ME Association January Summary of ME/CFS Published Research | 02 February 2019

February 2, 2019


Charlotte Stephens, Research Correspondent, ME Association.

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 January 2019.

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 January 2019

1. Ali S, et al. (2019)
Psychological and demographic factors associated with fatigue and social adjustment in young people with severe chronic fatigue syndrome/myalgic encephalomyelitis: a preliminary mixed-methods study
Journal of Behavioural Medicine [Epub ahead of print].

This mixed-methods study investigated factors associated with fatigue, disability and school attendance in young people with severe CFS/ME. Participants' illness experiences were also explored. Questionnaires were completed at baseline (T1) and approximately 5 months later (T2). There were 51 participants aged between 12 and 25, with a mean age of 18.8 years (SD 3.4).

At T1, participants reported severe fatigue and poor social adjustment. Stronger fear avoidance beliefs at T1 were associated with higher fatigue at T2, and with worse social adjustment at T1 and T2. Female gender was associated with lower work/school attendance at T1 and T2 but not with higher fatigue or worse social adjustment. Having accessed treatment was associated with reporting lower levels of work/school attendance at T1 and T2. Multivariate analyses of key outcomes identified significant associations between stronger fear avoidance beliefs and worse social adjustment at T2, and between female gender and lower work/school attendance at T2.

It was clear from the qualitative data that severe CFS/ME negatively impacted on many aspects of young people's lives. Fearful beliefs about activity could be targeted using cognitive-behavioural interventions.

2. Chu L, et al. (2019)
Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome.
Frontiers in Paediatrics [Provisionally accepted]
ME Association Research Summary Available.

Background: Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together.

Objective: Describe ME/CFS onset and course in one United States-based cohort.

Methods: 150 subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics.

Results: The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20%-25%). Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women’s symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course. Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included.

Conclusions: This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g. the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition.

3. Geraghty KJ and Adeniji C (2019)
The importance of accurate diagnosis of Myalgic Encephalomyelitis in children and adolescents: a commentary.
Frontiers in Pediatrics 6: 435.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness that causes a range of debilitating symptoms. While most research has focused on adults, the illness also presents in children and adolescents. Many physicians find it difficult to diagnose the illness.

In this commentary paper, we discuss a range of salient themes that have emerged from our ongoing research into the prevalence of ME/CFS in children and adolescents. We discuss reasons why pediatric prevalence estimates vary widely in the literature, from almost 0% to as high as 3%. We argue that there is considerable misdiagnosis of pediatric cases and over-inflation of estimates of pediatric ME/CFS. Many children and teenagers with general fatigue and other medical complaints may meet loose diagnostic criteria for ME/CFS.

We make recommendations for improving epidemiological research and identifying pediatric ME/CFS in clinical practice.

4. Lacerda EM, et al. (2019)
Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study.
Health Expectations [Epub ahead of print].

Background: The Clinical Understanding and Research Excellence in ME/CFS group (CureME) at the London School of Hygiene & Tropical Medicine has supported and undertaken studies in immunology, genetics, virology, clinical medicine, epidemiology and disability. It established the UK ME/CFS Biobank (UKMEB), which stores data and samples from three groups: participants with ME/CFS, Multiple Sclerosis (MS) and healthy controls. Patient and public involvement have played a central role from its inception.

Aim: To explore the views of participants with ME/CFS and MS on CureME research findings, dissemination and future biomedical research priorities.

Method: Five ME/CFS and MS focus groups were conducted at two UK sites. Discussions were transcribed and analysed thematically.

Results: A total of 28 UKMEB participants took part: 16 with ME/CFS and 12 with MS. Five themes emerged: (a) Seeking coherence: participants' reactions to initial research findings; (b) Seeking acceptance: participants explore issues of stigma and validation; (c) Seeking a diagnosis: participants explore issues around diagnosis in their lives; (d) Seeking a better future: participants' ideas on future research; and (e) Seeking to share understanding: participants' views on dissemination. Focus groups perceived progress in ME/CFS and MS research in terms of “putting together a jigsaw” of evidence through perseverance and collaboration.

Conclusion: This study provides insight into the emotional, social and practical importance of research to people with MS and ME/CFS, suggesting a range of research topics for the future. Findings should inform biomedical research directions in ME/CFS and MS, adding patients' voices to a call for a more collaborative research culture.

5. Lapp CW (2019)
Initiating Care of a Patient with Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.
Frontiers in Pediatrics 6: 415

This paper introduces the primary care physician to the unique and challenging aspects of initially diagnosing and managing a complex condition for which there are a plethora of symptoms, few physical findings, no known cause, and no specific treatments. While daunting, the rewards are many, and those who pursue an interest in ME/CFS find themselves at the forefront of medicine.

The approach to any complex problem is to break it down into small steps, and ME/CFS is no exception. The first office visit should be devoted to a history of the present illness, a physical examination, and collection of exclusionary laboratory tests. On follow-up the differential diagnosis and a treatment plan can be addressed.

Many individuals with ME/CFS have been humiliated or dismissed by other providers, so one will need to be as non-judgmental as possible and acknowledge that ME/CFS is not a psychological condition but a real illness. They need reassurance that you will work with them to seek a unifying diagnosis and prioritize management. 

6. McManimen SL, Sunquist ML and Jason LA (2019)
Deconstructing post-exertional malaise: an exploratory analysis.
Journal of Health Psychology [Epub ahead of print].

Post-exertional malaise (PEM) is a cardinal symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). There are two differing focuses when defining PEM: a generalized, full-body fatigue and a muscle-specific fatigue.

This study aimed to discern whether PEM is a unified construct or if it is composed of two smaller constructs, muscle fatigue and generalized fatigue. An exploratory factor analysis was conducted on several symptoms that assess PEM.

The results suggest that PEM is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.

7. Mueller C, et al. (2019)
Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy.
Brain Imaging and Behaviour [Epub ahead of print].
ME Association Research Summary Available.

Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS.

We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients.

Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups.

Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05).

We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

8. Park HY (2019)
Multidimensional Comparison of Cancer-Related Fatigue and Chronic Fatigue Syndrome: The Role of Psychophysiological Markers.
Psychiatry Investigations 16 (1): 71-79

Objective: The present study compared cancer-related fatigue (CRF) and chronic fatigue syndrome (CFS) using multidimensional measurements with the aim of better understanding characteristics and exploring markers of two similar fatigue syndromes.

Methods: Twenty-five patients with CRF and twenty patients with CFS completed questionnaires, including the Fatigue Severity Scale (FSS), Hospital Anxiety Depression Scale (HADS), Perceived Stress Scale (PSS), and Pittsburgh Sleep Quality Index (PSQI). Additionally, levels of high sensitivity C-reactive protein (hs-CRP), heart rate variability (HRV), and electroencephalography (EEG) were obtained. Neurocognitive functioning was also evaluated.

Results: Both groups showed comparable levels of psychological variables, including fatigue. Compared to CFS subjects, CRF patients had significantly higher hs-CRP levels and a reduced HRV-index. The within-group analyses revealed that the FSS score of the CRF group was significantly related to scores on the HADS-anxiety, HADS-depression, and PSQI scales. In the CFSgroup, FSS scores were significantly associated with scores on the PSS and the absolute delta, theta, and alpha powers in frontal EEG.

Conclusion: Findings indicate that different pathophysiological mechanisms underlie CFS and CRF. Inflammatory marker and HRV may be potential biomarkers for distinguishing two fatigue syndromes and frontal EEG parameters may be quantitative biomarkers for CFS.

9. Polli A, et al. (2019)
Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects.
Clinical Therapy [Epub ahead of print]

Purpose: Oxidative stress has been proposed as a contributor to pain in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). During incremental exercise in patients with ME/CFS, oxidative stress enhances sooner and antioxidant response is delayed. We explored whether oxidative stress is associated with pain symptoms or pain changes following exercise, and the possible relationships between oxidative stress and parasympathetic vagal nerve activity in patients with ME/CFS versus healthy, inactive controls.

Methods: The present study reports secondary outcomes from a previous work. Data from 36 participants were studied (women with ME/CFS and healthy controls). Subjects performed a submaximal exercise test with continuous cardiorespiratory monitoring. Levels of thiobarbituric acid-reactive substances (TBARSs) were used as a measure of oxidative stress, and heart rate variability was used to assess vagal activity. Before and after the exercise, subjects were asked to rate their pain using a visual analogic scale.

Findings: Significant between-group differences in pain at both baseline and following exercise were found (both, P < 0.007). In healthy controls, pain was significantly improved following exercise (P = 0.002). No change in oxidative stress level after exercise was found. Significant correlation between TBARS levels and pain was found at baseline (r = 0.540; P = 0.021) and after exercise (r = 0.524; P = 0.024) in patients only. No significant correlation between TBARS and heart rate variability at baseline or following exercise was found in either group. However, a significant correlation was found between exercise-induced changes in HRV and TBARS in healthy controls (r = -0.720; P = 0.001).

Implications: Oxidative stress showed an association with pain symptoms in people with ME/CFS, but no exercise-induced changes in oxidative stress were found. In addition, the change in parasympathetic activity following exercise partially accounted for the change in oxidative stress in healthy controls. More research is required to further explore this link.

10. Rajimakers RPH, et al. (2019)
Cytokine profiles in patients with Q fever fatigue syndrome.
Journal of Infectious Medicine [Epub ahead of print].

Background: Q fever fatigue syndrome (QFS) is a state of prolonged fatigue following around 20% of acute Q fever cases. It is thought that chronic inflammation plays a role in its aetiology. To test this hypothesis we measured circulating cytokines and the exvivo cytokine production in patients with QFS and compared to various control groups.

Methods: Peripheral blood mononuclear cells (PBMCs), whole blood, and serum were collected from 20 QFS patients, 19 chronic fatigue syndrome (CFS) patients, 19 Q fever seropositive controls, and 25 age- and sex-matched healthy controls. Coxiella-specific ex-vivo production of tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, and interferon (IFN) was measured, together with a total of 92 circulating inflammatory proteins.

Results: PBMCs of QFS patients produced more IL-6 (P = 0.0001), TNFα (P = 0.0002), and IL-1β (P = 0.0005) than the various control groups when stimulated with Coxiella antigen. QFS patients had distinct differences in circulating inflammatory markers compared to the other groups, including higher concentrations of circulating IL-6 and IFNγ.

Conclusion: QFS patients showed signs of chronic inflammation compared to asymptomatic Q fever seropositive controls, CFS patients, and healthy controls, of which the monocyte-derived cytokines TNFα, IL-1β, and especially IL-6, are likely crucial components.

11. Sirois FM and Hirsch JK (2019)
Self-compassion and Adherence in Five Medical Samples: the Role of Stress.
Mindfulness 10 (1): 46-54.

Emerging evidence indicates self-compassion can be beneficial for medical populations and for medical adherence; yet, research to date has not fully examined the reasons for this association.

This study examined the association of dispositional self-compassion to adherence across five medical samples and tested the extent to which perceived stress accounted for this association. Five medical samples (total N = 709), including fibromyalgia, chronic fatigue syndrome, and cancer patients, recruited from various sources, completed online surveys.

Self-compassion was positively associated with adherence in all five samples. A meta-analysis of the associations revealed a small average effect size (average r = .22, [0.15, 0.29]) of self-compassion and adherence and non-significant heterogeneity among the effects (Q (4) = 3.15, p = .532). A meta-analysis of the kappa2 values from the indirect effects of self-compassion on adherence revealed that, on average, 11% of the variance in medical adherence that was explained by self-compassion could be attributed to lower perceived stress.

Overall, findings demonstrate that dispositional self-compassion is associated with better medical adherence among people with fibromyalgia, chronic fatigue syndrome, and cancer, due in part to lower stress. This research contributes to a growing evidence base indicating the value of self-compassion for health-related behaviours in a variety of medical populations.

12. Sweetman E, et al. (2019)
Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome.
International Journal of Immunopathology and Pharmacology.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood disease affecting 0.2%–2% of the global population. To gain insight into the pathophysiology of ME/CFS in New Zealand, we examined the transcriptomes of peripheral blood mononuclear cells by RNA-seq analysis in a small well-characterized patient group (10 patients), with age/gender-matched healthy controls (10 control subjects).

Twenty-seven gene transcripts were increased 1.5- to sixfold and six decreased three- to sixfold in the patient group (P < 0.01). The top enhanced gene transcripts, IL8, NFΚBIA and TNFAIP3, are functionally related to inflammation, and significant changes were validated for IL8 and NFΚBIA by quantitative polymerase chain reaction (qPCR).

Functional network analysis of the altered gene transcripts (P < 0.01) detected interactions between the products related to inflammation, circadian clock function, metabolic dysregulation, cellular stress responses and mitochondrial function. Ingenuity pathway analysis (P < 0.05) provided further insights into the dysfunctional physiology, highlighting stress and inflammation pathways.

This analysis provides novel insights into the molecular changes in ME/CFS and contributes to the understanding of the pathophysiological mechanisms of the disease. 

13. Timbol CR and Baraniuk JN (2019)
Chronic fatigue syndrome in the emergency department.
Open Access Emergency Medicine 11: 15-28.

Purpose: Chronic fatigue syndrome (CFS) is a debilitating disease characterized by fatigue, postexertional malaise, cognitive dysfunction, sleep disturbances, and widespread pain. A pilot, online survey was used to determine the common presentations of CFS patients in the emergency department (ED) and attitudes about their encounters.

Methods: The anonymous survey was created to score the severity of core CFS symptoms, reasons for going to the ED, and Likert scales to grade attitudes and impressions of care. Open text fields were qualitatively categorized to determine common themes about encounters.

Results: Fifty-nine percent of respondents with physician-diagnosed CFS (total n=282) had gone to an ED. One-third of ED presentations were consistent with orthostatic intolerance; 42% of participants were dismissed as having psychosomatic complaints. ED staff were not knowledgeable about CFS. Encounters were unfavorable (3.6 on 10-point scale). The remaining 41% of subjects did not go to ED, stating nothing could be done or they would not be taken seriously. CFS subjects can be identified by a CFS questionnaire and the prolonged presence (>6 months) of unremitting fatigue, cognitive, sleep, and postexertional malaise problems.

Conclusions: This is the first investigation of the presentation of CFS in the ED and indicates the importance of orthostatic intolerance as the most frequent acute cause for a visit. The self-report CFS questionnaire may be useful as a screening instrument in the ED. Education of ED staff about modern concepts of CFS is necessary to improve patient and staff satisfaction. Guidance is provided for the diagnosis and treatment of CFS in these challenging encounters.

14. Valdez AR, et al. (2019)
Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning.
Frontiers in Pediatrics 6: 412.

Techniques of data mining and machine learning were applied to a large database of medical and facility claims from commercially insured patients to determine the prevalence, gender demographics, and costs for individuals with provider-assigned diagnosis codes for myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS).

The frequency of diagnosis was 519-1,038/100,000 with the relative risk of females being diagnosed with ME or CFS compared to males 1.238 and 1.178, respectively. While the percentage of women diagnosed with ME/CFS is higher than the percentage of men, ME/CFS is not a “women's disease.” Thirty-five to forty percent of diagnosed patients are men. Extrapolating from this frequency of diagnosis and based on the estimated 2017 population of the United States, a rough estimate for the number of patients who may be diagnosed with ME or CFS in the U.S. is 1.7 million to 3.38 million.

Patients diagnosed with CFS appear to represent a more heterogeneous group than those diagnosed with ME. A machine learning model based on characteristics of individuals diagnosed with ME was developed and applied, resulting in a predicted prevalence of 857/100,000 (p > 0.01), or roughly 2.8 million in the U.S.

Average annual costs for individuals with a diagnosis of ME or CFS were compared with those for lupus (all categories) and multiple sclerosis (MS), and found to be 50% higher for ME and CFS than for lupus or MS, and three to four times higher than for the general insured population.

A separate aspect of the study attempted to determine if a diagnosis of ME or CFS could be predicted based on symptom codes in the insurance claims records. Due to the absence of specific codes for some core symptoms, we were unable to validate that the information in insurance claims records is sufficient to identify diagnosed patients or suggest that a diagnosis of ME or CFS should be considered based solely on looking for presence of those symptoms.

These results show that a prevalence rate of 857/100,000 for ME/CFS is not unreasonable; therefore, it is not a rare disease, but in fact a relatively common one.

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