Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids.
Germain A1, Barupal DK2, Levine SM2, Hanson MR2.
The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 female subjects, equally sampled between controls and ME/CFS patients, which delivered data for about 1750 blood compounds spanning 20 super-pathways, subdivided into 113 sub-pathways. Statistical analysis combined with pathway enrichment analysis points to a few disrupted metabolic pathways containing many unexplored compounds. The most intriguing finding concerns acyl cholines, belonging to the fatty acid metabolism sub-pathway of lipids, for which all compounds are consistently reduced in two distinct ME/CFS patient cohorts. We compiled the extremely limited knowledge about these compounds and regard them as promising in the quest to explain many of the ME/CFS symptoms. Another class of lipids with far-reaching activity on virtually all organ systems are steroids; androgenic, progestin, and corticosteroids are broadly reduced in our patient cohort. We also report on lower dipeptides and elevated sphingolipids abundance in patients compared to controls. Disturbances in the metabolism of many of these molecules can be linked to the profound organ system symptoms endured by ME/CFS patients.
ME/CFS; acyl cholines; dipeptides; lipids; metabolomics; steroids
• Original Paper Published: 23 January 2020
The Prevalence of Pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in a Community-Based Sample
Child & Youth Care Forum (2020)C
Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample.
A sample of 10,119 youth aged 5–17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations.
The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latinx than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness.
Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.
Open Access: Published: 22 January 2020
Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study
N. Eaton-Fitch, S. C. Johnston, P. Zalewski, D. Staines & S. Marshall-Gradisnik
Quality of Life Research (2020)
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS.
Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL.
Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties.
This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.
Int J Mol Sci. 2020 Feb 8;21(3). pii: E1142. doi: 10.3390/ijms21031142.
Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Missailidis D, Sanislav O, Allan CY, Annesley SJ, Fisher PR.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood mononuclear cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase Target Of Rapamycin Complex 1 (TORC1).
These differences were correlated with disease severity, as measured by the Richardson and Lidbury weighted standing test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here, we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and receiver operating characteristic (ROC) curve analysis. We found that results from three different tests-lymphocyte death rate, mitochondrial respiratory function and TORC1 activity-could each individually serve as a biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination, they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity.
This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.
Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: a quantitative, controlled study using Doppler echography
Clinical Neurophysiology Practice 8.2.20
C. (Linda) M.C.van CampenaFreek W.A.VerheugtbPeter C.RowecFrans C.Vissera
https://doi.org/10.1016/j.cnp.2020.01.003Get rights and content
Extracranial Doppler technique to measure cerebral blood flow is feasible during head-up tilt testing.
Cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients is reduced during head-up tilt testing compared to healthy volunteers.
Using a lower limit of normal of the cerebral blood flow reduction during head-up tilt testing of 13%, 90 percent of ME/CFS patients showed an abnormal cerebral blood flow reduction.
Reduction in cerebral blood flow is correlated with symptoms of orthostatic intolerance.
Abstract: The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.
Methods: 429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we administered a verbal questionnaire to ascertain for 15 OI symptoms.
Results: End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P<.0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI symptoms with the degree of CBF reduction at mid-tilt (P<.0005).
Conclusions: During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.
Significance: This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.
Post-exertional malaise is associated with greater symptom burden and psychological distress in patients diagnosed with Chronic Fatigue Syndrome
Journal of Psychosomatic Research Volume 129, February 2020, 109893
MarcellaMayaSara F.MilradbDolores M.PerdomoaSara J.CzajacMary AnnFletcherdDevika R.JutagireDaniel L.HallfNancyKlimasdMichael H.Antonia
https://doi.org/10.1016/j.jpsychores.2019.109893Get rights and content
Patients high in PEM endorse greater symptom burden than those low in PEM.
Patients high in PEM endorse greater psychological adversity than those low in PEM.
Results suggest the Fukuda case definition does not define a heterogeneous group.
PEM may identify patients who would most benefit from psychological intervention.
Post-exertional malaise (PEM) is often considered a cardinal symptom of Chronic Fatigue Syndrome (CFS). There is no gold standard diagnostic method for CFS, however, and the Centers for Disease Control (CDC) Fukuda case definition does not require PEM. Research has identified differences in symptom burden between patients according to PEM, but whether it is associated with psychological distress has not been investigated.
Methods The CDC CFS Inventory, Fatigue Symptom Inventory, Profile of Mood States, Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and subscales of the Sickness Impact Profile were administered to 261 patients diagnosed with the Fukuda criteria. PEM status (loPEM/hiPEM) was determined via self-reported post-exertional fatigue severity. Analyses of covariance (ANCOVA), controlling for age and gender, assessed cross-sectional group differences, and cross-sectional linear regressions using the continuous PEM severity predictor paralleled these analyses.
Results hiPEM patients reported greater symptom intensity, frequency, and interference than loPEM counterparts (p's < .001). hiPEM patients also reported greater social disruption, depressive symptoms, and mood disturbance (p's ≤ .011). Groups did not differ in recent negative life experiences, perceived stress, or demographic variables. The results of regression analyses mirrored those of ANCOVAs.
Conclusion This study replicates the association between PEM and symptom burden and additionally associates PEM with psychological distress; psychological distress could, however, be a consequence of symptom burden. Differences between hiPEM and loPEM CFS patients highlight the heterogeneity of diagnoses resulting from the Fukuda criteria. It is also possible that PEM identifies particularly distressed patients for whom psychological intervention would be most beneficial.
Maximal handgrip strength can predict maximal physical performance in patients with chronic fatigue.
Jammes Y1, Stavris C2, Charpin C2, Rebaudet S2, Lagrange G2, Retornaz F3.
Clin Biomech (Bristol, Avon). 2020 Jan 9;73:162-165. doi: 10.1016/j.clinbiomech.2020.01.003
Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue.
Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances.
No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue.
We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Olli Polo,Pia Pesonen &Essi Tuominen
Pages 207-217 | Received 13 Sep 2019, Accepted 11 Nov 2019, Published online: 19 Nov 2019
Background: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a common medical condition that limits physical and cognitive functions, with no known effective medical treatment.
Methods: We report on the safety and effectiveness data accumulated in clinical practice when treating ME/CFS with low-dose naltrexone (LDN, 3.0 – 4.5 mg/day). The medical records from 218 patients who received ar diagnosis of ME/CFS and LDN treatment during 2010–2014 were retrospectively analyzed.
Results: Outcome data were available in 92.2% of patients with an average follow-up time of 1.7 years. A positive treatment response to LDN was reported by 73.9% of the patients. Most patients experienced improved vigilance/alertness and improved physical and cognitive performance. Some patients reported less pain and fever, while 18.3% of patients did not report any treatment response to LDN. Mild adverse effects (insomnia, nausea) were common at the beginning of the treatment. Neither severe adverse effects nor long-term adverse symptoms were reported.
Conclusions: The high frequency of treatment response and good safety profile observed in this retrospective open label study could prompt prospective controlled studies to confirm the feasibility of LDN in alleviating ME/CFS symptoms.
KEYWORDS: Chronic fatigue syndrome, myalgic encephalomyelitis, naltrexone, therapy, pharmacology
BMJ Case Reports
Vol 13 Issue 1.
Low-dose naltrexone as a treatment for chronic fatigue syndrome
Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterised by chronic profound fatigue, postexertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12 mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Int J Mol Sci 2020 Feb 6;21(3). pii: E1074. doi: 10.3390/ijms21031074.
An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients.
Missailidis D1, Annesley SJ1, Allan CY1, Sanislav O1, Lidbury BA2, Lewis DP, Fisher PR1.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or "PEM"), and by fatigue whose severity and associated requirement for rest are excessive and disproportionate to the fatigue-inducing activity. There is no definitive molecular marker or known underlying pathological mechanism for the condition. Increasing evidence for aberrant energy metabolism suggests a role for mitochondrial dysfunction in ME/CFS. Our objective was therefore to measure mitochondrial function and cellular stress sensing in actively metabolizing patient blood cells. We immortalized lymphoblasts isolated from 51 ME/CFS patients diagnosed according to the Canadian Consensus Criteria and an age- and gender-matched control group. Parameters of mitochondrial function and energy stress sensing were assessed by Seahorse extracellular flux analysis, proteomics, and an array of additional biochemical assays. As a proportion of the basal oxygen consumption rate (OCR), the rate of ATP synthesis by Complex V was significantly reduced in ME/CFS lymphoblasts, while significant elevations were observed in Complex I OCR, maximum OCR, spare respiratory capacity, nonmitochondrial OCR and "proton leak" as a proportion of the basal OCR. This was accompanied by a reduction of mitochondrial membrane potential, chronically hyperactivated TOR Complex I stress signaling and upregulated expression of mitochondrial respiratory complexes, fatty acid transporters, and enzymes of the β-oxidation and TCA cycles. By contrast, mitochondrial mass and genome copy number, as well as glycolytic rates and steady state ATP levels were unchanged. Our results suggest a model in which ME/CFS lymphoblasts have a Complex V defect accompanied by compensatory upregulation of their respiratory capacity that includes the mitochondrial respiratory complexes, membrane transporters and enzymes involved in fatty acid β-oxidation. This homeostatically returns ATP synthesis and steady state levels to "normal" in the resting cells, but may leave them unable to adequately respond to acute increases in energy demand as the relevant homeostatic pathways are already activated.
Complex V; TORC1; chronic fatigue syndrome; mitochondria; myalgic encephalomyelitis; seahorse respirometry
February 2020, 100028
Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation Brain, Behaviour and Immunity – Vol 2
Martin A.JonsjöabcJennyÅströmcdMichael Jonese BiankaKarshikoffd KarinLodindf LindaHolmströmcg LarsAgréusfRikard K.WickselldJohnAxelssonad MatsLekanderad Gunnar L.Olssonb MikeKemaniac AnnaAndreassonaeh
https://doi.org/10.1016/j.bbih.2019.100028Get rights and content
Investigation of the level of subjective sickness behavior, assessed with a validated questionnaire, in patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and in patients with chronic pain compared to clinical, non-clinical and experimental groups.
The level of sickness behavior is similarly high in ME/CFS and chronic pain, and equal to the level in experimentally induced inflammation via injection of bacterial endotoxin.
Higher levels of sickness behavior showed significant associations with lower levels of self-rated health and functioning.
Chronic sickness behavior is implicated in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain but the level of subjective sickness behavior in these conditions has not been investigated or compared to other clinical and non-clinical samples, or to the level in experimental inflammation. Furthermore, the relationship between sickness behavior and self-rated health and functioning is not known in patients with ME/CFS and chronic pain. The aim of the present study was to investigate how sickness behavior in patients with chronic conditions differs from that in individuals with experimental acute sickness, primary care patients, the general population and healthy subjects. In addition, we wanted to explore how sickness behavior is related to self-rated health and health-related functioning.
Sickness behavior was quantified using the sickness questionnaire (SicknessQ). Self-ratings were collected at one time-point in 6 different samples. Levels of sickness behavior in patients with ME/CFS (n = 38) and patients with chronic pain (n = 190) were compared to healthy subjects with lipopolysaccharide(LPS)-induced inflammation (n = 29), primary care patients (n = 163), individuals from the general population (n = 155) and healthy subjects (n = 48), using linear regression. Correlations and moderated regression analyses were used to investigate associations between sickness behavior and self-rated health and health-related functioning in ME/CFS, chronic pain and the general population.
LPS-injected individuals (M = 16.3), patients with ME/CFS (M = 16.1), chronic pain (M = 16.1) and primary care patients (M = 10.7) reported significantly higher SicknessQ scores than individuals from the general population (M = 5.4) and healthy subjects (M = 3.6) all p’s < 0.001). In turn, LPS-injected individuals, patients with ME/CFS and chronic pain reported significantly higher SicknessQ scores than primary care patients (p’s < 0.01). Higher levels of sickness behavior were associated with poorer self-rated health and health-related functioning (p’s < 0.01), but less so in patients with ME/CFS and chronic pain than in individuals from the general population.
Patients with ME/CFS and chronic pain report similar high levels of sickness behavior; higher than primary care patients, and comparable to levels in experimental inflammation. Further study of sickness behavior in ME/CFS and chronic pain populations is warranted as immune-to-brain interactions and sickness behavior may be of importance for functioning as well as in core pathophysiological processes in subsets of patients.
Front. Immunol., 21 November 2019 | https://doi.org/10.3389/fimmu.2019.02684
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a Hyper-Regulated Immune System Driven by an Interplay Between Regulatory T Cells and Chronic Human Herpesvirus Infections
Nuno Sepúlveda1,2*, Jorge Carneiro3, Eliana Lacerda4 and Luis Nacul4
- 1Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
Oxidative medicine and cellular longevity
Volume 2019 |Article ID 1684198 | 10 pages | https://doi.org/10.1155/2019/1684198
Modification of Immunological Parameters, Oxidative Stress Markers, Mood Symptoms, and Well-Being Status in CFS Patients after Probiotic Intake: Observations from a Pilot Study
Letizia Venturini,1 Sara Bacchi,2 Enrica Capelli,2 Lorenzo Lorusso,3 Giovanni Ricevuti,1 and Chiara Cusa1
Academic Editor: Maria Luca
The present study discusses about the effects of a combination of probiotics able to stimulate the immune system of patients affected by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To this purpose, patients diagnosed according to Fukuda’s criteria and treated with probiotics were analyzed by means of clinical and laboratory evaluations, before and after probiotic administrations. Probiotics were selected considering the possible pathogenic mechanisms of ME/CFS syndrome, which has been associated with an impaired immune response, dysregulation of Th1/Th2 ratio, and high oxidative stress with exhaustion of antioxidant reserve due to severe mitochondrial dysfunction. Immune and oxidative dysfunction could be related with the gastrointestinal (GI) chronic low-grade inflammation in the lamina propria and intestinal mucosal surface associated with dysbiosis, leaky gut, bacterial translocation, and immune and oxidative dysfunction. Literature data demonstrate that bacterial species are able to modulate the functions of the immune and oxidative systems and that the administration of some probiotics can improve mucosal barrier function, modulating the release of proinflammatory cytokines, in CFS/ME patients. This study represents a preliminary investigation to verifying the safety and efficacy of a certain combination of probiotics in CFS/ME patients. The results suggest that probiotics can modify the well-being status as well as inflammatory and oxidative indexes in CFS/ME patients. No adverse effects were observed except for one patient, which displayed a flare-up of symptoms, although all inflammatory parameters (i.e., cytokines, fecal calprotectin, ESR, and immunoglobulins) were reduced after probiotic intake. The reactivation of fatigue symptoms in this patient,
whose clinical history reported the onset of CFS/ME following mononucleosis, could be related to an abnormal stimulation of the immune system as suggested by a recent study describing an exaggerated immune activation associated with chronic fatigue.
Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome
Nadja Scherbakov Marvin Szklarski Jelka Hartwig Sebastian Lorenz Patricia Grabowski Wolfram Doehner Carmen Scheibenbogen
First published:10 March 2020 https://doi.org/10.1002/ehf2.12633 ESC Heart Failure
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from various studies showing cerebral hypoperfusion and orthostatic intolerance. The peripheral endothelial dysfunction (ED) has not been sufficiently investigated in patients with ME/CFS. The aim of the present study was to examine peripheral endothelial function in patients with ME/CFS.
Methods and results
Thirty‐five patients [median age 40 (range 18–70) years, mean body mass index 23.8 ± 4.2 kg/m2, 31% male] with ME/CFS were studied for peripheral endothelial function assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of ME/CFS was based on Canadian Criteria. Nine of these patients with elevated antibodies against β2‐adrenergic receptor underwent immunoadsorption, and endothelial function was measured at baseline and 3, 6, and 12 months follow‐up. ED was defined by reactive hyperaemia index ≤1.81. Twenty healthy subjects of similar age and body mass index were used as a control group. Peripheral ED was found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P < 0.05). Patients with ED, in contrast to patients with normal endothelial function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ± 16, P = 0.04), as well as more severe fatigue‐related symptoms (8.62 ± 0.87 vs. 7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile range 7.0–10.0) vs. 7.5 (interquartile range 6.0–9.25), P = 0.04]. Peripheral ED showed correlations with more severe immune‐associated symptoms (r = −0.41, P = 0.026), such as sore throat (r = −0.38, P = 0.038) and painful lymph nodes (r = −0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = −0.59, P = 0.005). There were no differences between the patient group with ED and the patient group with normal endothelial function regarding demographic, metabolic, and laboratory parameters. Further, there was no difference in soluble vascular cell adhesion molecule and soluble intercellular adhesion molecule levels. At baseline, peripheral ED was observed in six patients who underwent immunoadsorption. After 12 months, endothelial function had improved in five of these six patients (reactive hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06).
Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.
Stemming the Rising Tide of Human-Biting Ticks and Tickborne Diseases, United States
Lars Eisen Emerging Infectious Diseases. 2020;26(4):641-647.
Ticks and tickborne diseases are increasingly problematic. There have been positive developments that should result in improved strategies and better tools to suppress ticks, reduce human tick bites, and roll back tickborne diseases. However, we equally need to address the question of who is responsible for implementing the solutions. The current model of individual responsibility for tick control evolved from a scenario in the 1990s focusing strongly on exposure to blacklegged ticks and Lyme disease spirochetes in peridomestic settings of the northeastern United States. Today, the threat posed by human-biting ticks is more widespread across the eastern United States, increasingly complex (multiple tick species and >10 notable tickborne pathogens), and, across tick species, more spatially diffuse (including backyards, neighborhood green spaces, and public recreation areas). To mitigate tick-associated negative societal effects, we must consider shifting the responsibility for tick control to include both individual persons and professionally staffed tick-management programs.
Benefits of adding stretching to a moderate-intensity aerobic exercise programme in women with fibromyalgia: a randomized controlled trial
Miguel Gómez-Hernández, Tomás Gallego-Izquierdo, Patricia Martínez-Merinero, ..
First Published December 18, 2019 Research Article Find in PubMed
Objective: To investigate the effects of adding stretching to a moderate-intensity aerobic exercise programme in women with fibromyalgia.
Design: Randomized controlled trial.
Subjects: Sixty-four female patients who were diagnosed with fibromyalgia syndrome based on the American College of Rheumatology criteria were recruited (mean age: 54.27 ± 6.94 years).
Interventions: The control group (n = 32) underwent supervised moderate-intensity cycling (50%–70% of the age-predicted maximum heart rate) three times per week for 12 weeks. The experimental group (n = 32) underwent the same exercise programme plus a stretching programme once per week for 12 weeks.
Main measures:The main measures of this study were sleep quality assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, the impact of fibromyalgia on quality of life assessed by the Fibromyalgia Impact Questionnaire, and pain perception assessed by the visual analogue scale at baseline, after 4 weeks, and after 12 weeks.
Results: The experimental group experienced significant improvements at 4-week measure compared with control group: Pittsburgh Sleep Quality Index (P < 0.001); Epworth Sleepiness Scale (P = 0.002); Fibromyalgia Impact Questionnaire (0.93 ± 7.39, P < 0.001); and visual analogue scale (0.52 ± 0.05, P < 0.001). Also at 12-week measure, experimental group experienced significant improvements compared with control group: Pittsburgh Sleep Quality Index (P < 0.001), Epworth Sleepiness Scale (P < 0.001); Fibromyalgia Impact Questionnaire (1.15 ± 9.11, P < 0.001); and visual analogue scale (0.81 ± 0.62, P < 0.001).
Adding stretching to a moderate-intensity aerobic exercise programme increased sleep quality, decreased the impact of fibromyalgia on the quality of life, and reduced pain compared with just a moderate-intensity aerobic exercise programme in our sample of women with fibromyalgia.
Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Asgeir Lande, Øystein Fluge, Elin B. Strand, Siri T. Flåm, Daysi D. Sosa,
Olav Mella, Torstein Egeland, Ola D. Saugstad, Benedicte A. Lie & Marte K. Viken
Scientific Reports volume 10, Article number: 5267 (2020)
The etiology and pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are unknown, and autoimmunity is one of many proposed underlying mechanisms. Human Leukocyte Antigen (HLA) associations are hallmarks of autoimmune disease, and have not been thoroughly investigated in a large ME/CFS patient cohort. We performed high resolution HLA -A, -B, -C, -DRB1, -DQB1 and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian ME/CFS patients, diagnosed according to the Canadian Consensus Criteria. HLA associations were assessed by comparing to 4511 healthy and ethnically matched controls. Clinical information was collected through questionnaires completed by patients or relatives. We discovered two independent HLA associations, tagged by the alleles HLA-C*07:04 (OR 2.1 [95% CI 1.4–3.1]) and HLA-DQB1*03:03 (OR 1.5 [95% CI 1.1–2.0]). These alleles were carried by 7.7% and 12.7% of ME/CFS patients, respectively. The proportion of individuals carrying one or both of these alleles was 19.2% in the patient group and 12.2% in the control group (OR 1.7 [95% CI 1.3–2.2], pnc = 0.00003). ME/CFS is a complex disease, potentially with a substantial heterogeneity. We report novel HLA associations pointing toward the involvement of the immune system in ME/CFS pathogenesis.
HERV-K and HERV-W transcriptional activity in myalgic encephalomyelitis/chronic fatigue syndrome
Lucas S. Rodrigues, Luiz H. da Silva Nali, Cibele O. D. Leal, Ester C. Sabino, Eliana M. Lacerda, Caroline C. Kingdon, Luis Nacul & Camila M. Romano
Autoimmunity Highlights volume 10, Article number: 12 (2019)
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases.
Here the expression of Endogenous retroviruses K and W (HERV-K and HERV-W) was determined in blood from moderately and severely affected ME/CFS patients through real time PCR.
HERV-K was overexpressed only in moderately affected individuals but HERV-W showed no difference.
This is the first report about HERV-K differential expression in moderate ME/CFS. Although the relationship between HERVs and ME/CFS has yet to be proven, the observation of this phenomenon deserves further attention.
A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors
https://doi.org/10.1016/j.autrev.2020.102527Get rights and content
Autoimmunity reviews: Available online 1 April 2020, 102527
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (CFS/ME) is a complex and severely disabling disease with a prevalence of 0.3% and no approved treatment and therefore a very high medical need. Following an infectious onset patients suffer from severe central and muscle fatigue, chronic pain, cognitive impairment, and immune and autonomic dysfunction. Although the etiology of CFS/ME is not solved yet, there is numerous evidence for an autoantibody mediated dysregulation of the immune and autonomic nervous system.
We found elevated ß2 adrenergic receptor (ß2AdR) and M3 acetylcholine receptor antibodies in a subset of CFS/ME patients. As both ß2AdR and M3 acetylcholine receptor are important vasodilators, we would expect their functional disturbance to result in vasoconstriction and hypoxemia. An impaired circulation and oxygen supply could result in many symptoms of ME/CFS. There are consistent reports of vascular dysfunction in ME/CFS. Muscular and cerebral hypoperfusion has been shown in ME/CFS in various studies and correlated with fatigue. Metabolic changes in ME/CFS are also in line with a concept of hypoxia and ischemia.
Here we try to develop a unifying working concept for the complex pathomechanism of ME/CFS based on the presence of dysfunctional autoantibodies against ß2AdR and M3 acetylcholine receptor and extrapolate it to the pathophysiology of ME/CFS without an autoimmune pathogenesis.
MCP-1 is increased in patients with CFS and FM, whilst several other immune markers are significantly lower than healthy controls
NinaGrovenabEgil AndreasForscAstrid KamillaStunesdeSolveig KlæboReitanab
Brain, Behaviour and Immunity Volume 4, April 2020, 100067
https://doi.org/10.1016/j.bbih.2020.100067Get rights and content
MCP-1 is significantly increased in CFS and Fibromyalgia compared to controls.
CFS and Fibromyalgia share common features of inflammation
Decreased IL-1β, IL-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3, IL-10 and IL-17A are found in both CFS and Fibromyalgia.
The role of the immune system in the pathogenesis of Fibromyalgia (FM) and Chronic fatigue syndrome (CFS) is not clear. We have previously reported increased levels of C-reactive protein (CRP) in these patient groups compared to healthy controls and wanted to further explore the levels of circulating immune markers in these populations.
The population consisted of three groups, 58 patients with FM, 49 with CFS and 54 healthy controls. All participants were females aged 18–60. Patients were recruited from a specialised university hospital clinic and controls were recruited by advertisement among the staff and students at the hospital and university. Plasma levels of Interferon (IFN)-γ, Interleukin (IL)-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-17, Interferon gamma-induced protein (IP)-10, Monocyte Chemoattractant Protein (MCP)-1, Transforming Growth Factor (TGF)-β1, TGF-β2, TGF-β3 and Tumour Necrosis Factor (TNF)-α were analysed by multiplex. Differences between the three groups CFS, FM and controls, were analysed by Kruskal Wallis tests.
MCP-1 was significantly increased in both patient groups compared to healthy controls. IL-1β, Il-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3, IL-10 and IL17 all were significantly lower in the patient groups than healthy controls. IFN-γ was significantly lower in the FM group. For IL-8, IL-10 and IL-1ra there were no significant difference when controlled for multiple testing.
In conclusion, in our material MCP-1 seems to be increased in patients both with CFS and with FM, while several other immune markers are significantly lower in patients than controls.