Case Definition – Page 2 – American ME and CFS Society

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.

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)

Myalgic Encephalomyelitis or What? The International Consensus Criteria

Abstract:

Myalgic encephalomyelitis (ME) is a neuromuscular disease with two distinctive types of symptoms (muscle fatigability or prolonged muscle weakness after minor exertion and symptoms related to neurological disturbance, especially of sensory, cognitive, and autonomic functions) and variable involvement of other bodily systems. Chronic fatigue syndrome (CFS), introduced in 1988 and re-specified in 1994, is defined as (unexplained) chronic fatigue accompanied by at least four out of eight listed (ill-defined) symptoms. Although ME and CFS are two distinct clinical entities (with partial overlap), CFS overshadowed ME for decades.

In 2011, a panel of experts recommended abandoning the label CFS and its definition and proposed a new definition of ME: the International Consensus Criteria for ME (ME-ICC). In addition to post-exertional neuroimmune exhaustion (PENE), a mandatory feature, a patient must experience at least three symptoms related to neurological impairments; at least three symptoms related to immune, gastro-intestinal, and genitourinary impairments; and at least one symptom related to energy production or transportation impairments to meet the diagnosis of ME-ICC.

A comparison between the original definition of ME and the ME-ICC shows that there are some crucial differences between ME and ME-ICC. Muscle fatigability, or long-lasting post-exertional muscle weakness, is the hallmark feature of ME, while this symptom is facultative for the diagnosis under the ME-ICC. PENE, an abstract notion that is very different from post-exertional muscle weakness, is the hallmark feature of the ME-ICC but is not required for the diagnosis of ME. The diagnosis of ME requires only two type of symptoms (post-exertional muscle weakness and neurological dysfunction), but a patient has to experience at least eight symptoms to meet the diagnosis according to the ME-ICC. Autonomic, sensory, and cognitive dysfunction, mandatory for the diagnosis of ME, are not compulsory to meet the ME-ICC subcriteria for ‘neurological impairments’.

In conclusion, the diagnostic criteria for ME and of the ME-ICC define two different patient groups. Thus, the definitions of ME and ME-ICC are not interchangeable.

Source: Twisk, F. Myalgic Encephalomyelitis or What? The International Consensus Criteria. Diagnostics 2019, 9, 1. https://www.mdpi.com/2075-4418/9/1/1/htm (Full article)

Myalgic Encephalomyelitis (ME) or What? An Operational Definition

Abstract:

Myalgic encephalomyelitis (ME), identified as a new clinical entity with distinctive features in 1956, was originally considered as a neuromuscular disease. In 1988 the Centers for Disease Control and Prevention introduced the ill-defined concept of chronic fatigue syndrome (CFS). As predicted, CFS, unjustly considered to be a synonym for ME, pushed ME to the background. To develop effective therapies for of ME and CFS, it is essential to investigate patients with ME specifically. For that reason, an operational definition of ME is indispensable. This article proposes an operational definition based on the most recent formal definitions and symptoms observed in ME. ME is a multi-systemic illness, which

(1) often has a sudden onset, in most cases a respiratory and/or gastro-intestinal infection, but a gradual or more dramatic onset is also possible;

(2) has an epidemic and an endemic form;

(3) has an unique clinical pattern deviating from other post-viral states;

(4) is distinguished by muscle fatigability/prolonged muscle weakness after trivial exertion;

(5) is accompanied by symptoms relating to neurological disturbance, especially of cognitive, autonomic, and sensory functions;

(6) can be accompanied by symptoms associated with cardiac and other systems;

(7) is characterized by fluctuation of symptoms (within and between “episodes”);

(8) has a prolonged relapsing course; and

(9) has a tendency to become chronic.

In conclusion, a discriminative definition for ME contains four mandatory elements:

(1) muscle fatigability/post-exertional muscle weakness lasting for days;

(2) operational criteria for “neurological disturbance, especially of cognitive, autonomic and sensory functions”;

(3) fluctuation of symptoms; and

(4) a prolonged relapsing course. This tentative definition of ME justifies the qualification “neuromuscular disease”.

Source: Twisk F. Myalgic Encephalomyelitis (ME) or What? An Operational Definition. Diagnostics (Basel). 2018 Sep 8;8(3). pii: E64. doi: 10.3390/diagnostics8030064. http://www.mdpi.com/2075-4418/8/3/64 (Full study)

Meta-analysis investigating post-exertional malaise between patients and controls

Abstract:

Post-exertional malaise is either required or included in many previously proposed case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. A meta-analysis of odds ratios (ORs; association between patient status and post-exertional malaise status) and a number of potential moderators (i.e. study-level characteristics) of effect size were conducted.

Post-exertional malaise was found to be 10.4 times more likely to be associated with a myalgic encephalomyelitis/chronic fatigue syndrome diagnosis than with control status. Significant moderators of effect size included patient recruitment strategy and control selection. These findings suggest that post-exertional malaise should be considered a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome.

Source: Brown A, Jason LA. Meta-analysis investigating post-exertional malaise between patients and controls. J Health Psychol. 2018 Jul 1:1359105318784161. doi: 10.1177/1359105318784161. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29974812