International Consensus Criteria

The Myalgic Encephalomyelitis International Consensus Criteria is a medical case definition.

Authors
Bruce Carruthers, Marjorie van de Sande, Kenny de Meirleir, Nancy Klimas, Gordon Broderick, Terry Mitchell, Donald Staines, A C Peter Powles, Nigel Speight, Rosamund Vallings, Lucinda Bateman, Barbara Baumgarten-Austrheim, David Bell, Nicoletta Carlo-Stella, John Chia, Austin Darragh, Daehyun Jo, Donald Lewis, Alan Light, Sonya Marshall-Gradisnik, Ismael Mena, Judy Mikovits, Kunihisa Miwa, Modra Murovska, Martin Pall, and Staci Stevens

Criteria
A patient will meet the criteria for postexertional neuroimmune exhaustion (A), at least one symptom from three neurological impairment categories (B), at least one symptom from three immune/gastro-intestinal/genitourinary impairment categories (C), and at least one symptom from energy metabolism/transport impairments (D).

A. Postexertional neuroimmune exhaustion (PENE pen’-e): Compulsory
This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:


 * 1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
 * 2. Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
 * 3. Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
 * 4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.
 * 5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

Operational notes: ''For a diagnosis of ME, symptom severity must result in a significant reduction of a patient’s premorbid activity level. Mild (an approximate 50% reduction in pre-illness activity level), moderate (mostly housebound), severe (mostly bedridden) or very severe (totally bedridden and need help with basic functions). There may be marked fluctuation of symptom severity and hierarchy from day to day or hour to hour. Consider activity, context and interactive effects. Recovery time: e.g. Regardless of a patient’s recovery time from reading for ½ hour, it will take much longer to recover from grocery shopping for ½ hour and even longer if repeated the next day – if able. Those who rest before an activity or have adjusted their activity level to their limited energy may have shorter recovery periods than those who do not pace their activities adequately. Impact: e.g. An outstanding athlete could have a 50% reduction in his/her pre-illness activity level and is still more active than a sedentary person.''

B. Neurological impairments
At least one symptom from three of the following four symptom categories

1. Neurocognitive impairments

 * a. Difficulty processing information: slowed thought, impaired concentration e.g. confusion, disorientation, cognitive overload, difficulty with making decisions, slowed speech, acquired or exertional dyslexia
 * b. Short-term memory loss: e.g. difficulty remembering what one wanted to say, what one was saying, retrieving words, recalling information, poor working memory

2. Pain

 * a. Headaches: e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; migraine; tension headaches
 * b. Significant pain can be experienced in muscles, muscle-tendon junctions, joints, abdomen or chest. It is noninflammatory in nature and often migrates. e.g. generalized hyperalgesia, widespread pain (may meet fibromyalgia criteria), myofascial or radiating pain

3. Sleep disturbance

 * a. Disturbed sleep patterns: e.g. insomnia, prolonged sleep including naps, sleeping most of the day and being awake most of the night, frequent awakenings, awaking much earlier than before illness onset, vivid dreams/nightmares
 * b. Unrefreshed sleep: e.g. awaken feeling exhausted regardless of duration of sleep, day-time sleepiness

4. Neurosensory, perceptual and motor disturbances

 * a. Neurosensory and perceptual: e.g. inability to focus vision, sensitivity to light, noise, vibration, odour, taste and touch; impaired depth perception
 * b. Motor: e.g. muscle weakness, twitching, poor coordination, feeling unsteady on feet, ataxia

Notes: ''Neurocognitive impairments, reported or observed, become more pronounced with fatigue.Overload phenomenamay be evident when two tasks are performed simultaneously. Abnormal accommodation responsesof the pupils are common.Sleep disturbancesare typically expressed by prolonged sleep, sometimes extreme, in the acute phase and often evolve into marked sleep reversal in the chronic stage.Motor disturbancesmay not be evident in mild or moderate cases but abnormal tandem gait and positive Romberg test may be observed in severe cases.''

C. Immune, gastro-intestinal and genitourinary Impairments
At least one symptom from three of the following five symptom categories


 * 1. Flu-like symptoms may be recurrent or chronic and typically activate or worsen with exertion.e.g. sore throat, sinusitis, cervical and/or axillary lymph nodes may enlarge or be tender on palpitation
 * 2. Susceptibility to viral infections with prolonged recovery periods
 * 3. Gastro-intestinal tract: e.g. nausea, abdominal pain, bloating, irritable bowel syndrome
 * 4. Genitourinary: e.g. urinary urgency or frequency, nocturia
 * 5. Sensitivities to food, medications, odours or chemicals

Notes: ''Sore throat, tender lymph nodes, and flu-like symptoms obviously are not specific to ME but their activation in reaction to exertion is abnormal. The throat may feel sore, dry and scratchy. Faucial injection and crimson crescents may be seen in the tonsillar fossae, which are an indication of immune activation.''

D. Energy production/transportation impairments: At least one symptom

 * 1. Cardiovascular: e.g. inability to tolerate an upright position - orthostatic intolerance, neurally mediated hypotension, postural orthostatic tachycardia syndrome, palpitations with or without cardiac arrhythmias, light-headedness/dizziness
 * 2. Respiratory: e.g. air hunger, laboured breathing, fatigue of chest wall muscles
 * 3. Loss of thermostatic stability: e.g. subnormal body temperature, marked diurnal fluctuations; sweating episodes, recurrent feelings of feverishness with or without low grade fever, cold extremities
 * 4. Intolerance of extremes of temperature

Notes: ''Orthostatic intolerance may be delayed by several minutes. Patients who have orthostatic intolerance may exhibit mottling of extremities, extreme pallor or Raynaud’s Phenomenon. In the chronic phase, moons of finger nails may recede.''

Paediatric considerations
Symptoms may progress more slowly in children than in teenagers or adults. In addition to postexertional neuroimmune exhaustion, the most prominent symptoms tend to be neurological: headaches, cognitive impairments, and sleep disturbances.


 * 1. Headaches: Severe or chronic headaches are often debilitating. Migraine may be accompanied by a rapid drop in temperature, shaking, vomiting, diarrhoea and severe weakness.
 * 2. Neurocognitive impairments: Difficulty focusing eyes and reading are common. Children may become dyslexic, which may only be evident when fatigued. Slow processing of information makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people will not be able to maintain a full school programme.
 * 3. Pain may seem erratic and migrate quickly. Joint hypermobility is common.

Notes: Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically than in adults.

Classification
——— Myalgic encephalomyelitis

——— Atypical myalgic encephalomyelitis: meets criteria for postexertional neuroimmune exhaustion but has a limit of two less than required of the remaining criterial symptoms. Pain or sleep disturbance may be absent in rare cases.

Exclusions: As in all diagnoses, exclusion of alternate explanatory diagnoses is achieved by the patient’s history, physical examination, and laboratory/biomarker testing as indicated. It is possible to have more than one disease but it is important that each one is identified and treated. Primary psychiatric disorders, somatoform disorder and substance abuse are excluded. Paediatric: ‘primary’ school phobia.

Comorbid entities: Fibromyalgia, myofascial pain syndrome, temporomandibular joint syndrome, irritable bowel syndrome, interstitial cystitis, Raynaud’s phenomenon, prolapsed mitral valve, migraines, allergies, multiple chemical sensitivities, Hashimoto’s thyroiditis, Sicca syndrome, reactive depression. Migraine and irritable bowel syndrome may precede ME but then become associated with it. Fibromyalgia overlaps.

Background and purpose
The 2012 ICC is very clear on the topic of names:

Problem

The label ‘chronic fatigue syndrome’ (CFS), coined in the 1980s, has persisted due to lack of knowledge of its etiologic agents and pathophysiology. Misperceptions have arisen because the name ‘CFS’ and its hybrids ME/CFS, CFS/ME and CFS/CF have been used for widely diverse conditions. Patient sets can include those who are seriously ill with ME, many bedridden and unable to care for themselves, to those who have general fatigue or, under the Reeves criteria, patients are not required to have any physical symptoms. There is a poignant need to untangle the web of confusion caused by mixing diverse and often overly inclusive patient populations in one heterogeneous, multi-rubric pot called ‘chronic fatigue syndrome’. We believe this is the foremost cause of diluted and inconsistent research findings, which hinders progress, fosters scepticism, and wastes limited research monies.

Solution

The rationale for the development of the ICC was to utilize current research knowledge to identify objective, measurable and reproducible abnormalities that directly reflect the interactive, regulatory components of the underlying pathophysiology of ME. Specifically, the ICC select patients who exhibit explicit multi-systemic neuropathology, and have a pathological low threshold of physical and mental fatigability in response to exertion. Cardiopulmonary exercise test- retest studies have confirmed many post-exertional abnormalities. Criterial symptoms are compulsory and identify patients who have greater physical, cognitive and functional impairments. The ICC advance the successful strategy of the Canadian Consensus Criteria (CCC) of grouping coordinated patterns of symptom clusters that identify areas of pathology. The criteria are designed for both clinical and research settings.

1. Name: Myalgic encephalomyelitis, a name that originated in the 1950s, is the most accurate and appropriate name because it reflects the underlying multi-system pathophysiology of the disease. Our panel strongly recommends that only the name ‘myalgic encephalomyelitis’ be used to identify patients meeting the ICC because a distinctive disease entity should have one name. Patients diagnosed using broader or other criteria for CFS or its hybrids (Oxford, Reeves, London, Fukuda, CCC, etc.) should be reassessed with the ICC. Those who fulfill the criteria have ME; those who do not would remain in the more encompassing CFS classification. (bold emphasis mine)

2. Remove patients who satisfy the ICC from the broader category of CFS. The purpose of diagnosis is to provide clarity. The criterial symptoms, such as the distinctive abnormal responses to exertion can differentiate ME patients from those who are depressed or have other fatiguing conditions. Not only is it common sense to extricate ME patients from the assortment of conditions assembled under the CFS umbrella, it is compliant with the WHO classification rule that a disease cannot be classified under more than one rubric. The panel is not dismissing the broad components of fatiguing illnesses, but rather the ICC are a refinement of patient stratification. As other identifiable patient sets are identified and supported by research, they would then be removed from the broad CFS/CF category.

Research on ME: The logical way to advance science is to select a relatively homogeneous patient set that can be studied to identify biopathological mechanisms, biomarkers and disease process specific to that patient set, as well as comparing it to other patient sets. It is counterproductive to use inconsistent and overly inclusive criteria to glean insight into the pathophysiology of ME if up to 90% of the research patient sets may not meet its criteria (Jason 2009). Research on other fatiguing illnesses, such as cancer and multiple sclerosis (MS), is done on patients who have those diseases. There is a current, urgent need for ME research using patients who actually have ME. (bold emphasis mine)

4. Research confirmation: When research is applied to patients satisfying the ICC, previous findings based on broader criteria will be confirmed or refuted. Validation of ME being a differential diagnosis, as is multiple sclerosis (MS), or a subgroup of chronic fatigue syndrome, will then be verified.

5. Focus on treatment efficacy: With enhanced understanding of biopathological mechanisms, biomarkers and other components of pathophysiology specific to ME, more focus and research emphasis can target expanding and augmenting treatment efficacy.

International Consensus Primer (ICP)
Problem

Overly inclusive criteria have created misperceptions, fostered cynicism and have had a major negative impact on how ME is viewed by the medical community, patients, their families, as well as the general public. Some medical schools do not include ME in their curriculum with the result that very significant scientific advances and appropriate diagnostic and treatment protocols have not reached many busy medical practitioners. Some doctors may be unaware of the complexity and serious nature of ME. Patients may go undiagnosed and untreated; they may be shunned or isolated.

World Health Organisation
The World Health Organisation (WHO) lists ME and post viral fatigue syndrome under neurological conditions. The diagnostic code is G93.3 Importantly, it doesn’t include chronic fatigue syndrome there, or ME/CFS or CFS/ME. Fatigue syndromes are listed in "Other neurotic disorders."

Comparison with other criteria

 * Norwegian researchers compare the main criteria (Oxford, Fukuda, Canadian, International Consensus and SEID). They say "it is important to distinguish between myalgic encephalomyelitis and chronic fatigue syndrome” to improve understanding of the disease, treatment and patients’ lives, as using incorrect criteria can lead to incorrect treatment.


 * 'Scientists must agree on classifying patients’ Leonard Jason


 * Frank Twisk explains that ME and CFS are "distinct, partially overlapping, clinical entities such as ME and CFS"Frank Twisk 2016
 * Cae2BaLVAAEVfnn.jpg-large.jpg

Learn more

 * MEAdvocacy - The International Consensus Criteria: What is it? Do I fit the criteria?