Category: Case Definition

Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers

Abstract:

Background: Chronic fatigue syndrome (CFS) is defined according to subjective symptoms only, and several conflicting case definition exist. Previous research has discovered certain biological alterations. The aim of the present study was to explore possible subgroups based on biological markers within a widely defined cohort of adolescent CFS patients and investigate to what extent eventual subgroups are associated with other variables.

Methods: The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) has previously performed detailed investigation of immunological, autonomic, neuroendocrine, cognitive and sensory processing functions in an adolescent group of CFS patients recruited according to wide diagnostic criteria. In the present study, hierarchical cluster analyses (Ward’s method) were performed using representative variables from all these domains. Associations between clusters and constitutional factors (including candidate genetic markers), diagnostic criteria, subjective symptoms and prognosis were explored by standard statistical methods.

Results: A total of 116 patients (26.7% males, mean age 15.4 years) were included. The final cluster analyses revealed six clusters labelled pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity, respectively. There was substantial overlap between clusters. The pain intolerant & poor cognitions-cluster was associated with low functional abilities and quality of life, and adherence to the Canada 2003 diagnostic criteria for CFS. No other statistically significant cluster associations were discovered.

Conclusion: Within a widely defined cohort of adolescent CFS patients, clusters could be delineated, but no distinct subgroups could be identified. Associations between clusters and constitutional factors, subjective symptoms and prognosis were scarce. These results question the clinical usefulness of searching for CFS subgroups, as well as the validity of the most “narrow” CFS diagnostic criteria.

Source: Asprusten TT, Sletner L, Wyller VBB. Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers. J Transl Med. 2021 Jan 30;19(1):48. doi: 10.1186/s12967-021-02713-9. PMID: 33516248; PMCID: PMC7847574. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847574/ (Full text)

ME (Ramsay) and ME-International Case Criteria (ME-ICC): two distinct clinical entities

Excerpt:

The review of the differences and similarities in the different case definitions for myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) by Lim and Son [1] deserves appreciation. Based on their analysis the authors acknowledge the “distinct view of ME and CFS” [2] and recognize four categories of case definitions: ME, ME/CFS, CFS [3] and Systemic Exertion Intolerance Disorder (SEID) [4].

Indeed these labels reflect very different case definitions [5]. According to Lim and Son [1] the first category comprises two ‘ME’ case definitions: ME (Ramsay) [6] and ME according to the International Case Criteria (ME-ICC) [7]. However as can be deduced from Table 2 [1], ME [6] and ME-ICC [7] are two distinct clinical entities [8].

Source: Twisk FNM. ME (Ramsay) and ME-International Case Criteria (ME-ICC): two distinct clinical entities. J Transl Med. 2020 Nov 25;18(1):447. doi: 10.1186/s12967-020-02617-0. PMID: 33239008. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02617-0 (Full text)

Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown causes. From the perspectives on the etiology and pathophysiology, ME/CFS has been labeled differently, which influenced changes in case definitions and terminologies. This review sought to feature aspects of the history, developments, and differential symptoms in the case definitions.

Methods: A search was conducted through PubMed published to February 2020 using the following search keywords: case definition AND chronic fatigue syndrome [MeSH Terms]. All reference lists of the included studies were checked. Of the included studies, the number of citations and the visibility in the literatures of the definitions were considered for comparisons of the criteria.

Results: Since the first ‘ME’ case definition was developed in 1986, 25 case definitions/diagnostic criteria were created based on three conceptual factors (etiology, pathophysiology, and exclusionary disorders). These factors can be categorized into four categories (ME, ME/CFS, CFS, and SEID) and broadly characterized according to primary disorder (ME-viral, CFS-unknown, ME/CFS-inflammatory, SEID-multisystemic), compulsory symptoms (ME and ME/CFS-neuroinflammatory, CFS and SEID-fatigue and/or malaise), and required conditions (ME-infective agent, ME/CFS, CFS, SEID-symptoms associated with fatigue, e.g., duration of illness). ME and ME/CFS widely cover all symptom categories, while CFS mainly covers neurologic and neurocognitive symptoms. Fatigue, cognitive impairment, PEM, sleep disorder, and orthostatic intolerance were the overlapping symptoms of the 4 categories, which were included as SEID criteria.

Conclusions: This study comprehensively described the journey of the development of case definitions and compared the symptom criteria. This review provides broader insights and explanations to understand the complexity of ME/CFS for clinicians and researchers.

Source: Lim EJ, Son CG. Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med. 2020;18(1):289. Published 2020 Jul 29. doi:10.1186/s12967-020-02455-0 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02455-0 (Full text)

Solving the ME/CFS criteria and name conundrum: the aftermath of IOM

Abstract:

In 2015, the Institute of Medicine (IOM) proposed a new name and set of clinical criteria for what had previously been referred to as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). This committee recommended the adoption of the term systemic exertion intolerance disease (SEID) and clinical criteria that required specific symptoms such as post-exertional malaise and unrefreshing sleep.

This article reviews efforts to evaluate the revised criteria as well as reactions to the new criteria and name. Since these recommendations have been made, the proposed name change has not been widely adopted by the scientific or patient community. Even though the IOM’s proposed criteria were intended to be a clinical rather than a research case definition, over the past few years, an increasing number of studies have employed these criteria for research purposes. One unwitting consequence of the IOM criteria, which excludes few other illnesses, is the broadening of the number of individuals who are diagnosed and included in research studies.

There is still a need to implement the IOM’s recommendation to form a multidisciplinary committee to review research and policy changes following the release of the new criteria. We conclude by presenting a possible roadmap for overcoming barriers in order to make progress on developing a consensus for a name and criteria.

Source: Leonard A. Jason & Madeline Johnson (2020) Solving the ME/CFS criteria and name conundrum: the aftermath of IOM, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2020.1757809 https://www.tandfonline.com/doi/abs/10.1080/21641846.2020.1757809?journalCode=rftg20

The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE)

Abstract:

We have developed a Europe-wide approach to investigating the economic impact of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), facilitating acquisition of information on the economic burden of ME/CFS, and international comparisons of economic costs between countries. The economic burden of ME/CFS in Europe appears large, with productivity losses most significant, giving scope for substantial savings through effective prevention and treatment.

However, economic studies of ME/CFS, including cost-of-illness analyses and economic evaluations of interventions, are problematic due to different, arbitrary case definitions, and unwillingness of doctors to diagnose it. We therefore lack accurate incidence and prevalence data, with no obvious way to estimate costs incurred by undiagnosed patients. Other problems include, as for other conditions, difficulties estimating direct and indirect costs incurred by healthcare systems, patients and families, and heterogeneous healthcare systems and patterns of economic development across countries.

We have made recommendations, including use of the Fukuda (CDC-1994) case definition and Canadian Consensus Criteria (CCC), a pan-European common symptom checklist, and implementation of prevalence-based cost-of-illness studies in different countries using an agreed data list. We recommend using purchasing power parities (PPP) to facilitate international comparisons, and EuroQol-5D as a generic measure of health status and multi-attribute utility instrument to inform future economic evaluations in ME/CFS.

Source: Pheby DFH, Araja D, Berkis U, Brenna E, Cullinan J, de Korwin JD, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X. The Development of a Consistent Europe-Wide Approach to Investigating the Economic Impact of Myalgic Encephalomyelitis (ME/CFS): A Report from the European Network on ME/CFS (EUROMENE). Healthcare (Basel). 2020 Apr 7;8(2). pii: E88. doi: 10.3390/healthcare8020088. https://www.ncbi.nlm.nih.gov/pubmed/32272608

Myalgic encephalomyelitis/chronic fatigue Syndrome (ME/CFS): Investigating care practices pointed out to disparities in diagnosis and treatment across European Union

Abstract:

ME/CFS is a chronic, complex, multisystem disease that often limits the health and functioning of the affected patients. Diagnosing patients with ME/CFS is a challenge, and many different case definitions exist and are used in clinical practice and research. Even after diagnosis, medical treatment is very challenging. Symptom relief and coping may affect how patients live with their disease and their quality of life. There is no consensus on which diagnostic criteria should be used and which treatment strategies can be recommended for patients.

The purpose of the current project was to map the landscape of the Euromene countries in respect of national guidelines and recommendations for case definition, diagnosis and clinical approaches for ME/CFS patients. A 23 items questionnaire was sent out by email to the members of Euromene. The form contained questions on existing guidelines for case definitions, treatment/management of the disease, tests and questionnaires applied, and the prioritization of information for data sampling in research. We obtained information from 17 countries. Five countries reported having national guidelines for diagnosis, and five countries reported having guidelines for clinical approaches.

For diagnostic purposes, the Fukuda criteria were most often recommended, and also the Canadian Consensus criteria, the International Consensus Criteria and the Oxford criteria were used. A mix of diagnostic criteria was applied within those countries having no guidelines. Many different questionnaires and tests were used for symptom registration and diagnostic investigation. For symptom relief, pain and anti-depressive medication were most often recommended. Cognitive Behavioral Therapy and Graded Exercise treatment were often recommended as disease management and rehabilitative/palliative strategies.

The lack of consistency in recommendations across European countries urges the development of regulations, guidance and standards. The results of this study will contribute to the harmonization of diagnostic criteria and treatment for ME/CFS in Europe.

Source: Strand EB, Nacul L, Mengshoel AM, Helland IB, Grabowski P, Krumina A, Alegre-Martin J, Efrim-Budisteanu M, Sekulic S, Pheby D, Sakkas GK, Sirbu CA, Authier FJ; European Network on ME/CFS (EUROMENE). Myalgic encephalomyelitis/chronic fatigue Syndrome (ME/CFS): Investigating care practices pointed out to disparities in diagnosis and treatment across European Union. PLoS One. 2019 Dec 5;14(12):e0225995. doi: 10.1371/journal.pone.0225995. eCollection 2019. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225995 (Full article)

Myalgic encephalomyelitis and chronic fatigue syndrome case definitions: effects of requiring a substantial reduction in functioning

Abstract:

BACKGROUND: Current case definitions for myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) require an individual to report a ‘substantial reduction’ in activity levels, when compared to premorbid functioning. However, little guidance is provided on how to measure these reductions, as well as what level of reduction should be deemed ‘substantial,’ leading to inconsistencies in how this criterion is applied across research settings.

PURPOSE: The current study examined the influence of substantial reduction criterion on case definitions.

METHOD: The current study analyzed an international convenience sample of 1002 individuals with ME or CFS, 53 healthy controls, and 260 controls with other chronic illnesses.

RESULTS: Findings indicated that the utility of the substantial reduction criterion varied by case definition, with more stringent case definitions not needing this criterion to identify cases.

CONCLUSION: These results suggest that the requirement of a substantial reduction in functioning may be redundant when case definitions specify that individuals must endorse a set of core symptoms at specified frequency and severity levels.

Source: Scartozzi S, Sunnquist M, Jason LA. Myalgic encephalomyelitis and chronic fatigue syndrome case definitions: effects of requiring a substantial reduction in functioning. Fatigue. 2019;7(2):59-68. doi: 10.1080/21641846.2019.1600825. Epub 2019 Apr 1. https://www.ncbi.nlm.nih.gov/pubmed/31788347

From neurasthenia to post-exertion disease: Evolution of the diagnostic criteria of chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Changes in the terminology and diagnostic criteria for chronic fatigue syndrome/myalgic encephalomyelitis are explained in this paper. This syndrome is a complex and controversial entity of unknown origins. It appears in the medical literature in 1988, although clinical pictures of chronic idiopathic fatigue have been identified since the nineteenth century with different names, from neurasthenia, epidemic neuromyasthenia, and benign myalgic encephalomyelitis up to the current proposal of disease of intolerance to effort (post-effort). All of them allude to a chronic state of generalised fatigue of unknown origin, with limitations to physical and mental effort, accompanied by a set of symptoms that compromise diverse organic systems.

The International Classification of Diseases (ICD-10) places this syndrome in the section on neurological disorders (G93.3), although histopathological findings have not yet been found to clarify it. Multiple organic alterations have been documented, but a common biology that clarifies the mechanisms underlying this disease has not been established. It is defined as a neuro-immune-endocrine dysfunction, with an exclusively clinical diagnosis and by exclusion.

Several authors have proposed to include CFS/ME within central sensitivity syndromes, alluding to central sensitisation as the common pathophysiological substrate for this, and other syndromes. The role of the family doctor is a key figure in the disease, from the detection of those patients who present a fatigue of unknown nature that is continuous or intermittent for more than 6 months, in order to make an early diagnosis and establish a plan of action against a chronic disease with high levels of morbidity in the physical and mental sphere.

OBJECTIVE: To carry out a bibliographic review of the terminology and diagnostic criteria of the chronic fatigue syndrome/myalgic encephalomyelitis, in order to clarify the pathology conceptually, as a usefulness in the diagnosis of Primary Care physicians.

Copyright © 2019. Publicado por Elsevier España, S.L.U.

Source: Murga Í, Lafuente JV. From neurasthenia to post-exertion disease: Evolution of the diagnostic criteria of chronic fatigue syndrome/myalgic encephalomyelitis. Aten Primaria. 2019 Jun 7. pii: S0212-6567(19)30191-X. doi: 10.1016/j.aprim.2019.04.004. [Epub ahead of print][Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/31182238

Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches

Abstract:

PURPOSE OF REVIEW: A recent review implicates that myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), and chronic fatigue are part of the “fatigue spectrum” and recommends “longitudinal studies integrating biopsychosocial approaches to inform early management and targeted rehabilitation strategies.”

RECENT FINDINGS: ME is a neuromuscular disease distinguished by muscle fatigability (prolonged muscle weakness after minor exertion) and specific signs of neurological dysfunction. ME is not equivalent to CFS, as proposed by the authors. CFS is defined as unexplained chronic fatigue accompanied by at least four out of a list of eight specific symptoms. CFS is a distinct clinical entity and not merely a severe variant of CF, as suggested. Proof that CF, CFS, and ME are part of a “fatigue continuum” and that CF can convert to CFS at a later stage is lacking. Biopsychosocial approaches for early management and rehabilitation of CF, as promoted by the authors, are at odds with the current understandings of ME, CFS, and CF. The (bio)psychosocial explanatory models for ME and CFS have proven to be invalid, and the associated interventions, cognitive behavioral therapy and graded exercise therapy, have shown to be ineffective and even potentially harmful. ME, CFS, and CF are three very distinct clinical entities. Interventions justified by (bio)psychosocial models appear to be unsuccessful and potentially noxious. To develop effective treatments, it is crucial to make a clear distinction between ME, CFS, and CF and to leave the (bio)psychosocial explanations and therapies behind us.

Source: Twisk FNM. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches. Curr Rheumatol Rep. 2019 May 9;21(6):27. doi: 10.1007/s11926-019-0823-z. https://www.ncbi.nlm.nih.gov/pubmed/31073713

Chronic Fatigue Syndrome prevalence is grossly overestimated using Oxford criteria compared to Centers for Disease Control (Fukuda) criteria in a U.S. population study

Abstract:

BACKGROUND: Results from treatment studies using the low threshold Oxford criteria for recruitment may have been overgeneralized to patients diagnosed by more stringent CFS criteria.

PURPOSE: To compare the selectivity of Oxford and Fukuda criteria in a U.S. population.

METHODS: Fukuda (Center for Disease Control (CDC)) criteria, as operationalized with the CFS Severity Questionnaire (CFSQ), were included in the nationwide rc2004 HealthStyles survey mailed to 6,175 participants who were representative of the US 2003 Census population. The 9 questionnaire items (CFS symptoms) were crafted into proxies for Oxford criteria (mild fatigue, minimal exclusions) and Fukuda criteria (fatigue plus ≥4 of 8 ancillary criteria at moderate or severe levels with exclusions). The comparative prevalence estimates of CFS were then determined. Severity scores for fatigue were plotted against the sum of severities for the 8 ancillary criteria. The 4 quadrants of scatter diagrams assessed putative healthy controls, CFS, chronic idiopathic fatigue, and CFS-like with insufficient fatigue subjects.

RESULTS: The Oxford criteria designated CFS in 25.5% of 2,004 males and 19.9% of 1,954 females. Based on quadrant analysis, 85% of Oxford-defined cases were inappropriately classified as CFS. Fukuda criteria identified CFS in 2.3% of males and 1.8% of females.

DISCUSSION: CFS prevalence using Fukuda criteria and quadrant analysis were near the upper limits of previous epidemiology studies. The CFSQ may have utility for on-line and outpatient screening. The Oxford criteria were untenable because they inappropriately selected healthy subjects with mild fatigue and chronic idiopathic fatigue and mislabeled them as CFS.

Source: Baraniuk JN. Chronic Fatigue Syndrome prevalence is grossly overestimated using Oxford criteria compared to Centers for Disease Control (Fukuda) criteria in a U.S. population study. Fatigue. 2017;5(4):215-230. doi: 10.1080/21641846.2017.1353578. Epub 2017 Jul 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407870/ (Full article)