Hospital Mistreatment of Severe ME Patients Globally
This #SevereMEday, 8th August 2024, the World ME Alliance is highlighting the experiences of people with Severe ME in hospitals across the globe. People with ME everywhere experience stigma, denial of evidence-based science, disdain and dismissal of symptoms by healthcare providers. Yet for those with Severe ME requiring hospital care, the consequences may be fatal.
The grave dangers people with Severe ME are exposed to in hospital were underlined at the recent coroner’s inquest in the UK for Maeve Boothby O’Neill. Maeve, a 27 year old woman with Severe ME and resultant malnourishment, died in Oct 2021 following 3 hospital admissions where denial of emergency nutritional care led to her terminal decline.
Sadly, the mistreatment endured by Maeve Boothby O’Neill is far from rare. Carla Noaum, aged 23, diagnosed with ME over 8 years ago, has been battling to get appropriate care at West Middlesex Hospital in the UK since her admission in March 2024. Carla’s weight has dropped from 52kg to 35kg and she is suffering extreme digestive pain from a nasogastric feeding tube, yet a psychiatrist stopped her pain medication and insisted on exposing her to light. The BBC reported her father as saying she was “screaming from pain” and repeatedly losing consciousness over nine days as a result.
France
This pattern of neglect and harm is being repeated around the world. Severe ME patient Alicia Pallenchier from France recalls: “The last time I went to the hospital, I was deteriorating fast. They refused to admit me to the hospital where I live because they said I should just lose weight and see a psychiatrist. So I had to go 150 km away from home.
“At the beginning, I called them several times to take me to the bathroom, put on my pyjamas, or do things I could no longer do by myself. They opened the shutters and windows, even though I couldn’t stand the light. I was told that I shouldn’t do less in the hospital than I did at home. I told them that at home, I was dependent on my mother for almost everything.
“They offered me a shower every day because they didn’t understand that I wasn’t capable of having more than one shower a week. I had to ask for a nurse to bathe me but she didn’t understand as I am young.
“Almost no one came to help me. They never brought me the commode, even though I asked repeatedly. I had to get up several times a day to go pee, and I fell a few times. The meat was too hard to eat, but they didn’t offer to cut it. They even criticised me for my choice of breakfast because I can’t digest coffee or tea.
“They managed to lose my pill organiser on the first day. Missing the pill to stop menstruation was enough to trigger my period at the end of the week. They only offered me diapers. I left the hospital in an even more exhausted and compromised state than before.”
Greece
An anonymous patient in Greece reports: “Despite my Severe ME symptoms, hospital staff dismissed my condition as psychosomatic. They forced me through harmful tests and physical activities even when I couldn’t speak due to severe PEM.
“The staff mocked me and failed to provide appropriate care. I couldn’t eat their food because of severe MCAS so I was having to choose between constant reactions or not eating, and they exposed me to intense odours despite my extreme sensitivity. They refused to read relevant scientific literature on ME and their insistence that I was “overreacting” and that “it’s all in my head” contributed to an increase in abuse from my family.
“The Greek health system caused my condition to worsen, leaving me in a state of living death.”
Pakistan
Another anonymous patient summarised her experience of hospital in Pakistan: “No protection was offered against lights or sound. No pillows were given. Disability accommodations were forcefully taken away. I wasn’t allowed to use my collar (to support vertebrae compromised by EDS and CCI) or HR-monitoring watch. My IV fluids and pulse oximeter were removed. They told me to stop coming to the ER or I’ll be sent to the psych ward. They also made fun of me for trying to involve international ME doctors. I wouldn’t go to the ER again unless I was shot or in a car accident.”
Norway
Rachel Caroline from Norway states: “I am refused help. They say as long as I am not fatally sick, they won’t admit me to the hospital. It doesn’t matter if I am screaming in pain or unable to eat. Norway does not believe in energy-limiting conditions. Doctors say it’s just in my head, and I need to think myself healthy. I have no mental illness but still they just sent me home.
“I’m getting sicker every week. I scream with pain for 2 hours every day. I have stopped eating now. My poop is white. My urine is brown. There is often blood in my poop. And 40 other symptoms.”
“I’m not dying because of ME or Long Covid, I’m dying because the doctors are killing me by not investigating or helping me.”
Safe hospital care for Severe ME
Beyond medical neglect and gaslighting, hospital mistreatment that harms people with Severe ME to a life-threatening degree can amount to inhuman and degrading treatment.
The World ME Alliance hopes that the findings of Maeve Boothby O’Neill’s inquest will catalyse change for Severe ME patients globally.
Hospital care for Severe ME will always be challenging, but there are simple steps that can be taken to safeguard vulnerable patients and improve their experiences.
Learn about what safe hospital care should look like for people with Severe ME.
WAMES works with the World ME Alliance as they seek to:
create global change by engaging the World Health Organisation’s support in designing and delivering services for ME
enable ME organisations around the world to learn from, and support each other
Cancer drug cyclophosphamide shows ME/CFS is treatable
Dr Øystein Fluge & Dr Ingrid Rekeland
Norwegian scientists have been testing 2 cancer drugs on ME patients for 6 years, following a surprise recovery from ME when being treated for cancer. Patients with ME/CFS enrolled in the two clinical intervention trials RituxME and CycloME.
They have found that patients treated with cyclophosphamide reported greater and more lasting improvements than those treated with rituximab or placebo.
However these drugs are toxic and can cause severe side effects. They do not recommend cyclo as a treatment, but “these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.”
They also acknowledge that “it is difficult to assess whether symptom improvement in a clinical trial can be attributed to the intervention or to other factors. During the trials, placebo mechanisms may contribute, and participants can also be affected by being taken care of in a clinical study (“trial effect”). A modest, but evident rate of recovery in the placebo group indicates a potential for spontaneous improvement, suggesting that ME/CFS is in principle a reversible disease.
Objectives
In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials.
Methods
Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab.
The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires.
Result
Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years.
At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions.
Conclusions
After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.
This study found that although there is a wide variation in experience among the ME/CFS patient population, it does not differ significantly across different clinics. According to the authors “this suggests that expert clinicans are recognizing the same clinical entity, albeit one that is far from homogeneous.”
SUMMARY
This study aimed to assess whether different clinical practices across seven U.S. specialty clinics lead to variations in the identification of ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) characteristics.
Researchers utilized standardized questionnaires and data collection methods to compare patient characteristics and clinical features across these clinics.
The results showed that despite slight statistical differences in demographic and clinical characteristics across sites, there were no clinically significant differences in the presentation of ME/CFS symptoms and functions among the clinics.
This suggests that different clinical practices do not lead to significant variations in how ME/CFS is identified and managed among specialists.
The study confirmed a wide range of symptom severity and functional impairment among ME/CFS patients, highlighting the inherent heterogeneity of the disease. All clinics reported a broad distribution in symptom scores and health measures.
The study also examined the use of different case definitions for ME/CFS and found varying proportions of patients meeting each criterion across clinics, indicating that the choice of case definition can influence disease recognition and research outcomes.
DEFINITIONS
Case Definition: A set of standard criteria for determining whether a person has a particular disease or condition, used in research and clinical diagnostics to ensure consistency across studies and treatments.
Functional Impairment: A decrease in a patient’s ability to perform daily activities due to the effects of a medical condition.
Heterogeneity: In medical research, this refers to the variation in disease presentation and progression among different individuals with the same diagnosis.
RESEARCH ABSTRACT
Background:
One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity.
Methods:
We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic.
Results:
We found few statistically significant and no clinically significant differences between clinics in their patients’ standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures.
Conclusions:
Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case–control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms.
Although a lack of variation between clinics was identified, the participants within each clinic – and in the overall sample – showed a wide distribution in scores and measures, indicating overall disease heterogeneity.
ME/CFS & Long COVID patients have similar symptoms & quality of life
This Australian study compared 61 patients with ME/CFS with 31 patients with Long Covid (aka Post COVID-19 condition- PCC) and found few differences in symptoms between the two groups.
They say: “this publication documents the profound and widespread illness burden experienced by pwME/CFS and pwPCC in Australia, thereby necessitating health policy reforms that facilitate improved accessibility of necessary care and support services for Australians living with these illnesses.
The present study observed marginal differences in illness presentation between pwPCC and pwME/CFS, with notable similarities between the two cohorts in key symptoms typically experienced by pwME/CFS, such as post-exertional malaise, neurocognitive dysfunction and sleep disturbances.”
Other past studies also found all pwPCC experienced post-exertional malaise though 2 had found a lower prevalence of post-exertional malaise 82.8% and 78% “Post-exertional malaise is a noteworthy component of the PCC illness presentation and should be considered in diagnostic criteria and care provision.”
“Among the cardinal ME/CFS symptoms, only memory loss was significantly more prevalent and unrefreshed sleep significantly more frequent among pwME/CFS than pwPCC in the present study.”
The few remaining significant differences in symptom presentation between the cohorts included a higher prevalence of muscle weakness, lymphadenopathy and nausea, greater severity of light-headedness, and reduced frequency of heart palpitations among pwME/CFS. However, the existing literature is incongruous regarding the presentation of such symptoms among pwME/CFS and pwPCC .
Additionally, comparisons of illness presentation have largely focused on symptom prevalence and few investigations have compared symptom frequency and severity among these two illness cohorts.”
Hence, fulfilment of ME/CFS criteria following acute COVID-19 illness may be an indicator of illness trajectory and a means of identifying pwPCC at risk of long-term illness.
“The findings of the present study underscore the risk of developing permanent chronic illness and disability following acute COVID-19 illness and foreground the potential role of ME/CFS in the illness progression and diagnosis of PCC.
This also has important ramifications for estimating the future healthcare burdens of post-COVID-19 sequelae (as over 90% of people with ME/CFS experience life-long illness and emphasises the importance of reducing SARS-CoV-2 transmission.”
“Findings exemplify the physically disabling nature of ME/CFS and PCC, which must be considered in the provision of care for people with these illnesses… Importantly, the impacts on daily activities observed in this study emphasise the need for integrated approaches across the healthcare, disability and social support sectors for pwME/CFS and pwPCC in Australia.”
Translating reduced oxygen consumption to impairment status to treatment considerations
A study from US researchers has confirmed the results of previous small studies that found people with ME/CFS respond abnormally to exertion.
84 patients with ME/CFS and 71 sedentary controls completed cardiopulmonary exercise tests (CPET) on 2 succesive days. In contrast to the healthy controls, ME/CFS patients failed to reproduce CPET-1 measures on day 2, with significant declines in work, exercise time and other measurements.
“The Fick Principle reminds that oxygen utilization for energy production is wholly dependent on blood flow and tissue oxygen extraction. This is true for any tissue (e.g., brain, skeletal muscle, liver, etc.).
Treatment considerations
With this understanding and given the disordered hemodynamic and ventilatory responses to exertion in ME/CFS, it is plausible to consider treatment approaches that may help to re-regulate ANS signaling for improved oxygen delivery to the heart, skeletal muscle, gut, brain, and other tissues impacted by ME/CFS…
Unfortunately, relatively little attention and resources have been directed toward non-pharmacological approaches to reduce symptoms of ME/CFS. Despite compelling evidence of ANS dysfunction in ME/CFS there are no randomized controlled trials to assess treatment approaches.
Here, we offer strategies proffered variously by many with ME/CFS, trial and error, practice, and some clinical evidence that center on non-pharmacological opportunities to possibly mitigate pain and inflammation, and enhance blood flow, oxygen delivery, and/or tissue oxygenation.
Return of blood to the heart (venous return) may be assisted by use of compression garments (shorts, tights, stockings, shirt, sleeve) which are effective to aid recovery by improved blood flow in athletes and in ME/CFS for those who experience orthostatic intolerance. Massage may help to reduce depression, anxiety, stress, and perception of fatigue, and enhance overall mood and relaxation to indirectly promote blood flow, although it may not alter blood flow directly.
Core stability exercises
to maintain or improve effectiveness of muscles of the trunk and hips to support correct spinal alignment can help to improve circulation and oxygen delivery. These can be done while lying down so as not to exacerbate orthostatic symptoms. Most important when doing core stability exercises is to maintain correct spinal alignment during the exercise, more than duration or repetitions of the exercise.
The focus of core stability exercises is to improve the coordination of these muscle groups and intra-abdominal pressure regulation by the central nervous system. When first learning these exercises, working with one experienced and knowledgeable in teaching core or neuromuscular stabilization exercises , such as a physical therapist, athletic trainer, or strength/conditioning coach, would be advised to provide guidance and feedback.
As with all exercise, core stability exercises should be performed within the limitations of exertion tolerance, discussed below, so as not to exacerbate post exertion symptoms. Recognize, however, that local muscle sensitivity may arise when first beginning these types of activities which is common when first exerting muscles to perform an unfamiliar task.
Vagus nerve stimulation (VNS)
is an FDA-approved treatment for pharmacoresistant depression and epilepsy, producing clinically meaningful results. Implantation of a VNS device requires a surgical procedure and is not without risk. More recent attention has focused on transcutaneous vagus nerve stimulation (tVNS) using an external device to stimulate the vagus nerve at either the ear to access the auricular branch of the vagus nerve or the neck to target the cervical branch of the vagus nerve… For ME/CFS, preliminary findings suggest some efficacy of tVNS to reduce sympathetic stimulation of the heart, indicated by improved heart rate variability, but that ANS response varied depending on sex and tVNS stimulation parameters.
While more work is warranted to understand optimal treatment protocols, long-term effects, and other possible applications, substantial evidence indicates that tVNS can help to rebalance parasympathetic/sympathetic tone of the intrinsic cardiac nervous system to reduce heart rate.
Cryotherapy or cold therapy
is a therapeutic modality to decrease pain, reduce chronic and acute inflammation, and to aid recovery in athletes, among other applications. Cold exposure of the whole body stimulates ANS responses to increase core temperature toward normal body temperature by redirecting blood flow away from the skin and toward the heart and viscera. In doing so, a very brief, intensely cold whole-body exposure is believed to provoke ANS re-regulation toward homeostasis or stable equilibrium, and thereby improve symptoms of ME/CFS associated with cardiovascular autonomic dysregulation.
Coupling brief whole-body cryotherapy with static stretching improved symptoms of ME/CFS related to fatigue, sleep, and cognitive function. More work is needed to better elucidate the mechanisms involved in the effectiveness of whole-body cryotherapy, although preliminary data suggests a promising approach to consider for symptom mitigation.
Manual lymphatic drainage
Evidence of structural and functional abnormalities in the brain of some with ME/CFS may be related to accumulation of toxins associated with glymphatic dysfunction. Similarly, the primary respiratory mechanism, typically dysregulated in those with ME/CFS, is suggested to be synchronous with the rhythmic pulsation of lymphatic drainage from the brain and spinal cord, or neuraxis, induced by sympathetic nervous system activity.
Consequently, impaired cranial rhythmic impulse could lead to respiratory dysfunction, chronic fatigue, and other symptoms of ME/CFS. Some evidence indicates that a specific manual lymphatic drainage intervention may reduce fatigue symptoms in long COVID and chronic venous insufficiency which share many symptoms with ME/CFS.
Red-light therapy
Although not fully understood, photobiomodulation, also known as low-level laser therapy (LLLT) or red-light therapy, has been in existence for more than a half century. It is known to affect mitochondrial function by altering cytochrome c oxidase which is particularly able to absorb light in the near-infrared region, increasing electron transport activity and ultimately adenosine triphosphate production. More commonly used now in sport medicine and orthopedic rehabilitative settings to enhance recovery and repair, LLLT has been reported to decrease soreness, inflammatory markers, lactic acid, and oxidative stress, and enhance glucose uptake to support aerobic metabolism.
Nutrition
An additional approach to modulate systemic inflammation involves selection and timing of body fuels. Nutritional considerations to reduce inflammation include an anti-inflammatory diet, reduced consumption of refined sugar, a gluten-free diet, or intermittent fasting. A nutritional approach to ‘feed’ the gut microbiome can help with energy balance, glycemic control, and inflammation.
Fasciotomy
It has long been known, but possibly underappreciated, that the integrity of fascia in the maintenance of muscle tension and interstitial pressure is integral to healthy muscle function and force production, independent of muscle fatigue. As such, fasciotomy, the common approach to relieve the pain of muscle compartment syndrome by cutting the surrounding fascia, unfortunately also reduces muscle force output by 50% or more. However, fascia that is unusually restricted or foreshortened may increase neural tension and contribute to pain, altering muscle recruitment patterns, reducing muscle force production and intra-neural blood flow, and releasing inflammatory factors.
Myofascial release therapy
In those with ME/CFS, longitudinal strain to the nerves and soft tissue of the lower limb increased pain and many symptoms of PEM, including difficulty concentrating. Prolonged sitting, reclining bed rest, or driving with arms outstretched and right leg extended are examples of activities that could contribute to increased mechanical tension to the nervous system.
Efforts to reduce fascial restriction and mechanical tension using myofascial release therapy effectively decreased pain and improved range of motion and functionality in women following breast cancer surgery. Both the subcutaneous and subserous fascial planes slide independently but fuse at specific locations, particularly in the area of the pelvis, abdominal wall, and aperture of the thorax, suggesting that impingement of fascia in one area can ‘tug’ on an adjacent or even distal area provoking symptoms that seem unrelated to the point of restriction.
For example, a head injury may later contribute to pain lower in the body due to adhesions that ‘pull’ on the longitudinal axis of the fascia causing pain elsewhere. Approaches that may bring relief by way of liberating fascia include appropriate physical therapy, body work, breathing exercises, gentle stretches, stress reduction, acupuncture, foam rolling, FasciaBlaster®, heating pad or hot water bottle, and/or nutritional support for fascia. In addition to circumstances described above involving prolonged stationary positions, those who have experienced injury, surgery, or some type of bodily trauma that could cause fascial adhesions may want to consider these approaches.
Blood flow restriction training (BFR)
involves restriction of blood flow to arms or legs to trap blood in the local musculature during low-intensity resistance exercise, eliciting a strong hemodynamic response. It has been reported to increase strength and muscle size in healthy adults and reduce characteristics evident in chronic heart failure including muscle atrophy, shortness of breath, fatigue, increased ventilation, and sympathetic stimulation.
Exercise with BFR may also promote more angiogenesis-related factors mRNA expression and improve vascular function. Collectively, these findings suggest that BFR training may be of benefit to those with ME/CFS to mitigate muscle loss but also to improve functional performance. More work is warranted to better understand the mechanisms of action with BFR, as well as an appropriate protocol for use in ME/CFS to avoid possible dizziness that has been reported in some cases, but it appears to be a promising approach to reduce fatigue and improve muscle function.
Activity pacing
is a goal-directed behavioral approach that involves decision-making and planning to effectively manage available energy resources to reduce fatigue and symptoms of PEM in those with ME/CFS. It is an approach that has gained acceptance, not only for ME/CFS, but for other disabling conditions, including long COVID. The goal of pacing, as opposed to graded exercise therapy, is symptom reduction to improve well-being and overall function through self-regulatory behavior.
Effective pacing can reduce fatigue, psychological distress, depression, and improve overall physical function. Activity pacing relies on basic journaling of symptoms and activities to provide a ‘look-back’ in instances where PEM symptoms emerge to understand possible triggers of symptom exacerbation and inform future pacing-related decisions. Additionally, it is helpful to have an objective indicator of exertional threshold to provide on-going feedback. Based on data from the present study, it is evident that exertion above VAT provokes abnormal hemodynamic and ventilatory responses. The VAT level of energy production can be ascertained during a submaximal cardiopulmonary exercise test. When heart rate that corresponds to VAT (HR@VAT) is known, use of a simple heart rate monitor with an alarm set to 10 bpm below heart rate at VAT provides objective, auditory feedback to reduce exertion below threshold to avoid symptoms of PEM.
When heart rate at VAT is not known, RPE may provide an estimate of VAT. An upper exertion limit RPE of 10–12 (for a 6–20 scale) or RPE of 2–3 (for a 1–10 scale) are consistent with ranges in perceived exertion from ‘light and easy – non-taxing, very gentle and easy to maintain a conversation – could continue for hours’ to ‘comfortable pace – able to maintain a conversation without getting out of breath’. Pacing should begin with a conservative estimate of exertional threshold (e.g., 10/20 or 2/10, or less if indicated) while using journal entries from the previous 1 to 2 days to assess if the exertional limit is effectively mitigating symptom exacerbation. If not, then the exertional limit should be lowered, recognizing also that the cyclic nature of symptoms in ME/CFS may alter exertional tolerance levels at times.
Another exertional metric to begin pacing when heart rate at VAT is not known can be estimated by adding 15 bpm to resting heart rate (RHR + 15). Resting heart rate should be measured after 5 min of seated or supine rest in a quiet environment. Preliminary data from the Workwell Foundation suggests that RHR + 15 is a useful metric to guide pacing when HR@VAT is not known, with more information about pacing at www.workwellfoundation.org. A positive and protracted adaptation to, and familiarity with pacing is necessary before venturing to raise the exertional tolerance level. Effective pacing over time may allow for a very gradual escalation of physical and cognitive activities. Emergence of post-exertional symptoms is always an indicator that prior exertional levels exceeded exertional tolerance.
One indicator of successful symptom mitigation over time may be the measure of heart rate variability (HRV). This is the measure of variability in time between each heartbeat and is an indirect indicator of ANS tone. Increasing evidence suggests that the ANS regulates the inflammatory response. A decrease in HRV indicates an abnormal predominance of sympathetic activity and has been observed in patients with ME/CFS, fibromyalgia pain, post-traumatic stress disorder, type 2 diabetes, and as a general indicator of stress and health. Neuroimaging studies indicate a relationship between HRV and regional cerebral blood flow, suggesting that the interpretation of external phenomena as threat or negative (ie., ‘fight or flight’ response) can alter higher brain messaging to the brainstem and subsequent ANS signaling to the heart.
Additionally, one’s interpretation of psychosocial stress can be quantified by measuring cortisol release, which is closely associated with HRV, as an indicator of the physiological response to the stress [170]. In this way, HRV can be used to track changes in autonomic tone over time and as an indicator of productive symptom management in ME/CFS.
Breathing and circulation are related. Impaired respiratory function is universal in ME/CFS and so must be addressed to improve circulation of blood with oxygen to tissues for energy metabolism and circulation of lymph to remove metabolic byproducts. Although breathing is an involuntary process, intervention using voluntary slow or diaphragmatic breathing can effectively improve vagally-mediated HRV with only a little training. Slow breathing can reduce blood pressure in low-risk hypertensive and prehypertensive patients, hypertensive diabetics, and improve respiratory function in chronic obstructive pulmonary disease, reduce stress, anxiety, constipation, migraine, and other ANS-associated maladies. Among other effects, the diaphragm also influences postural stability, elimination, birthing, metabolic balance, cardiovascular and lymphatic systems. Given the broad reaching impact of improved breathing mechanics, this low-risk, low-cost, non-pharmacological approach to symptom mitigation should be a first-line approach.
Mindfulness training
Finally, ANS function is intimately associated with neurophysiological responses, including ‘fight or flight’, immune activation, pain sensitivity, and many other stress-related impacts. Understanding this is at the core of integrative approaches to help move away from ‘sickness’ and toward ‘health’. There is increasing evidence of the efficacy of some types of ‘mindfulness training’ to transcend the state of ‘ill’ and move toward a state of ‘well’ with regard to many diseases.
Recent work demonstrated the efficacy of meditation as an adjuvant therapy to alter bloodborne factors and resiliency to viral infection in the treatment of COVID-19 and has been reviewed elsewhere with promise for long COVID and ME/CFS. A multi-symptom disease such as ME/CFS is often addressed with a poly-pharmaceutical approach to symptom management. Consideration by both patient and physician of the approaches discussed herein could reduce the efforts to pharmacologically control one’s physiology through the understanding that many, if not all symptoms of ME/CFS implicate ANS dysfunction and may be positively influenced with non-pharmacological approaches. The body-brain axis is proving to be highly influential in control and regulation of energy metabolism.
Advice to physicians
The relationships between peak oxygen consumption, impairment severity, and patient responses on the MOS SF-36 questionnaire suggests that a first-line assessment by physicians might begin with completion of the MOS SF-36.”
An open response from parents and carers of people with Severe ME
A group of parents and carers of people with severe ME have welcomed Prof Edwards’ paper on the ‘Management of Nutritional Failure in People with Severe ME/CFS’, but want to also highlight the need for health professionals to understand the underlying pathology of ME and the importance of maintaining appropriate hydration / fluid balance.
“Our group suggests several additional factors not included in the preprint, which we see as critical to the analysis of the issues highlighted. This includes the need to acknowledge the growing body of scientific and clinical evidence explaining the underlying pathology in patients with Severe ME. We believe this to be critical to countering the misinformation and bias that often influences clinical and managerial decision-making about patients with this condition.”
“As carers, we strongly believe that the onus should be on acknowledging what is now known and knowable. This alone would strongly refute the notion of a need for a middle ground and would instead focus attention on the need to generate solutions from both evidence-based practice and practice-based evidence for managing symptoms, not only in relation to nutritional failure, but also (but not limited to): orthostatic intolerance, dysautonomia, hypovolemia, autoimmunity, sleep disorders, fluid balance, gastroparesis, mast cell activation, and pain.”
“The paper focuses on nutritional management. However, there is also overwhelming evidence from the lived experience of patients with Severe ME that maintaining appropriate hydration / fluid balance constitutes an equally important challenge. Patients with ME have not only been denied appropriate nutritional management but have also been denied appropriate management of fluids.”
“We believe our group has a unique vantage point and first hand lived experience from which to view this phenomenon.It is our collective view that there is a dangerous lack of understanding and awareness of the underlying pathology, especially in relation to Severe ME in NHS hospitals, which leaves patients vulnerable to harm and serious misunderstandings.
People with ME and their carers have experienced decades of marginalisation, discrimination, neglect, and often even a lack of compassion and understanding from some of the people they turn to for help.
Once again, we very much welcome this contribution that spotlights managing nutritional failure in patients with ME and would ask that the barriers to this and fluid management are scrutinised more closely. We agree with Dr Hemsley that action is indeed required at the highest level to address the need for informed, patient-led and safe care for the loved ones we care for, many of whom currently live with a rational fear of hospital admissions.”
More research needed into the lack of recovery time in PEM
The journal Science Norway looks at the key characteristic in ME/CFS of PEM, which can also be found in some people with Long COVID and Fibromyalgia.
It highlights that a type of test called repeated CPET measurements can precisely show how a session of physical activity affects a person’s condition afterwards – they perform worse and the lactic acid in their muscles builds up faster, they have poorer pain regulation and changes in the immune system and interaction with intestinal flora.
One study showed that strenuous mental tasks led to changes in the brains of ME/CFS patients that were not found in healthy people. The changes could correspond with the patients’ experiences of having an impaired ability to think and concentrate after the activity.
No research has been done into whether the same mechanisms can trigger PEM following social or mental exertion as from physical activity. It is not known if the same causes underlie fatigue and symptoms in the muscles and general fatigue throughout the system.
Researchers do not know if this is due to the same mechanisms as exercise-induced PEM. A 2016 study suggested that these might be different phenomena.
Prof Nina Vøllestad believes that existing research may provide a distorted picture, because the patients in the studies had to be able to complete a physical training session.
This probably means that the participants who were selected either had a lighter disease burden or were in a recovery phase, according to Prof Vøllestad and colleague Prof Emerita Anne Marit Mengshoel.
“When we engage in demanding activity, we get tired and need to recover,” Vøllestad says.
Vøllestad sees interesting similarities between PEM in ME/CFS patients and the symptoms of athletes with overtraining syndrome. Overtraining is where the athlete does not get enough recovery time between training sessions over a long period.
“They’re not back to baseline before they start again. So, they wear themselves out, and it can take half a year to recover. The symptoms are very similar to ME/CFS,” says Vøllestad.
The question is: Why don’t ME/CFS patients recover normally?
But here, there are few answers.
“We lack research on biological changes during the recovery phase,” she says.
Nation Radio holds Pride of Wales awards every year where people are nominated in 17 categories. The winner of Dad of the year for 2024 is Rob Messenger, carer of a son with severe ME, advocate, fundraiser and friend of WAMES.
Rob’s son Cerith was diagnosed with M.E. at the age of 11 and is still confined to a dark room twenty years later. Striving to be a voice for his son, Rob rose to the challenge and is speaking out for those suffering with M.E. and long covid.
A group of South African and British researchers have reviewed the literature and described ME/CFS in terms of symptoms, severity and burden, diagnostic criteria, causes and triggers; followed by an overview of the complex pathophysiology and management of the condition. They conclude by listing research priorities for the future.
They emphasise the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease’s complexity and the multifaceted approach required for its study and management.
ME/CFS symptoms
Patients display varying symptoms and several body systems are impacted: Immunological impairments; pain; gastrointestinal problems; autonomic dysfunction; respiratory issues. Although many of the symptoms overlap with other diseases, one feature that sets ME/CFS apart is a worsening of symptoms in response to relatively minor physical, cognitive, orthostatic or even emotional exertion. This phenomenon is known as post-exertional malaise (PEM) or PESE (post exertional symptom exacerbation).
The researchers find that research confirms our understanding of the range of severity of the disease and that despite its high prevalence, there are still no universally accepted clinical criteria to characterise ME/CFS, making early and accurate diagnosis difficult.
Probable causes of ME/CFS
The researchers conclude that “ME/CFS is likely to have a multifactorial origin, with multiple physiological processes implicated” in the way the disease develops. They discuss genetic presdisposition, viral triggers and reactivation, toxin and drug exposure.
The complex pathophysiology of ME/CFS
“As a consequence of infection and other stressors, such as poly-trauma for example, a state of acute inflammation and aberrant immune activation may occur. A compensatory anti-inflammatory mechanism then typically follows), causing an imbalance in immune responses combined with hypothesised autoimmunity. This may lead to subsequent physiological abnormalities including gut dysbiosis and systemic inflammation, eventually resulting in a pathological clotting system, chronic endothelialitis, vasoconstriction, and hypoxia, as found in similar conditions such as heat stroke. Additionally, dysfunctional energy metabolism along with oxidative stress are also hypothesised in the development of ME/CFS. It is hypothesised that these mechanisms occur in a spiralling, progressive way, toppling the host’s homeostatic equilibrium.” A detailed discussion is included.
Management of ME/CFS
No effective therapies and few established non-pharmacological treatments for ME/CFSwere found. Hence current advice is aimed at symptom management and lifestyle changes. The current available treatments/lifestyle modifications are summarised in the illustration.
The researchers conclude by making suggestions for future research and calls for increased support for the ME/CFS community. They also list some potential treatments for furhter investigation: Rintatolimod; steroids; mitochondrial nutraceutical; PPAR agonists; Activators of AMPK; Immunostimulative therapy; Antivirals; Antioxidants; Immunomodulators; B-cell depleting therapy; Immunoadsorption therapy.
Whilst not necessarily providing added information about ME/CFS, this review pools together information from multiple sources to provide a helpful overview of this complex disease.
Successful subcutaneous Immunoglobulin Therapy in patients with ME/CFS
Swedish researchers have found promising effects on symptoms in 17 people with infection associated ME/CFS from subcutaneous treatment (under the skin) with low-dose Immunoglobulin (IG) – Hizentra. Immunoglobulins are antibodies found in white blood cells that fight infection. Low levels suggest your immune system is not functioning well.
Patients were predominantly female (65%) with mild-to-moderate disease severity (82%) and with poor self-reported quality of life and working ability before treatment.
This is thought to be the first study of subcutaneous IG as previously studies tested intravenous or intramuscular IG treatment, which results in much higher drug doses.
The findings from this case series (i.e. not a Randomized control trial – RCT) merit further investigation through well-controlled trials on subcutaneous IG treatment of patients with ME/CFS selected for being potential responders to the treatment.
Purpose
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains an enigma with no curable treatment options at hand. Although patients with ME/CFS are a heterogeneous group, a large proportion of patients present with an infection-driven symptomatology, making them potential responders to immunologic treatments, such as immunoglobulin (IG). Previous studies on IG treatment in patients with ME/CFS have not been consistent but have described beneficial effects in subgroups of patients.
Methods
Here we present data on a series of cases (n = 17) with infection-related ME/CFS (as defined by disease history and ongoing recurrent infections) treated with subcutaneous low-dose IG (0.06 g/kg/mo) over 5 weeks with continuous monitoring of symptoms.
Findings
Patients were predominantly female (65%) with mild-to-moderate disease severity (82%) and with poor self-reported quality of life (median, 25 on a 0–100 scale) and working ability (median, 5 on a 0–100 scale) before treatment. After 5 weeks of treatment with low-dose IG, significant improvements in symptoms, quality of life, and working ability were noted (all P < 0.05). Among the 7 patients who reported the highest benefit of the treatment, quality of life increased by 35 units (on a 0–100 scale), with 1 patient reporting complete elimination of ME/CFS symptoms. No serious side effects were detected with the treatment.
Implications
In this limited-sized case series, we found pronounced beneficial effects of low-dose IG in a large proportion of patients with infection-related ME/CFS. Further well-controlled studies are needed to verify the potential benefits of IG treatment in patients with ME/CFS with infection-driven symptomatology.
NB
Back in 2021 our medical adviser Dr Nigel Speight and colleague Helen Brownlie wroe a paper suggesting a role for IG Therapy in ME/CFS.
Sadly, the mistreatment endured by Maeve Boothby O’Neill is far from rare. Carla Noaum, aged 23, diagnosed with ME over 8 years ago, has been battling to get appropriate care at West Middlesex Hospital in the UK since her admission in March 2024. Carla’s weight has dropped from 52kg to 35kg and she is suffering extreme digestive pain from a nasogastric feeding tube, yet a psychiatrist stopped her pain medication and insisted on exposing her to light. The BBC reported her father as saying she was “screaming from pain” and repeatedly losing consciousness over nine days as a result.
An anonymous patient in Greece reports: “Despite my Severe ME symptoms, hospital staff dismissed my condition as psychosomatic. They forced me through harmful tests and physical activities even when I couldn’t speak due to severe PEM.
create global change by engaging the World Health Organisation’s support in designing and delivering services for ME
create global change by engaging the World Health Organisation’s support in designing and delivering services for ME
“The 
An open response from parents and carers of people with Severe Myalgic Encephalomyelitis.pdf – Google Drive
Nation Radio holds Pride of Wales awards every year where people are nominated in 17 categories. The winner of Dad of the year for 2024 is Rob Messenger, carer of a son with severe ME, advocate, fundraiser and friend of WAMES.
Rob’s son Cerith was diagnosed with M.E. at the age of 11 and is still confined to a dark room twenty years later. Striving to be a voice for his son, Rob rose to the challenge and is speaking out for those suffering with M.E. and long covid.
This is thought to be the first study of subcutaneous IG as previously studies tested 
