2017 – Page 18 – American ME and CFS Society

Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before and after Exercise

Abstract:

Purpose. The aim of the present study was to elucidate the metabolic mechanisms associated with chronic fatigue syndrome (CFS) via an analysis of urine metabolites prior to and following exercise in a rat model.

Methods. A rat model of CFS was established using restraint-stress, forced exercise, and crowded and noisy environments over a period of 4 weeks. Behavioral experiments were conducted in order to evaluate the model. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS) in combination with multivariate statistical analysis before and after exercise.

Results. A total of 20 metabolites were detected in CFS rats before and after exercise. Three metabolic pathways (TCA cycle; alanine, aspartate, and glutamate metabolism; steroid hormone biosynthesis) were significantly impacted before and after exercise, while sphingolipid metabolism alone exhibited significant alterations after exercise only.

Conclusion. In addition to metabolic disturbances involving some energy substances, alterations in steroid hormone biosynthesis and sphingolipid metabolism were detected in CFS rats. Sphingosine and 21-hydroxypregnenolone may be key biomarkers of CFS, potentially offering evidence in support of immune dysfunction and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity in patients with CFS.

Source: Shao C, Ren Y, Wang Z, Kang C, Jiang H, Chi A. Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before and after Exercise. Biomed Res Int. 2017;2017:8182020. doi: 10.1155/2017/8182020. Epub 2017 Mar 22. https://www.hindawi.com/journals/bmri/2017/8182020/ (Full article)

Chronic fatigue syndrome and the immune system: Where are we now?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by multiple symptoms including fatigue, headaches and cognitive impairment, which have a significantly adverse effect on the normal functioning and well-being of the individual. These symptoms are often triggered or worsened following physical or mental exertion. ME/CFS has long been thought of as having a significant immunological component, but reports describing changes in immune function are often inconsistent between study groups.

Although the wide range of physical, neurocognitive and autonomic symptoms reported have seriously hampered attempts to understand pathophysiological pathways, investment in biomedical research in ME/CFS is finally increasing with a number of novel and promising investigations being published. The onset of ME/CFS may often be linked to (viral) infections which would be consistent with a variety of alterations in natural killer (NK) cell function as described by a number of different groups. Consistency in cytokine data has been lacking so far, although recently more sophisticated approaches have led to more robust data from large patient cohorts.

New hope has also been given to sufferers with the possibility that therapies that deplete B cells can result in clinical improvement. To understand the pathogenic mechanism in this complex condition, it is important to consider repeated analysis in different cohorts. In this review, we will discuss the potential of different components of the immune system to be involved in the pathogenesis of ME/CFS.

Source: Mensah FKF, Bansal AS, Ford B, Cambridge G. Chronic fatigue syndrome and the immune system: Where are we now? Neurophysiol Clin. 2017 Apr 11. pii: S0987-7053(17)30006-0. doi: 10.1016/j.neucli.2017.02.002. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28410877

Safety Survey of Intranasal Glutathione

Abstract:

Purpose: Glutathione depletion has been documented in several disease states, and exogenous administration has been hypothesized to have therapeutic potential for some conditions. In an effort to reach target tissues of the sinuses and central nervous system (CNS), glutathione is being prescribed as an intranasal spray, although no literature exists to support this mode of administration. The objective of this study was to describe patient-reported outcomes in a population of individuals who have been prescribed intranasal reduced glutathione, (in)GSH.

Methods: A survey was designed to assess individuals' perception of tolerability, adverse events, and health benefits associated with (in)GSH use. Using a pharmacy database, 300 individuals were randomly selected to receive a survey; any individual who had received one or more prescriptions for (in)GSH between March 2009 and March 2011 was eligible for participation.

Results: Seventy (70) individuals returned the survey (23.3% response rate) from 20 different states. Reported indications for (in)GSH prescriptions were multiple chemical sensitivity (MCS) (n=29), allergies/sinusitis (n=25), Parkinson disease (PD) (n=7), Lyme disease (n=3), fatigue (n=2), and other (n=10). Of the respondents, 78.8% (n=52) reported an overall positive experience with (in)GSH, 12.1% (n=8) reported having experienced adverse effects, and 62.1% (n=41) reported having experienced health benefits attributable to (in)GSH use. Over 86% of respondents considered the nasal spray to be comfortable and easy to administer.

Conclusions: This is the first study to evaluate patient-reported outcomes among individuals across the country who have been prescribed (in)GSH. The majority of survey respondents considered (in)GSH to be effective and without significant adverse effects. (in)GSH should be further evaluated as a method of treating respiratory and CNS diseases where free-radical burden is a suspected contributor to disease progression.

Source: Mischley LK, Vespignani MF, Finnell JS. Safety Survey of Intranasal Glutathione. Journal of Alternative and Complementary Medicine. 2013;19(5):459-463. doi:10.1089/acm.2011.0673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651682/ (Full article)

A content analysis of chronic fatigue syndrome and myalgic encephalomyelitis in the news from 1987 to 2013

Abstract:

Objectives The aim of this study was to analyze the content of American newspaper articles ( n=214) from 1987 to 2013, in order to understand how the public digests information related to Chronic Fatigue syndrome, a controversial and misunderstood illness.

Methods A novel codebook derived from the scientific literature was applied to 214 newspaper articles collected from Lexis Nexis Academic®. These articles were coded quantitatively and frequency tables were created to delineate the variables as they appeared in the articles.

Results The etiology was portrayed as organic in 64.5% ( n=138) of the articles, and there was no mention of case definitions or diagnostic criteria in 56.1% ( n=120) of the articles. The most common comorbidity was depression, appearing in 22.9% ( n=49) of the articles. In 55.6% ( n=119) of the articles, there was no mention of prevalence rates. In 50.9% ( n=109) of the articles, there was no mention of any form of treatment for the illness. A total of 19.4% ( n=42) of the headlines mislabeled the name of the illness.

Discussion Based on descriptive statistics of all 214 coded articles, media communicated mixed messages for salient variables such as the name of the illness, its etiology and treatment.

Source: Siegel ZA, Brown A, Devendorf A, Collier J, Leonard J. A content analysis of chronic fatigue syndrome and myalgic encephalomyelitis in the news from 1987 to 2013. Chronic Illn. 2017 Jan 1:1742395317703175. doi: 10.1177/1742395317703175. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28403636

CNS findings in chronic fatigue syndrome and a neuropathological case report

Abstract:

Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review and case report, we address central nervous system (CNS) involvement of CFS and present neuropathological autopsy findings from a patient who died with a prior diagnosis of CFS.

Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to AD plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia.

Taken together, these neuropathological findings warrant further studies into CNS disease associated with CFS.

Source: Kimberly Ferrero, Mitchell Silver, Alan Cocchetto, Eliezer Masliah, Dianne Langford. CNS findings in chronic fatigue syndrome and a neuropathological case report. Journal of Investigative Medicine. DOI: 10.1136/jim-2016-000390 Published 6 April 2017. http://jim.bmj.com/content/early/2017/04/06/jim-2016-000390

Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and debilitating disorder marked by cognitive and sensory dysfunction and unexplained physical fatigue. Classically, cases present after a prodrome consistent with infection; however, some cases are atypical and have a different presentation and comorbidities that pose challenges for differential diagnosis. We analyzed cerebrospinal fluid (CSF) from 32 cases with classical ME/CFS and 27 cases with atypical ME/CFS 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/CFS phenotype and lower CSF levels of the inflammatory mediators, interleukin 17A and CXCL9. Network analysis revealed an absence of inverse inter-cytokine relationships in CSF from atypical patients, and more sparse positive intercorrelations, than classical subjects. Interleukin 1 receptor antagonist appeared to be a negative regulator in classical ME/CFS, with patterns suggestive of disturbances in interleukin 1 signaling and autoimmunity-type patterns of immune activation.

Immune signatures in the central nervous system of ME/CFS patients with atypical features may be distinct from those with more typical clinical presentations.

Source: Hornig M, Gottschalk CG, Eddy ML, Che X, Ukaigwe JE, Peterson DL, Lipkin WI. Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations. Transl Psychiatry. 2017 Apr 4;7(4):e1080. doi: 10.1038/tp.2017.44. https://www.ncbi.nlm.nih.gov/pubmed/28375204

Scientists Discover Biological Evidence of “Atypical” Chronic Fatigue Syndrome

Press Release: NEW YORK, April 4, 2017. Scientists at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health are the first to report immune signatures differentiating two subgroups of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): “classical” and “atypical.” This complex, debilitating disease is characterized by symptoms ranging from extreme fatigue after exertion to difficulty concentrating, headaches, and muscle pain.

The study appears in the Nature Publishing Group journal, Translational Psychiatry.

Typically, symptoms of ME/CFS begin suddenly following a flu-like infection, but a subset of cases classified by the investigators as “atypical” follows a different disease course, either from triggers preceding symptoms by months or years, or accompanied by the later development of additional serious illnesses.

Continue reading “Scientists Discover Biological Evidence of “Atypical” Chronic Fatigue Syndrome” →

Characterization of a protein-bound polysaccharide from Herba Epimedii and its metabolic mechanism in chronic fatigue syndrome

Abstract:

OBJECTIVES: Herba Epimedii is one of the famous Traditional Chinese Medicines used to treat the chronic fatigue syndrome (CFS). The polysaccharides are the main active components in Herba Epimedii. The aim of this study is to discover the therapeutic effect and metabolic mechanism of Herba Epimedii polysaccharides against CFS.

METHODS: The polysaccharide conjugates named HEP2-a were isolated from the leaves of Herba Epimedii using a water extraction method, and the general physicochemical properties of HEP2-a were analysed. In addition, a CFS rat model was established, and then, urinary metabonomic studies were performed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in combination with multivariate statistical analysis.

RESULTS: The physicochemical properties revealed that HEP2-a had an average molecular weight of 13.6×104 Da and consisted of mannose (4.41%), rhamnose (5.43%), glucose (31.26%), galactose (27.07%), arabinose (23.43%), and galacturonic acid (8.40%). The amino acids in HEP2-a include glutamate, cysteine, leucine, tyrosine, lysine, and histidine. Molecular morphology studies revealed many highly curled spherical particles with diameters of 5-10µm in solids and 100-200nm for particles in water. Five metabolites in the HEP2-a group were oppositely and significantly changed compared to the CFS model group.

CONCLUSION: Two metabolic pathways were identified as significant metabolic pathways involved with HEP2-a. The therapeutic effects of HEP2-a on CFS were partially due to the restoration of these disturbed pathways.

Source: Chi A, Shen Z, Zhu W, Sun Y, Kang Y, Guo F. Characterization of a protein-bound polysaccharide from Herba Epimedii and its metabolic mechanism in chronic fatigue syndrome. J Ethnopharmacol. 2017 Mar 27. pii: S0378-8741(16)31138-2. doi: 10.1016/j.jep.2017.03.041. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28359851

Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study

Abstract:

Objective Trends in recorded diagnoses of chronic fatigue syndrome (CFS, also known as ‘myalgic encephalomyelitis’ (ME)) and fibromyalgia (FM) in the UK were last reported more than ten years ago, for the period 1990-2001. Our aim was to analyse trends in incident diagnoses of CFS/ME and FM for the period 2001-2013, and to investigate whether incidence might vary by index of multiple deprivation (IMD) score.

Design: Electronic health records cohort study.

Setting: NHS primary care practices in the UK.

Participants: Patients registered with general practices linked to the Clinical Practice Research Datalink (CPRD) primary care database from January 2001 to December 2013. Main outcome measure Incidence of CFS/ME, FM, post-viral fatigue syndrome (PVFS), and asthenia/debility.

Results: The overall annual incidence of recorded cases of CFS/ME was 14.8 (95% CI 14.5, 15.1) per 100,000 people. Overall annual incidence per 100,000 people for FM was 33.3 (32.8-33.8), for PVFS 12.2 (11.9, 12.5), and for asthenia/debility 7.0 (6.8, 7.2). Annual incidence rates for CFS/ME diagnoses decreased from 17.5 (16.1, 18.9) in 2001 to 12.6 (11.5, 13.8) in 2013 (annual percent change -2.8% (-3.6%, -2.0%)). Annual incidence rates for FM diagnoses decreased from 32.3 (30.4, 34.3) to 27.1 (25.5, 28.6) in 2007, then increased to 38.2 (36.3, 40.1) per 100,000 people in 2013. Overall annual incidence of recorded fatigue symptoms was 2246 (2242, 2250) per 100,000 people. Compared with the least deprived IMD quintile, incidence of CFS/ME in the most deprived quintile was 39% lower (incidence rate ratio (IRR) 0.61 (0.50, 0.75)), whereas rates of FM were 40% higher (IRR 1.40 (0.95, 2.06)). Conclusion: These analyses suggest a gradual decline in recorded diagnoses of CFS/ME since 2001, and an increase in diagnoses of fibromyalgia, with opposing socioeconomic patterns of lower rates of CFS/ME diagnoses in the poorest areas compared with higher rates of FM diagnoses.

Source: Collin SM, Bakken IJ, Nazareth I, Crawley E, White PD. Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study. J R Soc Med. 2017 Jan 1:141076817702530. doi: 10.1177/0141076817702530. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28358988

Studies on Cognitive Behavioral Therapy and Graded Exercise Therapy for ME/CFS are misleading

Abstract:

There have been a number of studies on Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS based on a treatment model where the disease is perpetuated by cognitive processes. Although the studies are flawed and the model lacks scientific support, the treatments are described as evidence based. The studies are non-blinded and rely on subjective outcomes. There are no objective measures of adherence. The diagnostic criteria vary, and the participating patients often have one or several psychiatric diagnoses apart from suffering from chronic fatigue. The underlying model has no theoretical foundation and is at odds with physiological findings. Surveys suggest that the efficacy of CBT is no better than placebo and that GET is harmful. Therefore, cognitive behavioral therapy and graded exercise therapy for ME/CFS are not evidence based.

Source: Sten Helmfrid. Studies on Cognitive Behavioral Therapy and Graded Exercise Therapy for ME/CFS are misleading.

This is a translation of an article published in Socialmedicinsk tidskrift, Stockholm, Sweden, on September 28 th , 2016. http://socialmedicinsktidskrift.se

Academic paper: Studies on Cognitive Behavioral Therapy and Graded Exercise Therapy for ME/CFS are misleading. Available from: https://www.researchgate.net/publication/309351210_Studies_on_Cognitive_Behavioral_Therapy_and_Graded_Exercise_Therapy_for_MECFS_are_misleading [accessed Apr 2, 2017].