TABLE 1 - uploaded by Peter Powles
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 Expert Medical Consensus Panel representing treating physicians, teaching faculty and res...
Similar publications
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...
Citations
... All ME/CFS cases were diagnosed by expert physicians according to the 2003 Canadian consensus criteria. 38 Participants in both groups were excluded if they were diabetic, smoked cigarettes, consumed excessive amounts of alcohol, had an orthopaedic limitation preventing them from performing the cardiopulmonary exercise test (CPET), or had any of the following diagnoses: an autoimmune disease, schizophrenia, major depressive disorder, bipolar disorder, or an anxiety disorder. Healthy subjects included in the present study were categorized as "low-active": they had a sedentary job and no regular organized physical activity in the past 6 months. ...
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness characterized by post‐exertional malaise (PEM), a worsening of symptoms following exertion. The biological mechanisms underlying PEM remain unclear. Extracellular vesicles (EVs) play a key role in cell–cell communication and may provide insight into ME/CFS pathophysiology post‐exertion. Emerging evidence suggests similarities between ME/CFS and Long COVID, including PEM and overlapping immune and metabolic dysfunctions, highlighting the need for deeper mechanistic understanding.
Methods
This study explores the EV proteome response to exercise in 10 males with ME/CFS and 12 well‐matched sedentary male controls. Participants underwent a maximal cardiopulmonary exercise test, and plasma samples were collected at baseline, 15 min, and 24 h postexercise. EVs were isolated from plasma using size‐exclusion chromatography and characterized with nanoparticle tracking analysis. EV protein abundance was quantified with untargeted proteomics (nanoLC‐MS/MS). Comprehensive analyses included differential abundance, pathway enrichment, protein–protein interaction networks, and correlations between EV protein dynamics and clinical or exercise physiology data.
Results
ME/CFS patients exhibited many significantly altered EV proteomic responses compared with controls, including downregulation of TCA cycle‐related proteins and upregulation of complement system proteins at 15 min postexercise. Changes in proteins involved in protein folding and the endoplasmic reticulum (ER) stress response during recovery were highly correlated with PEM severity, highlighting their potential as therapeutic targets. EV protein changes postexercise were also associated with disease severity and unrefreshing sleep. Correlations between EV protein levels and the exercise parameters VO₂ peak and ventilatory anaerobic threshold were observed in controls but were absent in ME/CFS patients, suggesting disrupted EV‐mediated physiological processes.
Conclusions
ME/CFS patients exhibit a maladaptive EV proteomic response to exercise, characterized by metabolic impairments, immune overactivation, and ER stress response dysregulation. These findings provide insight into the molecular basis of PEM and suggest promising targets for improving recovery and energy metabolism in ME/CFS.
Key points
EVs were isolated from plasma of ME/CFS patients and healthy controls at baseline, and 15 min and 24 h postexercise.
Untargeted proteomics revealed dysregulation in energy metabolism, the complement system, and the endoplasmic reticulum stress response.
Changes in EV protein levels postexercise are associated with post‐exertional malaise.
These findings suggest promising therapeutic targets for post‐exertional malaise and ME/CFS pathophysiology.
... Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness with key symptoms including (but not limited to) unrefreshing sleep, post-exertional malaise, and cognitive impairment [1][2][3]. Sleep difficulties are some of the most common symptoms experienced by patients with ME/CFS [4,5]. There are different subtypes of sleep disorders for those with ME/CFS [3,4,6], and suboptimal sleep quality is related to more frequent and severe ME/CFS symptoms [7]. ...
Background/objectives:
Impaired sleep is one of the core symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), yet the mechanisms and impact of sleep-related issues are poorly understood. Sleep dysfunctions for patients with ME/CFS include frequent napping, difficulties falling asleep, waking up early, and sleep reversal patterns (e.g., sleeping throughout the day and staying awake throughout the night). The current study focuses on sleep reversal for patients with ME/CFS.
Methods:
We explored the symptoms and functional impairment of those with and without sleep reversal by analyzing the responses of a large international sample (N = 2313) using the DePaul Symptom Questionnaire (DSQ) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36).
Results:
We found that those in our Sleep Reversal group (N = 327) compared to those without sleep reversal (N = 1986) reported higher symptom burden for 53 out of 54 DSQ symptoms and greater impairments for all six SF-36 subscales. The most accurate predictors of sleep reversal included age (p < 0.05), body mass index (p < 0.05), eleven DSQ symptoms (p < 0.01), and two SF-36 subscales (p < 0.01).
Conclusions:
These features provide clues regarding some of the possible pathophysiological underpinnings of sleep reversal among those with ME/CFS.
... Diagnosis criteria for ME/CFS rely on clinical symptoms [2][3][4], as no validated biomarker exists, with post-exertional malaise or PEM playing a significant role, including fatigue, pain, and cognitive, intestinal, and sleep disturbances, among others, limiting a patient's daily performance in mildly affected patients and driving bed confinement in ...
... Magnetic resonance imaging (MRI) in 2016, at age 26, revealed a small demyelinating juxtacortical lesion in the left temporal pole, but other investigations were unremarkable, leading to a diagnosis of ME/CFS. The patient met the 2011 International Consensus Criteria [2], as well as Canadian [3] and IOM (Institute of Medicine) 2015 criteria [4]. Prescribed supplements, including magnesium, NADH, D-ribose, L-carnitine, ubiquinol, melatonin, vitamin B1, alpha-lipoic acid, vitamin D, and LDN (Low-Dose Naltrexone), failed to improve his symptoms. ...
This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments. Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system. Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.
... This definition of ME/CSF symptoms conformed to the essential symptoms of Canadian consensus criteria for ME/CSF. 16 It was unnecessary to strictly meet the diagnostic criteria for ME/CFS because our goal was not to diagnose ME/CFS, but only to collect the primary symptoms of ME/CFS. The severity of acute COVID-19 was classified according to World Health Organization guidelines. ...
Background
Long‐COVID is a significant global health concern, regardless of age. However, few reports have longitudinally evaluated the characteristics, prevalence, and risk factors of long‐COVID in children.
Methods
Participants were Japanese children younger than 18 years hospitalized for COVID‐19 between November 2021 and October 2022, along with their COVID‐19 affected parents. During hospitalization and at 1‐, 3‐, and 6‐month follow‐ups, participants completed age‐appropriate questionnaires on long‐COVID symptoms. The quality of life (QOL) score was assessed in children older than 2 years. The prevalence of long‐COVID symptoms by age group was compared. Multivariable logistic regression analysis was conducted to investigate risk factors affecting long‐COVID. Analysis of covariance adjusted for potential confounders was conducted to determine which symptoms affect QOL score.
Results
Of 108 children enrolled, the prevalence of long‐COVID was 44.9%, 37.8%, and 22.8% at 1, 3, and 6 months, respectively, after SARS‐CoV‐2 infection. There were no specific risk factors for long‐COVID. Cough, fatigue, and sleep disturbance were the most common long‐COVID symptoms, with sleep disturbance associated with a change in lower QOL score from admission at all three follow‐ups (mean difference 9.25, 20.15, and 19.81; 95% CI, 1.58–16.91, 3.38–36.92, and 5.51–34.11). The prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms among 0–6 years was significantly lower than among 7–17 years and parents; there was no significant difference between 7 and 17 years and parents.
Conclusion
Even 6 months after SARS‐CoV‐2 infection, 22.8% of pediatric patients still had long‐COVID symptoms. Some of these symptoms were similar to those of ME/CFS, potentially affecting children's QOL.
... While adults are more likely to report pain, sore lymph nodes, and palpitations, children used to complain of headaches and fatigue. 7 Adults had been sick for a longer period and were more disabled and exhausted. Younger children were likelier to have a sore throat and less likely to exhibit cognitive signs. ...
A clinical disorder known as chronic fatigue syndrome (CFS) is characterized by severe fatigue causing physical and psychosocial limitations. CFS has an unclear etiology and prognosis. This study examines the empirical literature comparing the prevalence, risk factors, impact on everyday life, and management associated with pediatric CFS. Investigators searched Scopus and PubMed databases utilizing the key terms Pediatric CFS, CFS/ME, Prevalence, Incidence, Epidemiology, Risk Factors, Genetic predispositions, Psychosocial factors, Impact, Quality of life, Impairment, Management, Intervention, and Treatment. A preliminary literature search found 1,860 articles. The inclusion criteria were articles published in English from 1994 onwards, focusing on pediatric chronic fatigue syndrome. After screening based on inclusion criteria, objectives, and language, 24 articles were selected for review. The analysis showed significant regional and global differences in the prevalence of pediatric CFS. Genetic characteristics, premorbid childhood difficulties, history of infectious disease, maternal prenatal conditions, and socio-economic status have been identified as risk factors for CFS. Children experience disruption and losses in physical, social, and psychological aspects of life because of CFS. There is currently no approved treatment for CFS in the pediatric population, even though some community-based and psychosocial intervention shows improvements in symptoms. The study underscores the need for standardized diagnostic criteria. It emphasizes the multifactorial nature of CFS onset, urging further research to elucidate causal pathways. Additionally, it stresses the significant impact of CFS on children’s lives calling for comprehensive treatment strategies.
... Approximately two-thirds of ME/CFS cases report an infection at onset of their symptoms [3][4][5] . The hallmark symptom of ME/CFS is post-exertional malaise, when new symptoms arise, or previous ones worsen, following even minimal exertion that are disproportionate to the level of exertion, prolonged in recovery and not immediately alleviated by rest 6 . Additional symptoms are fatigue that does not go away with rest, pain including headache, cognitive dysfunction and multiple sensitivities 7 . ...
... Thus, one possible strategy for filtering C 2 is to only consider those who provided responses consistent with post-exertional malaise: namely the 1,073 individuals who answered 'yes', 'no', 'no' to p120117, p120115, p120116, respectively. Nevertheless, these three questions may not effectively define post-exertional malaise because they only capture 'tiredness', as opposed to a flare up of 'all symptoms', they overlook 'new symptoms' which are characteristic of post-exertional malaise 6 , and they do not account for people with ME/CFS pacing (e.g., 'resting' and not 'over-exerting'). Otherwise, a more permissive approach would be to include only those who answered 'yes' to p120117 (n=1,428). ...
Background Progress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) research is being slowed by the relatively small-scale studies being performed whose results are often not replicated. Progress could be accelerated by analyses of large population-scale projects, such as UK Biobank (UKB), which provide extensive phenotype and genotype data linked to both ME/CFS cases and controls. Methods Here, we analysed the overlap and discordance among four UKB-defined ME/CFS cohorts, and additional questionnaire data when available. Results A total of 5,354 UKB individuals were linked to at least one piece of evidence of MECFS, a higher proportion (1.1%) than most prevalence estimates. Only a third (36%; n=1,922) had 2 or more pieces of evidence for MECFS, in part due to data missingness. For the same UKB participant, ME/CFS status defined by ICD-10 (International Classification of Diseases, Tenth Revision) code G93.3 (Post-viral fatigue syndrome) was most likely to be supported by another data type (72%); ME/CFS status defined by Pain Questionnaire responses is least likely to be supported (43%), in part due to data missingness. Conclusions We conclude that ME/CFS status in UKB, and potentially other biobanks, is best supported by multiple, and not single, lines of evidence. Finally, we raise the estimated ME/CFS prevalence in the UK to 410,000 using the most consistent evidence for ME/CFS status, and accounting for those who had no opportunity to participate in UKB due to being bed- or house-bound.
... 24 Pacing is a physical therapy strategy that enables patients to increase or decrease their activity levels according to their daily condition, not to trigger PEM. 25 Patients and clinicians collaboratively determine the activity limits that can be tolerated. 2,3 On the other hand, based on the large randomized control study, there was a more designed behavior therapy, a combination of cognitive behavioral therapy and graded exercise therapy. 26 However, that study has faced criticism from both patients and clinicians regarding its methodology and the controversial disease theory. ...
... 30 It is important to discuss and determine patients' tolerable activity limits through a mutual decision-making process. 2,3,30 We also prescribed hochuekkito and tandospirone to reduce the debilitating fatigue and anxiety. Hochuekkito is anticipated to be beneficial for patients with cancer, 31 long COVID, 32,33 and ME/ CFS after the SARS-CoV-2 infection to alleviate fatigue. ...
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological adverse effect after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccinations. However, clinicians do not recognize the condition well, and no case report has shown a full recovery.
Case Presentation
We present a 65‐year‐old Japanese female who experienced severe fatigue, postexertional malaise, orthostatic intolerance, and various symptoms after her third SARS‐CoV‐2 vaccination. Following thorough examinations and excluding other potential diagnoses, she met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The symptoms persisted for 30 months and improved ultimately with comprehensive treatment and a self‐management strategy, including pacing management, pharmacological treatments, and psychiatric interventions to support those struggling with the despair over the devastating symptoms.
Conclusion
This case report describes ME/CFS following the SARS‐CoV‐2 vaccination and its full recovery. It illustrates the importance of considering the differential diagnosis of psychiatric disorders and addressing the condition through psychiatric interventions. Our findings provide new insights into treating ME/CFS and the vaccination‐related adverse effects.
... A betegség diagnosztikus kritériumait összefoglaló módon egy 2003-ban publikált kanadai ajánlásban olvashatjuk először (Canadian Consensus Criteria) [21], majd ezt 2011-ben nemzetközi konszenzusajánlás követte [22], amely után 2015-ben az Amerikai Orvostudományi Nemzeti Akadémia (US National Academy of Medicine) publikálta ezek alapján új ajánlását [1]. Korábban számos nehézséget okozott [23], hogy nem álltak rendelkezésre megfelelő diagnosztikus kritériumok a betegség felismerésére. ...
A krónikus fáradtság szindróma/myalgiás encephalomyelitis (újabban encephalomyelopathia) olyan betegségentitás, amely az elmúlt évtizedekben vált ismertté a nemzetközi szakirodalomban, a hazai orvosi irodalomban pedig még kevéssé ismert. Tünettana szerteágazó, szomatikus, kognitív, pszichológiai és funkcionális érintettséggel, az etiológiájára vonatkozó elképzelések ellentmondásosak. Ugyanakkor foglalkozni szükséges a kérdéssel, mert számos páciens kerül az egészségügyi rendszer látókörébe ezekkel a panaszokkal. Összefoglaló tanulmányunkban a fenti kérdéseket járjuk körül a nemzetközi szakirodalom és irányelvek bemutatása révén, célunk a hazai ellátórendszerben dolgozó szakemberek – orvosok, pszichológusok, gyógytornászok, dietetikusok – számára megfelelő információ biztosítása. A krónikus fáradtság szindróma/myalgiás encephalomyelopathia kezelésének lehetőségeire is javaslatot teszünk. Orv Hetil. 2025; 166(14): 523–531.
... Die myalgische Enzephalomyelitis/das chronische Fatigue-Syndrom (ME/CFS) ist eine schwere, chronische Multisystemerkrankung, die in der Regel -trotz verschiedener Fortentwicklungen [5,14,22,23] -anhand der von Carruthers et al. [4] entwickelten kanadischen Konsensuskriterien (CCC) diagnostiziert wird (. Tab. 1). ...
... Eine Vorläuferstudie im Rahmen der APAV-ME/CFS-Studie zeigte Anhaltspunkte dafür, dass dort ein Teil der erwachsenen Erkrankten ohne ärztliche ME/CFS-Diagnose die CCC [4] erfüllt [11]. An dieser Studie nahmen insgesamt 1238 Personen (ärztlich diagnostizierte ME/CFS-Erkrankte und Erkrankte ohne ärztliche Diagnose, die davon überzeugt waren, an ME/CFS zu leiden, sowie nahe Angehörige der Erkrankten) teil. ...
... OriginalarbeitTab. 1 Zusammenfassung der kanadischen Konsensuskriterien (Canadian Consensus Criteria, CCC) nach Carruthers et al.[4] Kanadische Konsensuskriterien (CCC) Die Erkrankung muss für mindestens 6 Monate bestehen, um ME/CFS von einer postinfektiösen Fatigue abzugrenzen. Für die Diagnose ME/CFS müssen zudem die folgende Kriterien erfüllt sein:(1) Alle drei Kriterien der Fatigue bzw. ...
Zusammenfassung
Die Multisystemerkrankung ME/CFS (myalgische Enzephalomyelitis/chronisches Fatigue-Syndrom) ist eine schwere Multisystem-Erkrankung mit vielfältiger Symptomatik. Viele ihrer Symptome treten auch bei anderen Erkrankungen auf. Kennzeichnend für ME/CFS sind „post-exertional malaise“ (PEM) und hochgradige Kraft- und Energielosigkeit (Fatigue). Ziel dieser Studie war es zu ermitteln, ob es möglich ist, bei Patient:innen mit der Überzeugung, an ME/CFS erkrankt zu sein, ME/CFS-Erkrankte von Patient:innen mit ME/CFS-ähnlicher Symptomatik zu unterscheiden. Als Teil des APAV‑ME/CFS-Surveys wurden die Daten von 749 Erwachsenen mit ärztlicher ME/CFS-Diagnose (DS1) mit denen von 191 erwachsenen Erkrankten ohne ärztliche Diagnose verglichen, die überzeugt waren, an ME/CFS erkrankt zu sein (DS2). Die DS2-Patient:innen wurden anhand eines einfachen DSQ‑SF- und DSQ‑PEM-basierten Screening-Tests in 2 Untergruppen unterteilt (kanadische Konsensuskriterien [CCC] erfüllt = DS3; CCC nicht erfüllt = DS4). Auf die deskriptive Auswertung folgte ein Vergleich der verschiedenen Gruppen (Pearson χ²-Test, ANOVA mit t‑Test; p = 0,05, bei Mehrfachnennung Bonferroni-Korrektur auf p = 0,003). Insgesamt erfüllten 51,6 % der DS2-Proband:innen die zentralen CCC-Merkmale (PEM, Fatigue). DS3 und DS4 unterschieden sich nicht hinsichtlich Alter, Geschlecht, Erkrankungsdauer und anderer Parameter. Hier gab es jedoch deutliche Unterschiede zwischen DS1 und DS3 sowie zwischen DS1 und DS4. DS1 und DS3 unterschieden sich nicht hinsichtlich der Häufigkeit typischer ME/CFS-Symptome, während es hier signifikante Unterschiede zwischen DS1 und DS4 gab. Nicht-ME/CFS-Patient:innen lassen sich somit anhand weniger, an den DSQ-SF und den DSQ-PEM angelehnter, vereinfachter Fragen von ME/CFS-Patient:innen unterscheiden (DSQ‑SF = DePaul Symptom Questionnaire – Short Form; DSQ‑PEM = DePaul Symptom Questionnaire – Post-Exertional Malaise). Da PEM und die spezifische Form der Fatigue typisch für ME/CFS sind, ist es wahrscheinlich, dass die DS3-Patient:innen an ME/CFS erkrankt waren. Ärzt:innen in der Routineversorgung und mit wenig Erfahrung in der ME/CFS-Diagnostik könnten so leicht ihre Verdachtsdiagnose ME/CFS erhärten. Zudem würde sich das Screening-Instrument aufgrund seiner Einfachheit besonders für die Diagnostik bei kognitiv eingeschränkten Patient:innen eignen. In einem nächsten Schritt müsste es jedoch noch im Vergleich zu einer zuverlässigen Diagnosestellung durch Expert:innen anhand der CCC validiert werden.
... The demographic information for both cohorts is summarized in Table 1, indicating reasonable age-and BMI-matching while demonstrating the significantly lower functional status of ME/CFS subjects, with lower scores for the Bell disability scale. The ME/CFS subjects fulfilled the Canadian consensus criteria for ME/CFS diagnosis [31]. Subject selection was performed by physicians, and blood collection was carried out at Ithaca College (Ithaca, NY, USA), Weill Cornell Medicine (NYC, NY, USA), and Workwell Foundation (Ripon, CA, USA). ...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by serious physical and cognitive impairments. Recent research underscores the role of immune dysfunction, including the role of autoantibodies, in ME/CFS pathophysiology. Expanding on previous studies, we analyzed 7542 antibody–antigen interactions in ME/CFS patients using two advanced platforms: a 1134 autoantibody Luminex panel from Oncimmune and Augmenta Bioworks, along with Rapid Extracellular Antigen Profiling (REAP), a validated high-throughput method that measures autoantibody reactivity against 6183 extracellular human proteins and 225 human viral pathogen proteins. Unlike earlier reports, our analysis of 172 participants revealed no significant differences in autoantibody reactivities between ME/CFS patients and controls, including against GPCRs such as β-adrenergic receptors. However, subtle trends in autoantibody ratios between male and female ME/CFS subgroups, along with patterns of herpesvirus reactivation, suggest the need for broader and more detailed exploration.
