I am a Christian, saved by grace alone through faith alone. I have had the neuroimmune disorder ME, Myalgic Encephalomyelitis, since 1991. From North Somerset, now in Northern Ireland. Please see my website for further information about ME.
• Most importantly, people with M.E. need to be believed and respected. Simple as that! If you have read our leaflet “8th August Severe Myalgic Encephalomyelitis Understanding and Remembrance Day” you know how serious M.E. can be. It is an awful illness – show your friend/relative that you know that.
• Even severe illness may not be instantly apparent – for example your friend/relative may be able to walk to the toilet, yet be too ill to go out in a wheelchair, watch TV or even sit up in bed for more than a few minutes. They may spend most of their energy on something as basic as eating. They may look remarkably well for half an hour or an hour, but then spend the rest of the day in pain in a darkened room.
• Flare up of symptoms after activity or stimuli is a key feature of the illness. The activity may be tiny by healthy standards and stimuli things you probably don't even notice (such as light, movement, or background noise). Here are a few ways to help: shut doors (to reduce noise), use headphones if watching TV nearby, be aware that talking uses energy – ask your friend/relative how long the conversation needs to be and try to stick to that. If they seem particularly energetic, ironically this may be a sign that they are doing too much (and running on adrenaline!) - ask if they need a rest.
• Severe Myalgic Encephalomyelitis is very isolating. People with this illness are too ill to work or go to school, and most miss out on all social events and family gatherings. They may be too ill to communicate with friends and family, or to see their doctor (even at home), and they may feel very misunderstood. You can help ease the isolation by including your friend/relative as far as their illness will allow. For example you could take a few pictures of changes in the neighbourhood, video a special event (if they are well enough for TV), send a card, or ask if they want anything when you go to the shop.
• Your friend/relative may be too ill to use the phone, or to receive visits. This doesn't mean they don't want contact. You can still send postcards, or where suitable keep in touch with a carer. Many people with M.E. can manage texts more easily than conversations, so this may be a possibility.
• The 25% group can arrange for information to be sent to any health care or social services professional either directly or through the enquirer – please ask if this might be helpful. We also have an advocacy service for anyone who is struggling with the benefits system.
• Research demonstrates an abnormal response to exercise in Myalgic Encephalomyelitis, and the illness can become more severe through attempting to 'push through' the symptoms. Patients need to pace small activities (whether physical or mental) with regular rests. This is extremely challenging, and takes a lot of self-control, as patients want to be getting on with their lives. You can help by being aware of the temptation to do too much, by asking your friend/relative whether they need a rest.
• 8th August is a day to remember those who have lost their lives to this illness, and those living with it. Please talk to your friends about Myalgic Encephalomyelitis to help spread awareness, post something on Facebook, and maybe share a link to www.25megroup.org Spend some time reading our website, to inform yourself about the illness.
• Donate! The 25% ME Group represents those who are severely affected by this illness, and we will make good use of any donations. You can send a cheque to the address below, or donate online via the donate button on the website.
Thank you for reading this leaflet and for caring about your friend/relative. If you have any more questions or concerns, please do contact us by email at: firstname.lastname@example.org
"After that ye have suffered awhile, make you perfect, stablish, strengthen, settle you."
1 Peter 5:10
You have seen the arch of heaven as it spans the plain: glorious are its colours, and rare its hues. It is beautiful, but, alas, it passes away, and lo, it is not. The fair colours give way to the fleecy clouds, and the sky is no longer brilliant with the tints of heaven. It is not established. How can it be? A glorious show made up of transitory sun-beams and passing rain-drops, how can it abide? The graces of the Christian character must not resemble the rainbow in its transitory beauty, but, on the contrary, must be stablished, settled, abiding. Seek, O believer, that every good thing you have may be an abiding thing. May your character not be a writing upon the sand, but an inscription upon the rock! May your faith be no "baseless fabric of a vision," but may it be builded of material able to endure that awful fire which shall consume the wood, hay, and stubble of the hypocrite. May you be rooted and grounded in love. May your convictions be deep, your love real, your desires earnest. May your whole life be so settled and established, that all the blasts of hell, and all the storms of earth shall never be able to remove you. But notice how this blessing of being "stablished in the faith" is gained. The apostle's words point us to suffering as the means employed-"After that ye have suffered awhile." It is of no use to hope that we shall be well rooted if no rough winds pass over us. Those old gnarlings on the root of the oak tree, and those strange twistings of the branches, all tell of the many storms that have swept over it, and they are also indicators of the depth into which the roots have forced their way. So the Christian is made strong, and firmly rooted by all the trials and storms of life. Shrink not then from the tempestuous winds of trial, but take comfort, believing that by their rough discipline God is fulfilling this benediction to you.
Sharpe and Greco ask the interesting question of why cognitive behaviour therapy (CBT) and graded exercise therapy (GET) are controversial in the field of chronic fatigue syndrome (CFS).
One reason is that the type of CBT prescribed for patients with CFS differs from the CBT used in other illnesses. CBT in CFS assumes that patients’ medical condition is reversible through cognitive and behavioral changes. In some trials, participants were encouraged to no longer see themselves as CFS patients.1 If persons suffering from cancer or multiple sclerosis were told that CBT could reverse their illness, one might assume this treatment would be controversial as well.
A second reason is that CFS is considered to be an “exertion intolerance disease”.2 The most characteristic symptom of CFS patients is not fatigue but post-exertional malaise. This means that patients suffer a relapse when they exceed their activity limit. If CFS patients try to push through and do more, they report getting worse.3 This is however what treatments such as GET and CBT aim to provoke. Patients are instructed to increase their activity level time-contingently and to no longer respond to an increase of symptoms by resting. Most of the randomized trials have not adequately addressed the possible harms of GET and CBT but in multiple surveys, patients report to have been harmed by this approach.4
A third reason is that both GET and CBT label characteristic CFS symptoms as unhelpful cognitive responses.5 When CFS patients, for example, report that physical activity makes their symptoms worse, this is seen as maladaptive avoidance behavior rather than a feature of the illness. When patients think their illness is awful and feel overwhelmed by it, this is labeled as ‘catastrophizing’, even though CFS patients have been found to be more functionally impaired than those with other disabling illnesses. And when CFS patients suspect they are suffering from a yet unknown biological illness, this is described as an unhelpful somatic attribution. With GET and CBT, CFS patients are encouraged to view their symptoms as the result of stress, anxiety or deconditioning, even though scientific evidence for such hypotheses is absent.
A fourth reason why GET and CBT are controversial is that, despite being frequently prescribed, these treatments are not effective in patients with CFS. Randomized trials demonstrate that objective outcomes such as work resumption, disability payments, actigraphy, exercise testing, and neurocognitive functioning do not improve after GET or CBT.6 Studies show moderate improvements on subjective outcomes such as fatigue questionnaires, but at long-term follow-up, there are often no longer significant differences in outcome between patients who received GET or CBT and those who did not.7 Critics claim that researchers have wrongly focused on the short-term improvements on subjective outcomes to assess the effectiveness of GET and CBT. They argue that because of a lack of blinding and an adequate control condition, these trials should focus on objective outcomes as these are less prone to biases.8 To resolve the controversy of GET and CBT further scrutiny of these trials is needed.
 Bazelmans E, Prins J, Bleijenberg G. Cognitive Behavior Therapy for Relatively Active and for Passive Chronic Fatigue Syndrome Patients. Cogn Behav Pract. 2006;13(2):157-166.
 Institute of Medicine, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, The National Academies Press, Washington, D.C., 2015.
 Institute of Medicine, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, The National Academies Press, Washington, D.C., 2015.
 Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018 Oct 8;5(2):2055102918805187.
 Sharpe M, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry. 2015 Dec;2(12):1067-74.
 Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychol Open. 2018 Oct 8;5(2):2055102918805187.
By Dr Charles Shepherd, Hon. Medical Adviser, and Ann Innes, Welfare Rights Adviser, ME Association.
This report follows a meeting at the House of Commons on Tuesday 18th June 2019 with Justin Tomlinson MP, Minister of State for Disabled People, Health and Work to discuss problems faced by people with ME/CFS when claiming Employment and Support Allowance (ESA) and Personal Independent Payment (PIP).
Justin Tomlinson MP, Minister of State for Disabled People, Health and Work, The Countess of Mar, Chair Forward ME, Carol Monaghan MP Glasgow North-West, Katherine Ladd, Researcher for Carol Monaghan, Dr Charles Shepherd, Hon. Medical Adviser, ME Association, Ann Innes, Welfare Rights Adviser, ME Association. A small team of civil servants who are responsible for the administration of ESA and PIP were also present at the meeting.
This meeting was arranged to take forward points and concerns about DWP benefits that were raised during the House of Commons debate on ME/CFS that took place in January 2019 and was led by Carol Monaghan MP.
As part of the information gathering process for the meeting people were asked on social media to contact either Carol Monaghan or the ME Association with problems they are facing with claims for ESA or PIP. Over 500 emails and social media comments were received. Key points were then summarised by the ME Association and by Katherine Ladd, Carol Monaghan’s research assistant, for use at the meeting.
Thank you to everyone who responded to this request for information. And to Carol Monaghan MP for securing this meeting, and to the Countess of Mar for all her continuing work in the House of Lords on DWP benefit issues as they affect people with ME/CFS.
As previously noted, there was not enough time to raise the often-complex individual problems that people are faced with when applying for welfare benefits. However, we did manage to cover a lot of ground during the meeting – which went on for longer than expected.
General information on ME/CFS in relation to DWP benefit applications
During the meeting we emphasised several important points relating to the symptoms and resulting disability that occurs in ME/CFS, many of which are not being taken into account during medical assessments for ESA and PIP. In particular:
1. The core symptoms of ME/CFS – activity-induced muscle fatigue and pain, cognitive dysfunction/brain fog, the inability to sustain physical and mental activity, and the resulting post-exertional malaise/symptom exacerbation if people go beyond their physical and cognitive limitations. The latter being important because claimants should only be able to carry out descriptor tasks if they do not suffer significant after effects.
2. The way in which ME/CFS symptoms often fluctuate throughout the day and from day to day – so ‘snapshot’ conclusions as to what someone can do once, or on a good day, are both inappropriate and inaccurate.
3. Many of the descriptors used in medical assessments for ESA and PIP do not measure or reflect the impact that the core symptoms of ME/CFS have on a person’s capacity to carry out meaningful employment.
4. The need to ensure that people are asked by the medical assessors if they can carry out descriptor tasks reliably, repeatedly, safely and in a timely manner. If they cannot do so they cannot be scored as being able to do so
5. Case law states that if someone cannot carry out a descriptor task for a significant period (i.e. more than an hour) within a day they should be considered as being unable to do that descriptor task for the entire day.
Specific points that were raised during the meeting
We were able to raise specific issues covering the whole claimant journey from completing an application to going through reconsiderations and challenging a DWP decision through an appeal:
1. People with cognitive dysfunction often require help and extra time to fill in the long and complex paperwork when applying for ESA (i.e. the ESA50 form) and PIP. We asked for a two-week extension period on request to the original return deadline limit for the ESA50 – in the same way that this applies for PIP. The DWP agreed to consider this relatively straightforward request. However, this is something that would have to be requested by the claimant, if the DWP do decide to adopt our suggestion. The DWP pointed out that it should be possible to arrange a home visit from one of their staff to help to fill in forms such as the PIP and ESA medical questionnaires if a request is made.
2. People should be able to have a medical assessment at home if this is supported by their GP. Just because someone may be able to cope with a visit to a nearby GP surgery does not mean that they can cope with travel to and from a medical assessment centre for a detailed interview and physical examination that could last for up to two hours. More use of paper-based assessments should be made in cases where a GP can confirm that the person is severely affected and housebound as a result. We were asked to submit any cases where home visits or paper-based assessments are refused without good cause.
3. It was pointed out that the medical assessors have a duty to make reasonable adjustments in assessment procedures (i.e. arranging a home assessment or terminating an interview/assessment when the person was clearly unwell or not able to properly answer questions). Failure to do so could be a contravention of the Equality Act.
4. Assessment centres must be suitable and accessible for people with mobility problems and/or are having to travel a long distance.
5. People with ME/CFS are often under no regular medical supervision – so it can be very difficult, or even impossible, to obtain supportive medical information in the time required.
6. People should not have to pay a GP to provide supportive medical evidence – evidence collected for the meeting indicates that this is quite common, and the charge can be up to £40. Medical evidence is also often ignored, and the decision is based solely on the assessment report. In evidence collected for the meeting, it was clear that some reports bore little resemblance to what the person had said during the assessment.
7. Evidence from private healthcare professionals, other health professionals, and carers should also be considered.
8. Some medical assessors do not have an accurate or adequate knowledge of ME/CFS. Training on symptoms, fluctuation and severity in ME/CFS is clearly required along with how this affects mobility, intellectual capacity, self-care and the ability to take on meaningful work. It was pointed out that members of the Forward ME group are involved with the preparation of professional development modules and other training initiatives.
9. Cognitive dysfunction (i.e. problems with memory, concentration, attention span, information processing) can be a very disabling aspect of ME/CFS. However, most people find that they are awarded low or no points for descriptor tasks that involve some form of assessment of cognitive function.
10. Training on ME/CFS for DWP decision makers and members of tribunal panels was also raised. NB: Administration and training of tribunal members is the responsibility of the Ministry of Justice.
11. Medical reports still contain inaccurate or guesswork conclusions, or even dishonest information, especially for descriptor tasks that require specific information (e.g. walking distances). Note: This has also been brought to the attention of the DWP by the House of Commons Committee on Work and Pensions.
12. All claimants should be able to have their medical assessment audio recorded and facilities for doing so should be readily available – which is not the case at present.
13. Re-assessments, which form part of the on-going review process, should be reduced in frequency where a person can supply medical evidence to show that their condition has stabilised for a period of years and that all appropriate approaches to management have been tried. Information on 5-year prognosis in ME/CFS from the CMO report was referred to here.
14. Some people with ME/CFS are now having to wait for a long period of time (in some cases over six months) between making an appeal and the appeal being heard.
15. The whole procedure can be very stressful, especially when a decision is being challenged. As a result, some people just give up trying to obtain a benefit that they should be entitled to.
Both sides agreed that this had been constructive and useful meeting. The points we made were listened to very carefully and we felt that the Minister had been well briefed and was genuinely interested and concerned by what we had to say.
The DWP ministerial group requested that we forward any cases to them with names and national insurance numbers where the law around being able to carry out a descriptor “reliably” was not being properly considered.
A further meeting, this time involving representatives from the three organisations – Atos, Capita and Maximus – that carry out medical assessments for the DWP is now being arranged.
Claimants are winning PIP and ESA appeals at the highest rate ever recorded, according to the latest Tribunals Service statistics. Overall, 70% of social security appeals are successful, with the claimant getting a better award than they originally received from the DWP. The success rates for benefits include:
The success rate for PIP is up 4% on a year ago, whilst the success rate for ESA has risen 5%.
The number of appeals is down, however. ESA appeals are down by 42% compared to a year ago, although much of this is due to the introduction of universal credit.
PIP appeals are also down, this time by 14% compared to a year ago. This may, in part, be due to a slowdown in the transfer of claimants from DLA to PIP.
Overall, social security and child support appeals are down 19% on a year ago.
The time it takes for appeals to be dealt with is rising, however, is spite of a diminishing caseload. The mean length of time for a case to be dealt with has risen to 30 weeks, up from 24 weeks a year ago.
by Jessica Taylor-Bearman (author of “A Girl Behind Dark Glasses” - click here).
It is National Loneliness Week and I want to talk about how loneliness has affected me within my M.E. journey. When I first became chronically unwell, my life changed dramatically. I had been a very sociable 14-year-old, who enjoyed school and being with my friends. The truth was, I didn’t have that energy to spare anymore. At the beginning, I didn’t have the mental or physical energy to spare to socialise and it was something that I missed greatly.
After a few months, my friends would see me less because they didn’t know when I was well enough for a visit, and I happened to live in a little village away from the school, so I missed out. It is amazing how a house can be full of people (I was in a family of five), yet still feel like you are totally alone. No one could really understand what I was going through, and this just added to the frustration and loneliness that I felt being so ill.
I moved to hospital at the end of 2006, and that was insufferable. My family stayed with me at first and became my advocates, and social stimulation. However, after a few months, they were not allowed to come to the hospital for more than ten minutes a day. This was when my loneliness hit its lowest. I craved communication, but the nurses didn’t really have the time to try and work out what I was trying to say and didn’t know how to listen to me. My family were chaperoned when they were with me, so I didn’t get to spend any quality time with them. My mood dropped. I stayed positive because I had to keep telling myself that it would get better, but I started to dream the day repeatedly. I didn’t know when I was in reality and when I was dreaming. It was miserable.
This was before the days of social media. We had a little bit in the form of MSN Messenger but there was no Facebook, Instagram or twitter to connect to more people suffering with M.E. or any other chronic health disease. I didn’t know any other people suffering from ill health, let alone chronic health. It was a completely new to me. Social media can be both a blessing and a curse. I would have loved it to be around at the beginning because I don’t think I would have felt quite as alone but also to see what all my friends were up to would have been quite upsetting because I couldn’t join in.
In the time that I was completely missing, I felt like my friends and family didn’t really know how to deal with me. I was unable to communicate and this was problematic. I watched as they all grew up, and I didn’t join them. It was incredibly hard to watch the changes and not be able to do anything about it. The world of one room became my safe haven. I knew what was going on in that room, it had become my whole world. I didn’t see anything outside these four walls. How could it be so lonely inside it?
When I started to re enter the big wide world and started to be able to see my friends a bit more, it made me realise quite how much I had missed. I had lost out on so much and it was incredibly painful. Friends were now at university, I hadn’t even got passed my GCSES at school. I was stuck in a time warp. I challenge anyone to not feel lonely when you realise what is lost or you can’t find your tribe of people who get you. This is where all the social media outlets became incredibly useful to explain my life to someone else. I felt like I could connect with people for as little or as long as I was able to. I started to learn what my identity was. For years, I think that the M.E. Monster was my identity. It had taken over every aspect of my life, I had nothing else. I have started to improve further, I think I struggle more to know who I can connect with. People don’t expect me to still be suffering from loneliness but it is still there, just in different aspects of my life. Connecting with other people who suffer from this is very helpful, but it doesn’t really solve the problem. If I could say one thing to a person who doesn’t suffer with ill health, it would be: don’t forget those who go a little quiet on you.
They are probably struggling in more ways than one and need people to rally around them.
The conference day was preceded by the 9th Invest in ME Research International Biomedical Research into ME Colloquium – a two day closed researchers’ meeting with almost 100 eminent researchers invited to attend from fourteen countries – and the full day Thinking the Future – Young/ECR Conference for young and early career investigators.
These three days prior to the IIMEC14 conference brought together researchers (both new to ME and experienced ME researchers) to collaborate and share knowledge for the benefit of future research into this disease by enhancing education and effectiveness of research efforts. The need for funding of biomedical research was underlined as the theme of ME Conference Week 2019 – #InvestinMEresearch
The IIMEC14 conference showed the major initiatives and research taking place, continuing an international collaborative strategy for biomedical research which Invest in ME Research has been championing for over fourteen years.
EFNA’s Executive Director, Donna Walsh, and Communication Manager, Elizabeth Cunningham, attended the conference – sharing news of EFNA’s advocacy work at European-level and on-going engagement with member organisation the European ME Alliance (EMEA).
Nancy Van Hoylandt, EFNA Board Member and EMEA representative, brought the #BrainLifeGoals campaign to the conference. Participants were delighted to share their #BrainLifeGoals and raise awareness of the issues facing the ME community.
[Dr Vallings report is long; I have just picked out a few bits of it. The full report can be read by clicking on the above link.]
On Friday 31st May 2019, I was privileged to attend the 14th Invest in ME Research International ME Conference in Westminster, London. The conference was attended by participants from all over the globe, and also a number of new young researchers, who had also attended a one-day (Thinking the Future) seminar to present their work. The main conference had also been preceded by a two-day colloquium (9th Biomedical Research into ME Colloquium BRMEC9), with some of the world’s leading ME/CFS researchers presenting their research.
The main conference was opened by Dr Ian Gibson, who welcomed us with the very positive thoughts that understanding of ME/CFS was advancing rapidly. This can all only lead to better diagnostic and therapeutic opportunities.
The first speaker was Dr Beth Unger (Atlanta, Georgia, USA) who is Chief of the Chronic Viral Diseases branch at the CDC. She described two large studies being undertaken:
1. MCAM with participants being taken from clinics, where diagnosis had been by expert clinicians. No specific case definition was used. Patients came from seven clinics around the USA. Data was provided to the Institute of Medicine. There was assessment as to whether patients differed between clinics, and a look at how the experts diagnosed and managed these patients.
2. BRFSS – this study potentially involved all states and a phone survey was done of 400,000 adults annually. Data was gathered from five states in 2014, and 3 states in 2016. There were 55,000 respondents. Co-morbidities with ME/CFS and other diseases was reviewed. The main concordance was with arthritis, depression and asthma. Most ME/CFS patients did have one co-morbidity, but there was no co-morbidity with cancer and ME/CFS. Comorbidities did have a negative impact on health, involving more doctor visits.
The SF36 was down in ME/CFS on all measures. Both physical and mental functional impairment was different to healthy controls. There were also barriers to health care in all areas for ME/CFS.
The overview was then followed by Dr Vickie Whittemore (NIH, Washington,DC) who gave an update on what was happening with research at the NIH. There are 27 institutes at the NIH, of which Vickie represents NINDS (the neurological division). They do fund research worldwide from their extramural division, and there is an ongoing intramural study based at the NIH campus now. This involves 25 ME/CFS patients and 20 healthy controls. She is talking to other countries to stimulate worldwide research, and it is possible for overseas people to apply for research funding.
Prof Maureen Hanson (Cornell) spoke on Immune Dysregulation in ME/CFS. She gave us a much-needed lesson on immunology, explaining how the bone marrow produces CD4 cells, which secrete cytokines, and CD8 cells which cause death of infected and cancer cells. The dendritic cell presents an antigen (T Cell) and signals are interchanged to activate the T cell. T cells are activated in the lab by adding cytokines. This causes a change in metabolism leading to proliferation and glycolysis. The “Seahorse” is used to measure glycolysis and oxidative phosphorylation. The cell gets ATP as a result of these functions. She used a study population from Incline Village. Patients scored low on all measures of SF36.
She then had looked at memory potential in mitochondria using flow cytometry. Mitochondria can be labelled, and mass and membrane potential can be measured. In the CD4 cells there were no differences, but CD8s were reduced in circulating cells. i.e. there was impaired glycolysis and reduced membrane potential i.e. the immune system is not working properly.
Prof Mady Hornig (Columbia, New York, USA) discussed fingerprinting the phenotypes of ME/CFS along the gut-immune-brain axis. She asked the question first “Why phenotype”? She feels it is important to gather as much information as possible on the chemical aspects of the illness, and also to look at the comorbidities. This can give clusters for research, treatment options or biomarkers.
She concluded that ME/CFS is associated with intestinal dysbiosis. IBS comorbidity is a strong driver, and there are different metabolic pathways in ME/CFS with or without IBS. There are also very different metabolomics.
Prof Donald Staines (Gold Coast, Australia) presented work on the transient receptor potential (TRP) ion channels in the aetiology and patho-mechanisms of ME/CFS. He explained how they are now using a patch clamp. Changes in ME/CFS are reflected in NK cells. The illness affects every system in the body. NK cells kill invading cells and also internal cells. NK cell dysfunction is accepted as part of the criteria for making a diagnosis, and this group measured function. SNP studies were done, and they noted SNPs belonging to TRP channels.
TRPM3 is expressed in many neurological channels, (CNS, ANS, PNS) including the eye, which has many symptoms in ME/CFS. TRP function is blocked by ononetin and activated by pregnenolone sulphate and nifedipine. 168 readings were taken from patients and controls in three cohorts. Addition of nifedipine (a calcium channel blocker) failed to reactivate. Nifedipine acts in a different part of the receptor.
All patients showed TRPMeastin3 abnormality, and no abnormalities were found in healthy controls. There was an association with acetylcholine receptors. TRPM2 is now being investigated. This is one of the system’s back-up systems. There in now potential for the patch clamp to be used for drug trials in ME/CFS.
Dr David Andersson (London, UK) went through the pathophysiological changes in Fibromyalgia (FM). He told us that approximately 2% of the world’s population suffer from fibromyalgia. There are many similar and overlapping symptoms with ME/CFS. The female to male ratio is 4:1. FM occurs on 10-30% of patients with a rheumatological diagnosis – therefore there was consideration as to whether autoantibodies may be involved.
The conclusion was that fibromyalgia is caused by autoantibodies, and there is sensitisation of nociceptors. Treatment should include coping strategies and gentle exercise. They will now look for novel mechanism-based therapies.
Dr Jesper Mehlsen (Copenhagen, Denmark) had looked at the characteristics and pathophysiological changes in a large cohort of Danish ME/CFS patients. A number of patients developed many symptoms after HPV immunisation. They were diagnosed initially as suffering from POTS and ME/CFS. There were 845 patients with possible side effects from this vaccine. The age group was 16-26 years and they had multiple symptoms. 80% fulfilled the IOM criteria for a diagnosis of ME/CFS.
Using the autonomic symptom questionnaire (Compass 31) there was a high level of severe autonomic symptoms. Measurements of mental and physical fatigue were as severe as in MS, and worse than post-stroke patients. Looking at autoantibodies, 59% were positive, and these are not usually present below the age of 14. They also looked at the autoantibodies involved in cardiovascular regulation. Many patients had an active stand test. Beta-blockers did reduce heart rate. One patient however using an asthma spray fainted due to very low BP.
The findings of autoimmunity in these patients may represent molecular mimicry or bystander activation via cytokines.
In conclusion, 1 per 1000 patients receiving the vaccine developed serious adverse events resembling ME/CFS. It is likely an autoimmune reaction directed against the autonomic nervous system. These findings will be useful for future research and treatment.
Developments at the Quadram Institute were then discussed by Professor Simon Carding (East Anglia, UK). He explained how the microbiome can be abnormal in ME/CFS and asked the question as to whether gut microbes may trigger the illness. The human microbiome has 100 trillion microbes: bacteria, viruses, fungi, protozoa and archaea. The gut microbes have been shown to link to diseases such as Parkinsons and Alzheimers. Environment and lifestyle both have an effect, and ideally controls need to be from the family or same household.
Their focus now tends to be on the more severe ME/CFS patents, who are often ignored. Only 0.5% studies have been on the severe group.
Prof Oystein Fluge (Bergen, Norway) then brought us up to date with what is happening in their trials. He explained the history of treating lymphoma patients who had ME/CFS with Rituximab. A subgroup did improve. The final trial looking at 151 patients including a placebo group looked at a wide range of outcomes. Many had been long-term ill people. 40% had first degree relatives with autoimmune diseases. The paper was published in April 2019 and is available on line.
There was no significant difference in physical function, and physical activity was the same. There were a small number of adverse serious events, and a few less severe events. The trial was clearly negative.
Metabolic profiling and associations to clinical data in ME/CFS was presented by Prof Karl Johan Tronstad (Bergen, Norway). He has used samples gathered during Oystein Fluge’s trials. The focus is on cell energy metabolism. ATP is used by all cells. Mitochondria are important for ATP productions. He then outlined the mechanism of ATP production from glucose to pyruvate during aerobic work, and how anaerobic work shuts off this process causing increase in blood lactate.
He has been using the blood samples to try to understand. He has looked for clues e.g. measuring amino acids – there are 3 categories depending on entry into the ATP pathway. When metabolism is under stress, they can be down and this is more obvious in females. There is impaired PDH function in ME/CFS – a valve that can open and close and that is particularly important during exercise. Amino and fatty acids are used as compensation. There may be a metabolic shift to cause a change in fuel consumption, changes in lipid metabolism and redox status. There are similarities in pathways such as hypoxia, starvation and training. He described ME/CFS as being “stuck in a semi-starvation state”.
Prof Nancy Klimas (Fort Lauderdale, USA) broke away from her traditional immunological approach to understanding and managing ME/CFS – and discussed the integrative approach their clinic is taking to management of this illness. She described how their institute has moved into integrative and functional medicine. She gave a brief history of integrative medicine describing how this involves taking care of the “whole” patient and society. The scientific model does not always work for chronic disease. They have set up an educational programme for patients for various reasons: many patients try such a large number of self-remedies, they need to understand the science, and they need to integrate other tools.
“Genetics loads the gun, environment pulls the trigger”.
She then outlined a sensible approach:
1. Clinicians are partners
2. Mind, spirit, community and body
3. Conventional and alternative medicine.
4. Interventions should be natural and less invasive ideally
5. Integrative does not reject conventional
6. Good medicine = good science
7. Health promotion and prevention is paramount
8. Practitioners of integrative medicine should exemplify principles and care of self.
ME/CFS is a complex multisystem illness, and integrative medicine integrates diagnosis and treatment-based with broad knowledge of physiology.
Dr Ronald Tompkins (Harvard, Boston, USA) talked about Harvard’s plans for clinical research. They now have a team of vibrant young researchers. He explained how many researchers have been working independently for years and are keen to collaborate. The Open Medicine Foundation have funded three centres, Harvard being the third. The others are Stanford, USA and Uppsala, Sweden. A number of research thrusts are in the pipeline. There is much interest in getting a centre of excellence established at Harvard. They need to establish a clinical infrastructure.
The talk by Dr Michael Van Elzakker (Harvard, Boston, USA) was titled “Physiological and fMRI measures before and after symptom provocation by invasive cardiopulmonary exercise testing”. He told us neuro-inflammation is synonymous with ME/CFS. The brainstem is central to pain processing. The vagus a mixed cranial nerve detects peripheral catecholamines. This can be the initiation of central glial illness response. If the vagus nerve is cut in rats, illness response does not occur. Glial response may occur with injury too. The microglia are the resident macrophages in the brain. They change shape and release chemicals equivalent to immune signalling. The microglia magnify signals rather like an amplifier. However, this is not a specific diagnostic tool.
Efferent vagus function is associated with failure of the anti-inflammatory reflex, parasympathetic autonomic control, POTS and it is measurable with invasive CPET. fMRI is associated with reduced cerebral perfusion.
The final speaker of the day was Prof Ron Davis (Stanford, USA). He presented work relating to ongoing search for a pathogen in 20 severely ill patients. There were less DNA viruses in patients than in controls. No parasites have been found yet. The search for RNA viruses is expensive, but in development. Search for fungi and bacteria are also in the planning. Searching for metabolites, there have been shown to be 63 out of 292 which are significantly changed.
The nanoneedle (very small) is used for diagnostics, and measurements are at 200/sec. Salt can be added early on, and this stresses the cells, and many changes are noted within an hour or two. However, there is a need to screen for other diseases for comparison, and ME/CFS diagnosis needs to be compared to controls. A design is needed for a better cheaper chip.
Deformability of red blood cells is impaired in several diseases, but in CFS there is less deformability than in controls. There was some discussion also about the effects of adding ME/CFS cells to healthy plasma and vice versa. The next stage is to screen for FDA approved drugs. Prof Davis mentioned two that might have potential: one of which can repair mitochondrial membrane.
As always, the conference concluded with a lively Q and A session and much animated discussion and excitement about all the research in the pipeline. There has been enormous development in research and management over the years, leading to greater understanding of this complex disease, which seems to become more complicated as we learn more! The answers are getting closer and there is so much hope now for the potential biomarkers to be confirmed, and treatment options to be forthcoming.
We believe in the eternal security of the saints. First, because they are Christ's, and He will never lose the sheep which He has bought with His blood and received of His Father.
Next, because He gives them eternal life, and if it be eternal, well then, it is eternal, and there can be no end to hell, and heaven, and God. If spiritual life can die out, it is manifestly not eternal life, and that effectually shuts out the possibility of an end.
Observe, further, that the Lord expressly says, "They shall never perish." As long as words have a meaning, this secures believers from perishing. The most obstinate unbelief cannot force this meaning out of this sentence.
Then, to make the matter complete, He declares that His people are in His hand, and He defies all their enemies to pluck them out of it. Surely it is a thing impossible even for the fiend of hell. We must be safe in the grasp of an almighty Saviour. Be it ours to dismiss carnal fear as well as carnal confidence and rest peacefully in the hollow of the Redeemer's hand.
(Taken from the Spring edition of “Breakthrough” magazine produced by ME Research UK.)
There is a considerable lack of information about those people with ME/CFS who are severely ill. They are often neglected—even though they have worse prospects of recovery—and under-represented in what little research is done.
A large part of the problem is that their challenging circumstances mean these individuals have difficulty accessing medical care and engaging in medical research. Is there any way of improving this situation?
With funding from ME Research UK, Victoria Strassheim and colleagues at Newcastle University have been conducting a programme of research concentrating on severely affected ME/CFS patients. Over the last couple of years, Victoria has published a review of existing research on severe ME, and an exploration of the effects of deconditioning in these patients. A third paper was recently published in BMJ Open, and looks specifically at how to include severely affected ME/CFS patients in research.
The first part of the project was to attempt to contact and evaluate patients with severe ME/CFS within the Northern England Clinical Network. The participants were adults with ME/CFS who were wheelchair-, house-, or bed-bound. A total of 483 questionnaire packs—including the Barthel Functional Outcome Measure and the De Paul fatigue questionnaire—were sent out to those people identified.
Unfortunately, only 63 packs were returned, although 76% to 88% of participants managed to complete the questionnaires successfully. The responses provided a host of information on the burden of symptoms and functional difficulties patients have to live with. The findings of the survey are freely available to download from the BMJ Open website: bit.ly/StrassheimSurvey.
The second part of the project involved making a series of home visits to five severely ill ME/CFS patients, and attempting to complete assessments previously conducted in people with mild or moderate ME/CFS.
Over the course of four visits, a number of activities were attempted, including various physical and respiratory tests, cognitive assessments, and several questionnaires. Two patients were able to complete all of the assessments, while the other three achieved around 50%, and were unable or refused to perform the other tests, or could not attend due to ill health.
The investigators conclude that people severely affected by ME/CFS can engage with research, but they have a considerable burden of symptoms and a poor quality of life, and they need more support during the research process. The use of “research advocates” is suggested, to help engage and recruit these individuals into clinical studies.