Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem chronic disease. The etiology and pathogenesis of ME/CFS are unknown. Infections of cytomegalovirus (CMV), Epstein‐Barr virus (EBV) and human herpesvirus‐6 (HHV‐6) are suspected as etiological agents for ME/CFS.
This study aims to estimate prevalence and type (active/latent) of EBV, CMV and HHV‐6 infections in Bulgarian ME/CFS patients. In the study were included 58 ME/CFS patients and 50 healthy controls.
Virus‐specific antibodies were detected by ELISA and viral genomic sequences in PBMCs and plasma samples ‐ by nPCR. We did not observe any significant differences in virus specific IgG and IgM positivity rates between ME/CFS patients and control group. In ME/CFS plasma samples EBV DNA was found in 24.1%, CMV DNA – in 3.4% and HHV‐6 DNA in 1.7% of samples. EBV DNA was detected in 4%, CMV and HHV‐6 DNA were not found in plasma samples of controls.
The frequency of viral genome detection in PBMCs of patients and controls was 74% vs 78% for CMV, 81% vs 84% for EBV, and 82.8% vs 82% for HHV‐6. The difference in frequency of EBV active infection in ME/CFS and control group was statistically significant (p=0.0027). No ME/CFS and control individuals with active CMV and HHV‐6 infection were observed.
In conclusion, our study using both serological and PCR‐based techniques for distinguishing between active and latent infection, showed high rate of active EBV infection among ME/CFS patients indicating that at least in a subset of cases EBV is important factor for development of disease.
From IBS to ME – The dysbiotic march hypothesis, by Arnold Berstad, Olav Hauso, Ketil Berstad, Johanna ER Berstad in Medical Hypotheses Vol 140, July 2020, 109648 [https://doi.org/10.1016/j.mehy.2020.109648]
Research abstract:
Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown.
Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”.
In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.
Conclusion:
The main findings among 1100 consecutive patients with IBS are an extensive past medical history (on average 26 years), during which 80%–90% of the patients, in addition to IBS, developed joint/muscle pain and chronic fatigue, and 65% developed ME. The vast majority of the 200 patients (86%) who were asked, reported extensive treatment with antibiotics during childhood. The observations suggest that IBS and subsequent comorbidities represent “a dysbiotic march” in response to antibiotic-induced “missing microbes”
Hence, our hypothesis is that «the dysbiotic march” begins with antibiotic-induced “missing microbes”, via abdominal discomfort, food intolerance and IBS, then years later, joint/muscle pain and chronic fatigue may develop and ultimately progress to ME. The progress of the disease, i.e. the march from IBS to ME, may well be due to new microbes or other infectious agents invading and conquering the biofilm to exploit its growth conditions.
Patients with chronic fatigue have often difficulties to perform a maximal exercise test.
Maximal handgrip strength was used to predict maximal exercise performance.
We explored 98 severely fatigued patients, 66 of them with chronic fatigue syndrome.
Handgrip strength was correlated with peak values of oxygen uptake and work rate.
Thus, handgrip strength is helpful when an ergometric cycle test cannot be performed.
Research abstract:
Background: Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue.
Methods: Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances.
Findings:
No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue.
Interpretation:
We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.
Conclusion: when an ergometric cycle test cannot be easily performed, the simple, low cost MHGS measurement may be useful to evaluate the maximal physical performance of patients with chronic fatigue, including those with ME/CFS. However, in ME/CFS patients the sole MHGS measurement cannot replace the information given by a maximal exercise test that are the altered muscle membrane excitability and the associated increase in exercise induced oxidative stress. MHGS can be used as a screening tool for patients who need to undergo a maximal exercise test. The usefulness of MHGS in chronic fatigue possibly opens future ways of research.
Extracranial Doppler technique to measure cerebral blood flow is feasible during head-up tilt testing.
Cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients is reduced during head-up tilt testing compared to healthy volunteers.
Using a lower limit of normal of the cerebral blood flow reduction during head-up tilt testing of 13%, 90 percent of ME/CFS patients showed an abnormal cerebral blood flow reduction.
Reduction in cerebral blood flow is correlated with symptoms of orthostatic intolerance.
Research abstract:
Objective:
The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using
Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.
Methods:
429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we
administered a verbal questionnaire to ascertain for 15 OI symptoms.
Results:
End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P<.0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI
symptoms with the degree of CBF reduction at mid-tilt (P<.0005).
Conclusions:
During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.
Significance:
This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.
Background:
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment.
Methods: We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies.
Results:
A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48–0.97].
The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48–0.97]) vs. men (0.86% [95% CI 0.48–0.97]), community-based samples (0.76% [95% CI 0.53–1.10]) vs. primary care sites (0.63% [95% CI 0.37–1.10]), adults ≥ 18 years (0.65% [95% CI 0.43–0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22–1.35]), CDC-1994 (0.89% [95% CI 0.60–1.33]) vs. Holmes (0.17% [95% CI 0.06–0.49]), and interviews (1.14% [95% CI 0.76–1.72]) vs. physician diagnosis (0.09% [95% CI 0.05–0.13]), respectively.
Conclusions:
This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.
What Do I Do?
As of today, there are no special recommendations for immune compromised people on how to avoid COVID-19 infection. Common sense suggests, though, that anyone with a compromised or wonky immune system should be extra careful. That includes people with ME or other immune illnesses, people over 65, people undergoing chemotherapy, etc. The good news is that you probably know at least one thing you can do to protect yourself from SARS-CoV-2 because you already know how to protect yourself from influenza, and the prevention measures are similar.
#1: Wash your hands.
Seriously, wash your hands. Use soap and water, and wash your hands for at least 20 seconds after using the bathroom or blowing your nose/sneezing. I also wash my hands before using a restroom in a public place. Edited to add: this is a fabulous video that demonstrates proper hand-washing technique. Wash your hands before eating. Wash your hands when you get home from a public place. If there is no soap and water available, use an alcohol-based sanitizer with at least 60% alcohol.
#2 Don’t touch your face.
If you are out in public, don’t touch your eyes, nose, or mouth. Once you start to pay attention to it, you will be amazed how many times you do this. But if you are in public–especially in a healthcare setting–don’t!
#3 Practice cough and sneeze etiquette.
Cough or sneeze into a tissue, and then throw the tissue away. Then wash or sanitize your hands. If you don’t have a tissue, try to cover your mouth with your elbow instead of your hand.
#4 Avoid sick (or potentially sick) people.
If someone you know is sick, especially with a respiratory illness, it’s better not to be in close contact with them. That can be hard if the sick person lives with you or is your carer, but try to minimize your exposure (and everybody should be washing their hands). It’s a good idea to avoid large numbers of people during flu season, if you can. Be especially careful to avoid coughing/sneezing people in healthcare settings. Don’t shake hands with people, either.
#5 Ask others to practice good hygiene/infection control.
People who visit you, live with you, or help care for you should all practice the same infection control measures. They should wash their hands upon entering your living space and before preparing your food. They should cough and sneeze into tissues, throw the tissues away, and then wash their hands. If they are sick–or if someone in their families is sick–then it is best for them to stay away. This is especially true for caregivers of severely ill ME patients. Caregivers must practice good hygiene and infection control measures.
#6 Sick people should wear masks.
CDC does not recommend that well people wear masks to protect themselves from SARS-CoV-2 (or influenza). However, people who are sick should wear masks to protect against infecting others. Note that commonly available surgical masks do not filter out most viruses because the particles are too small. The masks that are rated N95 or better will filter viruses, but they are hard to find (or the prices have been jacked up). N95 masks are also supposed to be fitted to the individual and then tested, and most people are not doing that.
#7 Have some supplies on hand, but don’t go crazy.
Some experts have recommended preparing the same way you would for a big storm: have nonperishable food and a two week supply of medications on hand. I wish one of them would tell my health insurance company that so I can actually get the two week supply ahead of schedule. Keeping easy to prepare food on hand is always a good idea for people with ME anyway, since we never know when a crash will make food shopping and prep impossible.
#8 Prepare for disruption of your routine.
I have personally found the angsting over quarantine to be a bit ableist, since millions of people with serious health conditions (including ME) are already living partially or entirely as if we are quarantined. Being told to stay at home is redundant for those of us that rarely leave it. However, restrictions on who can come to us, especially those who live alone and depend on outside help, would have a significant impact. Thinking through your backup plans in advance is a good idea. Can you get groceries delivered? What are your options for getting medications or other essential items if you can’t go out for a week or more? If the person/people who help you were unavailable, do you have backup help?
#9 Make a healthcare plan.
You may not be able to get to your doctor’s office easily even on a good day, if you have ME. If you are sick with an acute illness on top of ME, it will be even harder. Does your doctor offer any virtual services, such as video or phone consults? Make a plan with your primary care doctor or nearby urgent care so that you can get tested and treated if you have symptoms of any flu-like illness.
#10 Do not delay seeking healthcare.
Flu-like symptoms that might be of less concern in a healthy person can be very serious for people with ME, so consulting a healthcare provider should not be delayed if fever, cough, or congestion develop. The risk of complications is too high. In the past, I haven’t always bothered to call my doctor when I spiked a fever or had bad congestion. This year, I called my doctor the moment my temperature went up, and I was able to get treatment for suspected influenza that helped my recovery. If you get flu-like symptoms, call your doctor right away. Don’t wait and risk developing more severe illness.
#11 Stay informed, but in balance.
Use a reliable source to stay aware of developments in your area. You need to know if there are health advisories or local outbreaks that affect you. Once you have that information, though, stop. Unless you are a virus geek like me, the constant buzz of updates and breaking news may just wind you up. The bad weather analogy may be helpful here. You probably pay different levels of attention to storms that are 1,000 miles from you versus 100 miles versus 10 miles. The risk assessment for a viral outbreak is similar.
There is no way to virus-proof ourselves completely. However, if you follow these common sense public health recommendations, you will be better equipped to handle an infection if it comes. Do what you can to minimize disruptions to your routine. If you do get sick, take it seriously and seek healthcare.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood monocytic cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls.
We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase TORC1. These differences were correlated with disease severity, as measured by the Richardson and Lidbury Weighted Standing Test.
The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS.
Here we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and Receiver Operating Characteristic (ROC) curve analysis. We found that results from three different tests, lymphocyte death rate, mitochondrial respiratory function and TORC1 activity could each individually serve as biomarker with better than 90% sensitivity but only modest specificity vis a vis healthy controls.
However, in combination they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.
Aims: Chronic fatigue syndrome is an agnogenic disease worldwide. Nurses are at a high risk of chronic fatigue syndrome. However, no research has been done to examine the associations of workplace violence, organizational support and occupational stress with chronic fatigue syndrome among Chinese nurses. This study aimed to examine effects of these factors on chronic fatigue syndrome in this occupational group.
Design: Cross‐sectional. All participants voluntarily completed a questionnaire survey.
Methods:
The study was conducted in Liaoning province from December 2017 to January 2018. Self‐administered questionnaires were distributed to 1200 nurses, including Effort‐Reward‐Imbalance, Workplace Violence Scale, Survey of Perceived Organizational Support, together with age, gender, marital status, education levels, physical activities, job rank, monthly income and weekly working hours. Complete responses were obtained from 1080 (90%) participants. Chronic fatigue syndrome was diagnosed by doctors according to the Centers for Disease Control and Prevention criteria. Multivariable logistic regression was performed to examine these independent risk factors.
Results:
The prevalence of chronic fatigue syndrome was 6.76%. The results of logistic regression analysis showed that nurses who experienced serious higher levels of overcommitment, workplace violence and less organizational support were more likely to be classified as chronic fatigue syndrome.
Conclusion:
There was a high prevalence of chronic fatigue syndrome. Lower workplace violence, more organizational support and lower overcommitment could be effective resources for reducing chronic fatigue syndrome.
Impact:
Workplace violence, organizational support and occupational stress were related to chronic fatigue syndrome, which helped to explain why Chinese nurses suffered higher prevalance of chronic fatigue syndrome. Overcommitment explained chronic fatigue syndrome better than Effort/Reward Ratio, so intrinsic stress played a more critical role than extrinsic stress in chronic fatigue syndrome. Chinese nurses suffered serious sleep disorders and impairment of concentration and memory. These symptoms might also attributed to serious occupational stress, unsafe and unsupportive working environment. Creating a safe and supportive working environment, relieving intrinsic occupational stress should be considered as an institutional strategy to early prevent chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is classified by the World Health Organisation (WHO) as a non-communicable disease. Fatigue is a symptom commonly experienced by many individuals and is also a symptom associated with a wide variety of diseases, but once this fatigue becomes long lasting, persistent and debilitating, a case of CFS is considered.
Research of CFS dates back to the nineteen hundreds, but unfortunately, no definite underlying cause or one single positive treatment has been identified. Diagnosis also poses a difficult task due to different criteria available, but also because of the lack in confidence of diagnosing doctors in making a positive diagnosis, because this disease is still poorly understood.
Recent studies and research found promising evidence that mitochondrial dysfunction may be considered as a possible underlying cause of CFS. Because mitochondria are responsible for the release of energy in cells, the connection between mitochondrial dysfunction and the underlying energy deficiency in CFS patients may indicate a good starting point for further investigation. L-carnitine plays an important role in energy metabolism and could possibly be used as potential biomarkers for energy related diseases such as CFS.
The first part of the study focused on method development and validation. A pre-existing high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method coupled with electrospray ionisation (ESI) was further developed and validated to simultaneously quantify
The second part of the study included application of the developed and validated method to urine samples of controls and possible CFS patients. All carnitines of interest could be detected and identified with this method, although the longer chain aclylcarnitines posed some difficulty. The aim of this study was to identify altered acylcarnitine profiles associated with possible CFS patients compared to control samples. At the end, principal component analysis (PCA) statistical analysis could not differentiate between the two groups, but two acylcarnitines were identified by the Mann Whitney test to have significant p-values, namely octanoylcarnitine (C8) and decanoylcarnitine (C10).
Although the method can be applied for acylcarnitine identification in urine samples, it is advised to pay attention to detecting the long chain acylcarnitines more efficiently in order to get the whole profile for comparison.
Introduction: Chronic fatigue syndrome is associated with marked fatigue and sleep disturbance specifically the non-restorative sleep. This has led to a though process among the Scientists to rule out possibility of association of CFS with Sleep Disorders. Researchers have tried to investigate the causal relationship between the two by virtue of multiple experiments, however consensus on the same still lacks.
Methods and Results: In current review, critical analysis of individual studies was conducted evaluating credibility of experiments leading to a final opinion pertaining to Chronic Fatigue Syndrome association with Sleep Pathology. Possible overlaps among different mechanisms were also identified to provide robust conclusion.
Conclusion: Current review suggests that Chronic Fatigue Syndrome and Sleep Disorders can be more of comorbid rather than having a causal relationship. Hence there is a mix type of evidence which tries to build relationship between the two but definite conclusion clearly demonstrating CFS as a sleep disorder cannot be reached.
Virus‐specific antibodies were detected by ELISA and viral genomic sequences in PBMCs and plasma samples ‐ by nPCR. We did not observe any significant differences in virus specific IgG and IgM positivity rates between ME/CFS patients and control group. In ME/CFS plasma samples EBV DNA was found in 24.1%, CMV DNA – in 3.4% and HHV‐6 DNA in 1.7% of samples. EBV DNA was detected in 4%, CMV and HHV‐6 DNA were not found in plasma samples of controls.
