NICE Statement about graded exercise therapy in the context of COVID-19

Posted on 07/13/2020 by wames

Statement about graded exercise therapy in the context of COVID-19

 

NICE is aware of concerns about graded exercise therapy (GET) for people who are recovering from COVID-19. NICE’s guideline on ME/CFS (CG53) was published in 2007, many years before the current pandemic and it should not be assumed that the recommendations apply to people with fatigue following COVID19.

The recommendations on graded exercise therapy in CG53 only apply to people with a diagnosis of ME/CFS as part of specialist care, and CG53 is clear that this should be part of an individualised, person-centred programme of care, with GET only recommended for people with mild to moderate symptoms.

As the guideline is currently being updated, it is possible that these recommendations may change. The evidence for and against graded exercise therapy is one of the important issues the guideline committee is considering.

NICE plans to consult on the updated guidance in November 2020. NHS England has recently published guidance on After-care needs of inpatients recovering from COVID-19 that includes advice on fatigue.

July 2020

ME Association: Clinician’s Letter to NICE Results in Statement on Graded Exercise for Post-Covid-Syndrome

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Altered structural brain networks related to adrenergic/muscarinic receptor autoantibodies in CFS

Posted on 07/13/2020 by wames

Altered structural brain networks related to adrenergic/muscarinic receptor autoantibodies in Chronic Fatigue Syndrome, by Hiroyuki Fujii, Wakiro Sato, YukioKimura, Hiroshi Matsuda, Miho Ota, Norihide Maikusa, Fumio Suzuki, Keiko Amano Isu Shin, Takashi Yamamura, Harushi Mori, Noriko Sato in Journal of Neuroimaging · July 2020 [doi.org/10.1111/jon.12751]

 

Research Abstract:

BACKGROUND AND PURPOSE
Recent studies suggest that the autoantibodies against adrenergic/muscarinic receptors might be one of the causes and potential markers of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The purpose of this study was to investigate the structural network changes related to autoantibody titers against adrenergic/muscarinic receptors in ME/CFS by performing a single‐subject gray matter similarity‐based structural network analysis.

METHODS
We prospectively examined 89 consecutive right‐handed ME/CFS patients who underwent both brain MRI including 3D T1‐wighted images and a blood analysis of autoantibodies titers against β1 adrenergic receptor (β1 AdR‐Ab), β2 AdR‐Ab, M3 acetylcholine receptor (M3 AchR‐Ab), and M4 AchR‐Ab. Single‐subject gray matter similarity‐based structural networks were extracted from segmented gray matter images for each patient. We calculated local network properties (betweenness centrality, clustering coefficient, and characteristic path length) and global network properties (normalized path length λ, normalized clustering coefficient γ, and small‐world network value δ). We investigated the correlations between the autoantibody titers and regional gray matter/white matter volumes, the local network properties, and the global network properties.

RESULTS

Dorsolateral Prefrontal Cortex

Betweenness centrality showed a significant positive correlation with β1‐AdR‐Ab in the right dorsolateral prefrontal cortex. The characteristic path length showed a significant negative correlation with β2‐AdR‐Ab in the right precentral gyrus. There were no significant correlations between the antibody titers and the regional gray matter/white matter volumes, and the global network properties.

CONCLUSIONS
Our findings suggest that β1 AdR‐Ab and β2 AdR‐Ab are potential markers of ME/CFS.

 

Read full article

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Achieving symptom relief in patients with ME by targeting the neuro-immune interface & inducing disease tolerance

Posted on 07/09/2020 by wames

Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance, by Lucie ST Rodriguez, Christian Pou, Lakshmikanth Tadepally, Jingdian Zhang, Constantin Habimana Mugabo, Jun Wang, Jaromir Mikes, Axel Olin, Yang Chen, Joanna Rorbach, Jan-Erik Juto, Tie-Qiang Li, Per Julin, Petter Brodin in bioRxiv 2020.02.20.958249; [doi:org/10.1101/2020.02.20.958249]

 

Research abstract

Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection.

The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation.

Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ~30% reduction in overall symptom scores after eight weeks of treatment.

By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation.

The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.

Discussion – excerpt:

The symptom relief induced by INMEST targeting the vagus nerve is significant and distinct from placebo, but must still be confirmed in larger trials with sufficient statistical power. We believe that this should be done using a self-treatment system available for use at home since the repeated visits to the clinic are so demanding for patients with ME. The main purpose of the current study was instead to use the INMEST treatment as a perturbation to the immune system and autonomic inflammatory reflex, as a means of uncovering the pathogenesis of the disorder. To this end the current study was successful and the biomolecular correlates found corroborate several previously suggested aspects of ME pathogenesis.

The mechanism of action of the INMEST-treatment in ME is not known, although some things are clear. We know that the vagus nerve nucleus in the brainstem is activated by INMEST, but also higher level centers such as the limbic system are activated (24). The effect of INMEST on heart rate variability differs from that of traditional vagus nerve stimulating methods (23). One possibility is that INMEST influences incoming (afferent) signals from the gut, conveying signals of dysbiosis or chronic immune activation and inflammation. This hypothesis is in line with previous proposals of ME as a disease caused by microbial dysbiosis in the gut (48). One possible mechanism of symptom relief upon INMEST-treatment could be through limiting such signals of enteric dysbiosis via the afferent vagus nerve.

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Cardiopulmonary responses to exercise in an individual with ME/CFS during long-term treatment with intravenous saline: a case study

Posted on 07/08/2020 by wames

Cardiopulmonary responses to exercise in an individual with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome during long-term treatment with intravenous saline: A case study by Todd E Davenport, Michael K Ward, Staci R Stevens, Jared Stevens, Christopher R Snell, J Mark VanNess, in Work, pp. 1-7, 2020 [DOI: 10.3233/WOR-203214]

 

Research abstract:

BACKGROUND:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) causes significant impairment in daily activities, including the ability to pursue daily activities. Chronotropic intolerance is becoming better characterized in ME/CFS and may be the target of supportive treatment.

OBJECTIVE:

To document the effect of repeated intravenous (IV) saline administration on cardiovascular functioning and symptoms in a 38-year old female with ME/CFS.

METHODS:

The patient received 1 L of 0.9% IV saline through a central line for a total of 675 days. Single CPETs were completed periodically to assess the effect of treatment on cardiopulmonary function at peak exertion and ventilatory anaerobic threshold (VAT). An open-ended symptom questionnaire was used to assess subjective responses to CPET and self-reported recovery time.

RESULTS:

Improvements were noted in volume of oxygen consumed (VO2), heart rate (HR), and systolic blood pressure (SBP) at peak and VAT.

Self-reported recovery time from CPET reduced from 5 days to 1–2 days by the end of treatment. The patient reported improved quality of life related, improved capacity for activities of daily living, and reduced symptoms.

CONCLUSIONS:

IV saline may promote beneficial effects for cardiopulmonary function and symptoms in people with ME/CFS, which should be the focus of formal study.

Read full paper

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A demon on my life – a play about ME

Posted on 07/08/2020 by wames

A demon on my life – a play about ME  

 

A play written by JB Bruno has been premiered online and is now available to watch on YouTube.

 

“A demon on one’s life.

What a ripe metaphor for chronic fatigue syndrome (ME/CFS). A demon – a kind of slippery, malevolent, unearthly being – difficult to get one’s hands on. Difficult even to see… On one’s life. Not around one’s life but on it, pushing it, like the force of gravity, down.”

 

The play, dedicated to ME patients, tells an interesting, emotionally powerful story centred around a young woman, Liz, who has been sidelined by ME from her career as a dancer, and her husband, Mark.

Starts at 2 min 30 until 1h 46  – followed by a Q&A   [1h 44 long]

 

The writer JB Bruno explains how he came to write the play:

A friend from many years ago, who was dealing with ME/CFS, piqued his interest.

“I started researching and watching documentaries. Three things struck me most about the disease that made it different from others: it was very much misunderstood, it was often misdiagnosed, and compared to other diseases, it was significantly under-funded. All this for a disease whose origins are still disputed today and that right now has no cure in sight. ”

“This was clearly the story I needed to tell. “

Read more about the background to the play and its production from Cort Johnson on the Health Rising blog

 

Leigh Fitjzames as Liz, and Darren Lee as Mark, her husband – grappling with the changes in their lives.

A review of the performance by a person with ME

The cast did a truly wonderful job in this play. The crew responsible for putting the play on live via Zoom enhanced it greatly with the beautiful and creative “sets” (exquisite miniature dioramas) used in between acts and, minus the Zoom window shifts in between acts, I easily forgot I was watching Zoom. You have to use your imagination as an audience member, but they showed brilliantly that with talented actors, it can be done.

In the Q&A sessions after each live performance, the writer/director, cast and crew demonstrated their curiosity and empathy about ME and they deserve a big thank you for taking this on. Several mentioned they had known absolutely nothing about the disease before signing on.

Read more at “A Demon on My Life” Gets It Right About ME/CFS: A Review

 

The company plans to do a theatrical run in New York when the theaters open again. At that time, they hope to have the funds to do another livestream performance for an ME/CFS audience that would not be able to make a trip to a theatre. 10% of all proceeds will go to Solve ME/CFS Initiative, an advocacy group for research, treatment and awareness.

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Dental considerations for a patient with ME/CFS – a case study

Posted on 07/08/2020 by wames

Dental considerations for a patient with Myalgic Encephalopathy/ Chronic Fatigue Syndrome – a case study, by Serena Halsall in Journal of Disability and Oral Health Vol 20, #3  October 1, 2019

 

Abstract

Myalgic Encephalopathy, also known as Chronic Fatigue Syndrome (ME/CFS), is a chronic condition with: a range of fluctuating symptoms, no cure, and can cause a person to be bedbound. This case report identifies recommendations for dental care based on the experiences of a female 17-year-old living with severe ME/CFS.

Excerpt

Around the age of 16, Patient X’s functional ability improved, thus allowing her to tolerate the travel to her GDP with her carer and have a dental examination.

Reasonable adjustments were made with:

  • The appointment being booked at a time that corresponded with Patient X’s energy levels
  • A ramp to allow wheelchair accessibility into the practice and the surgery being on the ground floor
  • The patient wearing sunglasses and noise cancelling headphones to reduce visual and auditory stimulation
  • The dentist offering to carry out the examination with the patient in her wheelchair or on the dental chair
  • Oral hygiene instructions being given to the patient and their carer.

Conclusions

ME/CFS can have severe and unpredictable effects on a person’s life. With a prevalence of 1 in 250 people, it is important that the dental team understands its nature and potential severity, which can present a barrier to accessing dental care. For these high priority patients, it is essential that their dental health is not overlooked. To conclude, the
following recommendations are made:

  • The dental team must have a good understanding of ME/CFS, its symptoms and effects on access to healthcare, to support the patient and their carer(s) and to optimise oral health
  • The dental team should consider the variable and fluctuating symptoms of ME/CFS and should make the patient aware of the available support if symptoms of the condition worsen
  • After a discussion with the patient and their carer(s), the dental team should be able to identify the patient’s specific individual needs and make the necessary adjustments to improve their dental care
  • The dental team should recognise if a patient is unable to attend dental appointments and should act to facilitate their access to dental care, by liaising with other healthcare disciplines to provide special care dentistry
  • A multidisciplinary approach should be considered, to provide the most appropriate and accessible dental care, working with the patient’s wider healthcare team and other dental disciplines.
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“Long Haulers” to the rescue? Barrage of Covid-19 media stories, studies & registries spells hope for ME/CFS

Posted on 07/08/2020 by wames

Health rising blog post, by Cort Johnson: “Long Haulers” to the rescue? Barrage of Covid-19 media stories, studies and registries spells hope for ME/CFS, 5 July 2020

 

Media Barrage

Sars-Cov-2 has wreaked havoc but it does appear to be opening new possibilities for ME/CFS

A veritable avalanche of stories – the C19Recovery Awareness website provides a link to approximately 50 articles since June 1st – have highlighted  the problems that many people have had recovering from the coronavirus. With eight stories published in the past four days, they’re still coming at a good clip.

That is all good news. These media reports – some pitched by organizations like Solve ME/CFS and ME Action – are crucial in getting us more support. The U.S., inadvertently, is helping a great deal to keep the story in the news.  Six months into the coronavirus pandemic, infections have slowed down markedly in Europe, Asia and Australia but have picked up steam in the U.S., South America and other countries.

The U.S.’s inability to get its act together, as tragic as it is, does present a silver lining: the more people that get infected, the more people will likely have difficulty recovering, and the more people will come down with an ME/CFS-like condition. That’s bad news for them, but it’s good news for everyone saddled with a post-viral illness.

Plus it could be argued that the more people that get sick, the more chance we have of getting the resources to develop treatments that will help them and others get well.

This isn’t, after all, just about Covid-19 or chronic fatigue syndrome (ME/CFS). The insights learned from this research may be able to be applied to every disease that can be triggered by an infection including fibromyalgia, POTS and autoimmune diseases. Potentially millions of people could be helped.

The media is playing a crucial role in getting the COVID-19/ME/CFS link out, but some media stories are better than others. It’s crucial that a link be made between ME/CFS and problems recovering from the virus. The best media stories for us involve people who look like ME/CFS patients; i.e. they are healthy younger or middle-aged people who were never hospitalized and who remain ill several months later. The worst news stories focus on hospitalized patients, who often have underlying conditions and never mention ME/CFS.

Read more about the media stories of people’s recovery problems and the research into Covid-19

Conclusion

The media interest is there – and a follow up blog will show that it’s producing results for us. Two big longitudinal immune-based and “omics” NIH studies, and a smaller but intensive study featuring Avindra Nath, plus the OMF-funded Stanford and Harvard “omics” studies provide cause to hope that we may finally be able to catch ME/CFS in the act during that crucial period when an infection somehow devolves into a life-long illness.

They are a good start. We need more and we will hopefully get them as some of the 25 CMDRP grant applications get funded and as more NIH grants get funded as well. One would hope and expect that a well-funded Request for Applications (RFA) grant opportunity to study the long-term affects of COVID-19 will pop up soon at the NIH.

The birth of numerous COVID-19 registries and tracking efforts provides hope that the extent and seriousness of post-viral illnesses such as ME/CFS will finally hit home in the medical community. It’ll be interesting to see if, after six months, the still ill post-COVID-19 patients are given an ME/CFS diagnosis.

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Energy systems & pacing in ME/CFS

Posted on 07/06/2020 by wames

Frozen in Amber blog post, by Caroline Elisabeth: Energy systems and pacing in ME/CFS, 29 June 2020

 

Summary

  • The aerobic energy system is “broken” in ME/CFS and cannot be fixed with exercise (i.e., graded exercise therapy, also known as GET).
  • The anaerobic (glycolytic) system appears to be somewhat functional in ME/CFS (but see McGregor’s work) and, in theory, can be trained to be more efficient with a carefully-designed exercise protocol done under the guidance of an ME/CFS-literate physical therapist.
  • It is vitally important to avoid spending time above the anaerobic threshold, also known as “AT”.
  • It is also advisable to minimize the duration of aerobic activities, including cognitive tasks.
  • If the points above appear to contradict each other, in a sense they do! But a well-designed pacing program can minimize the negative effects of both aerobic and anaerobic metabolism while at the same time harness the benefits of each energy system.

 

Read the full article

 

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DNA Methylation & BDNF expression account for symptoms & widespread hyperalgesia in patients with CFS & FM

Posted on 07/03/2020 by wames

DNA Methylation and BDNF Expression account for symptoms and widespread hyperalgesia in patients with Chronic Fatigue Syndrome and Fibromyalgia, by Andrea Polli, Manosij Ghosh, Jelena Bakusic, Kelly Ickmans, Dora Monteyne, Brigitte Velkeniers, Bram Bekaert, Lode Godderis, Jo Nijs in Arthritis Rheumatol. 2020 Jun 20 [doi: 10.1002/art.41405]

 

Research abstract:

Background:

Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).

Methods:

A repeated-measures study in 54 participants (28 patients with CFS/FM and 26 matched healthy controls) was conducted.

Representation of a DNA molecule that is methylated.

Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. BDNF protein level was measured in serum (sBDNF) using ELISA, while polymorphism and DNA methylation were measured in blood, using pyrosequencing technology. To assess temporal stability of the measures, participants underwent the same assessment twice within four days.

Results:

Repeated-measures mixed linear models were performed for between-group analysis. sBNDF was higher in patients with CFS/FM (F=15.703; mean difference: 3.31 ng/ml, 95% C.I. 1.65 to 4.96; p=.001), whereas BDNF DNA methylation was lower in Exon IX (F=9.312; mean difference -2.38%, C.I. -3.93 to -0.83; p=.003). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF (F=4.910, t= -2.216, p=.029, 95% C.I. = -.712 to -.039) which in turn predicted participants’ symptoms (F=14.410, t= 3.796, 95% C.I.= 1.79 to 5.71, p=.001) and widespread hyperalgesia (F=4.147, t= 2.036, 95% C.I.= .01 to .08, p=.044).

Discussion:

sBDNF is higher in patients with CFS/FM and BDNF methylation in exon IX accounts for regulating protein expression. Altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.

Read full paper

 

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Protective effect of hemin against experimental CFS in mice: possible role of neurotransmitters

Posted on 07/02/2020 by wames

Protective effect of hemin against experimental Chronic Fatigue Syndrome in mice: possible role of neurotransmitters, by Vandana Thakur, Sumit Jamwal, Mandeep Kumar, Vikrant Rahi & Puneet Kumar  in Neurotoxicity Research (2020) [doi.org/10.1007/s12640-020-00231-y]

 

Research abstract:

Chronic fatigue syndrome (CFS) is a disorder characterized by persistent and relapsing fatigue along with long-lasting and debilitating fatigue, myalgia, cognitive impairment, and many other common symptoms.

The present study was conducted to explore the protective effect of hemin on CFS in experimental mice. Male albino mice were subjected to stress-induced CFS in a forced swimming test apparatus for 21 days. After animals had been subjected to the forced swimming test, hemin (5 and 10 mg/kg; i.p.) and hemin (10 mg/kg) + tin(IV) protoporphyrin (SnPP), a hemeoxygenase-1 (HO-1) enzyme inhibitor, were administered daily for 21 days.

Various behavioral tests (immobility period, locomotor activity, grip strength, and anxiety) and estimations of biochemical parameters (lipid peroxidation, nitrite, and GSH), mitochondrial complex dysfunctions (complexes I and II), and neurotransmitters (dopamine, serotonin, and norepinephrine and their metabolites) were subsequently assessed.

Animals exposed to 10 min of forced swimming session for 21 days showed a fatigue-like behavior (as increase in immobility period, decreased grip strength, and anxiety) and biochemical alteration observed by increased oxidative stress, mitochondrial dysfunction, and neurotransmitter level alteration.

Treatment with hemin (5 and 10 mg/kg) for 21 days significantly improved the decreased immobility period, increased locomotor activity, and improved anxiety-like behavior, oxidative defense, mitochondrial complex dysfunction, and neurotransmitter level in the brain.

Further, these observations were reversed by SnPP, suggesting that the antifatigue effect of hemin is HO-1 dependent. The present study highlights the protective role of hemin against experimental CFS-induced behavioral, biochemical, and neurotransmitter alterations.

Read full article

ME Research UK: Hemin protects against CFS-like symptoms in mice

Key findings

  • A CFS-like condition was induced in experimental mice, resulting in decreased activity, increased immobility and raised anxiety levels.
  • Treatment with hemin for 21 days improved all these symptoms, and also reduced oxidative stress, mitochondrial dysfunction and changes in the levels of several neurotransmitters.
  • It remains to be seen whether hemin has any effect in humans with ME/CFS, and might therefore be used as a therapy to alleviate symptoms.
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