Adolescent’s descriptions of fatigue, fluctuation and payback in chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): interviews with adolescents and parents

Abstract:

OBJECTIVE: As part of a larger qualitative study to explore outcomes important in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) and what improvements in fatigue and disability are key, interviews were undertaken with adolescents and their parents. This paper focuses on their descriptions of fatigue, fluctuation of symptoms and payback.

DESIGN AND SETTING: Semistructured qualitative interviews were undertaken between December 2014 and February 2015. Adolescents and parents were interviewed separately. Participants were recruited from a single specialist paediatric chronic fatigue service. Interviews were audio recorded, transcribed verbatim and analysed using thematic analysis.

PARTICIPANTS: We interviewed 21 adolescents and their parents (20 mothers and 2 fathers). The adolescents were aged between 12 and 17 years of age (mean age 14.4 years), mild to moderately affected by CFS/ME (not housebound) and the majority were female (16/21).

RESULTS: All adolescents with CFS/ME reported fatigue, a natural fluctuation of the condition, with good days and bad days as well as an increase in symptoms after activity (payback). However, adolescent’s descriptions of fatigue, symptoms and the associated impact on their daily lives differed. The variations included: fatigue versus a collection of symptoms, constant versus variable symptoms and variable symptom severity. There were differences between participants in the amount of activity taken to cause payback. The impact of fatigue and symptoms on function ranged from: limiting the duration and amount of leisure activities, struggling with daily activities (eg, self-care) to no activity (sedentary).

CONCLUSIONS: Fatigue, fluctuation of the condition and payback after activity are described by all adolescents with CFS/ME in this study. However, the individual experience in terms of how they describe it and the degree and impact varies.

Source: Parslow RM, Anderson N, Byrne D, Shaw A, Haywood KL, Crawley E. Adolescent’s descriptions of fatigue, fluctuation and payback in chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): interviews with adolescents and parents. BMJ Paediatr Open. 2018 Dec 4;2(1):e000281. doi: 10.1136/bmjpo-2018-000281. eCollection 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307594/ (Full article)

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the label given to a syndrome that can include long-term flu-like symptoms, profound fatigue, trouble concentrating, and autonomic problems, all of which worsen after exertion. It is unclear how many individuals with this diagnosis are suffering from the same condition or have the same underlying pathophysiology, and the discovery of biomarkers would be clarifying.

The name “myalgic encephalomyelitis” essentially means “muscle pain related to central nervous system inflammation” and many efforts to find diagnostic biomarkers have focused on one or more aspects of neuroinflammation, from periphery to brain. As the field uncovers the relationship between the symptoms of this condition and neuroinflammation, attention must be paid to the biological mechanisms of neuroinflammation and issues with its potential measurement.

The current review focuses on three methods used to study putative neuroinflammation in ME/CFS: (1) positron emission tomography (PET) neuroimaging using translocator protein (TSPO) binding radioligand (2) magnetic resonance spectroscopy (MRS) neuroimaging and (3) assays of cytokines circulating in blood and cerebrospinal fluid. PET scanning using TSPO-binding radioligand is a promising option for studies of neuroinflammation. However, methodological difficulties that exist both in this particular technique and across the ME/CFS neuroimaging literature must be addressed for any results to be interpretable.

We argue that the vast majority of ME/CFS neuroimaging has failed to use optimal techniques for studying brainstem, despite its probable centrality to any neuroinflammatory causes or autonomic effects. MRS is discussed as a less informative but more widely available, less invasive, and less expensive option for imaging neuroinflammation, and existing studies using MRS neuroimaging are reviewed. Studies seeking to find a peripheral circulating cytokine “profile” for ME/CFS are reviewed, with attention paid to the biological and methodological reasons for lack of replication among these studies.

We argue that both the biological mechanisms of cytokines and the innumerable sources of potential variance in their measurement make it unlikely that a consistent and replicable diagnostic cytokine profile will ever be discovered.

Source: Michael B. VanElzakker, Sydney A. Brumfield and Paula S. Lara Mejia. Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Front. Neurol., 10 January 2019 | https://doi.org/10.3389/fneur.2018.01033 https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full?fbclid=IwAR3KxhofUaLakZRPNiyBliNHSlJvUOdsVqVf5cED_i6o5gF9MCbWxpeS298#h7 (Full article)

Perceptions of chronic fatigue syndrome in the emergency department

Press release: January 10, 2019, Georgetown University Medical Center. Findings from a novel online questionnaire of people with chronic fatigue syndrome (CFS) who rated their perceptions of care in a hospital’s emergency department suggest the majority of these patients do not receive proper care, say researchers from Georgetown University Medical Center.

The study, published in the journal Open Access Emergency Medicine, is the first known investigation of the presentation of CFS in the emergency department (ED). The findings highlight a profound lack of understanding of CFS by health care workers, says the study’s senior investigator, allergist and immunologist James N. Baraniuk, MD, a professor of medicine at Georgetown who treats people with CFS.

He says two-thirds of respondents report they either would not go to an ED because they believed they wouldn’t be taken seriously, or had previous unsatisfactory experiences. Only a third of patients in the survey said they received appropriate treatment in the ED.

“The high proportion of patients who were basically told ‘It is all in your head’ by ED staff indicates that there is much misunderstanding and misgivings about the diagnosis of CFS. These patients should feel they are respected and that they can receive thorough care when they feel sick enough to go to an ED,” he says.

Baraniuk says more training is needed for ED staff and physicians to better understand the disorder.

The 282 participants in the survey all had physician-diagnosed CFS. Participants were predominantly women (87 percent), educated (70 percent had at least a college degree), and had a primary care physician (93 percent).

From the survey, researchers determined that:

Only 59 percent of CFS patients had gone to an ED. In this group, 42 percent were dismissed as having psychosomatic complaints.

33 percent had symptoms consistent with a condition known as orthostatic intolerance, which occurs when a person feels faint when standing or sitting upright because not enough blood is reaching the brain and heart. The symptoms only improve when a person lies down.

CFS patients who went to the ED collectively rated caregivers’ knowledge about CFS at 3.6 on a 10-point scale.

41 percent of CFS respondents did not go to the ED when ill because they felt nothing could be done or they would not be taken seriously.

“An already-available CFS Symptom Severity Questionnaire can be used in the ED to assist with the diagnosis of CFS, and to differentiate exacerbations of CFS symptoms from medical emergencies such as heart attacks or infections,” Baraniuk says.

The number one reason for going to the ED was orthostatic intolerance.

“This is of importance because it provides a starting point for diagnosis and treatment by ED physicians,” Baraniuk says. “This condition is something that can be readily addressed by ED caregivers. There is a real need for physician education that will improve their efficiency in identifying and treating CFS and in distinguishing CFS symptoms from other diseases in the exam room.”

“We found that intolerance of exercise and intolerance to alcohol consumption were common to those diagnosed with CFS so this may help distinguish CFS from other conditions,” says study co-author Christian R. Timbol, MD, who worked with Baraniuk as a medical student before becoming an emergency medicine resident physician at Thomas Jefferson University Hospital in Philadelphia.

Chronic fatigue syndrome affects between 836,000 and 2.5 million Americans, according to a National Academy of Medicine review of over 9,000 articles covering 64 years of research.

This reviewers renamed the syndrome “Systemic Exertion Intolerance Disease” to emphasize the disability, post exertional malaise or exhaustion that follows mild exertion, cognitive dysfunction and orthostatic intolerance (blood pressure and heart rate changes that cause dizziness) that are the salient features of the illness.

Journal Reference: Christian Timbol, James Baraniuk. Chronic fatigue syndrome in the emergency department. Open Access Emergency Medicine, 2019; Volume 11: 15 DOI: 10.2147/OAEM.S176843 https://www.dovepress.com/chronic-fatigue-syndrome-in-the-emergency-department-peer-reviewed-article-OAEM

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy

Abstract:

Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis /ChronicFatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain.

Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI),lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups.

Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

Source: Christina Mueller, Joanne C. Lin, Sulaiman Sheriff, Andrew A. Maudsley, Jarred W. Younger. Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy. Brain Imaging and Behavior. https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA%3D%3D (Full article)

Estimating Prevalence, Demographics and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning

Abstract:

Techniques of data mining and machine learning were applied to a large database of medical and facility claims from commercially insured patients to determine the prevalence, gender demographics, and costs for individuals with provider-assigned diagnosis codes for myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). The frequency of diagnosis was 519 – 1,038/100,000 with the relative risk of females being diagnosed with ME or CFS compared to males 1.238 and 1.178, respectively. While the percentage of women diagnosed with ME/CFS is higher than the percentage of men, ME/CFS is not a “woman’s disease.” Thirty-five to forty percent of diagnosed patients are men. Extrapolating from this frequency of diagnosis and based on the estimated 2017 population of the United States, a rough estimate for the number of patients who may be diagnosed with ME or CFS in the U.S. is 1.7 million to 3.38 million.

Patients diagnosed with CFS appear to represent a more heterogeneous group than those diagnosed with ME. A machine learning model based on characteristics of individuals diagnosed with ME was developed and applied, resulting in a predicted prevalence of 857/100,000 (p>0.01), or roughly 2.8 million in the U.S.

Average annual costs for individuals with a diagnosis of ME or CFS were compared with those for lupus (all categories) and multiple sclerosis (MS), and found to be 50% higher for ME and CFS than for lupus or MS, and three to four times higher than for the general insured population.

A separate aspect of the study attempted to determine if a diagnosis of ME or CFS could be predicted based on symptom codes in the insurance claims records. Due to the absence of specific codes for some core symptoms, we were unable to validate that the information in insurance claims records is sufficient to identify diagnosed patients or suggest that a diagnosis of ME or CFS should be considered based solely on looking for presence of those symptoms.

These results show that a prevalence rate of 857/100,000 for ME/CFS is not unreasonable; therefore, it is not a rare disease, but in fact a relatively common one.

Source: Ashley Valdez, Elizabeth E. Hancock, Seyi Adebayo, David Kiernicki, Daniel Proskauer, John R. Attewell, Lucinda Bateman, Alfred DeMaria, Jr, Charles W. Lapp, Peter C. Rowe and Charmian Proskauer. Estimating Prevalence, Demographics and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning. Front. Pediatr. | doi: 10.3389/fped.2018.00412  https://www.frontiersin.org/articles/10.3389/fped.2018.00412/full (Full article)

Multidimensional Comparison of Cancer-Related Fatigue and Chronic Fatigue Syndrome: The Role of Psychophysiological Markers

Abstract:

OBJECTIVE: The present study compared cancer-related fatigue (CRF) and chronic fatigue syndrome (CFS) using multidimensional measurements with the aim of better understanding characteristics and exploring markers of two similar fatigue syndromes.

METHODS: Twenty-five patients with CRF and twenty patients with CFS completed questionnaires, including the Fatigue Severity Scale (FSS), Hospital Anxiety Depression Scale (HADS), Perceived Stress Scale (PSS), and Pittsburgh Sleep Quality Index (PSQI). Additionally, levels of high sensitivity C-reactive protein (hs-CRP), heart rate variability (HRV), and electroencephalography (EEG) were obtained. Neurocognitive functioning was also evaluated.

RESULTS: Both groups showed comparable levels of psychological variables, including fatigue. Compared to CFS subjects, CRF patients had significantly higher hs-CRP levels and a reduced HRV-index. The within-group analyses revealed that the FSS score of the CRF group was significantly related to scores on the HADS-anxiety, HADS-depression, and PSQI scales. In the CFS group, FSS scores were significantly associated with scores on the PSS and the absolute delta, theta, and alpha powers in frontal EEG.

CONCLUSION: Findings indicate that different pathophysiological mechanisms underlie CFS and CRF. Inflammatory marker and HRV may be potential biomarkers for distinguishing two fatigue syndromes and frontal EEG parameters may be quantitative biomarkers for CFS.

Source: Park HY, Jeon HJ, Bang YR, Yoon IY. Multidimensional Comparison of Cancer-Related Fatigue and Chronic Fatigue Syndrome: The Role of Psychophysiological Markers. Psychiatry Investig. 2019 Jan 7. doi: 10.30773/pi.2018.10.26. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30605994

Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome

[Editor’s comment: Conspicuously absent from the reference section in this paper is the pioneering work of L. O. Simpson. In 1989 Dr. Leslie O. Simpson, a New Zealand pathologist, discovered that the blood of people with ME/CFS tends to have a higher proportion of cup-shaped red blood cells. (Simpson, L.O. “Nondiscocyte Erythrocytes in Myalgic Encephalomyelitis.” New Zealand Medical Journal 2(864):126-127,1989.) Cup-shaped cells are more difficult to squeeze through small capillaries than disc-shaped cells, making it harder for blood to oxygenate capillary-dependent tissues. In further investigations, Dr. Simpson also observed similar changes in red blood cell morphology in other diseases. He noted that red blood cell shape can change from minute to minute. A summary of Dr. Simpson’s work on red blood cell morphology in ME/CFS can be found HERE.]

Abstract:

BACKGROUND: Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS.

METHODS: We used a custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls.

RESULTS AND CONCLUSION: We observed from various measures of deformability that the RBCs isolated from ME/CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test

Source: Saha KA, Schmidt RB, Wilhelmy J, Nguyen V, Abugherir A, Do KJ, Nemat-Gorgani M, Davis WR, Ramasubramanian KA. Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome.Clin Hemorheol Microcirc. 2018 Dec 28. doi: 10.3233/CH-180469. [Epub ahead of print]  https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch180469 (Full article)

Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results

Abstract:

Introduction: Conflicting data have been published on the reduction of circulating blood volume in adults with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The aim of the present study was to compare blood volumes based on the presence or absence of orthostatic symptoms.

Methods and results: Twenty consecutive adults with ME/CFS participated in the study. All underwent dual isotope blood volume measurement and were evaluated for a clinical suspicion of orthostatic intolerance (OI). The mean age was 34 (10) years, and median duration of disease was 7.5 (6-10) years. The mean (SD) absolute blood volume was 59 (8) ml/kg, a value -11 (7) ml/kg below the reference blood volume. Of the 12 patients, 4 had no OI and 8 had a clinical suspicion of OI. In 8 patients with OI, absolute blood volumes were significantly lower than for the 4 without OI (56 [2] vs. 66 [5]; p < 0.05) as were the differences between the measured and the reference blood volume (-14 [2]; vs. -4 [3]; p < 0.02).

Conclusions: Adults with ME/CFS had a significantly lower blood volume if they had a clinical suspicion of OI compared to those without a clinical suspicion of OI, as well as a significantly lower blood volume compared to the expected value. The data suggest that accounting for symptoms of OI could enhance the detection of the subset with reduced blood volume.

Source: van Campen CLMC1, Rowe PC2, Visser FC1. Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results. Front Pediatr. 2018 Nov 15;6:352. doi: 10.3389/fped.2018.00352. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262290/ (Full article)

Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach

Abstract:

Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported.

In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l-carnitine, l-tryptophan, essential fatty acids, and coenzyme Q10) appear to be important in the severity and exacerbation of CFS symptoms. This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients.

Source: Bjørklund G, Dadar M, Pen JJ, Chirumbolo S, Aaseth J. Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach. Biomed Pharmacother. 2019 Jan;109:1000-1007. doi: 10.1016/j.biopha.2018.10.076. Epub 2018 Nov 5.  https://www.sciencedirect.com/science/article/pii/S0753332218342987?via%3Dihub (Full article)

Severe posterior hypometabolism but normal perfusion in a patient with CFS/ME

Abstract:

Chronic fatigue syndrome/myalgic encephalitis (CFS/ME) is a complex clinical condition defined by prolonged severe fatigue without medical or psychiatric causes, and by a subset of symptoms that mostly includes arthromyalgias, cognitive impairment, sleeping troubles, and unusual headaches [1]. Previous FDG-PET studies showed unspecific patterns of hypometabolism in the frontal and cingulate cortex in half of CFS patients compared to healthy controls [2].

We present 18F-FDG PET/MRI findings in a 21-year-old woman who fulfilled the criteria of CFS with a Fukuda score of 4. PET images (a) show severe and extensive hypometabolism in the posterior cortical regions (precuneus, parietal, temporal, and occipital), amygdalo-hippocampal complexes, and cerebellum. No structural abnormalities were found on T1 MPRAGE (b) or T2 FLAIR (c) MRI sequences. Interestingly, cerebral blood flow evaluated with Gadolinium first-pass method (d) was not decreased in these regions.

This peculiar pattern of hypometabolism was recently described in a large series of patients with aluminium-induced macrophagic myofasciitis (MMF) followed in our reference center [3]. However, the present patient had negative muscular biopsies for MMF. Neuropsychological testing showed severe impairment of short-term memory (immediate and working memory) in visual modality, and weakness of visual selective attention and executive functions, which are concordant with the pattern of hypometabolism. Finally, perfusion-metabolism uncoupling suggests that posterior hypometabolism may not be related to neuronal loss such as in degenerative diseases [4], but rather to an inflammatory or immunological process [5]. Further studies are warranted to investigate metabolism and perfusion using simultaneous PET/MRI in larger groups of patients with CFS/ME.

Source: S. Sahbai & P. Kauv & M. Abrivard & P. Blanc-Durand & M. Aoun-Sebati & B. Emsen & A. Luciani & J. Hodel & F-J. Authier & E. Itti. Severe posterior hypometabolism but normal perfusion in a patient with chronic fatigue syndrome/myalgic encephalomyelitis revealed by PET/MRI. Eur J Nucl Med Mol Imaging. 2018 Dec 14. doi: 10.1007/s00259-018-4229-3. [Epub ahead of print] https://forums.phoenixrising.me/index.php?threads/severe-posterior-hypometabolism-but-normal-perfusion-in-a-patient-with-cfs-me.62543/