http://www.nightingale.ca/documents/NightingalesDefinitionofME.pdf



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

Preface

Since the Nightingale Research Foundation's publication in 1992 of its
textbook, The Clinical and Scientific Basis of Myalgic Encephalomyelitis /
Chronic Fatigue Syndrome, there has been a tendency by some individuals
and organizations to assume that M.E. and CFS are the same illness. Over
the course of two International Association of Chronic Fatigue Syndrome
(IACFS, formerly the American Association of CFS) conferences, there
have been suggestions that the name CFS be changed to M.E., while
retaining the CFS definitions as a basis for such change. This does not
seem to me to be a useful initiative: it would simply add credence to the
mistaken assumption that M.E. and CFS represent the same disease
processes. They do not.

M.E. is a clearly defined disease process. CFS by definition has always
been a syndrome

At one of the meetings held to determine the 1994 U.S. Centers for Disease
Control and Prevention (CDC) definition of CFS, in response to my question
from the floor, Dr. Keiji Fukuda stated that numerous M.E. epidemics—he
cited the Los Angeles County Hospital epidemic of 1934, the Akureyri
outbreak of 1947-48 and the 1955-58 Royal Free Hospitals epidemics--
were definitely not CFS epidemics. Dr. Fukuda was correct.

The Psychiatric Label

Unfortunately many physicians and some senior persons in governments,
including Great Britain, Norway and to a lesser degree the USA and
Canada treat CFS as a psychiatric illness. This view has been arrived by
some physician's readings of the CFS definitions from CDC. Indeed,
despite clear signals in the 1994 CDC definition that CFS is not a
psychiatric disease, each of the CDC definitions and their addenda
referring to CFS remain open to interpretation as a psychiatric rather than a
physical illness. This is not a view to which I subscribe. It is the CFS
definitions themselves that give rise to this inaccuracy. Consider the
following:

(a) What other physical disease definitions essentially state that if you
discover the patient has any physical injury or disease, then the patient does
not have the illness CFS? In other words if you have CFS then it does not
result in or cause any major illness. What else could CFS then be but any
number of various psychiatric, social, hysterical or mendacious
phenomena?

(b) The various CDC administrations dealing with the subject have clearly
stated that CFS is a physical, not a psychiatric disease. However, is there
any other definition of any physical disease that is not provable by 
scientific
and clinical tests? Only psychiatric diseases are not clearly verifiable by
physical and technological tests.

(c) What other physical disease definition requires a six month waiting
period before the illness can be diagnosed? Any physician knows that to
treat a disease adequately you have to be able to define the disease at its
onset and treat it immediately in order to prevent chronic complications from
arising. There are simply no other disease definitions that have ever been
assembled similar to the CFS definitions.

(d) If you are still not convinced, check the Internet for the Diagnostic and
Statistical Manual of Mental Disorder definition of: DSMIII Somatization
Disorder. You will find that there is little substantial difference 
to distinguish
the DSMIII definition from the 1988 and 1994 CDC definitions of CFS. It is
difficult to believe that the CDC medical bureaucracy is not aware of this
similarity. It is thus understandable why the insurance industry, as well as
some psychiatrists and physicians, have simply concluded that CFS is
somatization disorder.

I believe it essential to define clearly Myalgic Encephalomyelitis. That is
what the Nightingale definition of M.E. sets out to do. The 
definition is based
upon two criteria:

(a) The excellent scientific work of respected physicians and scientists who
investigated the various M.E. epidemics

(b) Our Foundation's modern scientific testing techniques and the
knowledge resulting from examining thousands of M.E. patients using these
techniques.

The proposed M.E. definition is designed to improve early diagnosis and
treatment for the tens of thousands of patients stricken with M.E. It is not a
new definition of CFS nor should it be conceived as a rewording of any
previous CFS definition.


What follows is the primary M.E. definition for adults.

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


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 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 such as: (a) repetitive contact with a large number
of infectious persons,

(b) unusually long hours of exhausting physical and / or intellectual 
work, (c)
physical traumas, (d) immediate past immunizations, (e) epidemic disease
cases whose onset and periodicity appear to occur cyclically in a
susceptible population, (f) the effect of travel, as in exposure to a 
new subset
of virulent infections, or (g) 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 agents. 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: The first phase is an epidemic or endemic
infectious disease generally with an incubation period of three to seven
days; in most, but not all cases, an infection or infectious process 
is evident.
(See B. Hyde and A Jain, Clinical and Scientific Basis of M.E./CFS,
Chapter 13, Nightingale Research Foundation, Ottawa, Canada, pp.
124-126)

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: (f) fibromyalgialike pain syndromes. When occurring, these
various pain syndromes may include fibromyalgia-like 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. (See Clinical
and Scientific Basis of M.E./CFS, Chapter 5, pp. 58-62)

Testable and 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: 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
sub-cortical 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: 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. (See S. Bastien in Clinical and
Scientific Basis of M.E. / CFS, Chapter 51, pp. 453-460.)


7. Testable Major Sleep Dysfunction: This can include all forms of sleep
dysfunction. All or any of the following may be present: (a) impaired sleep
efficiency, (b) significant fragmented sleep architecture, (c) movement
arousals if there is an associated pain syndrome, (d) absence of type 3 and
4 sleep, (e) abnormal REM sleep pattern (f) changes in daytime alertness
and (g) sleep reversals.


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. Few centres are equipped or funded to make these
examinations.

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. 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. 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.

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 Disease: vasoconstriction, blanching, coldness and pain of
extremities. This is in part the cause for temperature dysfunctions seen in
M.E.

d. Circulating Blood Volume Decrease: this is a nuclear medicine test in
which the circulating red blood cell levels 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. Note: Body servomechanisms are genetically designed so
that blood flow and oxygen to the heart are always protected. Thus blood
flow to organs not necessary for short-term survival, such as the brain, the
gut and 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.

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 an infectious switch is turned on,
usually in late teens to early thirties. 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, (iii) touch the floor readily with the full palm
should be considered suspect for further examination. See S.I. Magalini,
S.C. Magalini, Dictionary of Medical Syndromes, pp. 251-252,
Lippincott-Raven Publishers, Philadelphia, 4th Edition, 1997.

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 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. 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 treat the
(i) genetic forms of vasculitis and 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 demonstrated when
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; 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 will allow the
patient to return to normal range of activities (e.g. school, career, etc).

10. Testable Endocrine Dysfunction: This feature is common and tends to
be a late appearance. It is 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 can be followed by ultrasound of the thyroid gland, where
a steady shrinking of the thyroid gland may occur in some 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 to 23 cc.
volume in male patients to below a volume of 6 cc. (Mayo Clinic averages).
Serum analysis of M.E. patients for thyroid pathology is simply not
adequate. Repeat thyroid ultrasound must be performed for all M.E. patients
to ascertain 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.

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 an 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.


Discussion


To various degrees all of the above historic findings have been observed
and discussed by Doctors Alexander Gilliam, Bjorn Sigurdsson, Alberto
Marinacci, Andrew Lachlan Wallis, A Melvin Ramsay (Elizabeth Dowsett
who assisted in much of his later work), John Richardson, Elizabeth Bell,
Alexis Shelokov, David C Poskanzer, W.H. Lyle, Sir E. Donald Acheson,
Louis Leon-Sotomayor, J. Gordon Parish and many others.

In varying degrees all of the following physicians have also noted the above
historical and the more recent investigational findings. They include
alphabetically, Doctors Peter Behan, David Bell, Dedra Buchwald, Paul
Cheney, Jay Goldstein, Seymour Grufferman, Anthony L Komaroff, Russell
Lane, Ismael Mena, Harvey Moldofsky, James Mowbray, Daniel Peterson,
Vance Spence and scores of others.

I have examined patients with M.E. since the late 1970s but only at the
urging of Dr. Charles Poser of Beth Israel Hospital at Harvard and John
Richardson in Newcastleupon- Tyne did I take up the study of these
unfortunate patients on a full time basis. The material in this 
definition is the
cumulative result of my listening and interpreting the work of all of 
the above
clinicians and my evaluation of over 3,000 M.E. and CFS patients since
1984. The essential concept of the indepth medical evaluation that is the
basis of my work on M.E. and CFS since 1995 was crystallized in my
discussions in Seattle Washington State in 2002 with Dr. Leonard A. Jason,
Patricia A. Fennell and Renee R. Taylor. This discussion was set down as
Chapter 3, "The Complexities of Diagnosis", in their book, The Handbook of
Chronic Fatigue Syndrome, John Wiley and Sons, Hoboken, New Jersey,
2003. I would also like to thank Elizabeth Dowsett and Jane Colby whose
work with children in the UK as well as their advice have been instrumental
in this definition. I must also thank each and every one of the members of
John Richardson's Newcastle Research Group who have provided me with
so much valuable information over the years and who have all supported my
continued investigations of M.E. patients.


What is new and different about the Nightingale M.E. definition?

A: A Testable Definition

The definition is set out in both a clinical diagnostic and scientifically
testable fashion. This will allow the physician both an early diagnostic
bedside or office understanding of the illness and a scientific and
technological method to investigate and confirm the diagnosis. It is well
known by all serious physicians that in order to assist the patient 
in a partial
or full recovery the illness must be (a) prevented from occurring by either
immunization or understanding and avoiding the causes, (b) diagnosed and
treated immediately following onset. The Nightingale Definition assists the
physician in diagnosis and early treatment.

B: A Vascular Pathophysiology

The subject of vascular pathology is not new. The fact of the 
children dying of
a Parkinsonian-like vascular injury to the basal ganglia in Iceland during the
Akureyri Epidemic is an obvious indication of the CNS vascular effects.
Vasculitis has been well documented by Dr. E. Ryll in his description of the
epidemic in the San Juan Mercy, Sacramento California Hospital in 1975.
He described this M.E. epidemic as an epidemic vasculitis. In the late
1980s Drs. Jay Goldstein and Ismael Mena confirmed and proved this initial
description by examining the changed brain microcirculation using brain
SPECT imaging in M.E. patients. Following my over twenty years of
examining M.E. and CFS patients and sixteen years of subjecting the M.E.
and CFS patients to brain imaging techniques suggested by Goldstein and
Mena, it has become obvious to me that we are dealing with both a
vasculitis and a change in vascular physiology.

Numerous other physicians have supported this finding. Dr. David Bell, who
rediscovered the work of Dr. David Streeten and his book, Orthostatic
Disorders of the Circulation: Mechanisms, Manifestations and Treatment,
New York: Plenum Medical, 1986, advanced this understanding of M.E. The
work of Dr. Vance Spence and his colleagues in Scotland have started to
nail this CNS-vascular relationship down even further with a series of major
research papers. The recent interpretation of the cause of Multiple Sclerosis
(MS) as an injury of the microvasculization causing the injury of the schwann
cells that in turn causes the demyelination injuries of MS has been added to
that of paralytic poliomyelitis as an essential vascular injury. Paralytic
poliomyelitis was thought to be a primary injury to the anterior horn cells of
the spinal cord but is now recognized as a vasculitis injuring the circulation
to the anterior horn cells. Poliomyelitis is generally a non-progressive,
specific site injury, although post-polio syndrome has challenged that belief.
MS is a recurrent more fulminant physiological vascular injury.

M.E. appears to be in this same family of diseases as paralytic polio and
MS. M.E. is definitely less fulminant than MS but more generalized. M.E. is
less fulminant but more generalized than poliomyelitis. This relationship of
M.E.-like illness to poliomyelitis is not new and is of course the reason that
Alexander Gilliam, in his analysis of the Los Angeles County General
Hospital M.E. epidemic in 1934, called M.E. atypical poliomyelitis.

C: The Lack of Mention of Fatigue

Myalgic Encephalomyelitis is not CFS. Fatigue was never a major
diagnostic criterion of Myalgic Encephalomyelitis. Fatigue, loss of stamina,
failure to recover rapidly following exposure to normal physical or 
intellectual
stressors occur in most if not all progressive terminal diseases and in a very
large number of chronic non-progressive or slowly progressive diseases.
Fatigue and loss of stamina are simply indications that there is something
wrong. They cannot be seriously measured, are generally subjective and do
not assist us with the diagnosis of Myalgic Encephalomyelitis or CFS or for
that matter any disease process.

D: Cause of Myalgic Encephalomyelitis

It is obvious that all cases of epidemic M.E. and all primary M.E. are
secondary to infectious / autoimmune phenomena. Many M.E. and M.E.-like
patients' illness is complicated by multiple other causes. This is why a
complete technological investigation has to be made on each chronically ill
M.E. or M.E.-like patient. Under epidemic and primary M.E. there is no
consensus as to the viral or infectious cause. Much of this lack of consensus
may be due to the non-separation of acute onset from gradual onset
patients in the M.E. and CFS groups of patients. Primary M.E. is always an
acute onset illness. Doctors A. Gilliam, A. Melvin Ramsay and Elizabeth
Dowsett, John Richardson of Newcastle-upon-Tyne, W.H. Lyle, Elizabeth
Bell of Ruckhill Hospital, James Mowbray of St Mary's and Peter Behan all
believed that the majority of primary M.E. patients fell ill 
following exposure
to an enterovirus (Poliovirus, ECHO, Coxsackie and the numbered viruses
are the significant viruses in this group).

I share this belief. Unfortunately, it is very difficult to recover polio and
enteroviruses from live patients. Dr. James Mowbray developed a test that
demonstrated enterovirus infection in many M.E. patients but I do not believe
he qualified his patients by acute or gradual onset type of illness. 
In my tests
in Ruckhill Hospital in Glasgow, I found confirmation of enteroviral infection
only in acute onset patients and not in any gradual onset patients. Few
physicians realize that almost all cases of poliovirus recovered from
poliomyelitis victims came from cadavers. At the very least, these
enteroviruses must be recovered from patients during their onset illness and
this has rarely been done. An exception is in the case of the
Newton-le-Willows Lancashire epidemic where Dr. W. H. Lyle's
investigation recovered ECHO enterovirus. Recent publications by Dr. J. R.
Kerr have also identified the fact that enteroviruses are one of the 
most likely
causes of M.E. If this belief is correct, many if not most of the 
M.E. illnesses
could be vanquished by simply adding essential enteroviral genetic material
from these enteroviruses to complement polio immunization.

I have not discussed non-infectious M.E.-type disease. Similar M.E.
phenomena can occur due to diffuse Central Nervous System injuries from
toxic chemical injury. I have seen this in police officers who have 
fallen into
toxic chemical ponds in pursuit of those suspected of criminal 
activity. I have
seen it in farmers, in hospital and industrial workers and in 
military personnel
in contact with toxic chemicals, specifically toxic gases. I plan to explore
these in a future publication as Secondary M.E. They do have one thing in
common, and that is the diffuse CNS injury as noted on brain SPECT scans.
Often these Secondary M.E. diseases are more severe than the Primary
M.E. cases.

E: Caution One

One should be careful in applying the diagnostic criteria discussed under
the Nightingale M.E. Definition without also completing a thorough
investigation. M.E., whether we are discussing primary or secondary forms,
involves a significant diffuse injury of the Central Nervous System and an
associated injury of the Immune System. This always implies the potential
for secondary injuries or secondary disease or pathology caused by a
dysfunctional brain and dysfunctional immune system. When the immune
system is injured there is an impairment of the patient's ability to 
resist the
development of malignancy or other important organ and systemic injuries.
Due to funding limitations, we have only been able to demonstrate in our
work only two characteristics of this corollary injury. The first is the high
incidence of thyroid cancer in M.E. patients. In the general public, cancer of
the thyroid occurs in 1 case per 100,000. In our studies, in the case of the
M.E. patient, thyroid cancer has an incidence of 6,000 cases per 100,000.
We have already mentioned the pervasive vascular injuries. We believe that
other pathological associations also occur. Failure to evaluate fully the M.E.
patient may result in the physician missing important secondary pathology
and possibly giving rise to patient death.

All M.E. patients as well as all chronic illness patients deserve a systematic
and total body investigation. No individual should go through life, 
ill, disabled
without knowing why he is ill. Simply offering a label, whether M.E. or CFS,
without looking at the pathophysiology, is both unacceptable and potentially
dangerous both for the patient and the patient's physician.

(See "The Complexities of Diagnosis" by Byron Hyde, in the Handbook of
Chronic Fatigue Syndrome, Chapter 3)

F: Caution Two

Insurance companies regularly employ reputedly independent psychologists
who demonstrate normal neuropsychological findings. This presents a grave
problem in that neuropsychological testing by a truly independent
neuropsychologist may be delayed for up to a year before the patient can be
properly tested. The conflicting results may tend to confuse any 
trial judge in
a legal case.

G: Depression, Anti-depressive Medications and Myalgic
Encephalomyelitis

Myalgic Encephalomyelitis is not depression. Myalgic Encephalomyelitis is
not hysteria. Myalgic Encephalomyelitis is not a conversion disorder nor is it
a somatization disorder. Myalgic Encephalomyelitis is an acute onset
diffuse injury of the brain. Psychiatrists should not ever be placed in charge
of diagnosis and treatment of M.E. patients. It is simply not their area of
expertise and their meddling has at times caused great harm to M.E.
patients. Also, during the 20 years that I have investigated M.E. patients I
have yet to see a single case of real M.E. that has responded to psychiatric
pharmacological treatment such that the patient has recovered and been
able to return to work or school.


This topic is a very large subject and demands a separate publication and
this is not the place for it. However I would like to note again the vascular
and cardiac pathologies that one encounters in M.E. patients and how M.E.
patients are often made worse by one antidepressive medication that is
considered benign. One of the most common antidepressive medications
employed by psychiatrists and physicians in general for M.E. patients is an
old pharmaceutical, Amitriptyline. Yet this medication may result in a
condition referred to as Torsade de Pointes, a cardiac irregularity giving
rise to resting tachycardia, QT interval prolongation and significant
orthostatic hypotension. Since there is already a high frequency of these
anomalies in M.E. patients, the use of Amitriptyline may assist sleep to
some degree but may also simply worsen existing M.E. symptomology. I
plan to return to this subject in another publication.


Definition Changes and Improvements

As with all definitions, the Nightingale Research Foundation's Definition of
Myalgic Encephalomyelitis will have to be looked at by many clinicians and
researchers and over the years, disagreed about, changed and improved
upon. But 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.

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, provided that this last paragraph and referral
back to our website are noted.



Byron Marshall Hyde MD, Ottawa - November 18, 2006



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