Case Definition – Page 6 – American ME and CFS Society

Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review

Abstract:

OBJECTIVE: To identify case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and explore how the validity of case definitions can be evaluated in the absence of a reference standard.

DESIGN: Systematic review.

SETTING: International.

PARTICIPANTS: A literature search, updated as of November 2013, led to the identification of 20 case definitions and inclusion of 38 validation studies.

PRIMARY AND SECONDARY OUTCOME MEASURE: Validation studies were assessed for risk of bias and categorised according to three validation models: (1) independent application of several case definitions on the same population, (2) sequential application of different case definitions on patients diagnosed with CFS/ME with one set of diagnostic criteria or (3) comparison of prevalence estimates from different case definitions applied on different populations.

RESULTS: A total of 38 studies contributed data of sufficient quality and consistency for evaluation of validity, with CDC-1994/Fukuda as the most frequently applied case definition. No study rigorously assessed the reproducibility or feasibility of case definitions. Validation studies were small with methodological weaknesses and inconsistent results. No empirical data indicated that any case definition specifically identified patients with a neuroimmunological condition.

CONCLUSIONS: Classification of patients according to severity and symptom patterns, aiming to predict prognosis or effectiveness of therapy, seems useful. Development of further case definitions of CFS/ME should be given a low priority. Consistency in research can be achieved by applying diagnostic criteria that have been subjected to systematic evaluation.

Source: Brurberg KG, Fønhus MS, Larun L, Flottorp S, Malterud K. Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. BMJ Open. 2014 Feb 7;4(2):e003973. doi: 10.1136/bmjopen-2013-003973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918975/ (Full article)

Chronic Fatigue Syndrome: Case Definitions and Diagnostic Assessment

Abstract:

Chronic fatigue syndrome (CFS) is a chronic, debilitating illness that has posed considerable challenges for both patients and health care providers. Individuals with CFS often deal with considerable stigma and difficulties accessing appropriate care. Many medical professionals are increasingly recognizing the devastating nature of this illness, but at this time, few health care workers are knowledgeable and experienced enough to provide adequate patient care. There is a need for further efforts to educate health care workers on CFS diagnostic, assessment, and treatment issues. The present article reviews controversies regarding CFS case definitions, diagnostic criteria, the name of the illness, and epidemiological and treatment studies. We conclude that an imprecise case definition underlies many of the problems with diagnostic and treatment issues.

Source: Williams YJ, Jantke RL, Jason LA. Chronic Fatigue Syndrome: Case Definitions and Diagnostic Assessment. N Y State Psychol. 2014 Winter;26(4):41-45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008849/ (Full article)

Contrasting Chronic Fatigue Syndrome versus Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Much debate is transpiring regarding whether chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) are different illnesses. Several prior studies that compared the Fukuda et al. CFS criteria to the Canadian ME/CFS criteria found that the Canadian criteria identified patients with more functional impairments and greater physical, mental, and cognitive problems than those who met Fukuda et al. criteria.[3,4] These samples were located in the Chicago metropolitan area, so the results could not be generalized to other locations. In addition, past studies used a symptom questionnaire that was not specifically developed to tap the Canadian criteria.

PURPOSE: The present comparative study of CFS and ME/CFS criteria was intended to correct the methodological problems of prior studies.

METHODS: This article used data from three distinct samples to compare patients who met criteria for the ME/CFS Canadian clinical case definition [1] to those who met the Fukuda et al. CFS case definition.[2].

RESULTS: Findings indicated that fewer individuals met the Canadian criteria than the Fukuda et al. criteria. Those who met the Canadian criteria evidenced more severe symptoms and physical functioning impairment.

CONCLUSIONS: Future research should continue to compare existing case definitions and determine which criteria best select for this illness.

Source: Jason LA, Brown A, Evans M, Sunnquist M, Newton JL. Contrasting Chronic Fatigue Syndrome versus Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fatigue. 2013 Jun 1;1(3):168-183. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728084/ (Full article)

Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions

Abstract:

The symptom spectrum of Myalgic Encephalomyelitis (ME) was first detailed in 1959 and later operationalised into a diagnostic protocol (Melvin Ramsey). In 1988 the Holmes case definition coined the term chronic fatigue syndrome (CFS). Fukuda’s Centers for Disease Control and Prevention criteria are very heterogeneous and comprise patients with milder symptoms than the Holmes case definition. The CDC Empirical Criteria for CFS lack sensitivity and/or specificity. Other CFS definitions, e.g. the Oxford criteria, delineate people with idiopathic fatigue. Some authors make the clinical CFS diagnosis when slightly increased self-rated fatigue scores are present. In 2011, Carruthers’ International Consensus Criteria attempted to restore the focus on selecting people who suffer from ME.

Cognitive bias in criteria construction, patient selection, data collection and interpretation has led to the current state of epistemological chaos with ME, CFS, CFS/ME and ME/CFS, and CF being used interchangeably. Moreover, none of the above mentioned classifications meet statistically based criteria for validation. Diagnostic criteria should be based on statistical methods rather than consensus declarations. Ongoing discussions about which case definition to employ miss the point that the criteria did not pass appropriate external validation.

In 2012, Maes et al. performed pattern recognition methods and concluded that CFS patients (according to Fukuda’s criteria) should be divided into those with CFS or ME, on the basis that people with ME display a worsening of their illness following increases in physical or cognitive activity. Both ME and CFS are complex disorders that share neuro-immune disturbances, which are more severe in ME than in CFS. This paper expands on that strategy and details a range of objective tests, which confirm that a person with ME or CFS has a neuro-immune disease.

By means of pattern recognition methods future research should refine the Maes’ case definitions for ME and CFS by including well-scaled symptoms, staging characteristics and neuro-immune biomarkers, including immune-inflammatory assays, bioenergetic markers and brain imaging.

Source: Morris G, Maes M. Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro Endocrinol Lett. 2013;34(3):185-99. https://www.ncbi.nlm.nih.gov/pubmed/23685416

Comment:

Ellen M Goudsmit

2014 Mar 01 2:10 p.m.
Dr. Melvin Ramsay began writing about the illness now known as ME after the outbreak in north London in 1955. I looked in his book (1988) for a paper written by him in 1959 and found none. The best known article from 1959 was written by the late Dr. Acheson, who gave ME its name in a leader in the Lancet (1956). Dr Ramsay offered a diagnostic protocol but not until the 1980s.

I agree with Morris and Maes that the core symptom of ME is an exacerbation of symptoms following minimal exertion (supported by Paul et al who referred to CFS but actually selected patients with ME, pers. comm.). It should also be noted that none of the existing criteria for ME and CFS have been found to have the required specificity and sensitivity. And that includes the 2011 version.
The abstract indicates a lack of attention to detail. This undermines the understanding of the issues and shows a lack of respect, not only for the researchers but also for the patients, 99% of whom would know how to spell the name of arguably one of the most knowledgeable experts in this field. This failure to check for accuracy is a major cause for confusion in the literature on ME and CFS. And what happened to peer review? Any peer would have noticed the problem with the first sentence.
People really interested in ME and CFS may like to purchase an excellent publication by Shepherd and Chaudhuri summarising the knowledge to date. It’s available from the ME Association in the UK. An authoritative and accurate review (2013).
Leading article. A new clinical entity? Lancet, 1956, 1, 789-790.
Paul, L et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. European Journal of Neurology, 1999, 6, 63-69.
Ramsay, AM. Myalgic encephalomyelitis and postviral fatigue states. Second Ed. Gower Medical Publ. 1988. now available from the MEA Association, UK.

The adoption of chronic fatigue syndrome/myalgic encephalomyelitis case definitions to assess prevalence: a systematic review

Abstract:

PURPOSE: Prevalence estimates have been based on several case definitions of chronic fatigue syndrome (CFS). The purpose of this work is to provide a rigorous overview of their application in prevalence research.

METHODS: A systematic review of primary studies reporting the prevalence of CFS since 1990 was conducted. Studies were summarized according to study design, prevalence estimates, and case definition used to ascertain cases.

RESULTS: Thirty-one studies were retrieved, and eight different case definitions were found. Early estimates of CFS prevalence were based on the 1988 Centers for Disease Control and Prevention, Australian, and Oxford. The 1994 Centers for Disease Control and Prevention, however, has been adopted internationally, as a general standard. Only one study has reported prevalence according to the more recent, Canadian Consensus Criteria. Additional estimates were also found according to definitions by Ho-Yen, the 2005 Centers for Disease Control and Prevention empirical definition, and an epidemiological case definition.

CONCLUSIONS: Advances in clinical case definitions during the past 10 years such as the Canadian Consensus Criteria have received little attention in prevalence research. Future assessments of prevalence should consider adopting more recent developments, such as the newly available International Consensus Criteria. This move could improve the surveillance of more specific cases found within CFS.

Source: Johnston S, Brenu EW, Staines DR, Marshall-Gradisnik S. The adoption of chronic fatigue syndrome/myalgic encephalomyelitis case definitions to assess prevalence: a systematic review. Ann Epidemiol. 2013 Jun;23(6):371-6. doi: 10.1016/j.annepidem.2013.04.003. https://www.ncbi.nlm.nih.gov/pubmed/23683713

The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis

Abstract:

PURPOSE: To perform a meta-analysis to examine variability among prevalence estimates for CFS/ME, according to the method of assessment used.

METHODS: Databases were systematically searched for studies on CFS/ME prevalence in adults that applied the 1994 Centers for Disease Control (CDC) case definition.1 Estimates were categorized into two methods of assessment: self-reporting of symptoms versus clinical assessment of symptoms. Meta-analysis was performed to pool prevalences by assessment using random effects modeling. This was stratified by sample setting (community or primary care) and heterogeneity was examined using the I (2) statistic.

RESULTS: Of 216 records found, 14 studies were considered suitable for inclusion. The pooled prevalence for self-reporting assessment was 3.28% (95% CI: 2.24-4.33) and 0.76% (95% CI: 0.23-1.29) for clinical assessment. High variability was observed among self-reported estimates, while clinically assessed estimates showed greater consistency.

CONCLUSION: The observed heterogeneity in CFS/ME prevalence may be due to differences in method of assessment. Stakeholders should be cautious of prevalence determined by the self-reporting of symptoms alone. The 1994 CDC case definition appeared to be the most reliable clinical assessment tool available at the time of these studies. Improving clinical case definitions and their adoption internationally will enable better comparisons of findings and inform health systems about the true burden of CFS/ME.

Source: Johnston S, Brenu EW, Staines D, Marshall-Gradisnik S. The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis. Clin Epidemiol. 2013;5:105-10. doi: 10.2147/CLEP.S39876. Epub 2013 Mar 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616604/ (Full article)

Diagnosis of myalgic encephalomyelitis: where are we now?

Abstract:

INTRODUCTION: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with “chronic fatigue syndrome.”

AREAS COVERED: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.

EXPERT OPINION: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this “chronic fatigue spectrum” should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

Comment in: Comment and reply on: ME is a distinct diagnostic entity, not part of a chronic fatigue spectrum. [Expert Opin Med Diagn. 2013]

Source: Maes M, Anderson G, Morris G, Berk M. Diagnosis of myalgic encephalomyelitis: where are we now? Expert Opin Med Diagn. 2013 May;7(3):221-5. doi: 10.1517/17530059.2013.776039. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/23480562

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria

Abstract:

BACKGROUND: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion.

METHODS: Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects.

RESULTS: Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS-Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R(2)=0.977; Cronbach’s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid.

CONCLUSIONS: Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.

Source: Baraniuk JN, Adewuyi O, Merck SJ, Ali M, Ravindran MK, Timbol CR, Rayhan R, Zheng Y, Le U, Esteitie R, Petrie KN. A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria. Am J Transl Res. 2013;5(1):53-68. Epub 2013 Jan 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560481/ (Full article)

Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study

Abstract:

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome.

38 CFS patients aged 12-18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007).

Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04).

In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.

Source: Wyller VB, Helland IB. Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study. Biopsychosoc Med. 2013 Feb 7;7(1):5. doi: 10.1186/1751-0759-7-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570350/ (Full article)

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

Abstract:

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).

Source: Maes M, Twisk FN, Johnson C. 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. Psychiatry Res. 2012 Dec 30;200(2-3):754-60. doi: 10.1016/j.psychres.2012.03.031. Epub 2012 Apr 21. https://www.ncbi.nlm.nih.gov/pubmed/22521895