2019 – Page 10 – American ME and CFS Society

Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome

Introduction:

The illness now called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was first described in the mid-1980s. At that time, nothing was known about its underlying biology. Indeed, because many standard laboratory test results were normal, some clinicians explained to patients that “there is nothing wrong.” There was, of course, an alternative explanation: the standard laboratory tests might not have been the right tests to identify the underlying abnormalities.

Over the past 35 years, thousands of studies from laboratories in many countries have documented underlying biological abnormalities involving many organ systems in patients with ME/CFS, compared with healthy controls: in short, there is something wrong. Moreover, most of the abnormalities are not detected by standard laboratory tests. In 2015, the Institute of Medicine of the National Academy of Sciences concluded that ME/CFS “is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients,” affects up to an estimated 2.5 million people in the United States, and generates direct and indirect expenses of approximately $17 billion to $24 billion annually.

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Source: Anthony L. Komaroff, MD. Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome. JAMA. Published online July 5, 2019. doi:10.1001/jama.2019.8312 https://jamanetwork.com/journals/jama/fullarticle/2737854 (Full article)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Induced by Repeated Forced Swimming in Mice

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue of at least 6 months, in addition to symptoms such as muscle pain and muscle weakness. There is no treatment provides long-term benefits to most patients. Recently, clinical research suggested the involvement of pyruvate dehydrogenase (PDH) in ME/CFS. PDH is a crucial enzyme in the mitochondria matrix that links glycolysis to the tricarboxylic acid cycle and oxidative phosphorylation. However, it is little known whether PDH could be a therapeutic target. The purpose of this study was to establish ME/CFS in mice and to investigate the involvement of PDH in ME/CFS.

To induce the chronic fatigue in mice, a repeated forced swimming test was conducted. To evaluate fatigue, we measured immobility time in forced swimming test and starting time of grooming. An open field test was conducted on day 8. After 25 d of the forced swimming test, the mitochondrial fraction in gastrocnemius muscle was isolated and PDH activity was measured. Moreover, we evaluated the effect of PDH activation by administering sodium dichloroacetate (DCA).

In ME/CFS mice group, the immobility time and starting time of grooming increased time-dependently. In addition, the moved distance was decreased in ME/CFS mice. PDH activity was decreased in the mitochondrial fraction of the gastrocnemius muscle of the forced swimming group. DCA treatment may be beneficial in preventing fatigue-like behavior in ME/CFS. These findings indicate that ME/CFS model was established in mice and that a decrease in mitochondrial PDH activity is involved with the symptom of ME/CFS.

Source: Ohba T, Domoto S, Tanaka M, Nakamura S, Shimazawa M, Hara H. Biol Pharm Bull. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Induced by Repeated Forced Swimming in Mice. 2019;42(7):1140-1145. doi: 10.1248/bpb.b19-00009. https://www.jstage.jst.go.jp/article/bpb/42/7/42_b19-00009/_article (Full article)

Chronic Fatigue Syndrome and chronic pain conditions – vitally protective systems gone wrong

Abstract:

Chronic Fatigue Syndrome (CFS) and chronic pain syndromes represent major health problems in society. These conditions are disabling and strongly associated with low quality of life. Even though CFS and chronic pain are separate conditions, they have strikingly much in common. Both pain and fatigue are important sensations with protective value in an acute situation. It can be life-threatening not to be aware of them.

However, as these symptoms become chronic, their protective roles decrease and instead they become health problems. Our understanding of the perception of pain and fatigue has shifted through the years, from a dualistic biomedical point of view to a holistic biopsychosocial understanding. This combined with the increasing evidence of how our brain works in a predictive/anticipatory manner, gives a deeper understanding of why treatments like cognitive behavior therapies and stress relief therapies can help these patients recover to better health.

Source: Pedersen M. Chronic Fatigue Syndrome and chronic pain conditions – vitally protective systems gone wrong. Scand J Pain. 2019 Jun 29. pii: /j/sjpain.ahead-of-print/sjpain-2019-0072/sjpain-2019-0072.xml. doi: 10.1515/sjpain-2019-0072. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31256069

Medically Documenting Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Cases

Introduction:

Patients with severe myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) experience debilitating physical and cognitive symptoms, which often result in the need to file disability claims. A significant number of ME/CFS patients are children or adolescents. ME/CFS patients often turn to physicians who are not trained to recognize and diagnose ME/CFS, and who might or might not understand that ME/CFS is a multi-system primarily physical illness. Such misperceptions can adversely affect the doctor-patient relationship, the clinical outcomes, as well as the results of disability claims.

According to the National Academies of Science, Engineering and Medicine, “Between 836,000 and 2.5 million Americans suffer from myalgic encephalomyelitis/chronic fatigue syndrome… This disease is characterized by profound fatigue, cognitive dysfunction, sleep abnormalities, autonomic manifestations, pain, and other symptoms that are made worse by exertion of any sort. ME/CFS can severely impair patients’ ability to conduct their normal lives.1” The prevalence of MECFS among children and adolescents has been estimated variously as between 0.11 and 4% (1). A large percentage of children and adolescents with ME/CFS suffer from orthostatic intolerance due to one or both of these syndromes: Neurally Mediated Hypotension (NMH) and Postural Orthostatic Tachycardia Syndrome (POTS). These elements of ME/CFS often respond well to proper treatment (2, 3).

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Source: Barbara B. Comerford and Richard Podell. Medically Documenting Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Cases. Front. Pediatr., 02 July 2019 | https://doi.org/10.3389/fped.2019.00231 (Full article) https://www.frontiersin.org/articles/10.3389/fped.2019.00231/full

The clinical value of cytokines in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous disorder with uncertain pathogenesis. Without effective therapy, CFS is characterized by disabling fatigue, depression, memory loss, and somatic discomfort. This comprehensive and impartial review aimed to assess the available evidence and examined the potential clinical value of using cytokines for the monitoring of CFS and as targets for the treatment of CFS.

Inflammatory reactions and immune modulation are considered to contribute to the pathophysiology of CFS, and it is well documented that cytokines present in both blood and cerebrospinal fluid (CSF) are closely associated with the progression and severity of CFS. However, pathophysiological and methodological limitations prevent using circulating cytokines as independent diagnostic indices. Moreover, there is no evidence to support the use of CSF cytokines as independent diagnostic indices.

Nevertheless, a comprehensive evaluation of changes in circulating and CSF cytokines may improve clinical understanding of the pathophysiology of patients with CFS, aiding in the establishment of an appropriate diagnosis. Importantly, the available evidence does not support the value of cytokines as therapeutic targets. We believe that an improved understanding of cytokine-related mechanisms will be helpful to explore new cytokine-related therapeutic targets.

Source: Yang T, Yang Y, Wang D, Li C, Qu Y, Guo J, Shi T, Bo W, Sun Z, Asakawa T. The clinical value of cytokines in chronic fatigue syndrome. J Transl Med. 2019 Jun 28;17(1):213. doi: 10.1186/s12967-019-1948-6 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1948-6 (Full article)

Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain

Abstract:

BACKGROUND: Few reports have examined the association between unemployment and work disability in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This study explored the key determinants of work disability in a CFS/ME cohort.

METHODS: A community-based prospective study included 1086 CFS/ME patients aged 18-65 years. Demographic and clinical characteristics and outcome measures were recorded. Multiple linear regression analysis was performed to identify key risk indicators of work disability.

RESULTS: Four hundred and fifty patients with CFS/ME were employed (41.4%) and 636 were unemployed (58.6%). Older age at pain onset (OR: 1.44; 95% CI: 1. 12-1.84, autonomic dysfunction (OR: 2.21; 95% CI: 1.71-2.87), neurological symptom (OR: 1.66; 95% CI: 1. 30-2.13) and higher scores for fatigue (OR: 2.61; 95% CI: 2.01-3.39), pain (OR: 2.09; 95% CI: 1.47-2.97), depression (OR: 1.98; 95% CI: 1. 20-3.26), psychopathology (OR: 1.98; 95% CI: 1.51-2.61) and sleep dysfunction (OR: 1.47; 95% CI: 1. 14-1.90) were all associated with a higher risk of work disability due to illness.

CONCLUSIONS: Using an explanatory approach, our findings suggest that unemployment is consistently associated with an increased risk of work disability due to CFS/ME, although further more rigorous research is now needed to help in targeting interventions at the workplace.

Source: Castro-Marrero J, Faro M, Zaragozá MC, Aliste L, de Sevilla TF, Alegre J. Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain. BMC Public Health. 2019 Jun 28;19(1):840. doi: 10.1186/s12889-019-7225-z. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7225-z (Full article)

Monitoring treatment harm in myalgic encephalomyelitis/chronic fatigue syndrome: A freedom-of-information study of National Health Service specialist centres in England

Abstract:

The use of graded exercise therapy and cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome has attracted considerable controversy. This controversy relates not only to the disputed evidence for treatment efficacy but also to widespread reports from patients that graded exercise therapy, in particular, has caused them harm. We surveyed the National Health Service-affiliated myalgic encephalomyelitis/chronic fatigue syndrome specialist clinics in England to assess how harms following treatment are detected and to examine how patients are warned about the potential for harms.

We sent 57 clinics standardised information requests under the United Kingdom’s Freedom of Information Act. Data were received from 38 clinics. Clinics were highly inconsistent in their approaches to the issue of treatment-related harm. They placed little or no focus on the potential for treatment-related harm in their written information for patients and for staff. Furthermore, no clinic reported any cases of treatment-related harm, despite acknowledging that many patients dropped out of treatment.

In light of these findings, we recommend that clinics develop standardised protocols for anticipating, recording, and remedying harms, and that these protocols allow for therapies to be discontinued immediately whenever harm is identified.

Source: McPhee G, Baldwin A, Kindlon T, Hughes BM. Monitoring treatment harm in myalgic encephalomyelitis/chronic fatigue syndrome: A freedom-of-information study of National Health Service specialist centres in England. J Health Psychol. 2019 Jun 24:1359105319854532. doi: 10.1177/1359105319854532. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31234662

Mediating Relatedness for Adolescents with ME: Reducing Isolation through Minimal Interactions with a Robot Avatar

Abstract:

This paper discusses how a networked object in the form of a small robot designed to mediate experiences of care, social connectedness, and intimacy, was used by adolescents with Myalgic Encephalomyelitis, a condition that reduces their normal functioning, including the ability to socialize. A study with nine adolescents, each using the robot for about a year in average, revealed that it was largely effective at mediating their everyday experiences of relatedness, triggering productive new habits and social practices. We interpret these findings to propose a set of strategies for designing technologies that support relatedness while requiring minimal interactivity and engagement. Balance, extension-of-self, coolness, and acts-of-care, in addition to commonly used physicalness, expressivity and awareness, enable the robot to extend the adolescents’ ability to relate to others, people and animals.

Source: Proceedings of the 2019 on Designing Interactive Systems Conference. (DIS ’19), pp 359-371. Date: June 23-28, 2019 https://dl.acm.org/citation.cfm?id=3322319 (Full text available through PDF download)

Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating syndrome of unknown origin, characterized by profound postexertional malaise and fatigue, unrefreshing sleep, cognitive impairments, immune dysfunction, pain, autonomic dysfunction, and neuroendocrine symptoms. Although ME/CFS is well documented within the medical literature, it remains difficult to diagnosis and manage.

Some of the current challenges include an absence of diagnostic markers, differing diagnostic criteria, and an overall lack of awareness within the medical community. As a result, patients are often frustrated by the difficulties in acquiring a diagnosis and from the overall lack of available treatments. In an effort to increase awareness, this review discusses disease pathophysiology, clinical presentation, and treatment options, while also highlighting the benefits of an osteopathic approach.

J Am Osteopath Assoc. 2019 Jul 1;119(7):446-455. doi: 10.7556/jaoa.2019.081.

Source: Larrimore C, Ramnot A, Jaghab A, Sarduy S, Guerrero G, Troccoli P, Hilton K, Bested A. Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review. J Am Osteopath Assoc. 2019 Jul 1;119(7):446-455. doi: 10.7556/jaoa.2019.081. https://www.ncbi.nlm.nih.gov/pubmed/31233110

Chronic fatigue syndrome and an illness-focused approach to care: controversy, morality and paradox

Abstract:

Contemporary medicine distinguishes between illness and disease. Illness refers to a person’s subjective experience of symptoms; disease refers to objective bodily pathology. For many illnesses, medicine has made great progress in finding and treating associated disease. However, not all illnesses are successfully relieved by treating the disease. In some such cases, the patient’s suffering can only be reduced by treatment that is focused on the illness itself. Chronic disabling fatigue is a common symptom of illness, for which disease-focused treatment is often not effective, but for which illness-focused treatments (psychological or behavioural) often are.

In this article, we explore a controversy surrounding illness-focused treatments for fatigue. We do this by contrasting their acceptance by people whose fatigue is associated with a disease (using the example of cancer-related fatigue) with their controversial rejection by some people whose fatigue is not associated with an established disease (chronic fatigue syndrome or CFS, sometimes called ME (myalgic encephalomyelitis)). In order to understand this difference in acceptability we consider the differing moral connotations of illness and disease and then go on to examine the limitations of the concepts of illness and disease themselves.

We conclude that a general acceptance of illness-focused treatments by all who might benefit from them will require a major long-term change in thinking about illness, but that improvements to the care of individual patients can be made today.

Source: Sharpe M, Greco M. Chronic fatigue syndrome and an illness-focused approach to care: controversy, morality and paradox. Med Humanit. 2019 Jun 18. pii: medhum-2018-011598. doi: 10.1136/medhum-2018-011598. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31213482