On 2014 Oct 10, Ellen M Goudsmit commented:

Case definitions should also recognise the progressive form of the disease.

Howes and Goudsmit (submitted) suggest that :

A diagnosis of progressive ME is supported by the following:

1. Sudden increase in sensitivities and gastro-intestinal symptoms.
2. Sudden worsening of existing neurological symptoms or new symptoms, e.g. blurred vision in one eye, weakness in one leg, incontinence.<br>
3. Improvements are limited, disability tends to show a downwards trend.
4. Patient has to spend more time at home or in bed.
5. New auto-immune diseases e.g. symptoms consistent with Sjogren’s syndrome.

Supportive evidence of pathology:

MRI, abnormal white matter lesions not indicative of MS.

On 2014 Jan 21, Ellen M Goudsmit commented:

The International Consensus Criteria or ICC initially appeared to be resolve a lot of problems relating to heterogeneity of the population, describing many of the symptoms of classic ME and avoiding the vagueness of the term ‘malaise’ used in case definitions for CFS. The ICC are more specific, referring to a pathological inability to produce sufficient energy on demand, “postexertional symptom exacerbation”, “postexertional exhaustion” , “a marked, rapid physical and/or cognitive fatigability in response to exertion”, a prolonged recovery period and “a low threshold of physical and mental fatigability (lack of stamina) resulting in a substantial reduction in pre-illness activity level”. Postexertional neuro-immune exhaustion (PENE) as they named this characteristic feature, had to cause marked disability and was compulsory for diagnosis. However, it's not easy to assess in practice. In a recent study by Jason et al. [1], more than 10% of the patients selected using the ICC did not report that minimal exercise made them tired. This is possibly because the researchers required only one of the characteristics of PENE to be present, rather than all.

A second study from Jason and his colleagues also compared the CDC criteria with the ICC and showed that while the latter identified a subset of patients with more functional impairments and physical, mental and cognitive problems, they also had a higher rate of psychiatric illness.[2] Indeed, 61.5% had a current psychiatric diagnosis compared to 27% who fulfilled the CDC criteria. Again, this may be a result of patients reporting evidence of post-exertional worsening but not meeting every characteristic of PENE. This 'short-cut', also likely to occur in clinical practice, might have led to misclassification.

For example, another interesting finding was that more than a half had a gradual onset. This plus the higher rate of psychiatric illness are at odds with descriptions of individuals with classic ME, more of whom report an acute infectious onset and symptoms such as muscle weakness and an intolerance to alcohol.[3 p.147, 4,5] They also tend to have lower rates of psychiatric illness.[6,7,8] According to Jason et al. [1], the requirement of a larger number of symptoms (at least eight for the ICC versus five for the CDC criteria) might “inadvertently increase the rate of psychiatric morbidity” and they recommended further refinement of case definitions focusing on a small set of core symptoms. Finally, based on a review of all criteria, they noted some of the disadvantages of polythetic case definitions that include patients on the basis that they experience a certain number of listed symptoms, many of which are ubiquitous and do not allow clinicians to differentiate between CFS and other disorders.[1,8,9]

[1] Jason LA, Sunnquist M, Brown A, Evans M, Vernon, SD, Furst JD, Simonis, V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue: Biomed Health Behav. Epub 2013 Dec 11. Available from: http://dx.doi.org/10.1080/21641846.2013.862993

[2] Brown AA, Jason LA, Evans MA, Brown M, Flores S. Contrasting case definitions: The ME international consensus criteria vs. the Fukuda et al. CFS criteria. North Am J Psychol. 2013;15(1):103–120.

[3] Shepherd C. Living with M.E. 2nd ed. London: Cedar; 1992.

[4] Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis a persistent enteroviral infection? Postgrad Med J, 1990;66:526 530.

[5] Smith DG. Understanding M.E. The phenomenon of myalgic encephalomyelitis and acute onset post viral fatigue syndrome. London: Robinson Publishing; 1989. p. 184-185.

[6] Dowsett EG, Welsby PD. Conversation Piece. Postgrad Med J. 1992; 68:63-65.

[7] Yeomans JDI, Conway SP. Biopsychosocial aspects of chronic fatigue syndrome (myalgic encephalomyelitis). J Infect. 1991;23:263-269.

[8] King C, Jason LA. Improving the diagnostic criteria and procedures for chronic fatigue syndrome. Biol Psychol. 2005;68: 87-106.

[9] Goudsmit E, Shepherd C, Dancey CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33.

On 2014 Jan 20, Ellen M Goudsmit commented:

There are other criteria for ME based on the work of experts such as Drs. Ramsay, Dowsett and Parish. Lack of interest in classic ME has made it extremely difficult to place these criteria in the scientific domain.

Myalgic Encephalomyelitis (ME). Criteria and clinical guidelines 2014.

Sandra Howes<br> Ellen M Goudsmit PhD FBPsS<br> Charles Shepherd MBBSc

Abstract

Myalgic encephalomyelitis (ME) is a disabling condition characterised by profound fatigue following minimal exertion and a delay in recovery after exertion ends. In 1988, when specialists introduced the concept of chronic fatigue syndrome (CFS), it was assumed that the illness in question was identical to ME but the lack of consensus criteria for the latter has prevented the testing of this assumption. In this article, we propose criteria and guidelines which can be used to study ME and determine whether it is a synonym for CFS or one of several subgroups contained within the CFS construct. If clinically meaningful differences are identified, the criteria may help to increase diagnostic precision and facilitate further research into the cause, course and treatment of ME.

Extract

The criteria for research into ME [1]

All patients should fulfil the following five criteria: 1. A new onset of significantly abnormal levels of muscle fatiguability and/or muscle weakness, precipitated by relatively minor levels of activity. Symptoms typically worsen during the next 24-48 hours. 2. The presence of symptoms indicating the involvement of the brain and central nervous system (e.g. impaired short-term memory and concentration, disturbed sleep patterns, balance problems). 3. Periods of impaired circulation compatible with autonomic dysfunction (e.g. facial pallor, disturbances in thermoregulation including inappropriate sweating and sensitivity to both heat and cold; postural hypotension and/or orthostatic intolerance). 4. Fluctuation of symptoms, from hour to hour and day to day. 5. These symptoms must have been present during the past three months (to exclude patients with the debility which often follows illnesses such as influenza).

Guidelines

Many symptoms experienced by people with ME are also reported by people with other disorders. The most prevalent of these include pain – which can be muscular, arthritic or neuropathic in character; hyperacusis and tinnitus; photophobia and blurred vision; frequency of micturition and hypersensitivity to chemicals and drugs. Also common are symptoms suggestive of immune system dysfunction and/or persisting infection, such as episodes of low-grade fever (not exceeding an oral temperature of 38.6C) combined with feeling feverish; sore throat which may be persistent or recurrent, and arthralgia.

While the presence of these symptoms are not discriminative, the marked diurnal fluctuations in severity are typical of ME. Exacerbations are frequently triggered by physical or mental exertion and this association should always be sought whilst taking the history.[2] Characteristic physical signs are sometimes seen in ME and in combination with the symptoms above also contribute to the validity of the diagnosis. Nevertheless their absence does not exclude the condition. They are as follows: 1. Pharyngitis. 2. Tenderness and possible enlargement of lymph nodes. 3. A positive Romberg test or Fukuda test.

Course

Although ME often follows an infection, usually a viral illness (which may be sub-clinical), it may also be triggered by other factors such as immunizations, trauma and exposure to chemicals. Furthermore, in a minority of patients, ME has a gradual onset with no apparent triggering factor. For these reasons, and in line with the criteria for CFS, evidence of a preceding viral illness is not a prerequisite for diagnosis or inclusion in a study group.

Assessment, investigation and diagnosis

Because it is vital that the samples used in research are as 'pure' as possible, the presence of certain co-morbid disorders would be grounds for disqualification. Some of the more common alternative diagnoses to be borne in mind before selecting a participant for a study on ME are listed in Shepherd and Chaudhuri[2,p.15]

Other reasons for exclusion from research into ME

It is of particular importance to identify cases of chronic fatigue which can be largely explained by psychological factors. For example, if there are signs of persistent anhedonia, apathy, low self-esteem, feelings of worthlessness and guilt, the possibility of primary depressive illness should be considered and, if there is any doubt, the participant should be excluded from the study. Similarly, if the patient has had any other illness or undertaken any treatments - orthodox, complementary or nutritional - in the previous three months, their inclusion may introduce additional variables which could confound the results.

Measures to aid diagnosis and selection of samples

We recommend that the Profile of Fatigue-Related Symptoms (PFRS) developed by Ray et al. [3] may help support the diagnosis and suggest that a person should score at least 2 out of six on the two items relating to the presence of muscle weakness. This is a core symptom and the score provides additional evidence of its presence and severity. The testing of muscle fatigue on two occasions, at least 24 hours apart, may also be of value.

A protocol was developed by Dr Parish, a rheumatologist who has studied ME since 1955. Using criteria almost identical to those proposed above (Wood, personal communication), Paul et al. [4] found a significant decline in quadriceps strength which persisted after 24 hours in all the participants. Moreover, there were significant differences between the patients and controls during the recovery phase, 200 minutes following exercise, when the results of the latter had returned to normal, and after 24 hours. This protocol is different to others that have evaluated post-exertional fatigue in that it demands a continually increasing energy cost throughout the duration of the exercise period, and therefore differs from the steady levels achieved in cycle ergometry used in other studies.<br> However, one cycling exercise test that deserves further consideration was recently described by Snell et al.[5] Although the patients were diagnosed with CFS, all reported a worsening of symptoms after physical activity. Various tests using a cycle ergometer were conducted to evaluate work efficiency, i.e., oxygen consumption and work output at the ventilatory/anaerobic threshold. The results revealed lower workloads and oxygen consumption at peak exercise compared to sedentary controls but none of the individual tests helped to discriminate between the groups on day 1. However, data from the second session showed a decrease in performance in patients that was not seen in controls and identified two measures which contributed most to the discrimination between the groups (workload at ventilatory threshold and peak workload). The researchers noted that their findings may have been affected by the heterogeneity of the sample but the results helped to correctly classify over 95% of the participants and demonstrated the importance of a second test.

[1] Goudsmit E et al. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33.

[2] Shepherd C, Chaudhuri A. ME/CFS/PVFS. An exploration of the key clinical issues. 4th ed. ME Association; 2008.

[3]Ray C et al. Development of a measure of symptoms in chronic fatigue syndrome: The profile of fatigue-related symptoms (PFRS). Psychol Health. 1992;7:27-43.

[4] Paul L et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol. 1999;6:63-69.

[5] Snell CR et al. Discriminative validity of metabolic and workload measurements to identify individuals with chronic fatigue syndrome. Phys Ther. 2013;93(11):1484-1492.

On 2014 Jan 20, Ellen M Goudsmit commented:

There are other criteria for ME based on the work of experts such as Drs. Ramsay, Dowsett and Parish. Lack of interest in classic ME has made it extremely difficult to place these criteria in the scientific domain.

Myalgic Encephalomyelitis (ME). Criteria and clinical guidelines 2014.

Sandra Howes<br> Ellen M Goudsmit PhD FBPsS<br> Charles Shepherd MBBSc

Abstract

Myalgic encephalomyelitis (ME) is a disabling condition characterised by profound fatigue following minimal exertion and a delay in recovery after exertion ends. In 1988, when specialists introduced the concept of chronic fatigue syndrome (CFS), it was assumed that the illness in question was identical to ME but the lack of consensus criteria for the latter has prevented the testing of this assumption. In this article, we propose criteria and guidelines which can be used to study ME and determine whether it is a synonym for CFS or one of several subgroups contained within the CFS construct. If clinically meaningful differences are identified, the criteria may help to increase diagnostic precision and facilitate further research into the cause, course and treatment of ME.

Extract

The criteria for research into ME [1]

All patients should fulfil the following five criteria: 1. A new onset of significantly abnormal levels of muscle fatiguability and/or muscle weakness, precipitated by relatively minor levels of activity. Symptoms typically worsen during the next 24-48 hours. 2. The presence of symptoms indicating the involvement of the brain and central nervous system (e.g. impaired short-term memory and concentration, disturbed sleep patterns, balance problems). 3. Periods of impaired circulation compatible with autonomic dysfunction (e.g. facial pallor, disturbances in thermoregulation including inappropriate sweating and sensitivity to both heat and cold; postural hypotension and/or orthostatic intolerance). 4. Fluctuation of symptoms, from hour to hour and day to day. 5. These symptoms must have been present during the past three months (to exclude patients with the debility which often follows illnesses such as influenza).

Guidelines

Many symptoms experienced by people with ME are also reported by people with other disorders. The most prevalent of these include pain – which can be muscular, arthritic or neuropathic in character; hyperacusis and tinnitus; photophobia and blurred vision; frequency of micturition and hypersensitivity to chemicals and drugs. Also common are symptoms suggestive of immune system dysfunction and/or persisting infection, such as episodes of low-grade fever (not exceeding an oral temperature of 38.6C) combined with feeling feverish; sore throat which may be persistent or recurrent, and arthralgia.

While the presence of these symptoms are not discriminative, the marked diurnal fluctuations in severity are typical of ME. Exacerbations are frequently triggered by physical or mental exertion and this association should always be sought whilst taking the history.[2] Characteristic physical signs are sometimes seen in ME and in combination with the symptoms above also contribute to the validity of the diagnosis. Nevertheless their absence does not exclude the condition. They are as follows: 1. Pharyngitis. 2. Tenderness and possible enlargement of lymph nodes. 3. A positive Romberg test or Fukuda test.

Course

Although ME often follows an infection, usually a viral illness (which may be sub-clinical), it may also be triggered by other factors such as immunizations, trauma and exposure to chemicals. Furthermore, in a minority of patients, ME has a gradual onset with no apparent triggering factor. For these reasons, and in line with the criteria for CFS, evidence of a preceding viral illness is not a prerequisite for diagnosis or inclusion in a study group.

Assessment, investigation and diagnosis

Because it is vital that the samples used in research are as 'pure' as possible, the presence of certain co-morbid disorders would be grounds for disqualification. Some of the more common alternative diagnoses to be borne in mind before selecting a participant for a study on ME are listed in Shepherd and Chaudhuri[2,p.15]

Other reasons for exclusion from research into ME

It is of particular importance to identify cases of chronic fatigue which can be largely explained by psychological factors. For example, if there are signs of persistent anhedonia, apathy, low self-esteem, feelings of worthlessness and guilt, the possibility of primary depressive illness should be considered and, if there is any doubt, the participant should be excluded from the study. Similarly, if the patient has had any other illness or undertaken any treatments - orthodox, complementary or nutritional - in the previous three months, their inclusion may introduce additional variables which could confound the results.

Measures to aid diagnosis and selection of samples

We recommend that the Profile of Fatigue-Related Symptoms (PFRS) developed by Ray et al. [3] may help support the diagnosis and suggest that a person should score at least 2 out of six on the two items relating to the presence of muscle weakness. This is a core symptom and the score provides additional evidence of its presence and severity. The testing of muscle fatigue on two occasions, at least 24 hours apart, may also be of value.

A protocol was developed by Dr Parish, a rheumatologist who has studied ME since 1955. Using criteria almost identical to those proposed above (Wood, personal communication), Paul et al. [4] found a significant decline in quadriceps strength which persisted after 24 hours in all the participants. Moreover, there were significant differences between the patients and controls during the recovery phase, 200 minutes following exercise, when the results of the latter had returned to normal, and after 24 hours. This protocol is different to others that have evaluated post-exertional fatigue in that it demands a continually increasing energy cost throughout the duration of the exercise period, and therefore differs from the steady levels achieved in cycle ergometry used in other studies.<br> However, one cycling exercise test that deserves further consideration was recently described by Snell et al.[5] Although the patients were diagnosed with CFS, all reported a worsening of symptoms after physical activity. Various tests using a cycle ergometer were conducted to evaluate work efficiency, i.e., oxygen consumption and work output at the ventilatory/anaerobic threshold. The results revealed lower workloads and oxygen consumption at peak exercise compared to sedentary controls but none of the individual tests helped to discriminate between the groups on day 1. However, data from the second session showed a decrease in performance in patients that was not seen in controls and identified two measures which contributed most to the discrimination between the groups (workload at ventilatory threshold and peak workload). The researchers noted that their findings may have been affected by the heterogeneity of the sample but the results helped to correctly classify over 95% of the participants and demonstrated the importance of a second test.

[1] Goudsmit E et al. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33.

[2] Shepherd C, Chaudhuri A. ME/CFS/PVFS. An exploration of the key clinical issues. 4th ed. ME Association; 2008.

[3]Ray C et al. Development of a measure of symptoms in chronic fatigue syndrome: The profile of fatigue-related symptoms (PFRS). Psychol Health. 1992;7:27-43.

[4] Paul L et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol. 1999;6:63-69.

[5] Snell CR et al. Discriminative validity of metabolic and workload measurements to identify individuals with chronic fatigue syndrome. Phys Ther. 2013;93(11):1484-1492.

On 2014 Jan 21, Ellen M Goudsmit commented:

The International Consensus Criteria or ICC initially appeared to be resolve a lot of problems relating to heterogeneity of the population, describing many of the symptoms of classic ME and avoiding the vagueness of the term ‘malaise’ used in case definitions for CFS. The ICC are more specific, referring to a pathological inability to produce sufficient energy on demand, “postexertional symptom exacerbation”, “postexertional exhaustion” , “a marked, rapid physical and/or cognitive fatigability in response to exertion”, a prolonged recovery period and “a low threshold of physical and mental fatigability (lack of stamina) resulting in a substantial reduction in pre-illness activity level”. Postexertional neuro-immune exhaustion (PENE) as they named this characteristic feature, had to cause marked disability and was compulsory for diagnosis. However, it's not easy to assess in practice. In a recent study by Jason et al. [1], more than 10% of the patients selected using the ICC did not report that minimal exercise made them tired. This is possibly because the researchers required only one of the characteristics of PENE to be present, rather than all.

A second study from Jason and his colleagues also compared the CDC criteria with the ICC and showed that while the latter identified a subset of patients with more functional impairments and physical, mental and cognitive problems, they also had a higher rate of psychiatric illness.[2] Indeed, 61.5% had a current psychiatric diagnosis compared to 27% who fulfilled the CDC criteria. Again, this may be a result of patients reporting evidence of post-exertional worsening but not meeting every characteristic of PENE. This 'short-cut', also likely to occur in clinical practice, might have led to misclassification.

For example, another interesting finding was that more than a half had a gradual onset. This plus the higher rate of psychiatric illness are at odds with descriptions of individuals with classic ME, more of whom report an acute infectious onset and symptoms such as muscle weakness and an intolerance to alcohol.[3 p.147, 4,5] They also tend to have lower rates of psychiatric illness.[6,7,8] According to Jason et al. [1], the requirement of a larger number of symptoms (at least eight for the ICC versus five for the CDC criteria) might “inadvertently increase the rate of psychiatric morbidity” and they recommended further refinement of case definitions focusing on a small set of core symptoms. Finally, based on a review of all criteria, they noted some of the disadvantages of polythetic case definitions that include patients on the basis that they experience a certain number of listed symptoms, many of which are ubiquitous and do not allow clinicians to differentiate between CFS and other disorders.[1,8,9]

[1] Jason LA, Sunnquist M, Brown A, Evans M, Vernon, SD, Furst JD, Simonis, V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue: Biomed Health Behav. Epub 2013 Dec 11. Available from: http://dx.doi.org/10.1080/21641846.2013.862993

[2] Brown AA, Jason LA, Evans MA, Brown M, Flores S. Contrasting case definitions: The ME international consensus criteria vs. the Fukuda et al. CFS criteria. North Am J Psychol. 2013;15(1):103–120.

[3] Shepherd C. Living with M.E. 2nd ed. London: Cedar; 1992.

[4] Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis a persistent enteroviral infection? Postgrad Med J, 1990;66:526 530.

[5] Smith DG. Understanding M.E. The phenomenon of myalgic encephalomyelitis and acute onset post viral fatigue syndrome. London: Robinson Publishing; 1989. p. 184-185.

[6] Dowsett EG, Welsby PD. Conversation Piece. Postgrad Med J. 1992; 68:63-65.

[7] Yeomans JDI, Conway SP. Biopsychosocial aspects of chronic fatigue syndrome (myalgic encephalomyelitis). J Infect. 1991;23:263-269.

[8] King C, Jason LA. Improving the diagnostic criteria and procedures for chronic fatigue syndrome. Biol Psychol. 2005;68: 87-106.

[9] Goudsmit E, Shepherd C, Dancey CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33.

On 2014 Oct 10, Ellen M Goudsmit commented:

Case definitions should also recognise the progressive form of the disease.

Howes and Goudsmit (submitted) suggest that :

A diagnosis of progressive ME is supported by the following:

1. Sudden increase in sensitivities and gastro-intestinal symptoms.
2. Sudden worsening of existing neurological symptoms or new symptoms, e.g. blurred vision in one eye, weakness in one leg, incontinence.<br>
3. Improvements are limited, disability tends to show a downwards trend.
4. Patient has to spend more time at home or in bed.
5. New auto-immune diseases e.g. symptoms consistent with Sjogren’s syndrome.

Supportive evidence of pathology:

MRI, abnormal white matter lesions not indicative of MS.