Phylogenetic analysis of short enteroviral sequences from patients with chronic fatigue syndrome

Abstract:

This study used phylogenetic analysis based on a region of the 5′ non-translated region (5’NTR) of a variety of enteroviral sequences to compare sequences associated with chronic fatigue syndrome (CFS) and those from enteroviruses causing acute infections. Direct sequencing of PCR products was used to obtain the nucleic acid sequences from CFS patients. The inferred phylogenetic tree identified three groupings, one correlating with the diagnosis of CFS.

The analysis identified a close relationship between the chronic fatigue enteroviral sequences, and showed that 19/20 were distinct from previously described enteroviruses. These results suggest there is persistence of enterovirus infection in some CFS patients and indicate the presence of distinct novel enterovirus sequences.

 

Source: Galbraith DN, Nairn C, Clements GB. Phylogenetic analysis of short enteroviral sequences from patients with chronic fatigue syndrome. J Gen Virol. 1995 Jul;76 ( Pt 7):1701-7. http://www.ncbi.nlm.nih.gov/pubmed/9049375

 

Inflammation correlates with symptoms in chronic fatigue syndrome

It is not unusual for patients who say they are sick to have normal results on standard laboratory testing. The physician often concludes that there is no “real” illness and that the patients’ symptoms likely stem from a psychological disorder. An alternative conclusion, often honored in the breach, is that the standard laboratory tests are measuring the wrong things.

Chronic fatigue syndrome (CFS)―also called myalgic encephalomyelitis/chronic fatigue syndrome―is such an illness. Often, the condition begins suddenly, following an “infectious-like” illness.

For years, patients do not return to full health. The illness waxes and wanes, and at its worst leads patients to be bedridden or unable to leave their homes. A report from the National Academies estimates that CFS affects up to 2.5 million people in the United States and generates direct and indirect expenses of $17–24 billion annually (1). The most widely used case definition (2) consists only of symptoms. This, along with typically normal results on standard laboratory tests, has raised the question of whether there are any “real” objective, biological abnormalities in CFS. In PNAS, Montoya et al. report the latest evidence that there are such abnormalities.

Indeed, research over the past 30 y has discovered pathology involving the central nervous system (CNS) and autonomic nervous system (ANS), energy metabolism (with associated oxidative and nitrosative stress), and the immune system, as described in a detailed review (4). This Commentary will briefly summarize the evidence, providing citations only to work published since this review. I will then place the report by Montoya et al. (3) in context, and speculate about the pathophysiology of the illness.

Source: Anthony Komaroff. Inflammation correlates with symptoms in chronic fatigue syndrome. PNAS  2017 ; published ahead of print August 15, 2017 doi: 10.1073/pnas.1712475114  http://www.pnas.org/content/early/2017/08/14/1712475114.extract

PACE team response shows a disregard for the principles of science

Abstract:

The PACE trial of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome/myalgic encephalomyelitis has raised serious questions about research methodology. An editorial article by Geraghty gives a fair account of the problems involved, if anything understating the case. The response by White et al. fails to address the key design flaw, of an unblinded study with subjective outcome measures, apparently demonstrating a lack of understanding of basic trial design requirements. The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed.

Source: Edwards J. PACE team response shows a disregard for the principles of science. J Health Psychol. 2017 Aug;22(9):1155-1158. doi: 10.1177/1359105317700886. Epub 2017 Mar 28. https://www.ncbi.nlm.nih.gov/pubmed/28805520

Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study

Abstract:

PURPOSE: To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24-h repeated exercise test.

METHODS: Ten CFS, seven MS and 17 age- and gender-matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR).

RESULTS: On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml  kg  min-1 ). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC.

CONCLUSION: These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions.

© 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Source: Hodges LD, Nielsen T, Baken D. Clin Physiol Funct Imaging. Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study. 2017 Aug 7. doi: 10.1111/cpf.12460. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28782878

Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: Case control study

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue after exertion. A systematic review suggested that transforming growth factor beta (TGF-β) concentrations are often elevated in cases of CFS when compared to healthy controls. This study attempted to replicate this finding, and investigate whether post-exertional symptoms were associated with altered cytokine protein concentrations and their RNA in CFS patients. Twenty-four patients fulfilling Centers for Disease Control criteria for CFS, but with no comorbid psychiatric disorders, were recruited from two CFS clinics in London, UK. Twenty-one healthy, sedentary controls were matched by gender, age, and other variables. Circulating proteins and RNA were measured for TGF-β, TNF, IL-8, IL-6 and IL-1β.

We measured six further cytokine protein concentrations (IL-2, IL-4, IL-5, IL-10, IL-12p70, and IFN-γ). Measures were taken at rest, and before and after both commuting and aerobic exercise. CFS cases had higher TGF-β protein levels compared to controls at rest (median (quartiles) = 43.9 (19.2, 61.8) versus 18.9 (16.1, 30.0) ng/ml) (p = 0.003), and consistently so over a nine-day period. However, this was a spurious finding due to variation between different assay batches.

There were no differences between groups in changes to TGF-β protein concentrations after either commuting or exercise. All other cytokine protein and RNA levels were similar between cases and controls. Post-exertional symptoms and perceived effort were not associated with any increased cytokines. We were unable to replicate previously found elevations in circulating cytokine concentrations, suggesting that elevated circulating cytokines are not important in the pathophysiology of CFS.

This article is protected by copyright. All rights reserved.

© 2017 British Society for Immunology

Source: Clark LV, Buckland M, Murphy G, Taylor N, Vleck V, Mein C, Wozniak E, Smuk M, White PD. Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: Case control study .Clin Exp Immunol. 2017 Aug 5. doi: 10.1111/cei.13023. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28779554

Pacing, Conventional Physical Activity and Active Video Games to Increase Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Protocol for a Pilot Randomized Controlled Trial

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious illness of biological origin characterized by profound physical and cognitive exhaustion and postexertion malaise. Pacing is a common strategy used to manage available energy and complete activities of daily living; yet little research has investigated this as a strategy to increase physical activity levels. Typically, people living with ME/CFS are faced by unique barriers to physical activity participation and are less physically active than healthy peers. As such they are at increased risk of physical inactivity-related health consequences. Active video games may be a feasible and acceptable avenue to deliver physical activity intervention by overcoming many of the reported barriers to participation.

OBJECTIVE: The primary objective of this pilot study is to determine the feasibility and acceptability of active video games to increase physical activity levels of people with ME/CFS. The secondary aims are to explore the preliminary effectiveness of pacing and active video gaming to pacing alone and pacing plus conventional physical activity to increase the physical activity levels of adults with ME/CFS and explore the relationship between physical activity and cumulative inflammatory load (allostatic load).

METHODS: This study will use a mixed method design, with a 3-arm pilot randomized controlled trial, exit interviews, and collection of feasibility and process data. A total of 30 adults with ME/CFS will be randomized to receive either (1) pacing, (2) pacing and conventional physical activity, or (3) pacing and active video gaming. The intervention duration will be 6 months, and participants will be followed up for 6 months postintervention completion. The intervention will be conducted in the participant’s home, and activity intensity will be determined by continuously monitored heart rate and ratings of perceived exertion. Feasibility and acceptability and process data will be collected during and at the end of the intervention. Health-related outcomes (eg, physical activity, blood samples, quality of life, and functioning) will be collected at baseline, end of intervention, and 6 months after intervention completion.

RESULTS: This protocol was developed after 6 months of extensive stakeholder and community consultation. Enrollment began in January 2017; as of publication, 12 participants were enrolled. Baseline testing is scheduled to commence in mid-2017.

CONCLUSIONS: This pilot study will provide essential feasibility and acceptability data which will guide the use of active video games for people with ME/CFS to increase their physical activity levels. Physical activity promotion in this clinical population has been poorly and under-researched, and any exploration of alternative physical activity options for this population is much needed.

TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12616000285459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370224 (Archived by WebCite at http://www.webcitation.org/6qgOLhWWf).

Source: Ferrar KE, Smith AE, Davison K. Pacing, Conventional Physical Activity and Active Video Games to Increase Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc. 2017 Aug 1;6(8):e117. doi: 10.2196/resprot.7242. http://www.researchprotocols.org/2017/8/e117/ (Full article)

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Abstract:

Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible.

To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding.

On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

Source: Montoya JG, Holmes TH, Anderson JN, Maecker HT, Rosenberg-Hasson Y, Valencia IJ, Chu L, Younger JW, Tato CM, Davis MM. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proc Natl Acad Sci U S A. 2017 Jul 31. pii: 201710519. doi: 10.1073/pnas.1710519114. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28760971

Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Abstract:

STUDY OBJECTIVES: Little is known about the type and severity of sleep disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) population, compared with healthy adolescents. Using a range of objective and subjective measures, the aim of this study was to investigate sleep quality, the relationship between objective and subjective measures of sleep quality, and their associations with anxiety in adolescents with CFS/ME compared with healthy controls.

METHODS: Twenty-one adolescents with CFS/ME aged 13 to 18 years (mean age 15.57 ± 1.40), and 145 healthy adolescents aged 13 to 18 years (mean age 16.2 ± 1.00) wore actigraphy watches continuously for 2 weeks to collect a number of objective sleep variables. The Pittsburgh Sleep Quality Index was used to obtain a subjective measure of sleep quality. Anxiety was measured by the Spence Children’s Anxiety scale.

RESULTS: On average over the 2-week period, adolescents with CFS/ME were found to have (1) significantly longer objective sleep onset latency, time in bed, total sleep time, and a later rise time (all P< .005), and (2) significantly poorer subjective sleep quality (P< .001), compared with healthy adolescents. The CFS/ME patient group displayed higher levels of anxiety (P< .05), and in both groups, higher levels of anxiety were significantly related to poorer subjective sleep quality (P< .001).

CONCLUSIONS: This study provides objective and subjective evidence of sleep disturbance in adolescents with CFS/ME compared with healthy adolescent controls.

Source: Josev EK, Jackson ML, Bei B, Trinder J, Harvey A, Clarke C, Snodgrass K, Scheinberg A, Knight SJ. Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). J Clin Sleep Med. 2017 Jul 28. pii: jc-17-00047. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28760189

Researchers identify biomarkers associated with chronic fatigue syndrome severity

Researchers at the Stanford University School of Medicine have linked chronic fatigue syndrome to variations in 17 immune-system signaling proteins, or cytokines, whose concentrations in the blood correlate with the disease’s severity.

The findings provide evidence that inflammation is a powerful driver of this mysterious condition, whose underpinnings have eluded researchers for 35 years.

You can read the rest of this article here: http://med.stanford.edu/news/all-news/2017/07/researchers-id-biomarkers-associated-with-chronic-fatigue-syndrome.html

Special issue on the PACE Trial

Abstract:

We are proud that this issue marks a special contribution by the Journal of Health Psychology to the literature concerning interventions to manage adaptation to chronic health problems. The PACE Trial debate reveals deeply embedded differences between critics and investigators. It reveals an unwillingness of the co-principal investigators of the PACE trial to engage in authentic discussion and debate. It leads one to question the wisdom of such a large investment from the public purse (£5 million) on what is a textbook example of a poorly done trial.

Source: David Marks. Special issue on the PACE Trial. Journal of Health Psychology. Vol 22, Issue 9, 2017. http://journals.sagepub.com/doi/full/10.1177/1359105317722370 (Full article)