Subgroup of ME/CFS also have IBS

Research abstract

BACKGROUND:
There is evidence that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by gastro-intestinal symptoms; and IgA and IgM responses directed against lipopolysaccharides (LPS) of commensal bacteria, indicating bacterial translocation.

METHODS:
This study was carried out to examine gastro-intestinal symptoms in subjects with ME/CFS versus those with chronic fatigue (CF). The two groups were dissected by dichotomizing those fulfilling and not fulfilling Fukuda’s critera. In these groups, we examined the association between gastro-intestinal symptoms and the IgA and IgM responses directed against commensal bacteria.

RESULTS:
Using cluster analysis performed on gastro-intestinal symptoms we delineated that the cluster analysis-generated diagnosis of abdominal discomfort syndrome (ADS) was significantly higher in subjects with ME/CFS (59.6%) than in those with CF (17.7%). The diagnosis of ADS was strongly associated with the diagnosis of irritable bowel syndrome (IBS). There is evidence that ME/CFS consists of two subgroups, i.e. ME/CFS with and without ADS. Factor analysis showed four factors, i.e. 1) inflammation-hyperalgesia; 2) fatigue-malaise; 3) gastro-intestinal symptoms/ADS; and 4) neurocognitive symptoms. The IgA and IgM responses to LPS of commensal bacteria were significantly higher in ME/CFS patients with ADS than in those without ADS.

CONCLUSIONS:
The findings show that ADS is a characteristic of a subset of patients with ME/CFS and that increased bacterial translocation (leaky gut) is associated with ADS symptoms. This study has defined a pathway phenotype, i.e bacterial translocation, that is related to ME/CFS and ADS/IBS and that may drive systemic inflammatory processes.
Evidence for the existence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with and without abdominal discomfort (irritable bowel) syndrome by M Maes, JC Leunis, M Geffard, M Berk in Neuro Endocrinol Lett. 2014 Nov 2;35(6):445-453. [Epub ahead of print]

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Long term prognosis study of patients with CFS

Research abstract

Objective: To examine the effect of early clinical and demographic factors on occupational outcome, return to work or awarded permanent disability pension in young patients with chronic fatigue syndrome (CFS).

Design: Longitudinal cohort study.

Intervention: A written self-management programme including a description of active coping strategies for daily life was provided.

Setting, participants: Patients with CFS after mononucleosis were evaluated at Department of Neurology, Haukeland University Hospital during 1996–2006 (contact 1). In 2009 self-report questionnaires were sent to all patients (contact 2).

Primary and secondary outcome measures:  Primary measure was employment status at contact 2. Secondary measures included clinical symptoms, and Fatigue Severity Scale (FSS) scores on both contacts, and Work and Social Adjustment Scale (WSAS) at contact 2.

Results: Of 111 patients at contact 1, 92 (83%) patients returned the questionnaire at contact 2. Mean disease duration at contact 1 was 4.7 years and at contact 2 11.4 years. At contact 1, 9 (10%) were part-time or full-time employed. At contact 2, 49 (55%) were part-time or full-time employed. Logical regression analysis showed that FSS≥5 at contact 2 was associated with depression, arthralgia and long disease duration (all at contact 1).

Conclusions: About half of younger patients with CFS with long-term incapacity for work experienced marked improvement including full-time or part-time employment showing better outcomes than expected. Risk factors for transition to permanent disability were depression, arthralgia and disease duration.

Strengths and limitations of this study:  Two strengths of the study are very long prospective follow-up period and focus on employment.

A limitation is that patients were recruited from a tertiary centre.

Long-term prognosis for young patients with chronic fatigue syndrome after mononucleosis is favourable for a large subgroup.

More than half of the patients with long-term incapacity for work are re-employed after mean disease duration of 11.4 years.

Factors associated with poor long-term prognosis include depression, arthralgia and disease duration.

Longitudinal follow-up of employment status in patients with chronic fatigue syndrome after mononucleosis, by Morten Nyland, Halvor Naess, Jon Steinar Birkeland, Harald in BMJ Open 2014;4  Published 26 November 2014

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The impact of a child’s CFS/ME on family relationships

Research abstract
Although there is a large body of research literature concerning the impact of childhood chronic illness on family relationships, very little of this has specifically focussed on the impact of childhood Chronic Fatigue Syndrome/Myalgic Encephalopathy (CFS/ME). The current study therefore aims to investigate the impact of having a child with CFS/ME on family relationships from the perspective of parents.

This study takes a qualitative approach. Semi-structured interviews were used to explore 18 parents’ experiences of having a child with CFS/ME and the impact this has had on family relationships. Interview data were transcribed and analysed using thematic analysis.

The analysis led to the identification of 5 main themes: “Long and Difficult Journey”,  Uncertainty”, “Isolation and Restriction”, “focus on the unwell person at the expense of family life” and “Parental roles”. They felt that life had become a constant struggle and often felt exhausted. They  felt uncertainty, isolation and restriction.

These parents talked about feeling like family life  had become focussed on their unwell child, such that some expressed a need to escape  from the situation. They also described how, as a consequence of managing their child’s  CFS/ME, family members could often feel marginalised and the illness could be seen as a destructive force.

However, many parents also described working as a team and feeling  that family relationships had benefitted in some way. The results of this study are in line with findings of other studies into other chronic illnesses. In addition, this is the first study to focus exclusively on the impact of CFS/ME on family relationships from the perspective of the parents, and is unique in that there is a dual focus on both mothers and fathers.

Clinicians should be aware that parents of children with CFS/ME may need additional  support, such as information as to what to expect at various stages of the illness and where to access the relevant support.

The impact of managing a child’s chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) on family relationships by Andrew Haig-Ferguson, Masters thesis  July 2014, University of the West of England

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Voices from the shadows – a film about ME, with a warning

The film ‘Voices from the Shadows’ is now available to watch for free until
the end of the year – on Vimeo – by entering a promo code of   VOICES
after clicking the “rent for $3” button.

Vimeo also requires you to register with a name, email address and password.

This film is not considered suitable viewing for children and young people with ME, but is intended for adults who are not familiar with the illness.

The film shows how harmful ignorance and misunderstanding about the illness Myalgic Encephalomyelitis or ME can be. Patients with mild or moderately severe ME have become very severely ill when their illness is mismanaged: largely due to the way many different conditions have been muddled together by inadequate definitions and vague criteria.

Lack of recognition of the delayed exacerbation of ME symptoms following overactivity and over exposure to stimuli has caused many patients to deteriorate and become chronically and severely ill. There is very little recognition of the clinical picture of very severe ME and these patients then become vulnerable to being misdiagnosed with functional illness. Alongside this, many patients are misdiagnosed as having CFS/ME, and their other illnesses remain undiscovered and untreated.

Please share this post but do not omit the warning that it could be very distressing for young people with ME to view it. Please try to prevent it being inappropriately accessed.

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ME in children – Specialist lectures on video

Seminar on children and young people with ME/CFS – 2014

On November 12, 2014 the National Association for ME in Sweden organized a seminar on children and young people with ME/CFS.

The seminar was conducted in cooperation with RME Stockholm and RME Scania and held at County Hall in Stockholm. They filmed lectures, accessed through the links below.

Introduction -Henrik Fransson, chairman RME Stockholm, Stig Nyman, councillor

Orthostatic intolerance and ME/CFS in children – Peter C. Rowe, Johns Hopkins Children’s Center, United States

ME/CFS in children – Diagnosis and Treatment – Nigel Speight, The University Hospital of North Durham, UK. Dr. Speight also discussed the “assault”  health professionals and other agencies expose children to because of misdiagnosis in cases of ME/CFS.

The immunological / viral / endocrine interactions in ME/CFS –  Dr. Amolak S. Bansal, Department of Immunology, St Helier Hospital, UK.

Living with ME/CFS as a child – Nathalie Gillberg 14 years and suffering, and Camilla Gillberg, parent says.

Panel Discussion

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The gut microbiome affects brain health

Research abstract

The human gut microbiome impacts human brain health in numerous ways:

(1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation.

(2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system.

(3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity.

(4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence.

(5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve.

Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied.

Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.

The Gut Microbiome and the Brain, by L Galland in J Med Food. 2014 Nov 17. [Epub ahead of print]

 

 

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Roburins, French oak-wood extract & CFS

Extract from article: New option for Chronic Fatigue Syndrome, by Michael Franco

Frustrated by a lack of treatment options, an international team of researchers has focused their attention on a group of unique molecules called roburins, which are derived from oak wood.

Roburin-rich oak wood extract has shown tremendous promise in managing a cluster of the symptoms that define chronic fatigue syndrome.

Evidence suggests that roburins are responsible for improving the functioning of our cellular ribosomes. Located in nearly every cell in the body, ribosomes are the sites of protein production and are intimately involved in the function of every tissue, organ, and system.

The science of “ribosomal biogenesis” is now capturing the interest of scientists as a potential method for improving energy and biological function in the aging body.

Hope From The Oak

Determined scientists at several research centers have discovered unique compounds in oak wood that are proving to be an effective therapy in treating chronic fatigue.

Humans have been exposed to oak wood extracts for as long as they have been storing alcoholic beverages in aged oak barrels. This practice was originally adopted because of the preservative effects of fresh oak on new wines and spirits, but it has continued because of the unique flavor and character the oak provides to the aging liquor.

As the roburin molecules have been isolated and analyzed in modern laboratories, they have become available for use in animal and human studies aimed at transferring some of the oak’s resilience and stress resistance to humans.

Roburins In The Human Body

Two major human studies demonstrate the potential of roburins for mitigating chronic fatigue syndrome symptoms.

In the first study, researchers were interested in understanding how roburin molecules were distributed and absorbed, as well as their compatibility in the human body. Following five days of oral supplementation with roburin-rich oak wood extract-three capsules of a proprietary, patented extract called Robuvit®-the scientists found a 100% increase in plasma total phenols (a general measure of absorption of molecules in this class), as well as the presence of roburin breakdown products (metabolites) in urine of healthy volunteers.

Since roburins are found only in oak wood,4 the data demonstrated vigorous absorption and conversion of roburins into substances including urolithins and ellagic acid, which are known to have potent biological activities.

This study also revealed that the oak wood roburins trigger a complex set of biological events in the body. Using a sophisticated technology that measures changes in gene expression, the researchers were able to show that blood serum from supplemented people in the study may beneficially alter the expression of several genes in human cells in culture.

Among the most consistent changes in gene expression induced by the serum from oak wood extract in supplemented patients had to do with the activities of ribosomes, the ultramicroscopic cellular organelles that are responsible for the “translation” of genes in DNA into specific proteins. Long regarded as simply tiny protein-manufacturing plants, ribosomes are now emerging as essential in the maintenance of normal cellular functions, and as key players in the science of “systemic aging” and disorders such as chronic fatigue syndrome.

What You Need to Know: Treating Chronic Fatigue With Oak Wood Extract

Chronic fatigue syndrome affects as many as 4 million Americans, but no clear-cut cause has yet been identified, and no effective treatment is available.

A novel extract of the French oak tree, Quercus robur, contains compounds called roburins that, under the influence of human intestinal organisms, are converted into bioactive molecules called urolithins.

This oak wood extract provides support for ribosomes, the tiny cellular factories responsible for accurately producing structural and functional proteins everywhere in the body.
Ribosomal dysfunction has been implicated in chronic fatigue syndrome, so the ribosomal support properties of oak wood extract are of great interest to scientists.
Research has shown that oak wood extract rich in roburins (Robuvit®) significantly improves symptoms of chronic fatigue syndrome in human patients after three months of supplementation.  Oak wood extract demonstrates a unique, systems-level approach to fighting this previously untreatable condition.

Roburins And Chronic Fatigue

The clinical impact of roburin-rich oak wood extract was made evident by a second important human study, this one conducted among patients with known chronic fatigue syndrome. In the study, adults with at least five primary chronic fatigue syndrome symptoms were treated with 200 mg/day of Robuvit® oak wood extract for a minimum of six months. A control group that did not use the supplement was also established among patients with the same chronic fatigue symptoms. The scientists found that oak wood extract was productive in alleviating many of the most troubling symptoms of chronic fatigue.

Among those who used the oak wood extract, there were significant reductions for a multitude of key symptoms of chronic fatigue, including:
18% reduction in weakness and exhaustion,
44% reduction in unrefreshing sleep,
29% reduction in short-term memory impairment,
63% reduction in muscle pain,
51% reduction in joint pain,
33% reduction in headaches, and
47% reduction in tender lymph nodes in the armpit and neck.

Additionally, impressive reductions from baseline were also found in most secondary symptoms of chronic fatigue syndrome, including:
51% reduction in sensitivity to noise, foods, medications, and chemicals,
38% reduction in dizziness,
58% reduction in depression,
49% reduction in mood swings,
40% reduction in weight fluctuation,
24% reduction in alcohol intolerance,
39% reduction in allergies, and
29% reduction in visual disturbances.
There were no significant changes from baseline in all of these parameters for the patient group not taking the oak wood extract. These weren’t all of the changes, though. On a standardized mood scale, supplemented subjects had significant increases in their scores on positive items including feeling active, happy, peppy, caring, calm, and loving, along with significant reductions in negative items such as feeling gloomy, fed-up, grouchy, sad, or tired. In fact, the overall mood evaluation score in supplemented subjects rose from an average of -6.93 at baseline to +4.32 at six months. For controls, the average score at baseline was -6.5 and rose only to -3.4 at six months.

In those with chronic fatigue syndrome, scientists have found that oxidative stress levels are usually elevated. At the start of this study, 65% of supplemented and 70% of control patients showed elevated oxidative stress on blood tests. Following the supplementation period, control patients showed no decrease in oxidative stress, but supplemented subjects had 8 and 10% reductions at three and six months, respectively.

A third study demonstrated the impact of oak wood extract on the response to histamine in normal subjects. Histamine is a substance released in the face of allergic or inflammatory stimuli, and there is some evidence suggesting that chronic fatigue syndrome may be related to excessive release of, or sensitivity to, histamine in skin, intestines, or brain tissue.

In this study, female participants were randomly assigned to control or supplement groups (300 mg Robuvit®/day) for three days, followed by an injection of pure histamine into the skin. A normal response to this injection produces a so-called “wheal and flare” response: a raised, itchy skin wheal associated with a red flare on the skin surface and with increased microcirculation in the immediate area. Compared with control subjects, those who had supplemented with Robuvit® had a significantly smaller wheal area (28%), smaller area of redness (13%), and lower levels of circulation increase in the immediate area (49%). These results suggest an additional mechanism, blockade of histamine effects, for this novel roburin-rich oak wood extract’s effects on chronic fatigue syndrome.

No side effects of the oak wood extract supplementation were reported in any of the participants in these studies.

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Are exercise tests useful in chronic pain, FM and fatigue disorders?

Systematic review abstract

Question: Are submaximal and maximal exercise tests reliable, valid and acceptable in people with chronic pain, fibromyalgia and fatigue disorders?

Design: Systematic review of studies of the psychometric properties of exercise tests.

Participants: People older than 18 years with chronic pain, fibromyalgia and chronic fatigue disorders.

Intervention: Studies of the measurement properties of tests of physical capacity in people with chronic pain, fibromyalgia or chronic fatigue disorders were included.

Outcome measures: Studies were required to report: reliability coefficients (intraclass correlation coefficient, alpha reliability coefficient, limits of agreements and Bland-Altman plots); validity coefficients (intraclass correlation coefficient, Spearman’s correlation, Kendal T coefficient, Pearson’s correlation); or dropout rates.

Results: Fourteen studies were eligible: none had low risk of bias, 10 had unclear risk of bias and four had high risk of bias. The included studies evaluated: Åstrand test; modified Åstrand test; Lean body mass-based Åstrand test; submaximal bicycle ergometer test following another protocol other than Åstrand test; 2-km walk test; 5-minute, 6-minute and 10-minute walk tests; shuttle walk test; and modified symptom-limited Bruce treadmill test. None of the studies assessed maximal exercise tests. Where they had been tested, reliability and validity were generally high. Dropout rates were generally acceptable.

The 2-km walk test was not recommended in fibromyalgia.

Conclusion: Moderate evidence was found for reliability, validity and acceptability of submaximal exercise tests in patients with chronic pain, fibromyalgia or chronic fatigue. There is no evidence about maximal exercise tests in patients with chronic pain, fibromyalgia and chronic fatigue.

Several submaximal exercise tests are reliable, valid and acceptable in people with chronic pain, fibromyalgia or chronic fatigue: a systematic review by J Ratter, L Radlinger, C Lucas in J Physiother. 2014 Jul 29. pii: S1836-9553(14)00079-4

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Could use of stress management skills improve PEM?

Research abstract

Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerbated by cognitive and/or physical exertion, referred to as post-exertional malaise (PEM).

In a variety of populations, the cortisol awakening response (CAR) has stood out as a marker of endocrine dysregulation relevant to the experience of fatigue, and may therefore be particularly relevant in CFS. This is the first study to examine PEM and the CAR in a sample of individuals with CFS.

The CAR has also been established as a stress-sensitive measure of HPA axis functioning. It follows that better management of stress could modulate the CAR, and in turn PEM.

In this cross-sectional study, we hypothesized that greater perceived stress management skills (PSMS) would relate to lower reports of PEM, via the impact of PSMS on the CAR.

A total of 117 adults (72% female) with a CFS diagnosis completed self-report measures of PSMS and PEM symptomatology and a two-day protocol of saliva collection. Cortisol values from awakening and 30 minutes post-awakening were used to compute the CAR. Regression analyses revealed that greater PSMS related to greater CAR and greater CAR related to less PEM severity. Bootstrapped analyses revealed an indirect effect of PSMS on PEM via the CAR, such that greater PSMS related to less PEM, via a greater CAR.

Future research should examine these trends longitudinally and whether interventions directed at improving stress management skills are accompanied by improved cortisol regulation and less PEM in individuals with CFS.

Stress Management Skills, Cortisol Awakening Response and Post-Exertional Malaise in Chronic Fatigue Syndrome by Daniel L Hall et al in Psychoneuroendocrinology July 5 2014 [published online]

Cort Johnson discusses this research study on his blog and concludes:

It’s important to understand what this study did not suggest. It did not suggest that better stress management skills can cure ME/CFS  or remove post-exertional malaise (PEM). All the patients, whether or not they had high PSMS skills, still had ME/CFS.  The study simply suggested that more stress management skills are associated with improved cortisol and reduced (but obviously still present) levels of PEM in ME/CFS.

(A Lenny Jason study, on the other hand, suggested that while many ME/CFS patients can benefit from stress management skills and pacing, a subset of the more severely ill may not.)

The level of Perceived Stress Management Skills in patients with ME/CFS does not appear to be different from patients suffering from other chronic illnesses.

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Assessment of measuring activity limitation in CFS

Research review abstract

Purpose:

To summarize measurement instruments used to evaluate activity limitations and participation restrictions in patients with chronic fatigue syndrome (CFS) and review the psychometric properties of these instruments.

Method:

General information of all included measurement instruments was extracted. The methodological quality was evaluated using the COSMIN checklist. Results of the measurement properties were rated based on the quality criteria of Terwee et al. Finally, overall quality was defined per psychometric property and measurement instrument by use of the quality criteria by Schellingerhout et al.

Results:

A total of 68 articles were identified of which eight evaluated the psychometric properties of a measurement instrument assessing activity limitations and participation restrictions. One disease-specific and 37 generic measurement instruments were found. Limited evidence was found for the psychometric properties and clinical usability of these instruments. However, the CFS-activities and participation questionnaire (APQ) is a disease-specific instrument with moderate content and construct validity.

Conclusion:

The psychometric properties of the reviewed measurement instruments to evaluate activity limitations and participation restrictions are not sufficiently evaluated. Future research is needed to evaluate the psychometric properties of the measurement instruments, including the other properties of the CFS-APQ. If it is necessary to use a measurement instrument, the CFS-APQ is recommended.

Implications for Rehabilitation:

  • Chronic fatigue syndrome (CFS).
  • Chronic fatigue syndrome causes activity limitations and participation restrictions in one or more areas of life.
  • Standardized, reliable and valid measurement instruments are necessary to identify these limitations and restrictions.
  • Currently, no measurement instrument is sufficiently evaluated with persons with CFS.
  • If a measurement instrument is needed to identify activity limitations and participation restrictions with persons with CFS, it is recommended to use the CFS-APQ in clinical practice and scientific research.

Assessment of activity limitations and participation restrictions with persons with chronic fatigue syndrome: a systematic review, by Kuni Vergauwen, Mira Meeus, Ivan P. J. Huijnen, Daphne Kos, Dominique Van de Velde, and Inge van Eupen, in Disability & Rehabilitation [Posted online on November 3, 2014]

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