Chronic viral infections in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome 

Currently available data on the role of chronic viral infection with ME/CFS is still controversial,

showing potential viral involvement for at least a subgroup of ME/CFS patients. Therefore, it is

necessary to assess the presence and markers of viral activity at the initial stage of the disease to evaluate

possible etiological factors and conduct longitudinal studies in order to assess active viral infection and

symptom severity variations over time. Moreover, results should be compared not only between

ME/CFS patients and controls, but also with other co-morbidities to assess specificity of suggested biomarkers.

Transient receptor potential melastatin 2 channels are over expressed in

Myalgic Encephalomyelitis & Chronic Fatigue Syndrome Patients

Five countries reported having national guidelines for diagnosis, and five countries reported having guidelines for clinical approaches. For diagnostic purposes, the Fukuda criteria were most often recommended, and also the Canadian Consensus criteria, the International Consensus Criteria and the Oxford criteria were used. A mix of diagnostic criteria was applied within those countries having no guidelines. Many different questionnaires and tests were used for symptom registration and diagnostic investigation. For symptom relief, pain and anti-depressive medication were most often recommended. Cognitive Behavioral Therapy and Graded Exercise treatment were often recommended as disease management and rehabilitative/palliative strategies. The lack of consistency in recommendations across European countries urges the development of regulations, guidance and standards. The results of this study will contribute to the harmonization of diagnostic criteria and treatment for ME/CFS in Europe.




Nov 2019 - Toll-like receptor 3 deficiency in autoimmune encephalitis post–herpes simplex encephalitis

The Toll-like receptor 3 (TLR3) pathway is a key component of the innate immunity that prevents replication of viruses in the CNS. Inborn errors of this pathway (TLR3-pathway deficiency), which includes defects in the genes TLR3, UNC93B1, TRIF, TRAF3, TBK1 and IRF3, occur in 10% of patients with herpes simplex encephalitis (HSE),1,2 and about 66% of these patients develop relapses of HSE.1 A recent study showed that 27% of patients with HSE develop autoimmune encephalitis (AE) in the weeks or months ensuing the infection.3 It is unknown whether TLR3-pathway deficient patients can also develop AE post-HSE. Here we report a patient with TLR3-pathway deficiency who developed HSE and a relapse of the viral infection followed by AE post-HSE, highlighting the fact that TLR3-pathway deficient patients should be carefully followed for both HSE relapses and AE.


Transient receptor potential melastatin 2 channels are overexpressed in myalgic encephalomyelitis and

chronic fatigue syndrome patients

This pilot study is the first to identify and characterise TRPM2 and CD38 surface expression on human NK cell subsets in vitro from ME/CFS patients. This investigation is also the first to examine the effects of IL-2, 8-Br-ADPR and N6-Bnz-cAMP drug treatment on TRPM2 and CD38 surface expression, as well as NK cell cytotoxicity. These new findings revealed a significant overexpression of TRPM2 on NK cells in ME/CFS patients. An overexpression in TRPM2 may function as a compensatory mechanism to alert a dysregulation in Ca2+ homeostasis and improve NK cell function. However, as baseline NK cell cytotoxicity was significantly reduced in ME/CFS patients compared with HCs, an impairment in the TRPM2 ion channel may result in alterations in [Ca2+]i, which is fundamental in driving NK cell cytotoxicity.

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods​


The above review focused on neuroinflammation and the methods used to measure it. We argued for the importance of anchoring methodological details in known biological mechanisms and existing research literature.

The ME/CFS research field has been stuck in a somewhat defensive posture, with a focus on demonstrating “this is a real condition” by showing significant biological differences between patients and controls. We believe this has led to a situation in which too much is made of the specifics reported by descriptive studies (such as the average “cytokine profile” present in cases vs. controls at the moment of assay) and not enough emphasis has been placed on potential mechanisms driving symptoms. The field is ready to move past proving “this is a real condition” and to start elucidating the specific relationship of ME/CFS symptoms to neuroinflammation.



Using PEM
Evidence of altered autonomic nervous system (ANS) regulation of cardiovascular function has been observed in patients with ME/CFS.  Patients commonly present with concurrent cardiovascular conditions such as postural orthostatic tachycardia syndrome (POTS), and disturbances in additional markers of ANS function including blood pressure variability, and altered responses to head-up tilt testing (HUTT).  However, these studies have used inconsistent methodologies and provided variable results, making it difficult to conclusively establish the nature and extent of any derangement of cardiovascular autonomic regulation.



Measles is one of the most contagious viruses known to man. It spreads like wildfire — if you catch it,

it can spread quickly to other people through coughing and sneezing, infecting between. 

But the virus has an even more terrifying impact on the human body. The measles can potentially

inflict major damage to our immune memory, according to new research.

Two investigations into a recent measles outbreak in the Netherlands, revealed that the virus deletes

parts of the immune system’s memory, much like wiping a hard drive. That leaves patients

vulnerable to a host of other infections, bacterias, pathogens, and diseases. The investigations were

published in the journals Science and Science Immunology.




Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.

Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups).


The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs.


It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimized, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment.



Intra brainstem connectivity is impaired in chronic fatigue syndrome

In ME/CFS, connectivity is impaired within the brainstem RAS and from the brainstem to key subcortical structures. This may explain many of the symptoms of ME/CFS. In ME/CFS, multiple hippocampal connections to the midbrain cuneiform nucleus and the medulla are enhanced, suggesting the hippocampus has a compensatory role for the impaired connections.




Methods were invented that made it possible to image peripheral nerves in the body and to image neural tracts in the brain. The history, physical basis, and dyadic tensor concept underlying the methods are reviewed. Over a 15-year period, these techniques—magnetic resonance neurography (MRN) and diffusion tensor imaging—were deployed in the clinical and research community in more than 2500 published research reports and applied to approximately 50 000 patients. Within this group, approximately 5000 patients having MRN were carefully tracked on a prospective basis.




Epstein–Barr virus ncRNA from a nasopharyngeal carcinoma induces an inflammatory response

that promotes virus production

The Epstein–Barr virus M81 strain, isolated from a nasopharyngeal carcinoma, induces potent spontaneous virus production in infected B cells. We found that the M81 non-coding Epstein–Barr-encoded RNA EBER2, which carries polymorphisms that are mainly restricted to viruses found in endemic nasopharyngeal carcinomas, markedly stimulated this process. M81 EBER2 increased CXCL8 expression, and this chemokine enhanced spontaneous lytic replication levels in M81-infected B cells. Both events resulted from the endocytosis of extracellular vesicles containing EBER2 that were generated by neighbouring M81-infected B cells, thereby generating a paracrine loop. These effects were strictly dependent on a functional Toll-like receptor 7 (TLR7), a sensor of single-stranded RNA located in the endosome of these cells. These unique properties of M81 EBER2 could be ascribed to its unusually high expression level and to the ability of its single-stranded region to activate TLR7; both of these properties were dependent on M81-specific polymorphisms. Thus, M81 induced chronic inflammation in its target cells and this resulted in increased virus production. These observations provide a mechanistic molecular link between M81 virus replication—a central viral function and a cancer risk factor—and the production of a chemokine involved in inflammation and carcinogenesis.



A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells

Enterovirus, a genus in the family Picornaviridae, consists of 13 species, and 7 of these species contain human pathogens. Human enteroviruses (HEVs), including poliovirus, coxsackieviruses, echoviruses, rhinoviruses and the subgroups enteroviruses, are ubiquitous worldwide1,2. These diverse enteroviruses cause a diverse array of clinical features, including aseptic meningitis; hand, foot, and mouth disease; neonatal sepsis-like disease; pancreatitis; encephalitis; myocarditis and pericarditis; paralysis and respiratory diseases. Enteroviruses are transmitted predominantly by the faecal–oral route or by respiratory droplets. Enteroviruses enter the host via the oral cavity or respiratory tract. The primary sites of replication are presumed to be the gastrointestinal and respiratory epithelium, from where these viruses can disseminate to the target organs via the blood circulation.




Work Rehabilitation and Medical Retirement for Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Patients.

A Review and Appraisal of Diagnostic Strategies.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome leads to severe functional impairment and work disability in a considerable number of patients. The majority of patients who manage to continue or return to work, work part‐time instead of full time in a physically less demanding job. The prognosis in terms of returning to work is poor if patients have been on long‐term sick leave for more than two to three years. Being older and more ill when falling ill are associated with a worse employment outcome. Cognitive behavioural therapy and graded exercise therapy do not restore the ability to work. Consequently, many patients will eventually be medically retired depending on the requirements of the retirement policy, the progress that has been made since they have fallen ill in combination with the severity of their impairments compared to the sort of work they do or are offered to do. However, there is one thing that occupational health physicians and other doctors can do to try and prevent chronic and severe incapacity in the absence of effective treatments. Patients who are given a period of enforced rest from the onset, have the best prognosis. Moreover, those who work or go back to work should not be forced to do more than they can to try and prevent relapses, long‐term sick leave and medical retirement. Funding: This research received no external funding. The article publication charges were paid for by Emerge Australia. An Australia‐wide organisation for information, support services, research and news about ME/CFS. Emerge Australia was not involved in the review or writing of the article.




Multidimensional Comparison of Cancer-Related Fatigue and Chronic Fatigue Syndrome:                                                            The Role of Psychophysiological Markers



Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and

Purine Metabolism Deregulation in ME/CFS Cases


Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis. We studied two subject groups meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched control (n = 25) sera were obtained from a Canadian study. ME/CFS (n = 25) sera were obtained from phase 1/2 Norwegian trials (NCT01156909). Sera from six healthy controls from the USA were included in the analysis. Canadian cases and controls were tested for a disease immunosignature.



Autonomic dysfunction in myalgic encephalomyelitis and chronic fatigue syndrome: comparing

self-report and objective measures

Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) have debilitating impacts on affected individuals. Core symptoms include post-exertional malaise, neurocognitive challenges, and sleep dysfunction. Additionally, a significant minority of patients experience autonomic symptoms, including orthostatic intolerance, gastrointestinal

disturbances, and circulation issues.



Cellular Immune Function in Myalgic Encephalomyelitis

All participants with ME/CFS or MS had previously received a confirmed medical diagnosis. Participants were aged between 18 and 60 years. PWME were reassessed by clinical research staff for compliance with the Canadian Consensus (2) and/or CDC-1994 (“Fukuda”) (1) criteria, which were the study case definitions, before recruitment into this study. Participants were excluded if they had (i) taken antiviral medication or drugs known to alter immune function in the preceding 3 months; (ii) had any vaccinations in the preceding 3 months; (iii) had a history of acute and chronic infectious diseases such as hepatitis B and C, tuberculosis, HIV (but not herpes virus or other retrovirus infection); (iv) another chronic disease such as cancer, coronary heart disease, or uncontrolled diabetes; (v) a severe mood disorder; (vi) been pregnant or breastfeeding in the preceding 12 months; or (vii) were morbidly obese (BMI ≥ 40). Once eligibility was confirmed, participants were invited to a recruiting centre for clinical assessment and blood sample collection: this included the healthy controls, PWME and people with MS.



Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review  Mark VinkAlexandra Vink-Niese




Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy




Scientists from Trinity College Dublin have discovered a potential new target for regulating inflammation, which drives a range of diseases including diabetes, cancer and Alzheimer's. The potential target is an ancient immune protein - SARM - that has been conserved throughout evolution and thus is very similar in humans, other mammals, flies and worms.




Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with

atypical and classical presentations

We analyzed cerebrospinal fluid (CSF) from 32 cases with classical ME and 27 cases with atypical ME using

a 51-plex cytokine assay. Atypical subjects differed in cytokine profiles from classical subjects. In logistic

regression models incorporating immune molecules that were identified as potential predictor variables

through feature selection, we found strong associations between the atypical ME phenotype and lower CSF levels

of the inflammatory mediators, interleukin 17A and CXCL9.



Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis

One approach to circumvent potential challenges associated with maximal exercise testing is the use of submaximal exercise testing. Submaximal exercise paradigms have been proposed as a safer alternative to maximal cardiopulmonary exercise testing, because it is thought to be less likely to create severe, long-lasting symptoms in people with ME. One example of a submaximal test paradigm involves a sustained 25-min bout of work at 70% of age-predicted maximum heart rate. This type of “submaximal” physiological stressor has been used in a number of studies involving patients with ME. However, the presence of abnormal heart rate responses to exercise in people with ME suggests a potential to over-estimate workload based on predicted heart rate, which in turn, risks having subjects exert harder than intended during tests that are putatively “submaximal.”



Australia started in 2016 and they have a published an update every year since. See links below.
From 2016
2017 tps://


Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection

Viruses that are typically benign sometimes invade the brainstem in otherwise healthy children. We report bi-allelic DBR1 mutations in unrelated patients from different ethnicities, each of whom had brainstem infection due to herpes simplex virus 1 (HSV1), influenza virus, or norovirus. DBR1 encodes the only known RNA lariat debranching enzyme. We show that DBR1 expression is ubiquitous, but strongest in the spinal cord and brainstem. We also show that all DBR1 mutant alleles are severely hypomorphic, in terms of expression and function. The fibroblasts of DBR1-mutated patients contain higher RNA lariat levels than control cells, this difference becoming even more marked during HSV1 infection. Finally, we show that the patients’ fibroblasts are highly susceptible to HSV1. RNA lariat accumulation and viral susceptibility are rescued by wild-type DBR1. Autosomal recessive, partial DBR1 deficiency underlies viral infection of the brainstem in humans through the disruption of tissue-specific and cell-intrinsic immunity to viruses.



Jonathon Kerr:  Department of Microbiology, West Suffolk Hospital Foundation Trust, Bury St Edmunds, United Kingdom

ME patients exhibit up regulation of EBV virus induced gene 2 (EBI2) mRNA in peripheral blood mononuclear cells (PBMC), and these patients appear to have a more severe disease phenotype and lower levels of EBNA1 IgG. EBI2 is induced by EBV infection and has been found to be upregulated in a variety of autoimmune diseases. EBI2 is a critical gene in immunity and central nervous system function; it is a negative regulator of the innate immune response in monocytes.



The biopolitics of CFS/ME.

Karfakis N. Stud Hist Philos Biol Biomed Sci. 2018.  Authors Karfakis N

Author information:  Business School, Alexander College/University of the West of England, 2 Artas Street, Aradippou 7110, Larnaca, Cyprus. Electronic address:


This paper argues that Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) constitutes a biopolitical problem, a scientific object which needs to be studied, classified and regulated. Assemblages of authorities, knowledges and techniques make CFS/ME subjects and shape their everyday conduct in an attempt to increase their supposed autonomy, wellbeing and health. CFS and CFS/ME identities are however made not only through government, scientific, and medical interventions but also by the patients themselves, a biosocial community who collaborates with scientists, educates itself about the intricacies of biomedicine, and contests psychiatric truth claims. CFS/ME is an illness trapped between medicine and psychology, an illness that is open to debate and therefore difficult to manage and standardise. The paper delineates different interventions by medicine, science, the state and the patients themselves and concludes that CFS/ME remains elusive, only partially standardised, in an on-going battle between all the different actors that want to define it for their own situated interests.



Here's a list of monoclonal antibodies, including Rituximab, which, of course was being trialed most famously in Norway.

Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with MS.


Cerebral Blood Flow Volume (CBFV) and Heart Rate Variability (HRV) and ME.  WHAT is HRV? HRV has to do with the amount of variation in the intervals between heartbeats.

Low HRV is when the intervals between your heartbeats are rather constant.  High HRV is if the length variates.  This is important for ME patients because we have problems with our autonomic nervous system.

From HRV article: "The autonomic nervous system regulates very important systems in our body, including heart and respiration rate and digestion. The autonomic nervous system has a parasympathetic (rest) and a sympathetic (activation) branch. Heart rate variability is an indicator that both branches are functioning – the parasympathetic in particular."

From the study: "We hypothesized that CBFV would be reduced in individuals with CFS compared to healthy controls, and that increased CBFV and HRV would be associated with lower levels of fatigue in affected individuals. Our results provided support for these hypotheses."   This article explains HRV pretty well:

The role of retroviruses in chronic illness is greatly disputed in academic circles. However, at the Sophia Health Institute Dr DIETRICH KLINGHARDT, MD, PhD, reports seeing significant improvement in treatment outcomes – in the most severely affected patients with chronic illness – when anti-retroviral strategies are included."



In summary, because there is no established cause of ME, no conclusive tests to determine its presence and no definitive outward signs that set it apart from other disorders, clinicians must rely on patients’ self-perceptions and reports. As such, identifying

distinct clinical features of ME is an important issue. Here, we have reported contrast sensitivity deficits in a group of ME patients.

We propose that these findings, along with other visual problems experienced by people with ME, may have implications for

diagnosis and may provide some insights into its aetiology.

They also raise a number of important questions that warrant further study. 

​"The significantly higher amounts of antiganglionic acetylcholine receptor antibodies in the serum of patients with postural

orthostatic tachycardia syndrome (POTS) adds support to the growing understanding of POTS as a possible autoimmune condition, the authors of a new study reported.


Strong scientific evidence for Medicinal Cannabis. 

There is strong scientific evidence supporting the following medical conditions:  For the treatment of chronic pain in adults (using all forms of cannabis).  As an anti-emetic (anti-nausea) in the treatment of chemotherapy-induced nausea and vomiting (in the form of oral cannabinoids).   For improving patient-reported multiple sclerosis spasticity symptoms (oral cannabinoids).  What’s important to note here is that smoking marijuana is only useful in treating chronic pain. For the other two indications, anti-nausea and multiple sclerosis, only the oral version of the drug, known as nabiximols, a highly specific extract from the cannabis plant, has shown efficacy. This contradicts a lot of the anecdotes and claims about the usefulness of marijuana in treating

nausea and certain symptoms of multiple sclerosis.  This also supports the idea that the

individual components of cannabis need to be identified, and the proper dosage of that component needs to be studied before we can make evidence-based claims about marijuana medical benefits.

I’ll keep saying this – if a component of marijuana has a medical benefit, real research will determine what that is, isolate or

synthesize it, put it into a form that safe for humans, and perform clinical trials and submit it to regulatory bodies, like the FDA,

before marketing it for an indication. I know that sounds like a lot of hard work, but that’s how science-based medicine works.




Dated May 2018

Layman's article: EBV appears to be able to trigger autoimmune diseases later in life and could conceivably play a role in ME.


Published in 1995

The Lancet dated April 2018 - Catching up on Lancet updates; came across this paper on Guillain-Barré and the complement system, from April. An auto-immune syndrome following an infection...

 Griffith University researchers have received the largest funding ever awarded for Chronic Fatigue Syndrome research, which will allow the development of a first-of-its-kind diagnostic blood test to identify genetic markers for #CFS. This breakthrough test will help put an end to the myths around the chronic illness and is also one of the key items being discussed at today’s Gold Coast Health and Medical Research Conference. #GCHMRC16 #MECFS Centre for Neuroimmunology and Emerging Diseases – NCNED


Brain inflammatory cascade controlled by gut-derived molecules  May 16th, 2018. 

In this paper in Nature, Rothhammer et al.2 describe how these two glial cell types communicate on a molecular level to influence inflammation in the CNS, and show that this interaction is controlled remotely by microbes that inhabit the gut.  Metabolite molecules produced by the gut’s microbes activate immune cells in the brain called microglia, which signal to astrocyte cells to mediate responses to inflammation in the central nervous system.  Some immunologists regard the central nervous system (CNS) as a no-man’s-land, avoided by immune cells and therefore uninteresting. But, in fact, the CNS has a vigorous immune potential that remains dormant in normal conditions but is awakened after injury. The switch that controls the brain’s immune microenvironment involves non-neuronal cells called glia — not only microglia, which are sometimes called the immune cells of the CNS, but also multifunctional cells called astrocytes.



Frank  Twisk.   diagnostics 2018, 8(2), 34. doi: 10.3390/diagnostics8020034. 

Commentary:  Recently, the Dutch Health Council published their advisory report on Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS), which is meant to determine the medical policy with regard to ME in the Netherlands.  The Health Council briefly discusses several diagnostic criteria and proposes to use new diagnostic criteria for "ME/CFS"  in research and clinical practice in the future.  The advisory report then  summarizes organic abnormalities observed in the last decades and concludes that "ME/CFS" is a "serious, chronic, multisystem disease".  According to the Health Council there are no curative treatments for "ME/CFS", due to lack of knowledge, but specific medication could bring symptomatic relief.  The Health Council ecommends conducting more research, to (re)educate medical professionals about "ME/CFS", to appoint three academic expertise centres, which will install a care network for patients, and to fairly judge the limitations (disability) of patients when they apply for a disability income, medical aid and care.  The advisory report was welcomed by many patients, because it puts an end to the dominance of the (bio)psychosocial explanatory model and seems to offer a perspective of improving the situation of patients.  However, the starting point of the advisory report,  a new definition of "ME/CFS", will have serious (long-lasting) consequences for patients and researchers.


Comparing Post-Exertional Symptoms Following Serial Exercise Tests:  A standardized exertional stimulus produces prolonged and more diverse symptoms in ME/CFS subjects compared with those seen in control subjects. Understanding PEM more comprehensively may provide clues to the underlying pathophysiology of ME/CFS and lead to improved diagnosis and treatment.



Fibromyalgia is present in as much as 2% of the population, causing pain, stiffness, and tenderness of the muscles. Upon accurate diagnostic, nonpharmacological and pharmacological therapies can be used to alleviate pain and manage other symptoms. However, lack of objective, universal applicable diagnostic criteria as well as vague and diffused symptoms, have made diagnosis difficult. In this context, our findings can shed light on potential value of CSF proteome for objectively diagnosing FM.



Via:  Frank Twisk:  Oddly enough, many patients in one ME-ICC patient subgroup reported they never or sometimes experience post-exertional 'malaise'.  Looking at the quote below, the authors don't seem to have read my article accurately It has been suggested that ME and CFS may represent distinct conditions, where patients with CFS would not necessarily report an infectious onset, and neither exhibit muscle pain nor neurological symptoms [66].  Twisk FNM.  An accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome requires strict clinical case definitions and objective test methods.  J. Med. Diagnost. Methods 5(2), 68–87 2017). 


This is not what I 'suggest'...   Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome.  

Aim:   To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on DNA methylation profiles and health scores.

Methods:   DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes.

Results:   We discovered four ME/CFS subtypes associated with DNA methylation modifications in 1939 CpG sites, three RAND-36 categories and five DePaul Symptom Questionnaire measures.  Methylation patterns of immune response genes and differences in physical functioning and post-exertional malaise differentiated the subtypes.

Conclusion:   ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology and provide additional evidence of the potential relevance of metabolic and immune differences in ME/CFS with respect to specific symptoms.



Abstract/Artist Statement:  Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functional ability. Recognizing the triggers, onset, symptoms and duration of PEM is important for the diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). PEM following serial exercise tests has not been examined.


Frank Twisk: 

Many researchers consider chronic fatigue syndrome (CFS) to be a synonym of Myalgic Encephalomyelitis (ME). However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease), as recently suggested.


Amy Proal's recent paper shows that ME is likely a polymicrobial disease.


Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome.  To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on DNA methylation profiles and health scores.


​Frank Twisk  for Video presentation online; Myalgic Encephalomyelitis, chronic fatigue syndrome, and Systemic Exertion Intolerance Disease: Three distinct clinical entities Challenges 2018, 9(1), 19; doi:


Contrary to a hopeful press release the effects of kpax002 are disappointing. 

The (CIS) Vermoeidheids score (minimum 20, maximum 140) Took off in the kpax group with 16,9,.  But also in the placebo group, the cis f vermoeidheids score decreased by 13,8 (almost 10 %).



The etiology of chronic fatigue syndrome (CFS) remains unclarified.

Recently, dysfunction of central nervous system by myalgic encephalomyelitis (ME) has been postulated as the cause of CFS. International Consensus Criteria identify patients with ME who are more physically debilitated and have greater physical and cognitive impairments. Orthostatic intolerance (OI) with symptoms of disabling fatigue, dizziness, diminished concentration, tremulousness and nausea while standing, appears to be a core symptom of ME, impairing the most basic activities of daily living. Cardiovascular dysfunction in association with a small heart or a small left ventricle (LV) and low cardiac output may be related to the pathophysiology of ME.

OI was prevalent in ME. Both systolic and diastolic blood pressures were low in ME. A small size of LV associated with low cardiac output due to diminished stroke volume was frequently observed in ME. A small heart appears to be related to the genesis of ME via both cerebral and systemic hypoperfusion, which could make it difficult for patients to meet the demands of everyday activity. A small heart with impaired cardiac performance due to decreased preload appears to be an important target for the treatment of ME.

Opa1 and inflammation:  The absence of a single mitochondrial protein causes severe inflammation.  A new study supports the notion that mitochondrial defects underlie a set of diseases of unknown origin that involve chronic muscle inflammation.   Opa1 is a mitochondrial fusion protein. It serves to fuse the internal membranes of mitochondria. Although present in all cells and tissues (except white blood cells), mitochondria are particularly abundant in muscle and liver, and their main function is to convert the energy in food into energy for cells. Mitochondria are highly dynamic; they join and separate, and grow and shrink constantly. These processes are known as mitochondrial dynamics.


Frank Twisk:  Summarizes the illogic and fundamental error of claims that the infectious neurological disease ME and the nonspecific fatigue conditions CFS and "SEID" (now renamed "ME/CFS" by the US CDC) are synonymous terms:  Abstract: Many researchers consider chronic fatigue syndrome (CFS) to be a synonym of Myalgic Encephalomyelitis (ME). However, the case criteria of ME and CFS define two distinct clinical entities.  Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfill the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient.  ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and  sensory symptoms.    The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multi-joint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h.  So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease), as recently suggested.



​Rethinking the treatment of chronic fatigue syndrome—

A reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT (PDF Download Available).

Available from: [accessed Mar 23 2018].

​Gastrointestinal Symptoms in POTS.  Study completed November 2017 and accepted March 2018.



Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome.  Jason LA*, Ohanian D, Brown A, Sunnquist M, McManimen S, Klebek L, Fox P and Sorenson M  College of Science and Health, DePaul University, USA.  Onset patterns of Myalgic Encephalomyelitis & Chronic Fatigue Syndrome;  Meredyth Anne Evans & Leonard A. Jason*



ME Community Research January 2018:  ​Rethinking the treatment of chronic fatigue syndrome—A reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT *

BACKGROUND: The PACE trial was a well-powered randomized trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.



Vision in ME - Jan 17th, 2018. 

Myalgic encephalomyelitis (ME) is a devastating disorder marked by debilitating fatigue. It not well understood and its diagnosis is controversial. It is very important therefore that significant clinical features are investigated. Visual symptoms in ME represent a group of distinct, quantifiable, clinical features that could significantly improve diagnosis and provide insights into underlying pathology. The purpose of the present study was therefore to explore the effect of ME on spatial windows of visibility using the spatial contrast sensitivity function. Contrast sensitivity was determined for stationary luminance-defined sinusoidal gratings spanning a five-octave range of spatial frequencies (0.5 to 16 c/deg) in a group of 19 individuals with ME and a group of 19 matched (age, gender) controls. Compared to controls, the ME group exhibited a restricted spatial window of visibility for encoding stimulus contrast. This was characterised principally by a contrast sensitivity deficit at lower spatial frequencies and a narrower bandwidth. Our findings suggest that contrast sensitivity eficits may represent a visual marker of ME, and be indicative of abnormal visual processing at the level of the retina and in the cortical and subcortical visual pathways.  or



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