Pain is associated with reduced quality of life and functional status in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:
Background and aims: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is challenging to live with, often accompanied by pervasive fatigue and pain, accompanied by decreased quality of life (QoL) as well as anxiety and/or depression. Associations between higher pain, lower QoL and higher anxiety and depression have been shown in patients with various chronic pain disorders. Few studies have however examined such associations in a sample of patients with ME/CFS.

The aims of the current study were to examine the impact of pain levels and compare levels of pain, health related QoL, anxiety and depression between patients with ME/CFS and healthy controls. In addition, the study aimed and to examine these relationships within the patient group only.

Methods: This is a cross-sectional questionnaire based study comparing 87 well-diagnosed patients with ME/CFS with 94 healthy controls. The De Paul Symptom Questionnaire (DSQ), the Medical Outcomes Study Short-Form Surveys (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were used to examine and compare pain, physical function, QoL, anxiety and depression in patients and healthy controls. Further the pain variables were divided into pain total, pain intensity and a pain frequency score for analyses of the above mentioned variables within the patient group only.

Results: Significantly higher levels of pain, anxiety and depression, and lower levels of QoL were found in the patient group compared with healthy controls. For the patient group alone, pain was significantly associated with lower QoL in terms of physical functioning, bodily pain, general health functioning, vitality and social functioning capacity. In this patient sample, only frequency of joint pain showed significant difference in psychological variables such as depression and anxiety – depression combined.

Conclusions: ME/CFS patients differ significantly from healthy controls in pain, health related QoL, anxiety and depression. Pain is significantly associated with reduced QoL and overall a lower level of functioning. The relation between pain and anxiety and depression appears less clear. Implications Pain is for many ME/CFS patients associated with reduced physical functioning and reduced QoL. A thorough pain assessment can therefore be essential for clinicians, and subsequent medical pain treatment combined with good pain coping skills may increase functioning level and QoL for these patients. The link between joint pain and psychological factors should also be focused in clinical practice in terms of mapping and counseling. Pain should be further examined to understand the importance it may have for functioning level as reduced function is a main criteria when diagnosing the patients.

Source: Strand EB, Mengshoel AM, Sandvik L, Helland IB, Abraham S, Nes LS. Pain is associated with reduced quality of life and functional status in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Scand J Pain. 2018 Oct 16. pii: /j/sjpain.ahead-of-print/sjpain-2018-0095/sjpain-2018-0095.xml. doi: 10.1515/sjpain-2018-0095. [Epub ahead of print]

Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – a secondary analysis of experimental comparative studies

Abstract:

Background and aims: The interaction between the immune system and pain has been thoroughly explored in the recent decades. The release of inflammatory mediators from immune cells has the capability of activating neurons and glial cells, in turn sensitizing the nervous system. Both immune system alterations and pain modulation dysfunctions have been shown in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) following exercise. However, no studies tried to explore whether these two phenomena are linked and can explain exercise-induced symptoms worsening in people with ME/CFS. We hypothesized that exercise-induced changes in descending pain modulation is associated to changes in immune system functions. We used complement system product C4a and elastase activity as indicators of immune system activity.

Methods: The study design was a secondary analysis of controlled experimental studies. Twenty-two patients with ME/CFS and 22 healthy sedentary controls were enrolled. In experiment 1, subjects performed an aerobic submaximal exercise test; in experiment 2 they underwent a self-paced exercise test. One week of rest period were set between the two exercise tests. Before and after each experiment, subjects underwent clinical assessment, pain thresholds (PPTs) measurement, and blood sampling. Immune system function was assessed measuring complement system C4a products and elastase activity.

Results: Changes in elastase activity were not associated to changes in PPTs. Associations were observed in the ME/CFS group between changes in PPTs and C4a products, following both types of exercise. After submaximal exercise, the change in C4a products was associated with the change in PPT at the thumb in patients (r=0.669, p=0.001). Similarly, after self-paced exercise the change in C4a products was associated witht the change in PPT at the calf in patients (r=0.429, p=0.047). No such correlations were found in healthy controls. Regression analysis showed that C4a changes after the submaximal exercise significantly predicted the change in PPTs (R2=0.236; p=0.02).

Conclusions: Moderate associations between exercise-induced changes in PPTs and immune system activity were found only in ME/CFS. The change in the complement system following submaximal exercise might be able to explain part of the change in patient’s pain thresholds, providing evidence for a potential link between immune system alteration and dysfunctional endogenous pain modulation. These results have to be taken with caution, as only one out of three measures of PPTs was found associated with C4a changes. We cannot reject the hypothesis that C4a might therefore be a confounding factor, and changes during exercise might be mediated by other mechanism. Implications Immune system changes following exercise might contribute to exercise-induced symptoms worsening in patients with ME/CFS. However, the role of the complement system is questionable.

Source: Polli A, Van Oosterwijck J, Meeus M, Lambrecht L, Nijs J, Ickmans K. Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – a secondary analysis of experimental comparative studies. Scand J Pain. 2018 Oct 16. pii: /j/sjpain.ahead-of-print/sjpain-2018-0075/sjpain-2018-0075.xml. doi: 10.1515/sjpain-2018-0075. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/30325737

WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue is increasingly common. Conventional medical care is limited in treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies, including herbal medicine.

OBJECTIVES: To assess the effectiveness of traditional Chinese medicine herbal products in treating idiopathic chronic fatigue and chronic fatigue syndrome.

SEARCH METHODS: The following databases were searched for terms related to traditional Chinese medicine, chronic fatigue, and clinical trials: CCDAN Controlled Trials Register (July 2009), MEDLINE (1966-2008), EMBASE (1980-2008), AMED (1985-2008), CINAHL (1982-2008), PSYCHINFO (1985-2008), CENTRAL (Issue 2 2008), the Chalmers Research Group PedCAM Database (2004), VIP Information (1989-2008), CNKI (1976-2008), OCLC Proceedings First (1992-2008), Conference Papers Index (1982-2008), and Dissertation Abstracts (1980-2008). Reference lists of included studies and review articles were examined and experts in the field were contacted for knowledge of additional studies.

SELECTION CRITERIA: Selection criteria included published or unpublished randomized controlled trials (RCTs) of participants diagnosed with idiopathic chronic fatigue or chronic fatigue syndrome comparing traditional Chinese medicinal herbs with placebo, conventional standard of care (SOC), or no treatment/wait lists. The outcome of interest was fatigue.

DATA COLLECTION AND ANALYSIS: 13 databases were searched for RCTs investigating TCM herbal products for the treatment of chronic fatigue. Over 2400 references were located. Studies were screened and assessed for inclusion criteria by two authors.

MAIN RESULTS: No studies that met all inclusion criteria were identified.

AUTHORS’ CONCLUSIONS: Although studies examining the use of TCM herbal products for chronic fatigue were located, methodologic limitations resulted in the exclusion of all studies. Of note, many of the studies labelled as RCTs and conducted in China did not utilize rigorous randomization procedures. Improvements in methodology in future studies is required for meaningful synthesis of data.

Source: Adams D, Wu T, Yang X, Tai S, Vohra S. WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev. 2018 Oct 15;10:CD006348. doi: 10.1002/14651858.CD006348.pub3. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30321452

Reciprocal associations between daily need-based experiences, energy, and sleep in chronic fatigue syndrome

Abstract:

OBJECTIVE: Previous findings indicate that patients with chronic fatigue syndrome (CFS) report significant day-to-day fluctuations in subjective energy and sleep. Herein, we examined whether daily variation in the satisfaction and frustration of the basic psychological needs for autonomy, competence, and relatedness would contribute to daily variation in subjective energy and quality and quantity of sleep. In addition, we examined whether daily variation in sleep would contribute to daily need-based experiences through (i.e., mediated by) daily fluctuations in subjective energy.

METHOD: CFS patients (N = 120; 92% female; Mage = 42.10 years, SD = 10.46) completed a diary for 14 days which assessed their need-based experiences and subjective energy every evening and sleep every morning.

RESULTS: Results indicated that subjective energy, sleep, and need experiences fluctuated significantly from day to day. Daily need satisfaction related to less daily fatigue and more daily vitality, while the opposite pattern was observed for daily need frustration. Daily need frustration was also uniquely related to poorer daily sleep quality. Lastly, better daily sleep quality was also uniquely related to more daily need satisfaction and less daily need frustration via (i.e., mediated by) daily variation in subjective energy. These reciprocal within-day associations remained significant after controlling for the previous day’s level of each outcome, with the exception of the relation between need frustration and sleep quality.

CONCLUSION: The present findings underscore the reciprocal day-to-day association between need-based experiences and subjective energy in CFS. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Source: Campbell R, Vansteenkiste M, Delesie L, Tobback E, Mariman A, Vogelaers D, Mouratidis A. Reciprocal associations between daily need-based experiences, energy, and sleep in chronic fatigue syndrome. Health Psychol. 2018 Oct 15. doi: 10.1037/hea0000621. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30321019

Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome.

Abstract:

Prior research has found a heightened risk of suicide in patients with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). It is possible that a number of factors including stigma, unsupportive social interactions, and severe symptoms could lead to the development of depression, suicidal ideation, and heightened risk of suicide in this patient population. Prior studies have indicated that patients often report the legitimacy of their illness being questioned by family, friends, and even their physicians.

This study aimed to determine whether stigma experienced, social support, symptomology, and functioning may be associated with depression and endorsement of suicidal ideation (SI) in patients with a self-reported diagnosis of ME or CFS. Findings indicated that participants that endorsed both SI and depression, in contrast to those that did not, experienced more frequent unsupportive social interactions in the form of blame for their illness, minimization of its severity, and social distancing from others.

In addition, 7.1% of patients with ME and CFS endorsed SI but do not meet the criteria for clinical depression These findings highlight the importance of stigma and unsupportive social interactions as risk factors for suicidal thoughts or actions among patients with ME and CFS. Community psychologists have an important role to play in helping educate health care professionals and the public to these types of risk factors for patients marginalized by ME and CFS.

Source: McManimen SL, McClellan D, Stoothoff J, Jason LA. Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Community Psychol. 2018 Nov;46(8):959-971. doi: 10.1002/jcop.21984. Epub 2018 May 4. https://www.ncbi.nlm.nih.gov/pubmed/30311972

Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review

Abstract:

The analysis of the 2017 Cochrane review reveals flaws, which means that contrary to its findings, there is no evidence that graded exercise therapy is effective. Because of the failure to report harms adequately in the trials covered by the review, it cannot be said that graded exercise therapy is safe. The analysis of the objective outcomes in the trials provides sufficient evidence to conclude that graded exercise therapy is an ineffective treatment for myalgic encephalomyelitis/chronic fatigue syndrome.

Source: Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018 Oct 8;5(2):2055102918805187. doi: 10.1177/2055102918805187. eCollection 2018 Jul-Dec.  https://www.ncbi.nlm.nih.gov/pubmed/30305916

Can a Chronic BPPV With a History of Trauma be the Trigger of Symptoms in Vestibular Migraine, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Whiplash Associated Disorders (WAD)? A Retrospective Cohort Study

Abstract:

BACKGROUND: In patients with chronic benign paroxysmal positional vertigo (BPPV), i.e., chronic vestibular multicanalicular canalithiasis (CVMCC), abnormal signals are transmitted from diseased labyrinths via the healthy vestibular nuclei complex to their end organs. The vestibulo-thalamo-cortical reflex as proposed in vestibular migraine is just one of these reflexes. In a group of patients diagnosed with CVMCC otolith repositioning maneuvers specific for each semicircular canal (SCC) ameliorated pain and other symptoms in 90%. Increased awareness of CVMCC may reduce suffering and continuous medication.

OBJECTIVE: To evaluate if CVMCC can be the trigger of symptoms in vestibular migraine, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and whiplash associated disorders (WAD).

STUDY DESIGN: Retrospective consecutive observational cohort study.

SETTING: Ambulatory at a private Otoneurology Centre.

PATIENTS: One hundred sixty-three patients with CVMCC and a history of trauma.

INTERVENTION: Based on the symptoms (structured symptom questionnaire), the patients are post hoc sub grouped according to the criteria of the different diagnoses.

MAIN OUTCOME MEASURE: Frequency of patients with CVMCC who fulfill the criteria of the different diagnoses.

RESULTS: 98% of all patients with CVMCC fulfill the Barany Society criteria of a probable vestibular migraine; 17% fulfill the International Classification of Headache Disorders defined vestibular migraine criteria; 63% fulfill the Fukuda criteria of ME/CFS; 100% of the patients with WAD suffer from CVMCC.

CONCLUSION: This survey supports the hypothesis that CVMCC can be the trigger of symptoms in vestibular migraine, ME/CFS, and WAD. The actual diagnosis the patient receives is often in accordance with the patient’s dominant symptom.

Source: Tjell C, Iglebekk W, Borenstein P. Can a Chronic BPPV With a History of Trauma be the Trigger of Symptoms in Vestibular Migraine, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and Whiplash Associated Disorders (WAD)? A Retrospective Cohort Study. Otol Neurotol. 2018 Oct 9. doi: 10.1097/MAO.0000000000002020. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30303941

Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes

Abstract:

In the last decade, a group of chronic disorders associated with fatigue (CDAF) emerged as the leading cause of chronic fatigue, chronic pain, and functional impairment, all of which have been often labeled in clinical practice as chronic fatigue syndrome (CFS) or fibromyalgia. While these chronic disorders arise from various pathophysiologic mechanisms, a shared autoimmune or immune-mediated etiology could shift the focus from symptomatic treatment of fatigue and pain to targeted immunomodulatory and biological therapy.

A clinical paradigm shift is necessary to reevaluate CFS and fibromyalgia diagnoses and its relationship to the CDAF entities, which would ultimately lead to a change in diagnostic and therapeutic algorithm for patients with chronic fatigue and chronic pain. Rather than uniformly apply the diagnoses of CFS or fibromyalgia to any patient presenting with unexplained chronic fatigue or chronic pain, it may be more beneficial and therapeutically effective to stratify these patients into more specific diagnoses in the CDAF group.

Source: Blitshteyn S, Chopra P. Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes. Eur Neurol. 2018 Oct 4;80(1-2):73-77. doi: 10.1159/000493531. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/30286454

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

BACKGROUND AND MAIN TEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies.

CONCLUSIONS: This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.

Source: Rasa S, Nora-Krukle Z, Henning N, Eliassen E, Shikova E, Harrer T, Scheibenbogen C, Murovska M, Prusty BK6; European Network on ME/CFS (EUROMENE). Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med. 2018 Oct 1;16(1):268. doi: 10.1186/s12967-018-1644-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167797/ (Full article)

No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls

Abstract:

INTRODUCTION: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue.

METHODS: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014 (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined.

RESULTS: The cohort consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and 16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07-5.49).

CONCLUSIONS: Fatigue ≥6 m and 3-6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.

Copyright © 2018 The Authors. Published by Elsevier Ltd. All rights reserved.

Source: Schurink-Van’t Klooster TM, Kemmeren JM, van der Maas NAT, van de Putte EM, Ter Wolbeek M, Nijhof SL, Vanrolleghem A5, van Vliet JA, Sturkenboom M, de Melker HE. No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls. Vaccine. 2018 Sep 19. pii: S0264-410X(18)31268-4. doi: 10.1016/j.vaccine.2018.09.019. [Epub ahead of print]  https://www.sciencedirect.com/science/article/pii/S0264410X18312684?via%3Dihub (Full article)