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/

Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis

Abstract:

To evaluate the magnitude of the difference in VO2peak between patients with Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) and apparently healthy controls, 7 databases (Cochrane, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus, Medline) were searched for articles published up to March 2018. Search terms included “chronic fatigue syndrom*”AND (“peak” OR “maxim*” OR “max”) AND (“oxygen uptake” OR “oxygen consumption” OR “VO2peak” or “VO2max”.

Eligibility criteria were adults>18 y with clinically diagnosed CFS/ME, with VO2peak measured in a maximal test and compared against an apparently healthy control group. The methodological quality of included studies was assessed using a modified Systematic Appraisal of Quality for Observational Research critical appraisal framework. A random effects meta-analysis was conducted on 32 cross-sectional studies (effects).

Pooled mean VO2peak was 5.2 (95% CI: 3.8-6.6) ml.kg-1min-1 lower in CFS/ME patients vs. healthy controls. Between-study variability (Tau) was 3.4 (1.5-4.5) ml.kg-1min-1 indicating substantial heterogeneity. The 95% prediction interval was -1.9 to 12.2 ml.kg-1min-1. The probability that the effect in a future study would be>the minimum clinically important difference of 1.1 ml.kg-1min-1 (in favour of controls) was 0.88 – likely to be clinically relevant. Synthesis of the available evidence indicates that CFS/ME patients have a substantially reduced VO2peak compared to controls.

Source: Franklin JD, Atkinson 1, Atkinson JM, Batterham AM. Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis. Int J Sports Med. 2018 Dec 17. doi: 10.1055/a-0802-9175. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30557887

A systematic review of enteric dysbiosis in chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is an illness characterised by profound and pervasive fatigue in addition to a heterogeneous constellation of symptoms. The aetiology of this condition remains unknown; however, it has been previously suggested that enteric dysbiosis is implicated in the pathogenesis of CFS/ME. This review examines the evidence currently available for the presence of abnormal microbial ecology in CFS/ME in comparison to healthy controls, with one exception being probiotic-supplemented CFS/ME patients, and whether the composition of the microbiome plays a role in symptom causation.

METHODS: EMBASE, Medline (via EBSCOhost), Pubmed and Scopus were systematically searched from 1994 to March 2018. All studies that investigated the gut microbiome composition of CFS/ME patients were initially included prior to the application of specific exclusion criteria. The association between these findings and patient-centred outcomes (fatigue, quality of life, gastrointestinal symptoms, psychological wellbeing) are also reported.

RESULTS: Seven studies that met the inclusion criteria were included in the review. The microbiome composition of CFS/ME patients was compared with healthy controls, with the exception of one study that compared to probiotic-supplemented CFS/ME patients. Differences were reported in each study; however, only three were considered statistically significant, and the findings across all studies were inconsistent. The quality of the studies included in this review scored between poor (< 54%), fair (54-72%) and good (94-100%) using the Downs and Black checklist.

CONCLUSIONS: There is currently insufficient evidence for enteric dysbiosis playing a significant role in the pathomechanism of CFS/ME. Recommendations for future research in this field include the use of consistent criteria for the diagnosis of CFS/ME, reduction of confounding variables by controlling factors that influence microbiome composition prior to sample collection and including more severe cases of CFS/ME.

Source: Du Preez S, Corbitt M, Cabanas H, Eaton N, Staines D, Marshall-Gradisnik S. A systematic review of enteric dysbiosis in chronic fatigue syndrome/myalgic encephalomyelitis. Syst Rev. 2018 Dec 20;7(1):241. doi: 10.1186/s13643-018-0909-0. https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-018-0909-0 (Full article)

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology

Abstract:

PURPOSE: Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP.

METHODS: Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure.

RESULTS: The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome.

CONCLUSION: IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.

Source: Hulens M, Rasschaert R, Vansant G, Stalmans I, Bruyninckx F, Dankaerts. The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology. J Pain Res. 2018 Dec 10;11:3129-3140. doi: 10.2147/JPR.S186878. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292399/ (Full article)

Stress, inflammation and natural treatments

Abstract:

Stress and inflammation have become the curses of our times and are the main pathogenetic factors in multiple diseases that are often comorbid and include allergies and asthma, eczema and psoriasis, fibromyalgia syndrome, mast cell activation syndrome, irritable bowel syndrome, myalgic encephalomyelitis/chronic fatigue syndrome and autism spectrum disorder (ASD). Unfortunately, there are no effective drugs.

Cross-talk between mast cells and microglia in the hypothalamus and amygdala could explain stress-induced inflammation. We recently showed that the “alarmin” IL-33 could play a major role through its synergistic action with the neuropeptide substance P to stimulate human mast cell secretion of the pro-inflammatory molecules IL-1β, TNF and VEGF. A new formulation using pure luteolin with Ashwagandha has now been developed and could be of significant benefit to patients suffering from these diseases.

Source: Theoharides TC, Kavalioti M. Stress, inflammation and natural treatments. J Biol Regul Homeost Agents. 2018 Nov-Dec;32(6):1345-1347. https://www.ncbi.nlm.nih.gov/pubmed/30574737

WE’RE PROVIDING HELP WHERE IT’S MOST NEEDED

“Through the financial help from AMMES I’ve been given the invaluable gift of time. Now that I’m not constantly experiencing fear and anxiety about being able to maintain a roof over my head, keep the lights on, or have any food to eat, I have some time to put any energy I do have towards healing. Thank you Erica, AMMES, and all its generous donors. Your gifts have enabled me to begin changing my mental outlook from despair to one of hope.” R in Colorado

Last March, the American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society (AMMES), a national non-profit, began fundraising for an ambitious, one-of-a-kind, project. We wanted to help severely ill patients who find themselves unable to pay their bills. The predicament of these patients has been known for a long time. Dr. Bell was reputed to have remarked that many of the people living in cars were CFS patients. The harsh reality is that for patients who have lost their income and have no other means of support, losing housing, being unable to pay for food, clothing, and medical expenses is a perpetual threat. It creates a situation in which patients become increasingly ill from the strain of trying to survive financially while struggling with a devastating illness.

Over the past six months, AMMES has given away over $25,000 to help these patients. The fund has paid for rent, clothing, food, utility bills, medical bills, phone bills, home care, and other basic necessities. The fund purchased a bed for a patient who had been sleeping on a couch, a co-pay for a wheelchair, and shoes for a patient who had only flip-flops after an abusive ex had destroyed all her clothing. By far the most common request is for rent. Several applicants have been on the verge of eviction. Nobody in this country should have to face living in a car, or on the street, or in a homeless shelter, let alone someone with a serious disease.

Who we help

Most of the people who apply for the program are severely ill, live alone, and have no financial support from family and friends. Some receive disability and food stamps, but rent and other necessities are seldom covered. In all cases, the applicants have been ill for many years, sometimes decades, with very little recognition.

When I asked one patient if she had experienced problems getting help, she replied “You are the first organization to help me, and you are the first to believe me.” This woman had been ill for over two decades. Her story has been repeated by everyone who has applied for the fund – years of getting little to no support, years of disbelief and hopelessness. This is the highly vulnerable population that AMMES’ financial crisis fund serves.

How it works

Applying for the financial crisis fund is fairly straightforward. Applicants fill out an application form with basic information, proof of financial necessity (this can be any form of government assistance, or an application for assistance or disability, even if it is denied), diagnosis of CFS, or something close to it, and documentation of what the grant is supposed to be for, so we know how much money to send. Once the application is received, the turnaround is one day.

Most people who have received funds have been astonished at the speed with which they receive support. As one patient explained, “Often, it would take days and sometimes a couple of weeks to complete all the paperwork and be told whether I qualified for assistance or not. During this time, I had no energy or time left to do anything else. Afterwards, I was so exhausted, all I could do was sleep. Many required that I provide proof of full-time work, which I could not do. All of the above did not understand the severity of the condition, or the devastating impact it was having in my life.”

AMMES does not make people jump through hoops. On the contrary, we get the funds to patients as soon as possible. We also we help patients fill out the application form if necessary. Some patients have significant cognitive problems, and may leave out important information. At times a single phone call is all that is necessary to verify information that is incomplete or ambiguous.

Find out more about the financial crisis fund here: https://ammes.org/ammes-financial-crisis-fund/

What AMMES needs

We want to help more people! Please make donations to our financial crisis fund! To keep it going for next year, we need $25,000. This will enable us to double the number of people we can help. We have not yet had to turn anyone away, and we hope that with enough contributions, we can help everyone who comes our way in 2019.

Something we also have great need of is a case worker. The crisis fund is good for emergencies, but what happens to these patients in the long-run? After this month’s rent is paid, what then? Someone with experience as a social worker or case worker could help patients meet long-term financial requirements. A case worker could also guide patients through the process of applying for government assistance. This can be a daunting task for people with cognitive problems and very little energy.

Please help! You can donate to AMMES here: https://ammes.org/donate/

AMMES is a 501(c)(3) nonprofit. Donations are tax deductible.

 

The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling disease characterized by unexplained incapacitating fatigue, accompanied by variable multi-systemic symptoms. ME/CFS causes a significant personal and public health burden, and urgently requires the coordination of research efforts to investigate its etiology and pathophysiology and to develop and validate sensitive and specific biomarkers to confirm diagnosis.

This narrative paper describes how people with ME/CFS, together with a multidisciplinary team of researchers, have established the UK ME/CFS Biobank (UKMEB), a unique research infrastructure specifically designed to expedite biomedical research into ME/CFS. We describe the journey that led to its conceptualization and operation, and how the resource has served as a model disease-specific biobank, aggregating human biospecimens alongside comprehensive health information on participants.

The UKMEB currently has data and samples from 600 donors including people with ME/CFS and a comparison group with multiple sclerosis and healthy controls. A longitudinal sub-cohort has been established of participants having follow-up assessments at multiple time-points. As an open resource for quality and ethical research into ME/CFS, biological samples and data have not only been analyzed within our research team but have also been shared with researchers across Europe, America and the Middle East. We continue to encourage researchers from academic and commercial sectors to access the UKMEB. Major steps have been taken and challenges remain; these include sustainability and expansion, and harmonization of processes to facilitate integration with other bioresources and databanks internationally.

Source: Lacerda EM, Mudie K, Kingdon CC, Butterworth JD, O’Boyle S, Nacul L. The UK ME/CFS Biobank: A Disease-Specific Biobank for Advancing Clinical Research Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Neurol. 2018 Dec 4;9:1026. doi: 10.3389/fneur.2018.01026.
eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288193/ (Full article)