Clinical Working Case Definition of ME/CFS from the Canadian Expert Consensus Document

A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendrocrine, and immune manifestations; and adhere to item 7.

1. Fatigue: The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity levels.

2. Post-Exertional Malaise and/or Fatrigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertional malaise' and/or fatigue and/or pain and a tendency for other associated symptoms within the patient's cluster of symptoms to worsen. There is a pathologically slow recovery period - usually 24 hours or longer.

3. Sleep Dysfunction: There is unrefreshed sleep or sleep quality or rhythm disturbances such as reversed or chaotic diurnal sleep rythms.

4. Pain: There is a significant degree of myalgia. Pain can be experienced in the muscles, and/or joints, and is often widespread and migratory in nature. Often there are significant headaches of a new type, pattern or severity.

5. Neurological/Cognitive Manifestations: Two or more of the following difficulties should be present:

6. At least one symptom from two of the following categories:

a. Autonomic Manifestations: orthostatic intolerance - neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension; light-headedness; exreme pallor; nausea and irritable bowel syndrome; urinary frequency and bladder dysfunction; palpitations with or without cardiac arrythmias; exertional dyspnea.

b. Neuroendocrine Manifestations: loss of thermostatic stability - subnormal body temperature and marked diurnal fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities; intolerance of extremes of heat and cold; marked weight change - anorexia or abnormal appetite; loss of adaptibility and worsening of symptoms with stress.

c. Immune Manifestations: tender lymph nodes, recurrent sore throat, recurrent flu-like symptoms, general malaise, new sensitivities to food, medications and/or chemicals.

7. The illness persists for at least six months: It usually has a distinct onset, although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for children.


To be included, the symptoms must have begun or have been significantly alered after the onset of this illness. It is unlikely that a patient will suffer from all symptoms in criteria 5 & 6. The disturbances tend to form symptom clusters that may fluctuate and change over time. Children often have numerous prominent syptoms but their order of severity tends to vary from day to day. There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset. Some patients have been unhealthy for other reasons prior to the onset of ME?CFS and lack detectable triggers at onset or have ore gradual or insidious onset.


Exclusions: Exclude active disease processes that explain most of the major symptoms of fatigue, sleep disturbance, pain, and cognitive dysfunction. It is essential to exclude certain diseases, which would be tragic to miss: Addison's disease, Cushing's Syndrome, hypothyroidism, hyperthyroidism, iron deficiency, other treatable forms of anemia, iron overload syndrome, diabetes mellitus, and cancer. It is also essential to exclude treatable sleep disorders such as upper airway resistance syndrome and obstructive or central sleep apnea; rheumatlogical disorders such as rheumatoid arthritis, lupus, poliomyositis and polymyalgia rheumatica; immune disorders such as AIDS; neurological disorders such as multiple sclerosis (MS), Parkinsonism, myesthenia grais and B12 deficiency; infectious diseases such as tuberculosis, chronic hepatitis, Lyme disease, etc.; primary psychiatric disordders and substance abuse. Exclusion of other diagnoses, which cannot be reasonably excluded by the patient's history and physical examination, is achieved by laboratory testing and imaging. If a potentially confounding medical condition is under control, then the diagnosis of ME/CFS can be entertained if patients meet the criteria otherwise.


Co-morbid Entities: Fibromyalgia Syndrome (FMS), Myofascial Pain Syndrome (MPS), Temporomandibular Joint Syndrome TMJ), Irritable Bowel Syndrome IBS), Interstitial Cystitis, Irritable Bladder Syndrome, Raynaud's Phenomenon, Prolapsed Mitral Valve, Depression, Migraine, Allergies, Multiple Chemical Sensitivities (MVS), Hashimoto's thyroiditis, Sicca Syndrome, etc. Such co-morbid entities may occur in the setting of ME/CFS. Others such as IBS may precede the development of ME/CFS by many years, but then beome associated with it. The same holds true for migraines and depression. Their association is thus looser than between the symptoms within the syndrome. ME/CFS and FMS often closely connect and should be considered to be "overlap syndromes".


Idiopathic Chronic Fatigue: If the patient has unexplained prolonged fatigue (6 months or more) but has insufficient symptoms to meet the criteria for ME/CFS, classify it as ideopathic chronic fatigue.


Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, van de Sande ME. MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Jornal of Chronic Fatigue Syndrome 11 (1):7-116, 2003.


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