Editorial

4 pages, 198 KiB

Open AccessEditorial

Special Issue “Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment”

by Lorenzo Lorusso and Giovanni Ricevuti

J. Clin. Med. 2022, 11(15), 4563; https://doi.org/10.3390/jcm11154563 - 04 Aug 2022

Cited by 2 | Viewed by 2278

Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), is a debilitating disease with unknown causes that is more common in women and tends to develop between patients’ mid-20s and mid-40s [...] Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

Research

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19 pages, 4609 KiB

Open AccessArticle

Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

by Jessica Van Oosterwijck, Uros Marusic, Inge De Wandele, Mira Meeus, Lorna Paul, Luc Lambrecht, Greta Moorkens, Lieven Danneels and Jo Nijs

J. Clin. Med. 2021, 10(19), 4527; https://doi.org/10.3390/jcm10194527 - 30 Sep 2021

Cited by 5 | Viewed by 5930

Abstract

Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of [...] Read more.

Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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14 pages, 1172 KiB

Open AccessArticle

Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping

by Jesús Castro-Marrero, Mario Zacares, Eloy Almenar-Pérez, José Alegre-Martín and Elisa Oltra

J. Clin. Med. 2021, 10(18), 4171; https://doi.org/10.3390/jcm10184171 - 15 Sep 2021

Cited by 4 | Viewed by 4931

Abstract

Background: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals’ healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions [...] Read more.

Background: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals’ healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions leading to exerting fatigue. However, studies evaluating complete and large blood datasets by combinatorial approaches to evidence ME/CFS condition or detect/identify case subgroups are still scarce. Methods: This study used unbiased hierarchical cluster analysis of a large cohort of 250 carefully phenotyped female ME/CFS cases toward exploring this possibility. Results: The results show three symptom-based clusters, classified as severe, moderate, and mild, presenting significant differences (p < 0.05) in five blood parameters. Unexpectedly the study also revealed high levels of circulating complement factor C1q in 107/250 (43%) of the participants, placing C1q as a key molecule to identify an ME/CFS subtype/subgroup with more apparent pain symptoms. Conclusions: The results obtained have important implications for the research of ME/CFS etiology and, most likely, for the implementation of future diagnosis methods and treatments of ME/CFS in the clinic. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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16 pages, 3264 KiB

Open AccessArticle

Effects of Non-Pharmacological Treatment on Pain, Flexibility, Balance and Quality of Life in Women with Fibromyalgia: A Randomised Clinical Trial

by Juan Rodríguez-Mansilla, Abel Mejías-Gil, Elisa María Garrido-Ardila, María Jiménez-Palomares, Jesús Montanero-Fernández and María Victoria González-López-Arza

J. Clin. Med. 2021, 10(17), 3826; https://doi.org/10.3390/jcm10173826 - 26 Aug 2021

Cited by 11 | Viewed by 2837

Abstract

Background: The functional deficits in people with fibromyalgia can be related to the level of physical activity performed. This study investigated the effectiveness of an active exercise programme versus exercise for well-being improving pain, flexibility, static balance, perceived exertion and quality of life [...] Read more.

Background: The functional deficits in people with fibromyalgia can be related to the level of physical activity performed. This study investigated the effectiveness of an active exercise programme versus exercise for well-being improving pain, flexibility, static balance, perceived exertion and quality of life of women with fibromyalgia; Methods: A randomised, single-blind, controlled trial was conducted. A total of 141 of women diagnosed with fibromyalgia were enrolled and randomised to an active exercise program group (n = 47), where they performed physical active exercises, an exercise for well-being group (n = 47), which performed the Qi Gong exercises named ‘the twenty Wang Ziping figures for health and longevity’, and a control group (n = 47), which did not receive any intervention, for a period of 4 weeks. Measures were taken at baseline and after the treatment. The primary outcome measures were static balance and centre of gravity (Wii-Fit Nintendo ©), flexibility (test de Wells and Dillon), pain (Visual Analogue Scale) and quality of life (Spanish-Fibromyalgia Impact Questionnaire). The secondary outcome measure was the perceived exertion during activity (BORG Scale). Results: In total, 93 participants completed the study. The mean value of the age was 52.24 ± 6.19. The post intervention results showed statistically significant improvements in the exercise for well-being and the active exercise programme groups vs. the control group in relation to pain (p = 0.006 active exercise programme group, p = 0.001 exercise for well-being group), static balance (p < 0.001 active exercise programme group) and quality of life (p < 0.001 active exercise programme group, p = 0.002 exercise for well-being group). In addition, the mean scores related to perceived fatigue during the sessions were 6.30 ± 1.88 for the active exercise programme group and 5.52 ± 1.55 for the exercise for well-being group. These differences were not significant. Conclusions: The active exercise program and exercise for well-being improved flexibility, static balance, pain and quality of life of women with fibromyalgia. The participants of the active exercise programme achieved better results that those of the exercise for well-being. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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13 pages, 994 KiB

Open AccessArticle

Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

by Helma Freitag, Marvin Szklarski, Sebastian Lorenz, Franziska Sotzny, Sandra Bauer, Aurélie Philippe, Claudia Kedor, Patricia Grabowski, Tanja Lange, Gabriela Riemekasten, Harald Heidecke and Carmen Scheibenbogen

J. Clin. Med. 2021, 10(16), 3675; https://doi.org/10.3390/jcm10163675 - 19 Aug 2021

Cited by 36 | Viewed by 12479

Abstract

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an acquired complex disease with patients suffering from the cardinal symptoms of fatigue, post-exertional malaise (PEM), cognitive impairment, pain and autonomous dysfunction. ME/CFS is triggered by an infection in the majority of patients. Initial evidence for [...] Read more.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an acquired complex disease with patients suffering from the cardinal symptoms of fatigue, post-exertional malaise (PEM), cognitive impairment, pain and autonomous dysfunction. ME/CFS is triggered by an infection in the majority of patients. Initial evidence for a potential role of natural regulatory autoantibodies (AAB) to beta-adrenergic (AdR) and muscarinic acetylcholine receptors (M-AChR) in ME/CFS patients comes from a few studies. Methods: Here, we analyzed the correlations of symptom severity with levels of AAB to vasoregulative AdR, AChR and Endothelin-1 type A and B (ETA/B) and Angiotensin II type 1 (AT1) receptor in a Berlin cohort of ME/CFS patients (n = 116) by ELISA. The severity of disease, symptoms and autonomic dysfunction were assessed by questionnaires. Results: We found levels of most AABs significantly correlated with key symptoms of fatigue and muscle pain in patients with infection-triggered onset. The severity of cognitive impairment correlated with AT1-R- and ETA-R-AAB and severity of gastrointestinal symptoms with alpha1/2-AdR-AAB. In contrast, the patients with non-infection-triggered ME/CFS showed fewer and other correlations. Conclusion: Correlations of specific AAB against G-protein-coupled receptors (GPCR) with symptoms provide evidence for a role of these AAB or respective receptor pathways in disease pathomechanism. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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17 pages, 1024 KiB

Open AccessArticle

Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study

by Elisha K. Josev, Rebecca C. Cole, Adam Scheinberg, Katherine Rowe, Lionel Lubitz and Sarah J. Knight

J. Clin. Med. 2021, 10(16), 3603; https://doi.org/10.3390/jcm10163603 - 16 Aug 2021

Cited by 5 | Viewed by 4087

Abstract

Background: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1–5 years) from diagnosis. Objectives were to (a) examine [...] Read more.

Background: The purpose of this study was to follow-up an Australian cohort of adolescents newly-diagnosed with ME/CFS at a tertiary paediatric ME/CFS clinic and healthy controls over a mean period of two years (range 1–5 years) from diagnosis. Objectives were to (a) examine changes over time in health and psychological wellbeing, (b) track ME/CFS symptomatology and fulfillment of paediatric ME/CFS diagnostic criteria over time, and (c) determine baseline predictors of ME/CFS criteria fulfilment at follow-up. Methods: 34 participants aged 13–18 years (25 ME/CFS, 23 controls) completed standardised questionnaires at diagnosis (baseline) and follow-up assessing fatigue, sleep quality and hygiene, pain, anxiety, depression, and health-related quality of life. ME/CFS symptomatology and diagnostic criteria fulfilment was also recorded. Results: ME/CFS patients showed significant improvement in most health and psychological wellbeing domains over time, compared with controls who remained relatively stable. However, fatigue, pain, and health-related quality of life remained significantly poorer amongst ME/CFS patients compared with controls at follow-up. Sixty-five percent of ME/CFS patients at baseline continued to fulfil ME/CFS diagnostic criteria at follow-up, with pain the most frequently experienced symptom. Eighty-two percent of patients at follow-up self-reported that they still had ME/CFS, with 79% of these patients fulfilling criteria. No significant baseline predictors of ME/CFS criteria fulfilment at follow-up were observed, although pain experienced at baseline was significantly associated with criteria fulfilment at follow-up (R = 0.6, p = 0.02). Conclusions: The majority of Australian adolescents with ME/CFS continue to fulfil diagnostic criteria at follow-up, with fatigue, pain, and health-related quality of life representing domains particularly relevant to perpetuation of ME/CFS symptoms in the early years following diagnosis. This has direct clinical impact for treating clinicians in providing a more realistic prognosis and highlighting the need for intervention with young people with ME/CFS at the initial diagnosis and start of treatment. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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14 pages, 5111 KiB

Open AccessArticle

Fibromyalgia Detection Based on EEG Connectivity Patterns

by Ramón Martín-Brufau, Manuel Nombela Gómez, Leyre Sanchez-Sanchez-Rojas and Cristina Nombela

J. Clin. Med. 2021, 10(15), 3277; https://doi.org/10.3390/jcm10153277 - 25 Jul 2021

Cited by 7 | Viewed by 3493

Abstract

Objective: The identification of a complementary test to confirm the diagnosis of FM. The diagnosis of fibromyalgia (FM) is based on clinical features, but there is still no consensus, so patients and clinicians might benefit from such a test. Recent findings showed that [...] Read more.

Objective: The identification of a complementary test to confirm the diagnosis of FM. The diagnosis of fibromyalgia (FM) is based on clinical features, but there is still no consensus, so patients and clinicians might benefit from such a test. Recent findings showed that pain lies in neuronal bases (pain matrices) and, in the long term, chronic pain modifies the activity and dynamics of brain structures. Our hypothesis is that patients with FM present lower levels of brain activity and therefore less connectivity than controls. Methods: We registered the resting state EEG of 23 patients with FM and compared them with 23 control subjects’ resting state recordings from the PhysioBank database. We measured frequency, amplitude, and functional connectivity, and conducted source localization (sLORETA). ROC analysis was performed on the resulting data. Results: We found significant differences in brain bioelectrical activity at rest in all analyzed bands between patients and controls, except for Delta. Subsequent source analysis provided connectivity values that depicted a distinct profile, with high discriminative capacity (between 91.3–100%) between the two groups. Conclusions: Patients with FM show a distinct neurophysiological pattern that fits with the clinical features of the disease. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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14 pages, 294 KiB

Open AccessArticle

Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

by Ingrid H. Baklund, Toril Dammen, Torbjørn Åge Moum, Wenche Kristiansen, Daysi Sosa Duarte, Jesus Castro-Marrero, Ingrid Bergliot Helland and Elin Bolle Strand

J. Clin. Med. 2021, 10(14), 3105; https://doi.org/10.3390/jcm10143105 - 14 Jul 2021

Cited by 10 | Viewed by 6982

Abstract

There is a lack of research regarding blood tests within individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and between patients and healthy controls. We aimed to compare results of routine blood tests between patients and healthy controls. Data from 149 patients diagnosed with [...] Read more.

There is a lack of research regarding blood tests within individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and between patients and healthy controls. We aimed to compare results of routine blood tests between patients and healthy controls. Data from 149 patients diagnosed with ME/CFS based on clinical and psychiatric evaluation as well as on the DePaul Symptom Questionnaire, and data from 264 healthy controls recruited from blood donors were compared. One-way ANCOVA was conducted to examine differences between ME/CFS patients and healthy controls, adjusting for age and gender. Patients had higher sedimentation rate (mean difference: 1.38, 95% CI: 0.045 to 2.714), leukocytes (mean difference: 0.59, 95% CI: 0.248 to 0.932), lymphocytes (mean difference: 0.27, 95% CI: 0.145 to 0.395), neutrophils (mean difference: 0.34, 95% CI: 0.0 89 to 0.591), monocytes (mean difference: 0.34, 95% CI: 0.309 to 0.371), ferritin (mean difference: 28.13, 95% CI: −1.41 to 57.672), vitamin B12 (mean difference: 83.43, 95% CI: 62.89 to 124.211), calcium (mean difference: 0.02, 95% CI: −0.02 to 0.06), alanine transaminase (mean difference: 3.30, 95% CI: −1.37 to -7.971), low-density lipoproteins (mean difference: 0.45, 95% CI: 0.104 to 0.796), and total proteins (mean difference: 1.53, 95% CI: −0.945 to 4.005) than control subjects. The patients had lower potassium levels (mean difference: 0.11, 95% CI: 0.056 to 0.164), creatinine (mean difference: 2.60, 95% CI: 0.126 to 5.074) and creatine kinase (CK) (mean difference: 37.57, 95% CI: −0.282 to 75.422) compared to the healthy controls. Lower CK and creatinine levels may suggest muscle damage and metabolic abnormalities in ME/CFS patients. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

17 pages, 2133 KiB

Open AccessArticle

Shadow Burden of Undiagnosed Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) on Society: Retrospective and Prospective—In Light of COVID-19

by Diana Araja, Uldis Berkis, Asja Lunga and Modra Murovska

J. Clin. Med. 2021, 10(14), 3017; https://doi.org/10.3390/jcm10143017 - 06 Jul 2021

Cited by 19 | Viewed by 5618

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, complex, multisystem disorder, with severe fatigue not alleviated by rest, and other symptoms, which lead to substantial reductions in functional activity and quality of life. Due to the unclear aetiology, treatment of patients [...] Read more.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood, complex, multisystem disorder, with severe fatigue not alleviated by rest, and other symptoms, which lead to substantial reductions in functional activity and quality of life. Due to the unclear aetiology, treatment of patients is complicated, but one of the initial problems is the insufficient diagnostic process. The increase in the number of undiagnosed ME/CFS patients became specifically relevant in the light of the COVID-19 pandemic. The aim of this research was to investigate the issues of undiagnosed potential ME/CFS patients, with a hypothetical forecast of the expansion of post-viral CFS as a consequence of COVID-19 and its burden on society. Methods: The theoretical research was founded on the estimation of classic factors presumably affecting the diagnostic scope of ME/CFS and their ascription to Latvian circumstances, as well as a literature review to assess the potential interaction between ME/CFS and COVID-19 as a new contributing agent. The empirical study design consisted of two parts: The first part was dedicated to a comparison of the self-reported data of ME/CFS patients with those of persons experiencing symptoms similar to ME/CFS, but without a diagnosis. This part envisaged the creation of an assumption of the ME/CFS shadow burden “status quo”, not addressing the impact of COVID-19. The second part aimed to investigate data from former COVID-19 patients’ surveys on the presence of ME/CFS symptoms, 6 months after being affected by COVID-19. Descriptive and analytical statistical methods were used to analyse the obtained data. Results: The received data assumed that the previously obtained data on the ME/CFS prevalence of 0.8% in the Latvian population are appropriate, and the literature review reports a prevalence of 0.2–1.0% in developed countries. Regarding the reciprocity of ME/CFS and COVID-19, the literature review showed a lack of research in this field. The empirical results show quite similar self-esteem among ME/CFS patients and undiagnosed patients with longstanding disease experience, while former COVID-19 patients show a significantly lower severity of these problems. Notably, “psychological distress (anxiety)” and “episodic fatigue” are significantly predominant symptoms reported by former COVID-19 patients in comparison with ME/CFS patients and undiagnosed patients prior to the COVID-19 pandemic. The results of our analysis predict that the total amount of direct medical costs for undiagnosed patients (out-of-pocket payments) is more than EUR 15 million p.a. (in Latvia), and this may increase by at least 15% due to the consequences of COVID-19. Conclusions: ME/CFS creates a significant shadow burden on society, even considering only the direct medical costs of undiagnosed patients—the number of whom in Latvia is probably at least five times higher than the number of discerned patients. Simultaneously, COVID-19 can induce long-lasting complications and chronic conditions, such as post-viral CFS, and increase this burden. The Latvian research data assume that ME/CFS patients are not a high-risk group for COVID-19; however, COVID-19 causes ME/CFS-relevant symptoms in patients. This increases the need for monitoring of patients for even longer after recovering from COVID-19′s symptoms, in order to prevent complications and the progression of chronic diseases. In the context of further epidemiological uncertainty, and the possibility of severe post-viral consequences, preventive measures are becoming significantly more important; an integrated diagnostic approach and appropriate treatment could reduce this burden in the future. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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13 pages, 1545 KiB

Open AccessArticle

Tolerability and Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study

by Carmen Scheibenbogen, Franziska Sotzny, Jelka Hartwig, Sandra Bauer, Helma Freitag, Kirsten Wittke, Wolfram Doehner, Nadja Scherbakov, Madlen Loebel and Patricia Grabowski

J. Clin. Med. 2021, 10(11), 2420; https://doi.org/10.3390/jcm10112420 - 29 May 2021

Cited by 5 | Viewed by 4180

Abstract

Background: Chronic fatigue syndrome (ME/CFS) is a complex disease frequently triggered by infections. IgG substitution may have therapeutic effect both by ameliorating susceptibility to infections and due to immunomodulatory effects. Methods: We conducted a proof of concept open trial with s.c. IgG in [...] Read more.

Background: Chronic fatigue syndrome (ME/CFS) is a complex disease frequently triggered by infections. IgG substitution may have therapeutic effect both by ameliorating susceptibility to infections and due to immunomodulatory effects. Methods: We conducted a proof of concept open trial with s.c. IgG in 17 ME/CFS patients suffering from recurrent infections and mild IgG or IgG subclass deficiency to assess tolerability and efficacy. Patients received s.c. IgG therapy of 0.8 g/kg/month for 12 months with an initial 2 months dose escalation phase of 0.2 g and 0.4 g/kg/month. Results: Primary outcome was improvement of fatigue assessed by Chalder Fatigue Scale (CFQ; decrease ≥ 6 points) and of physical functioning assessed by SF-36 (increase ≥ 25 points) at month 12. Of 12 patients receiving treatment per protocol 5 had a clinical response at month 12. Two additional patients had an improvement according to this definition at months 6 and 9. In four patients treatment was ceased due to adverse events and in one patient due to disease worsening. We identified LDH and soluble IL-2 receptor as potential biomarker for response. Conclusion: Our data indicate that self-administered s.c. IgG treatment is feasible and led to clinical improvement in a subset of ME/CFS patients. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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12 pages, 1297 KiB

Open AccessArticle

Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients

by Sławomir Kujawski, Joanna Słomko, Lynette Hodges, Derek F. H. Pheby, Modra Murovska, Julia L. Newton and Paweł Zalewski

J. Clin. Med. 2021, 10(11), 2327; https://doi.org/10.3390/jcm10112327 - 26 May 2021

Cited by 3 | Viewed by 4433

Abstract

Post-exertional malaise (PEM) is regarded as the hallmark symptom in chronic fatigue syndrome (CFS). The aim of the current study is to explore differences in CFS patients with and without PEM in indicators of aortic stiffness, autonomic nervous system function, and severity of [...] Read more.

Post-exertional malaise (PEM) is regarded as the hallmark symptom in chronic fatigue syndrome (CFS). The aim of the current study is to explore differences in CFS patients with and without PEM in indicators of aortic stiffness, autonomic nervous system function, and severity of fatigue. One-hundred and one patients met the Fukuda criteria. A Chronic Fatigue Questionnaire (CFQ) and Fatigue Impact Scale (FIS) were used to assess the level of mental and physical fatigue. Aortic systolic blood pressure (sBPaortic) and the autonomic nervous system were measured with the arteriograph and Task Force Monitor, respectively. Eighty-two patients suffered prolonged PEM according to the Fukuda criteria, while 19 did not. Patients with PEM had higher FIS scores (p = 0.02), lower central systolic blood pressure (p = 0.02) and higher mental fatigue (p = 0.03). For a one-point increase in the mental fatigue component of the CFQ scale, the risk of PEM increases by 34%. For an sBPaortic increase of 1 mmHg, the risk of PEM decreases by 5%. For a one unit increase in sympathovagal balance, the risk of PEM increases by 330%. Higher mental fatigue and sympathetic activity in rest are related to an increased risk of PEM, while higher central systolic blood pressure is related to a reduced risk of PEM. However, none of the between group differences were significant after FDR correction, and therefore conclusions should be treated with caution and replicated in further studies. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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18 pages, 2080 KiB

Open AccessArticle

Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients

by Sławomir Kujawski, Jo Cossington, Joanna Słomko, Monika Zawadka-Kunikowska, Małgorzata Tafil-Klawe, Jacek J. Klawe, Katarzyna Buszko, Djordje G. Jakovljevic, Mariusz Kozakiewicz, Karl J. Morten, Helen Dawes, James W. L. Strong, Modra Murovska, Jessica Van Oosterwijck, Fernando Estevez-Lopez, Julia L. Newton, Lynette Hodges, Paweł Zalewski and on behalf of the European Network on ME/CFS (EUROMENE)

J. Clin. Med. 2021, 10(7), 1542; https://doi.org/10.3390/jcm10071542 - 06 Apr 2021

Cited by 10 | Viewed by 5349

Abstract

Background: The therapeutic effects of exercise from structured activity programmes have recently been questioned; as a result, this study examines the impact of an Individualised Activity Program (IAP) on the relationship with cardiovascular, mitochondrial and fatigue parameters. Methods: Chronic fatigue syndrome (CFS) patients [...] Read more.

Background: The therapeutic effects of exercise from structured activity programmes have recently been questioned; as a result, this study examines the impact of an Individualised Activity Program (IAP) on the relationship with cardiovascular, mitochondrial and fatigue parameters. Methods: Chronic fatigue syndrome (CFS) patients were assessed using Chalder Fatigue Questionnaire (CFQ), Fatigue Severity Score (FSS) and the Fatigue Impact Scale (FIS). VO₂peak, VO₂submax and heart rate (HR) were assessed using cardiopulmonary exercise testing. Mfn1 and Mfn2 levels in plasma were assessed. A Task Force Monitor was used to assess ANS functioning in supine rest and in response to the Head-Up Tilt Test (HUTT). Results: Thirty-four patients completed 16 weeks of the IAP. The CFQ, FSS and FIS scores decreased significantly along with a significant increase in Mfn1 and Mfn2 levels (p = 0.002 and p = 0.00005, respectively). The relationships between VO₂ peak and Mfn1 increase in response to IAP (p = 0.03) and between VO₂ at anaerobic threshold and ANS response to the HUTT (p = 0.03) were noted. Conclusions: It is concluded that IAP reduces fatigue and improves functional performance along with changes in autonomic and mitochondrial function. However, caution must be applied as exercise was not well tolerated by 51% of patients. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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10 pages, 240 KiB

Open AccessArticle

MoCA vs. MMSE of Fibromyalgia Patients: The Possible Role of Dual-Task Tests in Detecting Cognitive Impairment

by Alvaro Murillo-Garcia, Juan Luis Leon-Llamas, Santos Villafaina, Paloma Rohlfs-Dominguez and Narcis Gusi

J. Clin. Med. 2021, 10(1), 125; https://doi.org/10.3390/jcm10010125 - 01 Jan 2021

Cited by 10 | Viewed by 2598

Abstract

Fibromyalgia is a syndrome that is characterized by widespread pain; fatigue; stiffness; reduced physical fitness; sleep disturbances; psychological symptoms, such as anxiety and depression; and deficits in cognitive functions, such as attention, executive function, and verbal memory deficits. It is important to analyze [...] Read more.

Fibromyalgia is a syndrome that is characterized by widespread pain; fatigue; stiffness; reduced physical fitness; sleep disturbances; psychological symptoms, such as anxiety and depression; and deficits in cognitive functions, such as attention, executive function, and verbal memory deficits. It is important to analyze the potentially different performance on the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) test in patients with fibromyalgia as well as examine the relationship of that performance with physical and cognitive performance. A total of 36 women with fibromyalgia participated in the study. Participants completed the MoCA test, the MMSE, and the TUG physical fitness test under dual-task conditions. The results obtained on cognitive tests were 28.19 (1.74) on the MMSE and 25.17 (2.79) on the MoCA. The participants’ performance on cognitive tests was significantly related to the results of the TUG dual-task test. In this way, cognitive performance on a dual-task test can be used to support the diagnosis of cognitive impairment in patients with fibromyalgia. The MoCA test may be a more sensitive cognitive screening tool than the MMSE for patients with fibromyalgia. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

Review

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17 pages, 1081 KiB

Open AccessReview

The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications

by Angelica Varesi, Undine-Sophie Deumer, Sanjana Ananth and Giovanni Ricevuti

J. Clin. Med. 2021, 10(21), 5077; https://doi.org/10.3390/jcm10215077 - 29 Oct 2021

Cited by 30 | Viewed by 7834

Abstract

The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue. Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn’s [...] Read more.

The well-known symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are chronic pain, cognitive dysfunction, post-exertional malaise and severe fatigue. Another class of symptoms commonly reported in the context of ME/CFS are gastrointestinal (GI) problems. These may occur due to comorbidities such as Crohn’s disease or irritable bowel syndrome (IBS), or as a symptom of ME/CFS itself due to an interruption of the complex interplay between the gut microbiota (GM) and the host GI tract. An altered composition and overall decrease in diversity of GM has been observed in ME/CFS cases compared to controls. In this review, we reflect on genetics, infections, and other influences that may factor into the alterations seen in the GM of ME/CFS individuals, we discuss consequences arising from these changes, and we contemplate the therapeutic potential of treating the gut to alleviate ME/CFS symptoms holistically. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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22 pages, 414 KiB

Open AccessReview

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview

by Undine-Sophie Deumer, Angelica Varesi, Valentina Floris, Gabriele Savioli, Elisa Mantovani, Paulina López-Carrasco, Gian Marco Rosati, Sakshi Prasad and Giovanni Ricevuti

J. Clin. Med. 2021, 10(20), 4786; https://doi.org/10.3390/jcm10204786 - 19 Oct 2021

Cited by 49 | Viewed by 9318

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods [...] Read more.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

7 pages, 2135 KiB

Open AccessReview

Prevalence of Chronic Fatigue Syndrome (CFS) in Korea and Japan: A Meta-Analysis

by Eun-Jin Lim and Chang-Gue Son

J. Clin. Med. 2021, 10(15), 3204; https://doi.org/10.3390/jcm10153204 - 21 Jul 2021

Cited by 15 | Viewed by 2995

Abstract

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness accompanied by fatigue unsolved by rest. However, ME/CFS is a poorly understood illness that lacks a universally accepted pathophysiology and treatment. A lack of CFS-related studies have been conducted in Asian countries. [...] Read more.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness accompanied by fatigue unsolved by rest. However, ME/CFS is a poorly understood illness that lacks a universally accepted pathophysiology and treatment. A lack of CFS-related studies have been conducted in Asian countries. This study aimed to estimate and compare the prevalence of ME/CFS in Korea and Japan and conducted a meta-analysis. Methods: We searched PubMed, EMBASE, Cochrane, and KMBASE for population-based prevalence studies of the two countries and synthesized the data according to the Fukuda case definition. Results: Of the eight studies (five in Korea, three in Japan) included, the total prevalence rate of Korean studies was 0.77% (95% CI 0.34–1.76), and 0.76% (95% CI 0.46–1.25) for the Japanese studies. The prevalence rate in females was approximately two-fold higher than males in Korean studies (1.31% female vs. 0.60% male), while the gender difference was less obvious in Japanese studies (0.76% female vs. 0.65% male). Conclusions: Further epidemiology studies on the female ME/CFS prevalence rate between countries may be required. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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13 pages, 1317 KiB

Open AccessReview

The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis

by Eun-Jin Lim, Eun-Bum Kang, Eun-Su Jang and Chang-Gue Son

J. Clin. Med. 2020, 9(12), 4040; https://doi.org/10.3390/jcm9124040 - 14 Dec 2020

Cited by 19 | Viewed by 9505

Abstract

Background: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional [...] Read more.

Background: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional impairment in ME/CFS patients. This study aimed to estimate the potential of the CPET. Methods: We reviewed studies of the two-day CPET and meta-analyzed the differences between ME/CFS patients and controls regarding four parameters: volume of oxygen consumption and level of workload at peak (VO_2peak, Workload_peak) and at ventilatory threshold (VO₂@VT, Workload@VT). Results: The overall mean values of all parameters were lower on the 2nd day of the CPET than the 1st in ME/CFS patients, while it increased in the controls. From the meta-analysis, the difference between patients and controls was highly significant at Workload@VT (overall mean: −10.8 at Test 1 vs. −33.0 at Test 2, p < 0.05), which may reflect present the functional impairment associated with PEM. Conclusions: Our results show the potential of the two-day CPET to serve as an objective assessment of PEM in ME/CFS patients. Further clinical trials are required to validate this tool compared to other fatigue-inducing disorders, including depression, using well-designed large-scale studies. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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12 pages, 844 KiB

Open AccessReview

Systematic Review of Primary Outcome Measurements for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in Randomized Controlled Trials

by Do-Young Kim, Jin-Seok Lee and Chang-Gue Son

J. Clin. Med. 2020, 9(11), 3463; https://doi.org/10.3390/jcm9113463 - 28 Oct 2020

Cited by 14 | Viewed by 3610

Abstract

Background: Due to its unknown etiology, the objective diagnosis and therapeutics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are still challenging. Generally, the patient-reported outcome (PRO) is the major strategy driving treatment response because the patient is the most important judge of whether changes [...] Read more.

Background: Due to its unknown etiology, the objective diagnosis and therapeutics of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) are still challenging. Generally, the patient-reported outcome (PRO) is the major strategy driving treatment response because the patient is the most important judge of whether changes are meaningful. Methods: In order to determine the overall characteristics of the main outcome measurement applied in clinical trials for CFS/ME, we systematically surveyed the literature using two electronic databases, PubMed and the Cochrane Library, throughout June 2020. We analyzed randomized controlled trials (RCTs) for CFS/ME focusing especially on main measurements. Results: Fifty-two RCTs out of a total 540 searched were selected according to eligibility criteria. Thirty-one RCTs (59.6%) used single primary outcome and others adapted ≥2 kinds of measurements. In total, 15 PRO-derived tools were adapted (50 RCTs; 96.2%) along with two behavioral measurements for adolescents (4 RCTs; 7.7%). The 36-item Short Form Health Survey (SF-36; 16 RCTs), Checklist Individual Strength (CIS; 14 RCTs), and Chalder Fatigue Questionnaire (CFQ; 11 RCTs) were most frequently used as the main outcomes. Since the first RCT in 1996, Clinical Global Impression (CGI) and SF-36 have been dominantly used each in the first and following decade (26.1% and 28.6%, respectively), while both CIS and Multidimensional Fatigue Inventory (MFI) have been the preferred instruments (21.4% each) in recent years (2016 to 2020). Conclusions: This review comprehensively provides the choice pattern of the assessment tools for interventions in RCTs for CFS/ME. Our data would be helpful practically in the design of clinical studies for CFS/ME-related therapeutic development. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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7 pages, 407 KiB

Open AccessBrief Report

Male vs. Female Differences in Responding to Oxygen–Ozone Autohemotherapy (O₂-O₃-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

by Salvatore Chirumbolo, Luigi Valdenassi, Marianno Franzini, Sergio Pandolfi, Giovanni Ricevuti and Umberto Tirelli

J. Clin. Med. 2022, 11(1), 173; https://doi.org/10.3390/jcm11010173 - 29 Dec 2021

Cited by 1 | Viewed by 2269

Abstract

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a syndrome that has fatigue as its major symptom. Evidence suggests that ozone is able to relieve ME/CFS-related fatigue in affected patients. (2) Objective: To evaluate whether differences exist between males and females in ozone [...] Read more.

(1) Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a syndrome that has fatigue as its major symptom. Evidence suggests that ozone is able to relieve ME/CFS-related fatigue in affected patients. (2) Objective: To evaluate whether differences exist between males and females in ozone therapy outputs in ME/CFS. (3) Methods: In total, 200 patients previously diagnosed with ME/CFS (mean age 33 ± 13 SD years) underwent treatment with oxygen–ozone autohemotherapy (O₂-O₃-AHT). Fatigue was investigated via an FSS 7-scoring questionnaire before and following 1 month after treatment. (4) Results: The Mann-Whitney test (MW test) assessed the significance of this difference (H = 13.8041, p = 0.0002), and female patients showed better outcomes than males. This difference was particularly striking in the youngest age cohort (14–29 years), and a KW test resulted in H = 7.1609, p = 0.007 for the Δ = 28.3% (males = 3.8, females = 5.3). (5) Conclusions: When treated with O₂-O₃-AHT, females respond better than males. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

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