Balance deficits in CFS with & without FM

Posted on 04/05/2018 by wames

Research abstract:

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia, by Jorge M Serrador, Karen S Quigley, Caixia  Zhao, Thomas Findley, Benjamin H Natelson in NeuroRehabilitation 2018;42(2):235-246

OBJECTIVE:
Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium. The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).

METHODS:
Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.

RESULTS:
Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5). CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores. CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect. Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).

INTERPRETATION:
The major findings are that poor balance may be associated with poorer self-reported physical health. In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct. The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.

Read full article

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Markers of non-coeliac wheat sensitivity in patients with ME/CFS

Posted on 04/03/2018 by wames

Research letter:

Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/ chronic fatigue syndrome, by Melanie Uhde, Alyssa C Indart, Xuechen B Yu, Sophie S Jang, Roberto De Giorgio, Peter H R Green, Umberto Volta, Suzanne D Vernon, Armin Alaedini in Gut March 2018

We recently reported in Gut that non-coeliac wheat sensitivity (NCWS) is associated with a state of systemic immune activation in conjunction with a compromised intestinal epithelium. Patients with NCWS experience GI symptoms, most commonly including abdominal pain and bloating, as well as extraintestinal symptoms, among which fatigue, headache and cognitive difficulties feature prominently.1 2 A principal component analysis of the generated data from our study, including markers of antibody reactivity to wheat gluten, intestinal cell damage and systemic innate and adaptive immune responses to microbial components, found clustering of the patients and controls into discernible groups and demonstrated the potential utility of the identified biomarkers for identifying patients with NCWS.1

Extreme fatigue, in particular one that does not improve with rest, is a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).3 Immune system abnormalities have been found to be associated with symptoms in a substantial number of patients with ME/CFS.4 5 Furthermore, many patients complain of GI symptoms of unknown aetiology.6–8 We considered whether a subset of patients with ME/CFS may exhibit serologic markers associated with NCWS, which might explain some of the corresponding symptoms.

We screened serum samples from 131 patients with ME/CFS and 86 healthy controls (table 1), recruited as previously described,9 for the same markers as those in the above-mentioned study on NCWS.1 Questionnaires were used to assess GI symptoms within the past 6 months, including abdominal pain, bloating and nausea. Severity of individual symptoms was scored from 1 to 5 (1=absent; 2=mild; 3=moderate; 4=severe; 5=very severe), and a total score, based on the sum of individual symptom scores, was calculated for each subject.

Using the previously generated data from the original cohorts of NCWS, coeliac disease and control subjects (table 1),1 we configured a discriminant function to identify potential cases of NCWS and coeliac disease among the subjects in the ME/CFS and associated control groups. Linear discriminant analysis (Minitab 17 (Minitab) software) was used to calculate the probability of each ME/CFS and control subject belonging to any one of the three categories of NCWS, coeliac disease and healthy control. The threshold for assigning a subject to a category was arbitrarily set at a calculated probability of 0.75. Accordingly, the algorithm identified one (0.76%) patient with ME/CFS and two (2.3%) control subjects as belonging to the coeliac disease group (P=0.3). In contrast, 20 (15.3%) patients with ME/CFS and 4 (4.6%) control subjects were categorised in the NCWS group (P=0.015). There was also a significant correlation between the calculated NCWS probability and the GI symptom severity total score in patients with ME/CFS (r=0.231, P=0.011).

Our results suggest that there may be a subset of patients with ME/CFS who have sensitivity to wheat and related cereals in the absence of coeliac disease, with potential relevance to some of their symptoms. ME/CFS is recognised as a condition with a spectrum of clinical phenotypes and underlying aetiologies. Characterisation of patients into subsets based on clinical and biological data is essential to gaining a better understanding of the condition and identifying useful biomarkers and therapeutic targets.

The results of this analysis provide a rationale for examining the clinical and therapeutic relevance of food sensitivity, particularly NCWS, in the context of ME/CFS in future studies.

References….

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Unrest at the Senedd – #TimeForUnrestWales

Posted on 04/02/2018 by wames

Unrest at the Senedd          #TimeForUnrestWales

On Wednesday 18th April Unrest comes to the Senedd in Cardiff Bay. This will be an opportunity to let Welsh politicians and the media know about ME and the poor state of health and social care for people with ME in Wales.

At the lunchtime event in April:

  • the first 20 minutes of the award winning documentary film Unrest will be screened
  • people with ME and carers will speak about their experience of the illness and their struggle to find care and support
    concerns will be raised about the failure of Health Boards to implement the recommendations of the Welsh Assembly Government’s 2014 Task & Finish Group Report on ME/CFS and FM
  • politicians, civil servants and the media can find out more at the Q&A
  • there will be an opportunity for AMs and others to pledge their support to work towards improving health and social care for people with ME and CFS.

The event is being sponsored by Mark Isherwood, AM for North Wales, and organised by WAMES and members of MESiG.

We will be announcing ways YOU can get involved in the #TimeForUnrestWales campaign – Watch this space!

 

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Rituximab impedes natural killer cell function in CFS/ME patients

Posted on 03/28/2018 by wames

Research abstract:

Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation by Natalie Eaton, Hélène Cabanas, Cassandra Balinas, Anne Klein, Donald Staines and Sonya Marshall-Gradisnik in BMC Pharmacology and Toxicology 2018 19:12 [Published: 27 March 2018]

Background:

A recent in vitro pilot investigation reported Rituximab significantly reduced natural killer (NK) cell cytotoxicity in healthy donors.

Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown etiology. A consistent finding is a significant reduction in NK cell cytotoxicity. Rituximab has been reported having questionable potential therapeutic benefits for the treatment of CFS/ME, however, the potential effects of Rituximab on NK cell cytotoxicity in CFS/ME patients are yet to be determined.

Methods:

A total of eight CFS/ME patients (48.63 ± 15.69 years) and nine non-fatigued controls (NFC) (37.56 ± 11.06 years) were included using the Fukuda case definition. Apoptotic function, lytic proteins and degranulation markers were measured on isolated NK cells using flow cytometry following overnight incubation with Rituximab at 10 μg/ml and 100 μg/ml.

Results:

There was a significant reduction in NK cell lysis between CFS/ME patients and NFC following incubation with Rituximab at 100 μg/ml at

12.5:1 and 6.25:1 effecter-target (E:T) ratios (p < 0.05). However, there was no significant difference for NFC following incubation with Rituximab at 10 μg/ml and 100 μg/ml.

There was no significant difference between CFS/ME patients and NFC for granzyme A and granzyme B prior to incubation with Rituximab and following overnight incubation with Rituximab at 10 μg/ml. There was a significant decrease in granzyme B in CFS/ME patients compared to NFC with 100 μg/ml of Rituximab prior to K562 cells stimulation (p < 0.05).

There was a significant increase in CD107a (p < 0.05) and CD107b expression (p < 0.01) in NFC after stimulation with K562 cells prior to incubation with Rituximab. There was a significant increase in CD107b expression between CFS/ME patients and NFC prior to incubation with Rituximab and without stimulation of K562 cells (p < 0.01).

Importantly, there was a significant increase in CD107b following overnight incubation with 100 μg/ml of Rituximab in NFC prior to K562 cells stimulation (p < 0.01).

Conclusion:

This study reports significant decreases in NK cell lysis and a significant increase in NK cell degranulation following Rituximab incubation in vitro in CFS/ME patients, suggesting Rituximab may be toxic for NK cells. Caution should be observed in clinical trials until further investigations in a safe and controlled in vitro setting are completed.

Griffith news blog post by Louise Durack, March 27, 2018 : Drug hoped to treat CFS causes impaired immune function, Griffith study says

… the use of Rituximab in CFS patients could incur problems with their immune cells and is not beneficial as a potential treatment. The Natural Killer (NK) cells have vital functions in fighting viruses, bacteria and tumours.

“We found that these functions were significantly impaired when exposed to Rituximab in CFS patients,” says Scientific Co-Director of NCNED, Professor Sonya Marshall-Gradisnik.

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Dutch report on CFS downgrades CBT & GET, calls for more research

Posted on 03/27/2018 by wames

The Dutch Health Council  report to their Parliament in the Hague on CFS, 19 March 2018.

Report in Dutch          Summary in Dutch        Background

Google translation of Report into English     Google translation of Summary into English 

Google translation of Background into English

The Report’s conclusions and recommendations:

  • Scientific research into ME / CFS is necessary to help patients better.
  • In the meantime it is essential that the diagnosis ME / CFS is put into practice, that the symptoms of patients are taken seriously and treated as well as possible.
  • Their functional limitations must also be fully recognized when assessing entitlements to income and other provisions.
  • The Minister of Health, Welfare and Sport gives ZonMw the assignment for a long-term and substantial research program for ME / CFS.
  • The research should mainly focus on substantiating the diagnosis, the development of the disease and the treatment of ME / CFS.
  • Those responsible for training and further training of health care providers ensure that in education and training attention is paid to the severe, chronic multisystem disease ME / CFS and to what caregivers can mean for the patients with this disease.
  • The Dutch Federation of University Medical Centers (NFU) and health insurers appoint a number of university medical centers that – in collaboration with patient representatives, other hospitals, general practitioners, rehabilitation centers, sleep centers and other health care providers in the region – open an outpatient clinic for ME / CFS. associated care networks and research groups.
  • Medical assessors in the context of occupational disability insurance, the Social Support Act, the Long-term Care Act and the Participation Act recognize that ME / CFS is a serious illness that is accompanied by substantial functional limitations and do not consider a patient’s choice not to do CBT or exercise therapy as’ not adequate recovery behavior ‘.

Cort Johnson blogs about the surprising conclusions from a country  that has long supported CBT and GET as treatments for CFS:

The Dutch Surprise: Federal Report Calls for More ME/CFS Research – Less CBT/GET

A Serious Disease 
It became clear the Committee was on a mission to convince its readers that chronic fatigue syndrome (ME/CFS) is a “serious chronic disease” which substantially limits functioning. One recommendation was that the government institute health care provider training which “highlight(s) the serious, chronic, multisystem (nature of the) disease ME/CFS.”

Prof David Tuller comments on the draft report: Trial By Error: The Dutch Review; My Trip; Bristol’s Silence

The draft stated flatly that, based on the evidence, “the committee sees no reason” for GET to be used in the Netherlands. As for CBT, the draft noted that “a small majority” of committee members believed it could be helpful for some patients. But those in this group also acknowledged that patients also reported having been harmed by the approach, and they suggested that the treatment should be pursued with care. The other committee members objected to any use of the kind of CBT designed for ME/CFS, in part given the therapy’s reliance on the theory of misguided illness beliefs. In any event, this split decision was hardly a full-throated endorsement of CBT.

ME Action blog post, 23 March 2018: Dutch Health Council Downgrades GET for ME/CFS

The report stated that patients must be free to decide whether or not to undergo Cognitive Behavioural Therapy (CBT) and/or GET, and that choosing to decline these treatments should not invalidate patients’ insurance or disability claims.

“The choice to refrain from CBT or GET should not lead to the judgment that the patient misses his chance of recovery, does not cooperate in his or her recovery or acts culpably,” the report stated.

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Cortene – a new drug trial & disease hypothesis for ME/CFS

Posted on 03/26/2018 by wames

Cortene

In his blog, Health Rising, Cort Johnson introduces a new drug trial and hypothesis for ME/CFS.

With the help of Dr Lucinda Bateman and Dr Suzanne Vernon a small drug company, Cortene, will be conducting a small proof-of-concept trial of a new drug, at the Bateman Horne Center in the US.

Their hypothesis is that a maladaptation within the limbic system, which shapes our response to stress, may underlie ME/CFS.  Specifically that a receptor called CRF2, which triggers neurons to release serotonin, has become unusually prevalent in parts of ME/CFS patients’ brains. Cortene believes that the elevated release of serotonin – in response to even small levels of stress – in turn causes ME/CFS.

 

Read more:

The Cortene Way: New Drug to Be Trialed in Chronic Fatigue Syndrome (ME/CFS) Soon – Pt. I

Cortene II: A New Drug & A New Hypothesis For Chronic Fatigue Syndrome (ME/CFS)

The Cortene Way: New Drug to Be Trialed in Chronic Fatigue Syndrome (ME/CFS) Soon – Pt. I

Cortene – A New Drug for Chronic Fatigue Syndrome (ME/CFS) Pt III: The Clinical Trial

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Forward ME Group writes to the Times: patients are ‘not simply deconditioned’

Posted on 03/23/2018 by wames

Times online letter, 22 March 2018: TREATMENT FOR PATIENTS WITH ME

Sir, The article by Tom Whipple, (“Findings of £5m ME chronic fatigue study ‘worthless’,” Mar 22) highlights a long-standing problem.

The National Institute for Health and Care Excellence (Nice) is in the process of replacing its guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but this will take time.

Patients with ME/CFS in this country continue to receive damaging treatment in the form of graded exercise therapy (GET). Despite evidence of disabling metabolic abnormalities in their muscles, patients are advised to “exercise back to fitness”. They are not simply “deconditioned” as claimed by many psychiatrists. Forced exercise above very low levels characteristically incapacitates most patients. The “exercise will make you better doctrine” applied to ME/CFS is profoundly incorrect and has no scientific evidence base.

The human cost is enormous, with many sufferers from ME/CFS rendered worse by inappropriate medical management. Even worse, such management is inflicted compulsorily on some patients, both adults and children, with their informed consent being bypassed via the use of mental health and child protection legislation.

Countess of Mar, Forward-ME; Dr William Weir, infectious disease consultant;
Dr Nigel Speight, paediatrician; Dr Charles Shepherd, ME association;
Dr Vance Spence, ME research UK; Jonathan Davies, ME research UK;
Dr Gareth Tuckwell, ME trust; Dr Paul Worthley, ME trust; Jane Colby, Tymes trust;
Helen Brownlie, 25 per cent ME group; Tanya and Christine Harrison, Brame;
William and Janice Kent, Remember; Hannah Clifton, ME trust;
Clare Ogden, Action for ME

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Rethinking the treatment of CFS – a reanalysis of the PACE trial

Posted on 03/22/2018 by wames

Research abstract:

Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT by Carolyn E. Wilshire, Tom Kindlon, Robert Courtney, Alem Matthees, David Tuller, Keith Geraghty and Bruce Levin in BMC Psychology BMC series  2018 6:6 [Published: 22 March 2018]

 

Background:

The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome.

Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.

Methods:

Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole.

Results:

On the original protocol-specified primary outcome measure – overall improvement rates – there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years.

Conclusions:

These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

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PACE Trial reanalysis in the news – Findings of £5m ME chronic fatigue study ‘worthless’

Posted on 03/22/2018 by wames

Times article, by Tom Whipple, Science Editor, 22 March 2018: Findings of £5m ME chronic fatigue study ‘worthless’ [register for free to read 2 articles a week]

Scientists have questioned the robustness of a study that recommended exercise and cognitive behavioural therapy for ME sufferers.

 BBC news article, by 22 March 2018: Chronic fatigue trial results ‘not robust’, new study says

Fresh analysis of a controversial study, which recommended exercise and psychological therapy for people with chronic fatigue syndrome, suggests their impact is more modest than first thought.

The PACE trial found the treatments to be “moderately effective”, leading to recovery in a fifth of patients. But this new analysis finds “no long-term benefits at all”.

The authors of the original trial in 2007 said they stood by their findings.

That randomised trial was designed to examine the effectiveness of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis, or ME.

Its findings were positive, but patient groups like the ME Association have always been critical of the way the trial was designed and the way the results were reported.

Goalposts ‘moved’
There has also been controversy over the release of data from the trial, with some arguing it should be made available to all researchers for further analysis.

The PACE trial reported that 59% of patients who received CBT and 61% who had exercise therapy had improved overall, compared with 45% in a control group.

When the results were re-examined, after data was obtained under a Freedom of Information request, researchers found that just 20% of CBT patients and 21% of GET patients improved, along with 10% of control patients.

Figures for those who recovered were originally reported as 22% for patients in each of the CBT and GET groups, but this reduced to 8% in the latest re-analysis.

Writing in the journal BMC Psychology, lead author Dr Carolyn Wilshire, from the University of Wellington in New Zealand, said the PACE trial moved the goalposts by changing the way treatment success was measured after the trial had begun.

She added: “Until there is positive evidence to suggest otherwise, the conclusion we must draw is that PACE’s treatment effects are not sustained over the long term, not even on self-report measures.

“CBT and GET have no long-term benefits at all. Patients do just as well with good basic medical care.”

Modestly effective treatment
The ME Association, which part-funded the new study, said it was no surprise that “impressive claims for recovery following CBT and GET are not statistically reliable”.

Dr Jon Stone, consultant neurologist at the Western General Hospital in Edinburgh, said better treatments for chronic fatigue syndrome were needed, or more effective forms of rehabilitation.

“Until we have these, the question is whether it is better to offer a modestly effective treatment supported by data from many other trials, with a realistic discussion of its pros and cons, than none at all.”

The three authors of the original PACE trial – Prof Michael Sharpe, from the University of Oxford, and Prof Trudie Chalder and Dr Kimberley Goldsmith, from King’s College London, said the new analysis had used only part of the data from the trial.

They also said many other trials and meta-analyses had replicated the findings of the PACE trial.

“In conclusion, we find little of substance in this critique and stand by our original reports.”

NICE is currently updating its guidance on the diagnosis and management of chronic fatigue syndrome.

 

ME association press release, 22 March 2018: Reanalysis of the PACE trial finds impressive claims for recovery following CBT and GET are ‘not statistically reliable’ 

The ME Association believes that it is very important to encourage research data sharing and, where appropriate, independent reanalysis – which is why we made a significant financial contribution towards the processing fee for publication of this paper.

“The message is clear – CBT and GET are not effective ways of treating a serious neuroimmune disease. The sooner this message gets across to health professionals the better.”

The Herald, 26 March: ME sufferers welcome ‘unreliable’ stamp on exercise report

The Canary, 22 March 2018: The mainstream medical community just declared war on people living with ME

AfME, 22 March 2018: PACE update: latest analysis and comment

Daily Mail, 22 March 2018: Findings of chronic fatigue study `not reliable´

ME/CFS Research review by Simon McGrath, 22 March 2018: PACE trial’s findings fundamentally challenged by a new study

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A metabolic ‘trap’ hypothesis for ME/CFS?

Posted on 03/21/2018 by wames

Open Medicine Foundation blog post, 14 March 2018: OMF-funded research: a metabolic ‘trap’ hypothesis for ME/CFS

On this #OMFScienceWednesday we highlight a new project that OMF is funding, which proposes a new metabolic ‘trap’ hypothesis for ME/CFS. This project is just getting started under the direction of Dr. Robert Phair, Chief Science Officer of Integrative Bioinformatics, Inc., an expert in computational modelling of biological processes. Dr. Phair has been collaborating with Dr. Ron Davis’ team at Stanford for nearly 2 years on investigating mechanisms behind ME/CFS. In this project, they will test a new hypothesis that could help to explain some of the genetic and metabolic characteristics of ME/CFS patients.

The big data study of severely ill ME/CFS patients that we funded identified several genes that carry damaging mutations. Dr. Phair’s hypothesis, based on computational predictions, suggests that some of these mutations may slow down enzymes that process important metabolites required for our energy, brain function, and immune system. If this is true, it could explain some of the symptoms of ME/CFS. Identifying interesting mutations is the (relatively) easy part, though – experimental evidence is needed to confirm their impact.

During this project, the team will test how cells with these mutations carry out the relevant metabolic reactions, using special ‘tracer’ metabolites that can be easily followed as they are processed by the cells. These experiments will determine whether the mutations are indeed creating a metabolic ‘trap’ that could lead to the neurological and/or immunological symptoms of ME/CFS. We’ll be happy to share more details as the results provide more evidence. Stay tuned!

Read more about the metabolic trap hypothesis

Read more about Dr. Phair and his research

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