chronic fatigue syndrome vs myalgic encephalomyelitis

A perspective on causation of the chronic fatigue syndrome by considering its nosology

Abstract:

The causes of chronic fatigue syndrome (CFS) remain unknown, with many failures to replicate new findings. This may be because the condition is hard to diagnose, difficult to classify, or because of its heterogeneous nature. Authors have problems in differentiating CFS from myalgic encephalomyelitis (ME), which leads many to label it as a hybrid CFS/ME or ME/CFS. Attempts to validate the many published criterion-based definitions have ended in failure. The International Classification of Diseases provide several different descriptions to choose from, although the latest 11th edition has narrowed this down. This paper describes conventional attempts to define and classify the illness, suggesting that this may be what leads to a failure to replicate putative causes. The approach to CFS/ME may require a shift in the assumption that the illness is homogeneous. An alternative approach is provided by studies suggesting that the condition is heterogeneous. ‘

CONCLUSION: The way forward may be to be over-inclusive regarding the diagnosis as a first step, while subdividing the condition into likely subgroups as a means of finding valid and reliable associations with potential causes. Studies of aetiology must involve prospective designs since cross-sectional studies cannot inform either aetiology or pathophysiology.

Source: White PD. A perspective on causation of the chronic fatigue syndrome by considering its nosology. J Eval Clin Pract. 2019 Aug 1. doi: 10.1111/jep.13240. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31373106

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

Estimating Prevalence, Demographics and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning

Abstract:

Techniques of data mining and machine learning were applied to a large database of medical and facility claims from commercially insured patients to determine the prevalence, gender demographics, and costs for individuals with provider-assigned diagnosis codes for myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). The frequency of diagnosis was 519 – 1,038/100,000 with the relative risk of females being diagnosed with ME or CFS compared to males 1.238 and 1.178, respectively. While the percentage of women diagnosed with ME/CFS is higher than the percentage of men, ME/CFS is not a “woman’s disease.” Thirty-five to forty percent of diagnosed patients are men. Extrapolating from this frequency of diagnosis and based on the estimated 2017 population of the United States, a rough estimate for the number of patients who may be diagnosed with ME or CFS in the U.S. is 1.7 million to 3.38 million.

Patients diagnosed with CFS appear to represent a more heterogeneous group than those diagnosed with ME. A machine learning model based on characteristics of individuals diagnosed with ME was developed and applied, resulting in a predicted prevalence of 857/100,000 (p>0.01), or roughly 2.8 million in the U.S.

Average annual costs for individuals with a diagnosis of ME or CFS were compared with those for lupus (all categories) and multiple sclerosis (MS), and found to be 50% higher for ME and CFS than for lupus or MS, and three to four times higher than for the general insured population.

A separate aspect of the study attempted to determine if a diagnosis of ME or CFS could be predicted based on symptom codes in the insurance claims records. Due to the absence of specific codes for some core symptoms, we were unable to validate that the information in insurance claims records is sufficient to identify diagnosed patients or suggest that a diagnosis of ME or CFS should be considered based solely on looking for presence of those symptoms.

These results show that a prevalence rate of 857/100,000 for ME/CFS is not unreasonable; therefore, it is not a rare disease, but in fact a relatively common one.

Source: Ashley Valdez, Elizabeth E. Hancock, Seyi Adebayo, David Kiernicki, Daniel Proskauer, John R. Attewell, Lucinda Bateman, Alfred DeMaria, Jr, Charles W. Lapp, Peter C. Rowe and Charmian Proskauer. Estimating Prevalence, Demographics and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning. Front. Pediatr. | doi: 10.3389/fped.2018.00412 https://www.frontiersin.org/articles/10.3389/fped.2018.00412/full (Full article)

A Comparison of Case Definitions for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

Abstract:

Many professionals have described the clinical presentation of myalgic
encephalomyelitis (ME), but recent efforts have focused on the development of ME
criteria that can be reliably applied. The current study compared the symptoms and
functioning of individuals who met the newly-developed Institute of Medicine (IOM)
clinical criteria to a revised version of the London criteria for ME. While 76% of a
sample diagnosed with chronic fatigue syndrome (CFS) met the IOM criteria, 44%
met the revised London criteria. The revised London criteria identified patients with
greater physical impairment. The results of this study indicate the need for a standard
case definition with specific guidelines for operationalization. The application of case
definitions has important implications for the number of individuals identified with ME,
the pattern of symptoms experienced by these individuals, and the severity of their
symptoms and functional limitations. Sample heterogeneity across research studies
hinders researchers from replicating findings and impedes the search for biological
markers and effective treatments.

Source: Madison Sunnquist, Leonard A. Jason, Pamela Nehrke, and Ellen M. Goudsmit. A Comparison of Case Definitions for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Journal of Chronic Diseases and Management. https://www.jscimedcentral.com/ChronicDiseases/chronicdiseases-2-1013.pdf (Full article)

Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward

Abstract:

Myalgic encephalomyelitis (ME), described in the medical literature since 1938, is characterized by distinctive muscular symptoms, neurological symptoms, and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, is chronic fatigue, which should be accompanied by at least four or more out of eight “additional” symptoms.

The use of the abstract, polythetic criteria of CFS, which define a heterogeneous patient population, and self-report has hampered both scientific progress and accurate diagnosis. To resolve the “diagnostic impasse” the Institute of Medicine proposes that a new clinical entity, systemic exercise intolerance disease (SEID), should replace the clinical entities ME and CFS. However, adopting SEID and its defining symptoms, does not resolve methodological and diagnostic issues.

Firstly, a new diagnostic entity cannot replace two distinct, partially overlapping, clinical entities such as ME and CFS. Secondly, due to the nature of the diagnostic criteria, the employment of self-report, and the lack of criteria to exclude patients with other conditions, the SEID criteria seem to select an even more heterogeneous patient population, causing additional diagnostic confusion. This article discusses methodological and diagnostic issues related to SEID and proposes a methodological solution for the current “diagnostic impasse”.

Source: Twisk FN. Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward. Diagnostics (Basel). 2016 Feb 5;6(1). pii: E10. doi: 10.3390/diagnostics6010010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808825/ (Full article)

Chronic fatigue syndrome versus sudden onset myalgic encephalomyelitis

Abstract:

A revised sudden onset case definition for Myalgic Encephalomyelitis (ME) has been developed (Jason, Damrongvachiraphan, et al., 2012 ) based on past case definitions. In a prior study, Jason, Brown, and colleagues ( 2012 ) compared patients recruited using the 1994 case definition of chronic fatigue syndrome (CFS) to contrast those meeting criteria for the revised ME criteria.

They found that this revised ME case definition identified patients with more functional impairments and physical, mental, and cognitive problems than those meeting the CFS criteria. The study by Jason, Brown, et al. ( 2012 ) only selected individuals who first met the CFS criteria, and it only relied on one Chicago-based data set. The current study replicated this comparison with two distinct data sets with different case ascertainment methods. Results indicate that the ME criteria identified a group of patients with more functional disabilities as well as more severe post-exertional malaise symptoms.

Source: Jason LA, Evans M, Brown A, Sunnquist M, Newton JL. Chronic fatigue syndrome versus sudden onset myalgic encephalomyelitis. J Prev Interv Community. 2015;43(1):62-77. doi: 10.1080/10852352.2014.973233. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295655/ (Full article)

Defining Essential Features of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome

Abstract:

Considerable debate surrounds the search for the defining features of patients with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Current case definitions were created through clinical consensus. Failure to operationalize these case definitions has led to considerable variability in the identification of patients. In addition, some case definitions (e.g., Fukuda et al., 1994) do not require cardinal symptoms of this illness, where as other case definitions do require core symptoms of this illness (Carruthers et al., 2003, 2011), and these latter case criteria appear to identify a more impaired group of patients.

Criterion variance is most likely to occur when operationally explicit criteria do not exist for diagnostic categories (Spitzer, Endicott, & Robins, 1978), or when there are varying criteria for contrasting case definitions, which is an impediment to the research in this field. To deal with this problem, it is possible to differentiate those that meet more loosely defined criteria from those that are more narrowly and defined, thus differentiating CFS from ME.

In order to progress the search for biological markers and effective treatments, essential features need to be operationalized and broadly used in order to increase the probability that individuals included in samples have the same underlying illness.

Source: Jason LA, Sunnquist M, Brown A, Reed J. Defining Essential Features of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. J Hum Behav Soc Environ. 2015;25(6):657-674. Epub 2015 May 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817848/ (Full article)

What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia

Abstract:

The current study had two objectives. (1) to compare objective and self-report measures in patients with chronic fatigue syndrome (CFS) according to the 1994 Center for Disease Control (CDC) criteria, patients with multiple sclerosis (MS), and healthy controls, and (2) to contrast CFS patients who only fulfill CDC criteria to those who also fulfill the criteria for myalgic encephalomyelitis (ME), the 2003 Canadian criteria for ME/CFS, or the comorbid diagnosis of fibromyalgia (FM).

One hundred six participants (48 CFS patients diagnosed following the 1994 CDC criteria, 19 MS patients, and 39 healthy controls) completed questionnaires assessing symptom severity, quality of life, daily functioning, and psychological factors. Objective measures consisted of activity monitoring, evaluation of maximal voluntary contraction and muscle recovery, and cognitive performance. CFS patients were screened whether they also fulfilled ME criteria, the Canadian criteria, and the diagnosis of FM.

CFS patients scored higher on symptom severity, lower on quality of life, and higher on depression and kinesiophobia and worse on MVC, muscle recovery, and cognitive performance compared to the MS patients and the healthy subjects. Daily activity levels were also lower compared to healthy subjects. Only one difference was found between those fulfilling the ME criteria and those who did not regarding the degree of kinesiophobia (lower in ME), while comorbidity for FM significantly increased the symptom burden.

CFS patients report more severe symptoms and are more disabled compared to MS patients and healthy controls. Based on the present study, fulfillment of the ME or Canadian criteria did not seem to give a clinically different picture, whereas a diagnosis of comorbid FM selected symptomatically worse and more disabled patients.

Source: Meeus M, Ickmans K, Struyf F, Kos D, Lambrecht L, Willekens B, Cras P, Nijs J. What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. Clin Rheumatol. 2016 Jan;35(1):191-203. doi: 10.1007/s10067-014-2793-x. Epub 2014 Oct 14. https://www.ncbi.nlm.nih.gov/pubmed/25308475

The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups

Abstract:

Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are used interchangeably, the diagnostic criteria define two distinct clinical entities. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after a minor exertion, are distinctive symptoms of ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic fatigue (syndrome), other disorders and deconditioning.

The introduction of the label, but more importantly the diagnostic criteria for CFS have generated much confusion, mostly because chronic fatigue is a subjective and ambiguous notion. CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and unrefreshing sleep. Most of the research into ME and/or CFS in the last decades was based upon the multivalent CFS criteria, which define a heterogeneous patient group.

Due to the fact that fatigue and other symptoms are non-discriminative, subjective experiences, research has been hampered. Various authors have questioned the physiological nature of the symptoms and qualified ME/CFS as somatization. However, various typical symptoms can be assessed objectively using standardized methods. Despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively, e.g., immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction.

However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms, as much as possible that well-defined clinical and biological subgroups of ME and CFS patients are investigated in more detail, and that patients are monitored before, during and after interventions with objective measures and biomarkers.

Source: Twisk FN. The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups. Front Physiol. 2014 Mar 27;5:109. doi: 10.3389/fphys.2014.00109. eCollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974331/ (Full article)

Are Myalgic Encephalomyelitis and chronic fatigue syndrome different illnesses? A preliminary analysis

Abstract:

Considerable discussion has transpired regarding whether chronic fatigue syndrome is a distinct illness from Myalgic Encephalomyelitis. A prior study contrasted the Myalgic Encephalomyelitis International Consensus Criteria with the Fukuda and colleagues’ chronic fatigue syndrome criteria and found that the Myalgic Encephalomyelitis International Consensus Criteria identified a subset of patients with greater functional impairment and physical, mental, and cognitive problems than the larger group who met Fukuda and colleagues’ criteria. The current study analyzed two discrete data sets and found that the Myalgic Encephalomyelitis International Consensus Criteria identified more impaired individuals with more severe symptomatology.

Source: Jason LA, Sunnquist M, Brown A, Evans M, Newton JL. Are Myalgic Encephalomyelitis and chronic fatigue syndrome different illnesses? A preliminary analysis. J Health Psychol. 2016 Jan;21(1):3-15. doi: 10.1177/1359105313520335. Epub 2014 Feb 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125561/ (Full article)