Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey

Abstract:

BACKGROUND: 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.

OBJECTIVES: To describe symptoms associated with and the time course of PEM.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Source:  Chu L, Valencia IJ, Garvert DW, Montoya JG. Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey. PLoS One. 2018 Jun 1;13(6):e0197811. doi: 10.1371/journal.pone.0197811. eCollection 2018. (Full study)

Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome

Abstract:

Prolonged, disabling fatigue is the hallmark of chronic fatigue syndrome (CFS). Previous neuroimaging studies have provided evidence for nervous system involvement in CFS etiology, including perturbations in brain structure/function. In this arterial spin labeling (ASL) MRI study, we examined variability in cerebral blood flow (CBFV) and heart rate (HRV) in 28 women: 14 with CFS and 14 healthy controls. We hypothesized that CBFV would be reduced in individuals with CFS compared to healthy controls, and that increased CBFV and HRV would be associated with lower levels of fatigue in affected individuals.

Our results provided support for these hypotheses. Although no group differences in CBFV or HRV were detected, greater CBFV and more HRV power were both associated with lower fatigue symptom severity in individuals with CFS. Exploratory statistical analyses suggested that protective effects of high CBFV were greatest in individuals with low HRV. We also found novel evidence of bidirectional association between the very high frequency (VHF) band of HRV and CBFV. Taken together, the results of this study suggest that CBFV and HRV are potentially important measures of adaptive capacity in chronic illnesses like CFS. Future studies should address these measures as potential therapeutic targets to improve outcomes and reduce symptom severity in individuals with CFS.

Source: Boissoneault J, Letzen J, Robinson M, Staud R. Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome. Brain Imaging Behav. 2018 May 31. doi: 10.1007/s11682-018-9897-x. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29855991

A Glimpse into Dr. Ron Davis’ Talk in London

From Open Medicine Foundation.
June 1, 2018

Dear Friends,

I prepared this statement for Ashley Haugen to read yesterday at the Western Massachusetts  Department of Public Health screening of Unrest. This is new information from the Severely ill Patient Study (SIPS) that I also presented in London:

“We have made considerable progress in analyzing the data from the severely ill patient study. This has taken some time because we have only had one bioinformatic scientist analyzing the massive amount of data.

We have found that there are a considerable number of mutations that are more common in ME/CFS patients than in healthy controls. This would suggest that these mutations make a patient more susceptible to having ME/CFS. It could also indicate that some of the mutations are responsible for the severity of the patients we studied. We also see a large number of metabolomic changes that have been previously seen in less severe patients. These metabolomic differences between healthy controls and our severely ill patients are often much bigger than in studies with less severe patients. A more detailed analysis of this data may aid us in developing treatments.

One area we are currently studying using the genetic and metabolomic data is the possibility there may be one or more metabolic traps. This is a metabolic state that a patient can develop, possibly caused by physical stress such as infection. Once a patient is in this state they cannot easily get out by rest.

We are conducting system biology and pathway analysis that shows that a metabolic trap is possible, and that some of the observed mutations make it more likely. If this is the case we should be able to push the patients out of this state by a specific metabolic intervention. We are very hopeful that this could be a one time treatment, take only a few days, and be relatively inexpensive.”

Sending greetings from London,

Ronald W. Davis, PhD
Director, OMF ME/CFS Scientific Advisory Board
Director, Stanford Genome Technology Center

Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients

Abstract:

Chronic fatigue syndrome (CFS) is a disorder associated with fatigue, pain, and structural/functional abnormalities seen during magnetic resonance brain imaging (MRI). Therefore, we evaluated the performance of structural MRI (sMRI) abnormalities in the classification of CFS patients versus healthy controls and compared it to machine learning (ML) classification based upon self-report (SR). Participants included 18 CFS patients and 15 healthy controls (HC). All subjects underwent T1-weighted sMRI and provided visual analogue-scale ratings of fatigue, pain intensity, anxiety, depression, anger, and sleep quality. sMRI data were segmented using FreeSurfer and 61 regions based on functional and structural abnormalities previously reported in patients with CFS. Classification was performed in RapidMiner using a linear support vector machine and bootstrap optimism correction.

We compared ML classifiers based on (1) 61 a priori sMRI regional estimates and (2) SR ratings. The sMRI model achieved 79.58% classification accuracy. The SR (accuracy = 95.95%) outperformed both sMRI models. Estimates from multiple brain areas related to cognition, emotion, and memory contributed strongly to group classification. This is the first ML-based group classification of CFS. Our findings suggest that sMRI abnormalities are useful for discriminating CFS patients from HC, but SR ratings remain most effective in classification tasks.

Source: Sevel LS, Boissoneault J, Letzen JE, Robinson ME, Staud R. Structural brain changes versus self-report: machine-learning classification of chronic fatigue syndrome patients. Exp Brain Res. 2018 May 30. doi: 10.1007/s00221-018-5301-8. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29846797

Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome

Abstract:

Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear. The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis.

Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ± 5.4 vs 6.1 nmol/L ± 6.3, p = 0.036). Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ± 2.1 vs 4.3 pg/mg ± 1.8, p = 0.062). After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022). This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

Source: Roerink ME, Roerink SHPP, Skoluda N, van der Schaaf ME, Hermus ARMM, van der Meer JWM, Knoop H, Nater UM. Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome. Horm Behav. 2018 May 25. pii: S0018-506X(17)30569-X. doi: 10.1016/j.yhbeh.2018.05.016. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29807037

Cortical Hypoactivation During Resting EEG Suggests Central Nervous System Pathology in Patients with Chronic Fatigue Syndrome

Abstract:

We investigated cognitive impairment to executive function in 50 patients with chronic fatigue syndrome (CFS) and 50 matched healthy controls (HC). Resting state EEG was collected from 19 scalp locations during a 3 minute, eyes-closed condition. Current densities were localized using exact low-resolution electromagnetic tomography (eLORETA). The Multidimensional Fatigue Inventory (MFI-20) and the Fatigue Severity Scale (FSS) were administered to all participants. Independent t-tests and linear regression analyses were used to evaluate group differences in current densities, followed by statistical non-parametric mapping (SnPM) correction procedures.

Significant differences were found in the delta (1-3 Hz) and beta-2 (19-21 Hz) frequency bands. Delta sources were found predominately in the frontal lobe, while beta-2 sources were found in the medial and superior parietal lobe. Left-lateralized, frontal delta sources were associated with a clinical reduction in motivation. The implications of abnormal cortical sources in patients with CFS are discussed.

Source: Zinn MA, Zinn ML, Valencia I, Jason LA, Montoya JG. Cortical Hypoactivation During Resting EEG Suggests Central Nervous System Pathology in Patients with Chronic Fatigue Syndrome. Biol Psychol. 2018 May 23. pii: S0301-0511(18)30407-1. doi: 10.1016/j.biopsycho.2018.05.016. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29802861

Comparison of Fatigue Severity and Quality of Life between Unexplained Fatigue Patients and Explained Fatigue Patients

Abstract:

BACKGROUND: Recently, despite the high prevalence of fatigue in patients, there is a lack of research on the quality of life (QoL) in unexplained fatigue patients, indicating that they are not properly diagnosed and treated. The aim of this study was to compare fatigue severity and QoL between patients with explained and unexplained fatigue.

METHODS: The study consisted of 200 Korean adults who complained of fatigue without underlying disease. Fatigue Severity Scale, Short Form Health Survey-36 version 2 (SF-36v2), and Beck Depression Inventory-II (BDI-II) self-questionnaires were administered. Participants were dichotomized to two groups, namely, patients with unexplained or explained fatigue, sorted according to laboratory examination results. The chi-square test, t-test, and Wilcoxon rank-sum test were used, and analysis of covariance was calculated after adjusting for age, sex, body mass index, smoking status, and physical component summary (PCS) of SF-36v2 or BDI-II.

RESULTS: PCS of SF-36v2 between the two groups showed significant difference. Compared to patients with explained fatigue, those with unexplained fatigue showed lower physical component scores of QoL.

CONCLUSION: QoL of patients with unexplained fatigue could largely diminish than those with explained fatigue. The primary clinician should be aware of poor QoL in patients with unexplained fatigue to identify who is in need of more attention and intervention.

Source: Yoo EH, Choi ES, Cho SH, Do JH, Lee SJ, Kim JH. Comparison of Fatigue Severity and Quality of Life between Unexplained Fatigue Patients and Explained Fatigue Patients. Korean J Fam Med. 2018 May;39(3):180-184. doi: 10.4082/kjfm.2018.39.3.180. Epub 2018 May 18.  http://kjfm.or.kr/journal/view.php?doi=10.4082/kjfm.2018.39.3.180 (Full article)

Cardiac sympathetic innervation associates with autonomic dysfunction in chronic fatigue syndrome – a pilot study

Despite hemodynamic abnormalities being well documented in chronic fatigue syndrome (CFS), it remains unclear the nature of the underlying autonomic nervous system problems that underpin these findings. Studies performed in subgroups of those with CFS suggest cardiac sympathetic denervation.

Meta-iodo-benzylguanidine (MIBG) imaging provides a quantitative measure of cardiac sympathetic innervation. Clinically, cardiac MIBG scanning is used to estimate local myocardial sympathetic nerve damage in heart disease and dysautonomia, particularly abnormalities arising due to sympathetic innervation [1,2]. In this study, we explored potential mechanisms that underpin the autonomic abnormalities seen in CFS using I125 MIBG participants that fulfilled Fukuda diagnostic criteria for CFS [3]. Participants were excluded if screened positive for a major depressive episode (Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders). Fatigue was measured using the Fatigue Impact Scale (FIS).

Read the rest of this article HERE.

Source: Petrides G, Zalewski P, McCulloch D, Maclachlan L, Finkelmeyer A, Hodgson T, Blamire A, Newton JL. Cardiac sympathetic innervation associates with autonomic dysfunction in chronic fatigue syndrome – a pilot study. Fatigue. 2017 May 4;5(3):184-186. doi: 10.1080/21641846.2017.1322235. eCollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942146/ (Full article)

Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort

Abstract:

OBJECTIVE/BACKGROUND: 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.

PATIENTS/METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Source: Collin SM, Norris T, Gringras P, Blair PS, Tilling K, Crawley E. Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort. Sleep Med. 2018 Jun;46:26-36. doi: 10.1016/j.sleep.2018.01.005. Epub 2018 Jan 31.  https://www.ncbi.nlm.nih.gov/pubmed/29773208

Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn

Abstract:

Recently, the Dutch Health Council published their advisory report on Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) which is meant to determine the medical policy with regard to ME in the Netherlands. The Health Council briefly discusses several diagnostic criteria and proposes to use new diagnostic criteria for “ME/CFS” in research and clinical practice in the future. The advisory report then summarizes organic abnormalities observed in the last decades and concludes that “ME/CFS” is a “serious, chronic, multisystem disease”.

According to the Health Council there are no curative treatments for “ME/CFS”, due to lack of knowledge, but specific medication could bring symptomatic relief. The Health Council recommends conducting more research, to (re)educate medical professionals about “ME/CFS”, to appoint three academic expertise centres, which will install a care network for patients, and to fairly judge the limitations (disability) of patients when they apply for a disability income, medical aid and care. The advisory report was welcomed by many patients, because it puts an end to the dominance of the (bio)psychosocial explanatory model and seems to offer a perspective of improving the situation of patients. However, the starting point of the advisory report, a new definition of “ME/CFS”, will have serious (long-lasting) consequences for patients and researchers.

Source: Twisk F. Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn. Diagnostics (Basel). 2018 May 16;8(2). pii: E34. doi: 10.3390/diagnostics8020034. http://www.mdpi.com/2075-4418/8/2/34 (Full article)