Cerebral blood flow is reduced in ME/CFS during head-up tilt testing
Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: A quantitative, controlled study using Doppler echography
- Doppler imaging to measure cerebral blood flow is feasible during tilt testing.
- Cerebral blood flow in ME/CFS patients is reduced during tilt testing.
- 90% of ME/CFS patients show abnormal cerebral blood flow reduction on tilt testing.
- Cerebral blood flow reduction correlates with symptoms of orthostatic intolerance.
The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.
429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we administered a verbal questionnaire to ascertain for 15 OI symptoms.
End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P < .0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI symptoms with the degree of CBF reduction at mid-tilt (P < .0005).
During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.
This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.
What is ME?
Video produced by A Broken Battery
From the description on the webpage –
ME is “a life-altering debilitating disease affecting the brain, the immune system and energy metabolism. The defining symptom of ME is that even minimal exertion can cause a flare in symptoms (a crash) that can last for days, weeks or even months.
Severity ranges from mild to very severe. Around 25% are house or bedbound, unable to properly care for themselves, sometimes for many years or decades at a time. The majority of severely affected patients are unable to access any services and are not offered home visits or specialist inpatient care. People with ME have a lower quality of life than people with Stroke, Cancer, Heart disease, Multiple Sclerosis, Rheumatoid arthritis. ME is not taught in most medical schools despite it affecting 15-30 million worldwide.
The WHO classified ME as neurological in 1969 but 80% of doctors still believe its psychosomatic. Many doctors still don’t know that over the last 35 years there have been over 9000 scientific publications that compared people with the illness to healthy people and they find a whole variety of abnormalities, like energy metabolism.
Dr Nina Muirhead ME Patient and Specialist Surgeon in Dermatology – The NICE guidelines “do not fit” with the patient experience and “perpetuated my misunderstanding” of ME by recommending Cognitive Behavioural Therapy and Graded Exercise. NICE is currently updating its guidance, which is expected in October 2020. The Centers for Disease Control and Prevention (CDC) in the US dropped Graded Exercise and Cognitive Behavioural Therapy as treatments for ME in 2017.
Patient surveys consistently report that Graded Exercise makes over 50% of patients worse. “In the absence of effective treatments, patients who are given a period of enforced rest from the onset have the best prognosis”. Pacing was consistently shown to be the most effective, safe, acceptable and preferred form of activity management”.
(See the webpage at the address above for references.)
From the ME Research UK website –
A revised version of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) is due to be implemented in January 2022.
The ICD is the diagnostic classification standard for all clinical and research purposes, and is therefore highly influential. Its many uses include identifying health trends, and monitoring and reporting diseases, resource allocation, safety and quality.
ICD-11 will include a new classification, Bodily Distress Disorder, which is defined as “characterized by the presence of bodily symptoms that are distressing to the individual and excessive attention directed toward the symptoms, which may be manifest by repeated contact with health care providers”.
There have been understandable concerns that ME/CFS would be grouped under this diagnosis of Bodily Distress Disorder in the new revision, which might mean that individuals with the illness would be directed through psychiatric care.
However, thanks to the sterling efforts of campaigners over many years, ICD-11 will NOT include Postviral Fatigue Syndrome, Chronic Fatigue Syndrome or Benign Myalgic Encephalomyelitis under the new classification.
At the moment, ICD-10 lists Benign Myalgic Encephalomyelitis in the ‘Diseases of the nervous system’ heading, under PostViral Fatigue Syndrome (Block 93.3, ICD 10th revision, 2007), as follows:
- Diseases of the nervous system
- Other disorders of brain
- Other disorders of the nervous system
- G93.3 Postviral fatigue syndrome
- Benign myalgic encephalomyelitis
ICD-11 will list both Benign Myalgic Encephalomyelitis and Chronic Fatigue Syndrome separately, but still under ‘Diseases of the nervous system’ and Postviral Fatigue Syndrome (Block 8E49, ICD 11th revision, 2019), as follows:
- Diseases of the nervous system
- Other disorders of the nervous system
- 8E49 Postviral fatigue syndrome
- Benign myalgic encephalomyelitis
- Chronic fatigue syndrome
From the 25% ME Group – Diagnostic Tests 4 Myalgic Encephalomyelitis
This is a summary of a highly detailed, sourced text describing measurable organic abnormalities that researchers and specialists have identified in testing of Myalgic Encephalomyelitis patients.
For various reasons, many of the articles on Myalgic Encephalomyelitis in the mainstream media (and even some of the medical texts on the illness) unequivocally proclaim not only that there are no tests which can be utilized to help confirm an ME diagnosis, but that despite extensive testing no objective or quantifiable abnormalities have ever been found in any patients with ME whatsoever. Despite their popularity, these are simply absurd claims. The reality is that objective evidence of quantifiable organic abnormalities in Myalgic Encephalomyelitis patients has existed since the 1950’s.
Not only are there a series of tests which readily allow an ME diagnosis to be confirmed, but more than 1,000 medical studies have shown a variety of measurable and in some cases extremely severe abnormalities in many different bodily systems of ME patients.
Abnormalities are also visible on physical exam. Tests will only all be normal in ME patients – as with all illnesses – if the completely wrong tests are done, or if those tested do not in fact have ME. Contrary to much of the propaganda surrounding the illness, it is also not “fatigue” or “tiredness” that is the one essential characteristic of ME, but central nervous system (CNS) dysfunction. As ME expert Dr. Byron Hyde, explains: “The one essential characteristic of ME is acquired CNS dysfunction, [not] chronic fatigue. A patient with ME is a patient whose primary disease is CNS change, and this is measurable. We have excellent tools for measuring these physiological and neuropsychological CNS changes: SPECT, xenon SPECT, PET, and neuropsychological testing.” Thus it is these tests which are most critical in the diagnosis of ME, although various other types of tests are also useful. Tests That Can Aid Diagnosis Some of the series of tests which can (in combination) help to confirm a suspected ME diagnosis include:
SPECT and xenon SPECT scans of the brain
SPECT scans have demonstrated decreased cerebral blood flow most frequently in the frontal, parietal, temporal, occipital, and brain stem areas of the brain. Eighty percent of ME-ICC patients will have abnormal SPECT scans. These abnormalities have also correlate with clinical status. Dr. Hyde adds that “I do not describe a patient as having ME unless there is an abnormal SPECT. If the SPECT is normal, I repeat it along with xenon SPECT. If the brain scans remain normal, I conclude it is unlikely to be ME.”
MRI scans of the brain
Punctate, subcortical areas of high signal intensity consistent with edema or demyelination were identified by MRI in 78 percent of ME patients (similar to those seen in MS). Research has shown that 50 percent to 80 percent of ME patients will have abnormal MRI scans. ME patients with abnormalities on MRI have been reported as being more severely impaired than those without such abnormalities.
PET scans of the brain
PET scans have shown decreased metabolism of glucose in the right mediofrontal cortex and generalized hypoperfusion of the brain with a particular pattern of decreased neuronal metabolism in the brain stem.
Of the CNS dysfunctions that make up ME, cognitive dysfunction is easily one of the most disabling characteristics of the illness. Neuropsychological testing can be used to identify cognitive dysfunction and/or to confirm a ME diagnosis. It should focus on the abnormalities known to differentiate ME from other causes of organic brain dysfunctions.
EEG brain maps and QEEG brain maps
Ninety-five percent of ME patients have been found to have abnormal cognitive-evoked EEG brain maps. But Dr. Hyde argues that QEEG brain maps are far more accurate, and that they “have been able to demonstrate not only lack of normal activity in ME patients but migration of the normal activity centers from injured areas to different parts of the brain.”
Neurological examination and the Romberg or tandem Romberg test
Most ME patients have abnormal neurological examination. The Romberg test is a useful test of brain stem function. It involves standing with eyes open and then with eyes closed with feet together or one behind the other for a minute or more. A patient tests positive for “Romberg’s sign,” or abnormal, if he or she can stand with the eyes open but falls when the eyes are closed. Professor Malcolm Hooper ME specialist at the University of Sunderland, England, explains that “In his 1995 Australian Workshop, Dr. Paul Cheney said that more than 90 percent of ME patients have an abnormal Romberg, versus 0 percent of controls.”
Tests of the immune system
The immune system abnormalities in ME patients mimic the immune pattern seen in viral infections. Specific findings include (but are not limited to):
- Increased numbers of activated cytotoxic T cells (most patients have evidence of Tcell activation)
- Low natural killer cell numbers/percentage and function (cytotoxicity)
- Elevated immune complexes
- Atypical lymphocyte count
- Significantly reduced CD8 suppressor cell population and increased activation marker (CD38, HLA-DR) on CD8 cells
- Abnormal CD4/CD8 ratio
- Elevations of circulating cytokines
- Immunoglobulin deficiencies (most often IgG 1 and IgG 3).
A more specific immune system abnormality has been discovered in MEICC of increased activity and dysfunction of the 2-5A RNase L antiviral pathway in lymphocytes. The dysregulation of the RNase L pathway strongly supports the hypothesis that viral infection plays a role in the pathogenesis of the illness. Between 80.0 percent and 94.7 percent of ME patients have evidence of an up-regulated 2-5A antiviral pathway. The degree of elevation of 37 kDa RNase L has also been shown to correlate with symptom severity. This test is as yet not widely available but will be one of the most useful tests in helping to diagnose ME in the future.
Erythrocyte sedimentation rate (ESR)
This is a common blood test used to detect and monitor inflammation based on the rate at which red blood cells settle in a test tube.] An unusually low ESR of < 5mm/hr is common in ME
Insulin levels and glucose tolerance tests
Derangement of insulin response is a frequent finding in ME patients. Glucose tolerance curves are often abnormal.
24-Hour Holter monitor
A 24-hour Holter monitor (a type of heart monitor) may show repetitively oscillating T-wave inversions, and/or a flat T-wave may be found. Holter monitors may also show heart rates as high as (or higher than) 150 beats per minute as an immediate or delayed response to the patient maintaining an upright posture, or at rest. Heart rates as low as 40 beats per minute may also be observed (during sleep).
Tilt table examination
Orthostatic intolerance is very common in ME patients, and may manifest as one of, or a combination of, the following: neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), or delayed postural hypotension.
Exercise testing and chemical stress tests
Cardiopulmonary exercise testing (CPX) is widely used for the diagnosis (and functional assessment) of various cardiac and metabolic disorders and can also be used in the diagnostic evaluation of ME patients. Heart rate and blood pressure responses during the exercise test may reveal abnormalities specific to ME, including: lower cardiovascular and ventilatory values at peak exercise (patients only being able to attain half the expected maximal workload and oxygen uptake compared to sedentary controls), elevated resting heart rates, and an inability to reach maximum age-predicted heart rates. Some ME patients can be tested via nuclear medicine (no treadmill) in Hospital.
As exercise tests are not appropriate for many ME sufferers, Dr. Byron Hyde, writes: “Patients with ME frequently cannot do exercise tests, so chemical testing as an option.”
There are also a variety of abnormalities visible on physical exam in ME patients. These abnormalities are not usual in healthy patients, but they are also found in people with other organic illnesses (so they are not specific to ME). The post-exertional paralytic muscle weakness unique to ME should also be tested for; a diagnosis of ME should never be made without this characteristic being present.
ME shares no characteristics of various “fatiguing conditions” with a variety of different etiologies made up of vague & mild “everyday” type symptoms and have no physical signs or no tests which can’t show abnormalities to aid diagnosis.
Myalgic Encephalomyelitis is a distinct organic neurological disorder (which can occur in both epidemic and sporadic forms) that has been recognized as such by the World Health Organization (WHO) in their International Classification of Diseases since 1969 with the code G93.3. It bears no relationship to any unrelated, vague, and hard-to-diagnose “fatiguing illnesses.”
“Unlike Somatization Disorder, Medically Unexplained Symptoms (MUS), Functional Neurological Disorder (FND), and Munchausen Syndrome, ME is not ‘medically unexplained.’ ME is a disease which, like lupus, has no single marker. ME is a multisystem disease with many organ and bodily systems affected, producing a myriad of symptoms, and many aspects of the pathophysiology of the disease have, indeed, been medically explained in volumes of research. These are well-documented, scientifically sound explanations for why patients are often bedridden and unable to maintain an upright posture.”
- See the full-length, fully-sourced article, “Testing for ME,” at Jodi Bassett’s Australia-based Website, A Hummingbirds’ Guide to ME, at https://www.hfme.org/ provides more information on the tests listed here as well as on many other aspects of diagnosis, plus a list of references.
- Dr. Byron Hyde, MD, is an internationally recognized ME specialist, and chairman of the Nightingale Research Foundation for the study and treatment of ME in Ontario, Canada. https://liberationislife.files.wordpress.com/2017/03/definitionofme_nrf_print.pdf
- Myalgic Encephalomyelitis: International Consensus Criteria
- GAME Website: https://artzstudios1.wixsite.com/globaladvocatesmeicc
From Let’s Do It For ME: New Total £960,000!
Invest in ME Research announced in their Christmas and New Year Funding Appeal that £960,000 has been raised and pledged to support the charity’s Centre of Excellence for Myalgic Encephalomyelitis projects.
The Let’s Do It for ME campaign is run by severely ill patients supporting the charity’s Centre of Excellence programme of biomedical research and medical education projects. Our original crowdfunding goal of £100,000 enabled this work to get underway in 2013 (patient samples for the lab work obtained since 2014) and we would love to reach £1,000,000!
So to start off the new year, we have created a grid with 40 vacant slots with a funding target of £1,000 each and invite you to contact us if you’d like to aim to raise £1,000 whether as an individual or group, private or business. Read more on the page for Our 40 x £1k Fundraisers Challenge.
Many thanks to everyone helping Invest in ME Research to achieve their goals relating to maintaining a programme of high quality biomedical reseach with international collaboration focused on establishing diagnostic tests and medical treatments for this disease.
The charity wrote in December,
“To our supporters we owe great thanks – you helped create something that was thought unachievable. A sustainable Centre of Excellence for ME is now harnessing the benefits of a strategy of collaborative international biomedical research in modern facilities with world-class researchers.”
With very best wishes to you for 2020 and the new decade ahead and grateful thanks for supporting Invest in ME Research.
In case you missed it, your input is needed to inform the agenda for an upcoming public engagement meeting at Quadram Institute.
A very Happy New Year to readers of my website, your families and friends.
A couple of weeks ago I was given a Christmas card containing a separate little tract with the following poem, which I trust may be an encouragement to you as we start another new year –
Throughout the New Year, and each step of the way,
May Christ be your portion, your joy and your stay.
With God’s precious precepts your daily delight
To lead and encourage in paths that are right.
“The Lord is my Shepherd,” how precious the word!
He’ll lead in green pastures, His promise is heard.
“Beside the still waters,” what comfort and rest!
What peace there is found upon Jesus’ breast.
His “goodness and mercy,” each day may you prove,
His comforting presence, His infinite love!
With richest compassions, each morning anew,
May multiplied mercies be showered on you!
“My cup runneth over,” His grace so abounds,
That fullest enjoyment in Jesus is found.
“The Lord is my portion,” this may your soul say,
And you will be happy each step of the way.
– Lois Beckwith (1896-1958)
A Holiday Message from Dr Ron Davis, 21 December 2019
Dr Ron Davis shares an update on research at the OMF-funded ME/CFS Collaborative Research Center at the Stanford Genome Technology Center. He shares holiday greetings and hope with the entire ME/CFS community.
Press Release from Invest in ME Research
for Immediate Release
UK Charity Pledges £500,000 for Research into ME in Norwich Research Park
UK Charity Invest in ME Research is pledging £500,000 for continued research into the disease myalgic encephalomyelitis (ME or ME/CFS) in Norwich Research Park, UK (NRP).
This major investment builds on the foundations already made for a UK/European Centre of Excellence for ME research hub in Norwich Research Park.
The pledge covers joint funding of a PhD position in partnership with University of East Anglia and over 70% of the required funding for a clinical trial of Faecal Microbiota Transplantation (FMT) being performed alongside other high-quality biomedical research at the Quadram Institute (QI).
QI’s world-class facility has seen four PhDs already employed on research into ME, focusing specifically on the gut microbiota and links to ME.
Invest in ME Research Chairman Kathleen McCall said: “This is a massive undertaking for a small charity but it underlines our confidence in the quality and direction of research at Quadram Institute. This research offers an opportunity to test a new form of treatment for ME in well-designed clinical trial. On top of the other initiatives being created in partnership with QI we believe this has the potential to change the face of research into this disease.”
Professor Simon Carding, Head of Gut Microbes and Health Research Programme at Quadram Institute Bioscience said: “We are incredibly grateful for the ongoing support from Invest in ME Research and their supporters. We are very excited at the prospect of undertaking the FMT clinical trial, as part of our ongoing investigations into the links between ME and the gut microbiome.”
This research news comes after recent meetings of the European ME Research Group (EMERG) and European ME Clinicians Council (EMECC) in which QI and UEA played major roles and which will form European collaborations and coordination of research into ME and clinical expertise development for this disease.
The continuing and developing research in Norwich Research Park holds out great hope for the future for ME patients and their families.
ME commonly presents with hugely diverse and debilitating symptoms including post-exertional malaise, unrefreshing sleep, cognitive dysfunction and widespread pain. ME has been estimated to affect around 250,000 people in the UK and direct and indirect economic costs have been estimated in the USA to be $20 billion annually. The severity of symptoms varies. Around 25% of sufferers may be classed as severely affected – often bed bound at some point in their lives with periods of relapse and remission common and only 6% returning to full health.
The pledge brings to five the number of PhD positions that the charity has funded/part-funded.
Notes for editors
About Invest in ME Research
Invest in ME Research (charity nr 1153730) is an independent UK charity finding, funding and facilitating biomedical research into ME.
Invest in ME Research is run by volunteers – patients or parents of children with ME – with no paid staff. Overheads are kept to a minimum to enable all funds raised to go to promoting education of, and facilitating and funding biomedical research into ME. The charity organises an annual International ME Conference Week in London which includes a two day research Colloquium, young/early career researcher conference and a public international conference that regularly has delegates from twenty countries attending.
The charity’s efforts are on developing the Centre of Excellence for ME to maintain a strategy of high-quality biomedical research into the disease and encouraging European collaboration in research and development of clinical expertise.
For more information visit www.investinme.org/pr01-Dec19
Contact details [Chairman Kathleen McCall, Invest in ME Research, PO BOX 561, Eastleigh SO50 0GQ, UK email: firstname.lastname@example.org]
About the Quadram Institute
The Quadram Institute (quadram.ac.uk) is an interdisciplinary research centre at the forefront of a new era of food and health research. It brings together researchers and clinicians under one roof and houses one of Europe’s largest endoscopy units and a clinical research facility.
Based on the Norwich Research Park, The Quadram Institute is a partnership between Quadram Institute Bioscience, the Norfolk and Norwich University Hospitals NHS Foundation Trust, the University of East Anglia and the Biotechnology and Biological Sciences Research Council (BBSRC).
Its mission is to deliver healthier lives through innovation in gut health, microbiology and food and its vision is to understand how food and microbes interact to promote health and prevent disease.
Four interconnected research themes in Quadram Institute Bioscience deliver a pipeline of research in plants, microbes, food and health: microbes in the food chain; the gut and the microbiome; food innovation and population health.
For media enquiries please contact:
Andrew Chapple, email@example.com, 01603 251490, 07713087883
About University of East Anglia
The University of East Anglia (UEA) is a UK Top 25 university and is ranked in the top 50 globally for research citations. Known for its world-leading research and good student experience, it was awarded Gold in the Teaching Excellence Framework and is a leading member of Norwich Research Park, one of Europe’s biggest concentrations of researchers in the fields of environment, health and plant science. www.uea.ac.uk
For media enquiries please contact:
Penny Powell, P.Powell@uea.ac.uk: 01603 591238
Ron Davis talks ME/CFS at Columbia and Princeton
Written by Janet Dafoe, PhD
Ron Davis spent the last week on the East Coast giving talks and talking individually to scientists and doctors about ME/CFS. First, he spent two days at Princeton University. He talked to individuals, groups of graduate students, and groups at lunches and dinners. He gave a talk in the huge Molecular Biology Department (includes immunology, microbiology, genetics, biochemistry, et al) in a big lecture hall with about 300 scientists. He sensed that they were surprised and shocked by how many people are affected and how severe the disease is. They were impressed by the progress Dr. Davis has made with such minimal NIH funding and relying on donations from patients.
Then Dr. Davis went to the Einstein Medical Center at Columbia University and gave a similar talk to 100 doctors and scientists in person and 184 more who logged in online. Again, they were surprised and shocked by the information he presented. He knew it was being Livestreamed so he didn’t take questions, but talked for 1 1/2 hours and incorporated questions that he is commonly asked. Nobody left. Ron really emphasizes the prevalence and severity of ME/CFS, the need for medical care, the urgent need for research, the growing group of great scientists that are working on it and the fact that none of them have enough funding from NIH.
The week before this, Dr. Davis gave the keynote address at Synchrony 2019, a large Autism conference in Pleasanton, California. Again, he had a large audience of researchers, doctors, and caregivers. They were really impressed by his research and were struck by some of the similarities between Autism and ME/CFS. OMF Scientific Advisory Board Member Robert Naviaux, MD, talked just before Ron. They are going to collaborate with Ron, sending some patients to his lab so they can investigate similarities and differences. The Autism group will be funded by one of the Autism Foundations since Ron only uses Open Medicine Foundation funds on ME/CFS.
Altered cardiac autonomic regulation
From the ME Research UK website –
Published in the journal, Medicine, last month was a systematic review looking at “evidence of altered cardiac autonomic regulation in ME/CFS”.
Simply put, “cardiac autonomic regulation” refers to the body’s control system that acts unconsciously to regulate the functions of the heart such as heart rate. This has been a recurring topic in projects funded by ME Research UK, and several of the studies referenced in this new review are from research supported by the charity, including those involving Prof. Julia Newton (Aug 2007, Apr 2009 and Aug 2011) and Prof. Jo Nijs.
The review included 64 publications looking at a number of different measurements in people with ME/CFS and healthy control subjects, including resting heart rate, maximal heart rate during exercise, heart-rate response to head-up tilt testing, and resting heart-rate variability.
A meta-analysis combining the results of multiple studies found that these parameters and more were significantly abnormal in ME/CFS patients compared with controls, indicating that the illness is associated with altered autonomic cardiac function. Although the differences were not sufficiently consistent for any of these parameters to be useful on their own for diagnosis.
These findings are not news if you have been following ME Research UK-funded studies over the last few years, but it is good to see the conclusions confirmed in a meta-analysis that includes results from many other researchers.
WE ME – a Community and ME
A new booklet from Invest in ME Research –
A condition such as ME presents not only a challenge to the patient who receives the diagnosis, nor only to the family where a child or partner contracts the illness. It tests the values and the fabric of a community. How does the community react?
The reactions and experiences describe how prepared or willing it is to overcome the challenges and support the patient with ME.
A condition such as ME presents not only a challenge to the patient who receives the diagnosis, nor only to the family where a child or partner contracts the illness.
Thanks to funding from an Awards for All grant Invest in ME Research have been able to have printed a small booklet that the team has produced giving an overview of how ME affects a community.
The booklet can be downloaded as a pdf file by clicking here.
From page 3 –
What is ME?
ME is a multisystem, complex, acquired illness with symptoms related mainly to the dysfunction of the brain, gastro-intestinal, immune, endocrine and cardiac systems. ME has been classified as a neurological disorder in the World Health Organisation’s International Classification of Diseases since 1969.
The Chief Medical Officer’s Report issued in January 2002, recognised that ME “should be classed as a chronic condition with long term effects on health, alongside other illnesses such as multiple sclerosis and motor neurone disease”. Similarly the Institute of Medicine report of 2015 stated that ME is “a serious, chronic, complex, multisystem disease that frequently and dramatically limits the activities of affected patients.”
The Third Annual Community Symposium on the Molecular Basis of ME/CFS
The Third Annual Community Symposium on the Molecular Basis of ME/CFS, sponsored by the Open Medicine Foundation, took place on September 7, 2019 at Stanford University.
All of the individual talks are now available to watch on YouTube –
Individual talks –
01 Ron Davis – Opening Remarks https://youtu.be/jWlJ0Clv6pw
02 Linda Tannenbaum and Chris Armstrong – Welcome https://youtu.be/2GSKnDE0biw
03 Janet Dafoe – Greetings https://youtu.be/mAnCWhEzNGg
04 Ashley Haugen – Symposium Logistics https://youtu.be/kEnS_d7q0u4
05 Raeka Aiyar – Revolutionizing Disease Research with Stem Cells https://youtu.be/gilWemHSI1k
06 Robert Harrington – Video from the Stanford Chair of Medicine https://youtu.be/jMApmri1YDI
07 Maureen Hanson – Thoughts and Data about ME/CFS https://youtu.be/2BZnL-ZKta4
08 Alain Moreau – Let’s Talk About You and ME https://youtu.be/AY5yrva1zYY
09 Oystein Fluge – Lessons from clinical trials in ME/CFS https://youtu.be/fGsqjx-N9yI
10 Q & A Panel Discussion – Morning Speakers https://youtu.be/T0VhJw2Fh-c
11 Ron Tompkins – OMF ME/CFS Collaboration at the Harvard Affiliated Hospitals https://youtu.be/hY6rpd4yf2M
12 Jonas Bergquist – A short video update https://youtu.be/mmIKU1OQH58
13 Juan Santiago – High-Resolution and High-Throughput Quantification of RBC Deformability https://youtu.be/LnG0TM88tes
14 Mike Snyder – Big Data, Wearables, and Health https://youtu.be/YoccazReqgU
15 Robert Phair – Metabolic Traps in ME/CFS https://youtu.be/d9oVHDh8rjk
16 Ron Davis – What’s Next? https://youtu.be/YdR6ujHxloo
17 Q & A Panel Discussion – Afternoon Speakers https://youtu.be/j5H8u4FXcHo
18 Ron Davis – Closing Remarks https://youtu.be/1wvw-idPRSQ
The PACE trial – Series Highlights
MPs, experts and patients discuss the harm and flaws of the controversial trial of Graded Exercise on ME patients. “One of the biggest scandals of the 21st century” Carol Monaghan MP.
Children with ME – Highlights
Highlights (~1 min) of the Children with ME video. 1 in 5 parents face child protection proceedings, in extreme cases parental rights have been removed. MPs, experts, charities and patients discuss some of the reasons this is happening and the impact it has had.
Watch the series –
Ron Davis discusses his research at Stanford and An Exciting Week for Advancing ME/CFS Research
Ronald W. Davis is a Professor of Biochemistry and Genetics at Stanford University and Director of the Stanford Genome Technology Center. He also has a personal connection to ME/CFS — his son was diagnosed almost 10 years ago.
In this interview with Llewellyn King, Ron discusses his research at Stanford.
The interview was posted on YouTube on September 13th 2019.
An Exciting Week for Advancing ME/CFS Research
I’m pleased to share with the OMF community that the OMF sponsored Stanford ME/CFS Working Group and Third Annual Community Symposium on the Molecular Basis of ME/CFS once again is helping to advance urgently needed research on this disease.
During the three days prior to the Community Symposium, 60 scientists from all over the world, including OMF Scientific Advisory Board members, actively participated in the Working Group. They gathered behind closed doors to brainstorm and openly discuss new ideas to move this field forward.
It was wonderful to see that this year there were new faces and early-career participants, including talented engineers, contributing to the discussions. From my conversations during the meetings, it struck me again how much kindness, passion and collaborative spirit all the participating scientists have.
At the lovely pre-symposium dinner on Friday evening at Dr. Ron Davis’s home, I had the pleasure to thank Dr. Davis as well as Dr. Ron Tompkins, Dr. Wenzhong Xiao, and Dr. Jonas Bergquist for the initiative they’ve taken in leading the OMF-funded Collaborative Research Centers, as well as the many scientists, donors, leaders and OMF staff for all their hard work.
On Saturday, the Community Symposium provided our outstanding panel of speakers an opportunity to share updates with the international ME/CFS community as well as those attending in person. Nearly 300 people were present, mostly from the U.S. but also from Sweden, Norway, Canada, Korea, Japan and Italy, and the Livestream broadcast and Facebook Live reached thousands more around the world.
In between presentations, patients, scientists and clinicians exchanged insights and ideas. It’s always inspiring to see how the scientists and clinicians in this field are personally invested in finding answers for patients fast, and how much they’re interested in learning from patients and using these events to interact with the community as much as possible.
Paolo Maccallini, a patient-expert who traveled from Italy to attend, described the experience perfectly: “Meeting all these top-notch scientists, gathered to share their perspectives on the latest advancements in the knowledge of ME/CFS, was thrilling. You deeply perceived the collaborative spirit and the professional trust they have for each other. This, along with the information they shared, made me confident for a hopeful future for patients.”
The Symposium ended on a very encouraging note, when all six speakers who were on stage for the closing panel discussion agreed, “We are very hopeful for the near future!”
In the years I’ve been working to end ME/CFS, I’ve never felt more hopeful and inspired. Our talented research collaborators have the expertise to figure this out, and the generous support of the community continues to grow so we can accelerate the pace of discovery.
With that in mind I want to emphasize to patients, keep hope alive; there’s light at the end of the tunnel, now more than ever!
Thank you all for being a part of this unique community effort, and I look forward to keeping you updated on the exciting ME/CFS research that you help make possible. We will share an overview of the Symposium from Dr. Chris Armstrong soon.
With hope for all,
Founder & CEO/President
Tribute paid to Professor Peter Behan – M.E. expert and ME Association patron
On the ME Association website –
Dr Charles Shepherd, Hon. Medical Adviser, ME Association.
I knew Peter Behan as a friend and colleague for almost 40 years.
I first met him when the late Dr Melvin Ramsay, who originally diagnosed my own M.E. following an episode of chickenpox encephalitis, suggested that I should go and see Peter at the Institute of Neurological Sciences at the University of Glasgow to help with the research that he was doing into the condition.
It was immediately obvious that Peter was a very kind and caring physician who knew all about ME.
Peter was also an outstanding neurologist who, along with his wife Professor Mina Behan and virologist Professor John Gow, was carrying out important research into brain, muscle and immune system function, along with the role of infection, in people with M.E.
Unlike most of his neurology colleagues he had no doubt that M.E. was a serious neurological illness and that the patients were being badly let down by both clinicians and the research community.
The papers that were published from his research group at the time played a significant role in helping to change medical opinion about M.E. and the whole situation regarding research.
The fact that M.E. was firmly on the medical curriculum at the Southern General Hospital also meant that a succession of neurologists working in Peter’s team gained a solid knowledge of the condition – Dr Abhijit Chaudhuri in particular, who now advises the ME Association on neurology.
Peter continued with his research interest well into retirement and helped to develop the research strategy for the MEA Ramsay Research Fund and made personal donations to the fund.
In recognition of his contribution to both clinical and research work he was invited to become a Patron of the ME Association – a position he held until his death at the end of August.
Peter was excellent and amusing company – either in Glasgow, or up in Denkeld where he was an accomplished fisherman with an encyclopaedic knowledge of salmon fishing. Each year at Christmas we would receive one of Peter’s whole smoked salmon from the Tay!
I kept in touch with Peter following his move to Edinburgh where, despite failing health in the past few years, he was always keen to know what was happening to research into M.E.
We all owe an enormous debt of gratitude to Peter. He will be sadly missed and I will be attending his funeral on Friday 13th September in Edinburgh on behalf of the ME Association.
BEHAN Professor Peter Oliver Professor Emeritus of Neurology, MD DSc FACP FRCP FLS, University of Glasgow Died peacefully at home, in Edinburgh on 31st August 2019, aged 84. Husband of the late Professor Wilhelmina Behan. Loving father to Charlotte, Miles and Edmund and devoted grandfather. Very dear friend to Dr Valerie Cairns. A service will be held at Warriston Crematorium, Lorimer Chapel, Edinburgh on Friday, 13th September at 1pm, to which all are welcome. Family flowers only. The Herald
Investigating sensory processing and cognitive function in people with ME: a pilot study
From the ME Research UK website –
Dr Sanjay Kumar and Dr Farzaneh Yazdani
Oxford Brookes University, Oxford, UK
Background and aim
Our senses are constantly being bombarded with information from our surroundings – the sights, sounds, sensations and smells around us, as well as the tastes in our mouths.
The brain has to work hard to process all this information simultaneously, and filter out what’s irrelevant so we can concentrate on what’s important at any given moment. But this ability can be impaired in people with certain clinical conditions, leading to a disabling hypersensitivity to the stimuli around them.
The resulting physical and mental overload can lead to poor coordination, dizziness, clumsiness, numbness, tingling and nausea, and may affect individuals’ ability to take in information and make decisions.
Dr Sanjay Kumar, Dr Farzaneh Yazdani and colleagues at Oxford Brookes University have previously looked at this phenomenon in people with post-concussion syndrome following head injury. And we recently awarded funding to the team to investigate the problem in ME/CFS.
Although hypersensitivity is not considered a primary factor in the diagnosis of ME/CFS, it is a common finding in people with the condition. This was borne out when the team met with people from a local ME support group, many of whom identified with the issue and said that it interfered with their daily life.
This prompted a series of investigations to understand the nature and impact of the sensory problems experienced by people with ME/CFS, and to determine whether they are associated with any functional or electrical changes in the brain.
The team aims to recruit 40 patients with ME/CFS and 40 healthy control subjects, and will begin their investigations by using a self-report questionnaire to assess patterns of sensory processing and how they affect functional performance.
The participants will then complete a series of neuropsychological tests (see below) to investigate a range of cognitive processes, followed by some simple computer-based tasks, while the electrical activity of the brain is measured non-invasively using electroencephalography.
The investigators’ hope is that the results of this preliminary work will help in our understanding of the brain mechanisms that underlie the abnormal sensory experiences of people with ME/CFS, and also lead to the development of interventions to help manage these problems.
Motor Screening Task – Participants are introduced to the format of the tests and responding via a touchscreen, and are asked to select on-screen crosses as they appear. Measures speed of response and accuracy, and tests for sensorimotor deficits or lack of comprehension.
Rapid Visual Information Processing – Assesses how well someone can keep attention on a task, in this case pressing an on-screen button when they see a predefined sequence of numbers (e.g. 2-4-6) within a random stream of numbers. Measures speed of responses and number of false alarms.
Delayed Matching to Sample – Assesses visual recognition and short-term visual memory by asking participants to match a pattern to one of four options shown below it. Measures speed of responses and number of correct patterns selected.
Stop Signal Task – Assesses how well someone can control their impulses. Participants are presented with an arrow and asked to press an on-screen button corresponding to whether it points left or right, but they must not respond if they also hear a beep. Measures reaction time and number of errors.
Two new videos about the PACE Trial
The PACE trial – Part 1: Moving the goalposts
The PACE trial – Part 2: Harm
Apparently there are more videos in the pipeline – you can look out for them on the YouTube playlist by clicking here.
The IDO Metabolic Trap
From the Open Medicine Foundation website –
By Christopher Armstrong, PhD
Dr. Robert Phair has recently published a paper detailing his “metabolic trap” hypothesis underlying ME/CFS, a theory that combines engineering and physiology put together by a man adept in both fields. Dr. Phair is co-founder and Chief Science Officer of Integrative Bioinformatics, Inc, a small company built around a unique software capable of modeling human biochemistry and theories of disease. Development of this theory was funded by Open Medicine Foundation (OMF). The paper, published in the open access journal, Diagnostics, is co-authored by Alex Kashi and Dr. Ron Davis, OMF Scientific Advisory Board Director and Director of the Stanford Genome Technology Center (SGTC).
Interestingly, understanding the theory of the “metabolic trap” opens the eyes to some unique elements of ME/CFS.
Like most chronic diseases, ME/CFS can be triggered by various factors and can run in families indicating a genetic element. Unlike other chronic diseases, ME/CFS can occur in outbreaks or epidemics. For outbreaks to exist, the genetic element of ME/CFS must be common enough for a large proportion of exposed people to get the disease. This thought process led Dr. Phair to look for damaging genetic mutations that were common in the broader population but present in 100% of ME/CFS patients. A search of public genome databases including the OMF-funded ME/CFS Severely ill Big Data Study led to IDO2. The IDO2 gene stood out because it has four common damaging mutations, and every ME/CFS patient in the Severely ill Big Data Study has at least one of them.
This story isn’t solely about IDO2 though, it’s also about its brother, IDO1. The IDO1 and IDO2 genes are named so similarly because they each encode for enzymes that transform an essential amino acid (tryptophan) into an important regulator of the immune system (kynurenine). The main difference is that when tryptophan is at high levels in a cell, the IDO2 enzyme increases its production of kynurenine while, surprisingly, the IDO1 enzyme decreases its production of kynurenine. If you have a problem with IDO2 (mutations in the gene) then you must rely solely on IDO1 to produce kynurenine from tryptophan. If for any reason the tryptophan levels in a cell rise too high, then IDO1 will stop making kynurenine and tryptophan levels will remain high. This is the IDO metabolic trap.
When we think of ME/CFS we often break the disease down into predisposing, triggering and maintaining factors. In this case, the predisposing factors are the damaging mutations in IDO2, the triggering factor is an elevation in tryptophan and the maintaining mechanism is that the IDO1 enzyme can’t convert tryptophan to kynurenine when tryptophan is high, therefore maintaining a high level of tryptophan and the low level of kynurenine in the cell. Mutations in IDO2 are common in the human population but it is unlikely that many would get ME/CFS. This is because the triggering is unlikely. Apparently, it is difficult to increase tryptophan enough to trigger the trap. That trigger likely requires an overlay of many factors, including pathogens, stressors and the environment.
This paper is avowedly theoretical; it elucidates the biochemical and mathematical foundations of the “IDO metabolic trap” as well as the experimental tests required to test the theory. Currently, these experimental tests are funded by OMF and ongoing at Stanford University in collaboration with Dr. Davis and his colleagues at the SGTC.
Read the full paper The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS.
How Can I Help Someone With Severe M.E.?
From The 25% M.E. Group –
• Most importantly, people with M.E. need to be believed and respected. Simple as that! If you have read our leaflet “8th August Severe Myalgic Encephalomyelitis Understanding and Remembrance Day” you know how serious M.E. can be. It is an awful illness – show your friend/relative that you know that.
• Even severe illness may not be instantly apparent – for example your friend/relative may be able to walk to the toilet, yet be too ill to go out in a wheelchair, watch TV or even sit up in bed for more than a few minutes. They may spend most of their energy on something as basic as eating. They may look remarkably well for half an hour or an hour, but then spend the rest of the day in pain in a darkened room.
• Flare up of symptoms after activity or stimuli is a key feature of the illness. The activity may be tiny by healthy standards and stimuli things you probably don’t even notice (such as light, movement, or background noise). Here are a few ways to help: shut doors (to reduce noise), use headphones if watching TV nearby, be aware that talking uses energy – ask your friend/relative how long the conversation needs to be and try to stick to that. If they seem particularly energetic, ironically this may be a sign that they are doing too much (and running on adrenaline!) – ask if they need a rest.
• Severe Myalgic Encephalomyelitis is very isolating. People with this illness are too ill to work or go to school, and most miss out on all social events and family gatherings. They may be too ill to communicate with friends and family, or to see their doctor (even at home), and they may feel very misunderstood. You can help ease the isolation by including your friend/relative as far as their illness will allow. For example you could take a few pictures of changes in the neighbourhood, video a special event (if they are well enough for TV), send a card, or ask if they want anything when you go to the shop.
• Your friend/relative may be too ill to use the phone, or to receive visits. This doesn’t mean they don’t want contact. You can still send postcards, or where suitable keep in touch with a carer. Many people with M.E. can manage texts more easily than conversations, so this may be a possibility.
• Watch the excellent film Voices from the Shadows. Some scenes may be distressing, so watch with care, especially if you have M.E. yourself. http://voicesfromtheshadowsfilm.co.uk/
• The 25% group can arrange for information to be sent to any health care or social services professional either directly or through the enquirer – please ask if this might be helpful. We also have an advocacy service for anyone who is struggling with the benefits system.
• Research demonstrates an abnormal response to exercise in Myalgic Encephalomyelitis, and the illness can become more severe through attempting to ‘push through’ the symptoms. Patients need to pace small activities (whether physical or mental) with regular rests. This is extremely challenging, and takes a lot of self-control, as patients want to be getting on with their lives. You can help by being aware of the temptation to do too much, by asking your friend/relative whether they need a rest.
• 8th August is a day to remember those who have lost their lives to this illness, and those living with it. Please talk to your friends about Myalgic Encephalomyelitis to help spread awareness, post something on Facebook, and maybe share a link to https://25megroup.org/ Spend some time reading our website, to inform yourself about the illness.
• Donate! The 25% ME Group represents those who are severely affected by this illness, and we will make good use of any donations. You can send a cheque to the address below, or donate online via the donate button on the website.
Thank you for reading this leaflet and for caring about your friend/relative. If you have any more questions or concerns, please do contact us by email at: firstname.lastname@example.org
SEVERE MYALGIC ENCEPHALOMYELITIS
UNDERSTANDING & REMEMBRANCE DAY
25% M.E. Group
21 Church Street,
TROON, Ayrshire KA10 6HT
Tel: 01292 318611
Advocacy Helpline: 0141 570 2938
See our WebPages on: https://25megroup.org/
Charity No: SC034265
PATRON: Dr Byron M Hyde MD
MEDICAL ADVISOR: Dr N Speight MA, MB, B Chir, FRCP, FRCPCH, DCH
SCIENTIFIC ADVISORS: Dr Vance Spence PhD
Prof M Hooper PhD. B.Pharm. C.Chem. MRIC
Why Graded Exercise Therapy and Cognitive Behaviour Therapy are Controversial in Chronic Fatigue Syndrome
Commentary by Michiel Tack
Sharpe and Greco ask the interesting question of why cognitive behaviour therapy (CBT) and graded exercise therapy (GET) are controversial in the field of chronic fatigue syndrome (CFS).
One reason is that the type of CBT prescribed for patients with CFS differs from the CBT used in other illnesses. CBT in CFS assumes that patients’ medical condition is reversible through cognitive and behavioral changes. In some trials, participants were encouraged to no longer see themselves as CFS patients.1 If persons suffering from cancer or multiple sclerosis were told that CBT could reverse their illness, one might assume this treatment would be controversial as well.
A second reason is that CFS is considered to be an “exertion intolerance disease”.2 The most characteristic symptom of CFS patients is not fatigue but post-exertional malaise. This means that patients suffer a relapse when they exceed their activity limit. If CFS patients try to push through and do more, they report getting worse.3 This is however what treatments such as GET and CBT aim to provoke. Patients are instructed to increase their activity level time-contingently and to no longer respond to an increase of symptoms by resting. Most of the randomized trials have not adequately addressed the possible harms of GET and CBT but in multiple surveys, patients report to have been harmed by this approach.4
A third reason is that both GET and CBT label characteristic CFS symptoms as unhelpful cognitive responses.5 When CFS patients, for example, report that physical activity makes their symptoms worse, this is seen as maladaptive avoidance behavior rather than a feature of the illness. When patients think their illness is awful and feel overwhelmed by it, this is labeled as ‘catastrophizing’, even though CFS patients have been found to be more functionally impaired than those with other disabling illnesses. And when CFS patients suspect they are suffering from a yet unknown biological illness, this is described as an unhelpful somatic attribution. With GET and CBT, CFS patients are encouraged to view their symptoms as the result of stress, anxiety or deconditioning, even though scientific evidence for such hypotheses is absent.
A fourth reason why GET and CBT are controversial is that, despite being frequently prescribed, these treatments are not effective in patients with CFS. Randomized trials demonstrate that objective outcomes such as work resumption, disability payments, actigraphy, exercise testing, and neurocognitive functioning do not improve after GET or CBT.6 Studies show moderate improvements on subjective outcomes such as fatigue questionnaires, but at long-term follow-up, there are often no longer significant differences in outcome between patients who received GET or CBT and those who did not.7 Critics claim that researchers have wrongly focused on the short-term improvements on subjective outcomes to assess the effectiveness of GET and CBT. They argue that because of a lack of blinding and an adequate control condition, these trials should focus on objective outcomes as these are less prone to biases.8 To resolve the controversy of GET and CBT further scrutiny of these trials is needed.
 Bazelmans E, Prins J, Bleijenberg G. Cognitive Behavior Therapy for Relatively Active and for Passive Chronic Fatigue Syndrome Patients. Cogn Behav Pract. 2006;13(2):157-166.
 Institute of Medicine, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, The National Academies Press, Washington, D.C., 2015.
 Institute of Medicine, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, The National Academies Press, Washington, D.C., 2015.
 Kindlon, T. Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Bulletin of the IACFS/ME. 2011;19(2):59-111. Available at: https://iacfsme.org/PDFS/Reporting-of-Harms-Associated-with-GET-and-CBT-in.aspx
 Tack M. The risk of labelling CFS symptoms as unhelpful cognitive responses. Clin Child Psychol Psychiatry. 2019. https://doi.org/10.1177/1359104519853849
 Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018 Oct 8;5(2):2055102918805187.
 Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry. 2015 Dec;2(12):1067-74.
 Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018 Oct 8;5(2):2055102918805187.
Meeting with Minister raised important concerns about welfare benefits for people with ME
From the ME Association website –
By Dr Charles Shepherd, Hon. Medical Adviser, and Ann Innes, Welfare Rights Adviser, ME Association.
This report follows a meeting at the House of Commons on Tuesday 18th June 2019 with Justin Tomlinson MP, Minister of State for Disabled People, Health and Work to discuss problems faced by people with ME/CFS when claiming Employment and Support Allowance (ESA) and Personal Independent Payment (PIP).
Justin Tomlinson MP, Minister of State for Disabled People, Health and Work, The Countess of Mar, Chair Forward ME, Carol Monaghan MP Glasgow North-West, Katherine Ladd, Researcher for Carol Monaghan, Dr Charles Shepherd, Hon. Medical Adviser, ME Association, Ann Innes, Welfare Rights Adviser, ME Association. A small team of civil servants who are responsible for the administration of ESA and PIP were also present at the meeting.
This meeting was arranged to take forward points and concerns about DWP benefits that were raised during the House of Commons debate on ME/CFS that took place in January 2019 and was led by Carol Monaghan MP.
As part of the information gathering process for the meeting people were asked on social media to contact either Carol Monaghan or the ME Association with problems they are facing with claims for ESA or PIP. Over 500 emails and social media comments were received. Key points were then summarised by the ME Association and by Katherine Ladd, Carol Monaghan’s research assistant, for use at the meeting.
Thank you to everyone who responded to this request for information. And to Carol Monaghan MP for securing this meeting, and to the Countess of Mar for all her continuing work in the House of Lords on DWP benefit issues as they affect people with ME/CFS.
As previously noted, there was not enough time to raise the often-complex individual problems that people are faced with when applying for welfare benefits. However, we did manage to cover a lot of ground during the meeting – which went on for longer than expected.
We also quoted from the section on Prognosis in the Chief Medical Officer’s (2002) report on ME/CFS and from Professor Malcolm Harrington’s first (2010) Independent Review of the Work Capability Assessment.
General information on ME/CFS in relation to DWP benefit applications
During the meeting we emphasised several important points relating to the symptoms and resulting disability that occurs in ME/CFS, many of which are not being taken into account during medical assessments for ESA and PIP. In particular:
1. The core symptoms of ME/CFS – activity-induced muscle fatigue and pain, cognitive dysfunction/brain fog, the inability to sustain physical and mental activity, and the resulting post-exertional malaise/symptom exacerbation if people go beyond their physical and cognitive limitations. The latter being important because claimants should only be able to carry out descriptor tasks if they do not suffer significant after effects.
2. The way in which ME/CFS symptoms often fluctuate throughout the day and from day to day – so ‘snapshot’ conclusions as to what someone can do once, or on a good day, are both inappropriate and inaccurate.
3. Many of the descriptors used in medical assessments for ESA and PIP do not measure or reflect the impact that the core symptoms of ME/CFS have on a person’s capacity to carry out meaningful employment.
4. The need to ensure that people are asked by the medical assessors if they can carry out descriptor tasks reliably, repeatedly, safely and in a timely manner. If they cannot do so they cannot be scored as being able to do so.
5. Case law states that if someone cannot carry out a descriptor task for a significant period (i.e. more than an hour) within a day they should be considered as being unable to do that descriptor task for the entire day.
Specific points that were raised during the meeting
We were able to raise specific issues covering the whole claimant journey from completing an application to going through reconsiderations and challenging a DWP decision through an appeal:
1. People with cognitive dysfunction often require help and extra time to fill in the long and complex paperwork when applying for ESA (i.e. the ESA50 form) and PIP. We asked for a two-week extension period on request to the original return deadline limit for the ESA50 – in the same way that this applies for PIP. The DWP agreed to consider this relatively straightforward request. However, this is something that would have to be requested by the claimant, if the DWP do decide to adopt our suggestion. The DWP pointed out that it should be possible to arrange a home visit from one of their staff to help to fill in forms such as the PIP and ESA medical questionnaires if a request is made.
2. People should be able to have a medical assessment at home if this is supported by their GP. Just because someone may be able to cope with a visit to a nearby GP surgery does not mean that they can cope with travel to and from a medical assessment centre for a detailed interview and physical examination that could last for up to two hours. More use of paper-based assessments should be made in cases where a GP can confirm that the person is severely affected and housebound as a result. We were asked to submit any cases where home visits or paper-based assessments are refused without good cause.
3. It was pointed out that the medical assessors have a duty to make reasonable adjustments in assessment procedures (i.e. arranging a home assessment or terminating an interview/assessment when the person was clearly unwell or not able to properly answer questions). Failure to do so could be a contravention of the Equality Act.
4. Assessment centres must be suitable and accessible for people with mobility problems and/or are having to travel a long distance.
5. People with ME/CFS are often under no regular medical supervision – so it can be very difficult, or even impossible, to obtain supportive medical information in the time required.
6. People should not have to pay a GP to provide supportive medical evidence – evidence collected for the meeting indicates that this is quite common, and the charge can be up to £40. Medical evidence is also often ignored, and the decision is based solely on the assessment report. In evidence collected for the meeting, it was clear that some reports bore little resemblance to what the person had said during the assessment.
7. Evidence from private healthcare professionals, other health professionals, and carers should also be considered.
8. Some medical assessors do not have an accurate or adequate knowledge of ME/CFS. Training on symptoms, fluctuation and severity in ME/CFS is clearly required along with how this affects mobility, intellectual capacity, self-care and the ability to take on meaningful work. It was pointed out that members of the Forward ME group are involved with the preparation of professional development modules and other training initiatives.
9. Cognitive dysfunction (i.e. problems with memory, concentration, attention span, information processing) can be a very disabling aspect of ME/CFS. However, most people find that they are awarded low or no points for descriptor tasks that involve some form of assessment of cognitive function.
10. Training on ME/CFS for DWP decision makers and members of tribunal panels was also raised. NB: Administration and training of tribunal members is the responsibility of the Ministry of Justice.
11. Medical reports still contain inaccurate or guesswork conclusions, or even dishonest information, especially for descriptor tasks that require specific information (e.g. walking distances). Note: This has also been brought to the attention of the DWP by the House of Commons Committee on Work and Pensions.
12. All claimants should be able to have their medical assessment audio recorded and facilities for doing so should be readily available – which is not the case at present.
13. Re-assessments, which form part of the on-going review process, should be reduced in frequency where a person can supply medical evidence to show that their condition has stabilised for a period of years and that all appropriate approaches to management have been tried. Information on 5-year prognosis in ME/CFS from the CMO report was referred to here.
14. Some people with ME/CFS are now having to wait for a long period of time (in some cases over six months) between making an appeal and the appeal being heard.
15. The whole procedure can be very stressful, especially when a decision is being challenged. As a result, some people just give up trying to obtain a benefit that they should be entitled to.
Both sides agreed that this had been constructive and useful meeting. The points we made were listened to very carefully and we felt that the Minister had been well briefed and was genuinely interested and concerned by what we had to say.
The DWP ministerial group requested that we forward any cases to them with names and national insurance numbers where the law around being able to carry out a descriptor “reliably” was not being properly considered.
A further meeting, this time involving representatives from the three organisations – Atos, Capita and Maximus – that carry out medical assessments for the DWP is now being arranged.
1. The House of Commons debate: Appropriate ME Treatment – January 2019
2. Pro forma PIP letter (see opposite) that has been designed by Ann Innes (Welfare Rights Adviser, ME Association). This can be used as an aid by health professionals to provide supportive medical evidence for applications.
3. ME Association Guides and Leaflets relating to Welfare Benefits incl. how to apply for Universal Credit (UC) and Personal Independence Payment (PIP). An updated guide to Employment Support Allowance will be published shortly.
4. Justin Tomlinson MP, Minister of State for Disabled People, Health and Work, CV.
Tribunal service stats on appeal rate success
Claimants are winning PIP and ESA appeals at the highest rate ever recorded, according to the latest Tribunals Service statistics. Overall, 70% of social security appeals are successful, with the claimant getting a better award than they originally received from the DWP. The success rates for benefits include:
The success rate for PIP is up 4% on a year ago, whilst the success rate for ESA has risen 5%.
The number of appeals is down, however. ESA appeals are down by 42% compared to a year ago, although much of this is due to the introduction of universal credit.
PIP appeals are also down, this time by 14% compared to a year ago. This may, in part, be due to a slowdown in the transfer of claimants from DLA to PIP.
Overall, social security and child support appeals are down 19% on a year ago.
The time it takes for appeals to be dealt with is rising, however, is spite of a diminishing caseload. The mean length of time for a case to be dealt with has risen to 30 weeks, up from 24 weeks a year ago.
Source: Benefits and Work website
Additional comment from Dr Charles Shepherd:
This high success rate on appeal for both ESA and PIP benefits indicates that it is well worth appealing against an unfavourable DWP decision if you believe you have a good case.
The success rate on appeal can be significantly improved by providing up to date and supportive medical attendance that is relevant to the claim and attending the tribunal in person.
Please seek advice from a welfare rights adviser to assess the strength of your case as your whole award is looked at again at the tribunal, not just the bits you disagree with.
So, if your evidence/case isn’t strong enough there is a risk to your existing award. If you have not been given an award, however, it is certainly worth appealing.
Children with ME
Out of sight… Recent work looking at how to involve severely ill ME/CFS patients in research
(Taken from the Spring edition of “Breakthrough” magazine produced by ME Research UK.)
There is a considerable lack of information about those people with ME/CFS who are severely ill. They are often neglected—even though they have worse prospects of recovery—and under-represented in what little research is done.
A large part of the problem is that their challenging circumstances mean these individuals have difficulty accessing medical care and engaging in medical research. Is there any way of improving this situation?
With funding from ME Research UK, Victoria Strassheim and colleagues at Newcastle University have been conducting a programme of research concentrating on severely affected ME/CFS patients. Over the last couple of years, Victoria has published a review of existing research on severe ME, and an exploration of the effects of deconditioning in these patients. A third paper was recently published in BMJ Open, and looks specifically at how to include severely affected ME/CFS patients in research.
The first part of the project was to attempt to contact and evaluate patients with severe ME/CFS within the Northern England Clinical Network. The participants were adults with ME/CFS who were wheelchair-, house-, or bed-bound. A total of 483 questionnaire packs—including the Barthel Functional Outcome Measure and the De Paul fatigue questionnaire—were sent out to those people identified.
Unfortunately, only 63 packs were returned, although 76% to 88% of participants managed to complete the questionnaires successfully. The responses provided a host of information on the burden of symptoms and functional difficulties patients have to live with. The findings of the survey are freely available to download from the BMJ Open website: bit.ly/StrassheimSurvey.
The second part of the project involved making a series of home visits to five severely ill ME/CFS patients, and attempting to complete assessments previously conducted in people with mild or moderate ME/CFS.
Over the course of four visits, a number of activities were attempted, including various physical and respiratory tests, cognitive assessments, and several questionnaires. Two patients were able to complete all of the assessments, while the other three achieved around 50%, and were unable or refused to perform the other tests, or could not attend due to ill health.
The investigators conclude that people severely affected by ME/CFS can engage with research, but they have a considerable burden of symptoms and a poor quality of life, and they need more support during the research process. The use of “research advocates” is suggested, to help engage and recruit these individuals into clinical studies.
He pioneered technology that fueled the Human Genome Project. Now his greatest challenge is curing his own son
By Ryan Prior, CNN
May 12, 2019
(CNN) – Multiple times a day, every day, Ron Davis sits with his head bowed, waiting outside his son’s bedroom for a subtle signal that it’s all right to come in.
He opens the door to the space where Whitney has spent most of the last decade.
Whitney lies motionless on a simple bed, his head shaved and his frame emaciated. He’s fed by a tube directly into his stomach. His lips haven’t uttered a word in five years.
Davis, who is 77, leads a lab that invented much of the technology that powered the Human Genome Project. Now he and his wife spend much of their days caring for their 35-year-old son, who is immobilized by myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS).
Sunday is ME/CFS International Awareness Day. There is no cure. But Davis is leading a global push to root out the molecular basis of what is laying waste to Whitney and millions of other sufferers around the world so that scientists can better treat the disease.
Davis signals to his wife, Janet Dafoe, that Whitney is ready. She goes in and wipes her son’s face. She pulls the covers up toward his head while he lies motionless.
She fixes an IV bag to a pole, which will drip water into her son’s veins.
Davis sinks to his knees and takes Whitney’s socks off. He clips his son’s toenails. He washes his son’s feet.
For the couple, it’s a holy moment.
Davis led a revolution in science
Davis and Dafoe will celebrate their 50th wedding anniversary in July. Decades ago, they would have never predicted their current situation.
Now their everyday lives are consumed with caring for their son. At least one of them must be at home every day to attend to Whitney.
“My wife and I can’t go away together anymore,” Davis says. They used to go to the beach every year, but it’s been more than seven years since they last went. On basically a single income, they struggle with finances.
“It has turned my life upside down in many respects. I decided to terminate everything I was working on before Whitney got sick,” Davis says. “Everything is ME/CFS now. It’s an emergency kind of effort.”
The couple have spent their careers in and around Stanford University. Davis worked for decades in the school’s biochemistry and genetics department while Dafoe, who just turned 70, works as a child psychologist. She has scaled back her hours to about five hours a week to care for her son.
After his PhD at Caltech, Davis completed his postdoc at Harvard studying under Nobel Laureate Jim Watson of “Watson and Crick” fame, who was immortalized in science textbooks for co-discovering the double-helix structure of DNA in 1953.
Davis joined Stanford’s biochemistry department in 1972 as an associate professor and quickly began making a name for himself.
He co-wrote one paper that created a map with a new way to link genes to the traits they caused, which became a cornerstone of the field of genomics. It led Davis and his colleague to write a “proposal for a map of the whole human genome.” The National Institutes of Health turned them down in 1979, saying their plan was too ambitious.
But Davis kept innovating, eventually accumulating more than 30 patents for technology he developed.
Finally, the world caught up to his vision. The $3.8 billion Human Genome Project began in 1990, with Davis’ gene-sequencing technologies at its core. Completed in 2003, it launched a revolution in science. Handing researchers that foundational blueprint for human life gave biologists and doctors what up to that point was an unimagined power to diagnose, treat and ultimately prevent the full gamut of human disease.
Davis was shortlisted by The Atlantic, along with SpaceX founder Elon Musk and Amazon founder Jeff Bezos, as someone tomorrow’s historians will consider today’s greatest inventors.
The same prescient mind that dreamed up the Human Genome Project now devotes days to what Davis calls “the last great disease to conquer.”
He may need all his brilliance to save his son.
But then his son got sick, and his priorities changed
Davis and Dafoe raised their two children in a quiet Palo Alto neighborhood. Each year they backpacked as a family in California’s Sierra mountains, disappearing for weeks at a time.
“I carried Whitney up there when he was young,” Davis says. On one of these trips 5-year-old Whitney impressed his father by walking nine miles in a single day. On another Sierras trip their baby daughter Ashley took her first steps at 5,000 feet above sea level.
“I haven’t gone in 10 years now,” Davis says. “I would love to do that with Whitney again.”
By 2008, Whitney, was 24 and living in a small town in Nevada, knocking on doors for then-Sen. Barack Obama’s presidential campaign.
But he often complained about being exhausted. A skilled photographer, Whitney captured images at Obama’s inauguration in 2009, but even then he could no longer work a full day.
After years of declining health, seeing numerous doctors and not getting answers, Whitney was finally diagnosed with ME/CFS.
As his health worsened, he moved in with his parents in May 2011. He tried to keep working as a wedding photographer but soon gave that up because he needed a week to recover from shooting a single wedding. He soon became mostly bedridden.
In his last post on his photography website, Whitney lamented that “chronic fatigue syndrome” couldn’t do justice to his condition. He preferred “total body shutdown.”
Whitney has lost the ability to speak — something a very small fraction of ME/CFS patients experience. Dafoe says he used to communicate with the family via text messages, but that skill is now lost too, as even the glow of a smartphone screen is too much stimulation for him. The heart emojis he sent to his caregivers are just memories now.
Eventually he could no longer eat solid food.
In one of his last texts to his parents, he wrote, “I’m sorry I’m ruining your golden years.”
To seek a cure, Davis recruited a dream team of researchers
Over a life spent at the frontiers of science, Davis has collaborated with many accomplished researchers. He’s cashing in on those relationships now in building a world-class team he hopes can find the molecular basis for ME/CFS.
“I made phone calls, and everybody I called said yes,” Davis says.
Some of his colleagues had never heard of the disease. He told them it affected 1% of the population, or about one in 300 Americans. He told them the National Institutes of Health at the time was dedicating less than $6 million annually to researching the disorder.
That poses a challenge in tackling an illness that lacks an FDA-approved treatment, doesn’t have a known cause or a singular lab test for clinicians to diagnose it. ME/CFS has lagged behind in the bio-medical imagination compared with cousins like multiple sclerosis, which also affects the immune system and the nervous system.
Following outbreaks in the 1980s, some dismissively called chronic fatigue syndrome the “yuppie flu.”
But its symptoms, which include constant exhaustion, pain, brain fog and unrefreshing sleep, can be as disabling as late-stage cancer. Taking a shower may leave someone with ME/CFS bed-bound and unable to do anything for days.
In 2017, NIH doubled its research spending on the disease to $12 million. But Davis argues that compared to other diseases of similar severity and prevalence, that’s not nearly enough. Multiple sclerosis, a disease that affects fewer patients than ME/CFS, attracts more than $100 million a year in NIH-funded research.
Davis now regularly convenes top scientists via an advisory board he set up through the Open Medicine Foundation, a California-based non-profit that’s raised $18 million to research the disease. Its hub is Davis’ Stanford Genome Technology Center, making Davis unique among living scientists in his ability to coordinate the discovery of a cure.
But to make the kind of progress he and his colleagues envision, they need a lot more money.
They are making slow but steady progress
ME/CFS patients, like those with multiple sclerosis and other diseases, fall on a spectrum. Some are still able to go to an office and work, while others are bedridden 23 or more hours a day.
At research conferences, Davis sometimes sits and talks with ME/CFS patients for hours.
“I’m very sympathetic to them,” he says. “It makes me feel that I have to solve this, but not in an arrogant way. I just know I have to put every ounce of energy into this to help all the patients, which also include my son.”
Davis and Dafoe know there’s a vibrant mind and spirit alive in their son’s weakened body. Whitney is a devout Buddhist, and their house is strewn with prayer flags. Dafoe thinks Whitney spends much of his day meditating.
When Whitney’s younger sister Ashley got married, Dafoe pointed to the ring on her finger to pantomime the happy news to her son. The two siblings had been very close. Whitney didn’t speak, but held his hands to his heart and wept with joy.
At Davis’ lab, Whitney’s blood samples are among many churning away in sequencing machines, contributing to what his organization believes is the deepest study of ME/CFS patients ever attempted.
This wouldn’t be the first time Davis has set his sights on a problem the scientific establishment found unsolvable. “You have to look for those,” he says.
He and his team have been hard at work the past few years. One of their inventions, a “nanoneedle” for testing blood, speaks to the need to find a single biomarker in patients’ blood.
A blood test which identifies a specific molecular abnormality unique to ME/CFS patients has long been a sticking point in researchers’ quest to get the disease more recognized. Having one could spur more drug development, because pharmaceutical companies would understand the root of what’s wrong with patients.
Davis’ team has tested their nanoneedle with initial success and recently published their findings in a scholarly journal. They discovered ME/CFS patients’ blood responds to the introduction of “stress” — in this case, salt — differently than the blood of healthy people. Davis hopes the device will ultimately produce a cheap clinical test by which doctors can identify ME/CFS quickly and accurately.
He also wants to explore measures to prevent the disease. For example, he wants to understand why people with mononucleosis often develop ME/CFS.
Those are just a few of many things Davis’ team are working on.
“We don’t have enough money, so we have to prioritize,” he says.
Davis flew to Washington in early April for a symposium about ME/CFS. He almost didn’t make the trip because it would leave his wife at home alone, caring for Whitney while she had the flu.
But she told him he had to go.
Caring for Whitney is a daily ritual
Davis and Dafoe sometimes wait for hours outside Whitney’s room, peering through a keyhole to see whether he has assumed a position in bed indicating it’s all right to come in. With words no longer an option, they must interpret Whitney’s postures and occasional hand signals.
Six times each day, every day, they perform this ritual, silently, dutifully, shut off from the gaze of the world.
They start around 2:30 p.m., first hooking up Whitney’s IV. On the next entry into his room, they hook up the pump for the “j-tube” that will send nutrients directly into their son’s stomach.
On the third visit, they wash and clean the small plastic vessels next to Whitney’s bed that he uses as urinals. Next they come back in to put the urinals on Whitney’s stomach for when he’s ready to use them again. On their last visit, often around 2:30 a.m., they’ll put ice on Whitney’s stomach to help soothe his excruciating digestive pains.
“I feel like I’m living in a different world. It’s hard to say anything when people ask ‘how are you doing?'” Dafoe says. “Our world has just been consumed by a chronic illness.”
There’s a disciplined intentionality behind their movements. For Whitney, the tiniest deviation in their procedure can be devastating.
“His cognitive processes don’t work right,” Dafoe says. She and her husband wear plain shirts with no lettering when they’re in Whitney’s room because the sliver of energy it takes his brain to process a word can cause him to crash. They even use tape to cover labels on tubes of Neosporin.
Such crashes cause Whitney severe stomach pain, which make it impossible for them to put more food in his feeding tube.
Dafoe wants her husband to get enough sleep so that he can stay fresh and focused on researching the disease. That means on many nights she’s up until 5 or 6 a.m. helping Whitney.
By 5 p.m. she’s back to caring for her son.
They hope their son’s suffering can have a greater purpose
“I got a PhD. That was hard,” Dafoe says. “I’ve climbed mountains. That was hard.”
But she says enduring Whitney’s illness is the most difficult thing she’s done in her life, “by a factor of thousands.”
One simple truth guides her. “He’s my son. I just love him.”
Dafoe receives messages from ME/CFS patients all over the world who say they are inspired by her husband and alarmed by her son’s severe condition. She says she feels like a mother to these people, many of whom are suicidal — a rational response to a life spent hovering just above death.
Many tell her Whitney is their north star. They say if he can go on living through hell, year after year, then their suffering must be endurable too.
“He’s saving lives,” Dafoe says. “Just by lying there.”
Nearly all her and her husband’s communication with Whitney is through pantomimed gestures. If he wants more of something he’ll hold his hands together, then bring them apart.
But every so often the fog lifts a little and Davis and Dafoe can speak more complex ideas aloud to Whitney. A few months ago, they told him how prominent his father has become in the field of scientists researching his disease.
“He was really excited about that,” Dafoe says.
Whitney punched the air like a boxer, signaling that he intends to fight on.
Ryan Prior is a cross-platform associate producer at CNN. He was diagnosed with chronic fatigue syndrome in 2007 and wrote about that experience here.
CBT for ME/CFS is not effective
Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review
Mark Vink, Alexandra Vink-Niese
First Published May 2, 2019
Analysis of the 2008 Cochrane review of cognitive behavioural therapy for chronic fatigue syndrome shows that seven patients with mild chronic fatigue syndrome need to be treated for one to report a small, short-lived subjective improvement of fatigue. This is not matched by an objective improvement of physical fitness or employment and illness benefit status. Most studies in the Cochrane review failed to report on safety or adverse reactions. Patient evidence suggests adverse outcomes in 20 per cent of cases. If a trial of a drug or surgical procedure uncovered a similar high rate, it would be unlikely to be accepted as safe. It is time to downgrade cognitive behavioural therapy to an adjunct support-level therapy, rather than a treatment for chronic fatigue syndrome.
For years, the recommended treatments for chronic fatigue syndrome (CFS) have been cognitive behavioural therapy (CBT) and graded exercise therapy (GET). These recommendations have been based on Cochrane reviews (Larun et al., 2017; Price et al., 2008) and a large randomised controlled trial by White et al. (2011), informally referred to as the PACE trial (‘Pacing, graded Activity, and Cognitive behaviour therapy; a randomised Evaluation’). This trial concluded that CBT and GET were moderately effective treatments, leading to recovery in 22 per cent of patients. Due to its size (n = 640) and promotion, it has been very influential in the promotion of CBT and GET as effective treatments for CFS (Wilshire et al., 2018b). Recently, a number of re-analyses of the PACE trial, including a special issue of the Journal of Health Psychology (Marks, 2017), have raised significant concerns with the published outcomes of the trial. If the PACE trial had not made a significant number of outcome changes, which led to an overlap in entry and recovery criteria, then there would not have been a difference in recovery rate between CBT and GET and the two control groups (no treatment (specialist medical care) and adaptive pacing therapy) (Geraghty, 2017a; Vink, 2016; Wilshire et al., 2018b). Essentially, the recovery rate would have been the same as the natural occurring one (Cairns and Hotopf, 2005). The absence of objective improvement in the PACE trial (fitness and 6-minute walk test (6MWT)) and the increase in illness and unemployment benefits, matched the findings from the evaluation of the use of CBT and GET in the Belgium CFS knowledge centres (Stordeur et al., 2008). As noted by O’Leary (2018), ‘although PACE [has] dictated management of ME/CFS across the globe for many years, the study fails to meet basic standards of scientific methodology’. ‘Indeed, it is difficult to imagine how such a large-scale investigation could have developed, proceeded and passed through the review process unless its scientific failings were actually characteristic of its field’. Analysis of the Dutch FITNET trial of Internet CBT for adolescents (Ghatineh and Vink, 2017), of the Dutch FatiGo trial of multidisciplinary rehabilitation treatment (Vink and Vink-Niese, 2018a) and of five Dutch hallmark CBT studies (Twisk and Corsius, 2017) supported this observation. A recent re-analysis of the Cochrane exercise review for CFS (Vink and Vink-Niese, 2018b) revealed a number of methodological concerns with many of the studies reviewed as part of the Cochrane review of GET for CFS and a lack of objective evidence for improvement in physical function. It also showed that the problems noted by O’Leary are not confined to Dutch studies. O’Leary also concluded that ‘the PACE controversy suggests a need to evaluate the scientific credibility of psychosomatic medicine generally’. As such, we carried out an analysis of the Cochrane review of CBT treatment for CFS by Price et al. (2008), to ascertain if this review contained any of the problems identified in Vink and Vink-Niese (2018b), by O’Leary (2018) or Geraghty (2017a) and also to assess whether or not the conclusions of this Cochrane review – that CBT is somewhat effective with moderate size effects – is justified by the data contained within the primary studies included in the review. In our analysis, we concentrated on the objective outcome measures to establish if improvements in self-report (fatigue) translate to observable improvement in objective tests (physical ability, fitness, etc.) as there is an inverse relationship between fatigue and physical activity (Rongen-van Dartel et al., 2014).
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Something in the blood
Remarkably, four independent groups have now found evidence that a factor in the blood can affect cell metabolism/mitochondria in ME/CFS and transfer the effect to healthy cells. Here is a summary of the provisional findings.
The first to find the effect were Dr Oystein Fluge and Professor Olav Mella in 2016.
They were studying energy production in the cell, a logical thing to do when trying to understand an illness where energy is in such short supply.
Cells have two ways to convert food molecules into usable energy. Glycolysis is a process in the cell cytoplasm that extracts a small amount of energy from carbohydrate molecules, producing lactate. But the real houses of energy production are mitochondria, which burn up food molecules with oxygen, producing large amounts of usable fuel.
Fluge and Mella used an expensive bit of kit called the Seahorse analyser, which measures glycolysis through the lactate production and mitochondrial activity through changes in oxygen levels.
They tested normal healthy muscle cells that had been grown in the lab. But they added to those cells serum taken from either ME/CFS patients or healthy controls. Serum is the fluid left over after blood has clotted and it contains small molecules and other soluble substances.
They have data for 12 people with ME/CFS and 12 healthy controls, a relatively small sample.
What they found was, surprisingly, that the muscle cells produced more lactate and burned more oxygen when they were incubated with ME/CFS serum than when incubated in serum from healthy controls. And the effect was particularly strong when the cells were made to work hard.
So something in the serum (which comes from blood) of ME/CFS patients is affecting healthy cells, and somehow making them work harder.
This is the only published study to date, but three other groups have revealed related findings at conferences.
Dr Ron Davis provided the most dramatic demonstration of the effect in a plasma swap experiment using his nanoneedle test. Plasma is the liquid left over when solid matter has been removed from blood: the the red and white blood cells, and platelets.
The nanoneedle chip measures electrical impedance of cells. In the presence of salt (which stresses the cells because they have to use energy to pump the salt out) the impedance of cells in ME/CFS blood increases much more than cells in blood taken from healthy controls.
Davis’s group then ran an elegant experiment using this set up. They put blood cells from healthy donors in plasma from ME/CFS patients and found that the healthy cells behaved like ME/CFS ones did, with a big increase in electrical impedance. And when they put ME/CFS cells in plasma from healthy controls, they found that these ME/CFS cells behave like healthy cells.
So plasma from ME/CFS patients makes healthy cells behave like ME/CFS ones. And plasma from healthy controls makes ME/CFS cells behave like healthy ones. These are stunning findings.
We don’t know the sample size for this study but hopefully more details will be available soon as a paper has been accepted for publication in the Journal PNAS.
Karl Morten, Oxford university
Like Fluge and Mella, Dr Karl Morten looked at mitochondria/energy metabolism in lab grown muscle cells and also saw an effect.
His group used a molecular probe to measure oxygen concentration within cells to track the activity of mitochondria.
They found that adding plasma from healthy controls made no difference to oxygen levels of the muscle cells. But adding plasma from ME/CFS patients caused oxygen levels to fall, indicating that the mitochondria were working harder (a similar result to Fluge and Mella).
Morton said he didn’t know why the mitochondria were working harder: he said it might be that they were working less efficiently, but the goal was to find out.
The study used over 30 patients and Morton noted that on average the levels were lower for patients than for controls. He suggested this might be due to a subgroup effect, where only some patients had the effect, with around a third of patients scoring below the lowest oxygen level for healthy controls.
Bhupesh Prusty, Wuerzburg university
Dr Bhupesh Prusty has also looked at the effect of a blood factor on mitochondria, but his work focuses on a less well-known role of mitochondria, in immunity against viruses.
Although mitochondria are normally shown as single bacteria- or bean-like units, the reality is more complex. In living cells, mitochondria constantly fuse together and separate, and the fact that they are often fused together, like a string of beans, is important for their ability to fight viruses.
Some viruses, including HHV-6, fight back by causing mitochondria to fragment back into their single forms, reducing their ability to fight viruses.
Serum from ME/CFS patients causes mitochondria that were fused together to fragment, whereas plasma from healthy controls does not.
So far, the group have only looked at five patients and three controls, so these are very provisional results.
In a separate experiment, his group showed that the effect was reversible (they washed away patient serum after three days and mitochondria gradually resumed normal fusing behaviour).
Fluge’s and Morten’s studies are directly linked to energy metabolism. Davis’s is indirectly: the salt added to the nanoneedle test forces the cell to use energy pumping sodium out of the cell. The Prusty research looks at mitochondria, but the changes in morphology are apparently linked to cell defence rather than to energy production.
At the recent NIH conference, Ron Davis said that their work indicates that the factor in the blood responsible for all this are exosomes, tiny membrane-bound packets of biomolecules released by cells. Exosomes are a type of extracellular vesicle, and these are taken up by cells and are believed to be involved in cell to cell communication, though their role is as yet unclear. Extracellular vesicles are being studied by Dr Maureen Hanson as part of her collaborative’s work.
So we have four groups finding that a factor in ME/CFS blood that has an effect on cells. These are still early days: only one study has been published so far, the sample sizes are relatively small and the findings need to be confirmed. But if things pan out, this development could prove to be an important step in understanding the biology of at least some types of ME/CFS.
Press Release: Biomarker for chronic fatigue syndrome identified
April 29, 2019
Stanford scientists devised a blood-based test that accurately identified people with chronic fatigue syndrome, a new study reports.
People suffering from a debilitating and often discounted disease known as chronic fatigue syndrome may soon have something they’ve been seeking for decades: scientific proof of their ailment.
Researchers at the Stanford University School of Medicine have created a blood test that can flag the disease, which currently lacks a standard, reliable diagnostic test.
“Too often, this disease is categorized as imaginary,” said Ron Davis, PhD, professor of biochemistry and of genetics. When individuals with chronic fatigue syndrome seek help from a doctor, they may undergo a series of tests that check liver, kidney and heart function, as well as blood and immune cell counts, Davis said. “All these different tests would normally guide the doctor toward one illness or another, but for chronic fatigue syndrome patients, the results all come back normal,” he said.
The problem, he said, is that they’re not looking deep enough. Now, Davis; Rahim Esfandyarpour, PhD, a former Stanford research associate; and their colleagues have devised a blood-based test that successfully identified participants in a study with chronic fatigue syndrome. The test, which is still in a pilot phase, is based on how a person’s immune cells respond to stress. With blood samples from 40 people — 20 with chronic fatigue syndrome and 20 without — the test yielded precise results, accurately flagging all chronic fatigue syndrome patients and none of the healthy individuals.
The diagnostic platform could even help identify possible drugs to treat chronic fatigue syndrome. By exposing the participants’ blood samples to drug candidates and rerunning the diagnostic test, the scientists could potentially see whether the drug improved the immune cells’ response. Already, the team is using the platform to screen for potential drugs they hope can help people with chronic fatigue syndrome down the line.
A paper describing the research findings was published online April 29 in the Proceedings of the National Academy of Sciences. Davis is the senior author. Esfandyarpour, who is now on the faculty of the University of California-Irvine, is the lead author.
Providing the proof
The diagnosis of chronic fatigue syndrome, when it actually is diagnosed, is based on symptoms — exhaustion, sensitivity to light and unexplained pain, among other things — and it comes only after other disease possibilities have been eliminated. It is also known as myalgic encephalomyelitis and designated by the acronym ME/CFS. It’s estimated that 2 million people in the United States have chronic fatigue syndrome, but that’s a rough guess, Davis said, and it’s likely much higher.
For Davis, the quest to find scientific evidence of the malady is personal. It comes from a desire to help his son, who has suffered from ME/CFS for about a decade. In fact, it was a biological clue that Davis first spotted in his son that led him and Esfandyarpour to develop the new diagnostic tool.
The approach, of which Esfandyarpour led the development, employs a “nanoelectronic assay,” which is a test that measures changes in miniscule amounts of energy as a proxy for the health of immune cells and blood plasma. The diagnostic technology contains thousands of electrodes that create an electrical current, as well as chambers to hold simplified blood samples composed of immune cells and plasma. Inside the chambers, the immune cells and plasma interfere with the current, changing its flow from one end to another. The change in electrical activity is directly correlated with the health of the sample.
The idea is to stress the samples from both healthy and ill patients using salt, and then compare how each sample affects the flow of the electrical current. Changes in the current indicate changes in the cell: the bigger the change in current, the bigger the change on a cellular level. A big change is not a good thing; it’s a sign that the cells and plasma are flailing under stress and incapable of processing it properly. All of the blood samples from ME/CFS patients created a clear spike in the test, whereas those from healthy controls returned data that was on a relatively even keel.
“We don’t know exactly why the cells and plasma are acting this way, or even what they’re doing,” Davis said. “But there is scientific evidence that this disease is not a fabrication of a patient’s mind. We clearly see a difference in the way healthy and chronic fatigue syndrome immune cells process stress.” Now, Esfandyarpour and Davis are expanding their work to confirm the findings in a larger cohort of participants. Recruitment for the larger project, which aims to further confirm the success of the diagnostic test, is being done on a rolling basis. Those who are interested in participating should contact clinical research coordinator Anna Okumu.
In addition to diagnosing ME/CFS, the researchers are also harnessing the platform to screen for drug-based treatments, since currently the options are slim. “Using the nanoelectronics assay, we can add controlled doses of many different potentially therapeutic drugs to the patient’s blood samples and run the diagnostic test again,” Esfandyarpour said.
If the blood samples taken from those with ME/CFS still respond poorly to stress and generate a spike in electrical current, then the drug likely didn’t work. If, however, a drug seems to mitigate the jump in electrical activity, that could mean it is helping the immune cells and plasma better process stress. So far, the team has already found a candidate drug that seems to restore healthy function to immune cells and plasma when tested in the assay. The drug, while successful in the assay, is not currently being used in people with ME/CFS, but Davis and Esfandyarpour are hopeful that they can test their finding in a clinical trial in the future.
All of the drugs being tested are either already approved by the Food and Drug Administration or will soon be broadly accessible to the public, which is key to fast access and dissemination should any of these compounds pan out.
Davis is a member of Stanford Bio-X, the Stanford Cancer Institute and the Stanford Maternal & Child Health Research Institute.
Other Stanford authors of the study are research scientists Neda Nemat-Gorgani and Julie Wilhelmy and research assistant, Alex Kashi.
The study was funded by the Open Medicine Foundation. Davis is the director of the foundation’s scientific advisory board.
ME Association: Forward ME and Oxford Brookes University Announce Results of Patient Survey on CBT and GET in ME/CFS | 03 April 2019
We are pleased to be able to let you see the results of the recent survey conducted on behalf of Forward-ME.
All the raw data was analysed and inserted into a comprehensive report by Professor Helen Dawes and Her team at Oxford Brookes University.
“The results show clearly that cognitive behavioural therapy and graded exercise therapy are unsuitable treatments or management approaches for ME/CFS. The changes in severity and the worsening of symptoms are clear indications that the therapies being offered are having adverse effects on the health of individuals.”
Forward ME, Executive Summary, April 2019.
Bearing in mind that this survey was organised at very short notice and that we are aware that there are some shortcomings – such as a selective bias in that only people with on-line access and the ability to complete the questionnaire were included – we are very grateful to all who responded so quickly.
The results have been well received by the Chairman of the NICE Guideline Development Group and will, we hope, be helpful to the Group as they develop the new guideline for ME/CFS.
NICE Patient Survey Outcomes CBT and GET: Forward ME Executive Summary (reproduced below).
NICE Patient Survey Outcomes CBT and GET: Full report: Evaluation of a survey exploring the experiences of adults and children with ME/CFS who have participated in CBT and GET interventional programmes (Published, 03 April 2019)
Latest Minutes: Forward ME with Professor Helen Dawes from Oxford Brookes University, 13 March 2019 (Published, 03 April 2019)
Evaluation of a survey exploring the experiences of adults and children with ME/CFS who have participated in CBT and GET interventional programmes
Executive Summary from Forward ME
This survey was commissioned by Forward ME following discussions between the Chair and Vice-Chair of the NICE Guideline Development Group, Members of Parliament and the Chair of Forward-ME about the lack of up-to-date data about providing additional patient evidence relating to long-term outcomes and harms following Cognitive Behavioural Therapy (CBT) and Graded Exercise Therapy (GET).
The survey was designed by a steering group of Forward ME members and an independent research unit within Oxford Brookes University, Oxford Clinical Allied Technology and Trials Services Unit (OxCATTS), was engaged to undertake the survey, collate, analyse and report on the response.
Due to the short timescales involved, the survey was only available online and it was not possible to allow paper responses. Please note, this will mean that a number of people with ME, particularly those who are severely affected, will not have been able to have their experiences considered.
The survey was designed to gather evidence from people who have been offered CBT and/or GET based on the current NICE Guidelines since 2007. Much of the evidence received echoes what we already know from previous surveys and feedback received by charities over a number of years.
The full report follows this executive summary. We set out below the key findings that we have drawn from it. We acknowledge that there may be some bias in the results of the survey due to its promotion by ME charities rather than NHS organisations.
There are also limitations in self-reported data however we feel the scale of the response demonstrates the strength of feeling and harm on the issue.
2,274 survey responses were received. Of these, 80.4% identified as female and 16.0% as male, with the remaining choosing ‘non-binary’ or ‘prefer not to say’.
98.5% said they experience post-exertional malaise. This is shown in the chart opposite.
8% were aged 18 or under and the age band with the highest responses rate was 41-50 at 26.6%.
Cognitive Behavioural Therapy (CBT)
789 people said they were offered a course of CBT with 84.9% starting the course.
We asked whether any symptoms worsened because of the treatment. 46.6% said yes and 48.5% said no. The most common symptoms mentioned were fatigue and pain. 21.6% also developed new symptoms.
We asked people ‘‘what severity is their condition both before and after treatment?’. The percentage of people describing their condition as severe before treatment was 10.9% and this increased to 19.1% after treatment. Of those who started the course, we asked ‘what impact did CBT have on their physical and mental health?’. See results in chart.
“CBT, while may be effective for a minority in helping with mental health challenges such as depression or anxiety, is shown to be ineffective in a considerable proportion of people and even led to almost half of respondents reporting worse symptoms.”
Forward ME, Executive Summary, April 2019.
Graded Exercise Therapy (GET)
542 people said they were offered a course of GET with 79% starting the course.
We asked whether any symptoms worsened because of the treatment. 81.1% said yes and 13.3% said no. The most common symptoms mentioned were fatigue and pain. 36.7% also developed new symptoms.
We asked people ‘‘what severity is their condition both before and after treatment?’. The percentage of people describing their condition as severe before treatment was 12.9% and this increased to 35.3% after treatment.
Of those who started the course, we asked ‘what impact did GET have on their physical and mental health?’. See results in chart.
“GET is shown to cause considerable deterioration in physical and mental health. It has led to people becoming more severe and the open questions have given us insight into the worsening symptoms that have developed when patients have increased their activity beyond their capabilities.”
Forward ME, Executive Summary, April 2019.
CBT with GET combined
943 people said they were offered a course of CBT with GET combined with 76.9% starting the course.
We asked whether any symptoms worsened because of the treatment. 58.3% said yes and 37.7% said no. The most common symptoms mentioned were fatigue and pain. 29% also developed new symptoms.
We asked people ‘‘what severity is their condition both before and after treatment?’. The percentage of people describing their condition as severe before treatment was 12.6% and this increased to 26.6% after treatment.
Of those who started the course, we asked ‘what impact did CBT with GET combined have on their physical and mental health?’. See results in chart.
GET combined with CBT
943 people said they were offered a course of GET with CBT with 75% starting the course.
We asked whether any symptoms worsened because of the treatment. 85.9% said yes and 10.3% said no. The most common symptoms mentioned were fatigue and pain. 44.4% also developed new symptoms.
We asked people ‘‘what severity is their condition both before and after treatment?’. The percentage of people describing their condition as severe before treatment was 13.2% and this increased to 41.9% after treatment.
Of those who started the course, we asked ‘what impact did GET combined with CBT have on their physical and mental health?’. See results in chart.
The results show clearly that cognitive behavioural therapy and graded exercise therapy are unsuitable treatments or management approaches for ME/CFS. The changes in severity and the worsening of symptoms are clear indications that the therapies being offered are having adverse effects on the health of individuals.
CBT, while may be effective for a minority in helping with mental health challenges such as depression or anxiety, is shown to be ineffective in a considerable proportion of people and even led to almost half of respondents reporting worse symptoms.
GET is shown to cause considerable deterioration in physical and mental health. It has led to people becoming more severe and the open questions have given us insight into the worsening symptoms that have developed when patients have increased their activity beyond their capabilities.
The results show that although NICE might not recommend GET for the severely affected, they are clearly being given GET at the clinical level. This could be because clinics are not tailoring their management advice to the individual (as NICE recommends) or are simply not aware of the unsuitability of aerobic/exercise for people with ME/CFS.
Alongside this the analysis of the survey provided by Oxford Brookes University show that people with ME/CFS have experienced negative effects with regard to welfare and benefits when choosing whether or not participate in these treatments. Results also show that the adverse effects of the treatment has had a considerable impact on the employment and education capabilities of individuals.
We acknowledge that there may be some bias in the results of the survey due to the promotion of the survey being organised by ME charities rather than NHS organisations. There are also limitations in self-reported data. However, we feel the scale of the response demonstrates the strength of feeling and harm on this issue.
As there is a commitment that this new guideline be ‘patient led’ we believe that the responses should carry considerable weight in the consideration of effective treatment or management approaches. There is also an ethical question whether the current management recommendations relating to CBT and GET can continue while the development is underway when their suitability is evident.
Our collective recommendation is that GET and CBT be removed from the NICE guideline for ME/CFS.
Information about Forward ME
Forward-ME consists of a fairly broad spectrum of charities and voluntary organisations invited by the Countess of Mar to meet from time to time. The Aim of Forward-ME is to promote effective joint working by ME and CFS organisations to maximise impact on behalf of all people with ME and CFS in the UK.
Forward-ME has no formal constitution. It exists to improve recognition, understanding, research, management, support and information for everyone whose life is affected by ME and CFS.
The linked organisations and associates are:
Countess of Mar (Chair), Carol Monaghan MP (vice chair), Dr Nigel Speight, Dr William Weir, Dr Nina Muirhead, ME Association, ME Research UK, Action for ME, TYMES Trust, reMEmberCFS, BRAME, ME Trust, BRAME, 25% ME Group, #MEAction.
MEA Summary Review: Assessing PEM – The characteristic symptom of ME/CFS
Charlotte Stephens, Research Correspondent, ME Association.
Post-exertional malaise (commonly referred to as PEM) is considered a hallmark characteristic of ME/CFS. However, it is not a requirement in many of the different diagnostic criteria.
There is currently no agreed upon definition of PEM, nor a formal assessment for its measurement, but creating one could improve future diagnosis of the disease.
Dr Melvin Ramsay – the clinical champion of M.E. and founding member of the ME Association – originally described what has since become known as PEM, as:
“Muscle fatigability whereby, even after a minor degree of physical effort, three, four, or five days, or longer, elapse before full muscle power is restored and constitutes the sheet anchor of diagnosis.”
“Without it I would be unwilling to diagnosis a patient as suffering from ME, but it is most important the stress the fact that cases of ME of mild or even moderate severity may have normal muscle power in remission.”
The Saga of the Royal Free Disease (50th Anniversary Reprint).
Since then the definition of PEM has expanded, but no single version or means of assessment has really prevailed (see References for recent research on this topic).
However, in recent years we have witnessed the development of objective evidence that supports PEM as a real and unique symptom.
Earlier this month Professor Lenny Jason and his team from the Center for Community Research at DePaul University in Chicago, published results of a large public survey on PEM.
They hope the analysis will lead to a definitive definition and will ultimately provide a validated clinical assessment tool.
In this review, we hope to explain what PEM is, cover some of the research surrounding it and give an overview of the results from this latest research.
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