Nightingale definition

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The Nightingale definition is a definition of Myalgic Encephalomyelitis that was published in 2007 by the Nightingale Research Foundation.

Authors[edit]

Byron Hyde

Definition[edit]

Primary M.E. is a chronic disabling, acute onset biphasic epidemic or endemic (biphasic) infectious disease process affecting both children and adults. There are both central and peripheral aspects to this illness.[1]

A) The Central Nervous System (CNS) symptoms, as well as the clinical and technological abnormalities, are caused bya 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 patho-physiological 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, and
(b) The technological examinations that confirm to the physician proof of his diagnosis.

Clinical Features[edit]

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 (sporadic) infectious disease process[edit]

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 such as:

  1. repetitive contact with a large number of infectious persons,
  2. unusually long hours of exhausting physical and / or intellectual work,
  3. physical traumas,
  4. immediate past immunizations, particularly if given when the patient has concurrent allergic or autoimmune or infectious disease or if the patient is leaving for a third world country within three weeks of receiving the immunization,
  5. epidemic disease cases whose onset and periodicity appear to occur cyclically in a susceptible population,
  6. the effect of travel, as in exposure to a new subset of virulent infections, or
  7. the effects of starvation diets.

(It should be noted that subsets c, d, e, f and g are all stressors associated with decreased immune adaptability plus an associated infection with an appropriate neurovascular infectious virus or other infectious agent. This may be due either to an immediate preexisting infectious disease or to a closely following infection, either of which may or may not be recognized.)

2. Primary Infection Phase[edit]

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. (See Clinical and Scientific Basis of M.E./CFS, Chapter 13, pps. 124-126)

3. Secondary Chronic Phase[edit]

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[edit]

The pain syndromes associated with the acute and chronic phases of M.E. may be described as Early and Late findings.

Early Findings:

  1. severe headaches of a type never previously experienced;
  2. these are often associated with neck rigidity and occipital pain;
  3. retro-orbital eye pain;
  4. migratory muscle and arthralgia pain;
  5. cutaneous hypersensitivity.

Late Findings: Any of the early findings plus:

  1. 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 & chemical stressors. (See Clinical and Scientific Basis of M.E./CFS, Chapter 5, pps. 58-62)

Testable & Non-testable Criteria[edit]

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[edit]

If the patient’s illness is not measurable using a dedicated brain SPECT scan such as a Picker 3000 or equivalent, then the patient does not have M.E. For legal purposes these changes may be confirmed by PET brain scans with appropriate software and /or QEEG. These changes can be roughly characterized as to severity and probable chronicity using the following two scales: A) Extent of injury and B) degree of injury of CNS vascular function.

Extent of Injury
Type 1: One side of the cortex is involved. Those patients labeled as 1A have the best chance of recovery.
Type 2: Both sides of the cortex are involved. These patients have the least chance of spontaneous recovery.
Type 3: Both sides of the cortex, and either one or all of the following: posterior chamber organs, (the pons and cerebellum), limbic system, the subcortical and brainstem structures are involved. Type 3B are the most severely affected patients and the most likely to be progressive or demonstrate little or no improvement with time.
Degree of injury
Type A: Anatomical integrity is largely maintained in the Brain SPECT scan.
Type B: Anatomical integrity is not visible in the CNS SPECT scan. Type 3B are some of the most severely and chronically injured patients.

6. Testable Neuropsychological Changes[edit]

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. Neuropsychological changes must be measured in relation to estimates of prior achievement. This feature may improve over a period of years in patients with adequate financial and social support and can be made worse by chronic stressors.

The neurophysiological changes are those observed by a qualified Neuropsychologist with experience in examining this type of disease spectrum. Some of the deficits that a Neuropsychologist should consider examining include:

  1. word finding problems,
  2. Subtle problems with receptive and expressive aphasia,
  3. Decreased concentration,
  4. Distractibility and the decreased ability to process multiple factors simultaneously,
  5. Dyscalculia,
  6. Decreased fine and gross motor problems,
  7. Dysfunction of spatial perception,
  8. Abstract reasoning,
  9. Compromised visual discrimination,
  10. Sequencing problems.

In Cochran’s Q Neuropsychological tests there is an increased observation of significant problems in both immediate and delayed verbal recall. In Dr Sheila Bastien’s investigations, over 50% of M.E. patients have delayed visual recall, TAP dominance, TPT N-Dominance and 40% or more have abnormalities of Immediate visual recall, Tap N-Dom, Grip N Dominance, & grip dominance problems. (Bastien, Sheila. The Clinical and Scientific Basis of M.E. / CFS. Chapter 51, pps. 453-460)

7. Testable Major Sleep Dysfunction[edit]

This can include all forms of sleep dysfunctions. All or any of the following may be present:

  1. impaired sleep efficiency,
  2. significant fragmented sleep architecture,
  3. movement arousals, particularly if there is an associated pain syndrome,
  4. absence or significant decrease of type 3 and 4 sleep,
  5. abnormal REM sleep pattern
  6. changes in daytime alertness and
  7. sleep reversals.

8. Testable Muscle Dysfunction[edit]

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. Few centres are equipped or funded to make these examinations. Unfortunately only a few major medical centres are equipped to study this type of dysfunction.

9. Testable Vascular & Cardiac Dysfunction[edit]

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 brain scans and clinically most evident in patients with:

a) POTS: severe postural orthostatic tachycardia syndrome.
Note: This group can be confused with diabetes insipidus due to the fact that they may have polydipsia from their attempt to increase their circulating blood volume by consuming large amounts of fluids. This group can be verified by the absence of pituitary adenoma or pathology and the fact that they can sleep through the night without waking to drink fluids. (Streeten, David)
Despite the great steps forward in the understanding of this relatively common pathophysiology seen routinely in M.E. patients, a pathology which is really related to either an autonomic injury to the CNS, injury to the vascular receptors or both, very little of the present treatment protocol is of much use. The situation is so bad that few major centres have any well-funded expertise in either autonomic or vascular receptor injury. Many of the M.E. patients that are dismissed by physicians as suffering from lack of activity have significant proprioceptive injuries in these areas. Nor can we always rely on the few autonomic laboratories and their tilt table testing abilities. Many of the tilt table examination reports return as normal, many as grossly abnormal. Yet all the physician has to do is have each M.E. patient stand for 8-12 minutes to realize that a large number of these normal tilt table patients simply cannot maintain a normal blood pressure and normal heart rate. Compare this to non-M.E. patients and one immediately can tell the difference. A large number of M.E. patients have significant autonomic difficulties.
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. (Hyde, B., Chapter on Cardiac Aspects): (Montague, T.,) Cardiac irregularity is closely related to the above discussion. In many M.E. patients there is an unusual daytime tachycardia, particularly since these patients are often very sedentary. In doing a 24-hour Holter monitor this may be missed since the 24 hour average is usually given. One should always ask for wake time and sleep time heart rates.
c) Raynaud’s Phenomenon: vasoconstriction of small arteries or arterioles of extremities, with change in colour of the skin, pallor and cyanosis. It is associated with coldness and pain of extremities. This is in part, the cause for temperature and pain dysfunctions seen in M.E. This phenomenon is found in many other conditions than M.E. Some of the associations are post-traumatic, neurogenic conditions, occlusive arterial diseases, toxic chemical associations and a wide range of rheumatoid conditions. Many of these conditions have associations with M.E. (See Magallni, S. for more detail.)
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. These patients do not generally have aenemia and are not blood deficient. 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. I have heard physicians repeatedly tell the patient they are not aenemic and therefore dismiss this important finding.
Note: So where does the blood go? Body servomechanisms are genetically designed so that blood flow and oxygen to the heart are always protected. Thus, when the body of the M.E. patient is stressed, the blood flow to organs not necessary for short-term survival, such as the brain, the gut and skeletal muscles, can be temporarily decreased. This of course gives rise to many of the M.E. symptoms.
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: This is a group of illnesses with a genetic predisposition to M.E. or M.E.- like illness. In fact it probably represents a spectrum of illnesses that start with (i) hyper-reflexia syndrome, moving through any of the (ii) various Ehlers-Danlos Syndromes and climaxing in (iii) Marfan Syndrome where there tends to be early death if the aortic and cardiac changes are not repaired. Ehlers-Danlos syndromes can go undetected until what appears to be a switch is turned on, usually in late teens to early thirties. The “switch” may be viral or possibly age or hormonal related. Raynaud’s phenomenon is usually associated.
Diagnosis: briefly, patients over the age of 16 who can (i) touch their nose with their tongue, (ii) touch their forearm with the thumb of the same extremity (joint laxity), (iii) touch the floor readily with the full palm should be considered suspect for further examination. There are several fascination variations of Ehlers-Danlos. They are generally considered to be a group of genetic illnesses but in my examination of M.E. patients most often are not manifested until well past puberty and in adulthood. Additional generalized features of this spectrum of illnesses include (v) India rubber or hyperelastic skin, (vi) easy bruisability (vascular fragility), (vii) Arachnodactyly (long spiderlike fingers). Many of the patients with a more severe form tend to be tall, slender with a dolichocephalic skull, high palate and long narrow feet with hammertoes verging on Marfan syndrome. (See Magalini, S. I., Magalini S. C. for both E-D Syndrome and Marfan 1 and Marfanoid hypermobility.)
g) Persantine Effect in M.E. Patients: Persantine is a chemical manufactured by Boehringer Ingelheim. It is employed to perform chemical cardiac stress testing when a patient cannot exercise sufficiently to stress the heart. It is a particularly safe medication but when employed with many M.E. patients it can cause severe muscle pain over the extremities and entire musculature. Normally this can be reversed by injection of an antidote but this does not always work rapidly in M.E. patients. Severe pain and fatigue can be intolerable and persist for minutes to days in some M.E. patients following Persantine use. Persantine works by dilating both peripheral and cardiac blood vessels and causing the heart rate to increase as in a POTS patient. Obviously one major pain and fatigue factor in M.E. patients is caused by abnormal dilatation of peripheral blood vessels. The resulting pain may be related to reflex vasospasm as in severe Raynaud’s phenomenon that I note elsewhere is one of the causes of M.E. pain. To my knowledge, no testing of M.E. patients with Persantine has ever been published by Boehringer Ingelheim or others. It is one of the reasons I believe that pain syndromes in M.E. patients are due to a pathological vascular physiology.
h) M.E. Associated Clotting Defects: M.E. represents both a vasculitis and a central and peripheral change in vascular physiology. All such vascular illnesses should be potentially treatable. We do not yet know how to adequately treat the (i) genetic forms of vasculitis & vascular patho-physiology mentioned here, nor (ii) the probable viral triggered genetic vascular pathologies also mentioned. Nor do we know how to treat those (iii) centrally caused injuries causing the circulating blood volume defects that are demonstratedwhen we do the “nuclear medicine circulating blood volume tests. It is important to do this test on all patients. POTS is poorly treatable and more often success in treatment presently escapes physicians’ ability. Eventually, I have no doubt that these will be treatable causes of M.E. type disease. However there is a significant group of M.E. patients who are ill due to a treatable form of vasculitis and can be treated if the physician takes the time to diagnose the subgroup. These patients are the clotting defect patients. Some of these clotting defects are genetic and some appear to be genetic with an age or viral switching mechanism, as I have mentioned elsewhere with Ehlers Danlos Syndromes; although they may develop in childhood, they are more frequently noted well after puberty and before the age of 40. Many of these patients can be diagnosed by the following tests: (1) Serum viscosity test, (2) Antiphospholipid Ab., (3) Protein C defects, (4) Protein S defects, (5) Factor V Leiden defect, to name the most common that we have uncovered. However, there are others for which we also test. These conditions are all potentially treatable and when treated adequately may allow the patient to return to school or work. Although any physician can order these tests, a haematologist should review all M.E. patients for these and other possible clotting anomalies. Most clotting defects are treatable and treatment has resulted in recovery in some cases. Remember M.E. is essentially a problem of microcirculation and any improvement in this area can have dramatically positive effects. It is well worthwhile for all physicians reading this definition who have an interest in M.E. to examine the Internet for Hughes Syndrome. Curiously, Hughes Syndrome was first outlined in St. Thomas’ Hospital London, the home of the Nightingale School of Nursing. Hughes Syndrome, a vascular syndrome also called Sticky Blood Syndrome, closely parallels the definition of M.E.
i) Anti-smooth muscle Antibodies: This is an antibody to the muscle tissue in the arterial bed. It is elevated in about 5% of M.E. patients but whether this is different in non-M.E. patients is unknown but unlikely. It rarely is over 1:40.
j) Cardiac Dysfunction: There are a large number of cardiac dysfunctions that can regularly appear in an M.E. patient. Certain are obvious and discussed under Ehlers-Danlos Syndrome and Marfan syndrome. I also discussed cardiac dysfunction in Chapter 42, The Clinical and Scientific Basis of M.E./CFS. Since that chapter was written a large number of other cardiac pathologies and pathophysiologies have been noted by various researchers and clinicians, particularly by Dr. Paul Cheney. Without a clear understanding of these significant problem areas it is simply indefensible and potentially dangerous to place an unsuspecting patient in a graduated exercise program. This is particularly true if the patient is not being tested in a cardiac unit. Although in our clinic we have performed what we believe to be a complete cardiac assessment on all patients seen, what the Ottawa Cardiac Institute and I believed was a complete assessment may be wanting. Over the next year we will reassess these patients with a more detailed cardiac examination and report on it in these diagnostic criteria.

10. Testable Endocrine Dysfunction[edit]

These features are common and tend to be of late appearance. They are most obvious in:

a) Pituitary-Thyroid Axis: Changes in serum TSH, FT3, FT4, Microsomal Ab., PTH, calcium and phosphorous rarely occur until several years after illness onset. This anomaly can best be followed by serial ultrasounds of the thyroid gland, where a steady shrinking of the thyroid gland may occur in some M.E. patients with or without the development of non-serum positive Hashimoto’s thyroiditis (a seeming contradiction in terms) and a significant increase in thyroid malignancy. In cases of thyroid wasting, serum positive changes tend to occur only after years and often not until the thyroid gland shrinks from the normal 13 to 21 cc. volume in an average adult female and 15-23 cc. volume in male patients to below a volume of 6 cc. (Mayo Clinic averages) (Rumack, Carol). The normal serum analysis of patients for thyroid dysfunction, TSH, FT4, microsomal antibodies etc., the golden rule of most physicians and endocrinologists, is simply not an adequate means of ascertaining thyroid dysfunction in most M.E. patients. Repeat thyroid ultrasound must be performed for all M.E. patients to observe the presence of dystrophic changes. It is also inadequate simply to accept the radiologist’s report of a normal thyroid. The volume of each lobe and its homogenicity must be requested and documented. Radiologists simply report normal thyroids when in effect they are hypo and hyper-trophic. Although the Mayo Clinic averages cited above may be criticized they are as good as any in ascertaining normal thyroid size.

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: This dysfunction occurs frequently in the early and in chronic disease in some people. In some instances this may be due to a form of diabetes insipidus, in other cases it is related to POTS-type illness where the patient is compensating for the inability to maintain vascular pressure by attempting to increase fluid volume. In other cases this may be due to interstitial cystitis or a form of polio-type-bladder particularly if the cause of the individual disease is an enterovirus. Dr. John Richardson also associated this finding with adrenal dysfunction that he measured.

Criticism[edit]

Learn more[edit]

See also[edit]

References[edit]

  1. This Nightingale Research Foundation’s Definition will be available with any updates or corrections, on the Nightingale Research Foundation’s Website, http://www.nightingale.ca 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. Nightingale ME Full Definition (pdf)


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