pattern recognition methods and have externally validated the new criteria by means of neuro-IO&NS biomarkers. Needless to say that case definitions which are not validated by statistical tests are not valid (Maes et al. 2012b). New case definitions should be based on pattern recognition analyses performed on symptom prevalence and biomarker data rather than consensus declarations or statements. "
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    ABSTRACT: Background: Chronic fatigue syndrome (CFS) or Myalgic Encephalomyelitis (ME) is characterized by neuro-psychiatric (e.g. depression, irritability, sleep disorders, autonomic symptoms and neurocognitive defects) and physio-somatic (fatigue, a flu-like malaise, hyperalgesia, irritable bowel, muscle pain and tension) symptoms. New ME/CFS case definitions based on consensus criteria among experts are largely inadequate, e.g. those of the US Institute of Medicine . Objectives: The aim of the present study was to delineate a new case definition of ME/CFS based on pattern recognition methods and using neuro-immune, inflammatory, oxidative and nitrosative stress (neuro-IO&NS) biomarkers as external validating criteria. Methods: We measured the 12-item Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale in 196 subjects with CFS (CDC criteria) and 83 with chronic fatigue. The "Neuro-IO&NS" biomarkers were: IgM / IgA responses against LPS of gut commensal bacteria (leaky gut), IgM responses to O&NS modified neoepitopes, autoimmunity to serotonin, plasma interleukin-1 (IL-1) and serum neopterin. Results: Cluster analysis showed the presence of two well-separated clusters with highly significant differences in symptoms and biomarkers. The cluster with higher scores on all FF items was externally validated against all IO&NS biomarkers and therefore this diagnostic group was labeled "Neuro-IO&NS Fatigue" or "Neuro-Inflammatory and Oxidative Fatigue" (NIOF). An algorithm was constructed which defined NIOF as chronic fatigue and 4 or more of the following 6 symptoms: muscle tension, memory disturbances, sleep disorders, irritable bowel, headache or a flu-like malaise. There was a significant overlap between NIOF and CFS although NIOF criteria were much more restrictive. Factor analysis showed two factors, the first a fatigue-hyperalgesia (fibromyalgic complaints) and the second a fatigue-depression factor.
    Full-text · Article · Oct 2015 · Neuro endocrinology letters
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    • "These data suggest that the ME/CFS case definition, which requires more cardinal features of this illness, such as post-exertional malaise, selected a more impaired group. This finding is also supported by the Maes, Twisk and Johnson study [11] described above, which compared those who met the Fukuda et al. criteria and also reported post-exertional malaise to those who met the Fukuda et al. criteria but did not report post-exertional malaise. This study found that the participants with post-exertional malaise had more severe symptoms and more immune abnormalities. "

    Full-text · Dataset · Jun 2014
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