The ME Association Research Round-up

September 21, 2020

Charlotte Stephens, Research Correspondent, ME Association

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

All research relating to ME/CFS can be located in the ME Association: Index of ME/CFS Published Research.

This extensive library of research is updated at the end of every month, and is correct to the end of August 2020. It is a free resource available to anyone.

The Index provides an A-Z of published research studies and selected key documents and articles, listed by subject matter, on myalgic encephalomyelitis, myalgic encephalopathy, and/or chronic fatigue syndrome (ME/CFS).

You can use it to easily locate and read any research in a particular area that you might be interested in, e.g. epidemiology, infection, neurology, post-exertional malaise etc.

You can also find the Research Index in the Research section of the website together with a list of Research Summaries that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 11 – 17 September 2020

This week, 4 new research studies have been published, highlights include:

  • Researchers from Norway compared pain symptoms in fatigued and non-fatigued adolescents six months after Epstein Barr virus (EBV) infection, and in healthy controls. The group with chronic fatigue had significantly higher scores for pain symptoms compared to the other two groups.
  • Researchers from the USA studied the effects of repeated intravenous (IV) saline administration over nearly 2 years in a woman with ME/CFS. They found that her Cardiopulmonary Exercise Test (CPET) results improved over time, as well as her self-reported recovery time from the CPET, which reduced from 5 days to 1-2 days. The patient also reported improved quality of life, improved capacity for activities of daily living and reduced symptoms. The researchers concluded that IV saline may promote beneficial effects for cardiopulmonary function and symptoms in people with ME/CFS and that further study into this is needed.

ME/CFS Research References and Abstracts

1. Brodwall E et al. (2020)
Pain in adolescent chronic fatigue following Epstein-Barr virus infection.
Scandinavian Journal of Pain [Epub ahead of print].

Objectives: Acute Epstein-Barr virus (EBV) infection is a trigger of Chronic Fatigue (CF) and Chronic Fatigue Syndrome (CFS). The aim of this cross-sectional study was to investigate pain symptoms and pressure pain thresholds in fatigued and non-fatigued adolescents six months after acute EBV-infection, and in healthy controls. This study is part of the CEBA-project (CF following acute EBV infection in adolescents).

Methods: A total of 195 adolescents (12–20 years old) that had undergone an acute EBV infection six months prior to assessment were divided into fatigued (EBV CF+) and non-fatigued (EBV CF−) cases based on questionnaire score. The EBV CF+ cases were further sub-divided according to case definitions of CFS. In addition, a group of seventy healthy controls was included. Symptoms were mapped with questionnaires. Pressure pain thresholds were measured through pressure algometry. One way ANOVA were used for between-group analyses. Linear regression analyses were used to explore associations between Pediatric Quality of Life (dependent variable), pain symptoms and other variables within the EBV (CF+) group.

Results: The EBV CF+ group had significantly higher scores for pain symptoms as compared with the EBV CF− group and healthy controls, but pressure pain threshold did not differ significantly. The number of pain symptoms as well as pain severity were strongly and independently associated with quality of life.

Conclusions: CF and CFS following acute EBV-infection in adolescents is characterized by high pain symptom burden, which in turn is associated with a decline in quality of life. Pain in CF and CFS is of considerable clinical importance, and should be a focal point for further investigation and intervention in these patient groups.

2. Davenport T et al. (2020)
Cardiopulmonary responses to exercise in an individual with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome during long-term treatment with intravenous saline: A case study.
Work 66 (2): 353-359.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) causes significant impairment in daily activities, including the ability to pursue daily activities. Chronotropic intolerance is becoming better characterized in ME/CFS and may be the target of supportive treatment.

Objective: To document the effect of repeated intravenous (IV) saline administration on cardiovascular functioning and symptoms in a 38-year old female with ME/CFS.

Methods: The patient received 1 L of 0.9% IV saline through a central line for a total of 675 days. Single CPETs were completed periodically to assess the effect of treatment on cardiopulmonary function at peak exertion and ventilatory anaerobic threshold (VAT). An open-ended symptom questionnaire was used to assess subjective responses to CPET and self-reported recovery time.

Results: Improvements were noted in volume of oxygen consumed (VO2), heart rate (HR), and systolic blood pressure (SBP) at peak and VAT. Self-reported recovery time from CPET reduced from 5 days to 1–2 days by the end of treatment. The patient reported improved quality of life related, improved capacity for activities of daily living, and reduced symptoms.

Conclusions: IV saline may promote beneficial effects for cardiopulmonary function and symptoms in people with ME/CFS, which should be the focus of formal study.

3. Lindheimer J et al. (2020)
An analysis of 2‐day cardiopulmonary exercise testing to assess unexplained fatigue.
Physiological Reports 8 (17).

Two consecutive maximal cardiopulmonary exercise tests (CPETs) performed 24 hr apart (2‐day CPET protocol) are increasingly used to evaluate post‐exertional malaise (PEM) and related disability among individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

This protocol may extend to other fatiguing illnesses with similar characteristics to ME/CFS; however, 2‐day CPET protocol reliability and minimum change required to be considered clinically meaningful (i.e., exceeding the standard error of the measure) are not well characterized.

To address this gap, we evaluated the 2‐day CPET protocol in Gulf War Illness (GWI) by quantifying repeatability of seven CPET parameters, establishing their thresholds of clinically significant change, and determining whether changes differed between veterans with GWI and controls. Excluding those not attaining peak effort criteria (n = 15), we calculated intraclass correlation coefficients (ICCs), the smallest real difference (SRD%), and repeated measures analysis of variance (RM‐ANOVA) at the ventilatory anaerobic threshold (VAT) and peak exercise in 15 veterans with GWI and eight controls.

ICC values at peak ranged from moderate to excellent for veterans with GWI (mean [range]; 0.84 [0.65 – 0.92]) and were reduced at the VAT (0.68 [0.37 – 0.78]). Across CPET variables, the SRD% at peak exercise for veterans with GWI (18.8 [8.8 – 28.8]) was generally lower than at the VAT (28.1 [9.5 – 34.8]). RM‐ANOVAs did not detect any significant group‐by‐time interactions (all p > .05).

The methods and findings reported here provide a framework for evaluating 2‐day CPET reliability, and reinforce the importance of carefully considering measurement error in the population of interest when interpreting findings.

4. Penson A et al. (2020)
Short fatigue questionnaire: Screening for severe fatigue.
Journal of Psychosomatic Research 137.

Objective: To determine psychometric properties, a cut-off score for severe fatigue and normative data for the 4-item Short Fatigue Questionnaire (SFQ) derived from the multi-dimensional fatigue questionnaire Checklist Individual Strength (CIS).

Methods: Data of previous studies investigating the prevalence of fatigue in ten chronic conditions (n = 2985) and the general population (n = 2288) was used to determine the internal consistency (Cronbach's alpha) of the SFQ, its relation with other fatigue measures (EORTC QLQ-30 fatigue subscale and digital fatigue diary), a cut-off score for severe fatigue (ROC analysis) and to examine whether the four SFQ items truly measure the same construct. Norms were calculated for ten patient groups and the Dutch general population.

Results: Cronbach's alpha of the SFQ were excellent in almost all groups. Pearson's correlations between the SFQ and the EORTC-QLQ-C30 fatigue subscale and a fatigue diary were respectively 0.76 and 0.68. ROC analysis showed an area under the curve of 0.982 (95% CI: 0.979–0.985) and cut-off score of 18 was suggested which showed a good sensitivity (0.984) and specificity (0.826) as well as excellent values for the positive and negative prediction values within all groups using the CIS as golden standard. Factor analysis showed a one factor solution (Eigenvalue: 3.095) with factor loadings of all items on the factor being greater than 0.87.

Conclusion: The SFQ is an easy to use, reliable and valid instrument to screen for severe fatigue in clinical routine and research.

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