Category: Overview

Chronic fatigue syndrome: source of controversy

Abstract:

Chronic fatigue syndrome (CFS) remains a controversial medical disorder. A combination of poorly executed studies using variable case definitions and diagnostic criteria have led to controversial results. These controversies cloud our vision on CFS, and lead to scepticism and frustration among patients, doctors and researchers. For future perspective, interdisciplinary studies of high quality with large well-defined patient groups and adequate controls are needed.

Source: Raijmakers RPH, van der Meer JWM. Het chronische-vermoeidheidsyndroom: bron van ophef [Chronic fatigue syndrome: source of controversy]. Ned Tijdschr Geneeskd. 2020 Dec 10;164:D5611. Dutch. PMID: 33332043. [Article in Dutch] https://pubmed.ncbi.nlm.nih.gov/33332043/

The case of Chronic Fatigue Syndrome-Myalgic Encephalomyelitis

Overview:

Chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) affect approximately 1 million Americans (Jason, Richman, Rademaker, Jordan, Plioplys, Taylor, et al., 199%); while some individuals believe that CFS and ME refer to the same illness, others characterize ME as a more severe, neurological disorder that is discrete from CES (Twisk, 2013). This controversy will be reviewed in detail. The widespread, debilitating symptoms of the illnesses include but are not limited to feeling sick after activity (known as post-exertional malaise), memory and concentration problems, and unrefreshing sleep (IOM, 2015).

Some researchers suggest that ME and CFS were first conceptualized under the diagnostic label ‘newrasthenia,’ defined as a neurological disease characterized by muscle weakness or fatigue. Notably, neurasthenia was one of the most frequently diagnosed illnesses in the late nineteenth century. However, use of this term had substantially decreased by the mid-twentieth century (Wessely, 1994)

Throughout the twentieth century, several outbreaks of idiopathic, fatigue-related illneses occurred, including ‘atypical poliomyelitis’ at Los Angeles County Hospital in 1934 (Meals, Hauser, & Bowe 1938), ‘encephalomyelits’ at the Royal Free Hospital in London in 1955 (Crowley, Nelon, & Stovi 1957), and ‘chronic mononucleosis-like syndrome’ in Lake Tahoe, Nevada, in 1984 (Barnes, 1986). After the Lake Tahoe outbreak, national attention began to focus on this illness (Wessely, 1994), and in 1988, it was named donc fatigue syndrome by the Centers for Disease Control and Prevention (CDC; Holmes, Kaplan, Gantz, Komaroff, Schonberger, Straus, ct al, 1988). For over two decades, the ease definition that the CDC developed (Fukuda, Straus, Hickic, Sharpe, Dobbins, & Komaroff, 1994) has bbeen prominently used in research and clinical practice; however, the Institute of Medicine (10M) recently developed an updated clinical case definition (IOM, 2015).

The annual direct and indirect costs of ME and CFS in the United States are estimated to be between $19 and $24 billion (Jason, Benton, Johnson, & Valentine, 2008). Individuals with ME and CES have an increased risk of cardiovascular-related mortality and a lower mean age of death by suicide and cancer in comparison to the general US population (McManimen, Devendorf, Brow Moore, Moore, & son, 2016).

In addition, arthritis, high blood pressure, fibromyalgia, and multiple chemical sensitivities are commonly comorbid (Jason, Porter, Hunnell, Brown, Rademaker, & Richman, 2011). Although no virus has been identified as the cause of ME and CFS, the immune system may be overactive (Fischer, William, Strauss, Unger, Jason, Marshall, etl, 2014), and there is and fibromyalgia using regression tree analysis and artificial neural network analysis, composed of computer-based models used to evaluate complex correlations. The patients were randomly divided into two groups. One group served to derive classification criteria sets by sophisticated procedures, including artificial neural networks in parallel. These criteria were then validated with the second group. Symptoms that best differentiated patients with ME and CES from the other patients were acute onset of fatigue and sore throat.

Additionally, a recent study highlighted that the duration of post-exertional malaise symptoms can distinguish ME and CFS from other chronic illnesses (Cotler, Holtzman, Dudun, & Jason, 2018). The lesson that is apparent from this section is that it is essential for a consensus on a case definition among investigators for establishing a solid empiric foundation in any illness or disease.

Source: Handbook of Research Methods in Health Psychology, Chapter 17: Chronic Illness, pp 228-241, Date:  November 29, 2020 and January 2021 URL: https://books.google.com/books?id=fPQCEAAAQBAJ&pg=PA228  Ref: https://www.routledge.com/Handbook-of-Research-Methods-in-Health-Psychology/Ragin-Keenan/p/book/9780429488320

 

Chronic fatigue syndrome: progress and possibilities

Abstract:

Chronic fatigue syndrome (CFS) is a prevalent condition affecting about one in 100 patients attending primary care. There is no diagnostic test, validated biomarker, clear pathophysiology or curative treatment. The core symptom of fatigue affects both physical and cognitive activities, and features a prolonged post-activity exacerbation triggered by tasks previously achieved without difficulty.

Although several different diagnostic criteria are proposed, for clinical purposes only three elements are required: recognition of the typical fatigue; history and physical examination to exclude other medical or psychiatric conditions which may explain the symptoms; and a restricted set of laboratory investigations. Studies of the underlying pathophysiology clearly implicate a range of different acute infections as a trigger for onset in a significant minority of cases, but no other medical or psychological factor has been reproducibly implicated.

There have been numerous small case-control studies seeking to identify the biological basis of the condition. These studies have largely resolved what the condition is not: ongoing infection, immunological disorder, endocrine disorder, primary sleep disorder, or simply attributable to a psychiatric condition. A growing body of evidence suggests CFS arises from functional (non-structural) changes in the brain, but of uncertain character and location. Further functional neuroimaging studies are needed.

There is clear evidence for a genetic contribution to CFS from family and twin studies, suggesting that a large scale genome-wide association study is warranted. Despite the many unknowns in relation to CFS, there is significant room for improvement in provision of the diagnosis and supportive care. This may be facilitated via clinician education.

Source: Sandler CX, Lloyd AR. Chronic fatigue syndrome: progress and possibilities. Med J Aust. 2020 Apr 5. doi: 10.5694/mja2.50553. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32248536

Legitimizing myalgic encephalomyelitis/chronic fatigue syndrome: Indications of change over a decade

Abstract:

This commentary identifies recent scientific and clinical milestones that appear to have increased legitimization of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These milestones include government-funded reports recognizing the seriousness of ME/CFS, new initiatives for biomedical research sponsored by the US National Institutes of Health, official endorsement of the ME/CFS name, publication of practitioner primers, and the launch of a new peer-review fatigue journal. These positive developments are tempered by ongoing illness challenges including patient stigma, absence of diagnostic markers, a lack of established treatments, and a dearth of researchers and knowledgeable, interested clinicians.

Source: Fred Friedberg (2020) Legitimizing myalgic encephalomyelitis/chronic fatigue syndrome: indications of change over a decade, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2020.1718292

Editorial: Advances in ME/CFS Research and Clinical Care

Editorial:

Advances in ME/CFS Research and Clinical Care spotlights Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a maligned, stigmatized, under-researched disease, which lacks a definitive, objective clinical test for its diagnosis, and definitive palliative and curative treatments. A few brave physicians attempt to alleviate the suffering of the afflicted. They rely upon the patients’ symptoms to guide them. Physicians can provide symptomatic relief and improve upon patients’ abnormal physiological and metabolic parameters by intervening to cause the latter to approach normal limits.

Documented to be more severely disabling than HIV-AIDS, ME/CFS receives disturbingly little funding in the United States and around the world. ME/CFS patients constitute an identifiable, underserved population that is in need of the recognition which would raise them from their current, underserved or non-served patient status into the mainstream of healthcare worldwide. ME/CFS is a common disease worldwide, affecting approximately 1 percent of the world’s population.

You can read the rest of this article HERE.

Source: Friedman KJ, Bateman L, Bested A, Nahle Z. Editorial: Advances in ME/CFS Research and Clinical Care. Front Pediatr. 2019 Sep 18;7:370. doi: 10.3389/fped.2019.00370. eCollection 2019. https://www.frontiersin.org/articles/10.3389/fped.2019.00370/full (Full article)

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.

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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)