Pitfalls in cytokine measurements – Plasma TGF-β1 in chronic fatigue syndrome

Abstract:

BACKGROUND: Serum TGF-β1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre-analytical procedures is essential. The objective of the current study was to measure circulating TGF-β1 concentrations in CFS patients compared to healthy controls, taking into account differences in pre-analytical procedures.

METHODS: Two cohorts of female CFS patients were included. In both studies patients were asked to bring a healthy, age-matched control. At baseline, TGF-β1 levels were measured in plasma and additionally P-selectin, a marker of platelet activity, was determined in a subgroup of participants.

RESULTS: 50 patients and 48 controls were included in cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there were no differences in TGF-β1 concentrations. However, between the cohorts there was a large discrepancy, which appeared to be caused by differences in g-force of the centrifuges used. The lower g-force used in cohort II (1361 g) caused more platelet activation, reflected by higher p-selectin concentrations, compared to cohort I (p < 0.0001), which was confirmed in a second independent experiment. There was a correlation between TGF-β1 and p-selectin concentrations (r 0.79, p < 0.0001).

CONCLUSION: These results demonstrate that control of pre-analytical procedures is an essential aspect when measuring circulating cytokines. No evidence for enhanced TGF-β1 in patients with CFS was found.

Source: Roerink ME, van der Schaaf ME, Hawinkels LJAC, Raijmakers RPH, Knoop H, Joosten LAB, van der Meer JWM. Pitfalls in cytokine measurements – Plasma TGF-β1 in chronic fatigue syndrome. Neth J Med. 2018 Sep;76(7):310-313. https://www.ncbi.nlm.nih.gov/pubmed/30220655

Near-Infrared Spectroscopy Screening to Allow Detection of Pathogenic Mitochondrial DNA Variants in Individuals with Unexplained Abnormal Fatigue: A Preliminary Study

Abstract:

Unexplained abnormal fatigue is characterized by chronic fatigue persisting for at least six months and not sufficiently explained by any recognized medical condition. In this pilot study, twelve individuals with abnormal fatigue remaining unexplained after thorough screening were investigated using a near-infrared (NIR) spectroscopy handgrip test.

Four of them were found to have an abnormal oxygen extraction pattern similar to participants with documented mitochondrial myopathy. In three of the four individuals, diverse mitochondrial abnormalities were documented by spectrophotometric, immunocytological, fluorescent, and morphological analyses performed in skeletal muscle and in cultured skin fibroblasts. Three of the four participants with decreased muscular oxygen extraction were each shown to harbor a different homoplasmic pathogenic mitochondrial DNA point mutation (m.961T > C, m.1555A > G, m.14484T > C). In the fourth participant, the presence of multiple large mitochondrial DNA deletions was suspected in muscle tissue. In contrast, none of the eight abnormally fatigued participants with normal NIR spectroscopy results harbored either a pathogenic mitochondrial DNA point mutation or large deletions ( P < 0.001).

This pilot study shows that NIR spectroscopy may serve as a noninvasive screening tool to delineate a subgroup (of participants) with mitochondrial dysfunction among the large group of individuals with unexplained abnormal fatigue.

Source: Celie BM, Mariman A, Boone J, Delesie L, Tobback E, Seneca S, De Paepe B, Vogelaers D, Van Coster RN, Bourgois JG. Near-Infrared Spectroscopy Screening to Allow Detection of Pathogenic Mitochondrial DNA Variants in Individuals with Unexplained Abnormal Fatigue: A Preliminary Study. Appl Spectrosc. 2018 May;72(5):715-724. doi: 10.1177/0003702818756647. Epub 2018 Feb 13.  https://www.ncbi.nlm.nih.gov/pubmed/29336589

A Brief Questionnaire to Assess Post-Exertional Malaise

Abstract:

Post-exertional malaise (PEM) is a key symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul Symptom Questionnaire (DSQ) were recommended as a first step in measuring this symptom for patients with ME and CFS by the National Institutes of Health/Centers for Disease Control and Prevention (NIH/CDC) Common Data Elements’ (CDE) working group.

The second step in this process, as recommended by the NIH/CDC CDE working group, involves assembling information from various sources to confirm the presence of PEM. There have not been any efforts, to date, to standardize this second-step process in the assessment of PEM.

The current study examined whether five supplementary items on the DSQ could be used to operationalize the second step of the recommendations made by the NIH/CDC CDE working group. The five supplementary DSQ PEM duration items correctly categorized patients with ME or CFS 81.7% of the time, while incorrectly categorizing multiple sclerosis (MS) and post-polio syndrome (PPS) as ME or CFS only 16.6% of the time. The findings suggested that a PEM second-step process could be operationalized using supplementary DSQ items.

Source: Cotler J, Holtzman C, Dudun C, Jason LA. A Brief Questionnaire to Assess Post-Exertional Malaise. Diagnostics (Basel). 2018 Sep 11;8(3). pii: E66. doi: 10.3390/diagnostics8030066.

Chronic fatigue syndrome and the somatic expression of emotional distress: Applying the concept of illusory mental health to address the controversy

Abstract:

OBJECTIVE: The process of somatization in chronic fatigue syndrome (CFS) was investigated using the concept of illusory mental health (IMH). IMH involves self-reporting low emotional distress alongside performance-based assessment of distress.

METHOD: We studied IHM and physical symptoms in 175 women across four groups: (a) CFS plus depression; (b) CFS with no depression (CFS-ND); (c) depressive disorder without CFS; and (d) healthy controls (HC). IMH was assessed using a self-report measure plus the performance-based Early Memory Index (EMI).

RESULTS: CFS-NDs were no more likely to have IMH compared with HCs. Among the CFS-NDs, IMH was associated with more physical symptoms. For CFS-NDs, EMI added meaningfully beyond self-reported mental health in predicting physical symptoms.

CONCLUSION: Findings refute reducing CFS to somatization, but there is a subgroup of CFS whose lacking access to emotional distress is associated with heightened physical symptomatology.

Source: Bram AD, Gottschalk KA, Leeds WM. Chronic fatigue syndrome and the somatic expression of emotional distress: Applying the concept of illusory mental health to address the controversy. J Clin Psychol. 2018 Aug 28. doi: 10.1002/jclp.22692. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30152867
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Netflix Launches “Afflicted,” a Docuseries about Chronic Illnesses

On Friday, August 10, Netflix is launching a docuseries called “Afflicted.” The series chronicles the stories of seven chronically ill people who are searching for answers to their baffling symptoms, and for relief.

“Afflicted” features ME patient Jamison Hill, a former bodybuilder and personal trainer, who became sick at the age of 22. His disease progressed to its most severe form, leaving him unable to speak, eat solid food, or leave his bed. His moving personal essays have been published in Men’s Journal, The Washington Post, VICE, and the New York Times. He was featured in “Forgotten Plague,” a full-length documentary about myalgic encephalomyelitis. Jamison maintains a popular blog on ME.

Visit him at jamisonwrites.com.

You can watch the trailer HERE.

You can read an interview with Jamison HERE.

Association of mitochondrial DNA variants with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms

Abstract:

Earlier this year, we described an analysis of mitochondrial DNA (mtDNA) variants in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients and healthy controls. We reported that there was no significant association of haplogroups or singe nucleotide polymorphisms (SNPs) with disease status. Nevertheless, a commentary about our paper appeared (Finsterer and Zarrouk-Mahjoub. J Transl Med14:182, 2016) that criticized the association of mtDNA haplogroups with ME/CFS, a conclusion that was absent from our paper.

The aforementioned commentary also demanded experiments that were outside of the scope of our study, ones that we had suggested as follow-up studies. Because they failed to consult a published and cited report describing the cohorts we studied, the authors also cast aspersions on the method of selection of cases for inclusion. We reiterate that we observed statistically significant association of mtDNA variants with particular symptoms and their severity, though we observed no association with disease status.

You can read the rest of this rebuttal here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175376/

 

Source: Hanson MR, Gu Z, Keinan A, Ye K, Germain A, Billing-Ross P. Association of mitochondrial DNA variants with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms. J Transl Med. 2016 Dec 20;14(1):342. doi: 10.1186/s12967-016-1104-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175376/ (Full article)

 

Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients frequently complain of muscle fatigue and abnormally slow recovery, especially of the upper limb muscles during and after activities of daily living. Furthermore, disease heterogeneity has not yet been studied in relation to recovery of muscle function in CFS. Here, we examine recovery of upper limb muscle function from a fatiguing exercise in CFS patients with (CFS+FM) and without (CFS-only) comorbid fibromyalgia and compare their results with a matched inactive control group.

DESIGN: In this case-control study, 18 CFS-only patients, 30 CFS+FM patients and 30 healthy inactive controls performed a fatiguing upper limb exercise test with subsequent recovery measures.

RESULTS: There was no significant difference among the three groups for maximal handgrip strength of the non-dominant hand. A significant worse recovery of upper limb muscle function was found in the CFS+FM, but not in de CFS-only group compared with the controls (P < 0·05).

CONCLUSIONS: This study reveals, for the first time, delayed recovery of upper limb muscle function in CFS+FM, but not in CFS-only patients. The results underline that CFS is a heterogeneous disorder suggesting that reducing the heterogeneity of the disorder in future research is important to make progress towards a better understanding and uncovering of mechanisms regarding the nature of divers impairments in these patients.

© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

 

Source: Ickmans K, Meeus M, De Kooning M, Lambrecht L, Nijs J. Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia. Eur J Clin Invest. 2014 Feb;44(2):153-9. doi: 10.1111/eci.12201. Epub 2013 Dec 9. https://www.ncbi.nlm.nih.gov/pubmed/24313704

 

Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway

Abstract:

BACKGROUND: We aimed to compare patients reporting acute infection with those reporting no infection at onset of chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: This study includes 873 patients with CFS referred to a tertiary centre on average 4.8 years after symptom onset. Assessment was by both observer query and self-reports. Antibody analyses against infectious agents including Epstein-Barr virus and enterovirus were performed in a majority of patients.

RESULTS: Females comprised 75.3% of the patient group, and the mean age was 33 years. Initial infection was reported by 77%. There was no difference as to antibody analyses. Logistic regression showed that initial infection was independently associated with acute onset of fatigue, improvement of fatigue at referral, and the following symptoms at referral: fever, tender lymph nodes, and myalgia.

CONCLUSION: CFS patients with initial infection as a precipitating factor more often report acute onset of fatigue, more frequent accompanying symptoms, and more frequent improvement on referral than do patients without initial infection.

 

Source: Naess H, Sundal E, Myhr KM, Nyland HI. Postinfectious and chronic fatigue syndromes: clinical experience from a tertiary-referral centre in Norway. In Vivo. 2010 Mar-Apr;24(2):185-8. https://www.ncbi.nlm.nih.gov/pubmed/20363992

 

Chronic fatigue syndrome: traditional and community-based approaches to rehabilitation

Abstract:

Chronic fatigue syndrome (CFS) is a controversial condition defined by 6 months or more of unexplained fatigue, and at least four out of eight cognitive and physical symptoms. Over the past 2 decades, CFS has been the subject of significant debate regarding its definition, cause and recommended treatment. Because a cure for the syndrome has not yet been located, efforts to improve functioning and overall quality of life through rehabilitation represent the most practised form of treatment to date.

However, controversy remains as to which approach to rehabilitation is most effective for individuals with CFS. Interventions which take place within real-world environments and utilise community-based organizations such as centres for independent living offer a newly explored means of support and rehabilitation.

The present paper reviews a variety of approaches to rehabilitation for individuals with CFS, describing their applications with different types of patients, and providing critical commentary on the research methodologies used to evaluate them. Innovative community-based rehabilitation programmes and their outcomes are described as an alternative with some promise that may compliment more traditional approaches.

 

Source: Taylor RR. Chronic fatigue syndrome: traditional and community-based approaches to rehabilitation. Health Soc Care Community. 2004 May;12(3):171-85. http://www.ncbi.nlm.nih.gov/pubmed/19777707

 

The relationship between illness attributions and attributional style in Chronic Fatigue Syndrome

Abstract:

OBJECTIVE: To examine the relationship between illness attributions and general attributional style in Chronic Fatigue Syndrome (CFS).

METHOD: Participants with CFS answered questions on their explanation for their illness and completed the Attributional Style Questionnaire (parallel form).

RESULTS: Of the participants, 58.3% attributed their illness to predominantly physical factors. A significant relationship was found between the presence of a self-serving attributional style and illness attributions.

CONCLUSION: Illness attributions were associated with an individual’s general attributional style. It is suggested that illness attributions may be less important with regards prognosis than, for example, other variables which influence a person’s general view of the world.

 

Source: Creswell C, Chalder T. The relationship between illness attributions and attributional style in Chronic Fatigue Syndrome. Br J Clin Psychol. 2003 Mar;42(Pt 1):101-4. http://www.ncbi.nlm.nih.gov/pubmed/12675983