Excerpts from:

The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)

"...what this definition does today is (a) separate clearly M.E. from CFS and (b) demonstrate that M.E. is an early diagnosable and provable disease - as are all true diseases, and (c) assist in the early treatment and cure of M.E. patients."
-Dr. Byron Hyde-

Primary M.E. is an acute onset biphasic infectious disease process, where there is always a measurable and persistent diffuse vascular injury of the Central Nervous System in both the acute and chronic phases. Primary M.E. is associated with immune and other pathologies.

Primary M.E. is a chronic disabling, acute onset biphasic epidemic or endemic infectious disease process affecting both children and adults. There are both central and peripheral aspects to this illness.

A: The Central Nervous System (CNS) symptoms, as well as the clinical and technological abnormalities, are caused by a diffuse and measurable injury to the vascular system of the Central Nervous System. These changes in the organization of the CNS are caused by a combined infectious and immunological injury and their resulting effect on CNS metabolism and control mechanisms. Much of the variability observed in an M.E. patient’s illness is due to the degree and extent of the CNS injury and the ability of the patient to recover from these injuries.

B: A significant number of the initial and long-term peripheral or body symptoms, as well as clinical and technological body abnormalities in the M.E. patient, are caused by variable changes in the peripheral and CNS vascular system. The vascular system is perhaps the largest of the body’s organs and both its normal and pathological functions are in direct relationship to CNS and peripheral vascular health or injury, to CNS control mechanisms and to the difficulty of the peripheral vascular system and organs to respond to CNS neuro-endocrine and other chemical and neurological stimuli in a predictable homeostatic fashion.

C: When pain syndromes associated with M.E. occur, they are due to a combined injury of (i) the posterior spinal cord and / or posterior root ganglia and appendages, (ii) patho-physiological peripheral vascular changes, and (iii) CNS pain reception homeostasis mechanisms.

Depending upon the degree and extent of the ongoing CNS and peripheral vascular injuries, these patho-physiological changes in turn may give rise to both transient and in many cases permanent systemic organ changes in the patient.

As with any illness, the diagnostic criteria of M.E. are divided into two sections:

(a) The clinical features and history of the ill patient that alert the physician to the initial diagnosis

(b) The technological examinations that confirm to the physician proof of the diagnosis.

Clinical Features

The clinical features of Myalgic Encephalomyelitis are consistent with the following characteristics that can easily be documented by the physician.

1. M.E. is an acute onset biphasic epidemic or endemic infectious disease:  Both
Epidemic and Non-Epidemic cases are often preceded by a series of repeated minor infections in a previously well patient that would suggest either a vulnerable immune system, or an immune system subject to overwhelming stressors.... [see details about the types of immune stressors in the complete version of The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)]

2. Primary Infection Phase: The first phase is an epidemic or endemic (sporadic) infectious disease generally with an incubation period of 4 to 7 days; in most, but not all cases, an infection or infectious process is evident.

3. Secondary Chronic Phase: The second and chronic phase follows closely on the first phase, usually within two to seven days; it is characterized by a measurable diffuse change in the function of the Central Nervous System. This second phase is the persisting disease that most characterizes M.E.

4. The Presence or Absence of Various Pain Syndromes is highly variable: The pain syndromes associated with the acute and chronic phases of M.E. may be described as Early and Late findings. Early Findings: (a) severe headaches of a type never previously experienced; (b) these are often associated with neck rigidity and occipital pain; (c) retro-orbital eye pain; (d) migratory muscle and arthralgia pain; (e) cutaneous hypersensitivity. Late Findings: Any of the early finding plus (f) fibromyalgia-like pain syndromes. This is only a partial list of the multiple pain syndromes. Many of the pain features tend to decrease over time but can be activated or increased by a wide range of external and chemical stressors.

Testable & Non-testable Criteria

The technological tests listed below can be used to (a) confirm the clinical diagnosis of Myalgic Encephalomyelitis and (b) to some degree gauge its severity and probability of persistence. The second and chronic phase that clearly defines M.E. is characterized by various measurable and clinical dysfunctions of the cortical and/or sub-cortical brain structures.

5. Diffuse Brain Injury Observed on Brain SPECT:  [see details about the types and degrees of brain injury in the complete version of The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)]

6. Testable Neuropsychological Changes: There are neuropsychological changes that are measurable and demonstrate short-term memory loss, cognitive dysfunctions, increased irritability, confusion, and perceptual difficulties. There is usually rapid decrease in these functions after any physical or mental activity. [see details about the types of neuropsychological changes in the complete version of The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)]

7. Testable Major Sleep Dysfunction: This can include all forms of sleep dysfunction. [see details about specific types of sleep dysfunction in the complete version of The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)]

8. Testable Muscle Dysfunction: This feature may be due to vascular dysfunction or peripheral nervous or spinal dysfunction and includes both pain and rapid loss of strength of muscle function after moderate physical or mental activity. This feature tends to improve over a period of years but many patients frequently remain permanently vulnerable to new disease episodes.  Unfortunately only a few major medical centres are equipped to study this type of dysfunction.

9. Testable Vascular Dysfunction: This is the most obvious set of dysfunctions when looked for and is probably the cause behind a significant number of the above complaints. All moderate to severe M.E. patients have one or more and at times multiple of the following vascular dysfunctions.  As noted, the primary vascular change is seen in abnormal SPECT scans and clinically most evident in patients with:

a. POTS: severe postural orthostatic tachycardia syndrome.
b. Cardiac Irregularity: on minor positional changes or after minor physical activity, including inability of the heart to increase or decrease in speed and pump volume in response to increase or decrease in physical activity.
c. Raynaud’s Phenomenon
d. Circulating Blood Volume Decrease:
this is a nuclear medicine test in which the circulating red blood cell levels in some M.E. patients can fall to below 50%, preventing adequate oxygenation to the brain, gut and muscles. This is undoubtedly a subcortical dysregulation. It is associated with serum and total blood volume measurements. This is a concept that many physicians have difficulty understanding.
e. Bowel Dysfunction:
vascular dysfunction may be the most significant causal basis of the multiple bowel dysfunctions occurring in M.E. (See d. above.)
f. Ehlers-Danlos Syndromes Group
g. Persantine Effect in M.E. Patients
h. M.E. Associated Clotting Defects

i.  Anti-smooth muscle Antibodies
j.  Cardiac Dysfunction:
 There are a large number of cardiac dysfunctions that can regularly appear in an M.E. patient.  Without a clear understanding of these significant problem areas it is simply indefensible and potentially dangerous to place and unsuspecting patient in a graduated exercise program. 

[More in-depth details about the testable vascular dysfunction in #9 above can be found in the complete version of The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)]

10. Testable Endocrine Dysfunction: These features are common and tend to be of late appearance. It is most obvious in:

a. Pituitary-Thyroid Axis 

The following changes, while uncommon, may also be related to an M.E.disease process:
b. Pituitary-Adrenal Axis Changes:
where changes and findings are infrequent.
c. Pituitary-Ovarian Axis Changes
d. Bladder Dysfunction Changes  

[More details about testable endocrine dysfunction in #10 can be found in the complete version of The Nightingale Definition of Myalgic Encephalomyelitis (M.E.)]

This Nightingale Research Foundation’s Definition will be available with any updates or corrections, on the Nightingale Research Foundation’s Website, This definition may be copied, translated, distributed by electronic or hard copy and may be included, in whole or in part in any publication without permission from the Nightingale Research Foundation or the authors, provided that this last paragraph and referral back to our website are noted.

Byron Marshall Hyde MD, Ottawa - January 29, 2007