*Grey* Information about ME/CFS -part 2

[Guest guest]

Reference:

*Grey* Information about ME/CFS (1956 – 1990), by Margaret

- Help ME Circle, 28 April 2011

For private members the original Word

document was attached, but can also be found at:

http://www.meactionuk.org.uk/Grey-Information-on-ME-CFS.htm

````

Below you will find part 2 (1991 – 1993) of this series:

The original Word Document is attached for private members,

but can also be found at:

http://www.meactionuk.org.uk/Grey-Information-Part-2.htm

~jan van roijen

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“Grey”

Information

about ME/CFS

Part 2:

1991 – 1993

Compiled by Margaret

5th May 2011

Part 1 of these extracts from the grey literature on ME/CFS

(1956 – 1990) can be seen at:

http://www.meactionuk.org.uk/Grey-Information-on-ME-CFS.htm

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 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 (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 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 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 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 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 anti- depressant agent, especially lithium, may be

beneficial”

(The chronic fatigue syndrome – myalgic encephalomyelitis or

postviral fatigue. S Wessely PK . In: Recent Advances

in Clinical Neurology (ed): 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”,

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

Bell, Cheney, Jay Goldstein and 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 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 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

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 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 Bell, Cheney,

Lapp and 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, ’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

Lapp, Dr 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 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 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

(“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”);

Komaroff

(“Our studies also indicate that two additional tests are

elevated more often in patients with CFIDS: immune

complexes and immunoglobulin G (IgG”);

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

(“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

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 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 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 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 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 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 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 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)