Figure - uploaded by Alison Christine Bested
Content may be subject to copyright.
Source publication
Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Ex- pert Medical Consensus Panel representing treating physicians, teaching faculty and r...
Contexts in source publication
Context 1
... of these normal life associated causes of fatigue do not last for greater than 6 months. Table 1 shows a relatively comprehensive list of these types of conditions where a combination of history, clinical examination and laboratory investigation are required to achieve the diagnosis. Some of the viral, bacterial and zoonotic infections will show a geographic distribution and not be applicable to all the readers of this journal. ...Context 2
... the subjects were examined by one physician (KDM), who interviewed the patients with respect to their signs and symptoms. Subjects were excluded if they were < 18 or 66 years of age, using one of the medications listed in Table 1, or reported an episode of diarrhoea or vomiting. All patients and controls were Caucasian. ...Similar publications
The Faculty of Pharmaceutical Medicine was established in the United Kingdom (UK) in 1989 to develop and maintain competence, ethics and the highest professional standards of practice in the discipline. This article charts the founding principles and history of the Faculty, details its composition and membership, and outlines the major functions an...
Citations
... Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), classified by the WHO with the ICD-11 8E49 code as a postviral fatigue syndrome, and fibromyalgia (FM) (ICD-11 MG30.0 for chronic primary pain) (Harrison et al., 2021), are chronic, disabling, acquired diseases, characterized by complex symptomatology that affects multiple organs (Bateman et al., 2021;Wolfe et al., 2010). Diagnosis of ME/CFS and FM continues to be based on the clinical assessment of unspecific symptoms, such as debilitating fatigue, generalized pain, cognitive impairment or intestinal, sleep, and immune disturbances (Carruthers et al., 2011;Carruthers et al., 2003;Wolfe et al., 2016;Wolfe et al., 2010;Wolfe et al., 1990). Their frequent co-diagnosis drove the hypothesis of a single syndrome and promoted the search for common or differentiating factors (Abbi and Natelson, 2013;Natelson, 2019;Wessely et al., 1999). ...
... In this study, we elevated these analyses to obtain genome-wide HERV profiles (HERV expression profiles) of patients having received ME/CFS, FM diagnosis, or both, hypothesizing that HERV expression profiles may reveal distinct underlying pathomechanisms that justify their classification as separate diseases, and/or common fingerprints explaining their joint high prevalence. To test our hypothesis, we scrutinized HERV and gene transcriptomes by using high-density microarray technology in a selected cohort of female patients carefully phenotyped by a single expert clinician into three defined groups of patients: patients fulfilling Canadian and International ME/CFS diagnosis criteria (Carruthers et al., 2011;Carruthers et al., 2003), patients fulfilling FM diagnosis ACR (American College of Rheumatology) criteria (Wolfe et al., 2016;Wolfe et al., 2010;Wolfe et al., 1990), or patients complying with both, ME/CFS and FM diagnosis criteria, being called co-diagnosed from now on. The results of comparing HERV profiles within PBMCs across these three patient groups as well as to HERV profiles of matched healthy subjects allowed, not only for the separation of patients from healthy individuals but also for perfect discrimination of patients into three distinct disease groups, suggesting distinct subjacent pathomechanisms. ...
... With no biomarkers available and unclear pathophysiology, ME/CFS and FM are often misdiagnosed, further complicating the identification of effective treatments. In this study, we tried to overcome patient heterogeneity by studying a very finely phenotyped cohort diagnosed by a single expert clinician, representing one of the few studies (Nepotchatykh et al., 2023) including samples of patients diagnosed with either ME/ CFS, FM, or both (co-diagnosed group) by two different clinical criteria (Canadian (Carruthers et al., 2003) and International Consensus (Carruthers et al., 2011) criteria, and the 1990 (Wolfe et al., 1990) and 2011 (Wolfe et al., 2016;Wolfe et al., 2010) ACR criteria, respectively). Due to previously reported sex-associated differences in these diseases, only female patients were included, limiting the external validity of the results in the male population while minimizing potential sex-associated bias. ...
Research of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM), two acquired chronic illnesses affecting mainly females, has failed to ascertain their frequent co-appearance and etiology. Despite prior detection of human endogenous retrovirus (HERV) activation in these diseases, the potential biomarker value of HERV expression profiles for their diagnosis, and the relationship of HERV expression profiles with patient immune systems and symptoms had remained unexplored. By using HERV-V3 high-density microarrays (including over 350k HERV elements and more than 1500 immune-related genes) to interrogate the transcriptomes of peripheral blood mononuclear cells from female patients diagnosed with ME/CFS, FM, or both, and matched healthy controls ( n = 43), this study fills this gap of knowledge. Hierarchical clustering of HERV expression profiles strikingly allowed perfect participant assignment into four distinct groups: ME/CFS, FM, co-diagnosed, or healthy, pointing at a potent biomarker value of HERV expression profiles to differentiate between these hard-to-diagnose chronic syndromes. Differentially expressed HERV–immune–gene modules revealed unique profiles for each of the four study groups and highlighting decreased γδ T cells, and increased plasma and resting CD4 memory T cells, correlating with patient symptom severity in ME/CFS. Moreover, activation of HERV sequences coincided with enrichment of binding sequences targeted by transcription factors which recruit SETDB1 and TRIM28, two known epigenetic silencers of HERV, in ME/CFS, offering a mechanistic explanation for the findings. Unexpectedly, HERV expression profiles appeared minimally affected in co-diagnosed patients denoting a new nosological entity with low epigenetic impact, a seemingly relevant aspect for the diagnosis and treatment of this prevalent group of patients.
... Participants met the ACR criteria, as indicated by their local medical center certificate [12,13]. They were also asked about a possible comorbid diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) according to the Canadian and/or international criteria for ME/CFS [7,44]. Participants were recruited between January and February 2019 through invitations from several associations of patients with FM in the Valencian Community. ...
Background: Fibromyalgia (FM) is a chronic disorder causing widespread musculoskeletal pain, often leading to physical deconditioning that affects posture and gait. This study evaluates the effects of a manual therapy protocol targeting dorsal muscles in the lower back on plantar pressure modifications, considering body mass index (BMI) influence. Methods: A single-arm, non-randomized clinical trial included 24 women diagnosed with FM for at least three years. They underwent an eight-session manual therapy protocol over four weeks, applying moderate pressure to dorsal muscles in the lower back. Baropodometric analyses were conducted pre- and post-intervention under dynamic conditions. Statistical analyses used paired t-tests and effect size calculations to assess intervention effects and BMI impact. Results: Significant improvements in plantar pressure distribution were observed in both the left foot (p = 0.01, d = −0.54) and the right foot (p = 0.008, d = −0.59). However, strength and peak pressure metrics showed no significant changes. Patients with normal BMI exhibited greater improvements than those in the overweight category. Conclusions: Preliminary findings suggest that manual therapy positively influenced plantar pressure distribution in FM patients, particularly in those with normal BMI. Further research is needed to explore long-term effects and broader clinical applications.
... In the context of the present review, pwME/CFS and pwPCC are defined as those fulfilling the most stringent corresponding diagnostic criteria available. Hence, all participants with ME/CFS meet the Canadian Consensus Criteria (CCC) [40] or International Consensus Criteria (ICC) [2] and all participants with PCC have an illness duration of at least 12 weeks consistent with the World Health Organization (WHO) case definition [23]. Although other PCC case definitions are similarly characterised by a minimum illness duration threshold of 12 weeks [22,24], the WHO case definition additionally requires symptoms to have a significant impact on functioning [23]. ...
Purpose
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC. To deliver appropriate care and optimise health outcomes for pwME/CFS and pwPCC, the development of evidence-based healthcare policies that recognise the disabling impacts of these illnesses must be prioritised. This systematic review summarises the health-related quality of life (HRQoL) of pwME/CFS and pwPCC when compared with healthy controls (HCs) to elucidate the impacts of these illnesses and guide healthcare policy reform.
Methods
CINAHL, Embase, MEDLINE, PubMed, PsycINFO and the Web of Science Core Collection were systematically searched from 1st January 2003 to 23rd July 2024. Eligible publications included observational studies capturing quantitative HRQoL data among pwME/CFS or pwPCC when compared with HCs. The use of validated patient-reported outcome measures (PROMs) was mandatory. Eligible studies were also required to employ the most stringent diagnostic criteria currently available, including the Canadian Consensus Criteria or International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC (PROSPERO ID: CRD42024501309).
Results
This review captured 16 studies, including eight studies among pwME/CFS, seven studies among pwPCC and one study among both illness cohorts. Most participants were female and middle-aged. All pwPCC had experienced prolonged COVID-19 symptoms for at least three months. When compared with HCs, all HRQoL domains were significantly impaired among pwME/CFS and pwPCC. Both illnesses had a salient impact on physical health, including pain and ability to perform daily and work activities. While direct comparisons between pwME/CFS and pwPCC were limited by inconsistencies in the PROMs employed, comparable impact trends across HRQoL domain scores were observed.
Conclusion
ME/CFS and PCC have similar, profound impacts on HRQoL that warrant access to multidisciplinary disability and social support services. Future research must harmonise HRQoL data collection and prioritise longitudinal investigations among pwME/CFS and pwPCC to characterise PCC subgroups (including those fulfilling ME/CFS criteria) and predictors of prognosis.
... Bereits Anfang der 2000er-Jahre wurden von Carruthers et al. Konsensuskriterien für die Diagnostik von ME/CFS entwickelt [2], die -trotz verschiedener Weiterentwicklungen (ICC [3]; IOM; [11], NICE [19], EUROMENE [17]) -noch heute als Grundlage für die Diagnosestellung bei ME/CFS dienen. . Tab. 1 zeigt eine Zusammenfassung dieser kanadischen Konsensuskriterien (CCC) [2]. ...
... Konsensuskriterien für die Diagnostik von ME/CFS entwickelt [2], die -trotz verschiedener Weiterentwicklungen (ICC [3]; IOM; [11], NICE [19], EUROMENE [17]) -noch heute als Grundlage für die Diagnosestellung bei ME/CFS dienen. . Tab. 1 zeigt eine Zusammenfassung dieser kanadischen Konsensuskriterien (CCC) [2]. Obwohl diese seit langem vorliegen, ist die Erkrankung vielen Ärzt:innen noch immer unbekannt [9]. ...
Zusammenfassung
Man geht bei der Myalgischen Enzephalomyelitis/dem Chronischen Fatigue-Syndrom (ME/CFS) von einer hohen Dunkelziffer aus. Ein Teil dieser undiagnostizierten Patient:innen vermutet, an ME/CFS zu leiden. Ziel dieser Studie war es zu ermitteln, ob und ggf. in welcher Hinsicht sich Erkrankte mit und ohne ärztliche ME/CFS-Diagnose unterscheiden.
Dazu wurden die Antworten von 736 erwachsenen, ärztlich diagnostizierten ME/CFS-Erkrankten (DS1) mit denen von 189 erwachsenen Erkrankten ohne ärztliche ME/CFS-Diagnose (DS2) verglichen. Das Sampling erfolgte durch Selbstaktivierung/Schneeballprinzip. Nach einer deskriptiven Ergebnisdarstellung wurden potenzielle Zusammenhänge zwischen den verschiedenen Variablen untersucht (Pearson χ²-Test/Fisher’s Exact-Test, Levene-Test, t-Test).
Beide Gruppen unterschieden sich nicht signifikant hinsichtlich Alter und Geschlecht. Die DS2-Kranken nahmen jedoch weniger ärztliche/alternativmedizinische Leistungen in Anspruch. Sie gaben weniger Symptome an, unterschieden sich jedoch nicht hinsichtlich ihres Symptomenspektrums. Im Gegensatz zur DS1-Gruppe nahm die Zahl der Symptome in der DS2-Gruppe nicht mit dem Alter ab, auch gab es hier keinen Geschlechtsunterschied. Anders als in Studien, die die Symptomhäufigkeit bei ME/CFS-Erkrankten mit Patient:innen vergleichen, die die kanadischen Konsensuskriterien (CCC) nicht erfüllen, ist die Differenz zwischen unseren beiden Gruppen deutlich geringer.
Das führt zur These, dass zumindest ein Teil unserer nicht-diagnostizierten Proband:innen die CCC erfüllt. Eine Bestätigung dieser Hypothese könnte dazu führen, dass die Diagnosestellung bei dieser Patientengruppe in Zukunft früher geschieht, sodass früher Maßnahmen ergriffen werden können, die den Krankheitsverlauf positiv beeinflussen können.
... Serum samples and clinical data from 121 PCS patients suffering from moderate-tosevere fatigue and exertion intolerance following mostly mild COVID-19 were collected between October 2020 and January 2024 at the ME/CFS outpatient clinic of the Institute of Medical Immunology, Charité, Berlin. From these, 72 met the CCC for diagnosis of ME/CFS [25,26]. Relevant cardiac, respiratory, neurological, or psychiatric comorbidities were excluded. ...
Background/Objectives: According to the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), an estimated 3–6% of people suffer from post-COVID condition or syndrome (PCS). A subset meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies have reported that SARS-CoV-2 proteins or RNA can persist after acute infection in serum or tissues, but their role in PCS is unclear. Methods: Here, SARS-CoV-2 spike protein was analyzed in the serum of 121 PCS patients with predominant fatigue and exertional intolerance, of whom 72 met diagnostic criteria for ME/CFS, 37 post-COVID recovered healthy controls, and 32 pre-pandemic healthy controls. Results: Spike protein was detected in the serum of 11% of recovered controls, 2% of PCS patients, and 14% of ME/CFS patients between 4 and 31 months after SARS-CoV-2 infection, but not in pre-pandemic samples. The occurrence and concentration of spike protein did not correlate with infection or vaccination timepoints. In ME/CFS patients, spike protein presence was not associated with the severity of symptoms or functional disability. In 5 out of 22 patients who under-went immunoglobulin depletion, spike protein levels were reduced or undetectable after treatment, indicating binding to immunoglobulins. Conclusions: In summary, this study identified serum spike protein in a subset of patients but found no association with ME/CFS.
... ME/CFS does not fit neatly into this approach as symptoms can arise from the musculoskeletal, immunological, cardiovascular, gastrointestinal, and neuroendocrine systems (Fig. 1). It challenges the current diagnosis procedure which are based on observable characteristics [19] (generic symptoms and subjective questionnaires) and rely on continuously evolving case definitions (Fukuda 1994 [20], Canadian Consensus Criteria 2003 [21], International Consensus Criteria 2011 [2], National Academy of Medicine 2015 [22], UK National Institute for Health and Care Excellence 2021 [23]). ME/CFS patients undergo extensive family and medical history assessments, series of tests, and may see numerous general practitioners and specialists to receive a clinical diagnosis [24]. ...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and multifaceted disorder that defies simplistic characterisation. Traditional approaches to diagnosing and treating ME/CFS have often fallen short due to the condition’s heterogeneity and the lack of validated biomarkers. The growing field of precision medicine offers a promising approach which focuses on the genetic and molecular underpinnings of individual patients. In this review, we explore how machine learning and multi-omics (genomics, transcriptomics, proteomics, and metabolomics) can transform precision medicine in ME/CFS research and healthcare. We provide an overview on machine learning concepts for analysing large-scale biological data, highlight key advancements in multi-omics biomarker discovery, data quality and integration strategies, while reflecting on ME/CFS case study examples. We also highlight several priorities, including the critical need for applying robust computational tools and collaborative data-sharing initiatives in the endeavour to unravel the biological intricacies of ME/CFS.
... Assessment includes physical and psychological examination, history taking, and differential diagnoses (based on, for example, blood tests, diagnostic imaging, and the use of depression and anxiety scales). The Norwegian guidelines base the diagnosis of CFS on the Canada consensus criteria (Carruthers et al. 2003;Helsedirektoratet 2015), which are considered to be conclusive for a diagnostic decision. These criteria measure and operationalize levels of fatigue by assessing whether a patient has a 50 percent reduced activity level, compared to self-reported previous activity levels. ...
... Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a clinical condition characterised by unexplained severe fatigue that is accompanied by a variety of symptoms related to cognitive, immunological, endocrinological and autonomic dysfunction. 1 In addition to persistent fatigue, individuals also experience postexertional malaise (PEM), which is defined as the worsening of ME/CFS symptoms following physical or mental exertion that can last for days or even weeks. The incidence of ME/CFS has been observed to peak between the ages of 10-19 years and 30-39 years and there is a notable female preponderance in both groups. ...
Introduction
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition that can affect adolescents during a vulnerable period of development. The underlying biological mechanisms for ME/CFS remain unclear and have rarely been investigated in the adolescent population, despite this period representing an age peak in the overall incidence. The primary objective of this is to provide a foundational set of biological data on adolescent ME/CFS patients. Data generated will be compared with controls and over several time points within each patient to potentially develop a biomarker signature of the disease, identify subsets or clusters of patients, and to unveil the pathomechanisms of the disease.
Methods and analysis
This protocol paper outlines a comprehensive, multilevel, longitudinal, observational study in paediatric ME/CFS. ME/CFS patients aged 12–19 years and controls will donate biosamples of urine, blood, and peripheral blood mononuclear cells for an in-depth omics profiling analysis (whole-genome sequencing, metabolomics and quantitative proteomics) while being assessed by gold-standard clinical and neuropsychological measures. ME/CFS patients will then be provided with a take-home kit that enables them to collect urine and blood microsamples during an average day and during days when they are experiencing postexertional malaise. The longitudinal repeated-measures study design is optimal for studying heterogeneous chronic diseases like ME/CFS as it can detect subtle changes, control for individual differences, enhance precision and boost statistical power. The outcomes of this research have the potential to identify biomarker signatures, aid in understanding the underlying mechanisms, and ultimately, improve the lives of children with ME/CFS.
Ethics and dissemination
This project was approved by the Royal Children’s Hospital’s Human Research Ethics Committee (HREC 74175). Findings from this study will be disseminated through peer-reviewed journal publications and presentations at relevant conferences. All participants will be provided with a summary of the study’s findings once the project is completed.
... Current ME/CFS studies employ tailored inclusion/exclusion criteria for both case and control groups to mitigate individual heterogeneity, which often results in limited sample sizes. Moreover, various ME/CFS diagnostic criteria [1][2][3][4] are used for participant recruitment producing inconsistent results across studies. The lack of powered studies and result validation has made research into reproducible biomarkers a priority, in particular, the application of metabolomics 5 . ...
Background
Diagnosing complex illnesses like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is complicated due to the diverse symptomology and presence of comorbid conditions. ME/CFS patients often present with multiple health issues, therefore, incorporating comorbidities into research can provide a more accurate understanding of the condition’s symptomatology and severity, to better reflect real-life patient experiences.
Methods
We performed association studies and machine learning on 1194 ME/CFS individuals with blood plasma nuclear magnetic resonance (NMR) metabolomics profiles, and seven exclusive comorbid cohorts: hypertension (n = 13,559), depression (n = 2522), asthma (n = 6406), irritable bowel syndrome (n = 859), hay fever (n = 3025), hypothyroidism (n = 1226), migraine (n = 1551) and a non-diseased control group (n = 53,009).
Results
We present a lipoprotein perspective on ME/CFS pathophysiology, highlighting gender-specific differences and identifying overlapping associations with comorbid conditions, specifically surface lipids, and ketone bodies from 168 significant individual biomarker associations. Additionally, we searched for, trained, and optimised a machine learning algorithm, resulting in a predictive model using 19 baseline characteristics and nine NMR biomarkers which could identify ME/CFS with an AUC of 0.83 and recall of 0.70. A multi-variable score was subsequently derived from the same 28 features, which exhibited ~2.5 times greater association than the top individual biomarker.
Conclusions
This study provides an end-to-end analytical workflow that explores the potential clinical utility that association scores may have for ME/CFS and other difficult to diagnose conditions.
... Finally, our study confirms that allergies, sensitivities, and intolerances are common in LC. Allergies and sensitivities to environmental and food antigens are common in ME/CFS, and are included in both the Canadian Consensus Criteria and International Consensus Criteria for diagnosis of ME/CFS (86,87). In an online survey of Dutch (n = 337) and US (n = 252) ME/CFS patients, 19.1% of the Dutch cohort and 46.8% of the US cohort reported "sensitivity to smells, food, medications, or chemicals" (88). ...
Background
Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.
Methods
Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.
Results
In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).
Conclusion
We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.
