Hair and salivary cortisol in a cohort of women with

Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome, by Megan E Roerink, Sean HPP Roerink, Nadine Skolud, Marieke E van der Schaaf, Ad RMM Hermus, Jos WM van der Meer, Hans Knoop, Urs M Nater in Hormones and Behavior Vol 103, July 2018, pp 1-6

 

Highlights:

  • Hypocortisolism has been described in CFS.
  • CFS patients have a decreased cortisol awakening response compared to healthy controls.
  • Long-term functioning of the HPA-axis has not been assessed previously in CFS.
  • There was a trend to lower hair cortisol concentrations in CFS patients.

Research abstract:

Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear.

The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis. Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ± 5.4 vs 6.1 nmol/L ± 6.3, p = 0.036).

Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ± 2.1 vs 4.3 pg/mg ± 1.8, p = 0.062). After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022).

This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

Posted in News | Comments Off on Hair and salivary cortisol in a cohort of women with

The putative glymphatic signature of CFS

The putative glymphatic signature of CFS: A new view on the disease pathogenesis and therapy, by Peter Wostyn, Peter Paul De Deyn in Medical Hypotheses Sept 2018, Vol 118, Pages 142–145

Abstract:

The underlying pathophysiology of chronic fatigue syndrome remains incompletely understood and there are no curative treatments for this disorder at present. However, increasing neuroimaging evidence indicates that functional and structural abnormalities exist in the brains of chronic fatigue syndrome patients, suggesting that the central nervous system is involved in this disorder and that at least some chronic fatigue syndrome patients may have an underlying neurological basis for their illness.

In the present paper, we speculate that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome.

We further postulate that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain. Although recent evidence indicates that at least some chronic fatigue syndrome patients may benefit from cerebrospinal fluid drainage, further studies are needed to confirm this finding and to determine whether this can be attributed to enhancement of glymphatic fluid flow and interstitial fluid clearance. If confirmed, this could offer promising avenues for the future treatment of chronic fatigue syndrome.

Clearly, given the relative invasive nature of cerebrospinal fluid diversion, such procedures should be reserved for chronic fatigue syndrome patients who are severely debilitated, or for those with severe headaches. Anyhow, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given that there are currently no effective treatments for this condition.

Read full article

Posted in News | Tagged , , , , , | Comments Off on The putative glymphatic signature of CFS

Identification of ME/CFS-associated DNA methylation patterns

Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns, by Malav S. Trivedi, Elisa Oltra, Leonor Sarria, Natasha Rose, Vladimir Beljanski, Mary Ann Fletcher, Nancy  G. Klimas, Lubov Nathanson in PLoS One Vol 13, #7, p e0201066 [Published: July 23, 2018]

Abstract:

Background:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex
condition involving multiple organ systems and characterized by persistent/ relapsing debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months.

Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, its status in ME/CFS remains uncertain. Our study aimed at identifying changes in the DNA methylation patterns that associate with ME/CFS.

Methods:
We extracted genomic DNA from peripheral blood mononuclear cells from 13 ME/CFS study subjects and 12 healthy controls and measured global DNA methylation by ELISA-like method and site-specific methylation status using Illumina MethylationEPIC microarrays. Pyrosequencing validation included 33 ME/CFS cases and 31 controls from two geographically distant
cohorts.

Results:
Global DNA methylation levels of ME/CFS cases were similar to those of controls. However, microarray-based approach allowed detection of 17,296 differentially methylated CpG sites in 6,368 genes across regulatory elements and within coding regions of genes. Analysis of DNA methylation in promoter regions revealed 307 differentially methylated promoters. Ingenuity pathway analysis indicated that genes associated with
differentially methylated promoters participated in at least 15 different pathways mostly related to cell signaling with a strong immune component.

Conclusions:
This is the first study that has explored genome-wide epigenetic changes associated with ME/CFS using the advanced Illumina MethylationEPIC microarrays covering about 850,000 CpG sites in two geographically distant cohorts of ME/CFS cases and matched controls. Our results are aligned with previous studies that indicate a dysregulation of the
immune system in ME/CFS. They also suggest a potential role of epigenetic de-regulation in the pathobiology of ME/CFS.

We propose screening of larger cohorts of ME/CFS cases to determine the external
validity of these epigenetic changes in order to implement them as possible diagnostic markers in clinical setting.

Posted in News | Tagged , , , , , , , , , | Comments Off on Identification of ME/CFS-associated DNA methylation patterns

WAMES’ response to draft NICE ME/CFS guideline scope

NICE ME/CFS guideline consultation – WAMES’ response to draft scope

Before work on the revised guidelines for ME/CFS can commence, the scope of the discussions needs to be agreed. On 26th July 2018 WAMES submitted final comments on the proposed NICE guideline scope.

Our comments reflected the views of patients and carers in Wales and we are grateful to all who who have been in touch with us.  We asked for a number of points to be included or changed e.g.:

Description of ME

WAMES found the description of the illness to be misleading and lacking key pieces of information, which could perpetuate the difficulties GPs and others have in using the guideline to accurately identify and diagnose the condition. The description should include:

  • ME/CFS is a chronic and potentially disabling disorder causing considerable disruption to daily life, relationships, work and education which has been found to lead to  a poorer quality of life of than other chronic  illnesses  such as MS, serious depression etc.
  • The Post-exertional response is the key characteristic of ME, not fatigue i.e. Symptoms deteriorate following minor physical or mental exertion, often delayed by a day or more and taking longer than normal to recover from.
  • A wide range of symptoms are experienced, which fluctuate over the course of the illness.
  • Triggers include viral illness, reactions to medication and toxic poisoning
  • Key symptoms include unrefreshing sleep, flu-like malaise, pain, extreme exhaustion/ weakness/ fatigability, orthostatic intolerance, digestive and cognitive dysfunction

Target audience

As well as patients, carers, health and social care workers, we thought the guideline would be useful for Benefits assessors.

Research into ME/CFS

Although a lot is not known about the cause and nature of ME/CFS, we wish the scope to include a positive statement about the many preliminary findings from biomedical research and the  growing number of clues to dysfunction in a wide range of the body’s systems. This switch of emphasis from the psycho-social research will shape the attitudes of health professionals and their approach to diagnosis and management, and hopefully remove the stigma, misunderstanding and disbelief currently hampering doctor/patient relationships.

Outcomes of management and treatment

  • It is important that evidence for management and treatment approaches is based on research with well-defined participant cohorts
  • Potential for, and evidence of harm, should be considered when searching for and assessing the research evidence or effectiveness of treatment options
  • As well as measuring improvements of sleep, pain, fatigue etc. absence of relapse could be another outcome, indicating successful management of the post-exertional response
  • Improvements in function and symptoms should be measured objectively, where possible, not just by subjective questionnaires

Read the final draft scope

Read the Equality Impact Assessment

Read WAMES’ full response

Posted in News | Tagged , | Comments Off on WAMES’ response to draft NICE ME/CFS guideline scope

The importance of screening for suicide risk in chronic invisible illness

The Importance of Screening for Suicide Risk in Chronic Invisible Illness, by Cathy L Pedersen in Journal of Health Science & Education Vol 2(4): 1-5 2018

Abstract: 

Many people suffering from chronic invisible illnesses like chronic fatigue syndrome/ myalgic encephalomyeletis (CFS/ME), fibromyalgia, Lyme disease, and postural orthostatic tachycardia syndrome (POTS) report increased suicidal ideation and past suicide attempts compared with the general population.

A number of factors contribute to suicide risk in chronic illness. Physical factors, like sleep disturbance and pain, as well as psychosocial issues like perceived burdensomeness (feeling like a burden to others), thwarted belongingness (lack of connection to a social group), loneliness, and depression may contribute to an increased suicide risk.

Healthcare practitioners are encouraged to actively screen for suicide risk in their chronically ill patients, and have a protocol in place to refer their patients to proper community resources.

Posted in News | Tagged , | Comments Off on The importance of screening for suicide risk in chronic invisible illness

Checking our blind spots: current status of research evidence summaries in ME/CFS

Checking our blind spots: current status of research evidence summaries in ME/CFS, by Todd E Davenport, Staci R Stevens, J Mark VanNess, Jared Stevens, Christopher R Snell in British Journal of Sports Medicine, July 2018

Editorial:

The evidence-based practice (EBP) model hierarchically organises scientific information by level, from lowly case studies to lofty systematic reviews and clinical trials. Clinical trials best influence recommendations because they putatively have the greatest internal
validity.1

This assumption is based on sound research ethics, such as scientific competence and good faith actors, as well as observed differences in outcomes. An EBP blind spot emerges when fundamental assumptions are unmet.

Based on findings of a 2018 PEDro evidence summary in BJSM 2 and elsewhere,3 it now seems clear that scientific research in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) resides in a blind spot.

The paper goes on to discuss the flawed results of the PACE trial into GET and CBT before concluding:

EBP also includes patient perspectives. We should follow the example of engaged patient advocates and citizen scientists in ME/CFS by involving patients as advisory board members on trials and as reviewers on published evidence summaries. Community- based participatory research designs should be elevated to ensure information flows from bedside-to-lab bench, in addition to lab bench-to-bedside. By including evidence from patients in clinical decisions and research, we can begin to address the important blind spots in how we think about and implement EBP.

Read full article

Posted in News | Tagged , , , , , , , , | Comments Off on Checking our blind spots: current status of research evidence summaries in ME/CFS

Reduced glycolytic reserve in isolated natural killer cells from ME/CFS patients

Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/ chronic fatigue syndrome patients: A preliminary investigation, by Thao Nguyen, D Staines, S Johnston, S Marshall-Gradisnik in Asian Pac J Allergy Immunol. 2018 Jul 8. [Epub ahead of print]

Abstract:

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is medically unexplained post-exertional fatigue associated with significant reduction in natural killer cell (NK) cytotoxicity activity. Cytotoxic activity relies on glycolytic flux and mitochondrial respiration to fulfill energetic cellular demands. While mitochondrial dysfunction has been reported in ME/CFS patients, no previous investigation has examined the bioenergetic profile of isolated NK cells from ME/CFS patients.

OBJECTIVE: This study was to determine the metabolic function in resting NK cells from ME/CFS patients.

METHOD: Six ME/CFS patients (aged 50.33±4.95) were age and sex-matched with non-fatigued healthy controls (aged 50.00±5.04). Mitochondrial stress tests measured parameters of mitochondrial function in the NK cells including basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity and bioenergetic health index. Glycolytic stress tests measured parameters of glycolytic function such as glycolytic reserve, glycolysis and glycolytic capacity in isolated NK cells from ME/CFS patients and healthy controls using an extracellular flux analyzer, Seahorse XFp.

RESULT: There was a significant reduction of glycolytic reserve in resting NK cells from ME/CFS patients (0.6±0.07 mpH/ min) compared with healthy control (2.25±1.3 mpH/min). Mitochondrial respiration in resting NK cells did not approach statistical significance between ME/CFS patients and healthy controls.

CONCLUSION: These findings suggest resting NK cells from ME/CFS patients have reduced ability to increase glycolytic flux to respond to high energetic demands for ATP production. Hence, the reduced glycolytic reserves we have identified in isolated resting isolated NK cells should be further investigated to assist in understanding ME/CFS pathogenesis.

Study finds reduced ability to respond to energy demands in ME patients’ immune systems

Posted in News | Tagged , , , , , , , | Comments Off on Reduced glycolytic reserve in isolated natural killer cells from ME/CFS patients

Suicidal ideation in non-depressed individuals: the effects of a chronic, misunderstood illness

Suicidal ideation in non-depressed individuals: the effects of a chronic, misunderstood illness, by AR Devendorf, SL McManimen, LA Jason in Health Psychol. 2018 Jul 1:1359105318785450  [Epub ahead of print]

Abstract:

Chronic illness is a risk factor for suicide but is often explained with depression. Research has shown an increased suicide rate in patients with myalgic encephalomyelitis and chronic fatigue syndrome, but specific risk factors have been unexplored. We qualitatively analyzed responses from 29 patients who endorsed suicidal ideation but did not meet depression criteria.

Two themes were developed:

(1) feeling trapped and

(2) loss of self, loss of others, stigma and conflict.

Myalgic encephalomyelitis and chronic fatigue syndrome caused patients severe disability, restructured their lives, and inflicted serious pain. Participants emphasized that they were not depressed, but felt trapped by the lack of treatments available.

Read full article

Posted in News | Tagged , , , , | Comments Off on Suicidal ideation in non-depressed individuals: the effects of a chronic, misunderstood illness

Nutritional modulation of the intestinal microbiota

Review abstract:

Nutritional modulation of the intestinal microbiota: future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease, by Vincent C Lombardi, Kenny L De Meirleir, Krishnamurthy Subramanian, Sam M Nourani, Ruben K Dagda, Shannon L Delaney, András Palotás in The Journal of Nutritional Biochemistry, Volume 61, November 2018, Pages 1-16

The gut-brain-axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut-microbiota-brain axis.

Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases.

In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota, and in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.

Read full article

Posted in News | Tagged , , , , , , | Comments Off on Nutritional modulation of the intestinal microbiota

New CFS test is 84% accurate

Medical News Today blog post, by Ana Sandoiu, 11 July 2018: New chronic fatigue syndrome test is 84 percent accurate

Myalgic encephalomyelitis/chronic fatigue syndrome does not currently have a diagnostic test. But this may soon change, as researchers have developed a test that can predict it with an unprecedented level of accuracy.

Currently, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect more than 1 million people in the United States, and up to 24 million people worldwide. This often debilitating condition is characterized by feelings of extreme exhaustion, muscle and joint pain, and insomnia, as well as difficulty concentrating or remembering things.

The causes of ME/CFS remain unknown, and in the absence of a proper diagnostic test for it, healthcare professionals have to exclude other disorders and examine a patient’s history before they can tell whether a person has ME/CFS or not.

However, this may soon change, as a team of researchers led by those at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health in New York City, NY, have engineered a highly accurate test for the disorder. The researchers detail their findings in a new study recently published in the journal Scientific
Reports. Dr. Dorottya Nagy-Szakal, a CII researcher, is the first author of the paper.

Engineering an ME/CFS diagnostic test

Dr. Nagy-Szakal and team examined the blood samples of 50 people with ME/CFS and compared them with those of 50 age-matched healthy controls. Using a special technique that identifies molecules by measuring their mass, the scientists found 562 metabolites that the ME/CFS patients had in common.

Metabolites are byproducts of the body’s metabolism – that is, its ability to process sugars, fats, and proteins. In the recent research, the scientists excluded metabolites resulting from antidepressants or other drugs.

Laboratory tests carried out by Dr. Nagy-Szakal and team revealed that certain metabolites were altered in a way that suggested that the patients’ mitochondria – which are the tiny organelles inside the cell responsible for turning nutrients into energy – were not functioning properly. The results are coherent with previous studies led by other researchers, as well as with research carried out by Dr. Nagy-Szakal and colleagues last year.

In 2017, the team found a distinct pattern of metabolites in people who had both irritable bowel syndrome (IBS) and ME/CFS. Other studies have reported that 35-90 percent of those with ME/CFS also have IBS. And in the new study, half of the ME/CFS patients also had IBS.

Test yields 84 percent accuracy

Dr. Nagy-Szakal and her colleagues combined biomarkers from both their  2017 study and their new study. The result was a predictive model with a 0.836 score, which translates into an accuracy rate of 84 percent.

‘This is a strong predictive model that suggests we’re getting close to the point where we’ll have lab tests that will allow us to say with a high level of certainty who has this disorder,’ explains Dr. Nagy-Szakal.

Corresponding author Dr. W. Ian Lipkin, director of CII and the National Institutes of Health (NIH) Center for Solutions for ME/CFS, also weighs in on the findings, saying,

‘We’re closing in on understanding how this disease works. We’re getting close to the point where we can develop animal models that will allow us to test various hypotheses, as well as potential therapies. For instance, some patients might benefit from probiotics to retune their gastrointestinal microflora or drugs that activate certain neurotransmitter systems.’

Posted in News | Tagged , , , , , , , , | Comments Off on New CFS test is 84% accurate