Tag: chronic fatigue syndrome vs fibromyalgia

Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are devastating metabolic neuroimmune diseases that are difficult to diagnose because of the presence of numerous symptoms and a lack of specific biomarkers. Despite patient heterogeneity linked to patient subgroups and variation in disease severity, anomalies are found in the blood and plasma of these patients when compared with healthy control groups. The seeming specificity of these “plasma factors”, as recently reported by Ron Davis and his group at Stanford University, CA, United States, and observations by our group, have led to the proposal that induced pluripotent stem cells (iPSCs) may be used as metabolic sensors for FM and ME/CFS, a hypothesis that is the basis for this in-depth review.

Aim: To identify metabolic signatures in FM and/or ME/CFS supporting the existence of disease-associated plasma factors to be sensed by iPSCs.

Methods: A PRISMA (Preferred Reported Items for Systematic Reviews and Meta-analysis)-based systematic review of the literature was used to select original studies evaluating the metabolite profiles of FM and ME/CFS body fluids. The MeSH terms “metabolomic” or “metabolites” in combination with FM and ME/CFS disease terms were screened against the PubMed database. Only original studies applying omics technologies, published in English, were included. The data obtained were tabulated according to the disease and type of body fluid analyzed. Coincidences across studies were searched and P-values reported by the original studies were gathered to document significant differences found in the disease groups.

Results: Eighteen previous studies show that some metabolites are commonly altered in ME/CFS and FM body fluids. In vitro cell-based assays have the potential to be developed as screening platforms, providing evidence for the existence of factors in patient body fluids capable of altering morphology, differentiation state and/or growth patterns. Moreover, they can be further developed using approaches aimed at blocking or reversing the effects of specific plasma/serum factors seen in patients. The documented high sensitivity and effective responses of iPSCs to environmental cues suggests that these pluripotent cells could form robust, reproducible reporter systems of metabolic diseases, including ME/CFS and FM. Furthermore, culturing iPSCs, or their mesenchymal stem cell counterparts, in patient-conditioned medium may provide valuable information to predict individual outcomes to stem-cell therapy in the context of precision medicine studies.

Conclusion: This opinion review explains our hypothesis that iPSCs could be developed as a screening platform to provide evidence of a metabolic imbalance in FM and ME/CFS.

Source: Monzón-Nomdedeu MB, Morten KJ, Oltra E. Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. World J Stem Cells. 2021 Aug 26;13(8):1134-1150. doi: 10.4252/wjsc.v13.i8.1134. PMID: 34567431; PMCID: PMC8422931. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422931/ (Full article)

Kynurenine metabolites and ratios differ between Chronic Fatigue Syndrome, Fibromyalgia, and healthy controls

Abstract:

Background: There is growing evidence that the kynurenine pathway is involved in the pathology of diseases related to the central nervous system (CNS), because of the neuroprotective or neurotoxic properties of certain metabolites, yet the role of each metabolite is not clear. The pathology of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) is currently under investigation, and the overlapping symptoms such as depression suggest that the CNS may be involved. These symptoms may be driven by enhanced neurotoxicity and/or diminished neuroprotection. However, the kynurenine metabolite status has not been well studied in these two possible related disorders of CFS and FM. The objective of this study was to investigate the metabolites and ratios of the kynurenine pathway in CFS and FM compared to healthy controls and examine the possible correlations with symptoms of anxiety and depression.

Method: In this study, females aged 18-60 were included: 49 CFS patients; 57 FM patients; and 54 healthy controls. Blood plasma was analysed for the following metabolites involved in the kynurenine pathway: Tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykykynurenine (HK), anthranilic acid, xanthurenic acid (XA), 3-hydroxyanthranilic acid, quinolinic acid (QA) and picolinic acid. The concentrations of these metabolites, as well as the ratios of different metabolites indicating enzymatic activity, were compared between the groups. Findings were controlled for age, body mass index (BMI), and symptoms of anxiety and depression.

Results: QA differed between CFS and FM patients (β = .144, p = .036) and was related to higher levels of BMI (β = .017, p = .002). The neuroprotective ratio given by KA/QA was lower for CFS patients compared to healthy controls (β = -.211, p = .016). The neuroprotective ratio given by KA/HK was lower for FM patients compared to healthy controls, and this lower neuroprotective ratio was associated with increased symptoms of pain. The kynurenine aminotransferase II (KAT II) enzymatic activity given by XA/HK was lower for FM patients compared to healthy controls (β = -.236, p = .013). In addition, BMI was negatively associated with enhanced KAT II enzymatic activity (β = -.015, p = .039). Symptoms of anxiety and depression were not associated with the metabolites or ratios studied.

Conclusion: Our study indicates associations between kynurenine metabolism and CFS and FM as well as characteristic symptoms like fatigue and pain. Forthcoming studies indicating a causative effect may place kynurenine metabolites as a target for treatment as well as prevention of these conditions in the future.

Source: Groven N, Reitan SK, Fors EA, Guzey IC. Kynurenine metabolites and ratios differ between Chronic Fatigue Syndrome, Fibromyalgia, and healthy controls. Psychoneuroendocrinology. 2021 May 27;131:105287. doi: 10.1016/j.psyneuen.2021.105287. Epub ahead of print. PMID: 34090138. https://pubmed.ncbi.nlm.nih.gov/34090138/

Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load

Abstract:

Objective: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are disorders of unknown etiology and unclear pathophysiology, with overlapping symptoms of – especially muscular -fatigue and pain. Studies have shown increased muscle fiber conduction velocity (CV) in the non-painful muscles of FM patients. We investigated whether CFS patients also show CV abnormalities.

Methods: Females with CFS (n = 25), with FM (n = 22), and healthy controls (n = 21) underwent surface electromyography of the biceps brachii, loaded up to 20% of maximum strength, during short static contractions. The mean CV and motor unit potential (MUP) velocities with their statistical distribution were measured.

Results: The CV changes with force differed between CFS-group and both FM-group and controls (P = 0.01). The CV of the CFS-group increased excessively with force (P < 0.001), whereas that of the controls increased only slightly and non-significantly, and that of the FM-group did not increase at all. In the CFS-group, the number of MUPs conveying very high conduction velocities increased abundantly with force and the MUPs narrowed.

Conclusion: Our results suggest disturbed muscle membrane function in CFS patients, in their motor units involved in low force generation. Central neural deregulation may contribute to this disturbance.

Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship

Abstract:

Introduction: Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and fibromyalgia (FM) are both debilitating syndromes with complex polysymptomatology. Early research infers that a relationship may exist even though the diagnosis provided may influence the management trajectory. In the absence of a diagnostic test and treatment, this study aims to confirm the symptoms and their severity, which may infer a relationship and influence future research.

Method: A quasi-experimental design was utilised, using Internet-based self-assessment questionnaires focusing on nine symptom areas: criteria, pain, sleep, fatigue, anxiety and depression, health-related quality of life, self-esteem and locus of control. The questionnaires used for data collection are as follows: the American Centre for Disease Control and Prevention Symptom Inventory for CFS/ME (American CDC Symptom Inventory); the American College of Rheumatology (ACR) Criteria for FM; Fibromyalgia Impact Questionnaire (FIQ); McGill Pain Questionnaire (MPQ); Multidimensional Fatigue Inventory (MFI); Pittsburgh Sleep Quality Index (PSQI); Health-Related Quality of Life SF-36 V2 (HRQoL SF-36 V2); Hospital Anxiety and Depression Scale (HADS); Multidimensional Health Locus of Control (MHLOC) and the Rosenberg Self-Esteem Scale (RSES).

Setting and participants: Participants were recruited from two distinct community groups, namely CFS/ME (n = 101) and FM (n = 107). Participants were male and female aged 17 (CFS/ME mean age 45.5 years; FM mean age 47.2 years).

Results: All participants in the CFS/ME and FM groups satisfied the requirements of their individual criteria. Results confirmed that both groups experienced the debilitating symptoms measured, with the exception of anxiety and depression, impacting on their quality of life. Results suggest a relationship between CFS/ME and FM, indicating the requirement for future research.

Source: Mckay PG, Martin CR, Walker H, Fleming M. Chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME) and Fibromyalgia (FM): the foundation of a relationship. Br J Pain. 2021 Feb;15(1):26-39. doi: 10.1177/2049463719875164. Epub 2019 Oct 5. PMID: 33633851; PMCID: PMC7882776. https://pubmed.ncbi.nlm.nih.gov/33633851/

Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design

Abstract:

Objective: To explore the relationship between symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM). The hypothesis predicated that there would be no significant differences between the group’s symptom experience.

Design: A quasiexperimental design. Structural equation modelling (SEM) and invariance testing.

Participants: Males (M) and females (F) >16 with a confirmed diagnosis of CFS/ME or FM by a general practitioner or specialist. CFS/ME (n=101, F: n=86, M: n=15, mean (M) age M=45.5 years). FM (n=107, F: n=95, M: n=12, M=47.2 years).

Outcome measures: Diagnostic criteria: the American Centers for Disease Control and Prevention (CDC) for CFS/ME and the American College of Rheumatology (ACR) criteria for FM. Additional symptom questionnaires measuring: pain, sleep quality, fatigue, quality of life, anxiety and depression, locus of control and self-esteem.

Results: Invariance was confirmed with the exception of the American CDC Symptom Inventory, Fibromyalgia Impact Questionnaire and Hospital Anxiety and Depression Scale (p<0.05) based on five questions. Consequently, it was erroneous to conclude differences. Therefore, the Syndrome Model was created. SEM could not have tested the ACR previously, as it comprised a single data point. Thus, it was combined with these three questionnaires, increasing the data points, to create this new measurable model. Results confirmed no significant differences between groups (p=0.07 (p<0.05)).

Conclusion: Participants responded in a similar manner to the questionnaire, confirming the same symptom experience. It is important to consider this in context with differing criteria and management guidelines, as this may influence diagnosis and the trajectory of patient’s management. With the biomedical cause currently unclear, it is the symptom experience and the impact on quality of life that is important. These findings are meaningful for patients, clinicians and policy development and support the requirement for future research.

Source: Mckay PG, Walker H, Martin CR, Fleming M. Exploratory study into the relationship between the symptoms of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and fibromyalgia (FM) using a quasiexperimental design. BMJ Open. 2021 Feb 1;11(2):e041947. doi: 10.1136/bmjopen-2020-041947. PMID: 33526500. https://bmjopen.bmj.com/content/11/2/e041947.long (Full text)

Circulating leptin levels in patients with myalgic encephalomyelitis, chronic fatigue syndrome or fibromyalgia: a systematic review protocol

Abstract:

Objective: The objective of the review is to evaluate circulating levels of leptin in people diagnosed with myalgic encephalomyelitis chronic fatigue syndrome or fibromyalgia syndrome and to investigate the differences compared with healthy controls.

Introduction: Myalgic encephalomyelitis chronic fatigue syndrome is a condition that has major symptoms, including self-reported fatigue, post-exertional malaise, and unexplained pain across the body. The widespread pain is measured in a systematic way and is often referred to as fibromyalgia. The two disorders have many similarities, but their association with leptin has indicated that leptin may affect the role of pro-inflammatory cytokines and symptom severity.

Inclusion criteria: This review will consider observational studies of varying study designs including prospective and retrospective cohort studies, case-control studies, time-series, and analytical cross-sectional studies that include both cases and healthy comparators. Cases will include a diagnosis of myalgic encephalomyelitis, chronic fatigue syndrome, and/or fibromyalgia. Controls are people without this diagnosis, usually healthy participants. Only studies published in English will be included due to limited resources for translation.

Methods: This protocol will be reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist and will follow the JBI methodology for systematic reviews of etiology and risk. A comprehensive search strategy will include PubMed, Embase, Scopus, Science Direct, and PsycINFO. Two reviewers will screen, critically appraise eligible articles, and extract data using a standardized data extraction tool informed by JBI SUMARI. The authors will complete a quantitative analysis that synthesizes findings across studies using pooled effect sizes and confidence intervals of the measures provided.

Source: Musker M, McArthur A, Munn Z, Wong ML. Circulating leptin levels in patients with myalgic encephalomyelitis, chronic fatigue syndrome or fibromyalgia: a systematic review protocol. JBI Evid Synth. 2020 Oct 30. doi: 10.11124/JBIES-20-00125. Epub ahead of print. PMID: 33136710. https://pubmed.ncbi.nlm.nih.gov/33136710/

Predictors of New Onsets of Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Fibromyalgia: The Lifelines Study

Abstract:

Background: It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM).

Methods: The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome.

Results: There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other.

Conclusions: Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

Source: Monden R, Rosmalen JGM, Wardenaar KJ, Creed F. Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study [published online ahead of print, 2020 Jun 17]. Psychol Med. 2020;1-9. doi:10.1017/S0033291720001774 https://pubmed.ncbi.nlm.nih.gov/32546287/

Physical Activity Measures in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Correlations Between Peak Oxygen Consumption, the Physical Functioning Scale of the SF-36 Questionnaire, and the Number of Steps From an Activity Meter

Abstract:

Background: Most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. This study compared three measures of physical activity in ME/CFS patients: the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) using an actometer, and the %peak VO2 of a cardiopulmonary stress test.

Methods: Female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ 3 months. Data from the three measures were compared by linear regression.

Results: In 99 female patients the three different measures were linearly, significantly, and positively correlated (PFS vs Steps, PFS vs %peak VO2 and Steps vs %peak VO2: all P < 0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER ≥ 1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P < 0.0001), strengthening the observation of the relations between them. Despite the close correlation, we observed a large variation between the three measures in individual patients.

Conclusions: Given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies in activity and may inform studies that compare methods of improving exercise capacity.

Source: van Campen CMC, Rowe PC, Verheugt FWA, Visser FC. Physical activity measures in patients with myalgic encephalomyelitis/chronic fatigue syndrome: correlations between peak oxygen consumption, the physical functioning scale of the SF-36 questionnaire, and the number of steps from an activity meter. J Transl Med. 2020;18(1):228. Published 2020 Jun 8. doi:10.1186/s12967-020-02397-7 https://pubmed.ncbi.nlm.nih.gov/32513266/

Chronic Pain Syndromes and Their Laryngeal Manifestations

Abstract:

IMPORTANCE: Fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), and chronic fatigue syndrome (CFS) are traditionally considered as distinct entities grouped under chronic pain syndrome (CPS) of an unknown origin. However, these 3 disorders may exist on a spectrum with a shared pathophysiology.

OBJECTIVE: To investigate whether the clinical presentation of FMS, IBS, and CFS is similar in a population presenting with voice and laryngeal disorders.

DESIGN, SETTING, AND PARTICIPANTS: This case series was a retrospective review of the medical records and clinical notes of patients treated between January 1, 2016, and December 31, 2017, at the Johns Hopkins Voice Center in Baltimore, Maryland. Patients with at least 1 CPS of interest (FMS, IBS, or CFS) were included (n = 215), along with patients without such diagnoses (n = 4034). Diagnoses, demographic, and comorbidity data were reviewed. Diagnoses related to voice and laryngeal disorders were subdivided into 5 main categories (laryngeal pathology, functional voice disorders, airway problems, swallowing problems, and other diagnoses).

MAIN OUTCOMES AND MEASURES: Prevalence and odds ratios of 45 voice and laryngeal disorders were reviewed. Odds ratios (ORs) were calculated by comparing patients with CPS with control patients.

RESULTS: In total, 4249 individuals were identified; 215 (5.1%) had at least 1 CPS and 4034 (94.9%) were control participants. Patients with CPS were 3 times more likely to be women compared with the control group (173 of 215 [80.5%] vs 2318 of 4034 [57.5%]; OR, 3.156; 95% CI, 2.392-4.296), and the CPS group had a mean (SD) age of 57.80 (15.30) years compared with the mean (SD) age of 55.77 (16.97) years for the control group. Patients with CPS were more likely to present with functional voice disorders (OR, 1.812; 95% CI, 1.396-2.353) and less likely to present with laryngeal pathology (OR, 0.774; 95% CI, 0.610-0.982) or airway problems (OR, 0.474; 95% CI, 0.285-0.789).

CONCLUSIONS AND RELEVANCE: The voice and airway presentation of patients with FMS, IBS, and/or CFS appears to be indistinguishable from each other. This finding suggests that these 3 diseases share upper airway symptoms.

Source: Piersiala K, Akst LM, Hillel AT, Best SR. Chronic Pain Syndromes and Their Laryngeal Manifestations. JAMA Otolaryngol Head Neck Surg. 2020 Apr 30. doi: 10.1001/jamaoto.2020.0530. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32352483

Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach

Abstract:

OBJECTIVE: Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are complicated medical disorders, with little known etiologies. The purpose of this research is to characterize FMS and CFS by studying the variations in cortisol secretion patterns, timings, amplitudes, the number of underlying pulses, as well as infusion and clearance rates of cortisol.

METHODS: Using a physiological state-space model with plausible constraints, we estimate the hormonal secretory events and the physiological system parameters (i.e., infusion and clearance rates).

RESULTS: Our results show that the clearance rate of cortisol is lower in FMS patients as compared to their matched healthy individuals based on a simplified cortisol secretion model. Moreover, the number, magnitude, and energy of hormonal secretory events are lower in FMS patients. During early morning hours, the magnitude and energy of the hormonal secretory events are higher in CFS patients.

CONCLUSION: Due to lower cortisol clearance rate, there is a higher accumulation of cortisol in FMS patients as compared to their matched healthy subjects. As the FMS patient accumulates higher cortisol residues, internal inhibitory feedback regulates the hormonal secretory events. Therefore, the FMS patients show a lower number, magnitude, and energy of hormonal secretory events. Though CFS patients have the same number of secretory events, they secrete lower quantities during early morning hours. When we compare the results for CFS patients against FMS patients, we observe different cortisol alteration patterns.

SIGNIFICANCE: Characterizing CFS and FMS based on the cortisol alteration will help us to develop novel methods for treating these disorders.

Source: Pednekar DD, Amin MR, Fekri Azgomi H, Aschbacher K, Crofford LJ, Faghih RT. Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach. IEEE Trans Biomed Eng. 2020 Mar 5. doi: 10.1109/TBME.2020.2978801. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32149617