Association of CFS with premature telomere attrition (& accelerated ageing)

Posted on 03/09/2018 by wames

Research abstract:

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]

Background:

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

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UK CFS/ME Research Collaborative plans to promote biological research

Posted on 03/07/2018 by wames

Action for ME blog post, 6 March 2018: UK CFS/M.E. Research Collaborative

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

  • To design, implement and analyse the outcome of a cross-stakeholder, comprehensive, national research strategy for CFS/ME and experimental medicine.
  • To create an open cross-sector platform for effective knowledge-exchange and datasharing both nationally and internationally, in order to optimise research, raise awareness of the disease, and influence policymakers and investors.

Values

  •  We are an intellectually generous community sharing data, best practice and technologies.
  • We are a creative community harnessing new ideas, new technologies and new ways of working.
  • We are a collaborative community inviting all stakeholders to join our programmes and shape our activity.
  • We are an enabling community, facilitating the leverage of further resources for CFS/ME research.

Find out more

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Finally – an objective measure of fatigue?

Posted on 03/06/2018 by wames

Health Rising blog post by Cort Johnson, 20 Feb 2018: Finally – An Objective Measure of Fatigue? An ME/CFS and Fibromyalgia Inquiry

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.

Read more

 

 

 

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Onset patterns of CFS & ME

Posted on 03/06/2018 by wames

Research abstract:

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.

 

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Ophthalmic correlates of ME/CFS

Posted on 03/05/2018 by wames

Research abstract:

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.

 

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Stigma in ME & its association with functioning

Posted on 03/02/2018 by wames

Research abstract:

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.

The Stigma Short-form scale

Never / Rarely / Sometimes / Often / Always

  • Because of my illness, some people avoided me
  • Because of my illness, I felt left out of things
  • Because of my illness, people avoided looking at me
  • I felt embarrassed about my illness
  • Because of my illness, some people seemed uncomfortable with me
  • I felt embarrassed because of my physical limitations
  • Because of my illness, people were unkind to me
  • Some people acted as though it was my fault I have this illness
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Higher prevalence of ‘low T3 syndrome’ (Euthyroid sick syndrome) in patients with CFS

Posted on 03/01/2018 by wames

Research abstract:

Higher prevalence of ‘low T3 syndrome’ in patients with chronic fatigue syndrome: A case-control study Begoña Ruiz-Núñez, Rabab Tarasse, Emar Vogelaar, Janneke Dijck-Brouwer and Frits Muskiet in Front. Endocrinol. [Published online 28 Feb 2018]

Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation.

We studied 98 CFS patients (21-69 years, 21 males) and 99 age- and sex-matched controls (19-65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation.

Most remarkably, CFS patients exhibited similar TSH, but lower FT3 (difference of medians 0.1%), TT4 (11.9%), TT3 (12.5%), %TT3 (4.7%), SPINA-GD (14.4%), SPINA-GT (14.9%), 24-hour urinary iodine (27.6%) and higher %rT3 (13.3%). FT3 below the reference range, consistent with the ‘low T3 syndrome’, was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% CI=1.00 – 6.54). Most observations persisted in two sensitivity analyses with more stringent cut-off values for BMI, hsCRP and WBC.

We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4 and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels.

The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of ‘non thyroidal illness syndrome’ and ‘low T3 syndrome’ experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with e.g. T3 and iodide supplements might be indicated.

Frontiers press release, 20 Mar 2018: Chronic fatigue syndrome possibly explained by lower levels of key thyroid hormones

Discovery of a crucial link between chronic fatigue syndrome and lower levels of key thyroid hormones raises hopes for treating this common yet debilitating disease

Mail online, 22 March 2018:  Debilitating chronic fatigue syndrome could be caused by low levels of thyroid hormones, finds study

  • The findings shed new light on the truth behind the condition, which is incurable
  • CFS, or ME, has prompted uproar among the medical community in recent years
  • Skeptics dismiss the extreme tiredness and lethargy as merely psychological
  • However, angry patients are adamant the condition has a biological cause
  • And the new Dutch research backs up the claims that it is a physical problem
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Infection elicited autoimmunity & ME/CFS: an explanatory model

Posted on 02/23/2018 by wames

Hypothesis and Theory article:

Infection elicited autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an explanatory model, by Jonas Blomberg, Carl-Gerhard Gottfries, Amal Elfaitouri, Muhammad Rizwan and Anders Rosén in Front. Immunol., 15 February 2018

Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging.

In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model.

ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance.

Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain.

In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.

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A systematic review of probiotic interventions for gastrointestinal symptoms & IBS in CFS/ME

Posted on 02/23/2018 by wames

Research abstract:

A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) by Matthew Corbitt, N Campagnolo, D Staines, S Marshall-Gradisnik in Probiotics and Antimicrobial Proteins, 2018 pp 1–12

Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME.

The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use. Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available.

A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms).

The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.

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