Introduction
Part 1 of
these extracts from the grey literature on ME/CFS (1956 – 1990)
can be seen
here - click here:
1991:
The Spring 1991 issue
of The CFIDS Chronicle was a Conference Issue reporting on the
CFIDS Association of America Research Conference held on 17th-18th
November 1990 at Charlotte, North Carolina. Amongst the notable
presentations were the following:
·
Marc Iverson,
President of the CFIDS Association,
said in his Introductory Remarks: “The impact of this disease
can be swift and relentless….I have never known a person with
full-blown CFIDS who has not considered suicide at some point or
points in his or her illness….The physical impact is often
absolutely devastating. Pain, weakness, exhaustion, dizziness
and more than another dozen other symptoms commonly occur….This
intellectual impairment is truly bizarre… we have trouble
finding words or our way home….Profoundly debilitated,
intellectually compromised, unable to emerge from the haze,
patients drop from sight….the things that matter to them –
relationships, jobs, incomes, homes, families – slip through
their fingers”.
·
Dr Paul Cheney
(speaking about The Clinical and Epidemiological Features of
CFIDS) said: “Early in the course…these patients exhibit
disturbances in balance. You can perform simple neurologic tests
in the clinic – Romberg and Tandem Stance. Patients
will exhibit difficulties, even athletic individuals, and
they’ll be quite surprised at how they can’t seem to stand up…
if, in fact, they do not fall over”.
·
Dr Irina
Rozovsky (speaking
about Levels of Lymphocytes, Soluble Receptors & IL-2 Inhibitors
in Sera from CFIDS Patients) said: “Chronic fatigue
syndrome can be described as an immune dysregulative state,
characterised by global immune upregulation with discrete immune
defects….Normally T-helper cell activation is
mediated by two intracellular signals. The first signal is the
activation of protein kinase C….The second major signal for
T-cell activation is the mobilisation of both cytotoxic and
extracellular calcium. This activation finally leads to the
secretion of interleukin-2 (IL-2) and the expression of IL-2
receptor on the surface of T cells….Soluble IL-2 receptors
have been found in…sera from patients with multiple sclerosis,
autoimmune diseases, AIDS, different types of lymphomas and
leukaemias and in cancer patients who use IL-2 therapy. It is
well-known that patients in IL-2 treatment have the same kind of
symptomatology as our chronic fatigue syndrome patients….We have
measured the levels of these soluble IL-2 receptors and T8
receptors in chronic fatigue syndrome patients….We have found
that our patients have an elevated level of IL-2 receptor
compared to healthy controls. Their level of soluble T8
receptor will also be significantly higher than for the control
group….These two soluble receptors [IL-2 and T8 receptors],
which reflect certain T-cell responses, could be very good
markers for the disease and may even reflect the degree of
severity of the illness”.
·
Dr John Martin
(speaking about Detection of Viral Sequences Using Gene
Amplification) said: “(We have used PCR) in helping to
establish that at least a significant number of patients
diagnosed as having CFIDS do have a persistent viral
infection associated with neurological dysfunction, accompanying
metabolic changes, and immunological changes”.
·
Dr Anthony
Komaroff said: “Our
model for CFIDS is…that fundamentally, the illness
involves a compromised immunity….This compromised immunity leads
to a reactivation of latent viruses including HHV-6 and EBV. In
some patients, it may well include the entero, coxsackie, echo,
and even polio viruses….In other patients, environmental toxins
could possibly compromise immunity….What all of the data
indicates to me is something that will come as no surprise to
any of you, and that is that CFIDS is not simply a state of
mind”.
·
Dr Daniel
Peterson said: “All
of us who treat patients, I think, would agree that there is
a subset of patients with CFIDS who are really very disabled.
Their lives resemble nothing of their former lives;
oftentimes they’re bedridden. They interact with nobody….I
have been impressed…by how few patients are malingering,
attempting to imitate this disease, or attempting to seek any
secondary gains”.
·
Dr Robert
Suhadolnik said: “The
2-5A synthetase/RNase L cell system is a mechanism by which we
are able to defend ourselves from viral infections….We have
patients whose RNase L is completely shut down….As we were
studying HIV-infected individuals, we found that the HIV
retrovirus shuts down the RNase L. Had we not done those
studies, we would not have had an explanation for what we’re
seeing here. If there is a retrovirus involved with CFIDS,
this would well explain why the system is shut down with respect
to the RNase L”.
·
Dr Jack
Lieberman (speaking
about serum ACE in ME/CFS, which is
angiotensin-converting-enzyme, angiotensin being one of the main
substances in the body that controls blood pressure) said:
“An elevated serum ACE could very well be a marker for (ME)CFS….(Because
high levels of ACE are found in sarcoidosis) a
relationship of chronic fatigue syndrome to sarcoidosis must
also be considered….Elevation of serum ACE in patients
with CFS lends credence to the concept that CFS is a true
disease”.
·
Dr Denis
Wakefield (an
immunopathologist from Australia) said: “I do not think that
we should blindly accept the CDC criteria for the diagnosis of
this disease….Last year we published, in the Australian Medical
Journal, a comprehensive study summarising the immunological
abnormalities found in 100 CFS patients compared with age-and
sex-matched controls. This group of patients had significant
lymphopenia, which occurred in both the helper and suppressor
T-cell subsets. They also had increased HLA DR antigen
expression on the peripheral blood mononuclear cells….The
primary reason your HLA DR antigen rises is because of
interferon….The major conclusion from this study is that the
abnormalities that we have observed in the T-cell mediated
immunity in people with CFS are not attributable to
depression…most of our studies now indicate that the site of
pathology in this disease must be within the central nervous
system”.
·
Dr Nancy Klimas said: “The most
compelling finding was that natural killer cell cytotoxicity in
chronic fatigue syndrome was as low as we have ever seen in any
disease. This is very, very significant data with very,
very low levels of lymphocyte response to mitogens….The actual
function was very,very low – 9% cytotoxicity; the mean for the
controls was 25. In early HIV and even well into ARC
(AIDS-related complex) NK cytotoxicity might be around 13
or 14 percent….Chronic fatigue syndrome patients represent the
lowest cytotoxicity of all populations we’ve studied”.
·
In the moderated
Question and Answer session, Dr Klimas warned that in almost
every case, any psychiatrically active drug that has been tested
has been shown to be immunosuppressive; she specifically warned
against the side effects of Prozac (“Prozac is anything but a
benign drug. I would caution anyone who prescribes it to know a
lot about the side effects of this drug”); she warned
against the use of the tricyclics in ME/CFS because they
suppress immune function and she pointedly warned against use
of lithium (a drug that Simon Wessely recommends for ME/CFS:
“There is no doubt that at least half of CFS patients have a
disorder of mood. The management of affective disorders is an
essential part of the treatment of CFS/ME. Numerous trials
attest to the efficacy of tricyclic antidepressants in the
treatment of fatigue states. Patients who fail to respond
should be treated along similar lines to those proposed for
treatment-resistant depression. Adding a second antidepressant
agent, especially lithium, may be beneficial” (The
chronic fatigue syndrome – myalgic encephalomyelitis or
postviral fatigue. S Wessely PK Thomas. In: Recent Advances in
Clinical Neurology (ed): Christopher Kennard. Churchill
Livingstone 1990: pp 85-131).
·
Dr Byron Hyde
said: “Brain mapping has started to change the ideas and
the views of physicians across North America. When
you show them a photograph of large areas of the brain injured
by this disease, they start thinking, maybe I will be next.
In Canada, we have a large number of physicians with CFIDS….Look
at the primary manifestations of this disease – they reflect
central nervous system damage….There are also major, major
cardiac aspects of this disease”.
·
Dr Carol Jessop
said: “I have been involved with CFIDS since 1983….I knew
that what (my patients) were telling me was something very
serious; it is one of the worst illnesses that I ever heard
described to me before….Nausea…seems to
increase as the illness goes on….balance problems increase
in the chronic stages….98% of patients acutely complained of
frequent urination…. Cold extremities are also very common….89%
of the patients had irritable bowel syndrome….I am not the only
one who has noted the high incidence of endometriosis….87% have
fibromyositis. General abdominal tenderness was very common, in
80% of patients….Low magnesium levels are common….Low zinc
levels are also common….Both of these trace minerals are
absorbed in the gut and, I think, are being malabsorbed by our
patients”.
·
Dr Alan Landay
said: “We have found changes in three markers which seem
to be the most significant. First, the CD 11 B
marker, which identifies the suppressor cell, decreases in CFIDS
patients….There is also an increase in the CD38 and the HLA DR
indicating activation….Flow (cytometry) has been a useful tool
for studying a number of diseases, including cancer, AIDS, and
autoimmune disease. It can identify individuals with immune
disorders by using a large panel of markers….Flow cytometry has
revealed evidence of CD8 activation in CFIDS”.
·
Dr Jay Levy
said: “if you look at the activation markers, they are raised
in both CFIDS and acute viral illness….Some individuals…will not
be able to turn off that activated state. The agent remains as
a constant thorn, forcing the immune system to be activated
until the agent is eliminated. In these individuals, the
immune system never returns to a normal resting state. So these
people are in a state of chronic immune activation. What is the
result of this chronic immune activation? If an activated white
cell is doing its duty, it has to be producing a certain number
of lymphokines or cytokines that are working to control the
agent that is infecting the body. But these cytokines can have
side effects….Cytokines affect the brain, the bowel, the muscle,
the liver (which) one sees in CFIDS. So, increased cytokine
activation can affect many different tissues in the body (and)
can also cause reactivation of other viruses….This disorder
could be controlled by eliminating the causative agent or
quieting down the hyperimmune system….There is much clinical
information showing that (CFIDS) has often led to other immune
diseases….The sequelae…include autoimmune disease and, on some
occasions, MS”.
Other speakers discussed functional
brain imaging, sleep disorders, abnormal memory processes and
speed, distinctive brain patterns seen in ME/CFS and cluster
outbreaks of the disease.
1991: In an article
entitled “Skeptical of Skeptics”, Thomas English, formerly
Assistant Clinical Professor of Surgery at Duke University in
the US who had to retire due to ME/CFS, wrote: “Skepticism
permeates our profession. It is ingrained during medical
training and reinforced by professional experience. To be
skeptical is to be detached, rational, and objective.
Skepticism is widely perceived as the prudent, conservative way
to deal with ambiguous situations….healthy skepticism is the
‘in’ attitude for intelligent, discriminating physicians. But
healthy for whom?….There is nothing in your experience in
medical school, residency, or practice with its gruelling hours
and sleep deprivation that even approaches the fatigue you feel
with this illness….You, too might wonder about some of your
symptoms had you not talked to other patients with similar
experiences or talked with physicians who have seen hundreds of
similar cases. With experience, a pattern emerges: the bizarre
and implausible become commonplace and credible….This is no
illness for cookbook doctors. It is a disease for medical
intellectuals with supple and open minds” (JAMA
1991:265:8:964).
1991:
In March 1991 The
CFIDS Association produced its first issue of “Physicians’
Forum”, with contributions from Drs David Bell, Paul Cheney, Jay
Goldstein and Charles Lapp. The issue addressed the treatment of
CFIDS/ME/CFS and the difficulties this posed because of the
complexity and diversity of symptoms; topics covered included
nutritional supplements that had been found helpful;
intramuscular gamma globulin, anti-inflammatory agents, calcium
channel blockers, ampligen, lifestyle adjustments, stress
reduction and symptomatic treatment of specific symptoms. The
over-riding message came from Dr David Bell: “The
treatment strategies for CFIDS are still in their infancy, and
very little progress will be made until the underlying cause or
causes of the illness are clearly defined”, a view not
shared by UK psychiatrists of the Wessely School (see below).
Another view expressed by the US
physicians that is not shared by the Wessely School was the
emphasis on the need to divide patients into several groups
(mild to moderately affected, moderate symptoms but prolonged
course, and those with severe symptoms), since the diversity in
the clinical picture is the determining factor in symptomatic
treatment, yet the Wessely School advocate a “one size fits all”
regime of cognitive restructuring (to persuade patients with
ME/CFS that they do not have a physical disease) combined with
graded aerobic exercise and adjunctive anti--depressants.
1991:
On 16th
April 1991, Dr Elaine DeFreitas addressed the US House of
Representatives Committee on Energy and Subcommittee on Health
and the Environment: “Let us note at the beginning that
CFIDS or CFS/ME is not about being tired. Researchers have
demonstrated numerous abnormalities of the immune, muscular,
cardiovascular, and central nervous systems in people with
CFS/ME; it is truly a multi-system disease with a strong
component of immune dysfunction. In fact, one respected
scientist called CFS/ME ‘A disease of acquired immunodeficiency’
”.
1991:
Highlights of the Los
Angeles Conference (Chronic Fatigue Syndrome: Current Theory and
Treatment; Patient Advocacy Convention) held on 18th-19th
May 1991 included presentation of new and important data
(reported in The CFIDS Chronicle Fall 1991). Dr Ismael Mena,
Director of the Division of Nuclear Medicine at Harbor-UCLA
Medical Centre, presented data from SPECT scans of ME/CFS
patients. He found “significant reduction in blood flow
(hypoperfusion) of the temporal lobes amongst CFIDS patients.
Seventy percent had hypoperfusion of the temporal lobes, while
45 percent showed reduced blood flow in the frontal lobe. The
parietal lobes of 40 percent of CFIDS patients indicated reduced
blood flow. These results were obtained from SPECT scans taken
while the patients were at rest….Dr Mena conducted a
second study to determine if there were any differences in blood
flow after exercise….Dr Mena summarised the result of this
study by saying: ‘We saw a depression in cerebral blood flow
after exercise when we should have observed an increase’.
Temporal and frontal lobes seemed to be most affected by
exercise. Hypoperfusion after exercise was more pronounced than
that exhibited while patients were at rest”.
Dr James Daly, Co-Director of the
Exercise Physiology Laboratory and Director of the Harbor-UCLA
Sleep Disorders Laboratory found that most CFIDS (ME/CFS)
patients “had low normal maximal exercise capacity and oxygen
consumption when compared to sedentary controls (the
controls were “the most deconditioned people we could find”).
In addition: “Several patients with no history of systemic
hypertension demonstrated an exaggerated increase in blood
pressure during exercise”. Daly also found that
“Many individuals, with no history of lung disease, had
low CO2 levels at rest. Low carbon dioxide levels lead to
shortness of breath after any amount of exertion and might
explain why some people with CFIDS experience bouts of ‘air
hunger’ ”.
1991:
In August 1991 the
ANZMES (Australia and New Zealand ME Society) magazine “Meeting
Place” No: 36 published “Clinical Protocols from America” in
which Dr David Bell said: “There is a huge spectrum of
disease severity in CFIDS (ie. ME/CFS)….Factors which
influence the likelihood of spontaneous resolution include the
pattern of onset, the severity during the first months or years
of illness, the age and sex of the CFIDS patient, and the
pattern of the present symptoms (no mention here of
maintaining factors being aberrant illness beliefs perpetuating
the perceived illness, ie. the Wessely School’s belief)….Patients
who have been ill for five years or longer, have prominent
neurologic symptoms, and had a gradual onset of symptoms are
less likely to experience spontaneous resolution of their
symptoms….Unfortunately, there are patients who are very ill
with CFIDS, many with very serious neurologic symptoms,
where it is unlikely that they will spontaneously recover to a
normal or near normal level of function….Very little progress
will be made until the underlying cause or causes of the illness
are clearly defined” (this should be compared with
Simon Wessely’s view that research into aetiology is
unnecessary: nine years later he stated: “Some illnesses are
treated without knowledge of the cause….examples include…
chronic fatigue syndrome (CFS)” – New research ideas in
Chronic Fatigue. RSM Press; 2000).
In the ANZMES article, Dr Anthony
Komaroff from Harvard said: “Chronic fatigue syndrome
represents a state of excessive cytokine production and
therefore vitamin utilisation pathways may be partially
blocked. For this reason we recommend that multivitamin therapy
be employed in the treatment of chronic fatigue syndrome
(sixteen years later NICE, influenced by the Wessely School,
effectively prohibited testing for vitamin levels and
vitamin/mineral supplementation in ME/CFS patients) ….SPECT
scanning often reveals larger areas of low blood flow within the
temporal lobes”; Komaroff went on to mention the “pressure-like
headaches and balance disturbances common to this disorder”.
1992:
The February 1992
issue of The CFIDS Chronicle carried on its front page a
Statement from Dr Walter Gunn, Principal Investigator of CFS
studies at the CDC (Centres for Disease Control): “Our
Surveillance Study does not support the notion that CFS is a
psychiatric illness, and in fact, suggests that it has an
organic basis. Recent published reports suggest that the immune
system may be involved in this illness. Additional published
research suggests that viruses may also be involved in CFS”.
1992:
The September 1992
issue of The CFIDS Association’s Physicians’ Forum (entitled
“CFIDS: The Diagnosis of a Distinct Illness”) carried important
articles by key players in the ME/CFS stakes, including Drs
David Bell, Paul Cheney, Charles Lapp and Nancy Klimas.
Dr Bell
stressed the importance of a thorough physical examination and
suggested an appropriate laboratory workup for those with
suspected ME/CFS; he said: “Fatigue, sore throat, abdominal
pain, headache, lymph node pain, myalgia and arthralgia suggest
the presence of viral infection. Neurologic symptoms such as
dizziness, balance disorder, parasthesias, and cognitive
disturbances involving short-term memory and attention may be
present….Neurological abnormalities may include hyper-reflexia
in the lower extremities, Romberg’s sign and impaired tandem
gait….Numerous immunologic abnormalities have been described in
patients with chronic fatigue syndrome….Decreased natural killer
cell function is perhaps the most reproducible immunologic
abnormality….The diagnosis is made on the basis of severe
fatigue, a characteristic pattern of symptoms, and exclusion of
other illnesses”. The seriousness of the disorder is
reflected by the fact that Dr Bell listed the differential
diagnoses as including rheumatoid arthritis, lupus
erythematosus, Lyme disease, multiple sclerosis, sarcoidosis,
hepatitis B, polymyalgia rheumatica, HIV virus infection and
malignant disease, whilst Leonard Calabrese categorised the
differential diagnoses as endocrinological (hypothyroidism,
Addison’s disease, diabetes); rheumatological (fibromyalgia,
Sjogren’s syndrome, polymyalgia rheumatica, polymyositis);
neurological (obstructive sleep syndrome, multiple sclerosis);
infectious (Lyme disease, HIV); haematological (anaemia,
lymphoma) and renal, hepatic or cardiac disease.
In his
presentation entitled “The Diagnosis of Chronic Fatigue
Syndrome: An Assertive Approach” that was co-authored by Dr
Charles Lapp, Dr Paul Cheney stressed the need for the case for
diagnosis by objective criteria. He said: “The central
problem is case selection. Many patients with CFS are excluded
from studies because they seem ‘too sick’ to have CFS….CFS cases
are mixed in with non-cases. Inappropriate controls are
sometimes used. Some investigators, aware or unaware of a bias,
attract or include in their studies the patients who best fit
their view of CFS. This so-called selection bias can markedly
affect the observations of a study….The medical evidence cited
for CFS asserts that the following are present more or less in
every patient during the course of his or her disease: T-cell
activation, discrete immune defects, viral activation or
re-activation, exercise-related dysfunction, and evidence of
brain dysfunction or injury. While none of these tests can
stand alone to ‘diagnose’ the illness, an array of these tests
can be used to support this diagnosis” (it is worth
recalling that in the UK, NICE has effectively proscribed these
tests). There are a number of criticisms given for using
(these) tests in the diagnosis of CFS. They include the
following: (1) We lack a gold standard for determining this
disorder: if a test abnormality has been shown in the medical
literature to be associated with a certain disease, such as a
positive ANA in lupus, then it is a valid test to be used in
supporting a clinical diagnosis…. (2) Even if there are test
abnormalities which can be associated with CFS there is no need
to make a more definite diagnosis because there is no treatment
for the disease: if this were a valid argument, then it would
also apply to multiple sclerosis, many cancers, and even AIDS.
Documentation of an illness by objective criteria is important
not only to confirm the diagnosis, but also to reassure the
patient…Though there may be no scientifically validated
treatment options for CFS…there are many therapeutic rationales
based on test abnormalities which can defend empiric therapy….In
the everyday practice of medicine, empiric therapy is often
warranted in severe or functionally devastating
illness….(Furthermore), the ability to successfully argue for
disability is an extremely important aspect of therapy for this
disorder….(3) CFS is a ‘self-limited illness’: this
misperception of CFS is pervasive among many clinicians and the
lay public. A debilitating illness lasting years or longer is
in fact not self-limited, and it deserves considerable medical
attention….Good documentation of this disorder lays the
groundwork for future empiric intervention”.
Cheney
then listed 22 physical findings in ME/CFS, stating that
“Contrary
to suggestions by some investigators, abnormalities on physical
examination, although sometimes subtle, are usually present”;
he listed 10 routine laboratory tests that are often present
in ME/CFS patients; he listed
his proposed set of
tests for ME/CFS which include 4 tests of immunity and 5 tests
of discrete immune defects; 5 tests of viral activation or
re-activation; 5 tests of exercise-related dysfunction, and
tests of brain dysfunction (structural scans, functional scans
and neuropsychometric tests, including the Halstead Reitan
battery). Cheney continued:
“CFS clinical and bench
researchers are developing an array of tests which are
increasingly sensitive and specific for CFS – particularly when
used in combination. When patients present with
symptoms that suggest CFS, we believe it is in their best
interests to …employ these tests to confirm the diagnosis and to
document the nature and extent of each case. This
information…enables the patient to make appropriate lifestyle
adjustments (including defence of disability claims when
necessary)”.
Cheney’s
article was followed by a comprehensive overview as an aid to
the diagnosis of ME/CFS by Dr Jay Goldstein, who addressed skin
disorders in ME/CFS; headaches; eye problems; ear, nose and
throat problems; pulmonary complications (“Dyspnoea,
either at rest or on exertion, is the most frequent [pulmonary]
complaint, but is probably centrally mediated”);
cardiac abnormalities (“coronary artery spasm and
microvascular angina should be considered”);
gastrointestinal problems (“Gastrointestinal complaints
are very common, and symptoms of irritable bowel form an
integral part of the CFS spectrum of symptoms” – this
should be compared with Professor Peter White’s assertion in
2006 that
“bowel symptoms are not
part of CFS/ME”; St Bartholomew’s Hospital Chronic
Fatigue Services, Stakeholder comments on Chapter 6 of the draft
NICE Guideline on “CFS/ME”, page 316); pelvic disorders (“Perhaps
the most common pelvic disorder in CFS is endometriosis….Adnexal
masses and polycystic ovarian syndrome occur with greater
frequency in CFS….A much higher percentage of my
patients in a CFS practice have developed ovarian carcinoma that
I experienced while practising family medicine”);
genitourinary complaints (“Dysmenorrhea is also more common
in CFS patients, even if endometriosis is not present….The
primary genitourinary complaint in the male with CFS involves
prostatic discomfort, frequency, and nocturia”);
musculoskeletal abnormalities; neurologic abnormalities (“fasciculations
are fairly common, as are tremors….A Hallpike test is sometimes
abnormal in vertiginous patients, as is the Romberg test.
Muscle weakness is common….Patients should be followed for the
development of multiple sclerosis or, more commonly in my
experience, immune polyneuropathy”); associated
carpal tunnel syndrome (CFS) and thoracic outlet syndrome (TOS)
(“carpal tunnel syndrome and thoracic outlet syndrome are
fairly common in CFS”); haematological abnormalities
(“CFS patients often complain of easy bruisability or
spontaneous ecchymoses….Platelet function studies are
sometime abnormal”). Goldstein noted that: “The sed
rate is often very low. Immune complexes and positive
anti-nuclear antibodies are encountered very frequently….Elevated
levels of various cytokines and their receptors are often seen”);
he discussed at length the cytokine abnormalities
found in ME/CFS and other distinct laboratory abnormalities, as
well as SPECT scan abnormalities, evoked responses testing, PET
scan abnormalities, lesions detectable by MRI scans,
abnormalities on neuropsychological testing, and functional
capacity evaluation (ie. an assessment of the patient’s ability
to perform work demands and activities of daily living).
Goldstein concluded by stating that he knew of no other
mechanism than a limbic encephalopathy that could produce the
diagnostic constellation seen in ME/CFS, but he pointed out that
“Secondary adrenal insufficiency due to a central
mechanism relating to CRH deficiency could be responsible for
many CFS symptoms” (in which he specifically included
vertigo, intermittent blurred vision and alopaecia).
Dr Nancy
Klimas wrote about “Diagnosing CFIDS: An Immunologist’s
Approach”, saying: “Our group in Miami has been actively
working to better understand CFIDS since 1985….Some of this
work has helped to develop a sense of diagnostic certainty in
the evaluation of CFIDS patients, as well as to identify
subgroups that are immunologically different from the majority
of CFIDS patients….We have found the immune evaluation to be
quite important, as it not only helps classify the patient, but
often helps to direct the care of the patient”. Dr
Klimas went on to discuss the level of T-cell activation seen in
ME/CFS patients, the diminished cell function, and the evidence
of viral reactivation.
Other
contributors to this issue of “Physicians’ Forum” who provided
their expertise on the diagnostic approaches to ME/CFS included
James Jones (“Unfortunately, the group of individuals
being given this diagnosis remains quite heterogeneous. Unless a
common definition is applied to all patients…the heterogeneity
of the population will preclude determination of diagnostic
tests”); Anthony Komaroff (“Our studies
also indicate that two additional tests are elevated more often
in patients with CFIDS: immune complexes and
immunoglobulin G (IgG”); Benjamin Natelson (“The major
lab tests I check are those indexing immunological dysfunction.
I do a standard clinical immunological profile, including
circulating immune complexes, complement levels and IgG
subclasses. I have found a rough correlation between disability
and the number of these tests that are positive….being able to
report such examples of immune dysfunction is often of practical
value in assisting the severely ill CFS patient in obtaining
disability”) and Daniel Peterson (“Often an
objective measurement of the fatigue, such as one obtained
through exercise tolerance testing with expired gas exchange,
will document impaired VO2 utilisation. This documentation often
helps to affirm the significance and extent of this aspect of
the disease”).
In the UK,
all this evidence of serious organic disease fell – and
continues to fall -- on the deliberately deaf ears of the
Wessely School and hence on the equally deaf ears of NICE, the
Medical Research Council and the NHS. Indeed, it was stated at
the time that the Wessely School and UK clinicians would
never accept the views of “people like Cheney”
(personal communication).
As
recently as March 2011, The British Association for Chronic
Fatigue Syndrome/ME (BACME), whose Chair is Dr Esther Crawley (a
keen Wessely School supporter and a member of the group which
produced the NICE Clinical Guideline 53, and who is currently
embroiled in altercations about her desire to use children with
ME in her study of the Lightning Process) issued glowing support
for the much-criticised PACE Trial, claiming the results provide
“convincing evidence that GET and CBT are safe and effective
therapies and should be widely available for patients with
CFS/ME as per the NICE guidelines….This trial shows that
approaches aimed at staying within limits imposed by the illness
are less effective than those that test such limits”.
BACME’s membership is open only to those UK healthcare
professionals and researchers who accept the recommendation of
the NICE Guideline 53 (ie. that CBT and GET are the best
“evidence-based” approaches to ME/CFS). The Association’s
objective is “To champion
evidence-based approaches to the treatment of CFS/ME, such as
those provided in the NICE guidelines” and BACME will
use “clinical expertise to inform healthcare policy”
and will “provide training for clinicians and researchers from
all disciplines involved in the diagnosis and treatment of
CFS/ME”. Of great concern is the fact that BACME
claims it has an “active training programme” and
“the ability to provide national training programmes” about
ME/CFS for UK healthcare professionals. As with other
adherents to the Wessely School’s belief that ME/CFS is a
behavioural disorder, BACME appears systematically to ignore the
biomedical evidence proving that ME/CFS is a serious
multi-system organic disease whose devastating impact cannot be
ameliorated by pretending otherwise.
1992:
A Press Release for
the Albany, New York, International Clinical and Research
Conference on ME/CFS (held on 2nd-4th
October 1992) from the Department of Neurology, Institute of
Neurological Science, University of Glasgow said: “We will
report…our new findings relating particularly to enteroviral
infection. We have now extended our PCR data to cover
hundreds of patients together with controls and have continued
to find a very significant proportion of the patients’ muscle
biopsies to contain enterovirus on PCR. In addition we have
used several different types of enteroviral primers and have
obtained identical results in the patients with these primers,
the control muscle biopsies from healthy subjects and patients
with other muscle diseases being entirely negative. We
furthermore have isolated RNA from patients and probed this with
large enterovirus probes which demonstrated that full length 7.4
kilobase virus was present in these patients. Indeed, detailed
studies including Northern Blot analysis showed that the
material was true virus….Furthermore, this virus was shown to be
replicating normally at the level of transcription. Sequence
analysis of this isolated material showed that it had 80%
homology with coxsackie B viruses and 76% homology with
poliomyelitis virus, demonstrating beyond doubt that the
material was enterovirus. We were able to extend these
studies…by being able to study post-mortem material from a
definite case of chronic fatigue syndrome….This showed that
enterovirus was present in skeletal muscle, in heart muscle, but
particularly was abundant in brain. Detailed studies of the
brain enterovirus revealed that it was most prevalent in
diencephalic, particularly hypothalamic, regions. Clinical
studies employing dynamic techniques of measuring neuroendocrine
neurotransmitter hypothalamic function showed that there was
disturbed hypothalamic regulation for neurotransmitters,
particularly for 5-hydroxytryptamine and for hormones governing
water metabolism in affected patients”.
1992:
Scientists and
clinicians at The Albany Conference discussed current concepts
in ME/CFS, the epidemiology of ME/CFS, clinical research, viral
studies, immunological studies, evidence of mitochondrial
dysfunction, abnormal neuroendocrine responses, including
defects in central control of respiration (ie. a defect in HPA
axis function), evidence from ergometry with gas analysis which
proves that patients are truly “weak”, evidence establishing two
gene markers that occur frequently in CFIDS patients but not in
the general population (persons with HLA Dr4 and Dq1, who
collectively represent less than 5% of the general population,
were found in 93% of the ME/CFS population tested, and both
markers are associated with decreased NK cell activity), ocular
manifestations, and public policy, including the economic impact
of ME/CFS. A review of the conference was published in The CFIDS
Chronicle, Summer 1993. The full proceedings were published in
the Journal of Clinical Infectious Diseases 1994:18: S1 (http://cid.oxfordjournals.org/content/18/Supplement_1).
1993:
In his now
world-famous Testimony before the US FDA Scientific Advisory
Committee on 18th February 1993, Dr Paul Cheney said:
“I have evaluated over 2,500 cases….We have seen the worst
and the best of the range of scenarios that can befall a patient
with this disorder. At best, it is a prolonged postviral
syndrome with slow recovery or improvement within one to five
years. At worst it is a nightmare of increasing disability with
both physical and neurocognitive components. The worst cases
have both an MS-like and an AIDS-like clinical appearance….We
have lost five patients in the last six months….The most
difficult thing to treat is the severe pain….The most alarming
is the neurological and neurocognitive elements of this
disease. Half have abnormal MRI scans, 80% have abnormal SPECT
scans, 95% have abnormal cognitive evoked EEG brain maps. Most
have abnormal neurologic examinations….40% have impaired
cutaneous skin test responses to multiple antigens. Most have
evidence of T-cell activation….From an economic standpoint, this
disease is a disaster. 80% of the cases evaluated in my clinic
are unable to work or attend school…The yearly case production,
if plotted, is exponential….The medico-legal aspects of our
practice steadily grow as this disease eats at the fabric of our
communities. We admit regularly to the hospital
(with)…inability to care for self….CFS is an emerging, poorly
understood disorder with a distinctive clinical presentation. I
am not at all sure that it is as heterogeneous as some would
lead you to believe….This disorder is a socio-economic as well
as medical catastrophe that will not end….This disease is too
complex to rely on standard medical orthodoxy to explain
it….Listen to patients with an open mind. Failing that, then
listen to those who have spent countless hours with a thousand
patients. Most of us have some wisdom to impart and most of
that came from patients”.
1993:
The Los Angeles
conference entitled “The Medical Neurobiology of Chronic Fatigue
Syndrome and Fibromyalgia” was held on 7th-9th
May 1993 and reported in the Summer 1993 CFIDS Chronicle.
Emphasis was again placed upon the importance of brain scans,
with the most talked-about technology being the results of Dr
Ismael Mena’s SPECT scans (conventional brain scans such as MRI
and CT scans look at brain structure over function, but SPECT
scanning examines brain function by measuring cerebral blood
flow or CBF). Results showed profound dysfunction in CFIDS
patients: “We are seeing a pattern of blood flow that is
quite different from the uniform pattern of distribution that we
see in the normal individual….CFIDS is characterised
by a diminution of CBF and diminished uptake of HMPAO (a
radioisotope used to track CBF), primarily in the right
hemisphere, extensively involving the frontal and the temporal
lobes….The study of CBF and its relationship to cerebral
function appears to be a very powerful biological marker for CFS”
(brain imaging for NHS patients with ME/CFS is not available in
the UK and requests are refused). The CFIDS article continued: “Cerebral
hypoperfusion is the most common finding in the CFIDS brain, and
researchers have associated it with nearly every CFIDS symptom”.
Drs Mena and Goldstein presented a series of SPECT scans “which
showed extreme hypoperfusion in the brain following
exercise. There appeared to be ‘holes’ where blood would
normally be flowing – the degree of hypoperfusion was
astonishing. Even 24 hours later, cerebral blood flow was
severely reduced”. Dr Byron Hyde from Canada said: “What
we’re going to tell the insurance companies from now on is not
ME, for which they won’t pay, and not CFS, but major acquired
brain dysfunction. And that is what these people actually have”.
Other researchers drew attention
to the presence of vertigo in patients with ME/CFS (caused by a
viral condition of the inner ear called endolymphatic hydrops,
which is “probably the result of the reactivation of viruses
caused by the dysregulated immune system”, according to Dr
Samuel Whitaker from UC Irvine); to a central defect in
the HPA axis that “prevents the immune system from shutting
down, and results in constant immune activation which makes
people with CFIDS feel sick” according to Dr Anthony
Komaroff from Harvard. Drs Lapp and Goldstein noted a
particular irregularity in tidal volume in CFIDS patients (“This
phenomenon has never been described before in any population
and…we think that it’s a diagnostic marker for CFS”).
The Cheney-Lapp study showed that neuroendocrine
responses were often reversed or blunted; Drs Lapp and Sietsema
reported that people with CFIDS reached anaerobic threshold much
sooner than predicted (the point at which a healthy person
becomes completely fatigued and cannot exercise any longer,
known as “hitting the wall”); Dr Byron Hyde explained
that what he called “a perfect virus” is one which can
live and propagate indefinitely in the host without detection,
and that “this infection would produce the immune activation
which is responsible for many CFIDS symptoms. ‘As long as the
cell is at rest…it can do what it wants. As soon as you put it
under stress, under work – whether it’s cognitive work or
physical work or sensory work makes no difference – that cell
doesn’t function’ ”.
A major section of the conference
addressed the immune defects in CFIDS patients: “Up-regulation
of the immune system has been well-documented in the CFIDS
literature….That this immune activation is responsible for many
CFIDS symptoms has been accepted by most researchers and
physicians”. Dr Catherine Rivier from the Salk
Institute in La Jolla, California, said: “Stress in any
form places undue pressure on the immune system….In a normal
immune system, interleukin (IL-1) is produced in response to
stress. In CFIDS, IL-1 may be obstructed, resulting in a
blockage of corticotropin releasing factor (CRF), an
immunosuppressor. If CRF is not released, the immune system
will remain activated indefinitely”. Dr Nancy
Klimas said: “There is considerable question whether all
CDC-defined CFIDS patients are suffering from the same
disorder….In a normal population, 20 percent of lymphocytes are
active at any given time. In CFS, up to 80 percent of the cells
are working….These lymphocytes and cytokines are so up-regulated
that they cannot be driven any harder. It is as if they have
been pushed as far as they can go and the immune system is
completely exhausted”.
1993:
The Summer 1993 issue
of The CFIDS Chronicle Research Update also devoted much space
to the finding of a retrovirus by Dr Elaine DeFreitas. The issue
documented the stringency of Dr DeFreitas’ research, her
willingness to share data and primers with the CDC, her offer to
travel to Atlanta at her own expense to conduct side-by-side
experiments using the same patient and control samples, the
CDC’s refusal to participate in such collaborative studies with
her, their damning dismissal of her work showing the presence of
a retrovirus in ME/CFS and their apparent inability to replicate
her results. It was noted that “certain scientists appear
eager to discount any possibility of a retrovirus with CFIDS”.
The same issue carried a
referenced article by Dr Paul Cheney in which he noted the
evidence of metabolic disorder in ME/CFS: “CFS patients
demonstrate low oxygen consumption, early transition to
anaerobic metabolism, disordered fat metabolism and sweet
cravings which fit well into a picture of mitochondrial
dysfunction….Evidence of liver dysfunction has recently been
observed in most CFS cases. Liver dysfunction would explain the
medication and chemical sensitivities so common to CFS. Gut
dysfunction, especially increased gut permeability, is presumed
to be the basis of cellular energy deficiency and is common to
CFS. This would compound the effects of liver dysfunction and
could also explain such diverse complaints as food sensitivities
or allergies, irritable bowel syndrome, chronic nausea and
arthralgias….Reduction in cellular ATP would profoundly
affect cellular active transport systems….Electrolyte and
mineral gradients would decline and result in further loss of
critical cell functions. Intracellular magnesium deficiency
reported in CFS would be one of the many examples of this
phenomenon….Most interesting of all, liver dysfunction as
well as central nervous system mitochondrial dysfunction could
explain the subacute encephalopathy so common to CFS. Indeed,
cognitive-evoked computer brain maps of severely ill CFS
patients are entirely consistent with a metabolic encephalopathy
including that seen in hepatic encephalopathy….CFS patients
crave carbohydrates (but) if they eat fat, they cannot consume
it in the mitochondria, due at least in part to acylcarnitine
deficiency, and therefore fat storage increases, as does body
weight. Serum cholesterol and triglycerides rise in some
individuals. An obvious approach would be to reduce fat intake
and raise carbohydrate intake….The loss of excess
intracellular minerals such as magnesium due to reduced cellular
ATP and subsequent reduced active transport is a special
problem….Cardiac function, as well as muscle function in
general, may also be profoundly affected by intracellular
magnesium deficiency”.
1993:
In The CFIDS Chronicle
Physician’s Forum, Fall 1993, Dr James McCoy from Louisiana
wrote: “Chronic fatigue and immune dysfunction syndrome (CFIDS)
has been shown to have an associated immune disorder that may be
the result of an acquired immunodeficiency….A dysfunctional
immune system may be related to the failure of other organ
systems frequently observed in CFIDS….Some CFIDS patients
produce very low levels of DHEA (dehydroepiandrosterone, a
naturally-produced hormone and a precursor of oestrogen and
testosterone in humans….Many CFIDS patients are very
sensitive to medications and do not tolerate
normally-recommended dose levels. Many drug agents, including DHEA, are toxic to CFIDS patients’ lymphocytes at
routinely-prescribed dose levels”. The same Chronicle
devoted considerable space to the issue of multiple chemical
sensitivity (MCS) in people with CFIDS (ME/CFS): “…some
chemicals are more likely to cause MCS than others. These
include dry cleaning fluids, car exhaust, pollution, solvents,
paints, new carpet, perfume, smoke, fire, drugs, organic and
inorganic chemicals. Commonly seen pollutants which may cause
brain dysfunction include acetone, trichloroethylene and
chlorinated hydrocarbons”. Two important points were
made in that issue of Physicians’ Forum; Dr Robert Sinaiko from
San Francisco mentioned something that is very common but
frequently dismissed by uninformed physicians: “Many CFIDS
patients experience lower right abdominal pain, which (Sinaiko)
hypothesises is mycotic mesenteric adenitis, an inflammation of
the lymph nodes in the abdomen as a result of immune activation”,
whilst Vicky Carpman pointed out: “Autoimmunity is
commonly seen in CFIDS….Once an autoimmune condition begins, it
cannot be reversed”.
Despite
the irrefutable evidence that ME/CFS is an organic disease, the
Wessely School continue to reject it and seem unable to tell the
difference between basic science and doctrine; they are certain
that their beliefs about ME/CFS are correct and that it is a
somatoform disorder.
One UK
consultant physician described their arrogance as “breath-taking”
and referred to them as “convinced tub-thumping
fundamentalists with no self-awareness”, pointing out that
whilst their mind-set demands proof and scientific certainty
before they will accept ME/CFS as an organic disorder, in their
own discipline of psychiatry there is no proof or scientific
certainty, as a psychiatric diagnosis is dependent upon an
individual’s opinion and interpretation, which is an illogical
position to uphold.
Given the
biomedical evidence outlined above, it is extraordinary if not
incomprehensible that the Wessely School persists in its
irrational rejection of this evidence.
(To be continued)
click
here for Part III of this article
click here for Part I
)