Category: Overview

Myalgic encephalomyelitis or chronic fatigue syndrome

Abstract:

In this review, we discuss the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is characterised by extreme mental and physical fatigue with associated symptoms of pain, disturbed sleep, cognitive and autonomic dysfunction, as well as post-exertional malaise. This condition is often preceded by an infection, severe physiological and/or psychological strain. Over the last decades, research has demonstrated mitochondrial, neuroendocrine, immunological, and metabolic perturbations in patients with ME/CFS, giving hope for the development of new biomarkers and new treatment modalities.

Source: Brinth L, Nielsen H, Varming K, Boonen SE, Ebsen ACG, Fernández-Guerra P, Schou AS, Mehlsen J, Gregersen N, Brandslund I, Olsen RKJ. Myalgic encephalomyelitis or chronic fatigue syndrome. Ugeskr Laeger. 2019 Jun 10;181(24). pii: V08180570. [Article in Danish] https://www.ncbi.nlm.nih.gov/pubmed/31267953

CDC Grand Rounds: Chronic Fatigue Syndrome – Advancing Research and Clinical Education

Abstract:

Chronic fatigue syndrome (CFS) is a complex and serious illness that is often misunderstood. Experts have noted that the terminology “chronic fatigue syndrome” can trivialize this illness and stigmatize persons who experience its symptoms (1). The name was coined by a group of clinicians convened by CDC in the late 1980s to develop a research case definition for the illness, which, at the time, was called chronic Epstein-Barr virus syndrome. The name CFS was suggested because of the characteristic persistent fatigue experienced by all those affected and the evidence that acute or reactivated Epstein-Barr virus infection was not associated with many cases (2).

However, the fatigue in this illness is striking and quite distinct from the common fatigue everyone experiences. A variety of other names have been used, including myalgic encephalomyelitis (ME), ME/CFS, chronic fatigue immune dysfunction, and most recently, systemic exertion intolerance disease (3). The lack of agreement about nomenclature need not be an impediment for advancing critically needed research and education. The term ME/CFS will be used in this article.

 

Source: Unger ER, Lin JS, Brimmer DJ, Lapp CW, Komaroff AL, Nath A, Laird S, Iskander J. CDC Grand Rounds: Chronic Fatigue Syndrome – Advancing Research and Clinical Education. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1434-1438. doi: 10.15585/mmwr.mm655051a4. https://www.cdc.gov/mmwr/volumes/65/wr/mm655051a4.htm (Full article)

 

Investigating unexplained fatigue in general practice with a particular focus on CFS/ME

Abstract:

Unexplained fatigue is not infrequent in the community. It presents a number of challenges to the primary care physician and particularly if the clinical examination and routine investigations are normal. However, while fatigue is a feature of many common illnesses, it is the main problem in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This is a poorly understood condition that is accompanied by several additional symptoms which suggest a subtle multisystem dysfunction. Not infrequently it is complicated by sleep disturbance and alterations in attention, memory and mood.

Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and indeed in virtually all countries around the world. However, unexplained fatigue and CFS/ME may be confidently diagnosed on the basis of specific clinical criteria combined with the normality of routine blood tests. The latter include those that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. Early diagnosis and intervention in general practice will do much to reduce patient anxiety, encourage improvement and prevent expensive unnecessary investigations.

There is presently an on-going debate as to the precise criteria that best confirms CFS/ME to the exclusion of other medical and psychiatric/psychological causes of chronic fatigue. There is also some disagreement as to best means of investigating and managing this very challenging condition. Uncertainty here can contribute to patient stress which in some individuals can perpetuate and aggravate symptoms. A simple clinical scoring system and a short list of routine investigations should help discriminate CFS/ME from other causes of continued fatigue.

 

Source: Bansal AS. Investigating unexplained fatigue in general practice with a particular focus on CFS/ME. BMC Fam Pract. 2016 Jul 19;17:81. doi: 10.1186/s12875-016-0493-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950776/ (Full article)

 

Comments

Ellen M Goudsmit 2016 Jul 24 07:44 a.m.
I am not persuaded that ME, as described by clinicians and researchers prior to 1988, has much to do with neurasthenia. Indeed, fatigue was not a criterion for the diagnosis of ME [1]. It presents as a more neurological disorder, e.g. muscle weakness after minimal exertion. References to CFS/ME are misleading where research used criteria for chronic fatigue or CFS, rather than ME. The assumption of equivalence has been tested and the differences are of clinical significance.

A useful strategy to avoid post-exertion related exacerbations is pacing [2]. I missed a reference.

1 Goudsmit, EM, Shepherd, C., Dancey, CP and Howes, S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychology Update, 2009, 18, 1, 26-33. http://www.bpsshop.org.uk/Health-Psychology-Update-Vol-18-No-1-2009-P797.aspx

2 Goudsmit, EM., Jason, LA, Nijs, J and Wallman, KE. Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: A consensus document. Disability and Rehabilitation, 2012, 34, 13, 1140-1147. doi: 10.3109/09638288.2011.635746.
Tom Kindlon 2016 Jul 21 8:49 p.m.
Some information on an unpublished study on pupil responses:
Dr Bansal mentions he has observed unusual responses by the pupils to light. I thought I would highlight a study that was done in the late 1990s looking at this. Unfortunately the researcher passed away before it could be published. Perhaps there are better sources than these lay articles but I thought they might be of some use in the hope that the finding might be followed up again.

Eye test hope for ME sufferers

Jenny Hope

A new eye test can ‘see’ changes in the brain triggered by the crippling disease ME. The advance comes from a number of research projects that could lead to better treatments for the illness once ridiculed as ‘yuppie flu’.

It gives fresh hope to an estimated 150,000 victims of chronic fatigue syndrome, which can leave those worst affected bedridden with pain, suffering short-term memory loss and unable to walk even short distances.

Scientists at the Royal Free Hospital and the City University in London have found a way to measure changes in the eyes of ME patients which may show they lack an important brain chemical.

A study by Dr Ian James and Professor John Barbur checked the pupils of 16 ME patients and 24 healthy individuals, using a computer to measure changes identified between the two groups.

They found patients with chronic fatigue had larger pupils and also had a stronger reaction to light and other stimuli. The changes could be linked to a deficiency of the brain chemical serotonin, which is known to occur in ME and is also linked to depression.

Professor John Hughes, chairman of the Chronic Fatigue Syndrome Research Foundation, said the research should make it possible to understand changes occurring in the brain of a sufferer.

This could help those studying the effect of different drugs and possibly help doctors diagnose CFS, he added.

At present there are no reliable tests, although a checklist of symptoms developed five years ago is being used by doctors worldwide.

BREAKTHROUGH FOR ME by Geraint Jones

For years, ME has been treated with suspicion by doctors. Many believe that for every genuine sufferer there is another who simply believes himself to be ill. Experts cannot agree on whether the condition is a physical illness or a psychological disorder which exists only in the victim’s mind. One reason for this scepticism is that, as yet, no one has been able to provide an accurate diagnosis for ME, or myalgic encephalomyelitis, which is known to affect 150,000 people in Britain. There is no known cure and treatment is often based on antidepressant drugs like Prozae, with limited success.

All this may be about to change. Dr Ian James, consultant and reader in clinical pharmacology at London’s Royal Free Hospital School of Medicine, believes that he has found a way of diagnosing the chronic fatigue syndrome and hopes to use it to develop a treatment programme. The breakthrough came after months of research spearheaded by Dr James and Professor John Barbur of London’s City University. It centres round the discovery that the eyes of ME sufferers respond to light and motion stimuli in an unusual way.

“Several doctors treating ME patients noticed that they showed an abnormal pupil response”, says Dr James. “When the pupil is subjected to changes in light, or is required to alter focus from a close object to one further away, it does so by constricting and dilating. ME patients’ eyes do this as well but there is an initial period of instability when the pupil fluctuates in size”.

Using a computerised “pupilometer”, which precisely measures eye responses, Dr James embarked on a detailed study of this phenomenon on ME patients, using non-sufferers as a control. A variety of shapes were flashed on to a screen and moved across it, while a computer precisely measured pupil reflex to each of the 40 tests. Results confirmed that the pupil fluctuation was peculiar to those participants who suffered from ME.

Dr James concluded that the abnormal pupil response is a result of some kind of interference in the transfer of impulses from the brain to the eye. He believes that ME is the result of a deficiency of a neuro-transmitter called 5HT, whose job it is to pass impulses through nerves to cells. The eyes of ME sufferers treated with 5HT behave normally. “I do not yet know how the ME virus causes abnormalities in 5HT transmission but it does inhibit its function”, says Dr James.

 

The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is comparable to multiple sclerosis, diabetes or rheumatoid arthritis in prevalence (∼0.2% to 1%), long-term disability, and quality of life,[1–5] yet the scale of biomedical research and funding has been pitifully limited, as the recent National Institutes of Health (NIH) and Institute of Medicine reports highlight.[6,7] Recently in the USA, NIH Director Francis Collins has stated that the NIH will be ramping up its efforts and levels of funding for ME/CFS,[8] which we hope will greatly increase the interest in, and resources for researching this illness. Despite scant funding to date, researchers in the field have generated promising leads that throw light on this previously baffling illness. We suggest the key elements of a concerted research programme and call on the wider biomedical research community to actively target this condition.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867862/

 

Source: Edwards JC, McGrath S, Baldwin A, Livingstone M, Kewley A. The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem. Fatigue. 2016 Apr 2;4(2):63-69. Epub 2016 Apr 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867862/

 

Simon McGrath 2016 May 30 4:05 p.m.

Authors’ abstract

(An abstract wasn’t required for this editorial, but the authors felt it would be helpful to add this one for PubMed. I am one of the authors.)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is as prevalent and disabling as multiple sclerosis, diabetes and rheumatoid arthritis but biomedical research into the condition has been grossly underfunded. However, the NIH is committed to ramping up funding for this illness and there are now promising research leads. We indicate clues to the biological mechanisms that may perpetuate the condition and suggest the key elements of a concerted research programme. In the absence of effective treatments, study of mechanism remains a key priority including the possible role of stochastic factors.

We identify the three most interesting major categories of causal model: (1) the brain is responding normally and symptoms are due to persistent signal input from peripheral tissues, such as cytokines or metabolites; (2) there is a persistent abnormality of ‘housekeeping’ processes in the brain, such as an increase in activation of microglia; and (3) there is a persistent abnormality in neural signalling in sensory pathways.

We recommend seven important, practical steps to make progress towards effective treatments: (1) build research infrastructure, including population-based cohorts with close attention to diagnostic criteria; (2) use new, developing techniques for brain imaging; (3) pursue promising immunological leads, such as natural killer cell abnormalities, cytokine shifts, auto-antibodies, and immune responses to viruses such as Epstein-Barr virus; (4) further explore autonomic/endocrine regulation; (5) extend the research on post-exertional changes in physiology; (6) attempt to replicate key findings to determine which are robust; and (7) present data in a way that allows subgroup analysis, and always provide raw data.

We conclude that the problem of ME/CFS now looks solvable and we call on the wider biomedical research community to target the condition.

Chronic Fatigue Syndrome

Excerpt:

Fatigue is a universal symptom, occurring in all individuals after prolonged exertion or lack of sleep. However, when fatigue is persistently present, without adequate environmental or medical explanation, fatigue has been recognised as the hallmark of a frequent and enigmatic clinical syndrome. Although difficult to precisely define and measure, fatigue is a pervasive sense of tiredness or lack of energy, that is not related exclusively to exertion. Fatigue may be appreciated centrally in terms of concentration, memory and motivation, or appreciated peripherally, where symptoms are often referred to the muscles. Chronic Fatigue Syndrome (CFS) is a term that was chosen and defined by Holmes et al., in 1988 to describe a combination of non-specific symptoms including profound fatigue, weakness, malaise and cognitive impairment with a remarkable lack of objective physical or laboratory abnormalities (1).

This syndrome had previously been known as “Chronic Epstein-Barr Virus Syndrome” and “Chronic Mononucleosis”. The terminology “CFS” was widely accepted because it implies no aetiology or specific pathological process. Several definitions of CFS have been developed, primarily to standardise research (2,3). It was not intended that they be used for clinical diagnosis. The Canadian Clinical Working Case Definition of Chronic Fatigue Syndrome was developed in response to an increasing need for such a definition for practising clinicians (4). It is the first definition that was created primarily to aid in clinical diagnosis, by encompassing many of the positive signs and symptoms of CFS, in order that it can be recognised as a distinct entity and distinguished from other clinical syndromes that have overlapping symptoms.

Copyright © 2000-2017, MDText.com, Inc.

 

Source: Torpy BDJ, Saranapala M. Chronic Fatigue Syndrome. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R,Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. 2014 Nov 20. https://www.ncbi.nlm.nih.gov/books/NBK279099/ (Full article)

 

Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness

Excerpt:

Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are serious, debilitating conditions that affect millions of people in the United States and around the world. ME/CFS can cause significant impairment and disability. Despite substantial efforts by researchers to better understand ME/CFS, there is no known cause or effective treatment. Diagnosing the disease remains a challenge, and patients often struggle with their illness for years before an identification is made. Some health care providers have been skeptical about the serious physiological — rather than psychological — nature of the illness. Once diagnosed, patients often complain of receiving hostility from their health care provider as well as being subjected to treatment strategies that exacerbate their symptoms.

Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome proposes new diagnostic clinical criteria for ME/CFS and a new term for the illness — systemic exertion intolerance disease(SEID). According to this report, the term myalgic encephalomyelitis does not accurately describe this illness, and the term chronic fatigue syndrome can result in trivialization and stigmatization for patients afflicted with this illness. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome stresses that SEID is a medical — not a psychiatric or psychological — illness.

This report lists the major symptoms of SEID and recommends a diagnostic process.One of the report’s most important conclusions is that a thorough history, physical examination, and targeted work-up are necessary and often sufficient for diagnosis. The new criteria will allow a large percentage of undiagnosed patients to receive an accurate diagnosis and appropriate care. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome will be a valuable resource to promote the prompt diagnosis of patients with this complex, multisystem, and often devastating disorder; enhance public understanding; and provide a firm foundation for future improvements in diagnosis and treatment.

Copyright 2015 by the National Academy of Sciences. All rights reserved.

 

Source: Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb.  The National Academies Collection: Reports funded by National Institutes of Health. https://www.ncbi.nlm.nih.gov/books/NBK274235/ (Full article)

 

Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome

Abstract:

OBJECTIVES: To investigate associated dimensions of fatigue regarding cognitive impairment, psychomotor performances, muscular effort power and circulating cytokine levels and their relations to symptom intensity in a sample of pure chronic fatigue syndrome (CFS) patients without overlapping objective sleepiness or sleep disorders.

METHODS: 16 CFS patients were compared to 14 matched controls. We assessed structured symptom-scales, polysomnography, multiple sleep latency tests, attention (Zazzo-Cancellation ZCT, digit-symbol-substitution DSST), psychomotor vigilance and speed (PVT, finger tapping test, FTT), dynamometer handgrip force (tonic and phasic trials) and circulating cytokines (IFN-γ, IL-1b, IL-6, IL-8, IL-10, TNF-α).

RESULTS: In addition to fatigue, CFS patients presented with higher affective symptom intensity and worse perceived sleep quality. Polysomnography showed more slow-wave sleep and microarousals in CFS but similar sleep time, efficiency and light-sleep durations than controls. Patients presented with impaired attention (DSST, ZCT), slower reaction times (PVT) but not with lower hit rates (FTT). Notwithstanding lower grip strength during tonic and phasic trials, CFS also presented with higher fatigability during phasic trials. Cytokine levels were increased for IL-1b, IL-8, IL-10 and TNF-α and fatigue intensity was correlated to grip strength and IL-8.

CONCLUSIONS: In contrast to sleepiness, chronic fatigue is a more complex phenomenon that cannot be reduced to one single measured dimension (i.e., sleep propensity). Showing its relations to different measurements, our study reflects this multidimensionality, in a psychosomatic disorder such as CFS. To obtain objective information, routine assessments of fatigue should rule out sleepiness, combine aspects of mental and physical fatigue and focus on fatigability.

 

Source: D, Mairesse O, Montana X, Gilson M, Corazza F, Lefevre N, Linkowski P, Le Bon O, Verbanck P. Dimensions of pure chronic fatigue: psychophysical, cognitive and biological correlates in the chronic fatigue syndrome. Eur J Appl Physiol. 2014 Sep;114(9):1841-51. doi: 10.1007/s00421-014-2910-1. Epub 2014 May 31. https://www.ncbi.nlm.nih.gov/pubmed/24878689

 

Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue (CF) are distinct diagnostic categories with regard to clinical symptoms, severity of illness and biomarkers. Patients with ME and CFS show higher scores on fatigue, neurocognitive disorders, hyperalgesia, autonomic symptoms, postexertional malaise and a subjective feeling of infection than patients with CF. ME is characterized by increased postexertional malaise, a subjective feeling of infection and neurocognitive disorders and is a more severe variant than CFS.

Fukuda’s 1994 CDC criteria are adequate to make a distinction between patients with ME/CFS and CF, while ME/CFS patients should be subdivided into those with and without postexertional malaise into ME and CFS, respectively. Different interrelated pathophysiological mechanisms play a role in ME/CFS, i.e. (1) inflammation and immune activation, (2) oxidative and nitrosative stress and lowered antioxidant defenses, (3) activation of cell signaling networks, e.g. nuclear factor ĸβ, the 2 9 ,5 9 -oligoadenylate/RNase-L and/or protein kinase R pathway, (4) a transition towards autoimmune reactions, and (5) bacterial translocation.

The inflammatory biomarkers are higher in ME/CFS than in CF and higher in ME than in CFS. The above-mentioned pathways may explain the onset of characteristic ME/CFS symptoms, such as fatigue, malaise, autonomic symptoms, hyperalgesia, and neurocognitive symptoms. Different etiological factors may trigger ME/CFS/CF, e.g. viral and bacterial infections, and (auto)immune and inflammatory disorders, while psychosocial and physical stressors act as modulating factors. New pathophysiologically driven drug candidates for ME and CFS are discussed which target the pathways that play a role in ME/CFS.

Copyright © 2013 S. Karger AG, Basel.

 

Source: Maes M. Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome. Mod Trends Pharmacopsychiatri. 2013;28:162-74. doi: 10.1159/000343982. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/25224898

 

Chronic fatigue syndrome: diagnosis and treatment

Abstract:

Chronic fatigue syndrome is characterized by debilitating fatigue that is not relieved with rest and is associated with physical symptoms. The Centers for Disease Control and Prevention criteria for chronic fatigue syndrome include severe fatigue lasting longer than six months, as well as presence of at least four of the following physical symptoms: postexertional malaise; unrefreshing sleep; impaired memory or concentration; muscle pain; polyarthralgia; sore throat; tender lymph nodes; or new headaches. It is a clinical diagnosis that can be made only when other disease processes are excluded. The etiology of chronic fatigue syndrome is unclear, is likely complex, and may involve dysfunction of the immune or adrenal systems, an association with certain genetic markers, or a history of childhood trauma. Persons with chronic fatigue syndrome should be evaluated for concurrent depression, pain, and sleep disturbances. Treatment options include cognitive behavior therapy and graded exercise therapy, both of which have been shown to moderately improve fatigue levels, work and social adjustment, anxiety, and postexertional malaise. No pharmacologic or alternative medicine therapies have been proven effective.

Comment in: Article on CFS does not reflect current best treatment practices. [Am Fam Physician. 2013]

 

Source: Yancey JR, Thomas SM. Chronic fatigue syndrome: diagnosis and treatment. Am Fam Physician. 2012 Oct 15;86(8):741-6. http://www.aafp.org/afp/2012/1015/p741.html (Full article)

 

Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units

Abstract:

BACKGROUND AND OBJECTIVE: The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units.

PATIENTS AND METHODS: We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment.

RESULTS: A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment.

CONCLUSIONS: CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity.

Copyright © 2011 Elsevier España, S.L. All rights reserved.

Comment in: Chronic fatigue syndrome: current situation. [Rev Clin Esp. 2011]

 

Source: Ruiz E, Alegre J, García Quintana AM, Aliste L, Blázquez A, Fernández de Sevilla T. Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units. Rev Clin Esp. 2011 Sep;211(8):385-90. doi: 10.1016/j.rce.2011.02.013. Epub 2011 Jul 27. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21794854