A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome

Abstract:

This is a comprehensive literature review of chronic fatigue syndrome (CFS). We provide a description of the background, etiology, pathogenesis, diagnosis, and management regarding CFS. CFS is a multifaceted illness that has many symptoms and a wide array of clinical presentations.

As of recent, CFS has been merged with myalgic encephalomyelitis (ME). Much of the difficulty in its management has stemmed from a lack of a concrete understanding of its etiology and pathogenesis. There is a potential association between dysfunction of the autoimmune, neuroendocrine, or autonomic nervous systems and the development of CFS. Possible triggering events, such as infections followed by an immune dysregulation resulting have also been proposed. In fact, ME/CFS was first described following Epstein Barr virus (EBV) infections, but it was later determined that it was not always preceded by EBV infection.

Patient diagnosed with CFS have shown a noticeably earlier activation of anaerobic metabolism as a source of energy, which is suggestive of impaired oxygen consumption. The differential diagnoses range from tick-borne illnesses to psychiatric disorders to thyroid gland dysfunction. Given the many overlapping symptoms of CFS with other illnesses makes diagnosing it far from an easy task.

The Centers for Disease Control and Prevention (CDC) considers it a diagnosing of exclusion, stating that self-reported fatigue for at minimum of six months and four of the following symptoms are necessary for a proper diagnosis: memory problems, sore throat, post-exertion malaise, tender cervical or axillary lymph nodes, myalgia, multi-joint pain, headaches, and troubled sleep. In turn, management of CFS is just as difficult.

Treatment ranges from conservative, such as cognitive behavioral therapy (CBT) and antidepressants, to minimally invasive management. Minimally invasive management involving ranscutaneous electrical acupoint stimulation of target points has demonstrated significant improvement in fatigue and associated symptoms in a 2017 randomized controlled study. The understanding of CFS is evolving before us as we continue to learn more about it. As further reliable studies are conducted, providing a better grasp of what the syndrome encompasses, we will be able to improve our diagnosis and management of it.

Source: Noor N, Urits I, Degueure A, Rando L, Kata V, Cornett EM, Kaye AD, Imani F, Narimani-Zamanabadi M, Varrassi G, Viswanath O. A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome. Anesth Pain Med. 2021 Jun 26;11(3):e113629. doi: 10.5812/aapm.113629. PMID: 34540633; PMCID: PMC8438707. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438707/  (Full text)

Long COVID and Chronic Fatigue Syndrome: A survey of elderly female survivors in Egypt

Abstract:

Objectives: This study aimed to investigate post COVID 19 symptoms amongst elderly females and whether they could be a risk factor for developing Chronic Fatigue Syndrome (CFS) later on.

Methods: This was a retrospective cross-sectional study, in the form of an online survey. A total of 115 responses were finally included.

Results: The mean age was 73.18±6.42. Eighty-nine reported symptoms in the post recovery period; of these 54 had no symptoms of CFS, 60 were possible, and only 1 was probable. Fatigue was reported by 66, musculoskeletal symptoms by 56, and sleep problems by 73. Twenty-nine patients visited a doctor’s office as a result. Post recovery symptoms were significantly related to stress, sadness and sleep disturbances. Also, stress, sadness, sleep disturbances, fatigue, cognitive impairment, and recurrent falls were all significantly associated with CFS like symptoms.

Conclusions: From our findings the presence of fatigue, cognitive impairment, stress, sadness, sleep disturbances, and recurrent falls in the post-recovery period were all significantly associated with CFS like symptoms. To conclude it would be reasonable to screen for Long COVID and consider the potential for developing CFS later on. Whether it can be a risk factor for developing CFS like other viral infections will need more larger scale studies to confirm this.

Source: Aly MA, Saber HG. Long COVID and Chronic Fatigue Syndrome: A survey of elderly female survivors in Egypt. Int J Clin Pract. 2021 Sep 19:e14886. doi: 10.1111/ijcp.14886. Epub ahead of print. PMID: 34537995. https://pubmed.ncbi.nlm.nih.gov/34537995/

The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility

Abstract:

Objective: To examine demographic and clinical characteristics of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with and without joint hypermobility We hypothesized that JH+ patients would have an earlier onset of ME/CFS symptoms as well as increased severity, greater number of co-morbid conditions, and lower health related quality of life.

Study design: From an observational cohort study of 55 individuals meeting the Fukuda criteria for ME/CFS, we compared groups using a Beighton score cut-off of 4 or higher to indicate JH. Chart data were collected to examine the age and type of onset of ME/CFS, and the presence of comorbid conditions. The impact on quality of life was assessed through questionnaires that included the Peds QL, Functional Disability Inventory, Peds QL Multidimensional Fatigue Scale, and Anxiety Subscale of the Symptom Checklist 90.

Results: There was no significant difference between groups in mean (SD) age at onset of ME/CFS (13.3 [3.3] years vs 13.3 [2.3] years; P = .92), sex, frequency, and severity of ME/CFS symptoms, orthostatic intolerance symptoms, or comorbid conditions. There was no significant difference between groups in measures of health-related quality of life using a Beighton score cut-off of 4 or a cut-off of 5 to define joint hypermobility.

Conclusions: Despite being a risk factor for the development of ME/CFS, JH as defined in this study was not associated with other clinical characteristics of the illness.

Source: Vogel SK, Primavera IR, Marden CL, Jasion SE, Cranston EM, Flaherty MAK, Violand RL, Rowe PC. The Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Influenced by the Presence or Absence of Joint Hypermobility. J Pediatr. 2021 Sep 16:S0022-3476(21)00887-8. doi: 10.1016/j.jpeds.2021.09.014. Epub ahead of print. PMID: 34537220. https://pubmed.ncbi.nlm.nih.gov/34537220/

Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations

Abstract:

Clinical sequelae of a disease as widespread as COVID-19 can be of great importance for primary care due to their prevalence and the morbidity they entail. The definition of long COVID and the establishment of its temporality are various, but some authors consider possible that this syndrome is actually myalgic encephalomyelitis.

Similarities are observed when comparing the International Consensus Criteria for the diagnosis of myalgic encephalomyelitis with the symptoms described for long COVID. Blood tests, pulse oximetry, chest radiography, and thoracic ultrasound are recommended in patients with persistent symptoms after acute infection. Management in both conditions consists of treating the main symptoms. The possibility that COVID-19 can lead to a chronic condition such as myalgic encephalomyelitis makes long-term follow-up of patients who have suffered from this infection essential.

Source: Espinosa Rodríguez, P et al. “COVID persistente: ¿es en realidad una encefalomielitis miálgica? Revisión bibliográfica y consideraciones” [Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations]. Semergen, S1138-3593(21)00091-5. 13 Sep. 2021, doi:10.1016/j.semerg.2021.03.006 [Abstract in English, Spanish] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437705/  (Full text)

Where Exactly Does ME/CFS Research Stand in 2021? Dr. Komaroff Explains

From the central nervous system to Long COVID to energy impairment, Dr. Anthony Komaroff provides his perspective on over 30 years of scientific research into myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and post-acute viral illnesses.

By Bronc and Eric Pyrrhus

Dr. Anthony Komaroff is really on a roll. For a sometimes reserved academic, he’s been speaking out more and more lately. What has he been talking about, and why now? Phoenix Rising spoke with the good doctor, and summarizes some of his recent publications and interviews here.

For those who may be unfamiliar with him, Dr. Komaroff is a distinguished Professor of Medicine at Harvard Medical School and Senior Physician at Brigham and Women’s Hospital in Boston. He has published over 230 research articles and two books.

He has been publishing research papers on ME/CFS since the late 1980s, and currently serves on the U.S. National Institutes of Health’s advisory body for research into ME/CFS.

“Since the resurgence of interest in ME/CFS 35 years ago, whole new technologies have become available that allow physicians and biomedical scientists to study human biology in ways that previously were not possible,” explained Dr. Komaroff in a recent commentary.

“In fact, these and other technologies have revealed things that the standard laboratory tests cannot — abnormalities that previously were invisible to doctors.”

When we asked him which new developments in ME/CFS research stood out for him, he answered:

The underlying biological abnormalities in ME that seem to me the most well established involve the brain and autonomic nervous system, chronic activation and exhaustion of parts of the immune system, defects in energy metabolism and a general hypometabolic state, and abnormalities of the gut microbiome. I think it is likely that they are all real, and all connected to one another. To me, the most important research agenda is to understand how these abnormalities are connected to each other.

Read the rest of this article HERE.

Source: Phoenix Rising, August 22, 2021

ME/CFS may be linked to failure in energy supply to the cells

By Elise Kjørstad

Researchers at the University of Bergen and Haukeland University Hospital were part of a research team for a new study that found differences in blood samples between ME/CFS patients and healthy people.

Patients with myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, had different levels of some substances that affect energy metabolism in the cells.

“What we think might be an explanation is that restricted blood flow during activity means the cells are receiving too little oxygen, and this leaves metabolic traces over time,” says Karl Johan Tronstad.

In the new study, the researchers performed an analysis of metabolites and other substances in blood samples from ME/CFS patients. Metabolites are metabolic products that are created when the cells convert different substances in the body.

The researchers analysed blood samples from 83 individuals with ME/CFS and 35 healthy controls.

The researchers measured about 1700 substances in the blood samples they took.

In the ME/CFS patients, they found an altered level of over 300 substances. Many of them involved the conversion of amino acids, which build up proteins, and lipids (fats).

Read the rest of this article HERE.

 

 

Research Summary – Are people with ME/CFS at higher risk of complications from COVID infection?

From the ME Association

Are people with ME/CFS at higher risk of complications from COVID infection? A recent publication by Malato et al. carried out using ME/CFS patients from Germany has shown that this could be the case.

This paper looked at two enzymes called ACE and ACE2 (human angiotensin-converting enzymes). The enzyme ACE2 is of significant importance due to it being found to be the main receptor used by the virus COVID-19 (SARS-CoV2) to enter human cells.

Patients with ME/CFS are often found to have an unbalanced immune system. Previous studies have suggested that the ACE enzyme could provide a potential biomarker with the ACE enzyme being elevated in 80% of patients (Lieberman and Bell, 1993). This study looked at increasing our knowledge of the role of the ACE2 enzyme as little is known about its role in ME/CFS to date.

Read the rest of this article HERE.

Fatigue and post-exertional symptom exacerbation in Covid

Long Covid rehabilitation should include educating people about resuming everyday activities conservatively: WHO

By SHAHISTHA HAQUE

Fatigue is a feeling of extreme exhaustion. One feels over tired, low level of energy and extreme urge to sleep. It is the most common symptom of long Covid. It is easily relieved by rest or sleep. It is not the result of usually difficult activity. It can limit functioning in day to day activities. It negatively impacts the quality of life.

Now talking about post-exertional symptom exacerbation (PESE), it is a disabling and often delayed exhaustion disproportionate to the effort made. It is something described as crash.
The activity that can trigger this worsening of symptoms can be something that was easily tolerated before such as a daily activity e.g., a shower, a social activity, walking, reading, writing or working at a desk, an emotionally charged conversation, being in a sensory environment e.g., loud music or flashing lights.
Many of the symptoms experienced by those living with long Covid are very similar to those of myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).
According to WHO, long Covid rehabilitation should include educating people about resuming everyday activities conservatively, at an appropriate pace that is safe and manageable for energy levels within the limit of current symptoms and exertion should not be pushed to the point of fatigue or symptom exacerbation.
Read the rest of this article HERE.

Science In The Age of Dogma: A Conversation with Dr. William Weir

by Bronc

Dr. William Weir is a retired infectious disease consultant who worked at the Royal Free Hospital in London. He has long been involved in treating myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) patients and has been a consistent critic of the psychological approach to treating ME/CFS.

From 1998 to 2002 Dr. Weir assisted the U.K. government’s CFS/ME Working Group, which produced a comprehensive advisory report for the U.K. Chief Medical Officer, Sir Liam Donaldson.

Along with Dr. Nigel Speight, Dr. Weir recently authored a paper entitled “ME/CFS: Past, Present and Future,” in which the authors reflect upon the history and controversy surrounding ME/CFS:

“Throughout history, a pattern tends to repeat itself when natural phenomena require explanation. Dogma usually arrives first, then it is eventually replaced by scientific understanding. The same pattern is unfolding in relation to ME/CFS, but supporters of the psychological dogma surrounding its causation remain stubbornly resistant, even in the face of compelling scientific evidence to the contrary.”​
—Dr. William Weir and Dr. Nigel Speight​

Over the last two years Dr. Weir has served on the U.K. government’s ME/CFS Guideline Development Group, tasked with developing official treatment guidelines for the National Institute for Health and Care Excellence (NICE). These clinical guidelines are especially important as they provide a framework of recommendations for health and social care services throughout the U.K.

Read the rest of this interview HERE.

Source: Phoenix Rising, Sept 12, 2021

Redox Imbalance: A Core Feature of ME/CFS and Acute COVID-19

By Dr. Anthony Komaroff

ME/CFS is defined exclusively by symptoms—subjective experiences that are hard to verify by objective testing. For that reason, since interest in ME/CFS began to grow in the 1980s, scientists have been looking for evidence of underlying objective abnormalities that might explain the symptoms.

A recent review, published August 24, 2021, in the Proceedings of the National Academy of Sciences USA, summarizes in detail the evidence demonstrating one of the several objective abnormalities in people with ME/CFS and acute COVID-19: redox imbalance.1 It speculates that redox imbalance may also be present in post-acute COVID-19 syndrome, or “long COVID-19”, although this remains to be studied.

Redox imbalance occurs when the molecules that are oxidants (particularly “free radicals” or reactive oxygen species) exceed the number of molecules that are antioxidants. Essentially, redox imbalance is the same as the more familiar term of “oxidative stress”.

Read the rest of this article HERE.