Characterization of Post-exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome is characterized by persistent and disabling fatigue, exercise intolerance, cognitive difficulty, and musculoskeletal/joint pain. Post-exertional malaise is a worsening of these symptoms after a physical or mental exertion and is considered a central feature of the illness. Scant observations in the available literature provide qualitative assessments of post-exertional malaise in patients with myalgic encephalomyelitis/chronic fatigue syndrome. To enhance our understanding, a series of outpatient focus groups were convened.

Methods: Nine focus groups totaling 43 patients who reported being diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome were held between November 2016 and August 2019. Focus groups queried post-exertional malaise in daily life and participants’ retrospective memory of post-exertional malaise that followed an exercise provocation with a cardiopulmonary exercise test. Data analysis followed the grounded theory method to systematically code and categorize the data to find meaningful patterns. A qualitative software package was used to move text into categories during data coding.

Results: A wide range of symptoms were attributed to exertion both in daily lives and following cardiopulmonary exercise testing. While three core symptoms emerged (exhaustion, cognitive difficulties, and neuromuscular complaints), participants’ descriptions were notable for their unique individual variations. Of 18 participants who responded to questions centered around symptoms following a cardiopulmonary exercise test, 17 reported that symptoms started within 24 h and peaked in severity within 72 h following the cardiopulmonary exercise test. Patients described post-exertional malaise as interfering with their ability to lead a “normal” life.

Conclusion: The experience of post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome varies greatly between individuals and leads to a diminished quality of life. myalgic encephalomyelitis/chronic fatigue syndrome patients describe post-exertional malaise as all-encompassing with symptoms affecting every part of the body, difficult to predict or manage, and requiring complete bedrest to fully or partially recover. Given the extensive variability in patients, further research identifying subtypes of post-exertional malaise could lead to better targeted therapeutic options.

Source: Stussman B, Williams A, Snow J, Gavin A, Scott R, Nath A, Walitt B. Characterization of Post-exertional Malaise in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurol. 2020 Sep 18;11:1025. doi: 10.3389/fneur.2020.01025. PMID: 33071931; PMCID: PMC7530890. https://www.frontiersin.org/articles/10.3389/fneur.2020.01025/full  (Full text)

Scraping on head and face combined with stepping technique of tuina along lower limbs for chronic fatigue syndrome

Abstract:

Objective: To observe the effect of scraping on head and face combined with stepping technique of tuina along lower limbs on fatigue symptom and mental state in patients with chronic fatigue syndrome.

Methods: A total of 100 patients with chronic fatigue syndrome were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 2 cases dropped off). In the control group, oryzanol tablets and compound vitamin B tablets were taken orally, both 2 tablets every time, 3 times every day for 30 days. On the basis of the treatment in the control group, scraping on head and face combined with stepping technique of tuina along lower limbs of three yin meridians of foot were applied in the observation group, once every 3 days, 10 times were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and somatic and psychological health report (SPHERE) were observed, and the clinical therapeutic effect was evaluated in the two groups.

Results: After treatment, the scores of FS-14 and SPHERE were reduced in the two groups (P<0.05), and the changes of those indexes in the observation group were larger than the control group (P<0.05). The total effective rate was 91.7% (44/48) in the observation group, which was superior to 54.2% (26/48) in the control group (P<0.05).

Conclusion: Scraping on head and face combined with stepping technique of tuina along lower limbs can improve fatigue symptom and mental state in patients with chronic fatigue syndrome.

Source: Lei LM, Wu QY, He YF. [Scraping on head and face combined with stepping technique of tuina along lower limbs for chronic fatigue syndrome]. Zhongguo Zhen Jiu. 2020 Oct 12;40(10):1057-60. Chinese. doi: 10.13703/j.0255-2930.20190801-k0006. PMID: 33068345. https://pubmed.ncbi.nlm.nih.gov/33068345/

Acupuncture of the Beishu acupoint participates in regulatory effects of ginsenoside Rg1 on T cell subsets of rats with chronic fatigue syndrome

Abstract:

Background: There are close relationships between the spleen and limb muscles and thoughts. The study aims to test the effects of ginsenoside Rg1 in combination with acupuncture of the Beishu acupoint on T cell subsets of rats with chronic fatigue syndrome (CFS).

Methods: The model was set up by combining forced cold-water swimming with chronic restraint. The rats were randomly divided into blank control, model, ginsenoside, acupuncture, and ginsenoside plus acupuncture groups (n=10). For the acupuncture group, the Beishu acupoint was acupunctured on the 2nd day after modeling. For the ginsenoside group, the ginsenoside Rg1 solution was injected into the tail vein on the 2nd day after modeling. For the combination group, both processes were conducted. These groups were compared regarding exhausted swimming time, number of struggles, resting time, serum levels of IgA, IgG, IgM, IFN-α, IFN-β, and IFN-γ, lymphocyte transformation rate, T cell subsets, and skeletal muscle activities of malondialdehyde (MDA), total antioxidative capacity (T-AOC) and acetylcholinesterase (Ache).

Results: The exhausted swimming time, number of struggles, and resting time of combination group surpassed those in the ginsenoside and acupuncture groups significantly (P<0.05). The serum levels of IgA, IgG, IgM, IFN-β, IFN-γ, T-AOC, and Ache, together with CD3+ and CD8+ T cell percentages of combination groups, were significantly higher than those of ginsenoside and acupuncture groups. However, the IFN-α level, MDA activity, and CD4+ T cell percentage were significantly lower (P<0.05). Compared with the model group, the CD4+/CD8+ T cell ratios of acupuncture, ginsenoside, and combination groups decreased significantly (P<0.05). Compared with the combination group, the ratio of the ginsenoside group increased significantly (P<0.05).

Conclusions: Both acupuncture of the Beishu acupoint and intravenous injection of ginsenoside Rg1 have anti-fatigue effects, and their combination works synergistically. This study supplies an experimental basis for joint therapy using acupuncture and drugs to combat fatigue synergistically.

Source: He J, Yu Q, Wu C, Sun Z, Wu X, Liu R, Zhang H. Acupuncture of the Beishu acupoint participates in regulatory effects of ginsenoside Rg1 on T cell subsets of rats with chronic fatigue syndrome. Ann Palliat Med. 2020 Sep;9(5):3436-3446. doi: 10.21037/apm-20-1714. PMID: 33065794. http://apm.amegroups.com/article/view/52609/html (Full text)

Reduced Heart Rate Variability in Patients with Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD

Abstract:

Objectives: Medically unexplained physical symptoms (MUPS) and related syndromes are common and place a substantial burden on both patients and society. Chronic psychological distress and dysregulation of the autonomic nervous system may be common factors associated with MUPS, although previous studies have reported mixed results. The aim of this meta-analysis is to provide an updated synthesis of studies investigating heart rate variability (HRV) indices associated with autonomic nervous system functioning in three common MUPS-syndromes and to explain inconsistencies in previous study findings.

Method: Literature search yielded 58 studies comparing HRV indices of reduced parasympathetic activity of healthy individuals to patients with chronic fatigue syndrome (Npatients = 271), irritable bowel syndrome (Npatients = 1005), and fibromyalgia (Npatients = 534). Separate random-effects meta-analyses were conducted on studies measuring root mean square of successive differences (RMSSD) and high frequency HRV (HF-HRV).

Results: Regardless of syndrome type, patients had significantly lower RMSSD (k = 22, Hedges’ g = – 0.37 [-0.53; -0.21], p < .001) and HF-HRV (k = 52, Hedges’ g = -0.69 [-1.03; -0.36], p < .001) than healthy individuals. Sample age and publication year explained substantial variation in RMSSD, whereas controlling for confounders in statistical analyses explained variation in HF-HRV.

Conclusions: Lower RMSSD and HF-HRV in patients with MUPS versus healthy controls indicates that autonomic nervous system dysregulation, particularly lower parasympathetic activity, may play a role in patients with these conditions. This conclusion may have important implications for the underlying mechanisms and treatment of MUPS and related syndromes.

Source: Vreijling SR, Troudart Y, Brosschot JF. Reduced Heart Rate Variability in Patients with Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD. Psychosom Med. 2020 Oct 14. doi: 10.1097/PSY.0000000000000874. Epub ahead of print. PMID: 33065584. https://pubmed.ncbi.nlm.nih.gov/33065584/

Oxidative stress caused by a dysregulated Wnt/β-catenin signalling pathway is involved in abnormal placenta formation in pregnant mice with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by extreme fatigue and disabling symptoms. Women with CFS often have a high risk of gynaecological problems such as irregular menstruation, endometriosis and pelvic pain and sexual dysfunction. Our previous results have shown that, in pregnant mice, CFS significantly decreased the progestational hormone level in serum, as well as learning and memory, and the function of the hypothalamus-pituitary-gonadal axis. In addition, the F1 generation also suffered from congenital hypothyroidism. At present, there has been no report about placenta formation and embryonic development in pregnant mice with CFS. The aim of the present study was to investigate the influence of CFS on the morphology, oxidative stress and Wnt/β-catenin signalling pathway during placenta formation.

In this study, we found that CFS decreased the number of implantation sites for blastocysts, and increased the number of absorbed, stillborn and malformed fetuses. The morphology and structure of the placenta were abnormal in pregnant mice with CFS. Further study found that the oxidative stress in serum, uterus and placenta was increased in pregnant mice with CFS, while the levels of antioxidase were decreased. CFS also inhibited the Wnt/β-catenin signalling pathway in the placenta. These results suggested that inhibition of the Wnt/β-catenin signalling pathway and enhanced oxidative stress play an important role in abnormal placentation in pregnant mice with CFS.

Source: Zhao H, Zhang J, Qian N, Wu S, Wu Y, Yao G. Oxidative stress caused by a dysregulated Wnt/β-catenin signalling pathway is involved in abnormal placenta formation in pregnant mice with chronic fatigue syndrome. Zygote. 2020 Oct 15:1-8. doi: 10.1017/S096719942000057X. Epub ahead of print. PMID: 33054899. https://pubmed.ncbi.nlm.nih.gov/33054899/

Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology lasting for a minimum of 6 months but usually for many years, with features including fatigue, cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Dysregulation of cytokine signaling could give rise to many of these symptoms. Cytokines are present in both plasma and extracellular vesicles, but little investigation of EVs in ME/CFS has been reported. Therefore, we aimed to characterize the content of extracellular vesicles (EVs) isolated from plasma (including circulating cytokine/chemokine profiling) from individuals with ME/CFS and healthy controls.

Methods: We included 35 ME/CFS patients and 35 controls matched for age, sex and BMI. EVs were enriched from plasma by using a polymer-based precipitation method and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and immunoblotting. A 45-plex immunoassay was used to determine cytokine levels in both plasma and isolated EVs from a subset of 19 patients and controls. Linear regression, principal component analysis and inter-cytokine correlations were analyzed.

Results: ME/CFS individuals had significantly higher levels of EVs that ranged from 30 to 130 nm in size as compared to controls, but the mean size for total extracellular vesicles did not differ between groups. The enrichment of typical EV markers CD63, CD81, TSG101 and HSP70 was confirmed by Western blot analysis and the morphology assessed by TEM showed a homogeneous population of vesicles in both groups. Comparison of cytokine concentrations in plasma and isolated EVs of cases and controls yielded no significant differences. Cytokine-cytokine correlations in plasma revealed a significant higher number of interactions in ME/CFS cases along with 13 inverse correlations that were mainly driven by the Interferon gamma-induced protein 10 (IP-10), whereas in the plasma of controls, no inverse relationships were found across any of the cytokines. Network analysis in EVs from controls showed 2.5 times more significant inter-cytokine interactions than in the ME/CFS group, and both groups presented a unique negative association.

Conclusions: Elevated levels of 30-130 nm EVs were found in plasma from ME/CFS patients and inter-cytokine correlations revealed unusual regulatory relationships among cytokines in the ME/CFS group that were different from the control group in both plasma and EVs. These disturbances in cytokine networks are further evidence of immune dysregulation in ME/CFS.

Source: Giloteaux L, O’Neal A, Castro-Marrero J, Levine SM, Hanson MR. Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study. J Transl Med. 2020 Oct 12;18(1):387. doi: 10.1186/s12967-020-02560-0. PMID: 33046133. https://pubmed.ncbi.nlm.nih.gov/33046133/

A relational analysis of an invisible illness: A meta-ethnography of people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and their support needs

Abstract:

Chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is indicated by prolonged, medically unexplained fatigue (amongst other symptoms), not alleviated by rest, and causing substantial disability. There are limited treatments on offer, which may not be effective and/or acceptable for all people, and treatment views are polarised. We, thus, aimed to take a step back from this debate, to explore more broadly preferences for formal and informal support among people with CFS/ME. We used a meta-ethnography approach to examine the substantial qualitative literature available. Using the process outlined by Noblit and Hare, and guided by patient involvement throughout, 47 studies were analysed.

Our synthesis suggested that to understand people with CFS/ME (such as their invisibility, loss of self, and fraught clinical encounters), it was useful to shift focus to a ‘relational goods’ framework. Emotions and tensions encountered in CFS/ME care and support only emerge via ‘sui generis’ real life interactions, influenced by how social networks and health consultations unfold, as well as structures like disability support. This relational paradigm reveals the hidden forces at work producing the specific problems of CFS/ME, and offers a ‘no blame’ framework going forward.

Source: Pilkington K, Ridge DT, Igwesi-Chidobe CN, Chew-Graham CA, Little P, Babatunde O, Corp N, McDermott C, Cheshire A. A relational analysis of an invisible illness: A meta-ethnography of people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and their support needs. Soc Sci Med. 2020 Sep 16;265:113369. doi: 10.1016/j.socscimed.2020.113369. Epub ahead of print. PMID: 33039734. https://pubmed.ncbi.nlm.nih.gov/33039734/

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Introduction: In a large study with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, we showed that 86% had symptoms of orthostatic intolerance in daily life and that 90% had an abnormal reduction in cerebral blood flow (CBF) during a standard tilt test. A standard head-up tilt test might not be tolerated by the most severely affected bed-ridden ME/CFS patients. Sitting upright is a milder orthostatic stress. The present study examined whether a sitting test, measuring cerebral blood flow by extracranial Doppler, would be sufficient to provoke abnormal reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: 100 severe ME/CFS patients were studied, (88 females) and were compared with 15 healthy controls (HC) (13 females). CBF was measured first while seated for at least one hour, followed by a CBF measurement in the supine position. Fibromyalgia was present in 37 patients. Demographic data as well as supine heart rate and blood pressures were not different between ME/CFS patients and HC. Heart rate and blood pressure did not change significantly between supine and sitting both in patients and HC. Supine CBF was not different between patients and HC. In contrast, absolute CBF during sitting was lower in patients compared to HC: 474 (96) mL/min in patients and 627 (89) mL/min in HC; p < 0.0001. As a result, percent CBF reduction while seated was −24.5 (9.4)% in severe ME/CFS patients and −0.4 (1.2)% in HC (p < 0.0001). In the ten patients who had no orthostatic intolerance complaints in daily life, the CBF reduction was −2.7 (2.1)%, which was not significantly different from HC (p = 0.58). The remaining 90 patients with orthostatic intolerance complaints had a −26.9 (6.2)% CBF reduction. No difference in CBF parameters was found in patients with and without fibromyalgia. Patients with a previous diagnosis of postural orthostatic tachycardia syndrome (POTS) had a significantly larger CBF reduction compared with those without POTS: 28.8 (7.2)% vs. 22.3 (9.7)% (p = 0.0008).

Conclusions: A sitting test in severe ME/CFS patients was sufficient to provoke a clinically and statistically significant mean CBF decline of 24.5%. Patients with a previous diagnosis of POTS had a larger CBF reduction while seated, compared to patients without POTS. The magnitude of these CBF reductions is similar to the results in less severely affected ME/CFS patients during head-up tilt, suggesting that a sitting test is adequate for the diagnosis of orthostatic intolerance in severely affected patients.

Source: C (Linda) MC van Campen, Peter C. Rowe, and Frans C Visser. Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Healthcare 2020, 8(4), 394; https://doi.org/10.3390/healthcare8040394 https://www.mdpi.com/2227-9032/8/4/394/htm (Full text)

Post COVID-19 syndrome associated with orthostatic cerebral hypoperfusion syndrome, small fiber neuropathy and benefit of immunotherapy: a case report

Abstract:

Coronavirus disease (COVID-19) is a novel highly contagious infectious disease caused by the coronavirus SARS-CoV2. The virus affects the human respiratory and other systems, and presents mostly as acute respiratory syndrome with fever, fatigue, dry cough, myalgia and dyspnea. The clinical manifestations vary from no symptoms to multiple organ failure. Majority of patients fully recover. Several postinfectious presumably autoimmune complications of COVID-19 affecting the brain or peripheral large nerve fibers have been reported. This report describes a post COVID-19 patient who developed chronic fatigue, orthostatic dizziness and brain fog consistent with orthostatic hypoperfusion syndrome (OCHOS), a form of orthostatic intolerance, and painful small fiber neuropathy (SFN). Initially, the patient was diagnosed with. OCHOS (detected by the tilt test with transcranial Doppler monitoring) and SFN (confirmed by skin biopsy), and both OCHOS/SFN were attributed to Post Treatment Lyme Disease Syndrome of presumed autoimmune etiology. Patient recovered on symptomatic therapy. COVID-19 triggered exacerbation of OCHOS/SFN responded to immunotherapy with intravenous immunoglobulins. This case suggests that post COVID-19 syndrome may present as an autoimmune OCHOS/SFN and that early immunotherapy may be effective. Further studies are necessary to confirm the link between OCHOS/SFN and COVID-19 disease as well as to confirm the benefit of immunotherapy.

Source: Novak P. Post COVID-19 syndrome associated with orthostatic cerebral hypoperfusion syndrome, small fiber neuropathy and benefit of immunotherapy: a case report. eNeurologicalSci. 2020 Dec;21:100276. doi: 10.1016/j.ensci.2020.100276. Epub 2020 Sep 20. PMID: 32984564; PMCID: PMC7502253. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502253/ (Full text)

EUROPEAN ME NETWORK (EUROMENE) Expert Consensus on the Diagnosis, Service Provision and Care of People with ME/CFS in Europe

Abstract:

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation is Science and Technology (COST) (https://www.cost.eu/cost-actions/what-are-cost-actions/ ) – COST action 15111 – from 2016 to 2020. The main goal of the Cost Action was to assess the existing fragmented knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report on the recommendations for clinical diagnosis, heath services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.

Source: Nacul, L.; Authier, J.; Scheibenbogen, C.; Lorusso, L.; Helland, I.; Alegre Martin, J.; Sirbu, C.A.; Mengshoel, A.M.; Polo, O.; Behrends, U.; Nielsen, H.; Grabowski, P.; Sekulic, S.; Sepulveda., N.; Esteves Lopez, F.; Zalewsk, P.; Pheby, D.; Castro-Marrero, J.; Sakkas, G.; Bergquist, J.; Capelli, E.; Brandslund, I.; Cullinan, J.; Krumina, A.; Murovska, M.; Vermuelen, R.; Lacerda, E. EUROPEAN ME NETWORK (EUROMENE) Expert Consensus on the Diagnosis, Service Provision and Care of People with ME/CFS in Europe. Preprints 2020, 2020090688.  https://www.preprints.org/manuscript/202009.0688/v1 (Full text downloadable as PDF file)