Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Non-restorative sleep is a hallmark symptom of chronic fatigue syndrome/myalgic encephalomyelitis. However, little is known about self-reported sleep disturbances in these subjects. This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort.

A prospective cross-sectional cohort study was conducted in 1,455 Spanish chronic fatigue syndrome/myalgic encephalomyelitis patients. Sleep quality, fatigue, pain, functional capacity impairment, psychopathological status, anxiety/depression and health-related quality of life were assessed using validated subjective measures. The frequencies of muscular, cognitive, neurological, autonomic and immunological symptom clusters were above 80%.

High scores were recorded for pain, fatigue, psychopathological status, anxiety/depression, and low scores for functional capacity and quality of life, all of which correlated significantly (all p < 0.01) with quality of sleep as measured by the Pittsburgh Sleep Quality Index. Multivariate regression analysis showed that after adjusting for age and gender, the pain intensity (odds ratio, 1.11; p <0.05), psychopathological status (odds ratio, 1.85; p < 0.001), fibromyalgia (odds ratio, 1.39; p < 0.05), severe autonomic dysfunction (odds ratio, 1.72; p < 0.05), poor functional capacity (odds ratio, 0.98; p < 0.05) and quality of life (odds ratio, 0.96; both p < 0.001) were significantly associated with poor sleep quality.

These findings suggest that this large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life.

Source: Castro-Marrero J, Zaragozá MC, González-Garcia S, Aliste L, Sáez-Francàs N, Romero O, Ferré A, Fernández de Sevilla T, Alegre J.  Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Sleep Res. 2018 May 16:e12703. doi: 10.1111/jsr.12703. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29770505

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia

Abstract:

OBJECTIVE: Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium. The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).

METHODS: Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.

RESULTS: Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5). CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores. CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect. Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).

INTERPRETATION: The major findings are that poor balance may be associated with poorer self-reported physical health. In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct. The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.

Source: Serrador JM, Quigley K, Zhao C, Findley T, Natelson BH. Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia. NeuroRehabilitation. 2018;42(2):235-246. doi: 10.3233/NRE-172245.

Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study

Abstract:

BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.

METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten CFS/FM patients, 11 RA patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/ml Naloxone) and placebo (2 ml Aqua) group. Pressure Pain Thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned Pain Modulation (CPM) efficacy and Deep Tissue Pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.

RESULTS: Deep Tissue Pain pressure was lower and temporal summation higher in CFS/FM (p=0.002 respectively p=0.010) and RA patients (p=0.011 respectively p=0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (p time =0.034). Accordingly, PPTs increased after placebo, and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, Deep Tissue Pain, temporal summation or CPM in the control group.

CONCLUSIONS: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced Deep Tissue Pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

This article is protected by copyright. All rights reserved.

Source: Hermans L, Nijs J, Calders P, De Clerck L, Moorkens G, Hans G, Grosemans S, Roman De Mettelinge T, Tuynman J, Meeus M. Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study. Pain Pract. 2017 Jul 19. doi: 10.1111/papr.12613. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28722815

A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls

Abstract:

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic pain syndrome. A plausible pathogenesis of the disease is uncertain and the pursuit of measurable biomarkers for objective identification of affected individuals is a continuing endeavour in FMS research. Our objective was to perform an explorative metabolomics study (1) to elucidate the global urinary metabolite profile of patients suffering from FMS, and (2) to explore the potential of this metabolite information to augment existing medical practice in diagnosing the disease.

METHODS: We selected patients with a medical history of persistent FMS (n = 18), who described their recent state of the disease through the Fibromyalgia Impact Questionnaire (FIQR) and an in-house clinical questionnaire (IHCQ). Three control groups were used: first-generation family members of the patients (n = 11), age-related individuals without any indications of FMS or related conditions (n = 10), and healthy young (18-22 years) individuals (n = 20). All subjects were female and the biofluid under investigation was urine. Correlation analysis of the FIQR showed the FMS patients represented a well-defined disease group for this metabolomics study. Spectral analyses of urine were conducted using a 500 MHz 1H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Matlab, R, SPSS and SAS software.

RESULTS AND DISCUSSION: Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites – succinic acid, taurine and creatine – that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis – area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group.

CONCLUSION: Our data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS.

Source: Malatji BG, Meyer H, Mason S, Engelke UFH, Wevers RA, van Reenen M, Reinecke CJ. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol. 2017 May 11;17(1):88. doi: 10.1186/s12883-017-0863-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426044/ (Full article)

Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia

Abstract:

BACKGROUND: Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) share some similar symptoms with fibromyalgia (FM). Prior research has found increased illness severity when patients have FM that is comorbid with ME and CFS. For example, post-exertional malaise (PEM) has been shown to be more severe in those with comorbid FM. However, PEM can be separated into two factors, Muscle and General PEM. It is unknown if the more severe PEM findings in comorbid FM are due to the Muscle or General PEM factor.

PURPOSE:The purpose of this study was to determine if the PEM differences seen between patients with and without comorbid FM exist for the Muscle or General PEM factors.

METHOD: An international convenience sample was collected via an online questionnaire. The questionnaire assessed the frequency and severity of several PEM-related symptoms. Additionally, participants provided information regarding the course and characteristics of their illness.

RESULTS: Participants that indicated a comorbid diagnosis of FM displayed significantly more frequent and severe PEM symptoms in the Muscle and General PEM factors. The FM group also indicated significantly worse physical functioning compared to the group without comorbid FM.

DISCUSSION: The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients' physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies.

Source: McManimen SL, Jason LA. Post-Exertional Malaise in Patients with ME and CFS with Comorbid Fibromyalgia. SRL Neurol Neurosurg. 2017;3(1):22-27. Epub 2017 Mar 10. https://www.ncbi.nlm.nih.gov/pubmed/28603794

Research Provides More Evidence That Chronic Fatigue Syndrome Is A Legitimate Medical Condition

Press Release: Researchers at Georgetown University Medical Center have found that chronic fatigue syndrome (CFS) may be rooted in distinct neurological abnormalities that can be medically tested. Although the sample studied was small, this research provides objective, physiological evidence that the controversial disorder can be considered a legitimate medical condition.

Chronic fatigue syndrome defines a range of illnesses including fibromyalgia and Gulf War syndrome, all of which have fatigue as a major symptom. Even among medical professionals, there is a disagreement about the causes, diagnosis and treatment of CFS because so much about the disorder remains unknown. One reason CFS is difficult to diagnose is because it shares symptoms with many other diseases, including multiple sclerosis and lupus. Even when other illnesses are ruled out and a CFS diagnosis is given, there is not a standardized course of treatment and it’s difficult for doctors to measure patient improvement. Estimates are that two to four times as many women as men are diagnosed with CFS.

The Georgetown study, published in the November edition of the BMC Neurology Journal, an online publication, reveals that patients diagnosed with CFS and its family of illnesses have a set of proteins in their spinal cord fluid that were not detected in healthy individuals. These proteins might give insight into the causes of CFS and could someday be used as markers to diagnose patients with the disorder.

“For years, patients with chronic fatigue syndrome have suffered from painful symptoms for which there is no blood test, diagnosable physical condition or any method for doctors to measure improvement,” said James Baraniuk, MD, assistant professor of medicine at Georgetown University Medical Center and first author on the study. “Our research provides initial evidence that chronic fatigue syndrome and its family of illnesses may be legitimate, neurological diseases and that at least part of the pathology involves the central nervous system.”

The disorder is characterized by profound fatigue that is not improved by bed rest and that may get worse with physical or mental activity, according to the Centers for Disease Control and Prevention. Persons with CFS usually function at a lower level of activity than they were capable of before the onset of illness, feeling too tired to perform normal activities or easily exhausted with no apparent reason. Patients also report various nonspecific symptoms, including weakness, muscle pain, impaired memory and/or mental concentration, insomnia and post-exertional fatigue lasting more than 24 hours.

The study looked at 50 individuals suffering from at least two disorders related to CFS, including fibromyalgia and Gulf War syndrome. By examining spinal cord fluid in patients with CFS and in healthy individuals, the researchers found that CFS patients have 16 proteins that healthy individuals do not. Five of these 16 proteins are found in all patients with the illnesses but in none of the controls. The results indicate that those 16 proteins could possibly serve as a “biosignature” for the disease and could someday be used to diagnose CFS.

“Although this is a small study and more research on the subject is necessary, these results indicate it might be possible to develop a simple laboratory test to diagnose these disorders in the future,” Baraniuk said.

Other co-authors on the paper include Begona Casada, PhD, and Hilda Maibach, MS, of Georgetown University Medical Center; Daniel J. Clauw, MD, of the University of Michigan; and Lewis K. Pannell, PhD, of the University of South Carolina; and Sonya Hess, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases.

 

Source: Georgetown University Medical Center. “Research Provides More Evidence That Chronic Fatigue Syndrome Is A Legitimate Medical Condition.” ScienceDaily. ScienceDaily, 10 January 2006. www.sciencedaily.com/releases/2006/01/060110013424.htm

Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes

Abstract:

OBJECTIVE: Patients with functional somatic syndromes (FSS) such as fibromyalgia and chronic fatigue syndrome have a poor outcome and can incur high healthcare and societal costs. We aimed to compare the medium-term (16 months) cost-effectiveness and the long-term (40 months) economic outcomes of a bespoke cognitive-behavioural group treatment (STreSS) with that of enhanced usual care (EUC).

METHODS: We obtained complete data on healthcare and indirect costs (i.e. labour marked-related and health-related benefits) from public registries for 120 participants from a randomised controlled trial. Costs were calculated as per capita public expenses in 2010 €. QALYs gained were estimated from the SF-6D. We conducted a medium-term cost-effectiveness analysis and a long-term cost-minimization analysis from both a healthcare (i.e. direct cost) and a societal (i.e. total cost) perspective.

RESULTS: In the medium term, the probability that STreSS was cost-effective at thresholds of 25,000 to 35,000 € per QALY was 93-95% from a healthcare perspective, but only 50-55% from a societal perspective. In the long term, however, STreSS was associated with increasing savings in indirect costs, mainly due to a greater number of patients self-supporting. When combined with stable long-term reductions in healthcare expenditures, there were total cost savings of 7184 € (95% CI 2271 to 12,096, p=0.004) during the third year after treatment.

CONCLUSION: STreSS treatment costs an average of 1545 €. This cost was more than offset by subsequent savings in direct and indirect costs. Implementation could both improve patient outcomes and reduce costs.

Copyright © 2017 Elsevier Inc. All rights reserved.

 

Source: Schröder A, Ørnbøl E, Jensen JS, Sharpe M, Fink P. Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes. J Psychosom Res. 2017 Mar;94:73-81. doi: 10.1016/j.jpsychores.2017.01.005. Epub 2017 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/28183406

 

Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli

Abstract:

Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity.

The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach’s alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson’s r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson’s r) with three measures of sensory testing: cold pain tolerance (-0.34); heat pain tolerance (-0.285); heat pain threshold (-0.271).

Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization.

 

Source: Dixon EA, Benham G, Sturgeon JA, Mackey S, Johnson KA, Younger J. Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli. J Behav Med. 2016 Jun;39(3):537-50. doi: 10.1007/s10865-016-9720-3. Epub 2016 Feb 12. https://www.ncbi.nlm.nih.gov/pubmed/26873609

 

Modeling diurnal hormone profiles by hierarchical state space models

Abstract:

Adrenocorticotropic hormone (ACTH) diurnal patterns contain both smooth circadian rhythms and pulsatile activities. How to evaluate and compare them between different groups is a challenging statistical task. In particular, we are interested in testing (1) whether the smooth ACTH circadian rhythms in chronic fatigue syndrome and fibromyalgia patients differ from those in healthy controls and (2) whether the patterns of pulsatile activities are different. In this paper, a hierarchical state space model is proposed to extract these signals from noisy observations. The smooth circadian rhythms shared by a group of subjects are modeled by periodic smoothing splines. The subject level pulsatile activities are modeled by autoregressive processes. A functional random effect is adopted at the pair level to account for the matched pair design. Parameters are estimated by maximizing the marginal likelihood. Signals are extracted as posterior means. Computationally efficient Kalman filter algorithms are adopted for implementation. Application of the proposed model reveals that the smooth circadian rhythms are similar in the two groups but the pulsatile activities in patients are weaker than those in the healthy controls.

Copyright © 2015 John Wiley & Sons, Ltd.

 

Source: Liu Z, Guo W. Modeling diurnal hormone profiles by hierarchical state space models. Stat Med. 2015 Oct 30;34(24):3223-34. doi: 10.1002/sim.6579. Epub 2015 Jul 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592415/ (Full article)

 

Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances

Abstract:

Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A -2.5 kb (CCTTT) n as well as Ser608Leu and NOS3 -786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects.

Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 -786T>C polymorphisms. Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A -2.5 kb (CCTTT)11 allele represents a genetic determinant for FM/CFS, and the (CCTTT)16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5 kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI.

 

Source: De Luca C, Gugliandolo A, Calabrò C, Currò M, Ientile R, Raskovic D, Korkina L, Caccamo D. Role of polymorphisms of inducible nitric oxide synthase and endothelial nitric oxide synthase in idiopathic environmental intolerances. Mediators Inflamm. 2015;2015:245308. doi: 10.1155/2015/245308. Epub 2015 Mar 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387900/ (Full article)