Tag: 2016

Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

Abstract:

It is unclear what key symptoms differentiate Myalgic Encephalomyelitis (ME) and Chronic Fatigue syndrome (CFS) from Multiple Sclerosis (MS). The current study compared self-report symptom data of patients with ME or CFS with those with MS. The self-report data is from the DePaul Symptom Questionnaire, and participants were recruited to take the questionnaire online.

Data were analyzed using a machine learning technique called decision trees. Five symptoms best differentiated the groups. The best discriminating symptoms were from the immune domain (i.e., flu-like symptoms and tender lymph nodes), and the trees correctly categorized MS from ME or CFS 81.2% of the time, with those with ME or CFS having more severe symptoms. Our findings support the use of machine learning to further explore the unique nature of these different chronic diseases

 

Source: Ohanian D, Brown A, Sunnquist M, Furst J, Nicholson L, Klebek L, Jason LA. Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis. Neurology (ECronicon). 2016;4(2):41-45. Epub 2016 Dec 19. https://www.ncbi.nlm.nih.gov/pubmed/28066845

 

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women

Abstract:

OBJECTIVE: Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms.

METHODS: Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index.

RESULTS: Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β=0.258, p=0.043), IL-6 (β=0.281, p=0.033), and tumor necrosis factor-alpha (TNF-α) (β=0.263, p=0.044). Worse sleep quality related to greater fatigue severity (β=0.395, p=0.003) and fatigue-related interference with daily activities (β=0.464, p<0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β=0.499, p<0.001, and β=0.556, p<0.001, respectively).

CONCLUSIONS: Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes.

Copyright © 2016 Elsevier B.V. All rights reserved.

 

Source: Milrad SF, Hall DL, Jutagir DR, Lattie EG, Ironson GH, Wohlgemuth W, Nunez MV, Garcia L, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women. J Neuroimmunol. 2017 Feb 15;303:43-50. doi: 10.1016/j.jneuroim.2016.12.008. Epub 2016 Dec 14. https://www.ncbi.nlm.nih.gov/pubmed/28038892

 

CDC Grand Rounds: Chronic Fatigue Syndrome – Advancing Research and Clinical Education

Abstract:

Chronic fatigue syndrome (CFS) is a complex and serious illness that is often misunderstood. Experts have noted that the terminology “chronic fatigue syndrome” can trivialize this illness and stigmatize persons who experience its symptoms (1). The name was coined by a group of clinicians convened by CDC in the late 1980s to develop a research case definition for the illness, which, at the time, was called chronic Epstein-Barr virus syndrome. The name CFS was suggested because of the characteristic persistent fatigue experienced by all those affected and the evidence that acute or reactivated Epstein-Barr virus infection was not associated with many cases (2).

However, the fatigue in this illness is striking and quite distinct from the common fatigue everyone experiences. A variety of other names have been used, including myalgic encephalomyelitis (ME), ME/CFS, chronic fatigue immune dysfunction, and most recently, systemic exertion intolerance disease (3). The lack of agreement about nomenclature need not be an impediment for advancing critically needed research and education. The term ME/CFS will be used in this article.

 

Source: Unger ER, Lin JS, Brimmer DJ, Lapp CW, Komaroff AL, Nath A, Laird S, Iskander J. CDC Grand Rounds: Chronic Fatigue Syndrome – Advancing Research and Clinical Education. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1434-1438. doi: 10.15585/mmwr.mm655051a4. https://www.cdc.gov/mmwr/volumes/65/wr/mm655051a4.htm (Full article)

 

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

Abstract:

Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor.

We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients.

The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients.

These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

 

Source: Fluge Ø, Mella O, Bruland O, Risa K, Dyrstad SE, Alme K, Rekeland IG, Sapkota D, Røsland GV, Fosså A, Ktoridou-Valen I, Lunde S, Sørland K, Lien K, Herder I, Thürmer H, Gotaas ME, Baranowska KA, Bohnen LM, Schäfer C, McCann A, Sommerfelt K, Helgeland L, Ueland PM, Dahl O, Tronstad KJ. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016 Dec 22;1(21):e89376. doi: 10.1172/jci.insight.89376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/ (Full article)

 

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)

 

Mitochondrial dysfunction in a family with psychosis and chronic fatigue syndrome

Abstract:

Mitochondrial impairment is hypothesized to be involved in chronic fatigue syndrome (CFS) and schizophrenia.

We performed a clinical, genetic and functional mitochondrial study in a family consisting of a female presenting schizophrenia in addition to CFS symptoms and her mother and older sister, both presenting with CFS. The three family members showed higher blood lactate levels, higher mitochondrial mass, lower mtDNA content and overall lower mitochondrial enzymatic activities and lower oxygen consumption capacities than healthy women.

This family presented mtDNA depletion; however, no mutation was identified neither in the mtDNA nor in the nuclear genes related with mtDNA depletion, even though C16179A and T16519A variants should be further studied.

Copyright © 2016. Published by Elsevier B.V.

 

Source: Torrell H, Alonso Y, Garrabou G, Mulet D, Catalán M, Valiente-Pallejà A, Carreño-Gago L, García-Arumí E, Montaña E, Vilella E, Martorell L. Mitochondrial dysfunction in a family with psychosis and chronic fatigue syndrome. Mitochondrion. 2016 Oct 27. pii: S1567-7249(16)30221-5. doi: 10.1016/j.mito.2016.10.007. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27989882

 

Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity

Abstract:

Myalgic encephalomyelitis (ME) is a complex, heterogeneous illness of unknown etiology. The search for biomarkers that can delineate cases from controls is one of the most active areas of ME research; however, little progress has been made in achieving this goal. In contrast to identifying biomarkers that are directly involved in the pathological process, an immunosignature identifies antibodies raised to proteins expressed during, and potentially involved in, the pathological process. Although these proteins might be unknown, it is possible to detect antibodies that react to these proteins using random peptide arrays.

In the present study, we probe a custom 125,000 random 12-mer peptide microarray with sera from 21 ME cases and 21 controls from the USA and Europe and used these data to develop a diagnostic signature. We further used these peptide sequences to potentially uncover the naturally occurring candidate antigens to which these antibodies may specifically react with in vivo.

Our analysis revealed a subset of 25 peptides that distinguished cases and controls with high specificity and sensitivity. Additionally, Basic Local Alignment Search Tool (BLAST) searches suggest that these peptides primarily represent human self-antigens and endogenous retroviral sequences and, to a minor extent, viral and bacterial pathogens.

 

Source: Singh S, Stafford P, Schlauch KA, Tillett RR, Gollery M, Johnston SA, Khaiboullina SF, De Meirleir KL, Rawat S, Mijatovic T, Subramanian K, Palotás A, Lombardi VC. Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity. Mol Neurobiol. 2016 Dec 15. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27981498

 

Epistemic injustice in healthcare encounters: evidence from chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) remains a controversial illness category. This paper surveys the state of knowledge and attitudes about this illness and proposes that epistemic concerns about the testimonial credibility of patients can be articulated using Miranda Fricker’s concept of epistemic injustice. While there is consensus within mainstream medical guidelines that there is no known cause of CFS/ME, there is continued debate about how best to conceive of CFS/ME, including disagreement about how to interpret clinical studies of treatments.

Against this background, robust qualitative and quantitative research from a range of countries has found that many doctors (and medical students) display uncertainty about whether CFS/ME is real, which may result in delays in diagnosis and treatment for patients. Strikingly, qualitative research evinces that patients with CFS/ME often experience suspicion by healthcare professionals, and many patients vocally oppose the effectiveness, and the conceptualisation, of their illness as psychologically treatable.

We address the intersection of these issues and healthcare ethics, and claim that this state of affairs can be explained as a case of epistemic injustice (2007). We find evidence that healthcare consultations are fora where patients with CFS/ME may be particularly vulnerable to epistemic injustice. We argue that the (often unintentional) marginalisation of many patients is a professional failure that may lead to further ethical and practical consequences both for progressive research into CFS/ME, and for ethical care and delivery of current treatments among individuals suffering from this debilitating illness.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

 

Source: Blease C, Carel H, Geraghty K. Epistemic injustice in healthcare encounters: evidence from chronic fatigue syndrome. J Med Ethics. 2016 Dec 5. pii: medethics-2016-103691. doi: 10.1136/medethics-2016-103691. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27920164

 

High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case Series

Abstract:

Structural and functional abnormalities of the prefrontal cortex seem to correlate with fatigue in patients with chronic fatigue syndrome (CFS). We consecutively applied facilitatory high-frequency repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) of seven CFS patients over three days. Five patients completed the 3-day protocol without any adverse events. For the other two patients, we had to reduce the stimulation intensity in response to mild adverse reactions. In most of the patients, treatment resulted in an improvement of fatigue symptoms. High-frequency rTMS applied over the DLPFC can therefore be a potentially useful therapy for CFS patients.

 

Source: Kakuda W, Momosaki R, Yamada N, Abo M. High-frequency rTMS for the Treatment of Chronic Fatigue Syndrome: A Case Series. Intern Med. 2016;55(23):3515-3519. Epub 2016 Dec 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216154/ (Full article)

 

Acupuncture and Moxibustion have Different Effects on Fatigue by Regulating the Autonomic Nervous System: A Pilot Controlled Clinical Trial

Abstract:

In order to investigate the different effects of acupuncture and moxibustion on chronic fatigue syndrome (CFS) and alterations in the autonomic nervous system by measuring heart rate variability (HRV).

Forty-five participants were recruited and randomly divided into 3 groups using a randomization schedule. The control group (CG, n = 15) and the acupuncture group (AG, n = 15) were treated by manipulation acupuncture, and the moxibustion group (MG, n = 15) was treated by indirect moxibustion. Primary outcomes were the scores of the Fatigue Assessment Instrument (FAI). Secondary outcomes were the HRV parameters which can reflect activity of the autonomic nervous system.

This trial considered both instantaneous changes and long-term effectiveness. FAI scores decreased after the 4th and 10th treatments in the 3 groups. The decrease in FAI in the MG was greater than that in the AG. Acupuncture was more effective in instantaneous changes of HRV and moxibustion in long-term aspects. Both acupuncture and moxibustion improved fatigue in CFS patients, but moxibustion was more effective.

The possible mechanism of the intervention may be through activation of the vagus nerve. Moxibustion was more effective than acupuncture in long-term treatment of CFS.

 

Source: Shu Q, Wang H, Litscher D, Wu S, Chen L, Gaischek I, Wang L, He W, Zhou H, Litscher G, Liang F. Acupuncture and Moxibustion have Different Effects on Fatigue by Regulating the Autonomic Nervous System: A Pilot Controlled Clinical Trial. Sci Rep. 2016 Nov 25;6:37846. doi: 10.1038/srep37846. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122953/ (Full article)