ME Association June Summary of ME/CFS Published Research | 04 July 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 June.

It provides a useful way to locate and then read all the 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.

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

Research abstracts from studies published in June 2018

1. Broadbent S, et al. (2018)
Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a pilot study
European Journal of Applied physiology [Epub ahead of print].

Abstract
This pilot pre-and post-intervention study investigated the effects of a short-term aquatic exercise programme on physiological outcomes, symptoms and exercise capacity in women with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

Eleven women (54.8 ± 12.4 year) volunteered for the 5-week program; an initial 20-min aquatic exercise session then two self-paced 20-min sessions per week for 4 weeks. Pre- and post-intervention outcomes were physiological measures, 6 min Walk Test (6MWT), perceived exertion (RPE), hand grip strength, Sit-to-Stand, Sit-Reach test, Apley's shoulder test, FACIT questionnaire, and 24-h post-test tiredness and pain scores (0-10 visual analogue scale). Heart rates, RPE, 24- and 48-h post-session tiredness/pain scores were recorded each session.

6MWT distance increased by 60.8 m (p = 0.006), left hand grip strength by 6 kg (p = 0.038), Sit-Reach test by 4.0 cm (p = 0.017), right shoulder flexibility by 2.9 cm (p = 0.026), FACIT scores by 8.2 (p = 0.041); 24-h post-test tiredness and pain decreased by 1.5 and 1.6, respectively (p = 0.002). There were significant post-intervention increases in exercising heart rates (6MWT 4- and 6-min time points), oxygen saturation at 2-min, and reduced RPE at 4-min. Weekly resting and exercising heart rates increased significantly during the study but RPE decreased; immediately post- and 24-h post-session tiredness decreased significantly. There were no reports of symptom exacerbation.

Conclusion:
Five weeks of low-moderate intensity aquatic exercise significantly improved exercise capacity, RPE and fatigue. This exercise mode exercise may potentially be a manageable and safe physical activity for CFS/ME patients.

2. Cambras D., et al. (2018)
Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
PLoS One 13 (6).

Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction.

This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year.

Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index.

Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary.

The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer.

Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter.

A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features.

Conclusion:
These findings suggest that circadian regulation and skin vasodilator responses may play a role in CFS/ME.

3. Chu L, et al. (2018)
Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey
PLoS One 13(6).

Abstract
Post-exertional malaise (PEM) is considered to be the hallmark characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, patients have rarely been asked in formal studies to describe their experience of PEM.

One hundred and fifty subjects, diagnosed via the 1994 Fukuda CFS criteria, completed a survey concerning 11 symptoms they could experience after exposure to two different types of triggers. We also inquired about onset and duration of PEM and included space for subjects to write in any additional symptoms.

Results were summarized with descriptive statistics; McNemar's, paired t-, Fisher's exact and chi-square goodness-of-fit tests were used to assess for statistical significance.

One hundred and twenty-nine subjects (90%) experienced PEM with both physical and cognitive exertion and emotional distress. Almost all were affected by exertion but 14 (10%) reported no effect with emotion.

Fatigue was the most commonly exacerbated symptom but cognitive difficulties, sleep disturbances, headaches, muscle pain, and flu-like feelings were cited by over 30% of subjects. Sixty percent of subjects experienced at least one inflammatory/ immune-related symptom. Subjects also cited gastrointestinal, orthostatic, mood-related, neurologic and other symptoms.

Exertion precipitated significantly more symptoms than emotional distress (7±2.8 vs. 5±3.3 symptoms (median, standard deviation), p<0.001). Onset and duration of PEM varied for most subjects. However, 11% reported a consistent post-trigger delay of at least 24 hours before onset and 84% endure PEM for 24 hours or more.

Conclusion:
This study provides exact symptom and time patterns for PEM that is generated in the course of patients' lives. PEM involves exacerbation of multiple, atypical symptoms, is occasionally delayed, and persists for extended periods.

Highlighting these characteristics may improve diagnosis of ME/CFS. Incorporating them into the design of future research will accelerate our understanding of ME/CFS.

4. Collin S, et al. (2018)
Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort
Sleep Medicine 46: 26-36.

Abstract
Sleep abnormalities are characteristic of chronic fatigue syndrome (CFS, also known as ‘ME'), however it is unknown whether sleep might be a causal risk factor for CFS/ME.

We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We describe sleep patterns of children aged 6 months to 11 years, who were subsequently classified as having (or not having) ‘chronic disabling fatigue' (CDF, a proxy for CFS/ME) between the ages 13 and 18 years, and we investigated the associations of sleep duration at age nine years with CDF at age 13 years, as well as sleep duration at age 11 years with CDF at age 16 years.

Children who had CDF during adolescence had shorter night-time sleep duration from 6 months to 11 years of age, and there was strong evidence that difficulties in going to sleep were more common in children who subsequently developed CDF.

The odds of CDF at age 13 years were 39% lower (odds ratio (OR) = 0.61, 95% CI = 0.43, 0.88) for each additional hour of night-time sleep at age nine years, and the odds of CDF at age 16 years were 51% lower (OR = 0.49, 95% CI = 0.34, 0.70) for each additional hour of night-time sleep at age 11 years.

Mean night-time sleep duration at age nine years was 13.9 (95% CI = 3.75, 24.0) minutes shorter among children who developed CDF at age 13 years, and sleep duration at age 11 years was 18.7 (95% CI = 9.08, 28.4) minutes shorter among children who developed CDF at age 16 (compared with children who did not develop CDF at 13 and 16 years, respectively).

Conclusion:
Children who develop chronic disabling fatigue in adolescence have shorter night-time sleep duration throughout early childhood, suggesting that sleep abnormalities may have a causal role in CFS/ME or that sleep abnormalities and CFS/ME are associated with a common pathophysiological cause.

5. Fragkos, et al. (2018)
Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature
Z Gastroenterology 56 (6): 573-577.

Abstract
Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions.

We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin.

On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses.

Serum eosinophil counts correlated well with the timing of the agents' administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration.

Conclusion:
Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin.

6. Geraghty K and Blease C (2018)
Myalgic encephalomyelitis/chronic fatigue syndrome and the biopsychosocial model: a review of patient harm and distress in the medical encounter
Disability and Rehabilitation 21: 1-10. 

See also: ME Association summary review written by Dr Geraghty.

Abstract
Despite the growing evidence of physiological and cellular abnormalities in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS), there has been a strong impetus to tackle the illness utilizing a biopsychosocial model. However, many sufferers of this disabling condition report distress and dissatisfaction following medical encounters. This review seeks to account for this discord.

A narrative review methodology is employed to synthesize the evidence for potential iatrogenesis. We identify seven potential modalities of iatrogenesis or harm reported by patients: difficulties in reaching an acceptable diagnosis; misdiagnosis, including of other medical and psychological conditions; difficulties in accessing the sick role, medical care and social support; high levels of patient dissatisfaction with the quality of medical care; negative responses to controversial therapies (cognitive behavioral therapy and graded exercise therapy); challenges to the patient narrative and experience; psychological harm (individual and collective distress).

Conclusion:
The biopsychosocial framework currently applied to ME/CFS is too narrow in focus and fails to adequately incorporate the patient narrative. Misdiagnosis, conflict, and harm are observable outcomes where doctors' and patients' perspectives remain incongruent.

Biopsychosocial practices should be scrutinized for potential harms. Clinicians should consider adopting alternative patient-centred approaches.

Implications for rehabilitation:
Patients with ME/CFS may report or experience one or more of the modalities of harms and distress identified in this review. It is important health and rehabilitation professionals seek to avoid and minimize harms when treating or assisting ME/CFS patients.

There are conflicting models of ME/CFS; we highlight two divergent models, a biopsychosocial model and a biomedical model that is preferred by patients. The ‘biopsychosocial framework' applied in clinical practice promotes treatments such as cognitive behavioral therapy and exercise therapy, however, the evidence for their success is contested and many patients reject the notion their illness is perpetuated by dysfunctional beliefs, personality traits, or behaviors.

Health professionals may avoid conflict and harm causation in ME/CFS by adopting more concordant ‘patient-centred' approaches that give greater prominence to the patient narrative and experience of illness.

7. Gleason K., et al. (2018)
Operationalizing Substantial Reduction in Functioning Among Young Adults with Chronic Fatigue Syndrome
International Journal of Behavioural Medicine [Epub ahead of print].

Abstract
Chronic fatigue syndrome and myalgic encephalomyelitis are fatiguing illnesses that often result in long-term impairment in daily functioning. In reviewing case definitions, Thrope et al. (Fatigue 4(3):175-188, 2016) noted that the vast majority of case definitions used to describe these illnesses list a “substantial reduction” in activities as a required feature for diagnosis. However, there is no consensus on how to best operationalize the criterion of substantial reduction.

The present study used a series of receiver operating curve (ROC) analyses to explore the use of the Medical Outcomes Study Short-Form-36 Health Survey (SF-36), designed by Ware and Shelbourne for operationalizing the substantial reduction criterion in a young adult population (18-29 years old). We compared the sensitivity and specificity of various cutoff scores for the SF-36 subscales and assessed their usefulness in discriminating between a group of young adults with a known diagnosis of chronic fatigue syndrome or myalgic encephalomyelitis (n = 98) versus those without that diagnosis (n = 272).

The four top performing subscales and their associated cutoffs were determined: Physical Functioning ≤ 80, General Health ≤ 47, Role Physical ≤ 25, and Social Functioning ≤ 50. Used in combination, these four cutoff scores were shown to reliably discriminate between the patients and controls in our sample of young adults.

Conclusion:
The implications of these findings for employing the substantial reduction criterion in both clinical and research settings are discussed.

8. Howard H. (2018)
Recent insights into 3 under recognized conditions: Myalgic encephalomyelitis–chronic fatigue syndrome, fibromyalgia, and environmental sensitivities–multiple chemical sensitivity
Canadian Family Physician 64 (6): 413-415.

Abstract
The Ontario Ministry of Health and Long-Term Care recently released the interim report of a task force charged with providing recommendations on 3 symptom-based conditions that have both shared and distinctive features: myalgic encephalomyelitis–chronic fatigue syndrome (ME-CFS), fibromyalgia (FM), and environmental sensitivities–multiple chemical sensitivity (ES-MCS).

• Fatigue and, to varying degrees, pain, sleep disturbances, and neurologic and cognitive symptoms

Distinct symptoms among each condition include the following:

• The fatigue in ME-CFS is chronic, profound, and not improved by rest, and there is postexertional malaise
• The chronic musculoskeletal pain in FM is widespread
• The symptoms of ES-MCS are provoked by exposure to low levels of multiple (and often unrelated) chemical, biological, or physical agents. Symptoms are usually neurocognitive, and might involve respiratory and other systems, with relief or improvement when inciting agents are removed

None of these conditions has consistent physical or laboratory findings, and the conditions vary in severity. Their underlying biological mechanisms remain unclear. As with many chronic conditions, patients are at risk of anxiety, depression, and other psychological symptoms. The foregoing attributes and the lack of proven treatments and clinical practice guidelines have led to decades of uncertainty regarding diagnosis, unnecessary investigations, ineffective treatment, and unmitigated suffering.

Conclusion:
Nevertheless, as noted in the report, recent insights reveal both the need and opportunities for finding solutions. First is evidence underscoring the prevalence of these conditions in Canada and their effect on health care use and employment. Second is mounting evidence of biological mechanisms that might lead to effective treatments. These insights, including those summarized within this article, deserve wide dissemination in the primary care community.

9. Karfakis N. (2018)
The biopolitics of CFS/ME
Studies in History and Philosophy of Biological and Biomedical Science [Epub ahead of print].

Abstract
This paper argues that Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) constitutes a biopolitical problem, a scientific object which needs to be studied, classified and regulated.

Assemblages of authorities, knowledges and techniques make CFS/ME subjects and shape their everyday conduct in an attempt to increase their supposed autonomy, wellbeing and health.

CFS and CFS/ME identities are however made not only through government, scientific, and medical interventions but also by the patients themselves, a biosocial community who collaborates with scientists, educates itself about the intricacies of biomedicine, and contests psychiatric truth claims.

CFS/ME is an illness trapped between medicine and psychology, an illness that is open to debate and therefore difficult to manage and standardise.

Conclusion:
The paper delineates different interventions by medicine, science, the state and the patients themselves and concludes that CFS/ME remains elusive, only partially standardised, in an on-going battle between all the different actors that want to define it for their own situated interests.

10. Roman P, et al. (2018)
Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review
Beneficial Microbes 9 (4): 603-611. [Previously published online ahead of print.]

Abstract
Evidence suggests that the gut microbiota might play an important role in fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). Our goal is to systematically review the reported effect of probiotic treatments in patients diagnosed with FMS or CFS.

A systematic review was carried out using 14 databases (PubMed, Cochrane Library, Scopus, PsycINFO, and others) in February 2016 to search for randomised controlled trials (RCTs) and pilot studies of CFS or FMS patient, published in the last ten years (from 2006 to 2016).

The Jadad scale was used to asseverate the quality of the clinical trials considered. Two studies (n=83) met the inclusion criteria, which were performed in CFS patients and both studies were considered as a ‘High range of quality score'.

The administration of Lactobacillus casei strain Shirota in CFS patients, over the course of 8 weeks, reduced anxiety scores. Likewise, this probiotic changed the faecal composition following 8 weeks of treatment. Additionally, the treatment with Bifidobacterium infantis 35624 in CFS patients, during the same period, reduced inflammatory biomarkers.

Conclusion:
The evidence about the usefulness of probiotics in CFS and FMS patients remains limited. The studied strains of probiotics have demonstrated a significant effect on modulating the anxiety and inflammatory processes in CFS patients. However, more experimental research, focusing mainly on the symptoms of the pathologies studied, is needed.

11. Rowe P, et al. (2018)
Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome
Journal of Pediatrics [Epub ahead of print].

Abstract
To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life.

Participants underwent a standardized examination of 11 areas of limb and spine ROM at baseline and at 3- to 6-month intervals for 2 years, resulting in a ROM score that ranged from 0 (normal throughout) to 11 (abnormal ROM in all areas tested).

We measured the time until the ROM score was ≤2 (the score in healthy age-matched controls). Change in ROM was measured by subtracting the 24-month from the baseline ROM score and by summing the degrees of change in the 10 tests with continuous outcomes. Health-related quality of life was measured using the Pediatric Quality of Life Inventory 4.0 (PedsQL).

The mean age at enrollment was 16.5 years (range 10-23). Two-year follow-up was available for 53 (96%). The proportion with a ROM score of >2 fell gradually over 2 years, from 78% at entry to 20% at 24 months (P < .001). ROM scores improved from a median of 5 at entry to 2 at 24 months (P < .001). The change in the summed degrees of improvement in ROM correlated positively with improvement in the PedsQL physical function subscale (r = 0.30; P < .03).

Conclusion:
In association with multimodal therapy, young people with chronic fatigue syndrome experienced progressively less impairment in ROM over 2 years, correlating with improvements in the physical function subscale of the PedsQL.

12. Tomas C and Newton J. (2018)
Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review
Biochemical Society Transactions 46 (3): 547-553. [Previously published online ahead of print.]

Abstract
Chronic fatigue syndrome (CFS), commonly known as myalgic encephalomyelitis (ME), is a debilitating disease of unknown etiology. CFS/ME is a heterogeneous disease associated with a myriad of symptoms but with severe, prolonged fatigue as the core symptom associated with the disease.

There are currently no known biomarkers for the disease, largely due to the lack of knowledge surrounding the eitopathogenesis of CFS/ME. Numerous studies have been conducted in an attempt to identify potential biomarkers for the disease.

This mini-review offers a brief summary of current research into the identification of metabolic abnormalities in CFS/ME which may represent potential biomarkers for the disease. The progress of research into key areas including immune dysregulation, mitochondrial dysfunction, 5′-adenosine monophosphate-activated protein kinase activation, skeletal muscle cell acidosis, and metabolomics are presented here.

Conclusion:
Studies outlined in this mini-review show many potential causes for the pathogenesis of CFS/ME and identify many potential metabolic biomarkers for the disease from the aforementioned research areas.

The future of CFS/ME research should focus on building on the potential biomarkers for the disease using multi-disciplinary techniques at multiple research sites in order to produce robust data sets.

Whether the metabolic changes identified in this mini-review occur as a cause or a consequence of the disease must also be established.

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