Tag: fatigue

The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker?

Abstract:

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men).

Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men.

Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.

Source: Murga I, Aranburu L, Gargiulo PA, Gómez-Esteban JC, Lafuente JV. The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker? J Transl Med. 2021 Dec 4;19(1):494. doi: 10.1186/s12967-021-03153-1. PMID: 34863209. https://pubmed.ncbi.nlm.nih.gov/34863209/

Investigating Fatigue and Exercise Intolerance in a University Immunology Clinic

Abstract:

Purpose: This manuscript reviews the experience of a University Immunology clinic with the evaluation of patients with idiopathic fatigue and exercise intolerance for the presence of metabolic disorders. Laboratory, biochemical and genetic studies were utilized in the evaluation.

Recent Findings: Of the 372 patients evaluated, 95% were found to have a treatable metabolic disorder. A defect in the glycogen storage pathway was found in 78 patients. Mitochondrial disorders were found in 258 patients. Myoadenylate deaminase deficiency was found in 7 patients. Various congenital myopathies were identified in 11 patients. Inflammatory myopathies were identified in 25 patients, 6 of whom had normal muscle enzymes on the initial evaluation.

Summary: The majority of patients (95%) referred with idiopathic fatigue and exercise intolerance after extensive evaluations were found to have underlying metabolic dysfunction. Frequently associated problems included gastrointestinal dysmotility disorders, recurrent infections, Raynaud’s, migraine headaches and various autoimmune diseases. Most patients showed symptomatic improvement with treatment of their metabolic dysfunction.

Source: Julian L A, Paul I, Molly M, John B, Lucia B. Investigating Fatigue and Exercise Intolerance in a University Immunology Clinic. Arch Rheum & Arthritis Res. 1(1): 2020. ARAR.MS.ID.000505. https://irispublishers.com/arar/fulltext/Investigating-Fatigue-and-Exercise-Intolerance-in-a-University.ID.000505.php (Full text)

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients

Abstract:

Objective: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients.

Patients and methods: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients’ response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols.

Results: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117).

Conclusions: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Source: Tirelli U, Franzini M, Valdenassi L, Pisconti S, Taibi R, Torrisi C, Pandolfi S, Chirumbolo S. Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients. Eur Rev Med Pharmacol Sci. 2021 Sep;25(18):5871-5875. doi: 10.26355/eurrev_202109_26809. PMID: 34604980. https://pubmed.ncbi.nlm.nih.gov/34604980/

Inflammation plays a causal role in fatigue-like behavior induced by pelvic irradiation in mice

Abstract:

Fatigue is a persistent and debilitating symptom following radiation therapy for prostate cancer. However, it is not well-understood how radiation targeted to a small region of the body can lead to broad changes in behavior. In this study, we used targeted pelvic irradiation of healthy male mice to test whether inflammatory signaling mediates changes in voluntary physical activity levels.

First, we tested the relationship between radiation dose, blood cell counts, and fatigue-like behavior measured as voluntary wheel-running activity. Next, we used oral minocycline treatments to reduce inflammation and found that minocycline reduces, but does not eliminate, the fatigue-like behavioral changes induced by radiation. We also used a strain of mice lacking the MyD88 adaptor protein and found that these mice also showed less fatigue-like behavior than the wild-type controls. Finally, using serum and brain tissue samples, we determined changes in inflammatory signaling induced by irradiation in wild-type, minocycline treated, and MyD88 knockout mice.

We found that irradiation increased serum levels of IL-6, a change that was partially reversed in mice treated with minocycline or lacking MyD88. Overall, our results suggest that inflammation plays a causal role in radiation-induced fatigue and that IL-6 may be an important mediator.

Source: Wolff BS, Alshawi SA, Feng LR, Juneau PL, Saligan LN. Inflammation plays a causal role in fatigue-like behavior induced by pelvic irradiation in mice. Brain Behav Immun Health. 2021 May 19;15:100264. doi: 10.1016/j.bbih.2021.100264. PMID: 34589770; PMCID: PMC8474574. https://pubmed.ncbi.nlm.nih.gov/34589770/

Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology

Abstract:

In a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band.

Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men.

Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS.

Source: Capdevila L, Castro-Marrero J, Alegre J, Ramos-Castro J, Escorihuela RM. Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology. Sensors (Basel). 2021 May 28;21(11):3746. doi: 10.3390/s21113746. PMID: 34071326. https://pubmed.ncbi.nlm.nih.gov/34071326/

A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination with a range of other disabling symptoms. There is no diagnostic test nor targeted treatment available for this illness. The pathomechanism also remains unclear. Mitochondrial dysfunctions have been considered a possible underlying pathology based on reported differences including structural and functional changes in ME/CFS patients compared to healthy controls. Due to the potential role that mitochondria may play in ME/CFS, mitochondrial-targeting nutraceutical interventions have been used to potentially assist in improving patient outcomes such as fatigue. The aim of this systematic review is to appraise literature assessing these nutraceuticals as a possible intervention for treating ME/CFS.

Methods: A systematic search of Pubmed, Embase, Medline (EBSCO host) and Web of Science (via Clarivate Analytics) for journal articles published between January 1995 and 10th November 2020 was conducted. Articles assessing nutraceutical interventions and ME/CFS patient outcomes were retrieved. Using specific inclusion and exclusion criteria, the list of articles was further refined. Quality was measured using the Rosendal scale.

Results: Nine intervention studies were included in this review. The studies investigated patient symptom severity changes such as altered fatigue levels in response to mitochondrial-targeting nutraceuticals. Improvements in fatigue levels were observed in six of the nine studies. Secondary outcomes assessed include biochemical, psychological, and quality of life parameters.

Conclusion: There is insufficient evidence on the effectiveness of mitochondria- targeting nutraceuticals in ME/CFS patients. Future well-designed studies are required to elucidate both the involvement of mitochondria in the pathomechanism of ME/CFS and the effect of mitochondrial-modifying agents on illness severity.

Source: Maksoud R, Balinas C, Holden S, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2021 Feb 17;19(1):81. doi: 10.1186/s12967-021-02742-4. PMID: 33596913; PMCID: PMC7890871. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02742-4  (Full text)

Reliability and Validity of the Modified Korean Version of the Chalder Fatigue Scale (mKCFQ11)

Abstract:

Fatigue can accompany various diseases; however, fatigue itself is a key symptom for patients with chronic fatigue syndrome (CFS). Due to the absence of biological parameters for the diagnosis and severity of CFS, the assessment tool for the degree of fatigue is very important. This study aims to verify the reliability and validity of the modified Korean version of the Chalder Fatigue Scale (mKCFQ11).

This study was performed using data from 97 participants (Male: 37, Female: 60) enrolled in a clinical trial for an intervention of CFS. The analyses of the coefficient between the mKCFQ11 score and the Fatigue Severity Scale (FSS), the Visual Analogue Scale (VAS) or the 36-item Short-Form Health Survey (SF-36) at two time points (baseline and 12 weeks) as well as their changed values were conducted. The mKCFQ11 showed strong reliability, as evidenced by the Cronbach’s alpha coefficient of 0.967 for the whole item and two subclasses (0.963 for physical and 0.958 for mental fatigue) along with the suitable validity of the mKCFQ11 structure shown by the principal component analysis. The mKCFQ11 scores also strongly correlated (higher than 0.7) with the VAS, FSS and SF-36 on all data from baseline and 12 weeks and changed values. This study demonstrated the clinical usefulness of the mKCFQ11 instrument, particularly in assessing the severity of fatigue and the evaluation of treatments for patients suffering from CFS.

Source: Ahn YC, Lee JS, Son CG. Reliability and Validity of the Modified Korean Version of the Chalder Fatigue Scale (mKCFQ11). Healthcare (Basel). 2020 Oct 24;8(4):E427. doi: 10.3390/healthcare8040427. PMID: 33114401. https://www.mdpi.com/2227-9032/8/4/427  (Full text)

Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

AIMS: 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).

CONCLUSIONS: 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.

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Source: Scherbakov N, Szklarski M, Hartwig J, Sotzny F, Lorenz S, Meyer A, Grabowski P, Doehner W, Scheibenbogen C. Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome. ESC Heart Fail. 2020 Mar 10. doi: 10.1002/ehf2.12633. [Epub ahead of print] https://onlinelibrary.wiley.com/doi/full/10.1002/ehf2.12633 (Full article)

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME.

METHODS: In this case-control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded.

RESULTS: CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls.

CONCLUSIONS: Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted.

Source: Escorihuela RM, Capdevila L, Castro JR, Zaragozà MC, Maurel S, Alegre J, Castro-Marrero J. Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2020 Jan 6;18(1):4. doi: 10.1186/s12967-019-02184-z. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943898/ (Full article)

The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) – associations with symptoms

Abstract:

BACKGROUND: Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often present with a range of flu-like symptoms resembling sickness behavior as well as widespread pain and concentration deficits. The aim of this study was to explore the association between inflammatory markers previously shown to be related to fatigue severity in ME/CFS and common ME/CFS symptoms post-exertional fatigue, impaired cognitive processing, musculoskeletal pain and recurrent flu-like symptoms, and the moderating effect of sex on these associations.

METHODS: 53 adult patients diagnosed with ME/CFS at a specialist clinic were included in the study. Fasting blood plasma was analyzed using the Olink Proseek Multiplex Inflammation panel (β-NGF, CCL11, CXCL1, CXCL10, IL-6, IL-7, IL-8, IL-10, IL-18, TGF-α, TGF-β-1 and SCF) and BioRad Human Cytokine Type 1 assay (TNF-α). Participants rated the average severity of symptoms (0-10) based on the 2011 International Consensus Criteria of ME/CFS during a structured clinical interview. Associations between inflammatory markers and symptom severity were analyzed using bivariate correlations and moderated regression analyses bootstrapped with 5000 repetitions.

RESULTS AND CONCLUSIONS: Only β-NGF was associated with the fatigue severity measure. However, higher levels of CCL11, CXCL10, IL-7, TNF-α and TGF-β-1 were significantly associated with higher levels of impaired cognitive processing and musculoskeletal pain, and sex was a significant moderator for CXCL10, IL-7 and TGF-β-1. Future studies should investigate the relationship between inflammatory markers and key symptoms in ME/CFS in a longitudinal design in order to explore if and for whom low-grade inflammation may contribute to illness development.

Copyright © 2019. Published by Elsevier Ltd.

Source: Jonsjö MA, Olsson GL, Wicksell RK, Alving K, Holmström L, Andreasson A. The role of low-grade inflammation in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) – associations with symptoms. Psychoneuroendocrinology. 2019 Dec 26;113:104578. doi: 10.1016/j.psyneuen.2019.104578. [Epub ahead of print] https://www.sciencedirect.com/science/article/pii/S0306453019313198?via%3Dihub (Full article)