Dr Maureen Hanson gives a radio interview about her recently published paper, “Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome“.
It is an interview designed to explain the study to lay people.
WRFI Community Radio interview with Dr Maureen Hanson 28 June 2016
OMF blog post, 1 July 2016: Open Medicine Ron Davis’ response to the NIH Request For Information (RFI): Input for New Research Strategies for ME/CFS.
We would like to share the information that Dr. Ron Davis sent in response to NIH’s Request for Input on new ME/CFS research strategies.
We are grateful for the opportunity to provide input to the Trans-National Institutes of Health (NIH) ME/CFS Working Group as they develop strategies to guide NIH’s research efforts and priority setting for research on ME/CFS. Our mission at the Stanford Chronic Fatigue Syndrome Research Center is to discover causes, a molecular diagnosis, and treatment options for ME/CFS. Through our research efforts, collaborations with the ME/CFS research and clinical community, and extensive engagement with patients, we have defined several elements of importance for future ME/CFS research programs.
Complex and multisystemic disease
A key consideration in ME/CFS research efforts is the complex and multisystemic nature of this disease, and we are happy to see the involvement of several NIH institutes in developing this plan. Because the causative factors driving the disease remain unknown, and because work from our team and others has indicated effects on neurology, metabolism, immunity, and more, it will be crucial that calls for proposals allow for open, unbiased, multifaceted, and systematic research. Broadening the scope of ME/CFS research will create opportunities for engaging researchers in other disciplines.
Similarly, investigating numerous organ systems and biological pathways perturbed in ME/CFS may well reveal informative parallels to other diseases – for example, we and others have observed symptomatic, transcriptomic, and metabolic overlap between ME/CFS and neurodegenerative disorders like Parkinson’s Disease. It is important not to limit research to single organs like the brain, and to integrate results from many different organs and molecular processes so that they can be understood at the systems level. Big data approaches and high-throughput, large-scale molecular profiling should therefore be prioritized. Such efforts hold promise to identify key genes or pathways underlying ME/CFS. Similarly, large-scale in vitro drug screening efforts would help point to a variety of molecules and molecular processes as therapeutic targets.
Molecular etiology of ME/CFS
Understanding the molecular etiology of ME/CFS is another important opportunity. A long-standing belief in the field is that an infectious agent causes the disease, and that the pathogenicity of the as-yet-undiscovered organism is responsible for the severity of the illness.
An equally plausible explanation is that a stressor such as trauma, infection, or genotoxic stress may trigger a series of events that lead to a hypometabolic state. This model is observed in children with congenital mitochondrial disorders, where the phenotype does not present itself until after a serious viral infection. This shift in thinking opens up the possibility that ME/CFS has strong genetic and environmental associations, which may also explain the extensive heterogeneity in its presentation, progression, and recovery across patients.
The search for novel infectious agents should continue, but research efforts should also focus on understanding individual host susceptibility and response to infection. For example, it may not be a particular infectious agent that results in the disease, but rather a particular host state as a function of numerous biological and external factors that governs an individual’s susceptibility.
This perspective mirrors the NIGMS-funded Glue Grant on Inflammation and Host Response to Injury, which used an integrated omics approach to define variable responses to infection and trauma. Characterizing host responses to infection and understanding the mechanisms of the long-term sequelae may reveal insights into ME/CFS that are relevant to numerous other diseases of infectious origin, such as Chronic Lyme Disease and Post-Ebola Syndrome (Mattia et al., 2016). Moreover, such precision medicine approaches would build a more comprehensive understanding of ME/CFS and offer richer opportunities for therapeutic intervention.
Prevalence and landscape
Another major challenge is our lack of understanding of the prevalence and landscape of ME/CFS, which is largely due to the difficulty in diagnosing the disease. The search for precise molecular biomarkers is a great opportunity afforded by this research program, which would be accelerated through multi-omics approaches in large patient cohorts.
Current estimates of the prevalence of ME/CFS vary widely (800,000 to 2.5 million cases in the US) due to varying diagnostic and data collection methods. There is an opportunity here to improve these estimates based on modernized methods and community-defined standards, including criteria specified in the 2015 Institute of Medicine Report, and by considering questionnaire-based responses like the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort in the United Kingdom (Collin et al., 2016).
Novel methods & technologies
Because of these complex scientific challenges, ME/CFS research presents an excellent opportunity for developing and piloting novel methods and technologies in discovering biomarkers, elucidating disease mechanisms, and revealing therapeutic possiblities. The methods we need to understand this complex disease may very well not exist yet.
Engineering and technology development efforts towards highly sensitive, quantitative molecular profiling and/or measuring novel cellular properties, as well as novel computational analyses that integrate multiple datatypes to define disease mechanisms, should be encouraged. Again, it is highly likely that such efforts will prove useful in the study of other diseases, be they infectious, genetic, or complex in origin.
Long term studies
Beyond scientific considerations, we would like to note several programmatic considerations that we believe are key for rapid progress. Long-term studies of patients are absolutely essential. Such a mechanism has proven effective in the NIGMS Glue Grants described above. Moreover, maintaining an open structure in RFAs will allow scientists to develop and refine their hypotheses as research progresses, as appropriate for the unknown/uncertain nature of the field.
Collaboration & data sharing
As highlighted in several places above, the opportunities for collaborative efforts within and beyond the ME/CFS research community to understand and treat this disease are numerous. There are numerous experts spread across the world, each taking their own approaches based on their own expertise. We believe future funding programs should not only encourage, but establish frameworks for highly collaborative data sharing and strategizing that bring together researchers and clinicians.
All data should be made publicly available as early as possible (even before publication), in both raw and accessible formats. This will not only facilitate collaboration (for example by encouraging biocomputing experts to engage with the data) and integrative analyses, but also empower patients to understand more about their disease and what progress is being made. As we have all seen, the ME/CFS patient community is extremely active, engaged, and eager for actionable results.
We thank you once again for the opportunity to provide input on this matter, and look forward to the new strategies for ME/CFS research efforts put forth by this working group.
Yours sincerely,
Ronald W. Davis, Ph.D.
Professor of Biochemistry and Genetics, Stanford University Director, Stanford Chronic Fatigue Syndrome Research Center and Stanford Genome Technology Center Director, Scientific Advisory Board, Open Medicine Foundation[
BACKGROUND: An estimated 10% of children and adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience eating difficulties; however, little is known about why these difficulties develop, what the impact is or how to manage them.
METHODS: Semi-structured interviews were conducted with adolescents (aged 12-17 years) attending a specialist service who have a primary diagnosis of CFS/ME and experience nausea, abdominal pain and/or eating difficulties. A total of 11 adolescents were interviewed (eight female, mean age: 15 years). Transcripts were analysed thematically using techniques of constant comparison which commenced soon after data collection and informed further interview protocols.
RESULTS: Adolescents perceived their eating difficulties were caused by abdominal symptoms, being too fatigued to eat and changes to their senses of taste and smell. Some of the adolescents recognised how their eating difficulties were exacerbated and maintained by psychological factors of low mood and anxiety. The adolescents eating difficulties had a negative impact on their weight, fatigue, socialising and family life. They perceived helpful interventions to include modifying their diets, families adjusting and also medical interventions (e.g. medication). Adolescents identified that early education and support about diet and eating habits would have been helpful.
CONCLUSIONS: If adolescents diagnosed with CFS/ME develop eating difficulties, this has a significant impact on their quality of life, illness and on their families. Not eating increases fatigue, low mood and anxiety which further exacerbates the eating difficulties. Clinicians should screen for eating difficulties in those with symptoms of nausea and abdominal pain, warn adolescents and their families of the risk of developing eating difficulties and provide interventions and support as early as possible.
Source: Harris S, Gilbert M, Beasant L, Linney C, Broughton J, Crawley E. A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis, by Sarah Harris, Matthew Gilbert, Lucy Beasant, Catherine Linney, Jessica Broughton and Esther Crawley in Clin Child Psychol Psychiatry. 2016 May 23. [Epub ahead of print]
Prohealth blog post by Karen Lee Richards, 27 June 2016: The crucial role CoQ10 plays in Fibromyalgia and ME/CFS
No two fibromyalgia or ME/CFS patients are exactly alike. Each has a unique set of symptoms with varying degrees of severity. There is, however, one common denominator for the vast majority – a serious, sometimes even profound, lack of energy.
What could possibly cause that kind of fatigue?
Multiple studies have suggested that mitochondrial dysfunction may play a significant role in both fibromyalgia and ME/CFS, which would explain much of the energy deficit experienced by patients.
Mitochondria are the engines – or energy producers – that power every cell in the body. It is the job of the mitochondria to take in nutrients, break them down and use them to create energy for the cells. The more energy a cell needs, the more mitochondria it contains. Cells that require a lot of energy – like the heart, brain and other vital organs – may have thousands of mitochondria.
How do the mitochondria produce energy? This is where CoQ10 (coenzyme Q10) comes in. CoQ10 is the catalyst that makes it possible for the mitochondria to produce ATP (adenosine triphosphate), the molecule upon which all cellular functions in the body depend. In fact, 95% of all cellular energy production depends on CoQ10.
Given that statistic, it’s not surprising to learn that, according to several different studies, people with FM and/or ME/CFS generally have very low levels of CoQ10. As we, therefore, might expect, many of the symptoms of a CoQ10 deficiency are remarkably similar to symptoms of FM and ME/CFS, such as:
• Fatigue
• Pain
• Headaches
• Exercise intolerance • Generalized weakness
• Memory loss
• Difficulty concentrating
• Depression
• Vision problems
• Seizures
• Heart failure
Because CoQ10 is essential to every cell in the body, a severe CoQ10 deficiency can cause mitochondrial dysfunction, which in turn has a serious negative impact on multiple organs and body systems.
Fibromyalgia and CoQ10
Since 2009, a team of Spanish researchers has led the way in conducting studies that link CoQ10, mitochondrial dysfunction and fibromyalgia. They have consistently found that FM patients are deficient in CoQ10 – often with a 40-50% reduction in CoQ10 levels compared to healthy controls.
Following are some of their significant findings:
Many well-known FM/ME/CFS physicians, like Dr. Mark Pellegrino, Dr. Charles Lapp and Dr. Jacob Teitelbaum, have been recommending CoQ10 for their patients for years. In fact, CoQ10 is one nutritional supplement that is almost universally endorsed by traditional and alternative FM/ME/CFS practitioners alike.
ME/CFS and CoQ10
As with fibromyalgia, ME/CFS patients have also been found to be deficient in CoQ10. In a 2009 study, plasma CoQ10 was analyzed in 58 ME/CFS patients and 22 normal controls. Researchers found that CoQ10 levels were significantly lower in the ME/CFS patients than in the normal controls. Additionally, they demonstrated a relationship between low CoQ10 levels and increased fatigue, autonomic and neurocognitive symptoms. The researchers went on to note that low CoQ10 levels are a predictor of chronic heart failure and may explain the early mortality rates of ME/CFS patients due to heart failure.(8)
A 2016 article in the journal BioFactors reported on two studies using oral ubiquinol-10 (an advanced form of CoQ10) supplementation on ME/CFS patients. The first was an open label trial with 20 patients and the second a double-blinded, placebo controlled trial with 43 ME/CFS patients. Both trials found that ubiquinol-10 supplementation was effective in improving autonomic nervous function and cognitive function in ME/CFS.(9)
In her paper, “Chronic Fatigue Syndrome and Mitochondrial Dysfunction,” Dr. Sarah Myhill, MD, a UK-based ME/CFS researcher and clinician, makes the case that ME/CFS is actually a symptom of mitochondrial failure.(10) Dr. Myhill recommends that ME/CFS patients have their CoQ10 levels checked and begin taking CoQ10 supplements if they are low. She also notes that CoQ10 will work best in conjunction with acetyl L-carnitine, magnesium, D-ribose and Vitamin B3 (niacinamide).(11)
Medications That Deplete CoQ10
There are numerous prescription and over-the-counter medications that can deplete the body of CoQ10. Unfortunately several of them are frequently prescribed for FM and ME/CFS, including many antidepressants, anticonvulsants and analgesic/anti-inflammatory medications.
Statins, prescribed for lowering cholesterol, are particularly notorious for hindering the body’s production of CoQ10. More and more doctors are strongly recommending CoQ10 for their patients who are taking statins.
All CoQ10 Is Not Created Equal
The form of CoQ10 found in most supplements is called ubiquinone. In order to produce cellular energy, the body must convert the ubiquinone to ubiquinol. It is the ubiquinol that carries electrons through the mitochondria and produces energy.
Young healthy people (under 25) can easily convert CoQ10 to ubiquinol. But as we age or when we have a chronic illnesses, our ability to convert CoQ10 to ubiquinol diminishes. Therefore, it is particularly important for people with FM or ME/CFS to take the ubiquinol form of CoQ10 so they’re not expending precious energy converting ubiquinone to its usable form.
A 2007 study compared how well humans absorbed ubiquinone and ubiquinol. The results showed that it takes eight times as much ubiquinone to equal the blood plasma concentrations of ubiquinol. More specifically, 150 mg. of ubiquinol was equal to 1200 mg. of standard CoQ10.(12)
Additionally, in an unpublished study with aged rats, blood concentrations were sustained longer with ubiquinol. After eight hours, the concentration of ubiquinol CoQ10 was 3.75 times greater than standard CoQ10.(13)
How to Take Ubiquinol CoQ10
The suggested dosage of Ubiquinol CoQ10 for FM and ME/CFS patients varies, but most experts start at around 150-200 mg./day. One FM/ME/CFS physician told me that many of his patients take 600 mg. or more each day. Check with your physician to determine the best starting dosage for you.
It’s important to note that Ubiquinol CoQ10 is not a quick fix that will give you an immediate energy boost. Each individual is different, but it generally takes two to three weeks to restore optimal CoQ10 levels in blood plasma and tissues. You may, however, begin to notice a difference as your plasma levels start to increase around the fifth day. If you don’t notice any difference after three weeks, you may want to discuss increasing the dosage with your doctor.
More info: Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome by S. Fukuda et al., 10 May 2016
Dr Myhill gave a talk to the AGM of OMEGA on Sat 5 March 2016.
This talk covered:
You can access the full PowerPoint slide show at this new webpage:
Objectives:
To explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.
Methods
Crdiac MR (MR) examinations were performed using 3 T Philips Intera Achieva scanner (Best, NL) in participants with CFS (Fukuda; n=47) and matched case-by-case controls. Total volume (TV), red cell volume (RCV) and plasma volume (PV) measurements were performed (41 CFS and 10 controls) using the indicator dilution technique using simultaneous 51-chromium labelling of red blood cells and 125-iodine labelling of serum albumin.
Results
Te CFS group length of history (mean±SD) was 14±10 years. Patients with CFS had significantly reduced end-systolic and end-diastolic volumes together with reduced end-diastolic wall masses (all p<0.0001). Mean±SD RCV was 1565±443 mL with 26/41 (63%) having values below 95% of expected. PV was 2659±529 mL with 13/41 (32%) <95% expected. There were strong positive correlations between TV, RCV and PV and cardiac end-diastolic wall mass (all p<0.0001; r2=0.5). Increasing fatigue severity correlated negatively with lower PV (p=0.04; r2=0.2). There were no relationships between any MR or volume measurements and length of history, suggesting that deconditioning was unlikely to be the cause of these abnormalities.
Conclusions
This study confirms an association between reduced cardiac volumes and blood volume in CFS. Lack of relationship between length of disease, cardiac and plasma volumes suggests findings are not secondary to deconditioning. The relationship between plasma volume and severity of fatigue symptoms suggests a potential therapeutic target in CFS.
What is already known about this subject?
What does this study add?
How might this impact on clinical practice?
Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study, by Julia L Newton, Andreas Finkelmeyer, George Petrides, James Frith, Tim Hodgson, Laura Maclachlan, Guy MacGowan and Andrew M Blamire in Open Heart Vol 3, Issue 1 2016
Funded by the (UK) Medical Research Council & ME Research UK
Health rising blog post, by Cort Johnson, 27 Jun 27 2016: Chronic Fatigue Syndrome: the small heart disease
Did you know that you probably have a smaller heart than normal? Four studies suggest that if you have chronic fatigue syndrome (ME/CFS) you probably do. The word on the small hearts for years has been that they’re probably caused by inactivity or deconditioning. This study suggested that they probably are indeed caused by inactivity – but not by deconditioning at all.
Small hearts appear to be common on ME/CFS – but not in the way the medical community has thought.
Newton’s earlier small study had found reduced heart mass and significantly reduced blood pumping by the heart, and Miwa in Japan has produced three studies showing that smaller hearts are present in people with chronic fatigue syndrome (ME/CFS).
Mirroring Dr. Cheney’s unpublished findings, both Newton and Miwa have also found reduced diastolic volume (30%). The diastolic phase of the heart cycle is the filling phase. During diastole, the ventricles relax and then, in an energy intensive process, expand so that they can fill with oxygen enriched blood. Reduced diastolic volume or preload indicates that the heart is not being filled as much as normal.
Both Newton’s and Miwa’s study published last year found significantly reduced diastolic volume and mass, stroke volume index and cardiac output. (Miwa targeted and consistently found reduced left ventricular volume and density. He did not measure right ventricular functioning. He or she also appears to be the first Japanese researcher to drop the term CFS and use myalgic encephalomyelitis exclusively throughout the latest paper. )
The Study
Now Newton is back doing more tests with a much larger and better defined cohort (n=41 ME/CFS patients / 10 healthy controls).
Newton measured how much blood entered the heart during the diastolic phase (end-diastolic volume) and systolic phases (end-systolic volume) then how much it spate out (stroke volume). She also assessed the size or mass of the heart.
This time, suspecting that reduced blood volume played a role in the poor cardiac performances, she analyzed blood volume three ways: total blood volume (TV), red blood cell volume (RCV) and plasma volume (PV).
As before, Newton found reduced blood volume during both the diastolic and systolic phases of the heart cycle and not just minor reductions either; ME/CFS patients had a whopping 25% less blood entering their hearts than the healthy controls. They also had about 25% less stroke volume and index and almost 30% smaller heart mass. These appear to be very large reductions in both heart mass and heart functioning in ME/CFS patients.
Blood pressure was affected as well; ME/CFS patients had significantly lower systolic (125-109) and diastolic (76-70) blood pressures than the healthy controls. The reduced blood pressure and stroke volumes could result from the poor heart functioning or they could produce the poor heart functioning by not pushing the heart to work harder.
Dr. Cheney appears to believe that reduced heart energetics are interfering with the hearts ability to contract enough to accommodate the blood entering it. Another possibility is that reductions in blood pressure have resulted in smaller hearts.
Another possibility is that there’s something wrong with the vascular system leading to the heart which is reducing blood flows to the heart. Reduced blood flows would result in a smaller heart. That’s the option Dr. Newton appears to be most interested in.
Non Compliant Veins?
Dr. Newton questioned whether a problem with “venous compliance” was present. Since 2/3rd’s of our blood is locked up in our veins the reduced diastolic volume or preload found in ME/CFS could reflect large amounts of blood that has somehow gotten stuck in our veins.
Venous compliance refers to the ability of veins to “push back” once they get extended with fluid. The more full of fluid they are, the more the veins should – like a rubber band that has been stretched – exert pressure on the fluid to move. If ME/CFS patients veins are non-compliant; that is, if they’re kind of flaccid in response to filling they may not be moving the blood along as they should.
That could lead to reduced preload (reduced diastolic volume).
Venous compliance can be affected by a number of factors including vasodilators and vasoconstrictors, the muscle tone of the smooth muscle tissue, and the renin–angiotensin system. One wonders if connective tissue problems (eg Ehlers Danlos Syndrome) could come into play as well.
Blood Volume
The blood volume results were assessed according to the norms expected. Blood volume was lower in the ME/CFS patients, but perhaps not to the extent that might have been expected. About half the ME/CFS patients had normal red blood cell volume and about half fell below the 95th percentile expected. About a third of ME/CFS patients had plasma volumes below the 95th percentile.
On the other hand, statistical analyses suggested that the reduced red blood volumes were strongly associated with reduced ventricular mass in ME/CFS. That suggests the ventricles may be smaller they’re not getting as much blood as usual.
There’s quite a bit of increased interest in blood volume right now. Medow’s study on the effects of saline solution on ME/CFS should be published soon. He is currently examining whether the World Health Organization’s oral rehydration formula could be helpful in ME/CFS. His ability to use phenylephrine to increase blood flows to the brain and completely knock out POTS during a tilt test was astonishing.
Dr. Newton proposes to increase the blood volumes of ME/CFS patients and see if the size of their heart’s increase to normal size.
Is Arnold Peckerman Smiling Somewhere?
Arnold Peckerman apparently passed away a couple of years ago but one wonders what he would be thinking of all this. Peckerman, LeManca and others working at Dr. Ben Natelson’s NIAID funded ME/CFS research center were hot on the trail of cardiovascular issues when NIAID pulled the plug on its ME/CFS research.
The group had produced some interesting results. The first heart study in 1999 showed increased heart rates and reduced blood flows during a tilt test and presaged the attention on orthostatic intolerance and POTS. The declines in heart rates and blood pressure during a stressful cognitive test they found may have been the first indication that the autonomic nervous system was prone to poop out under stress.
In 2003 their finding that people with ME/CFS were trying as hard as healthy controls knocked the legs out from under a prominent psychological interpretation. Next, Peckerman showed that people with severe ME/CFS (but not moderate ME/CFS) had a significantly lower stroke volume than healthy controls. Then he showed that the blood pressure responses of ME/CFS patients were off during exercise.
Could reduced heart blood flows after exercise help explain post-exertional malaise?
These results were positive but it was the last study, whose results were never published, which was a potential game-changer.
An MD, Peckerman, had seen post exertional malaise in some of his heart patients after the blood flows through their hearts had been stunted. Peckerman, therefore, decided to measured heart functioning before and after exercise in ME/CFS.
It was a small study – just 16 ME/CFS patients and four healthy controls but the results were astounding, and if they had been published and held up could have produced a simple and effective exercise test. Peckerman didn’t measure VO2 max – he measured blood flows – and it didn’t take him two exhausting exercise tests to get his result; he simply measured heart blood flows at rest, had his subjects exercise, and then measured blood flows at rest again.
In 2003 at the American Physiological Association conference Peckerman reported that 13/16 ME/CFS patients had significantly reduced blood flows at rest after exercise. WebMD ran a story titled “Tricky Heart May Cause Chronic Fatigue Syndrome” in which Peckerman, obviously no shrinking violet, stated that the reduction of blood flows he had seen was the very definition of heart failure.
An Emory cardiologist in the story agreed. The finding of reduced heart blood flows was, in fact, what he saw in people with serious heart disease:
“Typically we see this in people with three-vessel heart disease. A drop in [blood pumped by the heart] during exercise is not a typical response. It is actually a marker of significant coronary artery obstruction.”
Dr. Natelson described being quite excited at the results but we now know that “heart failure” is not present in ME/CFS. Heart failure is a progressive condition that ultimately ends in death for just about everyone who has it, and, the fact that ME/CFS patients were not dropping dead from heart failure puzzled both Peckerman and Miller. They both recommended that further study be done.
The study was never published, however, and we don’t know why. After one more study on ME/CFS – which did not find differences in cognition before or after exercise – Peckerman was done. He’d participated in 13 studies on ME/CFS and GWS and never published again.
The cardiovascular connection to ME/CFS has never died, however. As noted above both Newton and Miwa have found significantly reduced blood flows and filling in their studies. It now appears that those issues probably reflect significant problems with the cardiovascular system not the heart.
The outstanding question remaining from Peckerman’s unpublished study, though, is what happened during exercise to so dramatically affect the blood flows to the hearts of his ME/CFS cohort the next day? The vascular system in ME/CFS and FM is a subject that continues to fascinate.
Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed.
In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the
development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers’ speculations that their research results indicate a causal mechanism for CFS – consequently, patients now have great hope that ‘the cause’ of CFS has been found, and
thus, a cure is sure to follow.
I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical
research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients.
Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim.
In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows.
Unexpected findings and promoting monocausal claims, a cautionary tale, by Samantha Marie Copeland in Journal of Evaluation in Clinical Practice [Published online 10 Jun 2016]
NB The Norwegian researchers have never made a ‘monocausal claim’ for CFS and there is no sign that research has been limited as a result of their speculation.
The internet is increasingly being used as a source of health advice and information by individuals with long term conditions (LTCs). Specifically, online forums allow people to interact with others with similar conditions. However, it is not clear how online health information is assessed by those with LTCs.
This study aims to address this gap by exploring how individuals with contested and uncontested LTCs utilise internet forums. Semi-structured interviews were conducted with 20 participants with ME/CFS and 21 participants with type 1 and 2 diabetes and analysed using thematic analysis.
Participants were recruited via online and offline routes, namely forums, email lists, newsletters, and face-to-face support groups. The findings indicate that the use of online forums was a complex and nuanced process and was influenced by a number of individual and illness-specific factors.
Participants trusted those with similar experiences and perspectives as themselves, while also valuing conventional biomedical information and advice. By accessing support online, forum users were able to draw on a personalised form of support based on the lived experiences of their peers. However, the role of digital literacy in developing and maintaining online relationships must be acknowledged.
‘You get to know the people and whether they’re talking sense or not’: Negotiating trust on health-related forums, by Ellen Brady, Julia Segar, Caroline Sanders in Social Science & Medicine, vol 162, Aug 2016, pp 151–157 [published online 18 June 2016]
Nursing in practice article, by Dr Keith Geraghty, 27 June 2016: The ‘all in the mind’ myth of myalgic encephalomyelitis/chronic fatigue syndrome
Health professionals should be made aware that ME/CFS is not a psychological illness and in order to improve patient care, nurses need to better understand this illness and its impact on patients.
Nurses often witness close-up the impact of acute and chronic illness on patients. Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is one illness that nurses may encounter that causes profound life changes for many sufferers. This controversial illness is sometimes presented as a psychosomatic disorder that requires psychological treatment. However, there is no compelling evidence that ME/CFS is a mental health condition and increasing evidence shows it is a biological disease with a range of complex symptoms. This article discusses how the ‘all in the mind’ myth of ME/CFS has permeated both medical discourse and popular culture, with negative consequences for patients living with this poorly understood condition.
1. Is ME/CFS really a mental illness?
In a recent Nursing in Practice article, Roberts (2016)1 suggests that ME/CFS is a psychosomatic disorder, best treated with psychotherapy and mindfulness. The erroneous idea that mindfulness is an optimum treatment masks a hidden and more important story; that very little is understood about ME/CFS and many health professionals are sceptical about whether ME/CFS is even a real illness. For example, NICE guidelines do not mention mindfulness.2
A GP once exclaimed to me that ‘all these patients need is anti-depressants and a good pair of running shoes’. While discussing my ME/CFS research at a hospital in Leicester a nurse offered me a similar opinion by suggesting that ‘ME/CFS patients would get out of bed if you paid them £5000 per day’. Such negative views among doctors and nurses are not uncommon and are perhaps fueled by misinformation about the illness being psychological.
In a recent book, All in Your Head: True Stories of Imaginary Illness,3 Dr Suzanne O’Sullivan, a London-based consultant neurologist, includes a chapter on ME/CFS. O’Sullivan argues ME/CFS is strongly associated with psychological complaints and illness beliefs. In contrast, a growing body of scientific evidence suggests that ME/CFS is not an imagined illness, nor is it a psychological condition, but a complex biological disease that is often triggered by an infection that causes observable neuro-immune dysfunction. Far from being ‘all in the mind’, sufferers often experience life-changing and disabling physical symptoms and physiological abnormalities (see Table 1).
Table 1: Biological abnormalities observed in ME/CFS
The World Health Organization (WHO) classifies ME as a neurological disorder in the International Classification of Diseases (ICD-10: G 93.3; WHO, 1992).4
The US Institute of Medicine (2015) conducted an extensive review of the evidence and concluded that ME/CFS is ‘a serious, chronic, complex, systemic disease’.5
The US National Institutes for Health confirmed ME/CFS as a disabling physical illness and stated that the medical profession has been responsible for causing distress to patients with ME/CFS by ignoring patients’ calls for medical help and failing to adequately research the disease.6
2. So why is ME/CFS treated with psychotherapy?
Psychiatrists have long been interested in attempting to explain the medically unexplained. Sigmund Freud, the father of modern psychiatry, explored the connection between the mind and health. The famous French neurologist J. Charcot believed traumatic life events may bring about a form of hysteria or paralysis in patients; while George Beard put forward the theory of neurasthenia (exhaustion of energy within the nervous system).7 These theories continue to influence how doctors perceive medically unexplained illnesses, particularly ME/CFS.
A brief time-line of how ME (nuero-immune disease) became CFS (a psychosomatic fatigue syndrome)
1955: Melvin Ramsay describes a viral outbreak illness among staff at the Royal Free Hospital in London as a post-infectious disease affecting brain, nerves and muscle tissue (Myalgic Encephalomyelitis).
1970s: UK psychiatrists McEvedy and Beard state that ME is nothing more than a case of ‘mass hysteria’.
1980s: A London newspaper runs a story about ME being ‘Yuppie Flu’. Since then, ME has been indelibly linked with stressed-out professionals complaining about exhaustion.
1988: The US Centers for Disease Control recommend replacing ME with a new syndrome (Chronic Fatigue Syndrome).
1990s: UK psychiatrist Simon Wessely argues ME (now CFS) is a biopsychosocial syndrome, partly created by social trends and maintained by patients’ illness beliefs and behaviours.
2000s: Colleagues of Wessely, including nurse/researcher Professor Trudie Chalder, conduct clinical trials of psychotherapy to treat CFS, including the £5 million PACE trial testing cognitive behavioural therapy and graded exercise therapy.8
2007: The UK National Institute for Health and Care Excellence (NICE) conducts a review and recommends CBT and GET for the treatment of ME/CFS.2 This decision is criticised by ME/CFS patient groups who deem CBT and GET inappropriate treatments. In particular, GET attracts much criticism.
2015: A large patient survey finds CBT has little impact on the condition: 74% of patients report that GET makes their symptoms worse, while simple pacing is preferred by patients.9 Such concerns are echoed in scientific studies that suggest exercise therapy may be harmful, given biological abnormalities found in ME/CFS.10
3. So, does cognitive therapy or exercise therapy help anyone with ME/CFS?
The answer to this question is rather complex. ME/CFS is an umbrella term often used for patients with ongoing unexplained fatigue. Hooper (2006) points out that ‘Amorphous definitions and diagnostic symptom criteria have contaminated study cohorts and corrupted research data’.11 Essentially, it may be difficult to differentiate patients with ME/CFS from patients with fatigue or depression, given the generality of the diagnostic criteria for CFS: patients are often lumped together in studies, with depressed patients responding better to CBT compared with ME/CFS patients.12
In addition, CBT may help with the secondary depression or anxiety that occurs in most illness states. Clinical trials of CBT and GET tend to recruit mild to moderately unwell CFS patients, as more severe cases are too unwell to take part. Yet, even if we accept these research biases, the evidence for the success of psychological or exercise therapies in ME/CFS is unconvincing:
4. Why is it important to know the facts?
In a recent Centers for Disease Control ‘Grand Rounds’ event (2016) discussing ME/CFS research, Professor Anthony Komaroff of Harvard University stated that the medical profession were wrong to adopt the name Chronic Fatigue Syndrome in 1988, as this term led to inaccurate perceptions of the illness. Komaroff points out that that there are thousands of published articles on biological dysfunction in ME/CFS, with no compelling evidence to suggest the illness is psychogenic (an illness of the mind).16
Many ME/CFS sufferers and advocacy groups are deeply concerned about the portrayal of the disorder as a psychological illness in medical publications and the wider media. Misinformation may negatively impact patients. Patient surveys consistently reveal that many ME/CFS patients experience medical scepticism, difficult interactions with health professionals and poor care quality (AfME, 2001).17 Sufferers report finding it difficult accessing benefits and social care and often have to fend off accusations of laziness and hypochondria – perhaps a consequence of the perception that the illness is a self-generated psychological illness.
The 25% ME Group, a charity that supports the most severely ill sufferers, state that the medical establishment has largely ignored these ME/CFS patients.18 Many are housebound or bedbound, with family members as full-time care-givers.
We must consider the harrowing case of Miss Sophia Mirza, a young ME sufferer forcibly removed from her home and sectioned under the Mental Health Act to impose psychiatric treatment on her. Miss Mirza died in 2005 and is one of the first patients in the UK to have ME as the official cause of death. The reality that ME/CFS kills some patients and dramatically shortens life expectancy is rarely reported in the media. In addition, ME/CFS sufferers are six times more likely to commit suicide compared to the general population;19 most likely as the result of having to deal with debilitating symptoms, such as chronic pain and sleep deprivation, but perhaps also having to deal with feelings of social isolation and poor medical treatment.
5. What can nurses do to support ME/CFS patients?
Many nurses will encounter ME/CFS patients, particularly in primary care. Nurses often have the capacity to form close therapeutic relationships with patients. Offering empathy and understanding to patients experiencing distressing symptoms is a central part of the nursing role. In the absence of a cure for ME/CFS, nurses are well placed to provide supportive care. By understanding the symptoms generated by the illness, nurses may be able to offer patients better care. ME/CFS severity varies from mild to severe and patients experience the illness in different ways. Some sufferers may be able to continue work on a limited basis, while others may be bed-bound, reliant on family and carers. Retired nurse Greg Crowhurst, a care-giver to a wife with severe ME/CFS, writes eloquently about how nurses may support patients with the illness.19
Practical tips for nursing practice are as follows:
Nurses also have an another important role as advocates for ME/CFS patients, helping to liaise between the patient and doctor and also helping to promote the patient voice in the public domain. However, to fulfill this important role, nurses need to better understand the illness and to understand that ME/CFS is by no means ‘all-in-the-mind’.
Conclusion: The key message for nurses
Most people feel fatigued following illness, stressful events, or after working long hours. This is quite different from the severe fatigue and the range of symptoms that patients with ME/CFS endure, including: unrelenting painful joints and muscles; cognitive dysfunction, including memory problems; gastrointestinal complaints; transient paralysis; hypersensitivity to light, noise and touch; unrefreshing sleep; post-exertional malaise after minimal effort; and the inability to maintain an upright posture for any significant period.
Overwhelming evidence shows that these symptoms are not psychosomatic. Nurses have a valuable role to play in assisting and supporting patients with ME/CFS. Nurses should not underestimate the power and importance of the nursing position to relieve suffering, prevent harm and promote better care for ME/CFS patients.
References
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2. NICE. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) – Diagnosis and management of CFS/ME in adults and children. NICE 2007, 53. https://www.nice.org.uk/guidance/cg53/chapter/1-guidance
3. O’Sullivan S. All in Your Head: True Stories of Imaginary Illness, 2016.
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5. IOM (Institute of Medicine). Beyond myalgic encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, DC; 2015. ISBN: 978-0-309-31689-7.
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11. Hooper M. Gibson Inquiry – Day 1 April 18th 2006 – Group Testimonies, Comments by Professor Malcolm Hooper 21st April, 2006. http://www.meactionuk.org.uk/Hooper_on_Gibson_Inquiry_Day_One.htm
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16. Wearden A, Dowrick C, Chew-Graham C et al. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. British Medical Journal 2010;340:c1777.
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17. Action for ME. ‘Severely neglected’. Patient Survey, 2001.
18. 25% ME Group. Stakeholder Response to NICE CG53 Three Yearly Review, Nov, 2010. http://www.angliameaction.org.uk/docs/25megroup-nice-cg53-response-nov2010.pdf (accessed January 2016).
19. Roberts E, Wessely S, Chalder T et al. Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register, Lancet, (published online Feb 9.), 2016.
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About the Author
Dr Keith Geraghty
Honorary Research Fellow, Centre for Primary Care, University of Manchester
