*Grey* Information about ME/CFS

[Guest guest]

For private members the original Word

document by Margaret is attached.

~jvr

````

Grey Information about ME/CFS

(1)

Compiled by Margaret

April 2011

Introduction

Apart from historical landmark information and the

occasional quotation about ME/CFS from a medical

journal published in more medically enlightened

times, the following illustrations are mainly taken

from the " grey " literature on ME/CFS.

Grey literature includes international research

conference proceedings, presentations and papers

written by researchers and/or clinicians that have not

been published in peer-reviewed journals.

These include, for example, articles written for

patients' support group magazines such as The

CFIDS Chronicle during the 1980s and 1990s

(when the Chronic Fatigue & Immune Dysfunction

Syndrome [CFIDS, a US term for ME/CFS] Association

of America produced excellent Chronicles including

" A CIFDS Primer " and " Physicians' Forum " written by

leading clinicians and researchers) and articles or

reports (including case reports and parliamentary

reports) that have not been published by commercial

journals.

There is a wealth of important information about

ME/CFS in the grey literature that has been largely

ignored by those intent on denying the existence of

ME/CFS as an organic disorder.

Indeed, the UK NHS Policy Plus Guidance

" Occupational Aspects of the Management of Chronic

Fatigue Syndrome: a National Guideline "

(2006/273539 / DH Publications) with which the

three Principal Investigators of the PACE Trial

(Professors White, Sharpe and Trudie

Chalder) were involved states that the grey literature

on " CFS " was not comprehensively searched in the

preparation of that national guideline.

The early CFIDS Chronicles described CFIDS (ie.

ME/CFS) as a complex illness with a constellation of

symptoms that can resemble many disorders,

including multiple sclerosis, AIDS-related complex

(ARC), Lyme disease, fibromyalgia, post-polio

syndrome and autoimmune diseases such as lupus.

Listed symptoms included profound fatigue especially

after exercise; low grade fever; chills and night

sweats; sensitivity to heat and cold; sore throat;

swollen glands; muscle weakness; muscle twitching;

myalgia (often a vice-like pain in muscles); sleep

disturbance; headaches of a new type; chest pains;

irregular heartbeat; shortness of breath; dizziness

and balance problems; light-headedness; seizures;

numbness or burning of the face or extremities;

dryness of the mouth; rashes; allergies and

sensitivities to odours, chemicals and medication;

abdominal pain; diarrhoea; bladder problems;

migratory arthralgia without joint swelling or

redness; transient visual scotomata (spots before

the eyes); blurring of vision; eye pain; photophobia;

frequent prescription changes in spectacles needed

(because of difficulty in maintaining

accommodation); hair loss; hyperacusis;

forgetfulness; irritability; confusion; difficulty

thinking; inability to concentrate; spatial

disorientation; dyslogia; intolerance of alcohol; panic

attacks and emotional lability.

In the Summer 2008 issue of The CFIDS Chronicle,

Komaroff, Professor of Medicine at Harvard,

editor-in-chief of Harvard Health Publications and

senior physician at Brigham and Womens' Hospital,

Boston (who has published more than 230 research

papers on ME/CFS) wrote an article listing the top

ten biomedical research findings in ME/CFS.

These are summarised at

http://www.prohealth.com/library/showarticle.cfm?libid=14063

and include evidence that (1) many patients with

ME/CFS have no diagnosable psychiatric disorder and

that ME/CFS is not a form of depression; (2) there is

a state of chronic, low-grade immune activation, with

evidence of activated T cells and evidence of genes

reflecting immune activation, as well as evidence of

increased levels of cytokines; (3) there is substantial

evidence of poorly-functioning NK cells (white blood

cells that are important in fighting viral infections);

(4) there is evidence of white and grey matter

abnormalities in the brain; (5) there is evidence of

abnormalities in brain metabolism (and evidence of

dysfunction of energy metabolism in the

mitochondria); (6) there is evidence of abnormalities

in the neuroendocrine system, particularly in the HPA

axis but also in the hypothalamic-prolactin axis and

in the hypothalamic-growth hormone axis; (7) there

is evidence of cognitive difficulties, especially with

information processing, memory and/or attention; (8)

there is evidence of abnormalities in the autonomic

nervous system (including a failure to maintain blood

pressure, abnormal responses of the heart rate, and

unusual pooling of blood in the legs, as well as low

levels of blood volume); (9) there is evidence of

disordered gene expression, especially in those

genes that are important in energy metabolism and

in genes connected to HPA axis activity, to the

sympathetic nervous system and to the immune

system; (10) there is evidence of frequent infection

with viruses, especially herpesvirus and

enteroviruses.

The overwhelming degree of exhaustion in

ME/CFS is unmistakable and can never be

confused with chronic tiredness or " fatigue " ,

nor can the objective signs that are invariably

present in ME/CFS be mistaken for chronic

" fatigue " ; such signs include:

• labile blood pressure (this is a cardinal sign in

ME/CFS)

• nystagmus and vestibular disturbance (vestibular

dysfunction seen in 90% of patients with ME/CFS)

• sluggish visual accommodation

• fasciculation

• hand tremor

• neuromuscular incoordination

• cogwheel movement of the leg on testing

• muscular weakness

• marked facial pallor

• postural orthostatic tachycardia syndrome (POTS)

• positive Romberg

• abnormal tandem or augmented tandem stance

• abnormal gait

• evidence of Raynaud's syndrome and vasculitis

(vascular signs cross dermatomes)

• mouth ulcers

• hair loss

• singular reduction in lung function (shortened

breath-holding capacity seen in 60%)

• enlarged liver (not usually looked for by

psychiatrists)

Laboratory abnormalities in ME/CFS include:

abnormal SIgA; weakly positive IgG3 (linked to

gastrointestinal tract disorders); positive IgM;

increased T4:T8 ratio (which always corresponds with

disease severity); very low numbers of NK cells, with

decreased cytolytic activity; low levels of circulating

immune complexes (two-thirds of ME patients have

insoluble circulating immune complexes);

autoantibodies (especially antinuclear and smooth

muscle); a particular HLA antigen expression; PCR

evidence of abnormalities in muscle; a positive water

loading test with erratic arginine-vasopressin

release; a significant prolactin release in response to

a single buspirone challenge; positive SPECT scans

(which show reduced blood flow through the brain

stem in a particular pattern not found in any other

illness or disease process apart from ME/CFS –

QJMed 1995:88:767-773); abnormal fMRI scans;

abnormal EEG (80% of ME patients show prolonged

jitter); a positive VP1 test; positive mast cells; low

pancreatic exocrine function; low copper response

test; anomalies in trace element metabolism,

especially low red blood cell levels of magnesium,

zinc and chromium; low potassium levels; low

peripheral oxygenation levels, with poor perfusion

and pulsatilities, and increased hsCRP.

According to Behan, Professor of Neurological

Sciences at the University of Glasgow, as these

abnormalities have been shown to occur with such

regularity, if they are present and if the clinical

picture is right, then a firm diagnosis of ME can be

made.

In 2001, evidence was presented by SCM s et

al (including Cleare who co-authors papers

on ME/CFS with Simon Wessely) at the British

Society of Rheumatologists' Conference in Edinburgh

showing that 53% of ME/CFS patients were excreting

in their urine significant levels of creatine and other

muscle-related metabolites including choline and

glycine, indicating on-going muscle damage, as

creatine has been shown to be a sensitive marker of

muscle inflammation and is objective evidence of

muscle pathology.

Given the prevailing editorial bias of many medical

journals on the topic of ME/CFS and the sophistry of

the Wessely School, the important information

contained in the grey literature is in danger of

disappearing, but patients, clinicians and

non-medical policy-makers alike need ready access

to such central information in terms that are quickly

and easily understood.

This present document makes no attempt to

provide a comprehensive overview of the grey

literature on ME/CFS or to summarise the

proceedings of international clinical and research

conferences since 1988, but hopefully the

illustrations provided will strengthen patients'

correct perception that they suffer from a

serious organic disease that is neither reversible

nor curable by directive psychotherapy as

asserted by those associated with the MRC/DWP

PACE Trial.

However, people with ME/CFS and those who care for

them may wish to source for themselves the

presentations made at the following major

conferences on ME/CFS; these include the US NIAID

(National Institute of Allergy and Infectious

Diseases) Symposium held at the University of

Pittsburgh in September 1988; the Rhode Island

Symposium in 1988; the Rome Symposium in 1988;

the San Francisco conference in April 1989; the

British Post-Graduate Medical Federation Conference

in London in June 1989; the Los Angeles

International Conference in February 1990; the First

World Symposium held in 1990 at Cambridge

University, UK; the Charlotte Research Conference in

November 1990; the Canadian Workshop at the

University of British Columbia, Vancouver, in May

1991; the Dublin International Symposium in May

1994 (held under the auspices of The World

Federation of Neurology); the First World Congress

(also under the auspices of The World Federation of

Neurology) in Brussels in 1995; the Second World

Congress in Brussels in September 1999; the

Bloomington Conference in Minnesota in October

2001, and the International Clinical and Scientific

Meetings presented by the Alison Hunter Memorial

Foundation in Australia, especially the Third

International Meeting in Sydney in December 2001;

the biennial International Research and Clinical

Conferences hosted by the American Association of

CFS (AACFS, now the IACFS / International

Association of CFS), including the Albany, New York,

conference in October 1992; the Fort Lauderdale,

Florida, conference in October 1994; the San

Francisco conference in October 1996; the Boston,

Massachusetts, conference in October 1998; the

Seattle conference in January 2001; the Chantilly,

Virginia (Washington D.C.) conference in January –

February 2003; the Madison, Wisconsin, conference

in October 2004, the Professional Research

Conference in Fort Lauderdale in January 2007, and

the numerous Scientific Workshops such as the one

co-sponsored by the US National Institutes of Health

in June 2003 on neuro-immune mechanisms in

ME/CFS and the ME Research UK (MERUK, formerly

MERGE) workshops (including the Royal Society of

Edinburgh funded Workshop in 2003, the MERUK

Colloquium in July 2006 and the MERUK International

Research Conference on 25th May 2007 at

Edinburgh), the aim of all these conferences being to

facilitate links between research scientists and

clinicians working towards the common goal of

understanding the biomedical basis of ME/CFS.

Given that much of the knowledge and

information about ME/CFS quoted below has

been circulating for over quarter of a century,

how is it possible that Wessely School

psychiatrists are even today permitted to ignore

and/or dismiss it?

Professor Sharpe, who it seems has now left

Edinburgh and is back in Oxford, recently responded

to criticism of the PACE Trial

(doi:10.1016/j.jpsychores.2011.03.003) by

attempting to justify the use of the Oxford criteria

(of which he was lead author) stating:

" While we excluded people with generally accepted

organic brain diseases…we did not exclude people

who described their symptoms as those of ME " ,

yet ME is a WHO-classified neurological disorder, so

Sharpe's argument is intellectually inconsistent. His

position itself is intellectually inconsistent because

he bases it on " CFS/ME " being " disabling

longstanding fatigue " and gives no credence to the

presence of the symptoms that distinguish ME/CFS

from chronic fatigue.

Despite the proselytising of the Wessely School,

the golden rule of ME/CFS experts is: if a patient

improves with exercise, that person does not

have ME.

Moreover, unlike those with other post-viral states

who report that they catch opportunistic infections,

people with classic ME/CFS do not succumb to every

passing common cold because they have incredibly

up-regulated interferon production, which is another

distinguishing feature.

Why are the UK patients' support charities not

vigorously refuting the false reasoning of the

Wessely School about ME/CFS on every possible

occasion instead of colluding with it?

The relentless degree to which the Wessely

School disseminate misinformation about

ME/CFS needs to be equally relentlessly

countered with the dissemination of the

biomedical evidence that shows them to be

wrong, otherwise they will continue to suppress

and/or disregard it and patients will continue to

suffer iatrogenic harm.

The following illustrations present a picture of classic

ME/CFS that is nothing like the Wessely School's

" cognitive behavioural " model of " CFS/ME " which

ignores the key symptoms of ME/CFS and is based on

" fatigue " and which many people believe is such a

travesty of both medical science and human rights.

Illustrations

1956: Dr ED Acheson, later to become Sir

Acheson, UK Chief Medical Officer, coined the term

" benign myalgic encephalomyelitis " (ME).

1964: ME was recognised and registered as an

industrial disease and as grounds for compensation

that has been paid as a weekly pension to a former

Royal Free Hospital nurse since 1964; this was

confirmed at a meeting at the headquarters of the

Royal College of Nursing on 2nd May 1989.

1969: the World Health Organisation classified ME

as a neurological disorder.

1978: The Royal Society of Medicine accepted ME as

a nosological entity.

1981: The Lancet published a letter from Professor

CS Goodwin about necessary criteria for a diagnosis

of ME:

" Firstly, symptoms and signs in relation to muscles,

such as recurrent episodes of profound weakness

and exhaustion, easy fatiguability, and marked

muscle tenderness.

Secondly, neurological symptoms or signs –

pyramidal or cranial nerve lesions, especially

affecting the eyes; or weakness of peripheral

muscles as demonstrated by the voluntary muscle

test; or some loss of peripheral sensation; or

involvement of the autonomic nervous system

(orthostatic tachycardia, abnormal coldness of the

extremities, episodes of sweating or pallor,

constipation and bladder disturbances.

Thirdly, biochemical abnormalities, such as raised

urinary creatine, low serum pyruvate, or raised serum

myoglobin, or an abnormal electrophoresis pattern

with raised IgM "

(Lancet, 3rd January 1981).

1985: Dr RW Gorringe from New Zealand published

" Diagnostic Criteria and Tests for ME " in October

1985, which provided a comprehensive and useful

diagnostic tool; Gorringe warned that " the

commonest mistake doctors make is failing to take a

wide enough view and cover an adequate systems

review " .

He noted the classic symptoms of ME including

prominent but intermittent chest pain (severe

enough for hospital admission); sore muscles of the

shoulders, neck and back; muscles that become

shaky and tremulous; frequency of micturition;

irritable bowel (colicky abdominal pain and loose

bowels); moist chest; cough; palpitations; jerkiness

of limbs; difficulty in co-ordination; paraesthesias;

shooting pains up nerves; blurred vision; burning

pain behind the eyes; oesophageal spasm; food

allergies; sensitivity to light; intermittent swollen

glands and sore throat; dizziness and nausea.

Gorringe noted evidence of malabsorption and

hypoglycaemia (in ME/CFS patients, blood sugar is

known to be under poor control); he pointed out that

on TFT (thyroid function test), TSH was often normal

but that T3 may be low, with subclinical

hypothyroidism.

He also noted abnormal immunoglobulins,

particularly IgA (often low) and IgM (which goes up

in a relapse but may sometimes be depleted and

become markedly decreased), and abnormal CICs

(circulating immune complexes), with low C3 and C4

(the modified immunoglobulins do not make proper

complexes with allergens taken in, resulting in

(insoluble) circulating immune complexes in the

central nervous system, in the joints and in the

kidneys, which can be a very hazardous state).

1987: in his Medical Address at the AGM of the ME

Association on 25th April 1987, Mowbray,

Professor of Immunopathology, St 's Hospital

Medical School, London, said:

" When we meet a new infection…the first thing we

do is to make IgM antibodies and then in a matter of

a few weeks we switch over and make IgG

antibodies (which) last for a long time and protect

us. If someone has IgM antibodies they have either

been recently infected or they are still infected….We

developed a technique using a specialised

antibody…which detects a protein in enteroviruses

which is the same in all 72 enteroviruses (and) we

can use that antibody to look for the virus protein in

the blood.

Doing that, we have been able to find a very large

fraction of the ME patients have got an enterovirus

antigen…. Just because you find virus proteins in the

blood, does that mean they are infected? Yes, it

does….The virus is present in the intestine. It is

also shown to be present in the muscle….

Here is a muscle biopsy where you see the dark

brown infective muscle cells, where the probe has

bound to the virus genes in the muscle cell. (There

are) two ways which demonstrate that in the muscle

(in) a patient with ME, there is an enterovirus….What

does it do in the muscle?….(It) does the thing that

viruses usually do, they infect the cell and take

over…saying 'You must switch off all your genes and

read only my genes'.

So (the virus) switches off all the genes that

produce energy to the cells….The virus is being made

and is switching off host genes stopping the cells'

own energy production.

If you now exercise, you rapidly run out of energy in

the muscle and that has been shown by

sophisticated techniques….Whilst (the virus) is there,

it severely limits the ability of the muscle to

work….The thing that seems to make it worse is

exhausting the muscle….Sufferers know, they have a

kind of feeling for it, especially as time goes on,

about what is going to be too much….

When you have got the disease it is a good basis for

saying do not use up all the muscle energy, do not

get to that stage. It may lead to more virus

affecting that muscle….It is clear that it is not only

exhaustion in the muscle but also in the brain….

Either muscle or brain overdoing it is the same….if

you live within the limits of the disease while you

have got the disease, I think you will do much better

and we have now got some good scientific

background " .

1987: At the CFS Society, USA, conference held on

4th-7th November 1987, Infectious Diseases

specialist Dr Mark Loveless from the University of

Oregon said the disease was very prevalent, that the

musculoskeletal, neurological and vestibular systems

were involved, and that there are cardiovascular,

gastrointestinal and immunological abnormalities.

At the same conference, Dr Alfred said that

97% of (ME/CFS) patients have allergies and that

allergic patients have high helper (T4) cells and low

suppressor (T8) cells, causing over-reactivity.

Dr Cheney confirmed that the T4:T8 ratio is

elevated in two-thirds of cases, and that this is

considered a more reliable marker of the illness than

other markers.

He said there are " impressive abnormalities " in

mitogen stimulus status (an immune function test)

and that symptoms are caused by a hyper-immune

response.

He noted that MRI scans showed characteristic brain

lesions in 77% of patients tested (88 of 114

patients) as determined by two independent

neurologists.

1988: Professor Mowbray's team at St 's

Hospital, London, began to offer a test for the

detection of enteroviral protein in ME patients.

VP1 stands for Viral Protein 1, described in the ME

Association's magazine in Autumn 1988 as being:

" one of four proteins forming together the viral

capsid which surrounds the viral genetic material.

There is a particular portion of the VP1 protein which

is present in all 72 different enteroviruses " .

The ME Association offered the test to its members

for an administration fee of £3. The following year,

at the Clinical Session of the 1989 AGM of the ME

Association, Dr Byron Hyde from Canada referred to

the VP1 test, confirming what Professor Mowbray

himself had said:

ME patients with a positive VP1 test become chronic,

whilst those with a negative VP1 test recover.

Despite this, the VP1 test was dismissed by

psychiatrist Simon Wessely as:

" unsuitable for routine clinical use "

[Lancet 1989:1:1028-9] and it is no longer available

in the UK.

1988: An article by Elsie Brody (Occupational Health,

1988; 446-447) listed key symptoms of ME, including

severe headaches, neck pain, pain in back and limbs,

pins and needles in limbs, vertigo, severe sweating,

impaired memory and difficulty with words, panic

attacks (now known to be due to hyperadrenergic

orthostatic intolerance), tachycardia, extreme

fatigue, disturbed sleep, muscle weakness and

tenderness, diplopia, photophobia and chest pain.

Mrs Brody advised that:

" As OH professionals, it is our duty to recognise the

disease early (and) educate management on

recognising ME " .

1988: The ME Association's magazine " Perspectives "

carried an article on " Viruses and " ME " by consultant

microbiologist Dr Betty Dowsett, who wrote:

" Many viruses (including enteroviruses) can enter

and alter the function of the immune cells specially

designed to destroy them.

It is important to recognise that these immune

abnormalities are secondary to the virus

infection….The mopping up of free viruses in the

bloodstream can be counter-productive if excess

antibody is produced.

The insoluble 'immune complexes' that result can be

trapped in the blood vessels and tissues

and…maintain infection in the body….

The chemical composition of a virus may mimic that

of a normal body component (such as brain or

muscle protein) whereupon the immune attack is

misdirected against the host while the virus

disappears unnoticed.

Cardiac and other complications in ME are an

example of such an anomaly " .

1988: At a meeting on ME held at The Royal Free

Hospital on 16th May 1988, Professor Tim s

from Northwick Park Hospital said his team had

found abnormalities of Type II muscle fibres

(anaerobic) in ME patients, which were atrophied,

with hypertrophy of Type I muscle fibres; he had

measured total RNA in muscle cells and found it to

be significantly reduced in ME patients (if there is a

decline in RNA, there is a decline in the ability to

make muscle protein – infusion of tag-leucine

showed overall metabolism is clearly reduced and the

rate at which muscle is being formed is reduced).

1989: Professor s (then Professor of Clinical

Biochemistry and Consultant Chemical Pathologist at

Kings College Hospital, London) wrote on page 24 of

the magazine InterAction No: 3 of the charity ME

Action, now AfME:

" Exciting studies have recently been reported of

persistent viral RNA in biopsies from patients with

ME….

Based on these observations we have started to

investigate muscle protein synthesis; that is, the

ability of muscle to repair itself…in patients with

ME.

Measurements of muscle RNA, the machinery for

protein synthesis, showed consistently reduced

amounts in their biopsies.

Studies of whole body and, specifically, thigh muscle

protein synthesis rate in these patients show

reduced values and thus a pattern is beginning to

emerge of persistent viral infection, and possibly

re-infection, interfering with the machinery for

making tissue protein and thus impairing protein

synthesis " .

Discussing the view of those who claim that changes

in mitochondrial function and impaired muscle

synthesis are merely secondary events due to lack of

use of the muscles, Professor s continued:

" It is hard to see how (this) can explain the

persistence of enteroviral RNA in muscle

fibres….immobility leads to a selective loss of Type I

fibres, a feature not seen in patients with ME " .

The same issue of InterAction reported on page 22

the neurological abnormalities found by Carolyn

Warner and her team from Buffalo, NY (elevated IgG

synthesis, elevated CSF cell count, prolonged visual

evoked response latency, abnormal EEG and MRI

lesions, and neuromuscular abnormalities including

over 20% polyphasic motor units on quantitative

EMG, inflammatory infiltrates and Type II fibre

atrophy, these being reported in Neurology

1989:39:Suppl 1: 420).

Commenting on these abnormalities, Dr Goran Jamal,

Consultant in Clinical Neurophysiology at The

Institute of Neurological Sciences, Glasgow, affirmed

that those results are consistent with disturbed

immune function and persistent infection, and that it

proves once again that one can find neurological

abnormalities if one looks.

Still in the same issue of InterAction, Dr Jamal

himself wrote on page 26 about muscle fatigue in

ME:

" In recent years a lot of evidence has been

accumulating to suggest that the fatigue in ME is

organic in nature….Our findings clearly showed

evidence of disturbance of transmission of electrical

impulses along muscle fibres.

This study… provided one of the first and strongest

indications for the organicity of the syndrome.

This work has been reproduced again by our group

and elsewhere. In addition we have looked at other

groups of patients with various psychiatric illnesses

using the same technique of single fibre

electromyography, and these produced absolutely

normal findings….

Examination of individual muscle fibres under

electron microscopes…showed gross abnormalities of

the structures involved in providing energy for the

muscle fibres….NMR (nuclear magnetic resonance)

showed evidence of disturbed muscle

metabolism….Strong evidence of the presence of

viral particles in the muscles of ME patients has also

recently been shown….

Any assumptions that the fatigue in patients with

ME is entirely ' mental' or 'psychogenic' is not

only without any foundation but also ignores all

this solid scientific data " .

1989: Dr Cheney from the US presented his

findings at the San Francisco CFS Conference on 15th

April 1989; 70% of ME/CFS patients tested had

depressed levels of salivary IgA (SIgA), and ME/CFS

patients with low SIgA levels tended to have high

levels of insoluble circulating immune complexes.

Microscopic analysis of tissues showed lymphocytic

vasculitis (lymphoid infiltrates in the blood vessel

wall) in 75% of patients tested.

1989: In a talk given on 15th May 1989,

Behan (Professor of Neurological Sciences at the

University of Glasgow) said that ME is a viral

infection of the gut with gross exhaustion and

tachycardia accompanied by malaise.

He said the real tragedy of ME is the

far-reaching effects on the medical profession of

two not-very-talented psychiatrists in 1977, one

of whom had only just qualified.

Behan stressed the importance of separating

psychiatric fatigue from ME fatigue. He explained

that the brain produces Interleukin 1 (IL-1) as a

result of the cell being stimulated by a virus, and

IL-1 will cause the liver to be abnormal; it will affect

muscle and nerve cells, and it is found in extreme

fatigue. He said that in the majority of true ME

cases, IL-1 levels are extremely high.

1989: In the summer issue of the ME Association's

magazine, Dr wrote about slow-onset

ME:

" I am afraid that there is probably less chance of a

spontaneous cure, and in that disease undoubtedly

there is a natural progression of symptomatology….I

do believe that the slow onset type persistent

enterovirus infection is ME " .

In " A Letter from our President " in the winter issue

of the ME Associations' magazine, Dr Melvin Ramsay

wrote:

" The onset of the disease may be sudden or

gradual….The crucial difference between ME and

other forms of postviral fatigue syndrome lies in the

striking variability of the symptoms, not only in the

course of a day but often within an hour. This

variability and intensity of symptoms is not found in

postviral fatigue states " .

1989: In December 1989 the magazine of the

Australia and New Zealand ME Society (ANZMES

Meeting-Place issue 32) reproduced an article by

English MD, formerly Assistant Clinical

Professor of Surgery at Duke University in the US

who had to retire due to ME/CFS. English wrote:

" I issue a challenge to medical sceptics who suggest

that CFIDS (ie. ME/CFS) is only a form of depression

or 'psychoneurosis'.

The challenge is this: Give yourself a one month

course of alpha-interferon. Don't be timid; get your

serum levels up above 300 where mine have been.

Have the courage of your convictions; experience for

30 days what patients have endured for years….

If our illness is as trivial as you suggest, each of you

should be willing to step away from your

pseudo-intellectual façade of CFIDS scepticism.

After 30 days, tell us what you think.

I dare say that no CFIDS critic should be taken

seriously until he has done this " .

1990: On 17th March 1990 Professor Behan

from Glasgow made a presentation to the Mid-Anglia

branch of the ME Association in Cambridge.

He began by giving an over-view of the historical

perspective and went on to discuss the cardinal

symptoms of ME, these being (1) onset precipitated

by a viral infection; (2) local and generalised fatigue

arising from the brain as in multiple sclerosis; (3)

post-exercise myalgia, especially in the shoulder

girdle, back, neck and left side of the chest; (4)

mental changes, including poor control of emotions,

poor task performance and cognitive disturbances;

(5) sleep disturbance; (6) cardiac disturbances (a

significant number have cardiac symptoms) and (7)

vestibular disturbance, with dysequilibrium and

sometimes true vertigo.

He discussed the hypothalamic dysfunction, noting

that 50% of ME patients cannot produce steroids in

response to stimulus. He presented objective

evidence of Type II muscle fibre atrophy on

histological section and evidence of mitochondrial

damage, and showed identification of enteroviral

RNA in muscle.

1990: On 10th- 12th April 1990 the First World

Symposium on ME/CFS was held at the University of

Cambridge.

Speakers presented evidence on acute, latent,

persistent and reactive virus/host interaction; on

cytopathological studies; on electron microscopy

studies; on immunological abnormalities, genetics

and autoimmunity; on interferons and their role in

virus infections; on muscle studies of abnormal

metabolic function; on cardiac disease in ME/CFS; on

lesions in the brain and on paediatric ME/CFS.

The predominant view was of a persistent or chronic

viral infection which either gave rise to, or was the

result of, a continuing abnormal immune response

and abnormalities of the muscle and central nervous

system. Evidence was presented of an infective

vasculitis in ME/CFS.

The Symposium brought together leading

international researchers to review all aspects of

ME/CFS.

The proceedings were subsequently published as the

724 page seminal textbook on ME/CFS (The Clinical

and Scientific Basis of Myalgic Encephalomyelitis

Chronic Fatigue Syndrome, edited by Drs Byron Hyde,

Jay Goldstein and Jay Levy; The Nightingale

Research Foundation, Ottawa, 1992).

The conclusion of the Symposium was plain: ME/CFS

is a true organic disease, with abundant evidence of

its organicity.

1990: In September 1990 the CFIDS Association of

America produced a special " Research Breakthrough "

issue of its Chronicle. The Special Issue reported on

the press conference on CFIDS (ME/CFS) held on 5th

September 1990 in San Francisco, at which Dr

Cheney said:

" The most specific neurological symptom…is

dysequilibrium. These patients have a balance

disturbance and on certain simple neurological tests

they fall over. On more sophisticated tests of

vestibular function they're often grossly abnormal….

Other evidence of central nervous system

involvement can be demonstrated by tests looking

directly at the central nervous system.

These are slices of brain created by using magnetic

resonance imaging. These inflammatory and/or

demyelinating plaques can be seen in white matter,

in the cerebellum and white matter tracks

throughout the high cerebral convexities and in the

frontal lobes.

Over half of CFIDS patients will typically show

lesions within the central nervous

system….Switching from neurology to immunology, I

want to show you what I believe to be the most

striking immunologic defect in these patients. It is

most convincing.

This is the 2-5 A Synthetase/RNase L pathway….This

system turns on and protects cells from viral

infection and replication….This system is only turned

on by a virus….In terms of severity, this is

phenotypically unique to CFIDS….It's an absolutely

striking observation suggesting a viral problem in

these patients….These cells are infected with virus " .

Dr Cheney then discussed biopsies from ME/CFS

patients that showed an infiltration of mononuclear

cells around small blood vessels within the deep

dermis (causing, for example, loss of fingerprints).

Cheney said:

" It's called perivasculitis, or perivascular

cuffing….What's interesting about this kind of lesion

is that if this lesion occurred within the brain, in

small vessels within the brain, it would produce

many of the lesions we see on MRI scans. So I think

that this pathology is not limited to fingertips. It can

be found anywhere " .

Wishing to make sure that the press corps

understood how serious a disease ME/CFS is, Cheney

continued:

" I think it's really important for members of the press

to recognise that what we're talking about here is

not common fatigue….

What we're talking about here in this systemic

illness is that the debilitating fatigue is one of the

primary symptoms, as it is in almost all autoimmune

diseases and many other systemic diseases….We

need to constantly separate out people who have

common fatigue from people who have this

illness….People who have competent immune

systems don't get bad diseases like this in any

numbers….Retroviruses have the capacity to impair

immune systems in a subtle way " .

In response to a question as to why ME/CFS is more

common in women than in men, Cheney said:

" There are a number of immunologic problems in

which women dominate. Lupus and MS are examples.

Immunologic disturbances are seen more commonly

in women….In MS you have a ratio of two to three

women to men " .

At the conclusion of the press conference, when Drs

Cheney and Bell were asked to comment

on how seriously ill ME/CFS patients are, Dr Cheney

said:

" These patients' …ability to experience life is

destroyed. You see their entire social structures,

work interactions and family units, come crashing

down….It's an unbelievable illness "

and Dr Bell said:

" At the tip of the iceberg there are some patients

who have it in extremely severe form and it can

destroy their lives….So even without the injury

caused by medical mismanagement, there's a very

significant disability caused by this illness " .

23rd November 1990: Notes of the ME Study Group

Meeting record that, in complete disregard of all this

circulating biomedical evidence, contributors to a

Press Briefing on ME by the Royal Society (one of the

oldest scientific institutions in the world) that was

designed to inform medical correspondents about ME

emphasised the psychiatric approach:

muscle abnormalities were stated to be secondary to

inactivity, and reassurance together with graduated

exercise were considered to be the best therapeutic

approach.

Psychological factors that pre-disposed, precipitated

and perpetuated " fatigue " syndromes received

considerable prominence, and one contributor

attributed ME in children to school phobia.

(To be continued)