Monday 5 November 2018

ME Association October Summary of ME/CFS Published Research | 05 November 2018

 

ME Association Index of Published ME/CFS Research

The Index of Published ME/CFS Research has now been updated to take account of the research that has been published during the month of October 2018.

The Index is a useful way to locate and then read all relevant research on ME/CFS. It’s free to download and comes with an interactive contents table.

This is an A-Z list of all the most important ME/CFS research studies (and selected key documents and articles), listed by subject matter and author, with links to PubMed or to the Journal it was published in.

You can also find the index in the Research section of our website.

ME/CFS research abstracts from studies published in October 2018

1. Blitshteyn S and Chopra P (2018)
Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes

European Neurology 80 (1-2): 73-77.

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.

2. Brigden A, et al. (2018)
Defining the minimally clinically important difference of the SF-36 physical function subscale for paediatric CFS/ME: triangulation using three different methods
Health and Quality of Life Outcomes 16 (1): 202.

Abstract
Defining the minimally clinically important difference (MCID) is important for the design and analysis of clinical trials and ensures that findings are clinically meaningful. Studies in adult populations have investigated the MCID of The Short Form 36 physical function sub-scale (SF-36-PFS). However, to our knowledge no studies have defined the MCID of the SF-36-PFS in a paediatric population. We aimed to triangulate findings from distribution, anchor and qualitative methods to identify the MCID of the SF-36-PFS for children and adolescents with CFS/ME.

Quantitative methods: We analysed routinely-collected data from a specialist paediatric CFS/ME service in South-West England using: 1) the anchor method, based on Clinical Global Impression (CGI) outcomes at 6 months’ follow-up; 2) the distribution method, based on the standard deviation of baseline SF-36-PFS scores.

Qualitative methods: Young people (aged 12-17 years) and parents were asked to complete the SF-36-PFS, marking each question twice: once for where they would currently rate themselves/their child and a second time to show what they felt would be the smallest amount of change for them/their child to feel treatment had made a difference. Semi-structured interviews were designed to explore what factors were deemed important to patients and to what extent an improvement was considered satisfactory. We thematically analysed qualitative interviews from 21 children and their parents.

Quantitative results: Six-month follow-up data were available for 198 children with a mean age of 14 years. Most were female (74%, 146/198) and 95% gave their ethnicity as “White British”. Half the standard deviation of the baseline SF-36-PFS scores was 11.0. “A little better” on the CGI equated to a mean difference on the SF-36-PFS from baseline to 6-month follow-up of 9.0.

Qualitative results: Twenty-one children with CFS/ME participated: 16 females (76.2%) with a mean age of 14.4 years. Twenty mothers and two fathers were also interviewed. The median minimal improvement in the SF-36-PFS was 10. Participants indicated that small changes in physical function can lead to important improvements in valued social and family function. Patients and parents were positive about improvement even in the presence of persisting symptoms. Triangulation: The MCID based on the mean score from the three methods was 10.

Converging evidence indicates future studies in paediatric CFS/ME should use an MCID of 10 on the SF-36-PFS.

3. Campbell R, et al. (2018)
Reciprocal associations between daily need-based experiences, energy, and sleep in chronic fatigue syndrome

Health Psychology [Epub ahead of print]

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).

4. Cheshire A, et al. (2018)
Guided graded Exercise Self-help for chronic fatigue syndrome: patient experiences and perceptions

Disability Rehabilitation [Epub ahead of print]

Abstract
Purpose: This study explored patient experiences of Guided graded Exercise Self-help (GES) delivered as part of a randomised controlled trial for people with chronic fatigue syndrome/myalgic encephalomyelitis. The trial found that GES was better than specialist medical care at reducing fatigue and improving physical functioning.

Methods: Semi-structured interviews were conducted with patients reporting improvement (n = 9) and deterioration (n = 10), and analysis involved thematic “constant comparison.”

Results: The improved group described more facilitators to doing GES, and were more likely to describe high levels of self-motivation, whereas the deteriorated group described more barriers to GES (including worse exacerbation of symptoms after GES, greater interference from comorbid conditions, and obstacles to GES in their lives), and had been ill for longer. Having the capacity to do GES was important; of note, those with relatively lower levels of functioning sometimes had more time and space in their lives to support their GES engagement. We identified an important “indeterminate phase” early on, in which participants did not initially improve.

Conclusions: GES may be improved by targeting those most likely to improve, and teaching about the indeterminate phase. Implications for rehabilitation using the Guided Exercise Self-help booklet alone is unlikely to be sufficient to support patients through Guided Exercise Self-help successfully.

Additional guidance from skilled physiotherapists/health professionals who demonstrate an understanding of what it is like to cope with chronic fatigue syndrome/myalgic encephalomyelitis is also important.

Those using Guided Exercise Self-help may need additional support through a commonly experienced “indeterminate phase” – an initial phase in the programme where few benefits, along with various challenges associated with increasing activity, are experienced.

Individuals who have been ill with chronic fatigue syndrome/myalgic encephalomyelitis for a relatively longer period of time and/or have additional comorbid conditions may benefit from more bespoke therapies with greater health professionals input, delivered by appropriate therapists.

5. Dana J, et al. (2018)
Evaluation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) education materials in local health departments

Fatigue: Biomedicine, Health and Behaviour 6 (4).

Abstract
Purpose: To identify methods used by local health departments (LHDs) for reaching providers and the public with information about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Methods: During 2009–2012, we conducted LHD outreach in three stages: 1) materials needs assessment with LHDs in 18 states – 85% of 90 targeted LHDs; 2) dissemination to LHDs in 15 states – distributed 67,850 copies of ME/CFS printed materials to 121 LHDs; and 3) follow-up calls with LHDs 6 months after dissemination – 75% of 118 LHDs. The follow-up interview included 18 questions about ME/CFS material use, perception, and knowledge.

Results: Ninety-three percent of LHDs had no ME/CFS program or materials. ME/CFS was not rated a public health priority, yet 90% were interested in receiving ME/CFS materials. Of 89 LHDs completing the follow-up interview, 50% were in rural areas, 74% had heard about ME/CFS, and 80% had used the CDC-provided ME/CFS materials. LHDs incorporated these ME/CFS materials into existing programs and dissemination formats (e.g. kiosks and printed materials were preferred). Past use of provided materials did not impact LHDs’ plan to use materials in the future. Regardless of prior ME/CFS awareness, LHDs rated ME/CFS as an important health issue.

Conclusions: This paper highlights criteria to consider when developing outreach methods for LHDs including materials and dissemination. We learned materials should be concise and easily transportable to facilitate use in the community. Materials and outreach methods might require tailoring to LHDs as competing health priorities was the most common reason given by LHDs for not using ME/CFS materials.

6. Gunther OP, et al. (2018)
Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Molecular Neurobiology [Epub ahead of print].

Abstract
A random-sequence peptide microarray can interrogate serum antibodies in a broad, unbiased fashion to generate disease-specific immunosignatures. This approach has been applied to cancer detection, diagnosis of infections, and interrogation of vaccine response. We hypothesized that there is an immunosignature specific to ME/CFS and that this could aid in the diagnosis.

We studied two subject groups meeting the Canadian Consensus Definition of ME/CFS. ME/CFS (n = 25) and matched control (n = 25) sera were obtained from a Canadian study. ME/CFS (n = 25) sera were obtained from phase 1/2 Norwegian trials (NCT01156909). Sera from six healthy controls from the USA were included in the analysis. Canadian cases and controls were tested for a disease immunosignature.

By combining results from unsupervised and supervised analyses, a candidate immunosignature with 654 peptides was able to differentiate ME/CFS from controls. The immunosignature was tested and further refined using the Norwegian and USA samples. This resulted in a 256-peptide immunosignature with the ability to separate ME/CFS cases from controls in the international data sets.

We were able to identify a 256-peptide signature that separates ME/CFS samples from healthy controls, suggesting that the hit-and-run hypothesis of immune dysfunction merits further investigation. By extending testing of both our signature and one previously reported in the literature to larger cohorts, and further interrogating the specific peptides we and others have identified, we may deepen our understanding of the origins of ME/CFS and work towards a clinically meaningful diagnostic biomarker.

7. Jason LA, et al. (2018)
The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome

Journal of Health Psychology [Epub ahead or print]

Abstract
Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions.

Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients.

Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.

8. Knight SJ, et al. (2018)
School Functioning in Adolescents With Chronic Fatigue Syndrome

Frontiers in Paediatrics 6.

Abstract
Background: It is well known that adolescents with chronic fatigue syndrome (CFS) experience greater school absenteeism compared to healthy adolescents. Less is known about other important aspects of school functioning including school participation, school connectedness, and academic performance in students with CFS.

The aim of this study was to compare school functioning as a multifaceted construct in adolescents with CFS to healthy adolescent peers. We also explored whether illness factors were associated with school functioning in adolescents with CFS.

Methods: Thirty-nine participants with CFS and 28 healthy controls (aged 13–17 years) completed a range of subjective and objective measures of school functioning, as well as measures of fatigue and emotional symptoms.

Results: Adolescents with CFS demonstrated significantly higher rates of school absence, as well as poorer school-related quality of life, reduced school participation, poorer connectedness with school, and reduced academic performance. Fatigue severity and emotional symptoms were significantly associated with most aspects of school function.

Conclusions: Adolescents with CFS are at increased risk for poor school functioning across a range of indicators which extend beyond school absenteeism.

9. Loades ME, et al. (2018)
Does fatigue and distress in a clinical cohort of adolescents with CFS correlate with fatigue and distress in their parents?

Child Care, Health Development [Epub ahead of print]

Abstract
Objectives: Previous studies have found that parents of children with CFS are more fatigued, and mothers are more distressed than healthy controls. Managing the disabling symptoms of CFS can result in disruption and burden for the family. Most research has focused on mothers.

This study sought to further explore the associations between adolescent fatigue and distress, and parental fatigue and distress, as well as family functioning, including both mothers and fathers.

Design: Cross-sectional study of a clinical cohort of consecutive attenders at a specialist chronic fatigue unit.

Methods: Questionnaires were completed by adolescents (N = 115, age 11-18) with a confirmed diagnosis of CFS and their mothers (N = 100) and fathers (N = 65).

Results: Maternal fatigue was significantly correlated with maternal distress, but not with adolescent fatigue, depression, anxiety or functioning. This pattern held true for paternal fatigue.

Maternal and paternal anxiety and depression were significantly correlated with family functioning. Paternal and maternal distress were correlated with each other.

Mothers and fathers tended to have a consistent view of family functioning. Family functioning, specifically being overwhelmed by difficulties and scoring lower on strengths and adaptability was positively associated with adolescent depression.

Unexpectedly, higher levels of adolescent fatigue and poorer physical functioning were associated with better family functioning as rated by the mother.

Conclusions: Parents of adolescents with fatigue scored near to or within normative range for non-clinical samples on distress, fatigue and family functioning. Parental distress may contribute to or result from poorer family functioning.

Family functioning, particularly building strengths and adaptability, may be clinically important in CFS, as well as attending to parental, (particularly paternal) distress in families where adolescents are low in mood.

10. Mensah F, et al. (2018)
CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Frontiers in Immunology, 9.

Abstract
CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC).

Here, we investigated the relationship between CD24 expression and B cell maturation. In vitro stimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation). The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was also investigated using phospho-flow (phosphorylation of AMPK-pAMPK), 1proton nuclear magnetic resonance and Mitotracker Far-red (Mitochondrial mass-MM).

In vitro, in the absence of stimulation, there was an increased percentage of CD24+ viable B cells in ME/CFS patients compared to HC (p < 0.05) following 5 days culture. Following stimulation with B cell agonists, percentage of CD24+B cells in both naïve and memory B cell populations decreased. P < 0.01). There was a negative relationship between percentage of CD24+B cells with MM (R2 = 0.76; p < 0.01), which was subsequently lost over sequential cycles of proliferation. There was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro.

Short term ligation of the B cell receptor with anti-IgM antibody significantly reduced the viability of CD24+ memory B cells compared to those cross-linked by anti-IgD or anti-IgG antibody. A clear difference was found between naïve and memory B cells with respect to CD24 expression and pAMPK, most notably a strong positive association in IgD+IgM+ memory B cells.

In vitro findings confirmed dysregulation of CD24-expressing B cells from ME/CFS patients previously suggested by immunophenotype studies of B cells from peripheral blood. CD24-negative B cells underwent productive proliferation whereas CD24+ B cells were either unresponsive or susceptible to cell death upon BCR-engagement alone. We suggest that CD24 expression may reflect variations in energy metabolism on different B cell subsets.

11. Morris G, et al. (2018)
The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis
Sleep Medicine Reviews 41: 255-265.

Abstract
Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear and may involve the inter-play of several clinical variables and mechanistic pathways.

In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation.

Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene).

Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders.

We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders.

12. Polli A, et al. (2018)
Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – a secondary analysis of experimental comparative studies

Scandinavian Journal of Pain [Epub ahead or print]

Abstract
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.

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.

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).

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.

13. Rasa S, et al. (2018)
Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Journal of Translational Medicine 16 (1): 268.

Abstract
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.

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.

14. Schurink-van’t Klooster TM, et al. (2018)
No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls

Vaccine 36 (45): 6796-6802

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.

15. Strand EB, et al. (2018)
Pain is associated with reduced quality of life and functional status in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Scandinavian Journal of pain [Epub ahead of print]

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.

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.

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.

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.

16. Tjell C, et al. (2018)
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

Otology and Neurotology [Epub ahead of print]

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.

17. Tiziana P, et al. (2018)
Old muscle in young body: an aphorism describing the Chronic Fatigue Syndrome

European Journal of Translational Myology 28 (3).

Abstract
The chronic fatigue syndrome (CFS) otherwise known as myalgic encephalomyelitis (ME), is a debilitating syndrome whose identification is very complex due to lack of precise diagnostic criteria.

This pathology begins with limitations in duration and intensity of exercise and rapid onset of pain during physical activity. Its etiology is unknown, and symptoms are not limited to the muscles. Epidemiology is rather difficult to delimit, even if it affects mainly young (20-40 years), female subjects.

The results of muscular research show some peculiarities that can justify what has been observed in vivo. In particular:

  1. presence of oxidative damage of lipid component of biological membranes and DNA not compensated by the increase of the scavenger activity;
  2. Excitation-Contraction (E-C) alteration with modification of Ca2+transport;
  3. passage from slow to fast fiber phenotype;
  4. inability to increase glucose uptake;
  5. presence of mitochondrial dysfunction; and 6. genes expressed differentially (particularly those involved in energy production).

The skeletal muscles of CFS/ME patients show a significant alteration of the oxidative balance due to mitochondrial alteration and of the fiber phenotype composition as shown in sarcopenic muscles of the elderly. Vice versa, the muscle catabolism does not appear to be involved in the onset of this syndrome.

The data support the hypothesis that patients with CFS are subjected to some of the problems typical for muscle aging, which is probably related to disorders of muscle protein synthesis and biogenesis of mitochondria.

Patients with CFS can benefit from an appropriate training program because no evidence suggests that physical exercise worsens symptoms. Type, intensity and duration of any physical activity that activates muscle contraction (including Electrical Stimulation) require further investigation even if it is known that non-exhaustive physical activity decreases painful symptomatology.

18. Vink M and Vink-Niese A (2018)
Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review

Health Psychology Open 5 (2).

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.


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https://www.meassociation.org.uk/2018/11/me-association-october-summary-of-me-cfs-published-research-05-november-2018/

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