NICE takes a dim view of foreign work on ME/CFS

Posted on 10/25/2016 by wames

ME Association news blog post, 24 October 2016: NICE takes a dim view of foreign work on ME/CFS – Robin Ellis Freedom of Information request

The main supplier of England’s drugs and treatment guidelines, the National Institute for Health and Clinical Excellence (NICE), tends not to take foreign research into account when it produces work on ME/CFS.

In internal correspondence released this month under the Freedom of Information Act (FoI), the agency admitted that it has not yet considered the results of important US studies when deciding what is best for British M.E. patients.

NICE are holding back the review of their guidelines on ME/CFS until some time in 2017, saying the evidence to justify earlier reconsideration isn’t strong enough.

“It is not really for the NHS to respond to a report commissioned in another country and not yet examined by its commissioner”, the agency’s director for clinical practice wrote to colleagues as they were assembling their reply to a FoI request from Robin Ellis.

Professor Mark Baker wrote: “We would take seriously the views of the relevant esteemed medical associations in the UK, principally the RCP (Royal College of Physicians) and the RCPsych,(Royal College of Psychiatrists) when looking at reviewing this guidance.

“I am not aware of any reason to do anything before then unless some major new evidence on treatment emerges, and we know that no major studies are in progress”.

The applicant, Mr Ellis, filed three FoI requests earlier this year seeking the release of information held by NICE about the PACE Trial.

This time he wanted to know if NICE allowed its thinking on M.E. to be influenced by overseas research using easily observable symptoms – like testing for post-exertional fatigue using the 48-hour exercise test – the 2015 US Institute of Medicine report on the “devastating severity” of M.E – and the National Institutes of Health report which “retired” the Oxford criteria for CFS believing it to be harmful to people with the illness.

Mr Ellis also pointed to another US agency that had recently determined that CBT and GET were ineffective treatments given the poor outcomes reported all round – including in the PACE Trial.

Mr Ellis’s latest FoI request was formally entitled: Unique characteristics of pw ME/CFS as defined by the CCC and ICC and exercise physiologist experts eg Workwell Foundation, Snell, VanNess, Stevens, Klimas. He wanted to see what papers were held by NICE on these matters.

In the papers released by NICE, there is an intervention from the Countess of Mar, who chairs the Forward ME Group of charities.

The Countess wrote to NICE:

“I have to assume that you must agree that patients with ME/CFS are very much the same wherever they are in the world, and that there will be no difference between UK and US patients.

“I also assume that you must agree that very many more resources have been applied to this issue in the US than in the UK. Professor Baker reiterated his belief that there is no evidence that GET makes some patients worse.

“Absence of evidence is no evidence of absence, and there is plenty of evidence from the two major charities in the UK – Action for ME and the ME Association – which have both done major surveys of their members…”

Professor Baker replied that NICE will conduct a critique of the American work to consider “whether it adds anything to what we already know”.

He added: “You will be aware that the British academic establishment holds an entirely different view, though not necessarily any better informed.”

On October 19, Mr Ellis formally requested an internal review of NICE’s handling of his FoI request. “I asked for information around the decision NOT to update the NICE Guidelines, none was provided.”

The full exchange of correspondence can be read here: www.whatdotheyknow.com/request/unique_characeristics_of_pw_mecf#incoming-883778

The papers released can be read here:
www.whatdotheyknow.com/request/357691/response/883778/attach/2/FOI%20EH73066%20Redacted%20documents%20for%20release.pdf

The papers have been slightly redacted by NICE. The agency wrote that it did not want to show details of junior staff involved in the correspondence nor a third party who was consulted as part of the exercise.

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The ‘extreme’ side-effects of antidepressants

Posted on 10/24/2016 by wames

BBC news article, By Lesley Ashmall (BBC Victoria Derbyshire programme), 19 October 2016: The ‘extreme’ side-effects of antidepressants

Claire Hanley says she tried to take her own life twice after taking antidepressants
People who say their lives have been ruined by commonly prescribed antidepressants, known as SSRIs, are taking their case to Parliament on Wednesday. Some users say the tablets have made them suicidal.

“I was getting seizure-like symptoms, where my muscles were jolting around of their own accord,” Claire Hanley tells the BBC’s Victoria Derbyshire programme, explaining the effects she says antidepressants had on her body.

She had begun taking them while caring for her seriously ill mother and studying for her final exams at Cambridge University, but suffered severe side-effects after her GP prescribed a stronger dose of tablet.

“Within two weeks I’d tried to take my own life twice,” she says.

“I felt disorientated and sick and had digestive problems and infections, it was really extreme. I don’t even know how to begin. All I can remember is being on the bedroom floor in a kind of semi-conscious state having seizure after massive seizure.”

It has been 20 years since she first took the tablets, but Ms Hanley says she still suffers from the consequences of a cocktail of drugs doctors have prescribed to try to treat the side-effects of the original antidepressants.

She says she has constant muscle ache and fatigue, and spends most days in bed.

It is thought about one in 100 people experiences severe side-effects as a result of taking SSRIs.

The drugs are designed to increase serotonin levels in the brain, which can improve symptoms of depression.

Some experts, however, now believe many more people than was previously thought are suffering negative consequences.

Prof David Healy, from the psychiatric unit at Bangor University, believes the drugs make “one in four people become more anxious, rather than less”.

“Some people become very agitated and some go on from that to become suicidal,” he says.

“The drugs can become the problem that they’re then used to treat.”

The drugs companies have declined to comment, but Dr Sarah Jarvis, a GP in West London, is keen to point out that doctors do not prescribe antidepressants lightly.

She also stresses the vital role they can play in helping people with depression – saying, if untreated, “moderate depression and severe depression wreck lives, and very regularly cost lives”.

Dr Jarvis adds that for most people, the drugs are effective.

“I think for people with severe depression, they may need to try two or three [different types of antidepressant] before they find one that does work for them, but for most people we can find a medicine which will help them and for whom the benefits will outweigh the risks,” she says.

Antidepressants

  • Antidepressants cost the NHS £780,000 per day
  • Between 2005 and 2012, there was a 54% increase in the number of children prescribed antidepressants in the UK
  • Common side-effects include dizziness, headaches and feeling sick. These generally improve with time
  • Antidepressants can cause serotonin syndrome, which – while uncommon – can lead to seizures, an irregular heartbeat and unconsciousness in the most severe cases
  • In rare instances, some people experience suicidal thoughts and a desire to self-harm when they first take antidepressants. People under the age of 25 seem particularly at risk

Sources: Health and Social Care Information Centre, World Health Organization, NHS Choices

But according to some experts, such as Prof David Healy, the side-effects of antidepressants are not just felt when someone is taking them, but also when they try to reduce the dose or come off the tablets altogether.

“There’s a large number of people – and it seems to be more women than men – who have great difficulties trying to reduce the dose,” he says.

“And if they halt the treatment, they can become terribly agitated, they can become suicidal.”

“When you look at the clinical trials that have been done, the taper phase – the point where the person is trying to come off the drug – is the riskiest period.

“That’s the point where the person is most likely to commit suicide, or the most likely to do terrible things.”

Gemma – not her real name – says her withdrawal symptoms were so bad that she is now back on the tablets.

“I was told I could come off [antidepressants] no problem,” she says.

“But I was in a mess basically. I reached a point where I could barely function. I was incredibly anxious – I was highly anxious all the time, so I was very panicky, very agitated. I could barely sleep.”

Gemma had followed medical advice and come off the tablets slowly, but she suffered severe consequences nevertheless.

She says: “I was petrified. I was crying my eyes out. I didn’t know what on Earth was happening to me. I guessed it could be the medication, but I thought I had some kind of terminal illness. I just didn’t know what was happening.”

Gemma eventually decided to go back on the drugs, and the withdrawal symptoms quickly disappeared.

“I was shocked. All the migraines, the muscle aches – everything – just stopped instantly,” she says.

Many people find the effects manageable, but others – some of whom got in contact with us – say they have been severely affected. Here are a few.

Brigitte, from Exeter, said: “I couldn’t walk and was experiencing the most horrendous sensory sensations. My muscles were burning, I had facial twitches, terrible night sweats and numbness on my forehead.”

Pauline, from Hertfordshire, said: “I look and feel like a drug addict, I can’t focus my eyes. My eyes are like slits even if I’ve not been crying. I cannot sleep at all, and because it seems my body realises it is not getting the drug, every day is living hell.”

Christine said: “The fatigue is so bad that I have to go to bed in the afternoons and can do very little. I feel dizzy, nauseous, have blurred vision and a headache at the back of my head and on top.”

But others believe people who need medication should not be put off by those who have experienced severe symptoms.

Mehran, from south-east London, said: “I have been on and off antidepressants for over a decade. It is only natural to have withdrawal effects as the brain becomes comfortable with a certain level of chemicals. Usually, those people, like myself, who withdrew abruptly actually still needed the medication. I worry [that the stories of those with severe symptoms] put fear into the people that need medication.”

Mark, from London, said: “[When I started taking antidepressants] I did feel more, rather than less, anxious for the first two to three weeks – which was accompanied by muscle twitches, nausea and a general feeling of dissociation. But then I felt fine, I could function again and I got better. I believe SSRIs provided a crutch to support me through a difficult time, while I worked on finding a longer-term solution using psychotherapy.” Mark does not recall experiencing any withdrawal symptoms.

For Dr Jarvis, however, while some individuals may suffer prolonged side-effects from antidepressants – lasting months or, on occasion, years – she would be surprised if all of the reported effects related to the tablets.

“What we need to bear in mind is that some patients who have taken these have been very vulnerable, they’ve been very anxious and it can be very difficult to tell what is anxiety and what is the tablets,” she says.

But for Ms Hanley, the dangers must be taken more seriously by medical professionals.

“It may be a minority of people who have these extreme reactions, but they exist,” she says.

“If you look at the leaflets in the packets, and it says one in 100 will have this symptom, they’ve got to realise that that one person could be their patient. It does happen.”

NB In the ME Association survey of patients symptoms in 2010:

  • 46% found depression a major problem
  • 40% found depression a minor problem

Many were taking anti depressants.

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Nose & throat inflammation & HPV vaccinations in ME

Posted on 10/24/2016 by wames

ME Research UK article, 19 October 2016: Nose and throat inflammation

There are many different triggers for ME/CFS. In most people, the illness starts with an infection, often viral, but others report a vaccination or immunisation as the initial event. Although there has been very little research on this particular aspect, one Belgian report from 2002 found a small cluster of cases (around 5% of more than 1500 patients) where hepatitis B vaccination could have been involved in the initiation of ME/CFS  (read abstract), and there have been reports of ‘CFS-related’ adverse events after flu vaccinations  (read abstract).

Recently, there have been suggestions that vaccination against human papillomavirus (HPV) can lead to “patterned illness” involving chronic pain, headaches, fatigue, and problems on standing – very like the symptoms suffered by people with ME/CFS (read more). While HPV vaccination is considered beneficial overall, and there is little evidence of serious adverse effects in most recipients, the European Medicines Agency announced the launch of a ‘safety review’ of HPV vaccines in 2015 that will hopefully encourage healthcare professionals to look for unusual but potentially serious adverse effects (read more).

A Japanese study published this month in Immunological Research reports a possible association between HPV vaccination, chronic epipharyngitis (inflammation of the back of the nose and throat), and chronic symptoms. The researchers from the Hotta Osamu Clinic in Miyagi, Japan examined the nasopharynx in 41 young women (average age 17.3 years) who had developed ME/CFS-like symptoms following HPV vaccination.

Their symptoms included headache (in 97.6 %), general fatigue (95.1 %), sleep disturbance (87.8 %), stiffness of neck and upper back (85.3 %), photophobia (80.5 %), muscle weakness (75.6 %), and cognitive impairment (68.3 %). As a result, most of them (83%) were unable to attend school. They had been been treated using a number of approaches, but their condition had not significantly improved with any of these.

On closer examination, almost half of the patients had mild pharyngeal symptoms, but abrasion of the epipharyngeal mucous membrane with a cotton swab (which, the researchers say, tests for inflammation as chronic epipharyngitis is often not obvious by eye) and smear analysis showed that all 41 of them had severe epipharyngitis, identified by severe bleeding during the examination.

Sixteen patients were willing to come into hospital for treatment, consisting of a very dilute zinc chloride solution thoroughly applied to the epipharyngeal wall. While this treatment reduces the pain and inflammation at the back of the nose and throat, the most interesting finding was that in 13/16 patients there was also a marked reduction in symptoms overall after the procedure, with 4 patients eventually achieving a ‘cure’. As the authors say, “Given the degree of impairment of quality of life previously observed in these patients, the degree of response to this treatment was quite remarkable….” They point out that the extremely high incidence of severe epipharyngitis (100%) and dramatic improvement in patients’ general and multisystem symptoms after treatment strongly suggest an association between chronic epipharyngitis and the ME/CFS-like symptoms that developed after HPV vaccination.

Interestingly, the Japanese researchers outlined their results at a conference earlier this year, at the 4th International Symposium on Vaccines in Leipzig Germany (see the video presentation). In it, they point out that chronic epipharyngitis may have an important role in the development of various autoimmune diseases and disorders. They say that the epipharynx has high levels of immunologic activation and that, because of its anatomic location, chronic inflammation in the epipharynx can have systemic effects via autoimmunity and the autonomic nervous system.

It’s important to remember, however, that ‘chronic epipharyngitis’ is poorly recognised, and that the term is rarely used in the modern medical literature, particularly outside of Japan. For that reason, other studies need to validate and confirm these findings – in people with other medical conditions (autoimmune diseases and autonomic nervous disorders) as well as ME/CFS patients – and extend them to determine, for instance, the prevalence of chronic epipharyngitis in the population at large.

Are these results relevant to the majority of ME/CFS patients whose illness began with other triggers, mainly viral or other infections? Well, an accompanying Editorial in Immunological Research suggests so. Certainly, ‘sore throat’ at the early stages of illness had a prominent part  in descriptions of epidemics of myalgic encephalitis (read more), and the symptom is part of some definitions of ME/CFS, such as the Holmes criteria, and the International Consensus Criteria of 2011 as part of the ‘flu-like symptoms’ that may be recurrent (read more). A study examining the nasopharynx mucosa in a mixed-onset group of ME/CFS patients would well be revealing; if frank inflammation is present, a treatment trial could explore whether improvements occur in chronic symptoms as well as local inflammation.

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Perceptions of Myalgic Encephalomyelitis

Posted on 10/24/2016 by wames

Miscellanea blog post by Robert McMullen, September 2016: “Perceptions of Myalgic Encephalomyelitis”

A person with ME looks back at his experiences and at some prejudices that exist about people with ME in society and the medical profession.

Excerpt:

Before I was ill, I knew very little about ME. I was aware of the scepticism that surrounded it, which, combined with my ignorance, made me fairly cynical about those who “claimed” to have it. It had never occurred to me then that there might be people for whom this diagnosis – given to them – was unwelcome, despised or even denied.

When I was first unwell, before I was diagnosed, I detected no hostility or scepticism towards me. Mostly the doctors seemed sympathetic, concerned and curious to understand what was causing my symptoms. But once I was diagnosed and presented as a patient who had been diagnosed with ME I felt as though I was treated quite differently; as though I was someone I was not. Symptoms and character traits would be attributed to me that I have never had. I read articles by doctors who had never met me, denouncing me by association, as though I had diagnosed myself in order to join some sort of deluded cult of malingering hypochondriacs.

I couldn’t believe that any signatory to the Hippocratic Oath could be so cruel or ignorant to write with such venom without very good reason. My inclination was therefore to believe that I must be different to most other people who were diagnosed with ME, and that they, not the doctors, were the cause of the hostility I encountered.

For years I desperately sought an alternative diagnosis but none was offered. A neurologist once told me to have nothing to do with any of the ME organisations because most people who say they have ME are “just depressed”. But he assured me that I had an “organic illness” and that he would “get to the bottom of it”. His words were comforting to me at the time but the succour was short lived. The only alternative diagnosis he offered was that I had some sort of post-viral syndrome, which was even less useful than being told I that I had ME. In being discharged from his care, I was given the confident assurance that I would get better. Twenty two years later I am still waiting. And if he has not retired, he may well still be offering the same confident assurances to patients like me, oblivious to the outcomes of those he discharges.

Read more

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Privacy on long term condition health discussion forums

Posted on 10/21/2016 by wames

Research abstract:

Background:
The ethics of research into online communities is a long-debated issue, with many researchers arguing that open-access discussion groups are publically accessible data and do not require informed consent from participants for their use for research purposes. However, it has been suggested that there is a discrepancy between the perceived and actual privacy of user-generated online content by community members.

Objective:
There has been very little research regarding how privacy is experienced and enacted online. The objective of this study is to address this gap by qualitatively exploring the expectations of privacy on Internet forums among individuals with long-term conditions.

Methods:
Semistructured interviews were conducted with 20 participants with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and 21 participants with type 1 and 2 diabetes mellitus, and were analyzed using thematic analysis. Participants were recruited via online and offline routes, namely forums, email lists, newsletters, and
face-to-face support groups.

Results:
The findings indicate that privacy online is a nebulous concept. Rather than individuals drawing a clear-cut distinction between what they would and would not be comfortable sharing online, it was evident that these situations were contextually dependent and related to a number of unique and individual factors.

Conclusions:
Interviewees were seen to carefully manage how they presented themselves on forums, filtering and selecting the information that they shared about themselves in order to develop and maintain a particular online persona, while maintaining and preserving an acceptable level of privacy.

‘I Always Vet Things’: Navigating privacy and the presentation of self on health discussion boards among individuals with long-term conditions, by Ellen Brady, Julia Segar, Caroline Sanders in Journal of Medical Internet Research Vol. 18, #10, page e274, October 13, 2016

Keywords: privacy; ethics; research ethics; informed consent; patients;
social support

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Prof Jonathan Edwards comments on MEGA Big study oppostition

Posted on 10/21/2016 by wames

Opposing MEGA blog comment by Professor Jonathan Edwards about OMEGA Petition, 20 October 2016

Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine, commented on a Discussion – Petition: Opposing MEGA

jonathan-edwardsI was very concerned that a counter petition of this sort would be an own goal. However, reading this I cannot really fault it and am actually impressed by much of the wording and argument. The up front reference to researchers whose work has been shown to be substandard may seem inflammatory but we are past that now and I think being to the point is a strength. The point that MEGA is not the only game in town is well made. From my point of view I have yet to see any information that would convince me that any original thought has gone into the project. I am not a fan of Big Data. They jumped the gun and it is entirely legitimate to say so because it is an insult to the patients’ intelligence.

So I think I would encourage all members to sign. If the petition is there and is making a fair point good numbers of signatures would have impact.

Click here to see the petition

Give this MEGA project a chance to fly – don’t try to strangle it at birth, says Dr Charles Shepherd, 3 October 2016

MEGA research for M.E./CFS: pledge your support

MEGA Questions and Answers

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The real story about CFS: a devastating illness that needs a better name

Posted on 10/21/2016 by wames

Garnet news article by Maureen Hanson, 19 October 2016: The real story about Chronic Fatigue Syndrome: a devastating illness that needs a better name

Chronic Fatigue Syndrome is an illness that many may have heard of, but few, in reality, know much about.

The effect of the name

The misconception of the seriousness of the disease is in part caused by the use of the name Chronic Fatigue Syndrome (CFS), coined in 1988 by a committee convened at the Centers for Disease Control. Prior to that recommendation, the disease was known by the more intimidating name Myalgic Encephalomyelitis (ME), which is favored by many patients and still used in many countries overseas. Chronic Fatigue Syndrome trivializes the nature of the disease and its impact on the lives of the people who suffer with it.

For individuals severely ill with ME/CFS, merely arising from bed to take a shower, or leaving the house to go to a medical appointment, can cause them to be bedridden several days afterward. Some people cannot manage to get out of bed at all.

The name influences not only the public’s conception of the disease but also that of medical professionals. As a point, in fact, College students and medical trainees who were given identical scenarios were more likely to consider patients described as having myalgic encephalopathy as having a biomedical illness, while patients labeled as having chronic fatigue syndrome were more likely to be thought to be psychiatric cases.

Four times as many women as men fall ill with ME/CFS. Many doctors dismiss women’s descriptions of ME/CFS symptoms as depression or emotional disturbance.

A new name

Recognizing the effect of naming the disease Chronic Fatigue Syndrome on patients and doctors an Institute of Medicine study recommended changing the name Systemic Exertion Intolerance Disease.  The name refers to a primary symptom of the illness, post-exertional malaise, which is an increase in symptoms when a victim attempts to do some previously tolerable exertion.  Most patients reach a steady-state level of exertion that they know from experience that they can bear, and exceed it only when absolutely necessary, as they know the consequence will be a subsequent increase in pain, malaise, fatigue, and cognitive difficulties that will last days or weeks.

The images of the disease

But even a name change, which to be truthful, has not really caught on, won’t solve the problem when the imagery associated with the disease continues to be benign and misleading. As we all know, images are powerful and associating the wrong ones with the disease only helps to spread misinformation.

An exception is currently on an display in Times Square in New York: a video broadcast by the SolveME/CFS Initiative, a patient advocacy organization, which shows photos of genuine, severely ill Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients.

derails-destroys-steals

The SolveMe/CFS Initiative

New Research Encounters Same Bias

These images are quite a contrast to many that accompanied the multitude of news reports about the recent scientific publication about abnormalities in the gut microbiome in ME/CFS.  In June, a team of researchers which I was a part of, reported our discovery that the populations of bacteria in the gut of individuals with the disease are abnormal compared to healthy individuals.  Increased escape of bacteria from the gut into the bloodstream appears to trigger inflammation in some ME/CFS victims.

This new information was the topic of more than 70 articles in the lay and medical press.

All the attention on our work had a chance to educate people about the actual life-robbing nature of the disease.

But the photos chosen to illustrate many of these articles spread persistent misconceptions about the disease.

There were several categories of photographs used to illustrate the news reports about our gut microbiome findings: microscopic images of bacteria, anatomical drawings with intestines highlighted, and photographs of people thought to be experiencing ME/CFS.

But many of the photos of patients with the disease were completely inappropriate, resulting from the misunderstanding that fatigue is not only the primary, but also the only symptom of the disease.

Indeed, one article was entitled: “Gut bacteria can make you tired.”

Fatigue is a common effect of other diseases as well, including multiple sclerosis and cancer.  But no one would illustrate an article about either of those diseases with someone sleeping at her computer, a woman snoozing with coffee cup in hand, or a woman who has evidently just come home from work, gazing wearily at children’s toys scattered around the floor. Another photo shows a woman lying on a couch with light from a nearby window streaming onto her face.  ME/CFS victims are unlikely to be in such a pose, given that most are quite sensitive to light and some must confine themselves to dark bedrooms.

When the underlying cause of the disorder is finally understood, undoubtedly a new and more accurate name will arise.  In the meantime, it’s important for editors at news outlets and health news bloggers to not only cover the disease accurately but to select images that represent the true nature of the disease that is described by the Institute of Medicine as  “a serious, chronic, complex, and multisystem disease that frequently and dramatically limits the activities of affected patients.”

Maureen Hanson is Professor of Molecular Biology and Genetics at Cornell University and conducts NIH-supported research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. She is a Public Voices Fellow of The OpEd Project.

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Elevated energy production by non-mitochondrial sources in CFS sub-group

Posted on 10/20/2016 by wames

Research abstract:

Chronic Fatigue Syndrome (CFS) is a debilitating disease characterized by physical and mental exhaustion. The underlying pathogenesis is unknown, but impairments in certain mitochondrial functions have been found in some CFS patients. To thoroughly reveal mitochondrial deficiencies in CFS patients, here we examine the key aspects of mitochondrial function in blood cells from a paired CFS patient-control series.

Surprisingly, we discover that in patients the ATP levels are higher and mitochondrial cristae are more condensed compared to their paired controls, while the mitochondrial crista length, mitochondrial size, shape, density, membrane potential, and enzymatic activities of the complexes in the electron transport chain remain intact.

We further show that the increased ATP largely comes from non-mitochondrial sources. Our results indicate that the fatigue symptom in this cohort of patients is unlikely caused by lack of ATP and severe mitochondrial malfunction. On the contrary, it might be linked to a pathological mechanism by which more ATP is produced by non-mitochondrial sources.

Discussion:

CFS afflicts millions of people, but its underlying cause remains elusive. In this study, by examining mitochondrial phenotypes in depth in a patient-control series, we have revealed that there is no major mitochondrial defect in CFS patients. Despite finding that mitochondrial cristae are more condensed, the mitochondrial morphology, the ETC, and the ΔΨ remain intact in CFS patients compared to their paired controls. Intriguingly, we have shown that ATP production is stimulated in CFS patients, and the elevated ATP content mainly comes from non-mitochondrial sources.

Our results present an unorthodox view on CFS pathology: the fatigue is not caused by lack of ATP, and instead might be caused by a pathological process linked to non-mitochondrial ATP production such as glycolysis.

Mitochondrial crista architecture is exquisitely and dynamically maintained to support the changing mitochondrial aerobic respiratory rate 26-30. The membrane area and number of cristae are expanded upon energy need elevation to promote respiratory activities 31,32. The fact that the crista number is increased in CFS patients suggests that their energy demands might be unusually high, which triggers condensation of mitochondrial crista membranes.

The contrasting results of the ATP levels in different cohort of patients 11,13-15 (this study) indicate that CFS is a complex disease and the current diagnoses may include people with varying molecular dysfunctions. A better categorization of patients with differing cellular defects will allow researchers to better understand the underlying causes and improve treatment efficacy. Future studies are warranted to unravel why and how non-mitochondrial ATP production is activated in some patients, which will yield insights into novel strategies to address the pathological causes.

Elevated Energy Production in Chronic Fatigue Syndrome Patients, by N Lawson, CH Hsieh, D March, X Wang in J Nat Sci. 2016;2(10). pii: e221

 

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Case report of differences between twins where only one has ME

Posted on 10/20/2016 by wames

Case report abstract:

BACKGROUND: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with profound fatigue, flu-like symptoms, pain, cognitive impairment, orthostatic intolerance, and post-exertional malaise (PEM), and exacerbation of some or all of the baseline symptoms.

CASE REPORT: We report on a pair of 34-year-old monozygotic twins discordant for ME/CFS, with WELL, the non-affected twin, and ILL, the affected twin. Both twins performed a two-day cardiopulmonary exercise test (CPET), pre- and post-exercise blood samples were drawn, and both provided stool samples for biochemical and molecular analysis.

At peak exertion for both CPETs, ILL presented lower VO2peak and peak workload compared to WELL. WELL demonstrated normal reproducibility of VO2@ventilatory/anaerobic threshold (VAT) during  CPET2, whereas ILL experienced an abnormal reduction of 13% in VAT during  CPET2.

A normal rise in lactate dehydrogenase (LDH), creatine kinase (CK), adrenocorticotropic hormone (ACTH), cortisol, creatinine, and ferritin content was observed following exercise for both WELL and ILL at each CPET. ILL showed higher increases of resistin, soluble CD40 ligand (sCD40L), and soluble Fas ligand (sFasL) after exercise compared to WELL.

The gut bacterial microbiome and virome were examined and revealed a lower microbial diversity in ILL compared to WELL, with fewer beneficial bacteria such as Faecalibacterium and Bifidobacterium, and an expansion of bacteriophages belonging to the tailed dsDNA Caudovirales order.

CONCLUSIONS: Results suggest dysfunctional immune activation in ILL following exercise and that prokaryotic viruses may contribute to mucosal inflammation and bacterial dysbiosis. Therefore, a two-day CPET and molecular analysis of blood and microbiomes could provide valuable information about ME/CFS, particularly if applied to a larger cohort of monozygotic twins.

A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition by Ludovic Giloteaux, Maureen R. Hanson, Betsy A. Keller in Am J Case Rep 2016; 17:720-729

 

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Dr Mark Porter on the challenge of IBS, pregabalin & BAD

Posted on 10/19/2016 by wames

The Times article, by Dr Mark Porter, 18 October 2016: Not all of the six million Brits who think they have IBS need to hang on for the new wonder drug

“Part of the challenge is that IBS is unlikely to be one disorder”

At least six million people in the UK are regularly troubled by symptoms of irritable bowel syndrome (IBS), so it should come as no surprise that an effective treatment has long been the holy grail of pharmaceutical companies working in the gastrointestinal arena. They are yet to make a significant breakthrough.

The latest advance, however, comes from the US, where researchers at the prestigious Mayo Clinic have announced that pregabalin — a drug used to treat neuralgia and anxiety — eases the discomfort associated with IBS. Yet it is early days and pregabalin may go the way of other breakthroughs in this area, which have all failed to live up to early promise.

Part of the challenge is that IBS is unlikely to be one disorder. It is simply a diagnosis of exclusion — an umbrella term to explain groups of symptoms that can’t be attributed to anything else. At least that is what it is supposed to be.

In recent years it has become clear that many people with problems previously attributed to IBS may have another condition. If you have the type of IBS associated with diarrhoea/loose stools — about half of people do — your symptoms may be more manageable than you think; as many as half a million sufferers are thought to have idiopathic bile acid diarrhoea (BAD) caused by an excess of bile in the lower bowel. We all produce about eight litres of digestive juices each day, including up to a litre of bile that helps us to absorb fat. Nearly all of these juices are reabsorbed before they reach the lower part of the gut, but this process goes awry in BAD.

The volume of digestive juices is the reason why gastroenteritis can quickly lead to dehydration. If the intestinal transit time is dramatically increased by infection-induced inflammation, there is not enough time to absorb the digestive juices and you can pass litres a day, even if you have had only a cup of tea and nibbled on a biscuit. With BAD there is no infective virus or bacteria, but the unabsorbed bile has an irritant effect on the lower bowel, increasing transit time in a similar fashion.

There are some good medical reasons why the bile reabsorption mechanism is hampered in some people — ranging from inflammatory bowel disease to gall bladder removal — but for those with idiopathic BAD there appears to be a genetic glitch in the transport system responsible for collecting and recycling bile salts. The result is that too much bile reaches the colon.

As well as the characteristic bloating and discomfort you get with IBS, tell-tale signs of BAD include unusual-coloured stools (shades of green or yellow) that are difficult to flush away, and needing to go to the loo during the night. Symptoms tend to be worse after fatty meals because these induce more bile secretion.

Specialist gastroenterology clinics have access to a specific test to confirm BAD, but it is expensive and not routinely available. A more pragmatic approach is to consider a trial of therapy with a granular drink (cholestyramine) that mops up bile. If this works it suggests that your IBS is in fact BAD.

The trick is to reduce the cholestyramine (mixed with water into a rather unpleasant wallpaper paste-like drink) to the bare minimum dose that controls the symptoms — often one or two sachets a day are enough. Other tips include switching to a low-fat diet and making breakfast and lunch your main meals of the day and only snacking in the evening.

So, while we await a “cure” for IBS, our best hope remains research into other possible underlying causes. And I very much doubt BAD will be the only “new” discovery in this field as we increase our understanding of the gut and the billions of friendly bacteria that live in it.

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