Better care needed for young people with severe ME/CFS

A study of children and young people in the UK pre-pandemic found that investigation, referral and management of those with suspected severe ME/CFS do not always meet NICE recommendations.

This suggests patients may be receiving suboptimal care since alternative diagnoses are not appropriately excluded and specialist care is not provided. The low number of young people receiving domiciliary visits or social services assessment/support limits their access to management.

The researchers conclude that further work should focus not only on determining the most effective treatments for children with severe ME/CFS but also on exploring the barriers to accessing these services and how these can be addressed.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), is a disabling condition that affects people of all ages, including children and young people (CYP).
• NICE (The National Institute for Health and Care Excellence) published guidelines in 2021 recommending that CYP with suspected severe ME/CFS should have standardised screening investigations to exclude conditions other than ME/CFS that might cause similar symptoms.
• Those with a confirmed diagnosis should be referred to specialist care and this should include domiciliary visits, particularly for individuals unable to leave their homes. It is not known how often these recommendations are implemented.

WHAT THIS STUDY ADDS

• The standardised investigations recommended by NICE are inconsistently performed for CYP with suspected severe ME/CFS, and this is a barrier to confirmation of diagnosis.
• Referral guidelines are not met for nearly one-third of CYP diagnosed with severe ME/CFS.
• Medication to manage symptoms is prescribed for the majority but domiciliary visits and social service referrals are quite uncommon, received by only 12% of confirmed cases.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• This study suggests the provision for CYP with ME/CFS, including appropriate investigation and onward referral to specialist services requires standardisation in clinical practice.
• Further research is required to identify barriers to the NICE guideline’s implementation and how these can be tackled.

Management of severe ME/CFS in children and young people in the UK: a British Paediatric Surveillance Unit study  by Alexander Peter Royston, Sarah Burge,  Ilaria Idini,  Amberly Brigden, Katharine Claire Pike in BMJ Paediatrics Open 2024;8:e002436 [doi: 10.1136/bmjpo-2023-002436]

Research abstract:

Objective 

Severe myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) in children and young people (CYP) is a little-understood condition which significantly impacts education, development and quality of life.

We used data from a population-wide surveillance study to explore the screening investigation, referral and management of suspected cases of paediatric severe ME/CFS.

Methods 

A British Paediatric Surveillance Unit (BPSU) study reported cases of CYP with suspected severe ME/CFS between February 2018 and February 2019. Paediatricians reporting cases to BPSU and allied healthcare professionals in two large specialist paediatric ME/CFS centres were invited to complete questionnaires for CYP meeting the surveillance case definition. The study focused primarily on CYP with confirmed severe ME/CFS and the extent to which their care met NICE  (The National Institute for Health and Care Excellence) recommendations but also considered separately those with probable or possible severe ME/CFS.

Results

This study includes a total of 92 CYP with suspected severe ME/CFS; 33 meeting criteria for severe ME/CFS and an additional 59 classified as probable or possible severe ME/CFS. For 16 possible cases, incomplete investigation to exclude alternative diagnoses prevented confirmation of a severe ME/CFS diagnosis.

Only 21 of 33 (64%) confirmed severe ME/CFS cases had been referred to specialist services. The management provided varied considerably between patients and four received nothing at all. Of the management provided, the most frequent approaches were medication (67%), activity management (61%) and physiotherapy (61%).

Domiciliary assessments and support, and social services referrals were received by 12% and 6% of confirmed severe cases. Similar proportions of management approaches were seen in probable/possible severe ME/CFS.

Conclusion

Full investigation is frequently incomplete in CYP with suspected severe ME/CFS and recommendations for referral and management are poorly implemented, in particular the needs of CYP who are unable to leave their home might be poorly met.

Be part of the World ME Day 2024 campaign film

As we approach World ME Day 2024, WAMES and the World ME Alliance (WMEA) invites you to be a part of a new short film that aims to shed light on the reality of Myalgic Encephalomyelitis (ME).

The World Health Organization recognized ME 55 years ago, yet any treatment remains elusive, and millions more are now grappling with the aftermath of ME triggered by COVID-19. This global health crisis demands attention, and we need your voice to make a difference.

Take Part
Send us a short video of yourself reading out the script below.

This script has been developed by people with ME across four countries. We’ll join your videos together into one campaign film, to reach others and demonstrate that ME is a truly global health crisis. We’ll then use this to call on individuals, organisations and countries to join together as a #GlobalVoiceForME advocating for change.

Script for your video

“It’s 55 years since the World Health Organization officially recognised Myalgic Encephalomyelitis.

But there is still no cure. No treatments. And millions more are developing ME triggered by COVID-19.

Today, we estimate 55 million individuals worldwide are living with the debilitating effects of ME.

We demand recognition, research, and respect.

I am a [person with ME/ doctor/ researcher/ carer/ friend/ advocate/ family member/ nurse/ charity worker etc – tell us your relation to ME]

I am from [your country]

This is a global health crisis.

Take action with us for World ME Day.

Together, we are a Global Voice for ME.”

Severe ME – alternative participation
If it is difficult or impossible for you to read out a script, we still want you to participate. If you can, please upload a 5 second video of yourself looking directly into the camera. You don’t need to say anything.

We then aim to include this in the final cut, with subtitles that read “Many are too sick to speak”

Find out how to upload your video

The deadline for submissions is 1st April 2024

DecodeME results now due August 2025

The DecodeME team posted an update on 7 March 2024

• DecodeME was due to be completed by August of this year
• Extraction of the DNA from samples has taken far longer than anticipated.
• Our funders have agreed to a funded timeline extension
• DecodeME will now be completed before August of 2025 – results will be released as soon as possible before this date.

DecodeME will use small differences in the DNA of people with ME/CFS to look for biological causes of the disease.

We have an important project update to share with you.

DecodeME participants have done a great job completing questionnaires and returning spit samples. But the next step – extraction of DNA at UK Biocentre – has faced operational and capacity issues.

We have been working hard with UK Biocentre to resolve as many of these issues as possible and to avoid delays. While some issues were mitigated, it became obvious that we simply would not have enough time to perform all necessary data analyses by August 2024, the planned end date.

We discussed this situation with both our Scientific Advisory Board and funders. They agreed with our assessment and funding was awarded to extend the project until August 2025. This will give us sufficient time to finish the project.

We remain fully committed to completing this research to the highest possible scientific standards, ensuring that our findings are as robust as possible. We are acutely aware of the urgency to deliver the study results as soon as possible and we continue to work as hard as we can to fulfill these goals.

A message from our team:

“On the Patient and Public Involvement Steering Group, we recognise that this delay may be disappointing for you, as it is for us.  We live with, and see the impact of, ME/CFS on a daily basis. We’re grateful the funders are continuing to support this project with additional funding. DecodeME will deliver results as quickly as possible and we remain hopeful that the study will give us clues that lead to treatments”. Sian Leary, DecodeME PPI Steering Group member.

Watch our video message below

What’s next?

We continue to formulate plans to build on DecodeME. This includes discussing with other researchers plans for the replication and potential validation of any findings, and working towards securing the longer term future of the DecodeME cohort of participants.  We’ll share details of these plans as soon as we can.

We continue to be grateful for your support of, and engagement with, DecodeME. Your ongoing involvement, as a participant, continues to be essential for successfully completing the search for genetic causes of why people become ill with ME/CFS.

Find out more about the study from the website

ME/CFS NICE guideline based on a thorough review of the evidence

Criticisms by 50+ international researchers and clinicians of the ME/CFS NICE guideline were published in July 2023 and available on open access. In February 2024 a response from NICE was published, behind a paywall. After much lobbying this was made freely available on 7 March 2024

The criticisms 

• the new definition of CFS/ME, which “downgraded” some trial evidence
• omitted data from standard trial end points used to assess efficacy
• wrongly discounted trial data when assessing treatment harm
• minimised the importance of fatigue as an outcome
• did not properly use GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence) when assessing trial evidence.
• misinterpreted GET as requiring inflexible graded increases of activity
• did not follow NICE recommendations of rehabilitation for related conditions e.g. pain
• recommended an energy management approach which was not evidence based.

Criticisms are based on misunderstanding

“We outline how these opinions are based on a misreading or misunderstanding of the guideline process or the guideline, which provides a balanced and reasoned approach to the diagnosis and management of this challenging condition.”

Energy management is not a cure

“There is a lack of evidence supporting energy management in people with ME/CFS, and no evidence that it is a ‘cure’. But there is also no signal of harm or deterioration with energy management programmes, unlike with GET.”

Conclusions

“The new guideline on ME/CFS was produced by an independent committee of clinicians who look after people with the condition, and people with lived experience of ME/CFS. Development followed a transparent process that conformed to recognised standards for guideline development, including extensive consultation with stakeholders prior to publication.

All evidence needs interpretation: evidence alone cannot determine the content of a recommendation. Criticisms of the guideline discussed in this paper are misplaced. The guideline has been welcomed and widely accepted by patient groups and clinicians leading services for people with ME/CFS in the UK.

We hope that the guideline will lead to better care and the development of more effective therapies for people with ME/CFS.”

NICE guideline on ME/CFS: robust advice based on a thorough review of the evidence, by Peter Walter Barry, Kate Kelley, Toni Tan, Ilora Finlay in Journal of Neurology, Neurosurgery and Psychiatry 8 February 2024. [doi: 10.1136/jnnp-2023-332731]

In the media:

MERUK: NICE responds to claims of “a controversial U-turn” on GET and CBT

Video interview with David Tuller: Adam Lowe Explains the NICE Response to Uninformed “Eight Anomalies” Critique of ME/CFS Guidelines

Abstract
In 2021, the National Institute for Health and Care Excellence produced an evidence-based guideline on the diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling long-term condition of unknown cause. The guideline provides clear support for people living with ME/CFS, their families and carers, and for clinicians. A recent opinion piece published in the journal suggested that there were anomalies in the processing and interpretation of the evidence when developing the guideline and proposed eight areas where these anomalies were thought to have occurred. We outline how these opinions are based on a misreading or misunderstanding of the guideline process or the guideline, which provides a balanced and reasoned approach to the diagnosis and management of this challenging condition.

https://doi.org/10.1136/jnnp-2023-332731

Rob asks Dr Nina Muirhead ‘What is ME?’

Rob Messenger shared his motivations for raising funds and awareness for ME by walking 500 miles over 100 days and climbing a total of 65,000 feet in 2 previous blog posts: Fundraising success and Awareness raising. Now he shares reflections of his Discussions at Dawn videos:

I approached Dr Nina Muirhead (Doctors with ME) and Karen Leslie (Physios for ME) to lead off the first two discussions, and, to my delight, they both said “Yes”!

Unfortunately, ME has had a difficult and controversial history, to the great detriment of patients (it’s time this was put right!), and it’s an illness which is still often misunderstood by the public, and by health professionals who have traditionally received very little and/or poor training about it.  So, I gave the first Discussion at Dawn a straightforward title, ‘What is ME?’ – it seemed the obvious place to start.

What is ME?

As a person with ME, a senior doctor and medical educator, Dr Muirhead was really well placed to give an introduction to this question in an up-to-date, easy-to-understand way. She talked about the growing biomedical research evidence which shows that ME is an illness affecting multiple systems in the body, causing a wide range of debilitating symptoms which can profoundly impact people’s lives. She explained the meaning of post-exertional malaise, the ‘cardinal symptom’ of ME, its debilitating impact, and how difficult it can be to manage.

ME can be mild to very severe

We discussed the levels of severity at which the illness can be experienced, something not widely understood, even in the medical profession.  Dr Muirhead said,

“…the type of existence that a person with very severe ME has, is almost aligned with end-of-life care for very sick patients who are dying”.

No hyperbole here – our own severely affected son has spent time in palliative care.

At this point in our discussion there was a long pause whilst we both got a bit upset.

Dr Muirhead had been severely affected, herself, but had improved to the point where she now described herself as being at the ‘Mild’ level (Take a look at the severity levels in NICE Guidelines).

I asked what this meant in terms of her ability to function on a day-to-day basis. She explained that being ‘Mild’ meant that she had been able to return to work as a dermatological surgeon on a part-time basis, but this was dependent on her being able to plan ahead and build in days of rest, doing her admin from home, actually taking all week to do a half-time job.

She felt lucky that she’d been able to manage some short walks in the woods with her family again, but other activities she used to enjoy, like running and cycling, were out of reach. She was still dealing with ME symptoms every day, including sore throats, headaches, muscle pain, brain fog and cognitive difficulties (including reading for work) and her symptoms were fluctuating week on week, month on month. So, not so mild, after all!

Long COVID and ME?

I asked about Long Covid, and whether its emergence had led to a better understanding of ME. She explained that a significant subset of people with Long Covid are experiencing a wide range of symptoms which are

“…fitting into more of an ME-type picture…The only difference is that we know that Covid was the trigger for their chronic, post-viral, multi-system disease”.

The government needs to invest in biomedical research, she added, to get to the bottom of post-viral illness, because, with up to a million people in the UK estimated to be affected by Long Covid of whom about 400,000 are still experiencing symptoms after 3 years, there could be significant economic implications for the country in years to come.

The need to educate

Her personal experience of ME, an illness she knew almost nothing about before she became ill herself, has led to Dr Muirhead becoming an advocate for better medical education about the illness. Currently the condition is

 “…not only poorly understood, it’s poorly diagnosed with patients often waiting years for a diagnosis, and it’s poorly taught”, she said.

Her own research has revealed that the majority of UK undergraduate medical programmes have no taught element on ME. So, she has written a free on-line accredited CPD training module to start addressing this deficit. You can find it here

She’s also a director of Doctors with ME, a global professional association for medical professionals in the field – led by medics who suffer from ME themselves; Chair of the CFS/ME Research Collaborative Medical Education Working Group; a rep on the Forward ME group; an expert witness to the last review of the NICE ME/CFS Guideline.

A big THANK YOU to Dr Nina Muirhead for taking part in #500miles4ME and for all she’s doing to help raise awareness and improve the lives of people with ME.

A couple of comments we received from people who’d watched this Discussion at Dawn:

“Thank you so much for this. I have been living with ME for 20 years, and it is so encouraging and validating that people, particularly in the medical profession, are pushing for it to be taken seriously.”

“Thank you for doing this. I’ve been more or less bedbound for 6 years. Not left the house in 2 years. No carer. Human contact overwhelms my system. I just do what I can to survive.”

Next time in Blog 4:  I’ll talk about my Discussion at Dawn with Karen Leslie of Physios for ME, when I asked her “How come an old bloke like me, with dodgy knees, can walk 5 miles a day, push and puff my way up this steep hill, go home, have a rest, come back tomorrow and do it all again, and every day I’ll be getting fitter and it’ll be getting easier – but it’s not like that for people with ME?

See all Discussions at dawn interviews

Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies

Researchers for Melbourne Australia reviewed research into both ME/CFS and Long COVID.

“Research into both disorders is mutually beneficial as Long COVID can provide a unique opportunity to study early disease changes and map these changes over the duration of the disease,” Dr Annesley said.

Conversely the ME/CFS research, which typically involves patients with a longer disease duration, may provide clues as to the future disease pathology of Long COVID.”

The review found many similarities between the 2 conditions but with many questions still to be answered – they list key topics for further study. They believe that measuring certain types of RNA in ME/CFS could be the most accurate and clinically practicable biomarker, worthy of further research.

Unravelling shared mechanisms: insights from recent ME/CFS research to illuminate long COVID pathologies, by Sarah J Annesley, Daniel Missailidis, Benjamin Heng, Elisha K Josev, Christopher W Armstrong in Trends in Molecular Medicine March 04 2024 [doi.org/10.1016/j.molmed.2024.02.003]

Highlights

• Approximately half of patients with long COVID (LC) fulfil the diagnostic criteria for myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS).
• The two conditions share clinical similarities and proposed disease pathologies, but it is still unclear whether they also share common molecular abnormalities.
• Most consistently altered pathologies in ME/CFS and LC include an increased reliance on alternatives to carbohydrates as substrates for energy production and altered gut microbiota, with a reduction in butyrate-synthesising bacteria.
• Therapeutic approaches targeted at the autoimmune response showed early promising results, but have not passed further clinical trials.
• ME/CFS and LC research has identified potential biomarkers, which need to be replicated and validated, with the most accurate and clinically practicable appearing to be measurements of RNAs for ME/CFS.

Review abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic illness often triggered by an initiating acute event, mainly viral infections. The transition from acute to chronic disease remains unknown, but interest in this phenomenon has escalated since the COVID-19 pandemic and the post-COVID-19 illness, termed ‘long COVID’ (LC).

Both ME/CFS and LC share many clinical similarities. Here, we present recent findings in ME/CFS research focussing on proposed disease pathologies shared with LC. Understanding these disease pathologies and how they influence each other is key to developing effective therapeutics and diagnostic tests.

Given that ME/CFS typically has a longer disease duration compared with LC, with symptoms and pathologies evolving over time, ME/CFS may provide insights into the future progression of LC.

LaTrobe News: Chronic fatigue offers clues to Long COVID, News, La Trobe University

#500miles4ME: taking awareness raising to a different level!

Rob summed up his motivation and fundraising activities for his #500miles4ME fundraising walk in a previous blog. He now reflects on what made him take the decision to do more to raise awareness of ME:

In one of my #500miles4ME daily posts on social media, I said something like,

“If you have a family member, friend or colleague who has ME, one of the best things you can do for them is to learn about the illness”.

I decided to push the boat out and approach some people we admired in the ‘ME world’ to see if they would record a discussion with me over Zoom whilst I was up at Paxton’s Tower around sunrise.  But would they be willing?

Who am I, after all? Well, I had to talk to myself and say,“Maybe you’re actually a kind of ‘expert’, too – just a different kind. You’re not a doctor and you haven’t got ME, but with 3 in the family sharing this diagnosis, you have nearly 30 years of experience of living close to it, 20 of those caring for one child, and 10 years for two children, at a severe level, and interacting with the health professionals on their behalf. Maybe you’ve got a right to speak up and be heard for that reason alone”.

I’ve spent most of my career in the world of additional (special) learning needs, and latterly, with those whose very complex needs require Health, Education and Social Services to work together to find solutions to difficult problems, so I’m also used to dealing with fellow professionals across a range of disciplines.

But mostly, I was emboldened by my son’s plight – 20 years ill, unable to access education, employment, relationships, unable now to read, get himself to the toilet, or step outside into the light. For his sake, why should I be afraid of anything, or anyone? Why not give it a go?

I wanted those close to us to have a better understanding of ME – I was thinking about friends and family and work colleagues, and wondering what I’d want them to know – and if I got that right, there would be others, including health professionals, who might look in, listen and learn. So, the discussions would need to be accessible and have ‘cred’ at different levels.

Preparation and practice!

From a practical point of view I realised there would be a lot of preparation for the video recordings. First I had to invest in some gear – a small tripod, a remote shutter, a Zoom account – and then learn how to use Zoom and how to record, which was fiddly using a small touch screen, but I found there was a good signal and acceptable quality video from the Tower.

I would need to draft an outline, discuss possible content and agree beforehand a series of questions with each of the interviewees. And watching the weather forecast a few days ahead and choosing a morning without rain or too much wind would be important, and on the day, finding a sheltered spot where I could get set up.

It quickly became clear that there was plenty to learn. I had to re-record 2 discussions because, well, I was a beginner at interviewing and they just weren’t good enough. This was asking a lot of my interviewees! And video-editing proved time consuming for the same reason.

5 Discussion at dawn interviews

In the end we published 5 video interviews: with a doctor, a physiotherapist and reps from the 3 charities I was raising funds for. I had lots of ideas for other discussions, but ran out of time and would consider doing more in the future.

I was delighted to get some good feedback from people afterwards – family, friends and others unknown who’d seen the videos – saying e.g. it had given them a much better understanding of the illness, they’d learnt more about the charities’ work etc, and, from people with ME, thanks for raising awareness .

A ‘good story’ for the media

My family is Welsh speaking, and I was approached by BBC Cymru Fyw (BBC Welsh language on-line), who’d heard about our experience of ME and the walks and wanted to do an article. We were told it made a ‘good story’ which would also probably be of interest to English language TV/radio and newspapers in Wales. We discussed how much publicity we thought we could handle as a family, and decided that we would limit it to just this one article.

Clearly, there’s a need for wider publicity and awareness about ME in Wales in general, and I guess this decision will have reduced the impact we might have made to some degree – but this was the right thing for us in our circumstances,  and ‘you can only do what you can do’.

In the event, we had some really good feedback. You can read the article in Welsh here, and an English translation here.

Next time in Blog 3 I’ll talk about my Discussion at Dawn with Dr Nina Muirhead

You can watch the Discussions at Dawn by going here.

Brain abnormality, not muscle fatigue, found in ME/CFS

An in-depth study of 17 people with virally triggered ME/CFS has uncovered an imbalance in brain activity triggered by abnormalities in the immune system. They also found distinct differences between men and women with the disease.

Brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

They also analysed spinal fluid and found abnormally low levels of catecholamines and other molecules that help regulate the nervous system in people with ME/CFS.

Deep phenotyping of post-infectious myalgic encephalomyelitis/ chronic fatigue syndrome, by Avindra Nath et al in Nature Communications vol 15, no. 907 (2024)

Research abstract:

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available.

We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning.

Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex.

Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

See also:

MERUK: NIH ME/CFS Deep Phenotyping Study: Part 1. Overview

MERUK: NIH ME/CFS Deep Phenotyping Study: Part 2. Methods

Health rising: The Nath ME/CFS Intramural Study Pt. I: “It’s a Brain Disease…”

Health rising: The Nath Intramural ME/CFS Study Pt. II: Missed Opportunities, Misreadings and… Success (?)

Guardian: Scientists find link between brain imbalance and chronic fatigue syndrome

“The brain can respond to stimuli and impact on the body,” says Prof Karl Morten from Oxford University. “The brain is physically, biochemically not functioning properly and it’s the illness that’s doing that, not the patient.”

NIH: NIH study offers new clues into the causes of post-infectious ME/CFS

“We think that the immune activation is affecting the brain in various ways, causing biochemical changes and downstream effects like motor, autonomic, and cardiorespiratory dysfunction,” said Avindra Nath, senior author of the study.

JAMA: NIH Study Provides Long-Awaited Insight Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“Overall, what we show is that ME/CFS is unambiguously biological, with multiple organ systems affected,” researcher Nath said. “It’s a systemic disease, and the people living with it deserve to have their experiences taken seriously.”

Nath also noted that even if people who display ME/CFS-like symptoms don’t have ME/CFS, they may have another condition for which medical attention would be beneficial, it just hasn’t been diagnosed yet.

Sci Am: Large study of ME/CFS patients reveals measurable physical changes