Dysregulation of cytokine pathways in CFS & MS

Posted on 06/15/2017 by wames

Research abstract:

Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis by Matthew Sorenson, Jacob Furst, Herbert Mathews & Leonard A. Jason in Fatigue: Biomedicine Heath & Behavior pp1-14 [Published online 7 Jun 2017]

Background:

Cytokine studies in chronic fatigue syndrome (CFS) have yielded mixed findings.

Purpose:

This investigation evaluated whether network analysis of cytokine production differs between patients with CFS and multiple sclerosis (MS) as compared to a reference group of healthy controls.

Methods:

Three subgroups (N = 109) were included: 15 participants who met diagnostic criteria for CFS, 57 participants meeting criteria for MS, and 37 controls. Peripheral blood was obtained and production of a select cytokine profile was determined from stimulated and unstimulated mononuclear cells. Data were generated through the use of a multi-analyte bead suspension array. Pairwise associations were determined for each group, and these associations were used to create a graphical representation of the data. The graph was clustered using an eigenvector community algorithm and results visualized using edges to model the correlations by color and thickness to show direction and strength.

Results:

The control and MS groups produced a three-neighborhood relationship regardless of cell condition. While producing a three-neighborhood relationship, the MS group differed significantly from the control group as it displayed stronger relationships among pro-inflammatory cytokines. In contrast, the CFS group displayed a three-neighborhood solution when unstimulated. However, when cells from the CFS group were stimulated, a two-neighborhood model was found that exhibited stronger inter-cytokine correlations. The model found in CFS was significantly different from that found in the control and MS groups.

Conclusion:

CFS was characterized by a pattern of global immunologic activation using network analysis, fundamentally different from those found for either MS or control groups.

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Clinical similarities between ME/CFS & d-lactic acidosis: a systematic review

Posted on 06/14/2017 by wames

Review abstract:

Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and d-lactic acidosis: a systematic review, by Amy Wallis, Michelle Ball,
Sandra McKechnie, Henry Butt, Donald P. Lewis and Dorothy Bruck in Journal of Translational Medicine 2017 15:129 [Published: 7 June 2017]

Background:
The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of d-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of d-lactic acidosis (d-la).

Methods:
d-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high d-lactate levels. Fifty-nine d-la episodes were included in the qualitative synthesis comparing d-la symptoms with ME/CFS diagnostic criteria. A narrative review of d-la mechanisms and relevance for ME/CFS was provided.

Results:
The majority of neurological disturbances reported in d-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported d-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS.

Limitations:
Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for d-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined.

Conclusions:
Shared symptomatology and underlying microbiota–gut–brain interactions raise the possibility of a continuum of acute (d-la) versus chronic (ME/CFS) presentations related to d-lactate absorption. Measurement of d-lactate in ME/CFS is needed to effectively evaluate whether subclinical d-lactate levels affect neurological symptoms in this clinical population.

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Is “bad energy” core problem in FM & ME/CFS?

Posted on 06/08/2017 by wames

Health rising blogpost, by Cort Johnson, 31 May 2017: Study Suggests “Bad Energy” is Core Problem in Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS)

Lactate has become a big deal in both chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM).  A by-product of anaerobic energy metabolism, lactate ordinarily gets pumped out of our cells in large amounts during exertion. The lactate findings suggest that the energy needs of ME/CFS/FM patients are largely being addressed by glycolysis or anaerobic energy production. Anaerobic energy production plays an important role in energy production, but when aerobic energy production is not available and it becomes the major source of energy it produces metabolites that produce the burning muscles, fatigue and other symptoms we associate with over-exercise.

That makes it all the more shocking and puzzling to find high lactate levels in two diseases in which exercise is often hardly tolerated. That suggests that something is profoundly off with ME/CFS and possibly FM patients’ energy productions systems. The fact that increased lactate levels have been found in several different compartments of the body in these diseases only sharpens the interest.

We mostly focus on lactate in the muscles and blood, but high lactate levels have also been found in the brains of people with chronic fatigue syndrome (ME/CFS). Over the past ten years Dr. Shungu and Dr. Natelson have documented large lactate increases in the ventricles in the brains of ME/CFS patients. They’ve also found large decreases in brain glutathione levels as well.  In their latest study, they went a step further and examined lactate levels in the brains of FM patients as well.

Ventricular Lactate and the Cerebrospinal Fluid
The ventricles, which sit at the bottom of the brain, are filled with cerebral spinal fluid
When Shungu and Dr. Natelson refer to ventricular lactate, they’re also referring to the cerebral spinal fluid – a “tissue” that is becoming increasing important in ME/CFS and FM. The ventricles are four cavities sitting at the bottom of the brain where the cerebral spinal fluid (CSF) is produced. The CSF functions as a kind of cushion, a blood flow and neuro-endocrine-immune regulator and as an important waste removal outlet.

Analyzing the cerebral spinal fluid is the closest we can get to the brain short of a biopsy. CSF studies are able to uncover several different kinds of pathologies associated with the brain including bleeding, infection, inflammation and autoimmunity. Protein analyses of CSF have identified unique protein signatures for multiple sclerosis, lupus and other diseases.

CSF studies from the Simmaron Research Foundation and the Center for Infection and Immunity uncovered a pattern of immune upregulation / exhaustion and identified an atypical ME/CFS subset.  Other CSF studies found a different protein signature in ME/CFS vs. Lyme disease and evidence of increased intracranial pressure in ME/CFS. Low levels of glutathione suggest the brain’s antioxidant defenses are down.

This study examined the makeup of CSF – aka the brain ventricles – in ME/CFS, FM, and healthy controls

Read more about the study

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Controversy over exercise therapy for chronic fatigue syndrome: key lessons for clinicians and academics

Posted on 06/07/2017 by wames

Article summary:

Controversy over exercise therapy for chronic fatigue syndrome: key lessons for clinicians and academics, by Alex J. Mitchell in BJPsych Advances May 2017, 23 (3) 145-148

Chronic fatigue syndrome (CFS) is syndrome of unremitting fatigue of at least 6 months’ duration that causes significant disability. Exercise therapy has a proven track record in medicine and could be effective for some patients with CFS.

An updated Cochrane review of eight studies appeared to suggest that exercise helps fatigue symptoms, but with only a small probability of recovery and/or improvement in daily function. Provisional data on acceptability suggest that most patients are willing to participate.

However, one key study (PACE), which was well powered and influential in the Cochrane review, has been met with considerable controversy owing to lack of clarity on outcomes. Following release of the PACE study primary data, re-analysis suggested smaller effect sizes than initially reported.

Pheonix rising comment

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Bias, misleading information & lack of respect for alternative views have distorted perceptions of ME/CFS & its treatment

Posted on 06/05/2017 by wames

Article abstract:

Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment, by Ellen Goudsmit, Sandra Howes in Journal of Health Psychology [First Published May 29, 2017]

The PACE trial is one of the most recent studies evaluating cognitive behavioural therapy and graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome. These interventions are based on a model which assumes that symptoms are perpetuated by factors such as misguided beliefs and a lack of activity. Our analysis indicates that the researchers have shown significant bias in their accounts of the literature and may also have overstated the effectiveness of the above treatments. We submit that their approach to criticisms undermines the scientific process and is inconsistent with best practice.

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Endogenous pain facilitation rather than inhibition differs between people with CFS, MS, and controls

Posted on 06/01/2017 by wames

Research abstract:

Endogenous pain facilitation rather than inhibition differs between people with Chronic Fatigue Syndrome, Multiple Sclerosis, and controls: An observational study, by Simon M. Collin, Jo Nijs, Mira Meeus, Andrea Polli, Barbara Willekens, Kelly Ickmans in Pain Physician, May 2017, Volume 20, Issue 4 ppE489-E497 [Published 20 May 2017]

Background:
Commonalities in the core symptoms of fatigue and cognitive dysfunction experienced by chronic fatigue syndrome (CFS, also known as ME) and multiple sclerosis (MS) patients have been described. Many CFS and MS patients also experience chronic pain, which has been attributed to central sensitization in both groups of patients. However, the  characteristics of pain in CFS and MS patients have not been compared.

Objectives:
To compare experimental pain measurements in patients with CFS or MS and healthy controls.

Study design:
Observational study.

Setting:
This study took place in Belgium at Vrije Universiteit Brussel and the University of Antwerp.

Methods
Pressure pain thresholds, temporal summation, conditioned pain modulation, and occlusion cuff pressure thresholds rated as painful (1st cuff pressure threshold) and as 3/10 on a verbal numerical scale (2nd cuff pressure threshold) were measured in patients with CFS (n=48), MS (n=19) and healthy pain-free controls (n=30). Adjusted between-group differences were estimated using linear regression models.

Results
Finger pain pressure thresholds of patients with CFS, compared with patients with MS, were 25% lower (difference ratio 0.75 [95% CI 0.59, 0.95], P=0.02) and shoulder pain pressure thresholds were 26% lower (difference ratio 0.74 [0.52, 1.04], P=0.08).

Compared with patients with MS, patients with CFS had 29% lower first cuff pressure threshold (difference ratio 0.71 [0.53, 0.94], P=0.02) and 41% lower 2nd cuff pressure threshold (0.59 [0.41, 0.86], P=0.006). Finger temporal summation was higher in patients with CFS than in patients with MS (mean difference 1.15 [0.33, 1.97], P=0.006), but there were no differences in shoulder temporal summation or conditioned pain modulation at either site.

Differences between patients with CFS and MS tended to be greater than between either patient group and healthy controls. Pain pressure thresholds and cuff pressure thresholds tended to be positively correlated, and temporal summation negatively correlated, with higher physical function and lower fatigue in both groups of patients.

Subjective pain in patients with CFS but not in patients with MS was strongly negatively correlated with pain pressure thresholds and cuff pressure thresholds, and positively correlated with temporal summation.

Limitations:
The main limitations of our study are the relatively small sample sizes, its cross-sectional design, and its exploratory nature.

Conclusions:
We found differences in the characteristics of pain symptoms reported by patients with CFS and patients with MS, which suggest different underlying mechanisms. Specifically, overactive endogenous pain facilitation was characteristic of pain in patients with CFS but not in patients with MS, suggesting a greater role for central sensitization in CFS

Comment: Phoenix Rising Forum

 

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Dr Byron Hyde and ‘the terrible tale of Amy Brown’

Posted on 05/26/2017 by wames

Amy Brown is the pseudonym of an English child whose story is recounted by Dr Byron Hyde, a Canadian doctor who has been actively researching and treating people with ME for decades.

Dr Hyde describes the years 9 year old ‘Amy’ spent visiting many doctors without obtaining an accurate diagnosis, and the diagnosis he reached after her parents requested his help. He believes the story demonstrates:

‘convincing evidence that M.E. , distinct from CFS, is an enteroviral illness. This paper also demonstrates the stages of M.E.  illness… Amy’s story also points out what is generally not discussed, the severe and alarming explosive headaches which can occur at the M.E. disease onset, heralding an acute M.E. encephalopathy.’

Dr Hyde believes in the importance of adequate testing to make an accurate diagnosis. He uses the SEGAMI brain software (a uniform reading and processing environment for all SPECT and PET cameras) to demonstrate the significant hypo-perfusion brain injury of the left temporal region and the cingulate gyrus of the limbic system seen in all his ME patients.

An introduction to the work of Dr Hyde, followed by Amy’s tale can be read on the Health Rising website: The Doctors and Mr. Hyde: Amy Brown’s M.E Enterovirus Story

Dr Hyde founded the The Nightingale Research Foundation,  a Canadian registered charitable organization dedicated to the study and treatment of Myalgic Encephalomyelitis (M.E.) and Chronic Fatigue Syndrome (CFS) and related illnesses.

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A comparison of neuroimaging abnormalities in MS, Depression & CFS (ME)

Posted on 05/25/2017 by wames

Article abstract:

A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?, by Gerwyn Morris, Michael Berk, Basant K Puri in Mol Neurobiol. pp 1-18 [Published online 17 May 2017]

There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis).

Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes.

Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role.

Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

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Incidence of ME/CFS among U.S. nurses

Posted on 05/24/2017 by wames

Research abstract:

Incidence of myalgic encephalomyelitis/chronic fatigue syndrome in a large prospective cohort of U.S. nurses, by Natalia Palacios, Kathryn C. Fitzgerald, Anthony L. Komaroff, Alberto Ascherio in Fatigue: Biomedicine, Health & Behavior [Published online: 18 May 2017]

Background:

The incidence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the rates of both under-diagnosis and over-diagnosis, and the nature of the onset of the condition have not been assessed in large studies of health professionals.

Purpose

To determine the cumulative incidence of ME/CFS in a large population of health professionals, to examine the nature of the onset of the illness, and to estimate the frequency of both over-diagnosis and under-diagnosis of ME/CFS.

Methods

We sent an email questionnaire to participants in the Nurses’ Health Study II (NHS II), a large prospective cohort of female nurses.

Forty-two thousand three hundred and ninety-four women completed the questionnaire, which included the 1994 Centers for Disease Control and Prevention (CDC) criteria for ME/CFS.

Results

One-hundred and two women (240 per 100,000 surveyed) developed an illness that met criteria for ME/CFS between 1989 and 2009. The onset of ME/CFS was gradual in 40.6%, sudden (following flu-like illness or other precipitating events) in 18.8%, followed emotional or physical trauma in 32.3%, and was uncertain in the rest. Under-diagnosis was common: only 15 (15%) of the women who met criteria for ME/CFS reported having been diagnosed. Over-diagnosis also was common: four times as many subjects had been diagnosed with ME/CFS by community doctors as actually met criteria. The distribution of symptoms was not different in comparing cases with a sudden onset to those with a gradual onset.

Conclusions

In this large cohort of female nurses, we found a low cumulative incidence of ME/CFS. Over-diagnosis and under-diagnosis were high, even in this medically sophisticated population.

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For children with ME, school education can be a grave threat

Posted on 05/24/2017 by wames

Third Force News blog post, by Lesley Scott, 19 May 2017: For children with ME, school education can be a grave threat

Lesley Scott explains why the Scottish Government presumption that attending school is always best can affect the health of children with ME

Extract:

For children and young people with this illness, insistence on school attendance as required through the Scottish national framework GIRFEC (Getting it Right for Every Child), can impede recovery and is a key cause of deterioration and relapse often to a greater severity. Many children miss out completely on education when, with a more appropriate response, they could have maintained education and recovered their health more quickly. For children with ME, what is known as energy efficient education, such as home education, home tuition, distance or virtual learning, can maximise achievement whilst protecting health.

Education provision needs to fit the child, not the other way around.

Lesley Scott is Scottish officer for the Young ME Sufferers (Tymes) Trust

Read the full article

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