Friday 19 May 2023

Differences between Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS)


Image by JS

The overwhelming exhaustive experience of exertion intolerance as experienced in Myalgic Encephalomyelitis (ME), disproportionate to energy expended, is qualitatively and quantitatively different from fatigue as normally experienced, and it is not refreshed by any amount of rest and sleep.


In addition, there is a range of symptoms, including muscle pain, cognitive dysfunction, paralysis, cardiac issues, respiratory problems, gastrointestinal dysfunction, multiple sensitivities and more systems dysfunction not present in trivial tiredness.

ME has a clearly defined disease process, while CFS by definition has always been a syndrome.

At the heart of the confusion between ME and CFS lie the research and clinical definitions.  One of our goals is to present a clear understanding of the differences between ME and CFS.

The one essential characteristic of ME is acquired Central Nervous System (CNS) dysfunction, that of CFS is primarily chronic fatigue. 
The doctor and patient alike should remember that CFS is not a disease, it is a chronic fatigue state. 

About Myalgic Encephalomyelitis (ME)

 - Myalgic Encephalomyelitis got its name long ago based on what experts saw in patients with the disorder, as well as the autopsy results of many of these patients. What the autopsies showed was inflammation of the brain and spinal cord, deterioration of the dorsal root ganglia, and more. The name broadly meaning 'muscle pain and inflammation of the brain and spinal cord, was coined in 1956 in the UK after using evidence from a number of ME autopsies. In 1969, the World Health Organization (WHO) recognized this fact and officially classified Myalgic Encephalomyelitis as a neurological disease in the ICD as G93.3.
When broken down Myalgic Encephalomyelitis means: 

My = muscle, Algic = pain, Encephalo = brain, Mye = spinal cord, Itis = inflammation. 

- Myalgic Encephalomyelitis (ME) is a chronic, fluctuating, multi-systemic, neurological disease with many organ and bodily systems affected, producing a myriad of symptoms. It is characterized by neurological, immune, cardiac, energy production and ion transport dysfunction. The main feature is exertion intolerance where there is severe worsening of symptoms following any exertion. 

 - ME is a neurological disease and represents a major attack on the central nervous system (CNS) and an associated injury of the immune system by the chronic effects of a viral infection, and/or other possible causes. There is also transient and/or permanent damage to many other organs and bodily systems in ME. ME affects the body systemically, even minor levels of physical and cognitive activity, sensory input and orthostatic stress beyond an ME patient’s individual post-illness limits causes a worsening of the severity of the illness and of symptoms which can persist for days, weeks or months or longer. In addition to the risk of relapse, repeated or severe overexertion can cause permanent damage, e.g. to the heart, disease progression and/or death in ME. 

 - Many cases are preceded by a viral infection with onset being usually rapid (acute). However gradual onsets have also been reported. Affected individuals do not recover from the initial infection but instead go on to develop a wide variety of symptoms including the body’s inability to produce enough energy to function.

 - ME is a lifelong disease that can be extremely severe and cause a profound level of disability and suffering. ME can impose severe restrictions on all aspects of daily living including basic communication. More than 25% of patients have mobility issues and severely debilitating symptoms where they cannot leave their home, others more severe are permanently confined to bed. In some cases ME is fatal.

 - There are several levels of severity in ME, ranging from mild to profound ME and which include mild, moderate, severe, very severe and profound ME. Within each range of severity are other levels which means that within the mild range of ME  there may be significant impact on an individual’s health. Severe to very severe ME sufferers are profoundly affected.  They can be completely immobile, lying still in darkened rooms, requiring help with their basic needs.

 - People with ME can experience debilitating pain, inability to be active, lack of energy (ME is an inability to properly generate energy which prevents sufferers from being active mentally or physically), cognitive difficulties, multiple sensitivities, and a range of other symptoms associated with post-exertional neuroimmune exhaustion (PENE)  - the body and brain’s inability to recover after using even small amounts of energy, and marked fluctuation of symptom severity from day to day or hour to hour. To explain further - when a person with ME is active beyond their individual physical, cognitive, sensory or orthostatic limits this causes a worsening of various neurological, cognitive, cardiac, cardiovascular, immunological, endocrinological, respiratory, hormonal, muscular, gastrointestinal and other symptoms. 

The level of physical activity, cognitive exertion, sensory input or orthostatic stress needed to cause a significant or severe worsening of symptoms varies from patient to patient. The worsening of the illness caused by overexertion often does not peak until 24 - 72 hours or more later.

 - More than 60 different neurological, cognitive, cardiac, vascular, immunological, muscular, metabolic and other symptoms have been documented in ME. Although people with ME have a lot of different minor symptoms because of the way the central nervous system is affected, the major symptoms of ME really are quite distinct and almost identical from one patient to the next. Different people have a lot of different symptoms but the general pattern and evolution of major symptoms are remarkably coherent from patient to patient in ME. 

 - The physical symptoms of ME can be as disabling as multiple sclerosis, systemic lupus, rheumatoid arthritis, congestive heart failure and other chronic conditions. Research shows that people with ME score lower overall on health-related quality of life tests than most other chronic conditions.

 - The symptoms of ME do not necessarily resolve with rest, the symptoms and disabilities associated with ME are not just caused by overexertion; there is also a base level of illness which can be quite severe even at rest. 

 - Repeated overexertion can harm a patient’s chances for future improvement in ME. ME patients who are able to avoid overexertion have repeatedly been shown to have the most positive long-term prognosis. Some people make good progress or recover, many can remain ill for a number of years and may not get better. Not every ME sufferer has the potential for safe activity or stimulation limits within which they will not exacerbate their illness, which is very much the case for the very severely and profoundly affected. 

Feedback shows that those who can experience recovery and remission may relapse so it may always be necessary to manage the illness to avoid relapse, and that people who experience remission don’t go back to complete full health the way they were before they became ill, but they do recover sufficiently to lead a fairly fulfilling life. 

- About the energy issue in ME: Energy is needed to fuel the body’s internal functions. Cells cannot survive on their own. They need energy to stay alive. They need energy to perform functions such as growth, maintaining balance, repair, reproduction, movement, cognitive function and defence. All living organisms must obtain and use energy to live. All body organs work through receiving an energy supply. If the energy supply is impaired in any way the body’s organs will deteriorate over time.
When the body receives energy, it is converted into Adenosine triphosphate (ATP) which is considered to be the energy currency of life. It is the high-energy molecule that stores the energy we need to do just about everything we do. Similar to Multiple Sclerosis, patients with Myalgic Encephalomyelitis share many similar pathologies including impaired ATP. More here.
Let us give an example of the effect of lack of ATP production on one vital organ - the brain. Lack of cellular energy causing poor production of ATP will start out by the patient showing symptoms of cognitive dysfunction which could mean forgetting conversations, poor short-term memory, inability to hold conversations, inability to absorb new information, difficulty reading a book or following a film, difficulty finding the right words, intermittent dyslexia, etc. However, if energy disruption continues unabated, resulting in the lack of production of ATP, research is now showing us that this can lead to conditions like Dementia and Alzheimer's.

- ME, a debilitating, life-changing, catastrophic multi-system illness, negatively impacts on all systems of the body. Marked debilitating fatigue and weakness, sickness, cognitive dysfunction and symptom flare-up follows any physical or cognitive exertion requiring energy. This aspect of ME referred to as Post Exertional Neuroimmune Exhaustion (PENE) is a cardinal feature in ME as per the ICC. Essentially what it means is that any exertion, physical, cognitive or even emotional stress creates a prolonged reaction in the body where a relapse or worsening of all symptoms occur which can last for days, weeks, months or longer. Indeed, many people who have pushed far too hard beyond their limits have become bedbound and carer dependent for years.

- Classified by the World Health Organization ICD as a neurological condition (G93.3) and by the National Ability Support System (NASS) coded as G93.3, the disease causes unusually severe disability and most often manifests post-virally. It can also affect people of any age or demographic, including children.

- Prevalence: 0.4 – 1%. There are millions with ME worldwide, approx 250,000 in the UK and somewhere between 10,000 and 19, 000 in Ireland (estimates are based on international prevalence rates)

- People with ME are not just unusually neglected, quality of life scores are shocking, worse than many conditions encountered in primary and secondary care, such as HIV, heart disease, congestive heart failure, cancer, stroke, end stage renal failure, lung disease, type 2 diabetes, osteoarthritis, MS, epilepsy, eosinophilic gastroenteritis, cystic fibrosis, sciatica and many other conditions. They are unusually vulnerable, especially those with severe to profound ME, often with little to zero physical capacity to address issues that affect them, implying the need for additional care in primary care clinical services and in accessing community supports and services as well as welfare payments.

- People with ME are most affected by their inability to perform usual activities. Their mobility issues, self care, nutrition, housework, ability to work, to be active and to socialise are all affected by symptoms. The symptoms of ME are numerous and can include but are not limited to those described in the International Consensus Primer (ICP), and also in our previous post about symptoms.

- Medics such as GPs and specialists can follow the International Consensus Primer (ICP) to definitively diagnose ME and pursue some effective management and symptom treatments to help improve quality of life.

- ‘Normal’ test results do not mean there is nothing wrong. It means we don’t have the right tests.

- The daily reality of people with Severe ME is much worse than not having the 'basic energy' to engage in daily tasks, while that of people with Very Severe ME is so horrendous, there just aren't words to describe how awful it is - extreme pain, paralysis, multiple sensitivities, cognitive issues, terrible hypersensitivities, profound system dysfunction.
Much like the disease Multiple Sclerosis, people can be affected in different ways. Severe cases often leave affected individuals permanently bedridden, needing tube feeding and 24 hr care. Less severe cases are usually housebound with no basic energy to engage in ordinary simple self-care and household activities like showering, washing hair, brushing teeth, making a meal, etc. Milder cases may be able to function at a higher level, but energy is very limited, and each task involves pacing and prolonged resting to restore enough energy for the next task.

- High quality evidence-based care is worse than rare, ME is largely unaddressed or mismanaged. Despite being common and having reasonably clear diagnostic criteria, there is unusually low levels of understanding and knowledge amongst medical professionals of ME epidemiology, disability and management. Participants of an online CPD module in the UK were asked 'Would you agree that your medical training to date has helped you understand ME and given you the knowledge to manage ME?' responded with 54% who disagreed including 21% who strongly disagreed,19% agreed, including 4% who strongly agreed, and 27% responded with neutral.

 There is no cure or clear pathway to recovery. Evidence-implied management and risk-minimisation strategies exist. Individual symptoms can sometimes be treatable, and the systemic exertion intolerance that distinguishes ME from other illnesses must be managed to avoid post exertional neuroimmune exhaustion (PENE). 

 - Psychological support for those with ME is repeatedly found to be harmful and irrelevant. Such support can help patients cope with the debilitating chronic illness experience, as with any chronic illness, but should in no way be promoted as curative for ME.

 - The belief that ME has no diagnostic marker and is a diagnosis of exclusion is a misrepresentation. Exclusion is critical to avoid misdiagnosis of mental health or other physical diseases as ME, but exertion intolerance characterised by Post Exertional Neuroimmune Exhaustion (PENE) is a cardinal symptom. 

 - People with ME can benefit from straightforward diagnostic criteria that are clear such as the International Consensus Criteria and Primer. 

 - Common patterns in ME are often evident e.g. post-viral onset.  Abnormalities are observable in controlled research contexts with the two day cardio-pulmonary exercise tests (an inappropriate risk for many with ME especially those with severe ME) and in metabolic and other findings.

- Myalgic Encephalomyelitis may occur as an outbreak that affects a large group of people (epidemically) as seen in this paper or may only affect an individual (non-epidemically).

- The first outbreak of Myalgic Encephalomyelitis was recorded in 1934, however the term Myalgic Encephalomyelitis first appeared in the medical literature in 1956 when it was named by Dr. Melvin Ramsay. See excerpts from Dr Ramsay's 1986 book entitled The Clinical Features of Myalgic Encephalomyelitis

- Myalgic Encephalomyelitis is recognized as a distinct disorder and has been classified as a specific neurological disorder under G.93.3 by the World Health Organization (WHO) since 1969.

- The term ‘Myalgic Encephalomyelitis’ (ME) is used to conceptualise a specific neuroimmunological condition, assumed to be more severe and less psychologically attributed than CFS.

- ME needs to be acknowledged as a serious disease, causing significant impact on health and QOL, not only of the individual but also of their family. Education for healthcare practitioners must be introduced and updated to reflect this. 

- ME is a biological illness, not a psychologic disorder. Patients with ME are neither malingering nor seeking secondary gain. Inaccurate media narratives perpetuate socio-medical harm.

 - ME is a distinct illness, while both CFS and ME/CFS are umbrella terms for a group of symptoms common to many illnesses and conditions. This has led to ME symptoms being confused with the symptoms for neurasthenia, multiple chemical sensitivities, fibromyalgia syndrome, chronic mononucleosis, and much more.

- ME is a distinct clearly diagnosable neurological illness, similar to MS. Patients with Myalgic Encephalomyelitis share many similar pathologies including impaired ATP. See 2013 Morris and Maes research paper here and an easier to understand piece with similarities between ME and MS here.

- The overwhelming exhaustive experience of ME and exertion intolerance, disproportionate to energy expended, is qualitatively and quantitatively different from fatigue as normally experienced and it is not refreshed by any amount of sleep. In addition, there is a range of symptoms, including muscle pain and cognitive dysfunction, not present in mere tiredness.

More from the Hummingbirds Foundation for ME

List of characteristics associated with ME:

  • Acute onset (associated with a virus; an enterovirus)
  • The disease occurs in outbreaks as well as sporadically (the incubation period of the virus is 4-7 days)
  • Damage to the central nervous system (which is observable on brain scans, and which is similar to MS)
  • Consequences of neurological damage such as loss of homeostasis in many of the body’s systems
  • Abnormalities seen on many different objective tests (including ESR tests, NK cells tests, Holter monitors and physical exam) within weeks of disease onset
  • Seizures and paralysis
  • Cognitive dysfunction, involving concentration, memory and perceptual problems
  • Sensory disturbance and over-sensitivity
  • Reduced circulating blood volume and associated problems such as orthostatic intolerance, neurally mediated hypotension and POTS
  • Cardiac abnormalities such as tachycardia and reduced cardiac function
  • Mitochondrial dysfunction, resulting in loss of energy production, and impaired immunity and cellular repair capability
  • Immune dysfunction
  • Delayed effect following physical, mental or sensory overexertion (24 to 72 hours or more)
  • Worsening of illness, serious relapse or possibly death following overexertion
  • Severe disability lasting many years (most often lifelong) which may also result in death

"In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology."

 - Carruthers et al, Journal of Internal Medicine

About Chronic Fatigue Syndrome (CFS)

As the authors of the 2011 Consensus Criteria state: 'Using ‘fatigue’ as a name of a disease gives it exclusive emphasis and has been the most confusing and misused criterion. No other fatiguing disease has ‘chronic fatigue’ attached to its name, e.g. cancer/chronic fatigue, multiple sclerosis/chronic fatigue, except ME/CFS. Fatigue in other conditions is usually proportional to effort or duration with a quick recovery and will recur to the same extent with the same effort or duration that same or next day."  

Not so with M.E.  Many crushing symptoms are exacerbated with the slightest physical or mental exertion, and it takes days or weeks to recover to even the original low functionality, that is, if the exertion was not too far beyond the patient's threshold for recovery, and disease progression continues from a lower activity tolerance threshold.

ME is sometimes referred to by the problematic term “Chronic Fatigue Syndrome” or the acronym ME/CFS. The stigmatising nature of the term Chronic Fatigue Syndrome (CFS) is frequently compared to previously misapplied “hysterical paralysis” terminology used for MS patients. 

The double acronym ME/CFS exists for a few reasons, to bridge failures in naming a 1980s illness that occured in the US which focused only on fatigue and the illness Myalgic Encephalomyelitis; and to put an emphasis on fatigue and dilute the seriousness of ME.
The US Centers for Disease Control and Prevention (CDC) first defined CFS, with great emphasis on the word “fatigue”, in 1988. This definition, referred to as “Holmes”, was later replaced by the 1994 ”Fukuda”, then by the 2005 “Reeves”, and most recently by the 2015 IOM (Institutes of Medicine/NAM) report, still emphasizing fatigue. Definitions have also included the 1991 UK ”Oxford” report and the more well-known 2003 Canadian Consensus Criteria (CCC).

Within the HSE, a diagnosis of Chronic Fatigue Syndrome (CFS) or ME/CFS is often given. In paediatrics the preferred label is CFS. This mixed use of labels can make it confusing for many. 

The term “chronic fatigue syndrome” affects patients’ perceptions of their illness as well as the reactions of others, including medical personnel, family members, and others. This label can trivialize the seriousness of the condition and promote misunderstanding of the illness

 - ME/CFS can be viewed as meaning 'fatigue' or 'chronic fatigue'.

 - ME/CFS can be viewed as meaning 'post viral fatigue syndrome'.

 - ME and CFS have distinct diagnostic criteria, multi-system symptomatology and scientific consensus but there is no such disease classified as ME/CFS, i.e. there is no classification for ME/CFS.  In fact the 'ME/CFS' name is not compliant with the WHO classification rule that a disease cannot be classified under more than one rubric.

- Many people, including doctors, conflate the name Myalgic Encephalomyelitis (ME) with CFS (Chronic Fatigue Syndrome) despite there being differences between the two.

- The CFS label was first used in medical literature by the Centre for Disease Control(CDC), USA, during the 1980s to describe an outbreak of an ME like illness in Lake Tahoe. The criteria used for this ‘new’ illness focused on the fatigue elements of patients' symptoms and ignored the encephalitic (inflammation of the brain) features of the illness.

- CFS and ME/CFS are umbrella terms for a group of symptoms common to many illnesses and conditions. This has led to ME symptoms being confused with the symptoms for neurasthenia, multiple chemical sensitivities, fibromyalgia syndrome, chronic mononucleosis, and more.

- The name CFS trivialised the seriousness of how ill patients were and over time led to more and more people, with only fatigue as their primary symptom, to get a diagnosis of CFS.
And so, began the longterm confusion between ME and CFS leading to a commonly used hybrid term 'ME/CFS' for which there is no ICD code.

- Many people with CFS do not fulfil the criteria for ME and similarly many patients with ME who have received a CFS diagnosis do not fulfil the CFS criteria and as a result are left without appropriate healthcare and illness management.

- Over decades this conflation of the two illnesses has led to the severe neglect of people with ME, people who are suffering horrendous symptoms and who doctors simply see as a patient who has unexplained 'fatigue'.

- The distinction between both illnesses has continued to cause problems for researchers, doctors, governments and patient organisations. Many began to use the terms interchangeably or with the combined acronym ME/CFS, creating a broad disease category that has no official classification.

- This emphasis on fatigue unfortunately 'allowed' the disease of ME to become more and more disappeared and to be defined by some as a psychiatric illness, thus condemning some very seriously ill patients to a lack of proper diagnosis, lack of appropriate testing, lack of treatment and understanding of the symptoms and a lack of interest in pursuing biological research for the condition.

- Many organisations and health agencies worldwide classify “CFS” as a psychiatric condition using euphemistic terms like Central Sensitisation Syndrome (CSS) or Functional Neurological Disorder (FND). It has been easy to pose psychiatric diagnoses on ME and CFS patients since psychiatric diagnoses cannot be subjected to scientific examination. Psychiatrists rarely actually examine patients and almost never do an integrated patho-physiological patient investigation of the patient’s organs and systems. In the 70 plus years since the first major ME and CFS epidemics struck no psychiatric treatment has proven significantly effective in treating the ME and CFS patients and restoring them to health. 

- In recent years there are very reputable scientists now involved worldwide in ME research adopting appropriate and more stringent diagnostic criteria on trial participants. Unfortunately there are also research studies on ME taking place which are still using the wrong criteria on trial participants, ie CFS criteria, which makes it very difficult to accept trial results as precise and exact data in relation to ME.

- You cannot treat CFS because it is not a single illness but a whole collection of illnesses not yet diagnosed in the people diagnosed with CFS. Think of all the illnesses out there that cause some level of fatigue. People from all of those illnesses are being misdiagnosed with CFS. 

 - This is why researching CFS is a waste of funds. You cannot define CFS or find a single cause or treatment for it because there is no single 'it' to research. 

More here about CFS from the Hummingbirds Foundation for ME

List of characteristics associated with ‘CFS’ 

  • Gradual onset
  • Onset following overwork or stress
  • Onset following EBV infection (or other common viruses including flu, Ross River virus, hepatitis infections and so on)
  • Fatigue or exhaustion (as the defining or most severe symptom of the illness) or symptoms referred to as vague and ‘everyday’ type symptoms
  • Omission of the serious neurological and cardiac (and other) dysfunctions which define M.E.
  • Emotional state, personality type or psychological history associated with causing or prolonging illness
  • Short duration of illness and/or naturally resolving illness after a short period of time or illness which resolves or improves with exercise therapy, psychotherapy or antidepressant drugs (or similar)
  • Mild illness which cannot result in death

To see the differences between Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME) see this comparison chart by the Hummingbirds Foundation For ME (US). The chart shows, despite what many people claim, that ME and CFS are not the same.

"Where the one essential characteristic of ME is acquired CNS (central nervous system) dysfunction, that of CFS is primarily chronic fatigue."

- Dr Byron Hyde

Further Comments

Though the symptoms of CFS resemble those of ME, the differences are so significant that they would exclude ME patients from the 1988 and 1994 CDC diagnoses of CFS.  The following features of ME separate it from CFS: 

●  The acute onset.

●  The organ pathology, particularly cardiac.

●  Neurological signs in the acute and sometimes chronic phases.

●  The specific involvement of the autonomic nervous system.

●  The frequent subnormal patient temperature.

●  The fact that chronic fatigue is not an essential characteristic of the chronic phase of ME.

Persisting using the word 'fatigue', which is not a very useful symptom to try to single out any particular illness, because which illness does not have fatigue associated with it?, is holding back research into the physical cause of ME by bundling different illnesses together, confounding variables and diluting the reliability of the findings for ME sufferers.

While just about all patients with ME will fit the definition for CFS, not all of those with CFS will fit the definition for ME. But technically, the CDC CFS definition excludes those patients with other serious illnesses that include fatigue as a symptom.  Therefore a patient formally diagnosed with ME, a serious neurological illness of CNS dysfunction - debilitating fatigue being merely one of MANY disabling symptoms - would be ruled out of the CFS definition.

ME is recognised by the World Health Organisation as a neurological illness, for which the physical cause is as yet unknown and is categorised differently from Chronic Fatigue Syndrome (CFS).  Bundling fatiguing illnesses all together weakens any research, dilutes and distorts the findings, making it difficult, if not impossible, to generalise to any one particular illness and, therefore, hampers progress towards finding an appropriate treatment or cure for every one of them, packaged under the controversial umbrella term CFS, not just ME.

Disclaimer: The information in this post is for general information purposes only. While we endeavour to keep the information up to date and correct, we make no representations or warranties of any kind, express or implied, about the completeness, accuracy, reliability, suitability or availability with respect to the post or the information, products, services, etc contained in the post for any purpose. Any reliance you place on such information is therefore strictly at your own risk. The suitability of any solution is totally dependent on the individual. It is strongly recommended to seek professional advice and assistance in some instances. 

No comments:

Post a Comment