The Committee for Justice
and Recognition of Myalgic Encephalomyelitis
Learning about Myalgic Encephalomyelitis
The New Clinical
Definition & Diagnosis
A major Advance for Patients, an Expert panel leads the way,
with a modern Diagnostic criteria. A valuable opportunity to educate your
doctors.
============================================================================
Myalgic
Encephalomyelitis/
Chronic
Fatigue Syndrome:
Clinical
Working Case Definition,
Diagnostic and Treatment Protocols
Bruce
M. Carruthers, MD, CM, FRCP(C)
Anil
Kumar Jain,
Kenny
L. De Meirleir, MD, PhD
Daniel
L. Peterson, MD
Nancy
G. Klimas, MD
A.
Alison
C. Bested, MD, FRCP(C)
Pierre
Flor-Henry, MB,
Pradip
Joshi, BM, MD, FRCP(C)
A.
C. Peter Powles, MRACP, FRACP, FRCP(C), ABSM
Jeffrey
A. Sherkey, MD, CCFP(C)
Marjorie
I. van de Sande, BEd, Grad Dip Ed
http://www.haworthpressinc.com/store/product.asp?sku=J092
ã 2003 by The Haworth Press, Inc. All rights reserved.
10.1300/J092v11n01_02
ABSTRACT.
Recent years have brought growing recognition of the
need for clinical criteria for myalgic encephalomyelitis (ME), which is also
called chronic fatigue syndrome (CFS). An Expert Subcommittee of Health
KEYWORDS. Clinical
case definition, myalgic encephalomyelitis, chronic fatigue syndrome, ME, CFS,
diagnostic protocol, treatment protocol
Address correspondence to: Dr. Bruce M. Carruthers,
C58, Site 25, RR 1,
[Article copies available for a fee
from The
Myalgic
encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe systemic,
acquired illness that can be debilitating. It manifests symptoms predominantly
based on neurological, immunological and endocrinological dysfunction. While the
pathogenesis is suggested to be multi-factorial, the hypothesis of initiation
by a viral infection has been prominent. A wide range of viruses and other
infectious agents, such as Epstein-Barr Virus (1,2,3,4,5), Human Herpesvirus-6
and 7 (6,7,8,9,10), Enterovirus (11,12), Cytomegalovirus (13,14,15), Lentivirus
(16), Chlamydia (17), and Mycoplasma (18,19), have been investigated but
findings are mixed and there is no conclusive support for any one pathogen. As
antibody titers in standard laboratory tests usually employ a whole viral
preparation or a single viral polypeptide, an incomplete or mutated pathogen
replication could go undetected. It is unclear whether the pathogens play a
direct causal role, accompany an underlying infection, trigger reactivation/replication
of latent pathogens, represent reactivated latent pathogens, activate a neural
response or modulate the immune system to induce ME/CFS (20). Possibly a new
microbe will be identified. Viral involvement is supported by an infectious
initiating trigger in at least half of the patients (21), and by confirmed
findings of biochemical dysregulation of the 2-5A synthetase/ ribonuclease L
(RNase L) antiviral defense pathway in monocytes (22,23,24,25,26), a pathway
which is activated in viral disorders (27).
Before
acquiring the illness most patients were healthy, leading full and active
lifestyles. ME/CFS most frequently follows an acute prodromal infection,
varying from upper respiratory infections, bronchitis or sinusitis, or
gastroenteritis, or an acute “flu-like” illness. Other prodromal events that
may stress the neuroimmunoendocrine regulatory system include immunization,
anesthetics, and exposure to environmental pollutants (28), chemicals, and
heavy metals (29). Physical trauma such as a motor vehicle accident, a fall, or
surgery may also trigger ME/CFS. In rare occasions, ME/CFS has developed
following a blood transfusion. Within days or weeks of the initiating event,
patients show a progressive decline in health and develop a cascade of symptoms.
The subset of patients that have a gradual onset are less likely to show
discrete triggering events.
ME/CFS is
primarily an endemic disorder (30,31) but occurs in both epidemic (2,32), and
sporadic forms. It affects all racial/ethnic groups, is seen in all
socioeconomic strata (33,34,25). Epidemiological studies have indicated a wide
range of prevalence, from 75 to 2,600 per 100,000 (36,37,38,39,40,41) in
different care settings; however, in a large sample of over 28,000 adults, 422
per 100,000 or 0.42% suffered from ME/CFS (36). It is more prevalent in females
(522 per 100,000), as is arthritis and rheumatism. When comparing the ME/CFS
prevalence figures for women with those for other illnesses, such as AIDS (12
per 100,000), breast cancer (26 per 100,000) (36), lung cancer (33 per 100,000)
and diabetes (900 per 100,000), one realizes the need for a clinical definition
and research for ME/CFS.
In response
to cluster outbreaks of this illness, a working case definition for CFS was
published under the aegis of the Centers for Disease Control (CDC),
As the CDC
definition was primarily created to standardize research, it may not be
appropriate to use for clinical diagnoses, a purpose for which it was never
intended. There has been a growing demand within the medical community for a
clinical case definition for ME/CFS for the benefit of the family physician and
other treating clinicians. The CDC definition, by singling out severe,
prolonged fatigue as the sole major (compulsory) criterion, de-emphasized the
importance of other cardinal symptoms, including post-exertional malaise, pain,
sleep disturbances, and cognitive dysfunction. This makes it more difficult for
the clinician to distinguish the pathological fatigue of ME/CFS from ordinary
fatigue or other fatiguing illnesses.
Based on the
consensus panel’s collective extensive clinical experience diagnosing and/or
treating more than twenty thousand (20,000) ME/CFS patients, a working clinical
case definition, that encompassed The pattern of positive signs and symptoms of
ME/CFS, was developed. The objective was to provide a flexible conceptual
framework for clinical diagnoses that would be inclusive enough to be useful to
clinicians who are dealing with the unique symptomatic expression of individual
patients and the unique context within which their illness arises. The panel
felt there was a need for the criteria to encompass more symptoms in order to
reflect ME/CFS as a distinct entity and distinguish it from other clinical
entities that have overlapping symptoms. As fatigue is an integral part of many
illnesses, the panel concurred that more of the prominent symptoms should be
compulsory.
Our strategy
was to group symptoms together which share a common region of pathogenesis,
thus enhancing clarity and providing a focus to the clinical encounter. The
inclusion of more of the potential spectrum of symptomatology in the clinical
definition should allow a more adequate expression of the actual symptoms of
any given patient’s pathogenesis. We hope that the clinical working case
definition will encourage a consideration of the ongoing interrelationships of
each patient’s symptoms and their coherence into a syndrome of related symptoms
sharing a complex pathogenesis rather than presenting a “laundry list” of
seemingly unrelated symptoms. We believe this will sharpen the distinction
between ME/CFS and other medical conditions that may be confused with it in the
absence of a definite laboratory test for ME/CFS.
Since the development of our clinical criteria, we have
had an opportunity to review the analysis of symptoms in over 2,500 patients by
De Becker et al. (45). They found that the Holmes definition (42) of fatigue,
swollen/tender lymph nodes, sore throat, muscle weakness, re- current flu-like
symptoms, post-exertional fatigue, myalgia, memory disturbance, nonrestorative
sleep and replacing low-grade fever with hot flashes; and the addition of ten
other symptoms (attention deficit, paralysis, new sensitivities to food/drugs,
cold extremities, difficulties with words, urinary frequency, muscle
fasciculations, lightheadedness, exertional dyspnea and gastrointestinal
disturbance) strengthen the ability to select ME/CFS patients. Based on this
study, we added exertional dyspnea and muscle fasciculations to our clinical
definition. All the symptoms which the De Becker et al. study (45) recommended
adding to strengthen the ability to select ME/CFS patients are in our
definition except paralysis, which the panel did not consider prevalent enough
for inclusion in a clinical definition. The clinical definition has additional
symptoms, such as orthostatic intolerance, which we feel are important in a
clinical setting.
Although
it is unlikely that a single disease model will account for every case of
ME/CFS, there are common clusters of symptoms that allows a clinical diagnosis.
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, neuroendocrine 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 level.
2. Post-Exertional Malaise and/or
Fatigue: 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 quantity or rhythm disturbances such as reversed
or chaotic diurnal sleep rhythms.
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
new type, pattern or severity.
5. Neurological/Cognitive
Manifestations: Two
or more of the following difficulties should be present: confusion, impairment
of concentration and short-term memory consolidation, disorientation,
difficulty with information processing, categorizing and word retrieval, and
perceptual and sensory disturbances–e.g., spatial instability and
disorientation and inability to focus vision. Ataxia, muscle weakness and
fasciculations are common. There may be overload 1 phenomena: cognitive,
sensory–e.g., photophobia and hypersensitivity to noise–and/or emotional
overload, which may lead to “crash” 2 periods and/or anxiety.
6. At Least One Symptom from Two of
the Following Categories:
a. Autonomic Manifestations: orthostatic intolerance–neurally
mediated hypotenstion (NMH), postural orthostatic tachycardia syndrome (POTS),
delayed postural hypotension; light-headedness; extreme pallor; nausea and
irritable bowel syndrome; urinary frequency and bladder dysfunction;
palpitations with or without cardiac arrhythmias; 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 adaptability 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 altered after the onset of
this illness. It is unlikely that a patient will suffer from all symptoms in
criteria 5 and 6. The disturbances tend to form symptom clusters that may
fluctuate and change over time.
Children often have
numerous prominent symptoms 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 and/or have more 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; rheumatological disorders such as rheumatoid
arthritis, lupus, polymyositis and
polymyalgia rheumatica; immune disorders such as AIDS; neurological disorders
such as multiple sclerosis (MS), Parkinsonism, myasthenia gravis and B12
deficiency; infectious diseases such as tuberculosis, chronic hepatitis, Lyme
disease, etc.; primary psychiatric disorders 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 (MCS), 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 become 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, it should be classified
as idiopathic chronic fatigue.
General
Considerations in Applying the Clinical Case Definition to the Individual
Patient
1. Assess Patient’s Total Illness: The diagnosis of ME/CFS is not arrived
at by simply fitting a patient to a template but rather by observing and
obtaining a complete description of their symptoms and interactions, as well as
the total illness burden of the patient.
2. Variability and Coherence of
Symptoms: Patients
are expected to exhibit symptoms from within the symptom group as indicated,
however a given patient will suffer from a cluster of symptoms often unique to
him/her. The widely distributed symptoms are connected as a coherent entity
through the temporal and causal relationships revealed in the history. If this
coherence of symptoms is absent, the diagnosis is in doubt.
3. Severity of Symptoms: A symptom has significant severity
if it substantially impacts (approximately a 50% reduction) on the patient’s
life experience and activities. In assessing severity and impact, compare the
patient’s activity level to their premorbid activity level. Establishing the
severity score of symptoms is important in the diagnostic procedure (46,45),
and should be repeated periodically. A chart for severity of symptoms and
symptom hierarchy can be found in Appendix 3. While this numerical scale has
been developed as a tool to assist the clinician and position the patient
within the overall spectrum of ME/CFS severity, the severity and impact of
symptoms should be confirmed by direct clinical dialogue between physician and
patient over time.
4. Symptom Severity Hierarchy: Periodic ranking of symptom severity
should be part of the ongoing evaluation of the clinical course. (Appendix 3)
This hierarchy of symptom severity will vary from patient to patient and for an
individual patient over time. Thus, although fatigue and post-exertional
malaise are universal symptoms of ME/CFS, they may not be the most severe
symptoms in the individual case, where headaches, neurocognitive difficulties,
pain and sleep disturbances can dominate, at least temporarily. Establishing
symptom severity and hierarchy helps orient the treatment program.
Fatigue
The
fatigue of ME/CFS comes in many ‘flavours’ (47). Patients learn to recognize
the difference between ‘normal’ and ‘ME/CFS’ fatigue by its qualitative
flavour, its temporal characteristics and its correlation with other events and
activities. The patient must have a marked degree of unexplained, persistent or
recurrent fatigue. The fatigue should be severe enough to substantially reduce
the patient’s activity level, usually by approximately 50%. When considering
the severity of the fatigue, it is important to compare the patient’s activity
level to their premorbid activity level. For example, a former world class
athlete could have a substantially reduced activity level and still exceed the
norms for sedentary persons. Some patients may be able to do some work, but in
order to do that they have had to eliminate or severely reduce other aspects of
their life activities. Such interactive effects should be considered in the
assessment of whether activity reduction is substantial.
Evidence
of cognitive fatiguing should be sought in the history and may be evident
during the clinical interview. Over the duration of the interview the patient’s
responses may become slower and less coherent.
The patient may begin to have difficulty with choosing the correct
words, recalling information, or become confused. Occasionally asking more than
one question at a time may make the fatiguing more evident. However these
changes may be quite subtle, as patients have often learned to compensate for
cognitive fatigue with hyper-concentration, and have often developed strategies
for taking cognitive micro-rests such as changing the subject, taking postural
breaks, reducing sensory stimulation, etc. They may be quite unaware of these
strategies.
The
malaise that follows exertion is difficult to describe but is often reported to
be similar to the generalized pain, discomfort and fatigue associated with the
acute phase of influenza. Delayed malaise and fatigue may be associated with
signs of immune activation: sore throat, lymph glandular tenderness and/or
swelling, general malaise, increased pain or cognitive fog. Fatigue immediately
following activity may also be associated with these signs of immune
activation. Patients who develop ME/CFS often lose the natural antidepressant
effect of exercise, feeling worse after exercise rather than better. Patients
may have a drop in body temperature with exercise. Thus fatigue is correlated
with other symptoms, often in a sequence that is unique to each patient. After
relatively normal physical or intellectual exertion, a patient may take an inordinate
amount of time to regain her/his pre-exertion level of function and competence.
For example, a patient who has bought a few groceries may be too exhausted to
unpack them until the next day. The reactive fatigue of post-exertional malaise
or lack of endurance usually lasts 24 hours or more and is often associated
with impairment of cognitive functions. There is often delayed reactivity
following exertion, with the onset the next day, or even later. However,
duration of symptoms also varies with the context. For example, patients who
have already modified their activities to better coincide with the activity
level they can handle without becoming overly fatigued will be expected to have
a shorter recovery period than those who do not pace themselves adequately.
Sleep
Dysfunction
Sleep
and other diurnal rhythm disturbances may include early, middle or late
insomnia, with reversed or irregularly irregular insomnia, hypersomnia,
abnormal diurnal variation of energy levels, including reversed or chaotic
diurnal rest and sleep rhythms. This results in lack of tolerance for shift
work/activity or time zone shifts when travelling. Loss of the deeper phases of
sleep is especially characteristic, with frequent awakenings, and loss of
restorative feelings in the morning.
Restless leg syndrome and periodic limb movement disorder often
accompany sleep disturbance. A very small percentage of ME/CFS patients do not
have sleep dysfunction, but do not fit any other disease criteria.
Sleep
Study: It is important to rule out treatable sleep disorders such as upper
airway resistance syndrome, obstructive and central sleep apnea and restless
leg syndrome. Indications: the patient wakes up out of breath, or there is
great disturbance of the bed clothes, or a sleep partner indicates that the
patient snores and/or appears to stop breathing at times and/or has significant
movement of her/his legs while sleeping. If poor sleep is a troublesome
symptom, which does not improve with medication and sleep hygiene, it may be
appropriate to have the patient assessed at a sleep clinic.
Pain
Pain is
often generalized and ‘nonanatomical,’ i.e., not confined to any expected
structural or nerve root distribution. The pain occurs in unexpected places at
unexpected times. There are pains of many qualities: sharp, shooting, burning
and aching. Many patients have significant new onset headaches of many types,
including tension and pressure headaches and migraines. There is often
generalized myalgia and excessive widespread tenderness or pain that is usually
perceived to originate in the muscles but is not limited to the classical FMS
tender points. Patients have a lowered pain threshold or “chronic, widespread
allodynia”(48) with approximately 75% of ME/CFS patients exhibiting positive
FMS tender points (49). Pain may also spread from pressure on myo-fascial
trigger points (MTP). Arthralgia without joint swelling may be experienced but
is not discriminatory for ME/CFS (45,47). A very small percentage of ME/CFS
patients do not have appreciable pain, but do not fit any other disease
criteria. ME/CFS should only be entertained as a diagnosis for this group when
otherwise classical features follow an infectious illness, and where other
diseases have been adequately ruled out.
The
neurological/cognitive symptoms are more characteristically variable than
constant and often have a distinct fatiguing component to them. Especially
common are cognitive ‘fog’ or confusion, slowed information processing speed,
trouble with word retrieval and speaking or intermittent dyslexia, trouble with
writing, reading, and mathematics, and short-term memory consolidation. There
may be ease of interference from concomitant cognitive and physical activities,
and sensory stimulation. It is easy to lose track of things and/or many things
are forgotten: names, numbers, sentences, conversations, appointments, ones’
own intentions and plans, where things are in the house, where one has left the
car, whether one has brought the car, where one is and where one is going. The
memory dysfunction tends to primarily affect short-term memory. There are
selective deficits in memory processing arising against a background of
relatively normal cognitive functioning in ME/CFS patients. They experience more
difficulty in recalling information under conditions of greater semantic
structure and contextual cues, the opposite of what is found in controls and
patients with other sorts of CNS impairments. They also experience difficulty
maintaining attention in situations that cause them to divide their efforts,
e.g., between auditory and visual channels.
Perceptual Disturbances: Less ability to make figure/ground
distinctions, loss of depth perception or inability to focus vision and
attention. One may lose portions of the visual field or one can only make sense
of a small portion of it at a time. There are dimensional disturbances in
timing which affect the ability to sequence actions and perceptions, and cope
with complex and fast paced changes such as shift work and jet lag. Spatial
instability and disorientation come in many varieties, with gait tracking
problems, loss of cognitive map and inaccurate body boundaries–e.g., one bumps
into the side of the doorway on trying to go through it and/or walks off the
sidewalk, where the ground feels unstable.
Motor Disturbances: Ataxia, muscle weakness and
fasciculations, loss of balance and clumsiness commonly occur. There may be an
inability to automatically ‘attune’ to the environment, as in accommodating
footfall to irregular ground while walking and temporary loss of basic
habituated motor programs such as walking, brushing one’s teeth, making the bed
and/or dialing a telephone.
Overload
phenomena affect sensory modalities where the patient may be hypersensitive to
light, sound, vibration, speed, odors, and/or mixed sensory modalities.
Patients may be unable to block out background noise sufficiently to focus on
conversation. There is also cognitive/informational overload – inability to
multi-task, and trouble making decisions. There is emotional overload from
extraneous emotional fields that unduly disturb the patient. There is motor
overload – patients may become clumsy as they fatigue, and stagger and stumble
as they try to walk, are not able to keep a straight line, as well as showing
generalized and local weakness, and need to slow down their movements. All of
these overload disturbances may form symptom clusters characteristic of the
individual patient such as dizziness, numbness, tinnitus, nausea, or shooting pain.
These overload phenomena may precipitate a ‘crash’ where the patient
experiences a temporary period of immobilizing physical and/or mental fatigue.
Orthostatic intolerance is commonly seen in ME/CFS patients
and includes:
• Neurally mediated hypotension (NMH):
Involves disturbances in the autonomic regulation of blood pressure and pulse.
There is a precipitous drop that would be greater than 20-25 mm of mercury of
systolic blood pressure upon standing, or standing motionless, with significant
accompanying symptoms including lightheadedness, dizziness, visual changes,
sometimes syncope, and a slow response to verbal stimuli. The patient is weak
and feels an urgency to lie down.
• Postural orthostatic tachycardia syndrome
(POTS): Excessive rapidity in the action of the heart (either an increase of
over 30 beats per minute or greater than 120 beats per minute during 10 minutes of standing); and a fall in blood pressure,
occurring upon standing. Symptoms include lightheadedness, dizziness, nausea,
fatigue, tremor, irregular breathing, headaches, visual changes and sweating.
Syncope can but usually does not occur.
• Delayed postural hypotension: The drop
in blood pressure occurs many minutes (usually ten or more) after the patient stands
rather than upon standing.
Tilt Test: Further investigation by tilt test
is indicated if there is a fall in blood pressure and/or excessive rapidity of
heart beat upon standing, which improves when sitting or lying down. Patients
often report that they experience dizziness, feeling light-headed or ‘woozy’
upon standing, or feeling faint when they stand up or are standing motionless
such as in a store checkout line. Patients may exhibit pallor and mottling of
the extremities. These historical symptoms and signs are sufficient for the
initial diagnosis. As ME/CFS patients often have a delayed form of orthostatic
intolerance, taking the blood pressure after standing may not be effective in
diagnosis. Rather than having the patient stand for a period of time where
there is a risk of him/her falling, we recommend using the tilt test where the
patient is strapped down. The tilt test involves the patient lying horizontally
on a table and then tilting the table upright to a 60°-70° angle for
approximately 45 minutes during which time blood pressure and heart rate are
monitored. It is recommended that orthostatic intolerance be confirmed by tilt
testing prior to prescribing medication for it.
Palpitations with or without cardiac
arrhythmias may be present.
Further investigation by 24-Hour Holter Monitor may be indicated if a
significant arrhythmia is suspected. Repetitively oscillating T-wave inversions
and/or flat T-wave may be found. (Request to be informed of this pattern as it
may not be reported or subsumed under non-specific T-wave changes by the
interpreter.)
Other common symptoms related to ANS disturbances include
breathing dysregulation–holding the breath inappropriately, irregular
breathing, exertional dyspnea; intestinal irregularities and hypersensitivity
to pain–irritable bowel syndrome, diarrhea, constipation, alternating diarrhea
and constipation, abdominal cramps; bloating, nausea and anorexia. Bladder
dysfunction and pain sensitivity can manifest as urinary frequency, dysuria,
nocturia, and pain over the bladder region.
Neuroendocrine
Manifestations
Loss of
thermostatic stability may be experienced as altered body temperature–usually
subnormal and/or marked diurnal fluctuation. Having patients take their
temperature a number of times a day for a few days can confirm temperature
fluctuation. It may be helpful to have patients note their asctivity prior to
taking their temperature. Patients may have alternating feelings of hot or
cold, sometimes in unusual distribution, e.g., feet are often cold, fingers may
be hot, or the right side may feel hot while the left feels cold, or there may
be localized feelings of heat and flushing. Many patients are intolerant of
extremes in weather and experience worsening of symptoms. There are recurrent
feeling of feverishness and sweating episodes. There is often a marked weight
change–a reduction in some patients with loss of appetite or anorexia and a
weight gain in others and an appetite that is inappropriate to their activity
level.
Dysfunction
of the autonomic system and hypothalamic/pituitary/adrenal axis: bodymind
‘crashing’ may lead to a general loss of adaptation to situations of overload.
Excessive speed in the overloading situation or attempted response will
aggravate these ‘crashes.’ Anxiety states and panic attacks may also be part of
the syndrome and coherent with the other symptoms. They may not be tied to
environmental events that trigger them, or they may be secondary to the
symptoms. When ‘crashing,’ the patient becomes destabilized and disoriented,
and thus is naturally frightened. Anxiety and panic may also appear without any
external trigger. Patients with ME/CFS have worsening of their symptoms under
increased stress, and with excess physical and mental activity. They also show
slow recovery.
Immune
Dysfunctions
Some
but not all patients exhibit symptoms coming from immune system activation,
which may or may not be in response to an appropriate stimulus. For many
patients this type of symptom is prominent at the acute onset stage and then
diminishes or becomes recurrent as the illness becomes chronic. There is often
general malaise–flu like feelings of being ‘ill’ and feeling feverish. Tender
lymphadenopathy in the cervical, axillary inguinal or other regions may be
present. The patient may have a recurrent sore throat with or without faucial
injection. Such clinical evidence of immune system activation may occur in the
absence of demonstrable viral exposure and/or be associated with inappropriate
events such as physical exercise and stress. New sensitivities to food,
medications and/or various chemicals are common. Patients with an acute viral
onset tend to show more immune dysfunction compared to those whose onset is
gradual.
Faucial
injection and crimson crescents may be seen in the tonsillar fossae of many
patients but are not diagnostically specific. These red crescents are
demarcated along the margins of both anterior pharyngeal pillars. They will
assume a posterior position in the oropharynx in patients without tonsils.
Oscillating or diminished pupillary accommodation responses with retention of
reaction to light is also common.
Cervical and axillary lymph adenopathy, often tender, may be felt.
Positive fibromyalgia tender points and myofascial trigger points are common.
Neurological dysfunction is often seen, including hypersensitivity to vibration
sense, positive Romberg test and abnormal tandem gait.
Simple
mental status measures are often normal, but abnormal fatiguing on serial seven
subtraction testing is common. Mutual aggravation when tandem gait and serial
sevens are done simultaneously, may be evident when the baseline serial sevens
test and tandem gait are both normal. As more of these signs are elicited in
the same patient, the diagnosis of ME/CFS is increasingly confirmed.
There are selective deficits in memory processing arising against a background of relatively normal cognitive functioning in ME/CFS patients. The results of neurocognitive testing will depend on the focus of the test as well as many variables including the test, the milieu, schedule, pacing and duration of the test. A well controlled study (50) showed patients significantly overestimated their memory (meta memory), their performance on recall tests significantly worsened as the context increased (e.g., recognition), they made more errors when rehearsal was prevented, and had delayed mental scanning as memory load increased. Neuropsychological testing is expensive and the cost is rarely covered by provincial health plans.
Children can be diagnosed with ME/CFS if symptoms last
more than three months. They tend to have numerous symptoms of similar overall
severity but their hierarchy of symptom severity may vary from day to day (51).
Severe, generalized pain is a common feature. Children may become dyslexic,
tearful, physically weak, and exhibit exhaustion or profound mood changes.
Previously active children may shun physical activity and academic standings
deteriorate. They tend to do worse in mathematics and analytical subjects such
as science. They are often classified as having school phobia. A British study
showed that ME/CFS was the single most common cause of long-term absenteeism
from school in Britain (52).
The
clinical case definition provides the essential function of orientating the
various aspects of the clinical encounter and forms an integral part of the whole
clinical process. A clear diagnosis often has a considerable therapeutic
benefit as it reduces uncertainty and orients therapy, both specific and
nonspecific. Early diagnosis is important and may assist in lessening the
impact of ME/CFS in some patients.
Clinical
Evaluation of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
While it is a part of the discipline of differential diagnosis to exclude alternate explanations for a patient’s symptoms, it is also important to recognize the characteristic features of ME/CFS. Assess the total illness burden of the patient, taking a thorough history, physical examination and investigations as indicated to confirm clinical findings and to rule out other active disease processes. This patient evaluation is to be used in conjunction with the clinical definition. The sections on general considerations in applying the definition and the discussion of the major features give more detail.
1. Patient History: A thorough history, including a complete description of
patient’s symptoms as well as their severity and functional impact must be
taken before attempting to classify them.
a. Focus on the Principal Symptoms of ME/CFS: including fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, pain, and symptoms from neurological/cognitive, autonomic, endocrine and immune manifestations. Examine the course of the symptoms, with special attention to the worsening of symptoms after exertion, prolonged recovery, and fluctuating course.
b. Presenting Complaints and
Aggravating/Ameliorating Events
• date of onset
• trigger or prodromal event
• symptoms at onset
• progression of symptoms
• duration of symptoms
• hierarchy of quality and severity of current symptoms
• symptoms which worsen with exertion; symptoms which require prolonged
recovery
• separate secondary symptoms and aggravators; consider amelioration
factors
• quantify severity of total burden of symptoms, interaction effects, and
current level of physical function
c. Medication History: current and past, prescribed, natural
and other therapies
d. Sensitivities and Allergy History: including any new sensitivities to
food, medications and/or chemicals, allergies or change in status of
pre-existing allergies
e. Past History: earlier illnesses, exposure to
environmental, residential and occupational toxins
f. Family History
g. System Review: many symptoms involve more than one
system. Inquiry should be made for the key symptoms listed in the case
definition. Careful review of the symptoms is important to exclude other
conditions that may present with similar symptomatology.
• Musculoskeletal System: myalgia, muscle weakness, arthralgia
• CNS: cognitive fatigue, fatigue and post exertional
exacerbation, neurocognitive complaints, headaches, and sleep disturbances
• ANS & Cardiorespiratory System:
symptoms suggestive
of orthostatic intolerance, neurally mediated hypotension, postural orthostatic
tachycardia syndrome, delayed postural hypotension, palpitations, respiratory
disturbances, vertigo, light-headedness, extreme pallor
• ANS & GI & GU System: intestinal or bladder disturbances
with or without irritable bowel syndrome or bladder dysfunction
• Neuroendocrine System: loss of thermostatic stability,
heat/cold intolerance, abnormal appetite, marked weight change, loss of sleep
rhythm, loss of adaptability and tolerance for stress and slow recovery,
emotional lability
• Immune System: tender lymph nodes, sore throat,
recurrent flu-like symptoms, general malaise
2. Physical Examination: An appropriate physical examination
with focus on:
a. Musculoskeletal System: including FMS tender point
examination. There must be pain on palpation in 11 or more of the 18 designated
tender point sites to meet the diagnosis of FMS (see Appendix 6). Determine if
there are inflammatory changes in painful joints. Document muscle strength.
b. Neurological System: a thorough neurological examination
with emphasis on reflexes, tandem walk forwards and backwards, and Romberg
test.
• Neurocognitive Symptoms: an evaluation of cognitive symptoms
including ability to remember questions, cognitive fatiguing (e.g., serial 7
subtraction) and cognitive interference (e.g., serial 7 subtraction and tandem
done simultaneously).
c. Cardiorespiratory System: measure lying and standing blood
pressure. Arrhythmias should be noted.
d. Endocrine System: check for signs of thyroid, adrenal
and pituitary dysfunction.
e. Immune System: most positive findings of immune
system involvement in a physical examination are usually only present in the
acute stage and then diminish or become recurrent. Look for tender
lymphadenopathy in the cervical, axillary, inguinal regions especially early in
disease, and crimson crescents in the tonsillar fossae. Examine for
splenomegaly.
f. GI System: check for increased bowel sounds,
mild bloating and abdominal tenderness
3. Laboratory and Investigative Protocol
a. Routine Laboratory Tests: CBC, ESR, Ca, P, Mg, blood glucose,
serum electrolytes, TSH, protein electrophoresis screen, CRP, ferritin,
creatinine, rheumatoid factor, antinuclear antibody, CPK and liver function, as
well as routine urinalysis.
Additional Testing: In addition to the routine
laboratory tests, additional tests should be chosen on an individual basis
depending on the patient’s case history, clinical evaluation, laboratory
findings and risk factors for co-morbid conditions. Clinicians should carefully
consider the cost/benefit ratio of any investigative test for each patient, in
addition to avoiding unnecessary duplication of tests.
b. Further Laboratory Testing: diurnal cortisol levels, 24 hour
urine free cortisol; hormones including free testosterone, B 12 and folate
levels, DHEA sulphate, 5-HIAA screen, abdominal ultrasound, stool for ova and
parasites, NK cell activity, flow cytometry for lymphocyte activity, Western
blot test for Lyme disease, hepatitis B and C, chest x-ray, TB skin test and
HIV testing.
Do the 37-kDa 2-5A RNase L immunoassay when it becomes available.
c. Differential Brain Function and
Static Testing:
• MRI: those with significant neurological
finding should be considered for a MRI to rule out multiple sclerosis (MS), and
cervical stenosis. MRI interpretation: it is important to look for changes that
are easily overlooked such as dynamic disc bulges/herniation or minor stenosis,
which can be important in the pathogenesis.
• Quantitative EEG, SPECT and PET
Scans and Spectography: qEEG analysis of brain waves, SPECT estimation of dynamic brain blood
flow and PET analysis of brain metabolism show diagnostic promise and will
become more important as these techniques are refined and research confirms
their diagnostic value.
d. Tilt Table Test: if there is a fall in BP and/or
excessive rapidity of heart beat upon standing; and if patient is troubled by
dizziness, feeling light-headed or ‘woozy’ upon standing or when they are
standing motionless. Note: fall in BP when standing may be delayed by several
minutes in ME/CFS patients.
e. Sleep Study: if poor sleep is troublesome and
does not improve with medication or sleep hygiene. A sleep study can show poor
sleep architecture, particularly the decrease in time spent in stage 4 sleep
and can rule out treatable sleep dysfunctions such as sleep apnea, upper airway
resistance syndrome and restless leg syndrome. Indications include: the patient
wakes up out of breath, or there is great disturbance of the bedding, or sleep
partner indicates that the patient snores and/or appears to stop breathing at
times and/or has significant movement of their legs while sleeping.
f. 24-Hour Holter Monitoring: if a significant arrhythmia is
suspected. Characteristic repetitively oscillating T-wave inversions and/or
T-wave flats can be confirmed during 24-hour electrographic monitoring. This
pattern may not be reported or subsumed under non-specific T-wave changes by
interpreter.
g. Neuropsychological Testing: can be utilized to identify
cognitive dysfunction and/or confirm diagnosis. If done, it should focus on the
abnormalities known to differentiate ME/CFS from other causes of organic brain
dysfunctions.
4. Making a Positive Diagnosis for ME/CFS: If the patient's
presentation meets the diagnostic criteria for ME/CFS, classify the diagnosis
as ME/CFS except when the specified exclusions are present. If the patient has
prolonged fatigue but does not meet the criteria for ME/CFS, classify the
diagnosis as idiopathic chronic fatigue.
New Symptoms: People with ME/CFS can develop other
medical problems. New symptoms need to be appropriately investigated.
ã 2003 by The
Haworth Press, Inc. All rights reserved.
End of Section – Definition & Diagnosis
Much more - order the full document
Encourage your doctor, hospital, library, to order the Special edition of the JCFS, 2003, vol 11, # 1, Myalgic Encephalomyelitis
Clinical Working Case Definition, from The
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========================================================================
See
the Expert Panel review of the current research; http://www.oocities.org/tcjrme/fundamentals3.html
The Committee for
Justice
and Recognition
of Myalgic Encephalomyelitis
Return to Fundamentals Page; http://www.oocities.org/tcjrme/fundamentals.html
TCJRME F - 2
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