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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.”
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.
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.
Read full study:
Heterogeneity in Measures of Illness among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Explained by Clinical Practice: A Study in Seven U.S. Specialty Clinics, by by Elizabeth R Unger et al in
J. Clin. Med. 2024, 13, 1369. [doi.org/10.3390/jcm13051369]
Read ME Research UK’s overview:
Disease heterogeneity among people with ME/CFS
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.
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.”
Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study , by Breanna Weigel, Natalie Eaton-Fitch, Kiran Thapaliya, Sonya Marshall-Gradisnik in Qual Life Res. 2024 Jul 3 [doi: 10.1007/s11136-024-03710-3]
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.
Compression garments
Core stability exercises
Vagus nerve stimulation (VNS)
Cryotherapy or cold therapy
Manual lymphatic drainage
Red-light therapy
Nutrition
Fasciotomy
Myofascial release therapy
Blood flow restriction training (BFR)
Activity pacing
Mindfulness training
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.”
Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations, by Betsy Keller, Candace N. Receno, Carl J. Franconi, Sebastian Harenberg, Jared Stevens, Xiangling Mao, Staci R Stevens, Geoff Moore, Susan Levine, John Chia, Dikoma Shungu & Maureen R Hanson in Journal of Translational Medicine 05 July 2024
See also:
Health rising: Biggest 2-Day Exercise Study Ever Validates the Energy Problems in ME/CFS: Pt. I
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.”
See also:
Management of nutritional failure in severe ME
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.
500 miles for ME: Carer Rob’s fundraising challenge!
500 miles for ME: Carer Rob raises £1,000 for WAMES!
Rob’s #500miles4ME awareness raising reflections
Rob’s #500miles4ME awareness raising with Dr Nina Muirhead
Rob’s #500miles4ME awareness raising with physio Karen Leslie
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.
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.
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.
“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.
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.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease, by Hayley E Arron, Benjamin D Marsh, Douglas B. Kell, M Asad Khan, Beate R Jaeger, Etheresia Pretorius in Front Immunol. 2024; 15: 1386607 2024 Jun 3. [doi:10.3389/fimmu.2024.1386607]
ME Research UK: An overview of ME/CFS
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.
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.
Successful subcutaneous Immunoglobulin Therapy in a case series of patients with ME/CFS by Per Sjogren, Bjorn Bragée, Sven Britton in Clinical Therapeutics June 22, 2024 [doi.org/10.1016/j.clinthera.2024.05.010]
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.
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.
“In the United Kingdom, a small but steady stream of people diagnosed with ME/CFS have run into serious problems with nutrition because of difficulties with eating and drinking, and some have not survived.
The clinical problem is extremely difficult, with little or no formal evidence on which to base diagnosis-specific recommendations for care, or information about prognosis. In several cases, however, the problem has apparently been compounded by a lack of provision of adequate services, misunderstandings, and conflict between health care professionals over diagnosis and approach to management.
The following is a review of the clinical problem, including some suggestions for protocol content that might supplement NICE Guideline NG206.
The main conclusion is that there is an urgent need for a consensus amongst professionals that focuses on practice based reliable evidence rather than theory-laden diagnosis.”
All reasonable efforts should be made to avoid stimuli to which patients are intolerant, which can include light, sound, physical contact, and odours. Exposure to stimuli has in the past led to a breakdown in trust and care and failure of life support.
Prof Edwards’ suggestions are based on consultation with health care professionals with experience in the care of severe ME/CFS. They are in line with both NG206 and the section on nutritional support in the recent BACME Shared Clinical Practice Document on Severe and Very Severe ME/CFS (2024) and draws from A Physiotherapist’s Guide to Understanding and Managing ME/CFS (Clague-Baker et al., 2023).
The protocol should apply to any patient if:
Recommendations:
Management of Nutritional Failure in People with Severe ME/CFS: Review of the Case for Supplementing NICE Guideline NG206, by Jonathan Edwards in Qeios Jun 25 2024 [doi.org/10.32388/T9SXEU] Preprint
The development of health services for people with ME/CFS in Wales continues, although only one Health Board has fully launched their service. Staff recruitment is a slow business and Health Boards continue to experience internal pressures due to staff shortages and financial constraints.
Sixteen months ago, in March 2023, the Health Minister announced funding to:
“widen access to Wales’ long-Covid services… to people with other long term conditions whose rehabilitation and recovery are similar – for example, people with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), fibromyalgia and other post-viral associated conditions.”‘
WAMES has been working hard to explain to Health Boards how Post-Exertional Malaise (PEM) affects the lives of people with ME/CFS and how this impacts symptom management.
We are pleased that many Health Boards have been keen to hear about ME/CFS from those living with the condition in their area, and that some intend to consult further with patients. We hope this will translate into appropriate services for people with ME of all ages and severities.
This is what we know about the current state of development. Please let us know if you have additional information.
ABUHB are well advanced with the development of education and symptom management sessions for adults with a range of conditions. These can be accessed by referral from a GP or other health professional. They are also are exploring extending services to include children with ME/CFS.
Betsi Cadwaladr UHB
BCUHB is accepting a few people onto revised, albeit reduced, ME/CFS services in Llanfairfechan near Conwy and Connah’s Quay in the east. The Health Board continues to develop a Community Complex Conditions Service for adults, which aims to include the housebound. There are still plans to consult with residents, but this has been delayed.
The ME/CFS service offers individual biopsychosocial assessments, which can be face to face or virtual, some individual follow-up sessions if appropriate, and group work based on Acceptance and Commitment (ACT) principles. The group focuses on better managing symptoms and includes: Pacing of activity/energy management; improving sleep; diet; and stress management.
The development of a Long Term Conditions service in the Cardiff and Vale area is well under way, and a soft launch of some self-management support sessions has begun i.e they are accepting adult participants before all aspects of the service are up and running. They are also exploring the possibility of setting up a Complex illness clinic, which could cater for the severely affected. Their information about ME/CFS can be found on the optimistically named Keeping me well website. Continue reading
An open response from parents and carers of people with Severe Myalgic Encephalomyelitis.pdf – Google Drive
