Over 13,000 people in Wales could have ME and over 240,000 in the UK.
Find out more about research into the ME brain:
WAMES booklet: The ME brain
Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome? by Fiona Newberry, Shen-Yuan Hsieh, Tom Wileman, Simon R. Carding in Clinical Science Vol 135, #5, pp 523-542 [Published online March 9, 2018]
Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms.
Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome.
Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes.
However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies.
This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
Association of chronic fatigue syndrome with premature telomere attrition, by Mangalathu S. Rajeevan, Janna Murray, Lisa Oakley, Jin-Mann S. Lin, Elizabeth R. Unger in Journal of Translational Medicine Vol 16, #1, p 44 [Published: 27 February 2018]
Backgro
und:
Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a severely debilitating condition of unknown etiology. The symptoms and risk factors of ME/CFS share features of accelerated aging implicated in several diseases. Using telomere length as a marker, this study was performed to test the hypothesis that ME/CFS is associated with accelerated aging.
Methods:
Participant (n=639) data came from the follow-up time point of the Georgia CFS surveillance study. Using the 1994 CFS Research Case Definition with questionnaire-based subscale thresholds for fatigue, function, and symptoms, participants were classified into four illness groups: CFS if all criteria were met (n=64), CFS-X if CFS with exclusionary conditions (n=77), ISF (insufficient symptoms/fatigue) if only some criteria were met regardless of exclusionary conditions (n=302), and NF (non-fatigued) if no criteria and no exclusionary conditions (n=196).
Relative telomere length (T/S ratio) was measured using DNA from whole blood and real-time PCR. General linear models were used to estimate the association of illness groups or T/S ratio with demographics, biological measures and covariates with significance set at p<0.05.
Results:
The mean T/S ratio differed significantly by illness group (p=0.0017); the T/S ratios in CFS (0.90 p/m 0.03) and ISF (0.94 p/m 0.02) were each significantly lower than in NF (1.06 p/m 0.04). Differences in T/S ratio by illness groups remained significant after adjustment for covariates of age, sex, body mass index, waist-hip ratio, post-exertional malaise and education attainment.
Telomere length was shorter by 635, 254 and 424 base pairs in CFS, CFS-X and ISF, respectively, compared to NF. This shorter telomere length translates to roughly 10.1-20.5, 4.0-8.2 and 6.6-13.7 years of additional aging in CFS, CFS-X and ISF compared to NF respectively. Further, stratified analyses based on age and sex demonstrated that the association of ME/CFS with short telomeres is largely moderated by female subjects<45 years old.
Conclusions:
This study found a significant association of ME/CFS with premature telomere attrition that is largely moderated by female subjects<45 years old. Our results indicate that ME/CFS could be included in the list of conditions associated with accelerated aging. Further work is needed to evaluate the functional significance of accelerated aging in ME/CFS.
More info: The association of Chronic Fatigue Syndrome with premature telomere attrition
Investigation of mast cell toll-like receptor 3 in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Systemic Mastocytosis participants using the novel application of autoMACS magnetic separation and flow cytometry, by C Balinas, T Nguyen, S Johnston, P Smith, D Staines, S Marshall-Gradisnik in Asian Pac J Allergy Immunol. 2017 Dec 10 [Epub ahead of print]
BACKGROUND:
Viral infections and hypersensitivities are commonly reported by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. Mast Cells (MC) uniquely mediate type 1 hypersensitivities and resolve viral infections via toll-like receptor 3 (TLR3).
OBJECTIVE:
To characterise and compare mast cell progenitors (MCPs) in CFS/ME participants with a known MC disorder, Systemic mastocytosis (SM), and secondly, to investigate the role of MC TLR3 in CFS/ME participants following Polyinosinic:polycytidylic acid (Poly I:C) stimulation.
METHODS:
A total of 11 International Consensus Criteria defined CFS/ME participants (40.42 ± 10.31), 9 World Health Organisation defined systemic mastocytosis (SM) participants (47.00 ± 10.37) and 12 healthy controls (HC) (36.36 ± 9.88) were included. Following autoMACS magnetic separation, CD117+/Lin-MCPs were stimulated with Poly I:C for 24hr. MCP purity (CD117 and Lin2), maturity (CD34 and FcεRI), interaction receptors and ligands (CD154 and HLA-DR), and SM-specific (CD2 and CD25) markers were measured using flow cytometry.
RESULTS:
There was a significant decrease in HLA-DR+/CD154- expression between CFS/ME and SM groups pre and post Poly I:C stimulation. There were no significant differences in maturity MCPs, CD154, and CD2/CD25 expression between groups pre and post Poly I:C stimulation.
CONCLUSION:
This pilot investigation provides a novel methodology to characterise MCPs in a rapid, inexpensive and less invasive fashion.
We report a significant decrease in HLA-DR+/CD154- expression between CFS/ME and SM participants, and an observed increase in HLA-DR-/CD154+ expression post Poly I:C stimulation in CFS/ME participants.
Peripheral MCPs may be present in CFS/ME pathophysiology, however further investigation is required to determine their immunological role.
Since its inception in 2013, the UK CFS/M.E. Research Collaborative (CMRC) has successfully brought together significant numbers of researchers from across the UK and internationally with charities, mainstream funders and patients.
Aiming to drive interest and funding in CFS/ME research – which, as highlighted by the CMRC’s 2016 M.E./CFS Research Funding report, represents less than 1% of all active grants given by UK mainstream funding agencies – the CMRC has held four successful conferences, initiated and supported new collaborations, worked with mainstream funders and secured interest from pharma/industry, and brought researchers in from outside of the field as well as partners from charities covering overlapping illnesses.
Following a meeting of its Executive Board in February 2018, the CMRC agreed on a new purpose, objectives and values, which replace its previous Charter:
Our purpose
To promote the discovery of the biological mechanisms that underpin CFS/ME, which, together with clinical observation, will drive the development of targeted new treatments for this highly underserved patient population.
Our objectives
Values
Making Fatigue Real
Fatigue is like the Rodney Dangerfield of symptoms – it just gets no respect. The problem is the poor descriptive power of the word. It readily describes the everyday, manageable fatigue that most of the population regularly feels. That fatigue, though, has little relation to the pathological, functionally debilitating “fatigue” that people with chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), multiple sclerosis and some other diseases experience.
Studies indicate that the “fatigue” in these can be remarkably debilitating. Tony Komaroff’s large 1996 study indicated that people with ME/CFS were significantly more functionally impaired than people with congestive heart failure, type II diabetes mellitus, acute myocardial infarction, multiple sclerosis and hypertension. (Note that very severely ill ME/CFS patients were surely not included in this study.)
Self-tests and questionnaires to assess fatigue abound but are hardly trusted. What we really need is a test that objectively measures how much fatigue is present. Finding that has seemed kind of like the holy grail – a much desired goal but always seemingly out of reach. How do you measure such a seemingly subjective issue as fatigue?
One way is to identify a physiological attribute that changes depending on how much fatigue is present. The Japanese propose that a parasympathetic nervous system “collapse” that occurs after exertion in ME/CFS patients allows them to measure the amount of post-exertional malaise present.
See Fatigue – The Japanese Way
Staci Stevens’s two-day exercise test certainly shows up the functional impairments caused by exercise in ME/CFS in spades but is expensive, takes two days to complete, and requires exercise. The two-day test is superb for proving disability and understanding the amount of activity an ME/CFS/FM patient’s system can handle. An ideal measure of fatigue that could be readily used in studies, though, would be non-invasive, cheap and easy to administer.
A cheap, easy-to-administer, non-invasive test which could be conducted using a wearable, no less, has actually been the focus of research lately.
The ramifications could be huge. Researchers could objectively determine if say, NK cell cytotoxicity or ATP output was actually correlated with increased fatigue. Or a clinical trial could determine more accurately how a drug or treatment protocol was affecting fatigue levels. Functional vs “non-functional” fatigue (depression?) could be identified.
The Eyes – A Window into Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM)
The eyes are turning out to provide a surprisingly effective window into fibromyalgia and chronic fatigue syndrome (ME/CFS). Non-invasive methods have been used to detect small fiber neuropathy in the eyes of fibromyalgia patients. Recently, researchers have been using computational eyeglasses to assess the association between fatigue and rapid eye movements called ‘saccades’.
Saccades refer to a quick, simultaneous movement of both eyes which occurs in a kind of jumping motion. These types of movements occur when our eyes scan their immediate environment or when we’re reading. (Could reduced eye movements be involved with the reading problems some ME/CFS/FM patients have?)
These movements occur very, very quickly but their speed, amplitude (distance traveled) and other factors can be measured.
The link between a decrease in rapid eye movements and fatigue was first seen in 1979. Since then, studies of healthy controls have consistently shown that reduced rapid eye movements are associated with fatigue and/or sleepiness. A 2012 and 2017 study found that people with multiple sclerosis – a severely fatiguing disorder – displayed significantly reduced eye movement velocity, amplitude and latency during a fatiguing task, relative to healthy controls. The authors of the 2012 study concluded that:
Assessment of peak velocity, amplitude and latency in a saccade fatigue task is a promising approach for quantifying fatigue in MS patients.
The studies suggest that measuring rapid eye movements or saccades could provide a measure of fatigue-limited functionality; i.e. the inability of the eyes to scan their surroundings properly.
Side Note – Central Fatigue, Chronic Fatigue Syndrome, Caffeine and Dopamine….
On a side note, studies have shown that, at least in healthy humans, caffeine, when taken after exercise, can reduce or prevent the reduction in rapid eye movements seen. This suggests that the normal fatigue associated with exercise is at least partially caused by what’s called “central fatigue” – or fatigue produced by the brain.
Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis by Meredyth Anne Evans & Leonard A. Jason in Res Chron Dis (2018) 2(1), 001–0030
The onset of Chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME) is considered a key area of inquiry. Case criteria for ME and CFS and much of the academic literature suggest that patients typically experience one of two possible onset patterns: sudden or gradual.
The current study provided an in-depth investigation of ME and CFS onset in order to provide insight into early symptoms, onset duration, and the progression of functional disability. We collected qualitative descriptive data to gain a rich description of illness onset from the patients’ point of view.
Overall, qualitative findings revealed detailed descriptions of ME and CFS onset experiences. Major themes that emerged from the data included: onset/illness progression patterns, illness causes, methods of adapting and coping, hardworking and active lives prior to onset, healthy lives prior to onset, prior health problems, comorbid health conditions, emotional responses to onset, exertional effects, the illness as life limiting, stress, traumatic experiences, lack of support, support, and treatment limitations.
A closer examination of the onset/illness progression patterns that emerged from the data provided evidence that individuals with ME and CFS experience complex onset patterns. Furthermore, the study findings suggest that the method of categorizing individuals into sudden versus gradual onset groups fails to capture the more nuanced and varied onset experiences.
Prospective research studies that capture the onset period as it is developing could lead to improvements in the way we define and assess ME and CFS onset, and may also lead to methods for early detection, prevention, and individualized treatment approaches.
Ophthalmic correlates of Myalgic Encephalomyelitis (ME)/ Chronic Fatigue Syndrome (CFS), by Nadia Sultana Ahmed. MPhil thesis, University of Leicester [Published online 15 Feb 2018]
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disorder. With the exception of disabling fatigue, there are few definitive clinical features of the condition. As a consequence, patients often have difficulty gaining an appropriate
diagnosis. As such, identifying distinct clinical features of ME/CFS is an important issue.
One under researched area of ME/CFS associated symptoms concerns problems related to vision. People with ME/CFS consistently report a range of symptoms related to the quality of their vision including pain in the eyes, hypersensitivity to light, difficulty focusing on images, slow eye movements, and difficulty tracking object movement. However, there has been little attempt to verify patients’ self-reports using objective methods.
The purpose of the experiments presented in this thesis was to determine the effects of ME/CFS on: (i) performance on a range of tests of visual sensitivity and (ii) the morphology of the retina.
Compared to controls, the ME/CFS group exhibited reduced accommodation, larger pupil diameters, reduced colour discrimination and poorer contrast sensitivity towards lower spatial frequencies. Thinning in the photoreceptor layers of the retina (the Outer Segment & the Outer Nuclear layer) was also apparent.
These findings support the claims of people with ME/CFS that they experience problems related to their vision and its function. They also represent a potential marker of ME/CFS that may aid in its diagnosis.
Stigma in Myalgic Encephalomyelitis and its association with functioning, by Don M. Baken, Shane T. Harvey, David L. Bimler & Kirsty J. Ross in Fatigue: Biomedicine, Health & Behavior Volume 6, 2018 – Issue 1
Background:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is categorised by the World Health Organisation as a neurological condition. It is poorly understood and people with ME/CFS report experiencing stigma. Research suggests that stigma might be linked to functional ability.
Purpose:
This study investigated the relationship of stigma to factors associated with functional ability. Additionally, the use of standardised measures allowed for comparison of stigma severity in ME/CFS to other neurological conditions.
Method:
A convenience sample of 206 people diagnosed with ME/CFS completed mailed or online self-report standardised measures of stigma, health, ability to participate in social roles and activities, and their satisfaction with this ability. Findings were compared to
published data for three neurological conditions.
Results:
Stigma scores were significantly correlated (p < .0001) with all self-report health and functional measures (range: −.30 to −.42). The ME/CFS sample reported higher levels of stigma (d = 1..30) and lower levels of health (d = 1.86–2.16) and functioning (d = 1.63) than the comparison conditions.
Conclusions:
Consistent with studies over the last two decades, people with ME/CFS report higher levels of stigma when compared to the other conditions. The stigma is not just associated with health but also with specific measures of functional ability.
Never / Rarely / Sometimes / Often / Always
