Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms

Table 1 International Consensus Criteria for myalgic encephalomyelitis[18]

Post-exertional neuro-immune exhaustion:

A pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions

Neurological impairments

At least one symptom from three of the following four symptom categories: Cognitive impairments (information processing and short-term memory)

Pain (e.g., headache, muscle, joint, abdominal and/or chest pain)

Sleep disturbance (disturbed sleep patterns and unrefreshing sleep)

Neurosensory, perceptual and motor disturbances

Immune, gastro-intestinal and genitourinary impairments

At least one symptom from three of the following five symptom categories:

Flu-like symptoms, e.g., sore throat and tender lymph nodes

Susceptibility to viral infections with prolonged recovery periods

Gastro-intestinal tract complaints, e.g., irritable bowel syndrome

Genitourinary complaints: e.g., nocturia

Sensitivities to food, medications, odours or chemicals

Energy production and - transportation impairments

At least one of the following four symptoms:

Cardiovascular symptoms, e.g., (delayed) orthostatic intolerance

Respiratory problems, e.g., air hunger and fatigue of chest wall muscles

Loss of thermostatic stability, e.g., sweating episodes or feverish feeling

Intolerance of extremes of temperature

Table 2 Fukuda et al[19] Diagnostic Criteria for chronic fatigue syndrome

Primary symptom:

Clinically evaluated, unexplained, persistent or relapsing chronic fatigue

That is of new or definite onset; is not the result of ongoing exertion

That is not substantially alleviated by rest; and

That results in substantial reduction in previous levels of occupational, educational, social, or personal activities

Secondary symptoms:

The concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue:

Self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities

Sore throat

Tender cervical or axillary lymph nodes

Muscle pain

Multi-joint pain without joint swelling or redness

Headaches of a new type, pattern, or severity

Unrefreshing sleep

Post-exertional malaise lasting more than 24 h

Table 3 Empirical case definition for chronic fatigue (syndrome)[47]

Fatigue:

A score

≥ 13 (out of 20) on the general fatigue or

≥ 10 (out of 20) on the reduced activity

subscales of the multidimensional fatigue inventory[56]

Functional impairment:

A score

≤ 70 (out of 100) on the physical function, or

≤ 50 (out of 100) on role physical, or

≤ 75 (out of 100) on the social function, or

≤ 66.7 (out of 100) on the role emotional

subscales of the medical outcomes survey short form-36 (SF-36)[11]

Secondary symptoms:

≥ 4 of the following 8 symptoms:

Impaired memory or concentration

Unrefreshing sleep

Headaches

Muscle pain

Joint pain

Sore throat

Tender cervical nodes and

Unusual post exertional fatigue

And A score of ≥ 25 (out of 128)

On the Symptom Inventory Case Definition subscale[57]

Table 4 Symptoms and tests to assess the disability in myalgic encephalomyelitis/chronic fatigue syndrome objectively

Symptoms	Tests	Ref.
Lack of energy: physical weakness and ”fatigue”	CPET 1: workload and oxygen uptake at exhaustion and at the anaerobic threshold	[62,63]
Cognitive impairment	Specific neuropsychological tests	[64-67]
Post-exertional "malaise”
Physical effects	Repeated CPETs 1, 24 h apart
Cognitive effects	Specific neuropsychological tests
	before and after a CPET or
	before and during a tilt table test
	Repeated neuropsychological tests
Muscle weakness	Examination of the muscles (power, endurance, recovery)	[68-71]
Orthostatic intolerance	Tilt-table test	[72-74]
Defective stress response	Hormonal investigation (HPA axis, thyroid) in rest, at specific moments, e.g., at wakening, and during the day, after provocation, e.g., by adrenocorticotropic hormone and insulin, and in response to an exercise test or psychological stress test	[75-78]
Sleep impairment	Polysomnographic investigation (EEG)	[79-81]
	Maintenance of wakefulness test	[79,82,83]
	Multiple sleep latency test	[79,82,83]
Visual symptoms	Useful field of view tests	[84,85]
	Eye movement tests	[86,87]

CPET: Cardiopulmonary exercise test.

Table 5 Adverse effects of a CPET (CPET1) on the performance levels at a second CPET (CPET2) 24 h later: An example

	CPET Day 1	CPET Day 2
Rest
Heart rate	88	80
Oxygen uptake (VO2min)	6	6
Anaerobic threshold
Heart rate (HR AT)	105	89
Oxygen uptake (VO2 AT)	11	9
Workload (W AT)	54	35
Exhaustion
Heart rate (HRmax)	151	131
Oxygen uptake (VO2max)	23	22
Workload (Wmax)	159	133

CPET: Cardiopulmonary exercise testing.

Table 6 Manifestations of orthostatic cardiovascular abnormalities

Abnormality	Definition
Orthostatic systolic hypotension	A fall in the systolic blood pressure of 20 mmHg or more[74,193]
Orthostatic diastolic hypotension	A fall in the diastolic blood pressure of 10 mmHg or more[74,193]
Orthostatic diastolic hypertension	A rise in dBP to 98 mmHg or more[74]
Orthostatic postural tachycardia	An increase in heart rate of 28[74]/30[194] beats per minute (bpm) or a pulse of more than 110[74]/120[194] bpm
Orthostatic narrowing of pulse pressure	A fall in the pulse pressure to 18 mmHg or less[74]