ME Association April Summary of ME/CFS Published Research | 01 May 2019

May 1, 2019


Charlotte Stephens, Research Correspondent, ME Association.

ME Association Index of Published ME/CFS Research

The Index of Published ME/CFS Research has now been updated to take account of the research that has been published during the month of April 2019.

The Index is a useful way to locate and then read all relevant research on ME/CFS. It’s free to download and comes with an interactive contents table.

This is an A-Z list of all the most important ME/CFS research studies (and selected key documents and articles), listed by subject matter and author, with links to PubMed or to the Journal it was published in.

You can also find the index in the Research section of our website.

ME/CFS research abstracts from studies published in April 2019

1. Asprusten T et al. (2019)
EBV-requisitioning physicians’ guess on fatigue state 6 months after acute EBV infection.
BMJ Paediatrics Open 3 (1).

We assessed referring medical practitioner’s ability to predict chronic fatigue development in adolescents presenting with acute infectious mononucleosis.

Compared with ‘not fatigued’ being predicted as ‘unsurely fatigued’ and ‘likely fatigued’ were both strongly associated with developing fatigue 6 months later (OR 2.5, 95% CI 1.16% to 5.47% and 3.2, 95% CI 1.19% to 8.61%, respectively, P=0.012). The positive and negative predictive values were 66% and 62%, respectively.

Disentangling the physician’s intuition may be of interest in further investigations of risk factors and prophylactic factors for fatigue development.

2. Cabanas H et al. (2019)
Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.
Molecular Medicine 25 (1): 14.

Background: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a complex multifactorial disorder of unknown cause having multi-system manifestations. Although the aetiology of CFS/ME remains elusive, immunological dysfunction and more particularly reduced cytotoxic activity in natural killer (NK) cells is the most consistent laboratory finding.

The Transient Receptor Potential (TRP) superfamily of cation channels play a pivotal role in the pathophysiology of immune diseases and are therefore potential therapeutic targets. We have previously identified single nucleotide polymorphisms in TRP genes in peripheral NK cells from CFS/ME patients.

We have also described biochemical pathway changes and calcium signaling perturbations in NK cells from CFS/ME patients. Notably, we have previously reported a decrease of TRP cation channel subfamily melastatin member 3 (TRPM3) function in NK cells isolated from CFS/ME patients compared with healthy controls after modulation with pregnenolone sulfate and ononetin using a patch-clamp technique.

In the present study, we aim to confirm the previous results describing an impaired TRPM3 activity in a new cohort of CFS/ME patients using a whole cell patch-clamp technique after modulation with reversible TRPM3 agonists, pregnenolone sulfate and nifedipine, and an effective TRPM3 antagonist, ononetin.

Indeed, no formal research has commented on using pregnenolone sulfate or nifedipine to treat CFS/ME patients while there is evidence that clinicians prescribe calcium channel blockers to improve different symptoms.

Methods: Whole-cell patch-clamp technique was used to measure TRPM3 activity in isolated NK cells from twelve age- and sex-matched healthy controls and CFS/ME patients, after activation with pregnenolone sulfate and nifedipine and inhibition with ononetin.

Results: We confirmed a significant reduction in amplitude of TRPM3 currents after pregnenolone sulfate stimulation in isolated NK cells from another cohort of CFS/ME patients compared with healthy controls.

The pregnenolone sulfate-evoked ionic currents through TRPM3 channels were again significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients.

In addition, we used nifedipine, another reversible TRPM3 agonist to support the previous findings and found similar results confirming a significant loss of the TRPM3 channel activity in CFS/ME patients.

Conclusions: Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME.

3. Chalder T et al. (2019)
However CFS is operationalised young people's perspectives are important.

Journal of Behavioural Medicine [Epub ahead of print].


4. Cliff J et al. (2019)
Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Frontiers in Immunology 10: 796.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, unclear pathophysiology and with no diagnostic test or biomarker available.

Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive.

The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants.

In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis.

There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients.

Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants.

In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8+ T cells and decreased proportions of terminally differentiated effector CD8+ T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients.

These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection or may indicate future increased susceptibility to infection.

Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS.

5. Fluge Ø et al. (2019)
B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Annual of International Medicine [Epub ahead of print].

Background: Previous phase 2 trials indicated benefit from B-lymphocyte depletion in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: To evaluate the effect of the monoclonal anti-CD20 antibody rituximab versus placebo in patients with ME/CFS.

Patients: 151 patients aged 18 to 65 years who had ME/CFS according to Canadian consensus criteria and had had the disease for 2 to 15 years.

Intervention: Treatment induction with 2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months (n = 77), or placebo (n = 74).

Measurements: Primary outcomes were overall response rate (fatigue score ≥4.5 for ≥8 consecutive weeks) and repeated measurements of fatigue score over 24 months. Secondary outcomes included repeated measurements of self-reported function over 24 months, components of the Short Form-36 Health Survey and Fatigue Severity Scale over 24 months, and changes from baseline to 18 months in these measures and physical activity level. Between-group differences in outcome measures over time were assessed by general linear models for repeated measures.

Results: Overall response rates were 35.1% in the placebo group and 26.0% in the rituximab group (difference, 9.2 percentage points [95% CI, -5.5 to 23.3 percentage points]; P = 0.22). The treatment groups did not differ in fatigue score over 24 months (difference in average score, 0.02 [CI, -0.27 to 0.31]; P = 0.80) or any of the secondary end points. Twenty patients (26.0%) in the rituximab group and 14 (18.9%) in the placebo group had serious adverse events.

Limitation: Self-reported primary outcome measures and possible recall bias.

Conclusion: B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with ME/CFS.

6. Friedman K (2019)
Advances in ME/CFS: Past, Present, and Future.
Frontiers in Pediatrics 7: 131.

The forerunner of what is today termed myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was described by the U.S. Public Health Service in 1934. At the present time, we still do not know its cause and/or how to detect it by routine clinical laboratory tests. In consequence, the pathological nature of ME/CFS has been overlooked and the disease has been stigmatized by being mislabeled as psychosomatic or somatoform illness.

Such misperceptions of the disease have led to insufficient research exploration of the disease and minimal to absent patient care. A 2015 Institute of Medicine report on the illness declared ME/CFS a disease affecting up to 2.5 million Americans and chastised the U.S. government for doing little to research the disease and to support its patients.

Clinicians who currently treat this disease declare it to be more devastating than HIV/AIDS. A comparison of the histories of the two diseases, an examination of the current status of the two diseases, and a listing of the accomplishments that would be needed for ME/CFS to achieve the same level of treatment and care as currently experienced by patients with HIV/AIDS is provided.

7. Janse A et al. (2019)
Prediction of long-term outcome after cognitive behavioural therapy for chronic fatigue syndrome.
Journal of Pyschosomatic Research [Epub ahead of print].

Objective: To determine which variables predicted long-term outcome after cognitive behavioral therapy (CBT) for chronic fatigue syndrome (CFS).

Methods: A cohort of 511 CFS patients from four different CBT for CFS studies, i.e. two cohort studies and two RCT's. Before treatment, all patients fulfilled the 2003 US CDC criteria for CFS and treated with CBT, were assessed at long-term follow-up, up to 10 years after end of treatment. We tried to predict fatigue severity and physical functioning at follow-up with demographics, cognitive-behavioral perpetuating factors, and CFS characteristics as predictors in linear regression analyses. Logistic regression analysis was used to explore significant predictors of fatigue scores within normal limits at long-term follow-up.

Results: Lower fatigue severity at long-term follow-up was predicted by a shorter duration of CFS symptoms and lower fatigue levels at baseline, and lower frustration in response to fatigue and lower fatigue levels directly post-treatment. Fatigue scores within normal limits at follow-up was predicted by lower fatigue severity and lower levels of frustration in response to fatigue, both assessed directly post-treatment. Better physical functioning at follow-up was predicted by higher sense of control over fatigue, better physical functioning at post-treatment, and being younger at baseline. In some of the additional analysis pain at baseline also predicted physical functioning at follow-up.

Conclusions: The finding that lower fatigue severity and higher physical functioning at long-term follow-up were positively associated with its outcomes at post-treatment underline the importance of fully maximizing the positive effects of CBT for the sustainment of outcomes. Furthermore, augmenting sense of control and starting treatment sooner after diagnosing CFS could positively influence long-term outcome. Interventions aimed at pain management deserve more attention in research.

8. Loades ME et al. (2019)
Depressive symptoms in adolescents with chronic fatigue syndrome (CFS): Are rates higher than in controls and do depressive symptoms affect outcome?
Clinical Child Psychology and Psychiatry [Epub ahead of print].

Introduction: Previous research has indicated that co-morbid depression is common in adolescents with chronic fatigue syndrome (CFS).

Objectives: We sought to compare the characteristics of depressive symptoms in adolescents with CFS to those of healthy controls (HCs) and illness controls (adolescents with asthma).

Methods: A total of 121 adolescents with CFS who attended an initial assessment at two specialist CFS units completed the Children's Depression Inventory (CDI). Their responses were compared to 80 HCs and 27 adolescents with asthma (illness controls). The clinical cohort of adolescents with CFS completed questionnaires at assessment, and those who were seen subsequently for treatment at the CFS unit (68%) completed the measures again at their first treatment session.

Results: CFS participants scored significantly higher on all the depression subscales than participants with asthma and HCs. Depression score explained 11% of the variance in subsequent fatigue, but only 1.9% of the variance in physical functioning. Depression score also explained most (68%) of the variance in subsequent depression.

Conclusion: Depressive symptoms are more prominent in adolescents with CFS than in HCs or illness controls. These symptoms also appear to remain over time during a naturalistic follow-up where no treatment was provided. This highlights the need for further research into depression in CFS, including stratifying treatment outcomes by depression status to determine what is effective at addressing these symptoms.

9. Martin-Martinez E and Martin-Martinez M (2019)
Varied Presentation of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Needs for Classification and Clinician Education: A Case Series.
Clinical Therapeutics 41 (4): 619-624.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, heterogeneous and serious disease. In this article, we analyze the cases of 3 patients with ME/CFS.

Due to the disbeliefs, misconceptions, and stigmas that are attached to ME/CFS, patient diagnosis is made after years of disease progression. Over this period, physicians tried to determine the etiology of the disease, taking into account its onset and symptoms.

The suspected conditions correlated with possible subgroups that researchers speculate may exist in ME/CFS. Therefore, a registry of well-selected data on clinical history could help to cluster patients into more homogenous groups and could be beneficial for research.

10. Morris M et al. (2019)
Leveraging Prior Knowledge of Endocrine Immune Regulation in the Therapeutically Relevant Phenotyping of Women With Chronic Fatigue Syndrome.
Clinical Therapeutics 41 (4): 656-674.

Purpose: The complex and varied presentation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has made it difficult to diagnose, study, and treat. Its symptoms and likely etiology involve multiple components of endocrine and immune regulation, including the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, and their interactive oversight of immune function.

We propose that the persistence of ME/CFS may involve changes in the regulatory interactions across these physiological axes. We also propose that the robustness of this new pathogenic equilibrium may at least in part explain the limited success of conventional single-target therapies.

Methods: A comprehensive model was constructed of female endocrine-immune signaling consisting of 28 markers linked by 214 documented regulatory interactions. This detailed model was then constrained to adhere to experimental measurements in a subset of 17 candidate immune markers measured in peripheral blood of patients with ME/CFS and healthy control subjects before, during, and after a maximal exercise challenge. A set of 26 competing numerical models satisfied these data to within 5% error.

Findings: Mechanistically informed predictions of endocrine and immune markers that were either unmeasured or exhibited high subject-to-subject variability pointed to possible context-specific overexpression in ME/CFS at rest of corticotropin-releasing hormone, chemokine (C-X-C motif) ligand 8, estrogen, follicle-stimulating hormone (FSH), gonadotropin-releasing hormone 1, interleukin (IL)-23, and luteinizing hormone, and underexpression of adrenocorticotropic hormone, cortisol, interferon-γ, IL-10, IL-17, and IL-1α.

Simulations of rintatolimod and rituximab treatment predicted a shift in the repertoire of available endocrine-immune regulatory regimens. Rintatolimod was predicted to make available substantial remission in a significant subset of subjects, in particular those with low levels of IL-1α, IL-17, and cortisol; intermediate levels of progesterone and FSH; and high estrogen levels.

Rituximab treatment was predicted to support partial remission in a smaller subset of patients with ME/CFS, specifically those with low norepinephrine, IL-1α, chemokine (C-X-C motif) ligand 8, and cortisol levels; intermediate FSH and gonadotropin-releasing hormone 1 levels; and elevated expression of tumor necrosis factor-α, luteinizing hormone, IL-12, and B-cell activation.

Implications: Applying a rigorous filter of known signaling mechanisms to experimentally measured immune marker expression in ME/CFS has highlighted potential new context-specific markers of illness.

These novel endocrine and immune markers may offer useful candidates in delineating new subtypes of ME/CFS and may inform on refinements to the inclusion criteria and instrumentation of new and ongoing trials involving rintatolimod and rituximab treatment protocols.

11. Murray R et al. (2019)
Duvet woman versus action man: the gendered aetiology of Chronic Fatigue Syndrome according to English newspapers.
Feminist Media Studies.

Media portrayals of conditions such as Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) demand exploration as the media is a potent source of information and meaning, and as such has the potential to inform public and professional understandings. To date, there is little systematic exploration of print media representations of CFS/ME.

In this study, we address that gap by exploring the voices of CFS/ME sufferers in the English print media (1998–2015) from a constructionist feminist perspective. We found that portrayals of CFS/ME differ meaningfully, depending on gender.

The psychological and emotional tended to be foregrounded where women were concerned and the scepticism surrounding CFS/ME as a “non disease” was much more evident. On some occasions this was dealt with directly, whilst on others it was “leaked in” or hinted at. This serves to delegitimise the illness in women. In contrast, the physical was usually foregrounded in the case of men suffering from the condition and their experiences were accredited greater legitimacy.

We problematise these representations and discuss the potential impact upon public and professional sympathy, treatment options and long-standing, gendered constructions of illness.

12. Nacul L et al. (2019)
Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study.

Diagnostics 9 (2).

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease presenting with extreme fatigue, post-exertional malaise, and other symptoms. In the absence of a diagnostic biomarker, ME/CFS is diagnosed clinically, although laboratory tests are routinely used to exclude alternative diagnoses.

In this analytical cross-sectional study, we aimed to explore potential haematological and biochemical markers for ME/CFS, and disease severity. We reviewed laboratory test results from 272 people with ME/CFS and 136 healthy controls participating in the UK ME/CFS Biobank (UKMEB).

After corrections for multiple comparisons, most results were within the normal range, but people with severe ME/CFS presented with lower median values (p < 0.001) of serum creatine kinase (CK; median = 54 U/L), compared to healthy controls (HCs; median = 101.5 U/L) and non-severe ME/CFS (median = 84 U/L). The differences in CK concentrations persisted after adjusting for sex, age, body mass index, muscle mass, disease duration, and activity levels (odds ratio (OR) for being a severe case = 0.05 (95% confidence interval (CI) = 0.02-0.15) compared to controls, and OR = 0.16 (95% CI = 0.07-0.40), compared to mild cases).

This is the first report that serum CK concentrations are markedly reduced in severe ME/CFS, and these results suggest that serum CK merits further investigation as a biomarker for severe ME/CFS.

13. Newton F (2019)
Meeting the Educational Needs of Young, ME/CFS Patients: Role of the Treating Physician.
Frontiers in Paediatrics 7:104.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling, chronic disease characterized by the body's inability to produce sufficient energy for normal everyday activities.

Children with ME/CFS experience debilitating fatigue referred to as post-exertional malaise (PEM) after minimal mental or physical exertion which is not relieved by sleep. It can significantly reduce the ability of the child to take part in personal, educational, or social activities and can compromise executive function, and can result in a moderate to severe disability.

As many as 1% of school-age children suffer from this disease in varying degrees of severity, and ME/CFS has been shown to negatively impact school attendance, participation, connectedness, and academic performance (1). Some studies suggest that ME/CFS may be the major cause of extended school absences (2).

Whereas, the literature supplying practice-based guidance for other chronic conditions affecting children in school, such as Autism and Attention Deficit Hyperactivity Disorder (ADHD) will be found in educational journals, very little guidance for students with ME/CFS appears in the clinical medicine literature. Although school nurses are beginning to play a larger role in supporting these children, physicians or healthcare providers retain primary responsibility of informing the school system of the needed adjustments for the young ME/CFS patient to succeed in the school environment.

This article argues that the physician has a much broader responsibility to provide diagnostic, symptomatic, and treatment information about ME/CFS than they would with other conditions such as Autism or ADHD that qualify students for special services. For students with ME/CFS, the physician's letter required in the school's evaluation process is a critical resource to advise and guide education professionals regarding appropriate student placement, classroom support, and instructional accommodations or modifications. The specifics of what should be included in a model physician's letter are included.

14. Pederson M et al. (2019)
Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study.
Journal of Psychosomatic Research [Epub ahead of print].

Objective: Acute Epstein-Barr virus (EBV) infection is a known trigger of both acute and chronic fatigue. The aim of this study was to investigate associations to fatigue in adolescents with EBV infection during the initial stage and six months after, as well as in healthy controls.

Methods: 200 adolescents (12–20 years old) with EBV infection were assessed as soon as possible after the onset of symptoms (EBVbaseline) and six months later (EBVsix months, 5 drop-outs). Also, 70 healthy controls (HC) were included. Associations between current fatigue and 148 different variables (including symptoms, functional abilities and biomarkers) were investigated separately for EBVbaseline, EBVsix months and HC using linear regression modelling.

Results: Fatigue was associated with symptoms of sleeping difficulties, negative emotions, and quality of life under all circumstances. Fatigue was independently associated with markers of immune response at EBVsix months and in HC, not at EBVbaseline. An association between fatigue and markers of autonomic cardiovascular control was only present at EBVsix months. Cognitive functioning shifted from a positive association to fatigue at EBVbaseline to a negative trend at EBVsix months.Markers of infection were not associated with fatigue at EBVbaseline, EBVsix months nor in HC.

Conclusions: Irrespective of the cause, fatigue is important for quality of life and is highly associated with negative emotions. Markers of infection and immune response had respectively none and barely any association to fatigue. Autonomic alterations and cognitive dysfunction were exclusively associated with fatigue long after infection, corroborating findings from studies of the Chronic Fatigue Syndrome.

15. Scartozzi S et al. (2019)
Myalgic encephalomyelitis and chronic fatigue syndrome case definitions: effects of requiring a substantial reduction in functioning.
Fatigue: Biomedicine, Health and Behaviour.

Background: Current case definitions for myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) require an individual to report a ‘substantial reduction’ in activity levels, when compared to premorbid functioning. However, little guidance is provided on how to measure these reductions, as well as what level of reduction should be deemed ‘substantial,’ leading to inconsistencies in how this criterion is applied across research settings.

Purpose: The current study examined the influence of substantial reduction criterion on case definitions.

Method: The current study nalyse an international convenience sample of 1002 individuals with ME or CFS, 53 healthy controls, and 260 controls with other chronic illnesses.

Results: Findings indicated that the utility of the substantial reduction criterion varied by case definition, with more stringent case definitions not needing this criterion to identify cases.

Conclusions: These results suggest that the requirement of a substantial reduction in functioning may be redundant when case definitions specify that individuals must endorse a set of core symptoms at specified frequency and severity levels.

16. Sebaiti M et al. (2019)
Macrophagic myofasciitis-associated dysfunctioning: An update of neuropsychological and neuroimaging features.
Best Practise and Research Clinical Rheumatology [Epub ahead of print].

Macrophagic myofasciitis (MMF) syndrome is a subtype of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld’s syndrome, characterized by the presence of stereotyped inflammatory lesions at muscle biopsy attesting the long-term persistence of nalyse hydroxide particles at the site of previous immunization. Most frequently reported symptoms are chronic arthromyalgias and fatigue and cognitive complaint.

MMF-associated cognitive disorder (MACD) is characterized by the dysfunctioning of attention, executive functions, short-term term and long-term memory, and, in some instances, left ear extinction. MACD is expressed in a chronic, nonevolving, well-defined syndromic framework within which the expression in terms of severity differs from one patient to another. While brain MRI is usually noncontributive, functional imaging using SPECT and PET has revealed the existence of a suggestive pathological pattern with involvement of posterior associative areas, temporal lobes, limbic system, and cerebellum.

Put together, neuropsychological and functional neuroimaging investigations support the view that MACD relates to organic central nervous system involvement.

17. Shao et al. (2019)
Therapeutic Effect and Metabolic Mechanism of A Selenium-Polysaccharide from Ziyang Green Tea on Chronic Fatigue Syndrome.
Polymers 10 (11).

Ziyang green tea was considered a medicine food homology plant to improve chronic fatigue syndrome (CFS) in China. The aim of this research was to study the therapeutic effect of selenium-polysaccharides (Se-TP) from Ziyang green tea on CFS and explore its metabolic mechanism.

A CFS-rats model was established in the present research and Se-TP was administrated to evaluate the therapeutic effect on CFS. Some serum metabolites including blood urea nitrogen (BUN), blood lactate acid (BLA), corticosterone (CORT), and aldosterone (ALD) were checked. Urine metabolites were nalyse via gas chromatography-mass spectrometry (GC-MS). Multivariate statistical analysis was also used to check the data.

The results selected biomarkers that were entered into the MetPA database to nalyse their corresponding metabolic pathways. The results demonstrated that Se-TP markedly improved the level of BUN and CORT in CFS rats. A total of eight differential metabolites were detected in GC-MS analysis, which were benzoic acid, itaconic acid, glutaric acid, 4-acetamidobutyric acid, creatine, 2-hydroxy-3-isopropylbutanedioic acid, l-dopa, and 21-hydroxypregnenolone.

These differential metabolites were entered into the MetPA database to search for the corresponding metabolic pathways and three related metabolic pathways were screened out. The first pathway was steroid hormone biosynthesis. The second was tyrosine metabolism, and the third was arginine-proline metabolism. The 21-hydroxypregnenolone level of rats in the CFS group markedly increased after the Se-TP administration.

In conclusion, Se-TP treatments on CFS rats improved their condition. Its metabolic mechanism was closely related to that which regulates the steroid hormone biosynthesis.

18. Theoharides T (2019)
A Timely Multidisciplinary Update on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Clinical Therapeutics 41 (4): 610-611.


19. Thompson et al. (2019)
Cognitive factors are associated with disability and pain, but not fatigue among physiotherapy attendees with persistent pain and fatigue.
Physiotherapy [Epub ahead of print].

Objectives: Most research exploring the relationship between cognitive factors and pain, disability and fatigue in patients with persistent pain/fatigue has been performed in multi-disciplinary environments. It is unclear whether these associations are consistent in other contexts.

This study therefore aimed to establish the relationships between these factors in patients with persistent pain/fatigue referred for physiotherapy treatment.

Participants: 166 patients with persistent pain and fatigue disorders chronic widespread pain, fibromyalgia and chronic fatigue syndrome/myalgic encephalopathy.

Main outcome measures: Disability was assessed using the Fibromyalgia Impact Questionnaire, whilst mental and physical fatigue were assessed with the sub-scales of the Chalder Fatigue Scale. Pain intensity was measured with a Numeric Pain Rating Scale, self-efficacy with the Chronic Pain Self-efficacy Questionnaire and catastrophizing with the Pain Catastrophizing Scale.

Results: Cognitive factors were significantly associated with pain (self-efficacy beliefs β=-0.30, P<0.05; catastrophizing β=0.24, P<0.05) and disability (self-efficacy beliefs β=-0.62, P<0.05), but not fatigue.

Conclusions: Similar associations were observed in patients referred to physiotherapy as to those observed in patients treated in multi-disciplinary clinical environments.

Self-efficacy beliefs appear to be particularly strong determinants of disability but exert a lesser influence over pain or fatigue. Targeting self-efficacy may be an effective method to reduce disability in patients with persistent pain and fatigue disorders.

20. Xu Y et al. (2019)
Acupuncture in the treatment of chronic fatigue syndrome based on “interaction of brain and kidney” in TCM: a randomized controlled trial.
Zhongguo Zhen Jiu 39 (2): 123-7.

Objective: To observe the effects of acupuncture on the fatigue symptoms of chronic fatigue syndrome, the potential symptoms and cytokines on the base of the theory as “interaction of brain and kidney” and explore its clinical therapeutic effects and the potential mechanism.

Methods: A total of 68 patients were randomized into an observation group and a control group, 34 cases in each one. In the control group, oryzanol and vitamin B1 were prescribed for oral administration and the patients were required to have a proper rest and physical exercise. In the observation group, on the base of the theory as “interaction of brain and kidney”, acupuncture was added to Baihui (BL 20), Fengchi (GB 20), Pishu (BL 20), Shenshu (BL 23), Sanyinjiao (SP 6) and Taixi (KI 3).

The treatment was given once a day, 5 treatments a week, with 2 days break. The consecutive treatment for 4 weeks was required. Before and after treatment, the score of the fatigue scale-14 (FS-14), the score of the somatic and psychological health report (SPHERE) and the score of the Pittsburgh sleep quality index (PSQI) were observed in the patients of the two groups separately. The enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of serum interleukin-6 (IL-6) and interferon-γ (INF-γ) before and after treatment.

Results: After treatment, FS-14 scores, SPHERE scores and PSQI scores were all reduced as compared with the scores before treatment in the two groups (P<0.05, P<0.01). After treatment, the levels of IL-6 and INF-γ in the serum in the observation group were reduced as compared with the levels before treatment (both P<0.01). After treatment, the scores of FS-14, SPHERE and PSQI as well as the levels of serum IL-6 and INF-γ in the observation group were all lower than the results in the control group (P<0.05, P<0.01).

Conclusion: On the base of the theory as “interaction of brain and kidney”, acupuncture therapy relieves the fatigue symptoms and the potential symptoms and improves the sleep quality in the patients of chronic fatigue syndrome. The effect mechanism is probably related to the decrease of the levels of IL-6 and INF-γ in serum.

21. Xu Y et al. (2019)
Clinical research of auricular gold-needle therapy in treatment of chronic fatigue syndrome of qi deficiency constitution.
Zhongguo Zhen Jiu 39 (20): 128-132.

Objective: To observe the clinical therapeutic effects of auricular gold-needle therapy on chronic fatigue syndrome of qi deficiency constitution and explore its potential mechanism.

Methods: A total of 120 patients were randomized into an auricular gold-needle therapy group, an auricular point pressure therapy group and a Chinese herb group, 40 cases in each one. Additionally, a health control group (40 cases) was set up, without any intervention.

In the auricular gold-needle therapy group, the gold needle was used to stimulate the auricular points on one side and the cowherb seed pressure therapy on the other side.

In the auricular point pressure therapy group, the cowherb seed pressure therapy was adopted only on one side.

The auricular points were shen (CO10), xin (CO15), fei (CO14), pizhixia (AT4), etc. in the two groups. The auricular points on both sides were used alternatively.

The treatment was given once a week, 4 treatments as one course and the consecutive 3 courses of treatment were required.

In the Chinese herb group, buzhong yiqi wan was prescribed for oral administration, 6 g, twice a day, the medication for 1 month was as one session and the consecutive 3 sessions of medication were required.

Before and after treatment, separately, the clinical symptom score, the levels of the serum immunoglobulins, i.e. IgA, IgG and IgM were observed in the patients of the three groups.

The therapeutic effects were evaluated in the three groups.

Results: The total effective rate was 90.0% (36/40) in the auricular gold-needle therapy group, better than 80.0% (32/40) in the auricular point pressure therapy group and 82.5% (33/40) in the Chinese herb group (both P<0.05). Before treatment, the clinical symptom scores of the patients in the three groups were obviously higher than the health control group (all P<0.001).

After treatment, the symptom scores were all reduced as compared the scores before treatment in the three groups (all P<0.001) and the symptom scores in the auricular gold-needle therapy group were better than the auricular point pressure therapy group and the Chinese herb group (both P<0.01).

Before treatment, the levels of serum IgA, IgG and IgM of the patients in the three groups were lower than the health control group (all P<0.001). The levels were all improved after treatment in the three groups (all P<0.01), and the levels in the auricular gold-needle therapy group was better than the auricular point pressure therapy group and the Chinese herb group (all P<0.05).

Conclusion: The auricular gold-needle therapy achieves the significant therapeutic effects on chronic fatigue syndrome of qi deficiency constitution and its mechanism is probably related to the regulation of immune function.

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