Friday, October 31, 2008

Germs hang around for days on door handles

Germs hang around for days on door handles, TV remote -


"Someone in your house have the sniffles? Watch out for the refrigerator
door handle. The TV remote, too. A new study finds that cold sufferers often
leave their germs there, where they can live for two days or longer."

"Next, the researchers deliberately contaminated surfaces with participants'
mucus and then tested to see whether rhinovirus stuck to their fingers when
they turned on lights, answered the phone or did other common tasks. More
than half of the participants got the virus on their fingertips 48 hours after
the mucus was smeared."

In other words, it's not even necessary for someone to have coughed or
sneezed directly in my face for me to have gotten the virus that precipitated my
CFS. I rode the commuter bus; someone on another run may have left the germs
on the seat or the door -- someone I never even crossed paths with. I worked
in a multi-story office building, and the ground-floor tenant was a bank: a
thousand people each day touched the door handles that I had to use to get
into the building.

They recommend frequent hand-washing to avoid the spread of germs, but what
if you wash your hands and then pick up the germ on your clean hands when you
turn off the faucet or open the bathroom door? You think your hands are
clean enough to eat your lunch safely, but really, you've just added new germs.

8 years ago, when even going to the doctor 4 blocks away was enough exertion
to send me to bed for days, I went out precisely once in a two-week span: to
the corner store to buy milk. There were no other customers when I arrived,
and the owner did not appear to be sick. Nonetheless, I came down with
something, which clearly was picked up from the handle of the dairy cooler,
because I hadn't been out of the house for over a week and hadn't touched anything
else. Then I transferred the bug to whatever I touched between buying the
milk and washing my hands -- my keys, my doorknob, my clothes, my fridge, the
faucet knobs... so even if I'd washed my hands immediately after putting the
milk in the fridge, the bugs were now in my house waiting to be picked up on
my clean hands.

Many CFS patients describe a particularly virulent illness, one strong
enough to overwhelm even the healthiest habits and immune system. Don't think
that you can't get it just because you didn't see a sick person while you were
out and about; the virus could be lurking anywhere for you to pick it up.

CFS is a contagious disease, and there's no vaccine against it. If you
don't have it yet, you may get it tomorrow. But CDC is more interested in
playing word games talking about "stress" than to address the proven
biological/infectious cause, so you and your family are at risk. And a lot of people have
noted "karma", that the people who dispute the reality of CFS often are
disabused of their beliefs when they get it themselves.

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Immuno-neuroendocrine evidence disregarded by NICE

Permission to Repost

Immunological, neuroendocrine and neurological evidence (including evidence
of CNS inflammation) documented in ME/CFS that NICE chose to ignore in the
production of its Clinical Guideline 53

Margaret Williams                    

Executive Summary

"ME is not a new disorder; there are many reports in the medical literature
spanning at least 70 years and in April 1978 the Royal Society of Medicine
accepted ME as a distinct entity. It is a serious and complex disorder which
can affect virtually every major system in the body, with neurological,
immunological, cardiovascular, respiratory, hormonal, gastrointestinal and
musculo-skeletal manifestations" (M Hooper; "The Mental Health Movement: The Persecution of Patients?"
  December 2003 pp 17-18  ).

In the light of the above it is simply remarkable that the Guideline
Development Group (GDG) which produced the NICE Clinical Guideline CG53 on
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) chose to
ignore decades of medical and scientific literature, literature that
includes an evidence-base of over 4,000 biomedical publications regarding
the disorder that they set out to consider.

Whilst it is true that ME/CFS is a serious multi-system organic disorder
affecting virtually all the organs and systems in the body, this document
looks in particular at the abnormalities found in three specific areas: the
immune system, the neuroendocrine system, and central nervous system.  For
each of these three areas illustrations of research findings are given, all
of which provide evidence of biomedical abnormalities found in patients with
ME/CFS, and all of which the GDG chose to ignore.  In addition, the document
starts by briefly considering the issue that the term "CFS/ME" as used by
NICE was in fact misleading.

Some of the key points in the document are summarised as follows:

(i) The term "CFS/ME" used by NICE was misleading

The Wessely School's modus operandi of combining all states of unexplained
fatigue into one heterogeneous label ("CFS/ME") has had detrimental
consequences for patients, as noted as long ago as 1994.

By ignoring the existing evidence-base for ME/CFS, the GDG was able to
ignore the documented biomarkers that separate ME/CFS from "CFS/ME" and was therefore expediently able to recommend only behavioural interventions.

NICE has essentially reduced "CFS/ME" to chronic tiredness and just one
other symptom.

(ii) Illustrations of immunological dysfunction in ME/CFS from the published
literature that NICE

"Our investigations suggest that this syndrome is characterised by objective
laboratory abnormalities (and) immune dysfunction appears to be a hallmark
of the disease process"
"In a normal population, 20% of lymphocytes are active at any given time.
'In (ME)CFS, up to 80% 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"
"Our observations strongly suggest that a large population of (ME)CFS
patients have immunologic disorders and that their symptoms could be
explained by a chronic immune activation state (and) that (ME)CFS represents
a type of autoimmune disease in which a chronically activated immune system
reacts against the host"
"The exacerbation of symptoms after exercise differentiates (ME)CFS from
several other fatigue-associated disorders.  Research data point to an
abnormal response to exercise in patients with (ME)CFS compared to healthy
sedentary controls, and to an increasing amount of evidence pointing to
severe intracellular immune dysregulation in (ME)CFS patients"
"The data presented in this report are consistent with the presence of an underlying, detectable abnormality in immune cell behaviour of many ME/CFS patients, consistent with an activated inflammatory process, or a toxic state".

(iii) Illustrations of neuroendocrine dysfunction in ME/CFS from the
published literature that NICE disregarded

"There is an increasing volume of evidence to support the view that patients
with (ME)CFS have unique endocrinology patterns.  The cardinal findings
include attenuated ACTH responses to CRH and low 24-hour urinary cortisol.
These are compatible with a mild central adrenal insufficiency"

"Our group has established that impaired activation of the HPA axis is an
essential neuroendocrine feature of (ME)CFS"
"The right and left adrenal gland bodies were reduced by over 50% in the
(ME)CFS subjects, indicative of significant adrenal atrophy in a group of
(ME)CFS with abnormal endocrine parameters"
"We compared cortisol response in the (ME)CFS subjects with the response in
control subjects and in those with secondary adrenal insufficiency. We have
shown that cortisol increment at 15 and 30 minutes is significantly lower in
the (ME)CFS group than in controls. However, there was no difference between
the (ME)CFS group and those with secondary adrenal insufficiency in any of
the parameters. Consequently, reduced adrenal responsiveness to ACTH exists
in (ME)CFS".

(iv) Illustrations of neurological dysfunction in ME/CFS from the published
literature that NICE disregarded

"Some people think that (ME)CFS can look like MS and there are clinical features that are overlapping. The most specific neurologic symptom is dysequilibrium.  These patients have a balance disturbance and on certain simple neurologic tests they fall over. On more sophisticated neurologic tests of vestibular function they are often grossly abnormal. Nearly every patient had something abnormal within the central nervous system (CNS), and also neuromuscular problems. Over half of (ME)CFS patients will typically show lesions within the central nervous system"
"The symptoms of (ME)CFS have long been viewed as a neurologic pattern, as
indicated by other names for the condition such as myalgic encephalomyelitis
(and) atypical poliomyelitis.  Neurologic involvement is beginning to be
confirmed by documentation of abnormalities in cerebral perfusion,
hypothalamic function, and neurotransmitter regulation.  A link is being
forged between the symptom pattern and objective evidence of CNS
The view that (ME)CFS is a primary emotional illness has been undermined by research findings"
"A complete neurological examination should be an integral part of the
diagnostic assessment of illnesses described as CFS"
"Our data suggest that (ME)CFS may involve a primary neurological
abnormality.  (ME)CFS patients also show dysfunction in complex auditory
processing that is of the same magnitude as that found in patients with
multiple sclerosis. Other data show that patients with ME/CFS had
significantly lower brain stem perfusion ratios than either healthy or
depressed controls"
"(ME)CFS involves altered central nervous system signals in controlling
voluntary muscle activities, especially when the activities induce fatigue.
Physical activity-induced EEG signal changes may serve as physiological
markers for more objective diagnosis of (ME)CFS".

Immunological, neuroendocrine and neurological evidence (including evidence
of CNS inflammation) documented in ME/CFS that NICE chose to ignore in the production of its
Clinical Guideline 53

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a complex
multi-system biomedical disorder, hence there is considerable overlap of
multi-system symptomatology. This document should therefore be read in
conjunction with the four preceding documents already submitted: (1)
"Evidence that the Guideline Development Group that produced the NICE
Guideline on CFS/ME (CG53) failed to fulfil its remit, particularly in
relation to the danger of graded exercise therapy" (7th July 2008);  (2)
"Background information and illustrations of evidence that CBT cannot
improve ME/CFS which NICE disregarded" (25th July 2008); (3) "Evidence of
cardiovascular problems in ME/CFS that NICE disregarded" (4th August 2008)
and (4) "Medication and ME?" (27th August 2008), which provides evidence of
mitochondrial (muscle) dysfunction that has been demonstrated in ME/CFS that
NICE also disregarded.

This present document provides illustrations of evidence concerning
immunological, neuroendocrine and neurological dysfunction that has been
documented in ME/CFS, all of which the Guideline Development Group (GDG)
that produced the NICE Guideline CG53 ignored (J Inf 2007:55:6:567-571),
thus enabling the GDG to recommend that only the pre-ordained intervention
(behavioural modification and incremental aerobic exercise) be delivered
throughout the nation to people with "CFS/ME".

By ignoring the existing evidence-base for ME/CFS, the GDG was able to
ignore the documented biomarkers that separate ME/CFS from "CFS/ME" (a term
coined by Wessely School psychiatrists - who claim to specialise in
"CFS/ME" -- to denote somatoform disorder, which includes all states of
unexplained "tiredness") and was therefore expediently able to recommend
only behavioural interventions.

The Guideline, however, is a Clinical Guideline, and part of its remit was
to aid diagnosis, but the GDG failed to identify or define the disorder to
which its Guideline purports to relate.

Instead, the GDG intentionally combined all states of "medically unexplained
chronic fatigue" within the heterogeneous label "CFS/ME" which was in direct
defiance of the many international calls for sub-grouping (see below).

It was, however, in accordance with the ethos of the Wessely School, which
is that amalgamating "fatiguing illnesses" will clarify the pathophysiology
of "fatigue".

Referring to the CDC Fukuda 1994 case definition of "CFS" (in the production
of which Michael Sharpe and Simon Wessely were involved), Michael Sharpe et
al state: "The exclusion of persons (with psychiatric disorders) would
substantially hinder efforts to clarify the role that psychiatric disorders
have in fatiguing illnesses" (Ann Intern Med 1994:121:12:953-959).

The Wessely School's modus operandi of combining all states of unexplained
fatigue into one heterogeneous label ("CFS/ME") has had detrimental
consequences for patients, as noted as long ago as 1994 in the National Task
Force Report on CFS/ME/PVFS produced by the charity Westcare (now subsumed
into Action for ME) that was supported by the Department of Health, and as
noted by many international researchers (see below).

This amalgamation of "fatigue states" also pertained in the Chief Medical
Officer's (CMO) Working Group's Report of January 2002, which was dismissive
of the need for sub-grouping: "This question may be considered a matter of
semantics and personal philosophy"  (Annex 4:3, written by Professor Anthony
Pinching, Lead Adviser on "CFS" to the Department of Health, who was
responsible for setting up the "CFS" Centres in the UK).

That NICE has indeed adopted the Wessely School paradigm (i.e. the
psychosocial / behavioural model of "CFS/ME") has been confirmed.

The influence of Wessely's team on the NICE Guideline on "CFS/ME" featured
in the 2007 R&D (Research & Development) annual reports by NHS organisations
in England (Department of Health), in which the South London and Maudsley
NHS Trust stated in section 2A ("Examples of impact on health and social
care"): "We begin by summarising key achievements and follow with six
examples that illustrate the impact of our research. The examples that
follow have been selected to illustrate the breadth of our portfolio of
research and evidence-based practice". The section on "Chronic Fatigue
Syndrome" boasts: "In October 2006, NHS Plus published "Occupational Aspects
of the Management of Chronic Fatigue Syndrome: a National Guideline". It was
accompanied by two additional leaflets, one for Health Care professionals
and one for employers. This report was heavily influenced by research
carried out at our Chronic Fatigue (sic) Unit. The NICE CFS/ME guideline
also includes priority recommendations to which our research, led by Trudie
Chalder and colleagues, has contributed: 'When the adult or child's main
goal is to return to normal activities, then the therapies of first choice
should be CBT or GET because there is good evidence of benefit for this
condition in mild to moderately affected adults and some evidence in mild to
moderately affected children'. As a result of our research we have developed
our chronic fatigue syndrome service to include treatment at home. In
addition we now offer telephone treatment routinely after demonstrating its

There could be no clearer confirmation of the impact of the Wessely School's
beliefs about "CFS/ME" on the NICE Guideline, which recommends only
mind-altering therapies in conjunction with incremental aerobic exercise.

The term "CFS/ME" used by NICE is misleading

It was in September 2003 that a Working Group including ME/CFS experts
Professor Nancy Klimas and Professor Leonard Jason advised the US Department
of Health and Human Services of the unsuitability and inadequacy of the term
"CFS".  Their submission stated:

"The vast majority of patients and physicians believe that the name CFS too
narrowly focuses upon a single, poorly-defined symptom (fatigue) and
promotes misunderstanding of the illness"

"Patients feel the name CFS has substantially contributed to the disparaging
manner in which they are perceived and treated by physicians, family, and
the general public (and) that this misunderstanding has directly and
negatively impacted the quality of medical care and support they are able to

"We recommend a new name (under which) subgroups of patients can be more
accurately stratified according to variations in illness presentation,
pathophysiology (and) results of diagnostic testing"

"Foundation for our recommendation was guided by several important
principles. First, the name must not imply that the aetiology is clearly
understood.  Second, it must reflect common symptoms reported by most
patients. Third, our recommendation must be supported by data published in
the peer-reviewed literature"

"The number of symptoms reported by patients is very large.  However, most of the commonly reported symptoms are associated with (or may be indicative of dysfunction of) the neurologic, neuroendocrine and / or immunologic systems"

"(We) recommend a new term called neuroendocrineimmune dysfunction syndrome (NDS). The recommendations are based on (1) the profile and frequency of the commonly reported symptoms and (2) the published evidence (that) supports an
aberration or dysfunction of the neurologic, neuroendocrine, and immunologic

The Working Group attached a list of the published evidence in support of
their recommendation, pointing out that: "The following scientific
publications provide a sound basis (for the term NDS) that reflects common
symptoms. The articles were selected because they have withstood scientific
scrutiny and represent critical findings.  While other publications are
available, the chosen articles are widely respected, cited and (are)
representative of current understanding of the science".

The full submission and the listed articles (separated into categories of
Neurologic System -- sub-divided into autonomic nervous system,
neuroendocrine system and neurocognitive problems -- and Immune System) are
available at

In stark contrast, NICE has essentially reduced "CFS/ME" to chronic
tiredness and just one other symptom (Full Guideline, p 165). In doing so,
NICE has ignored the existing evidence-base of over 4,000 biomedical
publications on the disorder.

Further, NICE claims to have been guided by the 2002 Report of a Working
Group to the Chief Medical Officer, whose membership was heavily
over-represented by the Wessely School. Not only does that Report recommend
GET and CBT ("The majority of the Working Group agreed that graded exercise
therapy can benefit many outpatients with CFS/ME" [page 47] and "The
majority of the Working Group accepts that CBT can improve functioning in
many patients with CFS/ME"  [page 49] ), it was strongly criticised because
it advises clinicians (page 40) that the specialist investigations (ie.
immunological assays and nuclear medicine imaging) which are delivering hard
evidence of organic pathology in ME/CFS are neither necessary nor
appropriate for these patients.
  That was a matter for concern at the time,
and remains a matter of concern, since the NICE Guideline adopts the same

It is also a matter for concern that NICE has recommended only behavioural
interventions for such a clearly complex and serious biomedical disorder
when there is substantial evidence of immunological, endocrine and
neuroendocrine dysfunction in ME/CFS, with persistence of illness

At the ME Research UK international conference held at the University of
Cambridge on 6th May 2008, Nancy Klimas, Professor of Medicine at the
University of Miami and Director of the (ME)CFS Research Centre reviewed
some of this evidence.

Although the Cambridge conference post-dated the publication of the NICE
Guideline (on 22nd August 2007), much of the reviewed evidence pre-dated
publication and was available to the GDG, yet it was comprehensively

Professor Klimas noted that chronic immune activation has long been thought
to be a component of ME/CFS, with T-lymphocytes being chronically
activated - indeed CD8 cells in ME/CFS patients typically demonstrate an
increase in activation markers (CD38; HLA-DR) and a reduction in CD8
suppressor cells. Furthermore, there is evidence that the homeostasis
between the cell-mediated (T-helper, or Th1) immune response and the humoral
(Th2) immune response is disrupted in ME/CFS, and there is evidence of
increased pro-inflammatory cytokine expression (TNFa; IL1 and IL6).

Professor Klimas reviewed the evidence for viral persistence and
reactivation (eg. enterovirus, HHV6 and EBV) and discussed the evidence for
endocrine dysfunction, particularly reduced cortisol.  She noted that
autonomic dysfunction has been measured as neurally-mediated hypotension,
orthostatic hypotension, parasympathetic dysfunction and sympathetic

She also spoke about gene expression microarray data having become a highly
productive tool for understanding ME/CFS research, noting studies that
included the differential expression of 35 genes for T-cell activation,
neuronal and mitochondrial regulatory abnormalities, and that pre- and
post-exercise challenge gene studies have indicated differences in genes
that regulate ion transport and intracellular functions.

Dr Jo Nijs from the Vrije University, Brussels, examined the accumulating
evidence of intracellular immune dysfunction in ME/CFS and concluded that
proteolytic cleavage of the native RNase-L is characteristic of
dysregulation of intracellular immunity in people with ME/CFS, and that
there is increasing evidence for up-regulation of various aspects of the
2-5A synthetase / RNase-L pathway (an important anti-viral pathway) and for
immune cell apoptosis in ME/CFS.  Notably, the dysregulation and
up-regulation of the 2-5A synthetase / RNase-L pathway in ME/CFS are not
just epiphenomena: there is hard evidence supporting their clinical
importance.  Nijs explained that decreased natural killer (NK) cell
function, the presence of infections and intracellular immune dysfunctions
are all inter-related components of ME/CFS pathophysiology.

Professor Julia Newton from the University of Newcastle (UK) spoke of her
work on autonomic dysfunction in ME/CFS and its effects on respiration,
bladder and bowel function, and on cardiovascular function such as
maintenance of heart rate and blood pressure. Autonomic dysfunction is a
frequent finding in people with ME/CFS. Her research group has shown that
89% of ME/CFS patients experience symptoms on standing (orthostatic
intolerance) and her studies examining haemodynamic responses to standing
have shown that ME/CFS patients have Positional Orthostatic Tachycardia
Syndrome, and that cardiovascular parameters correlate with increasing

(The above summary is taken from the Report on the Cambridge conference "New
Horizons 2008" by Dr Neil Abbot of MERUK, to whom grateful acknowledgement
is made: a set of 4 DVDs of the whole conference is available for £5 from
MERUK: telephone: 01738-451234; email: ; website:  ).

The scientific evidence in this summary alone renders incomprehensible the failure of the GDG to heed the serious biomedical abnormalities that have been demonstrated in ME/CFS.

The ignoring of the existing evidence-base on ME/CFS would seem to make the
GDG's recommendation for behavioural modification as the single management
approach for "CFS/ME" (which they stipulate includes the WHO ICD-10
classified neurological disorder ME) tantamount to serious professional
negligence, especially given that the NICE Guideline ignores the many
international calls for more specialist laboratory investigations and
actually proscribes such testing.

Further, the Guideline does not recommend biomedical research into these key
areas as a matter of priority.  Quoting the Gibson Report of November 2006,
it does briefly refer to the need for research into the  "biological basis
of CFS/ME" (page 169) but then changes this to the "encouragement of further
appropriate research to identify causative factors" (page 187).

As far as the Wessely School psychiatrists are concerned (who were advisers
to NICE and who are renowned for their intransigent belief that ME does not
exist and that what they term "CFS/ME" is an aberrant illness belief),
"appropriate research to identify causative factors" is centred on their own
(unproven) psychosocial model, not on essential biomedical research.

As far as State-sponsored research is concerned, the Medical Research
Council (MRC) categorises "CFS/ME" as a mental disorder and it is a matter
of record that Wessely School psychiatrists control the purse strings in
relation to "CFS/ME" funding, so perhaps it is not surprising that the MRC
has a track record of rejecting funding for biomedical research into ME/CFS,
despite paying lip-service in 2003 by announcing its 'research strategy for
CFS/ME'. There is undisputed evidence of psychiatric bias on the part of the
MRC, because approximately 91% of the MRC's total grant-spend on ME/CFS in
five years has gone on psychiatric trials of behavioural interventions
(CBT/GET), with the MRC stating: "CBT will be based on the illness model of
fear avoidance (and) GET will be based on the illness model of
deconditioning and exercise avoidance"
(Dr Neil Abbot; "Breakthrough",
Autumn 2008: 8-9; MERUK).

In contrast, the MRC is known to have turned down no less than 33 biomedical
and pathophysiological research projects on ME/CFS.  It is unlikely that
these 33 applications were all so badly written that they could be rejected,
since some were from established researchers with a sound track record. It
is held by many that the MRC has a case to answer over the non-funding of
biomedical research into ME/CFS.

By recommending only mind-altering therapies combined with incremental
aerobic exercise, the NICE Guideline is perpetuating this psychiatric bias.

Despite the many calls for appropriate immunological investigations in the
following illustrations, the Guideline firmly rejects the need for such

It is perhaps significant that in the 1996 Joint Royal Colleges Report on
"CFS" that was orchestrated by the Wessely School psychiatrists, Simon
Wessely, Peter White et al specifically advised Government bodies against
immunological investigations:

·        "The Royal Colleges have stressed that approaches to these patients
should not be based on simple biomedical models" (page 2)

·        "Since the case definition has been revised (i.e. by Wessely School
psychiatrists themselves) it is no longer necessary to exclude those with
common psychiatric disorders" (page 8)

·        "The possibility that abnormalities of immune function play a role
in the pathogenesis of CFS has attracted considerable attention. Some use
the results of immunological tests as evidence for a so-called 'organic'
component in CFS.  Such abnormalities should not deflect the clinician from
the (psychosocial) approach and should not focus attention towards a search
for an 'organic' cause" (page 13)

·        "No investigations should be performed to confirm the diagnosis"
(page 45) (CFS: Report of a Joint Working Group of the Royal Colleges of
Physicians, Psychiatrists and General Practitioners. Royal College of
Physicians, CR54, October 1996).

Illustrations of immunological dysfunction in ME/CFS from the published
literature that NICE disregarded in the production of its Clinical Guideline
53 (illustrations of neuroendocrine and neurological dysfunction follow this
section on immunological dysfunction)


Irving Salit, Associate Professor of Medicine and Microbiology at the
University of Toronto and Head of the Division of Infectious Diseases at
Toronto General Hospital, noted: "Findings include mild immunodeficiency,
slightly low complement, anti-DNA antibodies and elevated synthetase, which
is an interferon-associated enzyme commonly increased in infections
. This
illness is of major importance because it is so prevalent and because it has
such devastating consequences: afflicted patients are frequently unable to
work or carry on with usual social activities.  We have found that a wide
variety of infections may precipitate this illness (including Coxsackie B
and mycoplasma). Some patients have mild elevations of IgM or IgG (and) low
levels of anti-nuclear antibody. Patients tend to tolerate medications very
poorly and many have a history of drug allergies.  Most patients do not
improve on anti-depressants and are usually exquisitely sensitive to the
side effects. It is important for the physician to understand their
suffering. There are enough abnormalities of organic disease to suggest that
(it) is not purely a psychological ailment
" (Clin Ecol 1987/8:V:3:103-107).


US clinicians and researchers who became world leaders in ME/CFS (including
Paul Cheney, Daniel Peterson and Anthony Komaroff) noted: "These studies
demonstrated that a majority of patients with (ME)CFS have low numbers of
NKH1+T3- lymphocytes, a population that represents the great majority of NK
cells in normal individuals
. (ME)CFS patients had normal numbers of NKH1+T3+
lymphocytes, a population that represents a relatively small fraction of NK
cells in normal individuals. When tested for cytotoxicty against a variety
of different target cells, patients with (ME)CFS consistently demonstrated
low levels of killing. In humans, studies suggest a correlation between low
NK activity and serious viral infections in immunocompromised hosts. We have
carried out extensive phenotypic and functional characterisation of NK cells
in patients with this syndrome (and have) found that the majority had
abnormally low numbers of NKH1+ cells.
Further characterisation of such
cellular subset abnormalities and the resulting alteration in quantitative
and qualitative NK cytotoxic function will hopefully improve our
understanding of the immunopathogenesis of this illness" (M Caliguri et al.
The Journal of Immunology 1987:139:10: 3306-3313).


"We report patients (who) had a specific deficiency of IgG1 subclass. The
finding of IgG1 subclass deficiency in these patients is novel, as lone
deficiency of this subclass is rare and affected patients appear to have
common variable hypogammaglobulinaemia.
  Further scrutiny of cases (of
ME/CFS) may reveal a range of subtle immunological abnormalities" (Robert
Read, Gavin Spickett et al. Lancet, January 30 1988:241-242).


"(ME)CFS has been associated with abnormal T cell function. These patients
have diminished phytohaemagglutinin-induced lymphocyte transformation and
decreased synthesis of interleukin.
  We studied the display of CD3, CD5,
CD2, CD4, CD8 and Leu-M3-defined antigen in peripheral blood mononuclear
cells in (ME)CFS who fulfilled the (1988 Holmes et al) criteria.  Patients
had reduced expression of CD3. These data indicate that in (ME)CFS, some
patients have T lymphocytes (CD2- and CD5- positive cells) without
immunoreactive CD3" (ML Subira et al. The Journal of Infectious Disease


"Disordered immunity may be central to the pathogenesis of (ME)CFS.  Reduced
IgG levels were common (56% of patients), with the levels of serum IgG3 and
IgG1 subclasses particularly affected
. The finding of significantly
increased numbers of peripheral blood mononuclear cells that express
Class-II histocompatibility antigens (HLA-DR) in our patients implies
immunological activation of these cells.  Once activated, these cells may
continue to produce cytokines which may mediate the symptoms of (ME)CFS"
(AR Lloyd et al. The Medical Journal of Australia 1989:151:122-124).


"Our investigations suggest that this syndrome is characterised by objective
laboratory abnormalities (and) immune dysfunction appears to be a hallmark
of the disease process. The best marker appears to be lowered NK activity"
(NL Eby, S Grufferman et al. In: Natural Killer Cells and Host Defense. 5th
International NK Cell Workshop, Hilton Head, SC.  Ed: Ades EW, Lopez C.
Basel, Karger 1989:141-145).


"In order to characterise in a comprehensive manner the status of laboratory
markers associated with cellular immune function in patients with this
syndrome, patients with clinically defined (ME)CFS were studied. All the
subjects were found to have multiple abnormalities in these markers. The
pattern of immune marker abnormalities observed was compatible with a
chronic viral reactivation syndrome.
A substantial difference in the
distribution of lymphocyte subsets of patients with (ME)CFS was found when
compared with normal controls. Lymphocyte proliferation after PHA and PWM
stimulation was significantly decreased in patients (by 47% and 67%
respectively) compared with normal controls. Depression of cell-mediated
immunity was noted in our study population, with over 80% of patients having
values below the normal mean.  The present report confirms that a
qualitative defect is present in these patients' NK cells (which) might
represent cellular exhaustion as a consequence of persistent viral stimulus.

Results from the present study indicate that there is an elevation in
activated T cells.  A strikingly similar elevation in CD2+ CDw26+ cells has
been reported in patients with multiple sclerosis. In summary, the results
of the present study suggest that (ME)CFS is a form of acquired
immunodeficiency.  This deficiency of cellular immune  function was present
in all the subjects we studied" (Nancy G Klimas et al. Journal of Clinical
Microbiology 1990:28:6:1403-1410).


"(A) subnormal number of CD8 lymphocytes, a raised serum IgE level and a
positive VP1 antigen are sufficiently frequent to suggest that they should
become part of the routine screening of such patients.  In the present ME
study, patients show a 40% incidence of both clinical and laboratory
evidence of atopy.
  It has been shown that T cell deficiency, particularly
of the suppressor subset, can predispose to atopy without a genetic family
history.  We have undertaken extensive T cell subset measurements in normal
subjects subjected to psychological stress and would point out in none of
these did we see CD8 levels as low as in some 40% of our ME patients" (JR
Hobbs, JA Mowbray et al. Protides of Biological Fluids 1990:36:391-398).


"Compared with controls, (ME)CFS patients showed an increase in CD38 and
HLA-DR expression.  These data point to a high probability (90%) of having
active (ME)CFS if an individual has two or more of the CD8 cell subset
alterations. Laboratory findings among (ME)CFS patients have shown low level
autoantibodies, which may reflect an underlying autoimmune disorder.
persistent hyperimmune response of the remaining CD8 cells might lead to an
outpouring of cellular products and cytokines (eg. interferon, tumour
necrosis factor, interleukin-1) that are characteristically associated with
myalgia, fatigue, (and) neurological signs and symptoms associated with
acute viral infections. Unless the immune system is brought back into
balance, this chronic activation affects the individual further and might
eventually lead to other clinical illnesses
" (Alan L Landay et al. Lancet


In "Review of laboratory findings for patients with chronic fatigue
syndrome" Buchwald and Komaroff et al listed the following (yet NICE claims
there are no abnormal laboratory findings): "Various abnormalities revealed
by laboratory studies have been reported in adults with (ME)CFS. Those most
consistently reported include depressed natural killer cell function and
reduced numbers of natural killer cells; low levels of circulating immune
complexes; low levels of several autoantibodies, particularly antinuclear
and antithyroid antibodies; altered levels of immunoglobulins (and)
abnormalities in number and function of lymphocytes"
  (Reviews of Infectious
Diseases 1991:13 (Suppl 1): S12- S28).


A major study looking at neurological, immunological and virological aspects
in 259 (ME)CFS patients found that neurological symptoms, MRI findings and lymphocyte phenotyping studies suggest that patients "may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system"  and that "Magnetic resonance scans of the brain
showed punctate, subcortical areas of high signal intensity consistent with
oedema or demyelination in 78% of patients
.  We think that this is probably
a heterogeneous illness that can be triggered by different environmental
factors (including stress, toxins and infectious agents), all of which can
lead to immune dysfunction and the consequent reactivation of latent
viruses" (D Buchwald, Paul Cheney, Daniel Peterson, Robert C Gallo, Anthony
Komaroff et al. Ann Int Med 1992:116:2:103-113).


At the 1993 Los Angeles Conference on (ME)CFS, evidence was presented by
Professor Nancy Klimas from the University of Miami that she and her team
have been able to accurately predict 88% of (ME)CFS patients with a
mathematical model of immunological parameters.  This model combines levels
of activated T cells and CD4 inducers of cytotoxic T cells with NK cell
count and function:
"In a normal population, 20% of lymphocytes are active
at any given time. 'In (ME)CFS, up to 80% 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" (CFIDS Chronicle: Summer 1993).


"Using the immunophenotypic data presented, we were able to demonstrate that
almost 50% of (ME)CFS patients, especially those with severe symptoms,
showed signs of CD8+ cell activation and an abnormal suppressor / cytotoxic
CD8+ cell ratio. Our observations strongly suggest that a large population
of (ME)CFS patients have immunologic disorders and that their symptoms could
be explained by a chronic immune activation state (and) that (ME)CFS
represents a type of autoimmune disease
in which a chronically activated
immune system reacts against the host.  The 3:1 female/male ratio would not
be unexpected: autoimmune syndromes are more common in women
. Because of the
autoreactive nature of this condition, it might also lead to other immune
disorders, such as well-recognised autoimmune diseases and multiple
sclerosis" (Jay A Levy et al. Contemp Issues Infec Dis 1993:10:127-146).

According to Dr Elizabeth Dowsett, former President of the ME Association,
at least 13% of ME/CFS patients are indistinguishable from patients with
multiple sclerosis
(personal communication).


"The chronic fatigue immune dysfunction syndrome (CFIDS) is a major subgroup
of the chronic fatigue syndrome (CFS). We and other investigators have
reported a strong association between immune dysfunction and a serological
viral activation pattern
among patients in this group. This finding appeared
similar to that for a variety of conditions, such as chronic active
hepatitis and systemic lupus erythematosus, in which a definite association
between a particular HLA-DR/DQ haplotype and increased disease frequency has
been reported.  We thus elected to examine a cohort of patients with CFIDS,
with use of HLA-DR/DQ typing. A significant association between CFIDS and
the presence of HLA-DQ3 was noted
.  The association with HLA-DQ3 could
represent an additive effect for patients who also have HLA-DR4 and/or
HLA-DR5. (Our) results are intriguing.  DQ3 was significantly more prevalent
in patients than controls.  It is possible that DR4 and DR5 are also
associated with an increased risk of developing CFIDS.  These findings
strongly suggest that further evaluation of persons with CFIDS, including an
investigation of an HLA Class I linkage dysequilibrium, are warranted. The
data presented herein suggest that CFIDS, together with a variety of
immune-mediated diseases, may share similar sequences of pathogenic
mechanisms (and) in a subpopulation (of CFIDS), a genetic predisposition may
be triggered immunologically by any number of potential stimuli, resulting
in a state of chronic immune dysequilibrium.  This model could easily
explain findings with regard to viral infection (and) allergies" (RH Keller,
N Klimas et al. Clin Inf Dis 1994:18: (Suppl 1): S154-156).


"These data suggest a correlation between low levels of NK cell activity and
severity of CFIDS.  Compromised or absent natural immunity is associated
with acute and chronic viral infections such as AIDS, CFIDS and various
immunodeficiency syndromes.
Stratification of patients with CFIDS into
distinct groups according to the severity or duration of physical
abnormalities might allow identification of laboratory abnormalities that
are associated with severity.  The fact that NK cell activity decreases with
increased severity and duration of certain clinical variables suggests that
measurement of NK cell function could be useful for stratification of
patients and possibly for monitoring therapy for and / or the progression of
CFIDS" (EA Ojo-Amaize et al. Clin Inf Dis 1994:18: (Suppl 1):S157-159).


"The immune system is a readily accessible, sensitive indicator of
environmental or internal changes, and studies conducted by different groups
over the past few years have provided valuable evidence for changes in
immune status among individuals with (ME)CFS.  To gain insight into the
nosology and aetiology of (ME)CFS, we assessed patterns of soluble immune
mediator expression at the protein and mRNA levels in individuals with
(ME)CFS.  The data presented in this report are consistent with previous
evidence of immune dysregulation among patients with (ME)CFS and point to a
dysregulation of TNF (tumour necrosis factor) expression as a distinctive
feature of this condition. Imbalances in TNF and associated changes in
levels of other cytokines may underlie many of the characteristic features
of (ME)CFS. In addition, TNF-a can have deleterious effects on the central
nervous system"
(Roberto Patarca, Nancy G Klimas et al. Clin Inf Dis
1994:18: (Suppl 1):S147-153).

Tumour necrosis factor is a cytokine involved in systemic inflammation.  Its
primary role is in the regulation of immune cells.  Increased TNF causes
apoptosis, inflammation and tumorigenesis.


"The up-regulated 2-5A pathway in (ME)CFS is consistent with an activated
immune state and a role for persistent viral infection in the pathogenesis
of (ME)CFS.
  The object of this study was to measure key parameters of the
2-5A synthetase/RNase-L antiviral pathway in order to evaluate possible
viral involvement in (ME)CFS.  The data presented suggest that 2-5A
synthetase/RNase L pathway is an important biochemical indicator of the
anti-viral state in (ME)CFS. Evidence that this pathway is activated in
(ME)CFS was identified in this subset of severely disabled individuals as
related to virological and immunologic status. This pathway phenotype could
result from chronic over-stimulation due to chronic viral reactivation" (RJ
Suhadolnik et al.  Clin Inf Dis 1994:18(Suppl 1):S96-S104).


"In the study of a complex illness such as (ME)CFS, the most important
aspect is case definition. Patients whose symptoms are primarily related to
upper respiratory tract infections may have different precipitating agents
and pathogenesis than those with predominantly gastrointestinal
disturbances.  It has been noted for a number of years that a history of
allergies appears to be an important risk factor for (ME)CFS.  In addition
to a history of allergy, other factors, such as exposure to chemicals, were
noted to be possible triggers.  The spectrum of illnesses associated with a
dysregulated immune system now must include (ME)CFS
" (Paul H Levine. Clin
Inf Dis 1994:18(Suppl 1):S57-S60).


"One rationale for the immunological approach stems from the experience
accumulated with similar syndromes such as autoimmune and
environmentally-triggered diseases. (ME)CFS may be associated with certain
HLA Class II antigens, as are some forms of environmental disease. These
observations underscore the distinction between (ME)CFS and psychiatric
Viruses are frequently reactivated in association with immune
system dysregulation in (ME)CFS and may contribute to symptomatology"
(Roberto Patarca. JCFS 1995:vol I:3/4:195-202).


An important paper from Konstantinov and Tan et al demonstrated the
occurrence of autoantibodies to a conserved intracellular protein (lamin
B1), which provides laboratory evidence for an autoimmune component in
ME/CFS.  The authors found that 52% of patients with ME/CFS develop
autoantibodies to components of the nuclear envelope (NE), mainly nuclear
lamins, suggesting that in addition to the other documented disturbances of
the immune system, humoral autoimmunity against polypeptides of the NE is a
prominent immune derangement
in ME/CFS.  67% of ME/CFS patients were
positive for NE reactivity compared with 10% of normal controls.
Autoantibodies to NE proteins are relatively infrequent and most fall into
the category of an unusual connective tissue disease characterised by brain
or skin vasculitis
.  The authors concluded that such activation "could be
the result of various triggering agents, such as infections or environmental
toxins.  Future work should be directed at a better understanding of the
autoimmune response of (ME)CFS patients  to other NE antigens" (K
Konstantinov et al. J Clin Invest 1996:98:8:1888-1896).


In 1996, Hilgers and Frank developed a score for severity of ME/CFS to
correlate with parameters of immune activation. This was effected by a
30-point criteria score, basic laboratory programmes and immunological
profiles in 505 patients.  In addition, tests of the complement system,
immune activation markers, hormones and viral / bacterial intracellular
serology were evaluated.  Seventeen significant symptoms not currently in
the CDC case definition were added, these being respiratory infections,
palpitations, dizziness, dyspepsia, dryness of mouth / eyes, allergies,
nausea, paresthesia, loss of hair, skin alterations, dyscoordination (sic),
chest pain, personality changes, eczema, general infections, twitches and
urogenital infections.
  A significant correlation between the criteria score
and immunological parameters could be evaluated in 472 of the 505 patients.
The data confirm that a reduced or unstable immune control or delayed immune
reaction to persisting viruses or bacterial intracellular pathogens,
possibly triggered by common infections or other environmental factors, can
lead to a chronic neuroimmune activation state and autoimmune disorders
(JCFS 1996:2: (4):35-47).


"The level of bioactive transforming growth factor b was measured in serum
from patients with (ME)CFS and compared with normal controls, patients with
major depression, patients with systemic lupus erythematosus and patients
with multiple sclerosis. Patients with (ME)CFS had significantly higher
levels of bioactive TGFb than the healthy controls, patients with major
depression, patients with systemic lupus erythematosus and patients with
multiple sclerosis.
Of greatest relevance to (ME)CFS are the effects of TGF
b on cells of the immune and central nervous systems.  There is accumulating
evidence that TGFb may play a role in autoimmune and inflammatory diseases"
(AL Bennet, AL Komaroff et al. J Clin Virol 1997:17:2:160-166)


"(ME)CFS is associated with dysregulation of both humoral and cellular
immunity, including mitogen response, reactivation of viruses, abnormal
cytokine production, diminished natural killer (NK) cell function, and
changes in intermediary metabolites.  The biochemical and immunologic data
presented here identified a subgroup of individuals with (ME)CFS with an
RNase L enzyme dysfunction that is more profound
than previously observed
(and) is consistent with the possibility that the absence of the 80-kDa and
40-kDa RNase L and presence of the LMW RNase L correlate with the severity
of (ME)CFS clinical presentation" (Robert Suhadolnik, Daniel Peterson, Paul
Cheney et al. Journal of Interferon and Cytokine Research 1997:17:377-385).

Professor Suhadolnik explained in lay terms the significance of this paper
(reported by Patti Schmidt in CFIDS Chronicle, Summer 1997, page 17): "He
has found a particular place in the immune system, the 2-5 RNase L antiviral
pathway, where something is wrong. 'The whole antiviral pathway heats up out of control' explained Suhadolnik. 'You're really sick physiologically.  Your body just keeps going and going like the Energiser bunny, making ATP and breaking it down.  No wonder you're tired'. He's found a novel protein in
CFIDS patients in that viral pathway. 'In most cases, the human body is able
to resist infection thanks to a cascade of biochemical events triggered by
the body's immune system. If these antiviral defence pathways are
functioning correctly, the spread of the virus is prevented'.  Suhadolnick
believes that (ME)CFS patients' bodies are responding to a central nervous
system virus that interferes with their viral pathways' ability to fight off
infection ".


A highly-respected paper by Vojdani and Lapp et al stressed the importance
of cell apoptosis (and the pivotal role of protein kinase RNA in this) in
ME/CFS:  "A prominent feature of (ME)CFS is a disordred immune system.
Recent evidence indicates that induction of apoptosis might be mediated in a
dysregulated immune system by the up-regulation of growth inhibitory
cytokines. The purpose of this study was to evaluate the apoptotic cell
population, interferon-a and the IFN-induced protein kinase RNA (PKR) gene
transcripts in the peripheral blood lymphocytes of (ME)CFS individuals, as
compared to healthy controls. One of the distinguishing manifestations of
(ME)CFS is abnormal immune function, characterised by a decreased NK
cell-mediated cytotoxic activity, reduced mitogenic response to lymphocytes,
altered cytokine production, elevated titres of antibodies to a number of
viruses, and abnormal production of interferon (IFN).
The induction of
apoptosis through immune defence mechanisms is an important mechanism for
elimination of cancer cells as well as virus-infected cells. In the present
study, the up-regulation of IFN-a and the IFN-induced PRK in (ME)CFS
individuals is accompanied by the induction of apoptosis.  In addition,
dysregulation of cell cycle progression is associated with the induction of
apoptosis in (ME)CFS
individuals. Quantitative analysis of apoptotic cell
population in (ME)CFS individuals has shown a statistically significant
increase compared to healthy controls.  The population of apoptotic cells in
76% of (ME)CFS individuals was well above the apoptotic cell population in
the control cells. 
Activation of PKR can result in induction of apoptosis.
This activation of the PRK pathway could result from (a) dysregulated immune
system or chronic viral infection" (A Vojdani et al. Journal of Internal
Medicine 1997:242:465-478).


"The increased expression of Class II antigens and the reduced expression of
the costimulantory receptor CD28 lend further support to the concept of
immunoactivation of T-lymphocytes in (ME)CFS and may be consistent with a
viral aetiopathogenesis in the illness.
  We report, for the first time,
increased expression of the apoptosis repressor protein bcl-2 (and) we
demonstrated changes in different immunological parameters, each of which
correlated with particular aspects of disease symptomatology (and) measures
of disease severity" (IS Hassan, WRC Weir et al. Clin Immunol & Immunopathol


"It is of great importance to develop biomarker(s) for differentiation
between viral induced (ME)CFS (without sensitivity to chemicals) versus
chemically-induced (ME)CFS.  Since interferon induced proteins 2-5A
Synthetase and Protein Kinase RNA (PKR) have been implicated in the viral
induction of (ME)CFS, the objective of this study was to utilise 205A and
PKR activity for differentiation between (ME)CFS induced by either viruses
or chemicals. A clear induction of 2-5A and PKR was observed when MDBK cells
were exposed to HHV6, MTBE, and benzene.  We conclude that 2-5A and PKR are
not only biomarkers for viral induction, but biomarkers to other stressors
that include (chemicals)" (Vojdani A, Lapp CW. Immunopharmacol Immunotoxicol


An article from researchers at the Institute of Immunology in Moscow
discussed immunity impairment as a result of neurohormonal disorders and
noted that at the base of (ME)CFS lie disturbances of the central nervous
system, the endocrine system and the immune system: "It was found back in
1987/8 that there is an increase in the level of HLA DR and IL-2 receptors
and an increase in the ratio CD4/CD8
in patients suffering from this
syndrome"  (Artsimovich NG et al. Russ J Immunol 1999:4(4):343-345).

It is notable that Russian researchers were aware of these cardinal biomarkers of ME/CFS as long ago as 1999, but that eight years later, the NICE Guideline Development Group (who are acclaimed by NICE as "experts" in the disorder) still were apparently ignorant of these diagnostic biomarkers.


"The purpose of the present study was to investigate the relationship
between immunologic status and physical symptoms in (ME)CFS. (Results)
revealed significant associations between a number of immunologic measures
and severity of illness.  Specifically, elevations of T-helper/inducer
cells, activated T cells, activated cytotoxic/suppressor T cells, and
CD4/CD8 ratio were associated with greater severity of several symptoms.
Furthermore, reductions in T-suppressor/cytotoxic cells also appeared
related to greater severity of some (ME)CFS-related physical symptoms and
illness burden"  (SE Cruess, Nancy Klimas et al. JCFS 2000:7(1):39-52).


"Blood and lymph nodes samples were obtained from patients with (ME)CFS.
While a greater proportion of T lymphocytes from both lymph nodes and
peripheral blood of (ME)CFS patients are immunologically naïve, the
proportions of lymphocytes with a memory phenotype predominate in lymph
nodes and peripheral blood of (ME)CFS patients. (ME)CFS has been proposed to
be a disease of autoimmune aetiology and in this respect it is interesting
to note that decreased proportions of CD45RA+T (naïve) cells are also seen
in the peripheral blood of patients with autoimmune diseases"
(Mary Ann
Fletcher, Nancy Klimas et al. JCFS 2000:7(3):65-75).


A major and detailed Review of the immunology of (ME)CFS was published by
internationally-renowned immunologists Professors Robert Patarca and Nancy
Klimas, together with the distinguished long-time ME/CFS research
immunologist Mary Ann Fletcher.  It contains 212 references.  It is clear
that people with (ME)CFS have two basic problems with immune function: (1)
immune activation and (2) poor cellular function.
These findings have a
waxing and waning temporal pattern consistent with episodic immune
dysfunction.  The interplay of these factors can account for the
perpetuation of (ME)CFS with remission / exacerbation cycles.  The Review
considers the evidence of immune cell phenotypic distributions; immune cell
function; cytokines and other soluble immune mediators; immunoglobulins;
autoantibodies; circulating immune complexes; Type I to Type II cytokine
shift and the relationship between stressors, cytokines and symptoms. The
data summarised indicate that (ME)CFS is associated with immune
abnormalities that can account for the physiopathological symptomatology,
and recommends that future research should further elucidate the cellular
basis for immune dysfunction in (ME)CFS and its implications (JCFS


In "Detection of immunologically significant factors for (ME)CFS using
Neural-Network Classifiers", authors Hanson, Gause and Natelson were able to
demonstrate what had previously been hypothesis: "Of significant interest
was the fact that, of all the cytokines evaluated, the only one to be in the
final model was IL-4 (which) suggests a shift to a Type II cytokine pattern.
Such a shift has been hypothesised, but until now convincing evidence was
lacking" (Clin Diagn Lab Immunol 2001:8(3)658-662).


"The present review examines the cytokine response to acute exercise stress.
The magnitude of this response bears a relationship to the intensity of
effort but many environmental factors also modulate cytokine release. The
main source of exercised-induced IL-6 production appears to be the
exercising muscle.  Cytokine concentrations are increased in (ME)CFS.

Exercise-induced modulations in cytokine secretion may contribute to
allergies (and) bronchospasm" (Shepherd RJ. Crit Rev Immunol


A study was carried out by Belgian researchers to determine whether
bronchial hyper-responsiveness (BHR) in patients with (ME)CFS is caused by
immune system abnormalities.  Measurements included pulmonary function
testing, histamine bronchoprovocation test, immunophenotyping and
ribonuclease (RNase) latent determination. There were 137 (ME)CFS
participants.  "Seventy three of the 137 patients presented with bronchial
hyper-responsiveness.  The group of patients in whom BHR was present
differed most significantly from the control group, with eight differences
in the immunophenotype profile in the cell count analysis, and seven
differences in the percentage distribution profile.  We observed a
significant increase in cytotoxic T-cell count and in the percentage of BHR+
patients.  Immunophenotyping of our sample confirmed earlier reports on
chronic immune activation in patients with (ME)CFS compared to healthy
controls, (with) BHR+ patients having more evidence of immune activation
(Nijs J, De Meirleir K, McGregor N et al. Chest 2003:123(4):998-1007).


Japanese researchers focused on immunological abnormalities against
neurotransmitter receptors in (ME)CFS using a sensitive radioligand assay.
They examined serum autoantibodies to recombitant human muscarinic
cholinergic receptor 1 (CHRM1) and other receptors in patients with (ME)CFS
and the results were compared with those in patients with autoimmune disease
and with healthy controls. The mean anti-CHRM1 antibody index was
significantly higher in patients with (ME)CFS and with autoimmune disease
than in controls.  Anti-nuclear antibodies were found in 56.7% of patients
with (ME)CFS. The patients with positive autoantibodies to CHRM1 had a
significantly higher score of  'feeling muscle weakness' than negative
patients among (ME)CFS patients. The authors conclude: "Autoantibodies to
CHRM1 were detected in a large number of (ME)CFS patients and were related
to (ME)CFS symptoms.
  Our findings suggest that subgroups of (ME)CFS are
associated with autoimmune abnormalities of CHRM1" (Tanaka S, Kuratsune H et
al. Int J Mol Med 2003:12(2):225-230).


Looking at complement activation in (ME)CFS in the light of the need to
identify biological markers in (ME)CFS, US researchers used an exercise
challenge to induce symptoms of (ME)CFS and to identify a marker that
correlated with those symptoms. "Exercise challenge induced significant
increases of the complement split product C4a at six hours after exercise
only in the (ME)CFS group"
(Sorensen B et al. J All Clin Immunol


"(ME)CFS is an increasing medical phenomenon leading to high levels of
chronic morbidity.  The aim of this study was to screen for changes in gene
expression in the lymphocytes of (ME)CFS patients. In a small but
well-characterised population of (ME)CFS patients, differential display has
been used to clone and sequence genetic markers that are over-expressed in
the mononuclear cells of (ME)CFS patients. Many researchers have recognised
that current methods of diagnosis lead to the selection of a heterogeneous
sample, and these data support that view.  It is encouraging that the wide
'spread' of data seen in (ME)CFS patients is not seen in the control
samples.  The data presented here add weight to the idea that (ME)CFS is a
disease characterised by over-expression of genes, some of which are known
to be associated with immune system activation
.  Identifying the triggering
events for the induction of these genes will increase our understanding of
this disease. Some interesting possibilities include viral infection,
neuroendocrine disturbances, and allergen exposure.  A link with allergy may
be particularly pertinent since approximately 80% of (ME)CFS patients are
atopic.  Some of the genes identified in this study may therefore be linked
with the increase in allergic effects seen in (ME)CFS"  (R Powell, S Holgate
et al. Clin Exp Allergy 2003:33:1450-1456).


In an Invited Review, Patrick Englebienne from the Department of Nuclear
Medicine, Vrije University, Brussels, explained in simple terms the
significance of RNase L: "RNase L (2-5-oligoadenylate-dependent ribonuclease
L) is central to the innate cellular defence mechanism induced by Type I
interferons during intracellular infection. In the absence of infection, the
protein remains dormant.  Recent evidence indicates, however, that the
protein is activated in the absence of infection and may play a role in cell
differentiation (and) immune activation. A de-regulation of this pathway has
been documented in immune cells of (ME)CFS patients
. This protein escapes
the normal regulation (resulting in) a cascade of unwanted cellular events.
Recent data indicate that the RNase L system role is not limited to the cell
defence mechanism against intracellular infection but extends to the
complete innate and adaptive immune systems, including NK and T-cell
proliferation and activation, as well as to cell differentiation and
proliferation. The presence of unregulated active RNase L fragments in
immune cells may lead to deleterious effects which are inherent to the
cellular targets of the protein (because) an unregulated destruction of rRNA
and of mitochondrial RNA leads to cell apoptosis.  Should the RNase L
de-regulation exist in muscle cells, it would necessarily restrain normal
muscular development and hence activity (and) muscular weakness is a common
feature of (ME)CFS
" (JCFS 2003:11(2):97-109).


"The exacerbation of symptoms after exercise differentiates (ME)CFS from
several other fatigue-associated disorders
.  Research data point to an
abnormal response to exercise in patients with (ME)CFS compared to healthy
sedentary controls, and to an increasing amount of evidence pointing to
severe intracellular immune dysregulation
in (ME)CFS patients. The
dysregulation of the 2-5A synthetase/RNase L pathway may be related to a
chanelopathy, capable of initiating both intracellular hypomagnesaemia in
skeletal muscles and transient hypoglycaemia.  This might explain muscle
weakness and the reduction of maximal oxygen uptake, as typically seen in
(ME)CFS patients.  The activation of the protein kinase R enzyme, a
characteristic feature in at least a subset of (ME)CFS patients, might
account for the observed excessive nitric oxide (NO) production in patients
with (ME)CFS.  Elevated NO is known to induce vasodilation, which may cause
and enhance post-exercise hypotension" (J Nijs, K De Meirleir, N McGregor, P
Englebienne et al.  Med Hypotheses 2004:62(5):759-765).


"Immunological aberration (in ME/CFS) may be associated with an expanding
group of neuropeptides and inappropriate immunological memory.
neuropeptides act as hormones, neurotransmitters, immune modulators and
neurotrophes.  They are immunogenic and known to be associated with a range
of autoimmune conditions.  They are widely distributed in the body,
particularly in the central, autonomic and peripheral nervous systems and
have been identified in the gut, adrenal gland, reproductive organs,
vasculature, blood cells and other tissues.  They have a vital role in
maintaining vascular flow in organs and are potent immune regulators with
primary anti-inflammatory activity.  They have a significant role in
protection of the nervous system (from) toxic assault.  This paper provides
a biologically plausible mechanism for the development of (ME)CFS based on
loss of immunological tolerance to the vasoactive neuropeptides following
infection or significant physical exercise. Such an occurrence would have
predictably serious consequences resulting from the compromised function of
the key roles these substances perform" (Staines DR. Med Hypotheses


"Patients (with ME/CFS) are more likely to have objective abnormalities of
the immune system than control subjects
. We measured the frequency of
certain HLA antigens (and) restricted our analysis to Class II molecules, as
these appear to be more specific predictors of susceptibility to
immunologically-based disorders. The frequency of the HLA-DQ1 antigen was
increased in patients compared to controls.  This association between
(ME)CFS and the HLA-DQ1 antigen translates into a relative risk of 3.2" (RS
Schacterle, Anthony L Komaroff et al. JCFS 2004:11(4):33-42).


"(ME)CFS is a serious health concern (and) studies have suggested an
involvement of the immune system. A Symposium was organised in October 2001
to explore the association between immune dysfunction and (ME)CFS, with
special emphasis on the interactions between immune dysfunction and
abnormalities noted in the neuroendocrine and autonomic nervous systems of
individuals with (ME)CFS.  This paper represents the consensus of the panel
of experts who participated in this meeting (which was co-sponsored by the
US Centres for Disease Control and the National Institutes of Health). Data
suggest that persons with (ME)CFS manifest changes in immune responses that
fall outside normative ranges.  It has become clear that (ME)CFS cannot be
understood based on single measurements of immune, endocrine, cardiovascular
or autonomic nervous system dysfunction. The panel encourages a new emphasis
on multidisciplinary research into (ME)CFS.  The panel recommends the
implementation of longitudinal studies that include the following key
elements: well-characterised cases and controls; assays designed to measure
immune function: (a) natural killer cell activity; (b) percentage of
peripheral blood lymphocytes expressing activation markers; (c)
pro-inflammatory cytokines and soluble receptors; (d) Th-1 and Th-2
responses; (e) activity of the 2-5A synthetase pathway, and (f) serum
immunoglobulin levels; selected measures of autonomic nervous system and
neuroendocrine functioning; functional magnetic resonance imaging studies;
studies to demonstrate the presence or absence of viral/microbial genetic
The use of interdisciplinary, multi-site (including international)
longitudinal studies to explore links between the variations noted in
(ME)CFS patients' immune, neuroendocrine, and cardiovascular systems is
critical. Three primary methodological barriers impair the investigations of
(ME)CFS: poor study design, the heterogeneity of the CFS population, and the
lack of standardised laboratory procedures. The quality of previous CFS
research (is hampered by) multiple differences in methods of subject
recruitment and classification (and) clinical definitions applied and
outcome measures used.  It is our obligation to overcome the methodological
barriers outlined above" (Gerrity TR et al.  Neuroimmunomodulation

It is to be noted that the term "multidisciplinary research" used by
non-psychiatrists means what it says, whereas when the same term is used by
Wessely School psychiatrists and UK Government agencies, it means the
involvement of psychiatrists.

It is also to be noted that UK Government agencies (including the CMO, the
MRC and NICE) all specifically advise against the recommendations above that
are designated by US experts as being of "critical" importance, and
proscribe the use of immunological assays and nuclear medicine imaging for
patients with ME/CFS in the UK.


"Many patients with (ME)CFS have symptoms that are consistent with an
underlying viral or toxic illness
. Because increased neutrophil apoptosis
occurs in patients with infection, this study examined  whether this
phenomenon also occurs in patients with (ME)CFS.  Patients with (ME)CFS had
higher numbers of apoptotic neutrophils, lower numbers of viable
neutrophils, and increased expression of the death receptor, tumour necrosis
factor receptor-1 on their neutrophils than did healthy controls.  These
findings provide new evidence that patients with (ME)CFS have an underlying
detectable abnormality in their immune cells
" (Kennedy G et al.  J Clin
Pathol 2004:57(8):891-893).

Commenting on this paper, Dr Neil Abbot, Director of Operations at ME
Research UK, noted: "The new paper by Dr Gwen Kennedy (MERGE Research
Fellow) and colleagues reports evidence of increased neutrophil apoptosis
(programmed cell death) in ME/CFS patients.  Neutrophils represent 50-60% of
the total circulating white blood cells and are fundamental to the
functioning of an intact immune system.  The data presented in this report
are consistent with the presence of an underlying, detectable abnormality in
immune cell behaviour of many ME/CFS patients, consistent with an activated
inflammatory process, or a toxic state
" (Co-Cure RES MED 30th July 2004).


"Arguments exist as to the cause of (ME)CFS.  Some think that it is an
example of symptom amplification indicative of psychogenic illness, while
our group thinks that some (ME)CFS patients may have brain dysfunction.  We
did spinal taps (lumbar puncture) on (ME)CFS patients. We found that
significantly more (ME)CFS patients had elevations either in protein levels
or numbers of cells than healthy controls and (some) patients had protein
levels and cell numbers that were higher than laboratory norms.  In
addition, of the 11 cytokines detectable in spinal fluid, (some) were lower
in patients than in controls (and some) were higher in patients.  The
results support two hypotheses: that some (ME)CFS patients  have a
neurological abnormality and that immune dysregulation within the central
nervous system may be involved in this process
. A recent study showing
elevations of IL-8 and IL-10 levels during chemotherapy-induced symptoms
resembling some of those seen in (ME)CFS
provides additional evidence for
this hypothesis" (Benjamin H Natelson et al. Clin Diagn Lab Immunol


An article in The Scientist pointed out the need to measure cytokines in
diverse disorders: "The immune system is often likened to the military.  The
body's army has weapons such as antibodies and complement, and soldiers such
as macrophages and natural killer cells.  The immune system sports an
impressive communications infrastructure in the form of intracellular
protein messengers called cytokines and the cellular receptors that
recognise them.  The cytokine family consists of such soluble growth factors
as the interleukins, interferons, and tumour necrosis factor, among others.
Their measurement has become an integral part of both clinical diagnostics
and biomedical research" (JP Roberts. The Scientist 2005:19:3:30).

It again needs to be noted that the NICE Clinical Guideline 53 proscribes
such measurements (as did the MRC's "CFS/ME Research Advisory Group Research
Strategy" Report of 1st May 2003, as did the CMO's Report of 2002, and as
did the Joint Royal Colleges Report of 1996).


"Hyperactivation of an unwanted cellular cascade by the immune-related
protein RNase L has been linked to reduced exercise capacity in persons with
  This investigation compares exercise capabilities of (ME)CFS
patients with deregulation of the RNase L pathway and CFS patients with
normal regulation. The results implicate abnormal immune activity in the
pathology of exercise intolerance in (ME)CFS and are consistent with a
channelopathy involving oxidative stress and nitric-oxide toxicity" (Snell
CR et al. In Vivo 2005:19(2):387-390).


"Diminished NK cell cytotoxicity is a frequently reported finding (in
ME/CFS).  However, the molecular basis of this defect has not been
described.  Perforin is a protein found within intracellular granules of NK
and cytotoxic T cells. Quantitative fluorescence flow cytometry was used to
the intracellular perforin content in (ME)CFS subjects and healthy controls.
A significant reduction in the NK cell associated perforin levels in samples
from (ME)CFS patients compared to healthy controls was observed.  There was
also an indication of a reduced perforin level within the cytotoxic T cells
of (ME)CFS subjects, providing the first evidence (of) a T cell associated
cytotoxic deficit in (ME)CFS.  Because perforin is important in immune
surveillance and homeostatis of the immune system, its deficiency may prove
to be an important factor in the pathogenesis of (ME)CFS and its analysis
may prove useful as a biomarker in the study of (ME)CFS" (Maher KJ, Klimas
NG, Fletcher MA. Clin Exp Immunol 2005:142(3):505-511).


"Previous research has shown that patients with (ME)CFS present with an
abnormal exercise response and exacerbations of symptoms after physical
activity.  The highly heterogeneous nature of the CFS population and the
lack of uniformity in both diagnostic criteria and exercise testing
protocols preclude pooling of data.  Still, we conclude that at least a
subgroup of CFS patients present with an abnormal response to exercise.
Importantly, the exacerbation of symptoms after exercise is seen only in the
(ME)CFS population and not in fatigue-associated disorders such as
. Earlier (studies) revealed that in (ME)CFS patients, irrational
fear of movement is not related to exercise performance
. The aim of this
study was to examine the interactions between several intracellular immune
variables and exercise performance in (ME)CFS. These data add to the body of
literature showing impairment of intracellular immunity in patients with
(ME)CFS.  The results provide evidence for an association between
intracellular immune dysregulation and exercise performance in patients with
(ME)CFS" (J Nijs, N McGregor, K De Meirleir et al. Medicine & Science in
Sports & Exercise 2005:Exercise Immunology in CFS:1647-1654).


"The hypothesis of the present study is that the appearance of cell-specific
autoimmune antibodies may define subsets of (ME)CFS. (ME)CFS is clinically
similar to several autoimmune disorders that can be diagnosed and
characterised by autoantibody profiles.  For this reason, we conducted an
exhaustive evaluation of 11 ubiquitous nuclear and cellular autoantigens in
addition to two neuronal specific antigens. Very few studies have evaluated
the presence of autoantibodies in people with (ME)CFS. The findings of this
study hint that evaluation of certain autoantibodies may give clues to
on-going pathology in subsets of (ME)CFS subjects. Among (ME)CFS subjects,
those who had been sick longer had higher rates of autoantibodies
" (S Vernon
et al. Journal of Autoimmune Diseases May 25th, 2005:2:5).

"The diagnostic criteria of CFS define a heterogeneous population composed
of several subgroups.  This study was designed to examine NK cell activity
as a potential subgroup biomarker. The results (provide) evidence in support
of using NK cell activity as an immunological subgroup marker in (ME)CFS.
Improved treatment options will only come with better understanding of the
syndrome's underlying pathophysiology The present study specifically
investigated the existence of an immunological subgroup of CFS patients.
Reduced NK cell activity may contribute to enhanced cytokine production.
Given the role that NK cells play in targeting virally infected cells, a
clinically significant reduction in NK cell activity may lead to activation
of latent viruses and new viral infections. (ME)CFS is a misunderstood
condition. Research in the last two decades has produced little advancement
in the understanding of the pathophysiology of (ME)CFS.  Unfortunately, this
lack of progress seems to have further contributed to the belief among some
members of the medical community that (ME)CFS is not an actual organic
(Scott D Siegel, Mary Ann Fletcher, Nancy Klimas et al. J
Psychosom Res 2006:60:6:559-566).


"(ME)CFS is a poorly defined medical condition which involves inflammatory
and immune activation.  The Type I interferon antiviral pathway has been
repeatedly shown to be activated
in the most afflicted patients. An abnormal
truncated form of ribonuclease L (37-kDa RNase L) is also found in (ME)CFS
patients and this protein has been proposed as a biological marker for
(ME)CFS. The levels of this abnormal protein have been significantly
correlated to the extent of inflammatory symptoms displayed by (ME)CFS
patients.  (Our) results suggest that chronic inflammation due to excess
nitric oxide plays a role in (ME)CFS and that the normal resolution of the
inflammatory process is impaired"
(M Fremont, K De Meirleir et al. JCFS

2007 (April)  (the NICE Guideline was published on 22nd August 2007)

"For decades, (ME)CFS patients were - and still are - dismissed as lazybones
or hypochondriacs.  Many medical doctors and insurance companies still
assert that (ME)CFS is a mental condition. The mainstream treatment for
(ME)CFS is CBT, which means that patients with (ME)CFS are being treated as
having a mental illness with 'treatments' that do not treat any underlying
cause.  Doctors who treat (ME)CFS patients as suffering from an organic
disorder and scientists who examine the biological causes of (ME) are  often
considered quacks by their colleagues (and) insurance companies, which are
sometimes even officially supported by governments in their attempts to
eliminate the scientific view that (ME)CFS is an organic disorder.  The
official acceptance of the latter obviously would mean that the national
health care systems are obliged to financially support those patients who
are now considered hypochondriacs and, therefore, may easily be suspended
from the national health care systems.  There is, however, evidence that
(ME)CFS is a severe immune disorder with inflammatory reactions and
increased oxidative stress.  Maes et al show that patients with (ME)CFS show
very high levels of nuclear factor kappa beta in their immune cells.  NFkb
is the major mechanism which regulates inflammation and oxidative stress.
Thus, the increased production of NFkb in the white blood cells of patients
with (ME)CFS is the cause of the inflammation and oxidative stress (seen) in
(ME)CFS" (Maes et al. Neuroendocrinology Letters, 2007.  ).

Evidence has continued to mount since the publication of the NICE Clinical
Guideline, for example:


"Recent research has evaluated genetic signatures, described biologic
subgroups, and suggested potential targeted treatments. Acute viral
infection studies found that initial infection severity was the single best
predictor of persistent fatigue.
Studies of immune dysfunction (have)
extended observations of natural killer cytotoxic cell dysfunction of the
cytotoxic T cell through quanitative evaluation of intracellular perforins
and granzymes.
  Other research has focused on a subgroup of patients with
reactivated viral infection. Our expanded understanding of the genomics of
(ME)CFS has reinforced the evidence that the illness is rooted in a biologic
pathogenesis that involves cellular dysfunction and interactions between the
physiologic stress response and inflammation.  A large body of evidence
links (ME)CFS to a persistent viral infection. (ME)CFS patients exhibited a
distinct immune profile
compared with fatigued and non-fatigued individuals.
These patients displayed increased anti-inflammatory cytokines.
Investigators noted the tropism with brain and muscle and suggested that the
neuroinflammation seen in neuroimaging studies of a subgroup of CFS patients
may result from enteroviral infection
.  (Note that the NICE Guideline
proscribes neuroimaging studies in the UK). The clinical implications are
consistent with an immune system that may allow viral reactivation and
raises a concern for tumour surveillance as well. The preponderance of
available research confirms that immune dysregulation is a primary
characteristic of (ME)CFS.  These advances should result in targeted
therapies that impact immune function, hypothalamic-pituitary-adrenal axis
regulation, and persistent viral reactivation
" (Nancy G Klimas et al.
Current Rheumatology Reports 2007:9:6:482-487).

Illustrations of neuroendocrine dysfunction in ME/CFS from the published
literature that NICE disregarded in the production of its Clinical Guideline
53  (for reasons of space, this is only a small sample)


"Several lines of evidence suggest that the various components of the
hypothalamic-pituitary-adrenal (HPA) axis merit further study in these
patients.  Debilitating fatigue, an abrupt onset precipitated by a stressor,
feverishness, arthralgias, myalgias, adenopathy, postexertional fatigue,
exacerbation of allergic responses are all characteristic of glucocorticoid
Compared to controls, patients with (ME)CFS showed a
significant reduction in basal total plasma cortisol (and) a proportionately
higher response to the amount of ACTH released during stimulation with oCRH.
We suggest that the hyper-responsiveness of the adrenal cortex to ACTH in
patients with (ME)CFS reflects a secondary adrenal insufficiency in which
adrenal receptors have become hyper-responsive to inadequate levels of ACTH.
In the light of the post-infectious presentation of (ME)CFS in the majority
of patients, it should be noted that viral infections can alter
neurotransmitter and / or neuroendocrine regulation
"  (Mark A Demitrack et
al. Journal of Clinical Endocrinology and Metabolism 1991:73:6:1224-1234).


"The syndrome of (ME)CFS has a lengthy history in the medical literature.
The clinical presentation, with evidence of persistent immune stimulation,
lends support to the idea that (ME)CFS represents a clinical entity with
potential biological specificity. We showed that patients with (ME)CFS
demonstrate a significant hypocortisolism
" (Mark A Demtrack et al.  Biol
Psychiatry 1992:32:1065-1077).


"Patients with (ME)CFS lose muscle protein synthetic potential, but not
muscle bulk.  These perturbations may contribute to the feature of muscle
weakness associated with persistent viral infection in the muscles
themselves. 80% of patients had serological indications of current or
on-going VP1 positive enterovirus infection
. There has to be persistent
enterovirus infection to produce the response; it does not rely on the body's
development of antibody. Furthermore, skeletal muscle RNA was significantly
reduced. This reflects a reduced capacity to synthesise proteins. Our
results imply that there is a subgroup of patients with (ME)CFS in which
symptoms of skeletal muscle weakness may be related to proximal myopathy.
Direct evidence has been obtained for a subcellular metabolic defect in the
muscle per se.  These studies indicate that up to 80% of patients with
(ME)CFS have identifiable mitochondrial abnormalities
"  (VR Preedy   TJ
Peters  et al. J Clin Pathol 1993:46:722-726).


"The baseline AVP values were significantly lower in patients with (ME)CFS
when compared to healthy controls. The mean total body potassium (TBK) was
9% lower than predicted.
This study also showed that  some patients with
(ME)CFS appear to have an increased total body water content when compared
with healthy controls. Abnormalities of water metabolism in patients with
(ME)CFS have previously been reported.  This interference with hypothalamic
function may be due to the presence of persistent virus, most likely
enterovirus.  In such a chronic infection, Oldstone has shown that the agent
may persist in cells without producing any evidence of damage but effecting
a profound disturbance of hormones and neurotransmitters"
  (AMO Bakheit et
al. Acta Neurol Scand 1993:87:234-238).


"One of the characteristic complaints of patients with (ME)CFS is the
skeletal muscle-related symptom.  We show that patients had a deficiency of
serum acylcarnitine.  This deficiency might induce an energy deficit and/or
abnormality of the intramitochondrial condition in the skeletal muscle,
resulting in general fatigue, myalgia, muscle weakness and postexertional
malaise in patients with (ME)CFS. The measurement of acylcarnitine would be
a useful tool for the diagnosis and assessment of (ME)CFS
"  (H Kuratsune et
al.  Clin Inf Dis 1994:18: (Suppl 1):S62-S67).

Note that in the UK, this measurement is proscribed by NICE.


"The role of steroids in growth hormone production was determined in
patients with (ME)CFS.  There were abnormal responses of growth hormone
production to administered steroids in patients with (ME)CFS.  These data
suggest an abnormality in the glucocorticoid receptor bearing neurones that
control growth hormone responses
in affected patients. These data clearly
pointed to an abnormality in neuroendocrine control. Another condition that
bears striking similarities to (ME)CFS is post-polio syndrome"
(T Majeed et
al. Journal of the Irish Colleges of Physicians and Surgeons


In a study examining abnormality of adrenal function, Japanese researchers
found that "these abnormalities are quite different from those found in
patients with mental or physical diseases reported previously
" (Yamaguti K
et al. JCFS 1995:2:2/3:124-125).


"In reviewing stress-response systems, it is important to keep in mind that
activity of stress-response systems is determined by genetic and
environmental factors. In (ME)CFS we have demonstrated a significant
increase in plasma levels of the serotonin metabolite 5-hydroxyindoleacetic
acid. Patients with a longer duration of disease do tend to have more severe
basal abnormalities in cortisol levels
" (LJ Crofford et al. Rheum Dis Clin N
Am 1996:22:2:267-284).


"There is an increasing volume of evidence to support the view that patients
with (ME)CFS have unique endocrinology patterns
.  The cardinal findings
include attenuated ACTH responses to CRH and low 24-hour urinary cortisol.
These are compatible with a mild central adrenal insufficiency. It is
well-documented that infectious diseases are often accompanied by various
forms of neuroendocrine disturbances with acute viral infections activating
the HPA axis.
An increase in peripheral turnover of 5-HT may explain the
heightened allergic responsiveness as well as the musculoskeletal pain seen
in (ME)CFS" (LV Scott  TG Dinan. JCFS 1996:2:4:49-59).


"It is notable that the pattern of alteration in the stress response
suggests a sustained inactivation of central nervous system components of
this system. It has not escaped the view of clinical authors that (ME)CFS
and its historical antecedents shares many of the characteristics with
endocrine disease states
(in which there is) functional interdependence of
the endocrine system and the nervous system. It is only recently that
clinical researchers have clearly documented that neuroendocrine
disturbances are evident in patients with (ME)CFS
(which) have brought into
view a broader understanding of the variety of physiologic accompaniments of
this condition. (ME)CFS appears to wax and wane with periods of  increased
stress. Results of this work provide confirmatory support for an impairment
(of) the HPA axis (and) is consistent with the view that adrenocortical
function is impaired" (MA Demitrack. J psychiat Res 1997:31:1:69-82).


"Our group has established that impaired activation of the HPA axis is an
essential neuroendocrine feature of (ME)CFS. It is now recognised that
(ME)CFS leads to significant physical and psychological debility
in a large
segment of the population. We have suggested that the findings of reduced
adrenal glucocorticoid function in (ME)CFS are most consistent with a
central nervous system defect in the activation of this axis
. (We found) a
basal hypocortisolism.  On its own, this observation is a striking finding.
These observations provide an important clue to the development of more
effective treatment for this disabling condition" (MA Demitrack, LJ
Crofford. Ann N.Y. Accad Sci 1998:840:684-697).


"The right and left adrenal gland bodies were reduced by over 50%  in the
(ME)CFS subjects, indicative of significant adrenal atrophy in a group of
(ME)CFS with abnormal endocrine parameters" (Scott LV et al.
Psychoneuroendocrinology 1999:24:7:759-768).


"Baseline adrenaline levels were significantly higher in (ME)CFS patients.
We conclude that (ME)CFS is accompanied by a resistance of the immune system
to regulation by the neuroendocrine system
.  Based on these data, we suggest
(ME)CFS should be viewed as a disease of deficient neuroendocrine-immune
communication" (Kavelaars A et al. J Clin Endocrinol Metab


"In the investigation of (ME)CFS, fine needle aspiration (FNA) cytology has
been tested in addition to conventional biochemical thyroid function tests.
Of 219 patients, 40% were diagnosed with definite cytological lymphocytic
We strongly advocate FNA cytologic assessment of the thyroid in
patients with (ME)CFS" (B Wikland et al. Lancet 2001:357:956-957).

In a subsequent letter, Wikland stated: "In a letter published in The Lancet
(24th March 2001) we report on fine needle aspiration cytology of the
thyroid in (ME)CFS. No less than 40% of our patients showed definite
autoimmune thyroiditis.  Less than half of these patients fulfilled
conventional biochemical criteria of hypothyoidism. In our opinion, this
aspect merits wider recognition" (Bo Wikland. eBMJ 9 January 2002).


"One of the most consistent findings in (ME)CFS is a decrease in
Th1-mediated immune responses. (ME)CFS patients have been shown to display a
disturbed HPA axis and have low levels of cortisol
.  We speculate that in
these patients IL-10 and IL-12 are differently affected by glucocorticoids.
The present study shows that, in particular, IL-10 secretion (and its
sensitivity to GC) differs from that in healthy controls" (J Visser et al.
Journal of Neuroimmunology 2001:119:2:343-349).


"Endocrinologists were not included in the working groups that prepared two
recent reports on (ME)CFS, despite its clinical overlap with Addison's
disease, which is a classic endocrine disease.  The failure to include at
least one endocrinologist in those panels may explain why in their reports
there is not a single word about the 42 clinical features that (ME)CFS
shares with Addison's disease.
The failure of both the English and
Australian reports to mention other important endocrine abnormalities of
(ME)CFS represents a serious omission. Cognitive behaviour therapy may have
benefited depressed subjects (but) not patients with (ME)CFS. (ME)CFS and
Addison's disease also share reduced cardiac dimensions, increased heart
rate, postural hypotension, orthostatic tachycardia, dizziness upon
standing, dehydration, anorexia, nausea (and) diarrhoea.  Moreover (they)
also share leucocytosis, lymphocytosis, elevations of transaminase values,
enhanced TSH secretion, respiratory muscle dysfunction, reduction in
exercise capacity and increased sensitivity to chemical exposures
.  Reason
suggests that the clinical overlap of (ME)CFS with Addison's disease
reflects the endocrine and adrenal abnormalities found in (both disorders)
and omitted unjustifiably in both the English and Australian reports, namely
hypocortisolism, impaired adrenal cortical function, reduced adrenal gland
size, antibodies against the adrenal gland, and impaired production of DHEA.
Richard Horton, editor of The Lancet, has recently written (JAMA
2002:287:2843-2847): 'Failure to recognise the critical footprint of primary
research weakens the validity of guidelines and distorts clinical knowledge
" (R Baschetti. Eur J Clin Invest 2003:33:1029-1031).

Baschetti was referring to the 2002 UK Report of the CMO's Working Group and
the Australian Report in the Medical Journal of Australia 2002:176:S17-S56.
There was no endocrinologist on the NICE Guideline Development Group which
produced the NICE Guideline in August 2007.


"Patients with (ME)CFS typically present a normal thyroid function. From
(our) observations, we raise the hypothesis that molecular mechanisms could
explain the development of a clinical hypothyroid state in the presence of a
normal thyroid function.
Whilst biochemically euthyroid, (ME)CFS patients
are clinically hypothyroid. Signal transduction mechanisms could account for
a peripheral T3 resistance syndrome leading to a clinically hypothyroid but
biochemically euthyroid state, as observed in diseases characterised by
dysregulations in the antiviral pathway or during the therapeutic use of INF
a / b" (P Englebienne et al. Med Hypotheses 2003:60:2:175-180).


The following article is in Serbian and comes from the Institute of
Endocrinology, Belgrade; no author is listed:

"Similarities between the signs and symptoms of (ME)CFS and adrenal
insufficiency prompted the research of the HPA axis derangement in the
pathogenesis of (ME)CFS.  We compared cortisol response in the (ME)CFS
subjects with the response in control subjects and in  those with secondary
adrenal insufficiency. We have shown that cortisol increment at 15 and 30
minutes is significantly lower in the (ME)CFS group than in controls.
However, there was no difference between the (ME)CFS group and those with
secondary adrenal insufficiency in any of the parameters. Consequently,
reduced adrenal responsiveness to ACTH exists in (ME)CFS" (Srp Arh Celok Lek

It should be noted that Wessely School psychiatrists have carried out
several endocrinological studies on "CFS" patients and have had varying
results, possibly because of their chosen case definition.  Despite the
compelling evidence of international researchers, the Wessely School
psychiatrists found no evidence of endocrine abnormality in some of their
studies, whilst in others they did find evidence of such abnormalities.
Overall, these Wessely School researchers concluded that even though a
distinct abnormality was found (low cortisol), it was likely to be "an
epiphenomenon caused by the behavioural changes typical of CFS" (GJ Rubin, M
Hotopf, A Cleare et al. Psychosom Med 2005:67:3:490-499).

Following the publication of the NICE Guideline, Wessely School
psychiatrists have continued to publish studies on "CFS", the results of
which do not accord with existing biomedical science, for example: "It has
been argued that perceived functional incapacity might be a primary
characteristic of CFS.  (Our) sample consisted of 73 patients with a
diagnosis of CFS according to the Oxford criteria randomly selected from
clinics in the Departments of Immunology and Psychiatry at St Bartholomew's
Hospital, London. The findings suggest that perceived functional incapacity
is a primary characteristic of CFS" (Priebe S et al. Psychopathology

To refer to "perceived incapacity" in these patients is not only offensive to patients but is also an insult to  the many clinicians and researchers who have uncovered the reality of the incapacity through the scientific process (in which psychiatry plays no part).

Illustrations of neurological dysfunction in ME/CFS from the published
literature that NICE disregarded in the production of its Clinical Guideline
(for reasons of space, this is a limited sample)

Evidence of inflammation in the central nervous system:

Despite denials by Wessely School psychiatrists, there is evidence of
inflammation of the central nervous system in ME/CFS

Just a few illustrations of published evidence of inflammation of the
central nervous system that NICE chose to disregard include: Pellew RAA (Med
J Aust:1955:42:480-482); Innes SGB (Lancet:1970:969-971); Buchwald, Cheney,
Peterson D, Komaroff, Gallo et al (Ann Int Med: 1992:116:103-113): Schwartz
RE et al (Am J Roentgenology:1994:162:935-941); Komaroff AL
(JAMA:1997:278:14:1179-1184).  There are other more recent papers such as
Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco P et al.
Brain positron emission tomography (PET) in chronic fatigue syndrome:
preliminary data.  Am J Med 1998:105:54S-58S;  Chaudhuri A, Behan PO.  In
vivo magnetic resonance spectroscopy in chronic fatigue syndrome.
Prostaglandins, Leukotrienes and Essential Fatty Acids 71 (2004) 181-183;
Yamamoto S et al.  Reduction of serotonin transporters of patients with
chronic fatigue syndrome. NeuroReport 2004:15:2571-2574.

Evidence of neurological dysfunction:


ME/CFS was included by the distinguished neurologist Lord Brain in his
textbook "Diseases of the Nervous System", Oxford University Press, sixth
edition: pp355 " (ME) is the term applied to a disorder which has been
recognised in many parts of the world.  Its features are the severity of the
symptoms in relation to the slightness of the physical signs. A
characteristic feature of the muscular weakness is the intermittency of
power of muscular contraction. Changes which are believed to be
characteristic have been found on electromyography
. A striking feature is
the tendency for relapses to occur during  the months, and in some cases
even years, after the infection".


Extract from a Press Conference by Professor Paul Cheney held in San
Francisco in September 1990 and reported in CFIDS Chronicle, September 1990:

"I believe this is a disease that affects the central nervous system (CNS)
and I'll show you some slides to help convince you of that.  We are going to
(look at) what evidence there is for neurologic disease in these patients.
This is a study done by Dr Carolyn Warner from the Dent Neurologic Institute
in Buffalo, New York, which specialises in multiple sclerosis.  Some people
think that (ME)CFS can look like MS and there are clinical features that are
The most specific neurologic symptom is dysequilibrium.  These
patients have a balance disturbance and on certain simple neurologic tests
they fall over. On more sophisticated neurologic tests of vestibular
function they are often grossly abnormal. Nearly every patient had something
abnormal within the central nervous system, and also neuromuscular problems,
or muscle itself
.  These patients are cognitively impaired and you can prove
it by formalised psychometric tests. Other evidence of CNS involvement can
be demonstrated by tests looking directly at the CNS.  These are slices of
brain created by using magnetic resonance imaging.  These inflammatory
and/or demyelinating plaques can be seen in the white matter, in the
cerebellum and white matter tracts throughout the high cerebral convexities
and in the frontal lobes.  Over half of (ME)CFS patients will typically show
lesions within the central nervous system
.  Professor Ismael Mena, chairman
of the Department of Nuclear Medicine at Harbourview UCLA Medical Centre,
found that there were defects in perfusion of temporal lobes primarily. He
looked at regional cerebral blood flow and found that in (ME)CFS patients
compared to controls, there was a diminishment of cerebral blood flow in the
right temporal lobe that was significant. In other words, blood flow to the
right temporal lobe was impaired in these patients. The temporal lobe seems
to get really hit by this disease. I want to point out that 71% of patients
with (ME)CFS are abnormal by this technique

It is again noted that in the UK, NICE proscribes nuclear imaging scans.


"Patients with (ME)CFS often complain of dysequilibrium. Data suggests that
their symptoms of dysequilibrium can be substantiated with quantitative
laboratory testing.  The abnormalities are more suggestive of CNS deficits
than of peripheral vestibular deficits"
(JMR Furman. Rev Inf Dis 1991:13:
(Suppl 1):S109-111).


In a CME (continuing medical education) credit article, Dr David Bell, an
internationally-acclaimed paediatrician specialising in ME/CFS, wrote in
Postgraduate Medicine: "Findings now point to CNS involvement: Recent
research has yielded remarkable data (and has) provided a steady current of
scientific additions to our understanding of (ME)CFS". Reviewing the
immunological abnormalities (and noting that the patients who were the most
disabled had the highest levels of interleukin-1), Bell pointed out that a
consistent pattern of immune dysfunction is emerging
, which helps to
characterise and define the illness. He noted the elevated levels of
cytokines, particularly those that affect neuronal tissue.  He reviewed the
evidence for retroviral markers, the pituitary and hypothalamic
abnormalities, and the neuroendocrine abnormalities. He reviewed the
cerebral perfusion abnormalities and highlighted the importance of elevated
serum ACE levels seen in ME/CFS: "Another addition to the bewildering array
of laboratory abnormalities found in patients with (ME)CFS is an increased
serum concentration of angiotensin-converting enzyme (ACE).  This is a
marker not only for sarcoidosis but also for diseases involving the blood
  This finding is of importance because of the clinical similarities
between (ME)CFS and sarcoidosis.  Shared symptoms include fatigue,
neurologic dysfunction and arthalgia. In patients with an elevated ACE
level, attention to the lymph nodes and eyes is called for".  Bell
concluded: "The symptoms of (ME)CFS have long been viewed as a neurologic pattern, as indicated by other names for the condition such as myalgic encephalomyelitis (and) atypical poliomyelitis.  Neurologic involvement is beginning to be confirmed by documentation of abnormalities in cerebral perfusion, hypothalamic function, and neurotransmitter regulation.  A link is being forged between the symptoms pattern and objective evidence of CNS dysfunction.  A majority, and perhaps all, of the symptoms of (ME)CFS may be neurologic in origin. The view that (ME)CFS is a primary emotional illness has been undermined by research findings" (David S Bell. Postgraduate Medicine 1994:96:6:73-81).


"Because a complete neurological examination is not emphasised as part of
the diagnostic workup, it is possible that less obvious neurological
findings may be overlooked
. Careful evaluation of neurological features may
be one approach to distinguishing subtypes. The neurological symptoms and
signs were neuropsychological changes, cutaneous sensory changes, paresis,
abnormal muscle movements, abnormal muscle tone, deep tendon reflex changes,
cranial nerve signs, posterior column signs, ataxia, and vasomotor
instability. Activity or exercise was a precipitant or exacerbation or
Many of the neurological signs and symptoms were not reported on.
A complete neurological examination should be an integral part of the
diagnostic assessment of illnesses described as CFS"  (NC Briggs, Paul
Levine. Clin Inf Dis 1994:18: (Suppl 1):S32 -S42).


To assess the clinical impression that patients with (ME)CFS do not walk
normally, the gait kinematics of patients with (ME)CFS were studied.
Results showed that (ME)CFS patients were significantly slower at running
speed than the controls.  Further analysis revealed that patients with
(ME)CFS took smaller steps than the controls. "The data indicate that
(ME)CFS patients have gait abnormalities when compared to sedentary
controls.  These could be due to balance problems, muscle weakness, or
central nervous system dysfunction"
(Boda WL, Natelson BH et al.  Journal of
the Neurological Sciences 1995:156-161).


"A growing literature exists suggesting that a component of (ME)CFS may
include abnormalities in cardiovascular control
.  Vagal power, a measure of
cardiac parasympathetic activity, was computed. In an earlier study, we
showed that patients with (ME)CFS had significantly less vagal power than
healthy controls during controlled breathing. Our findings suggest that
vagal dysregulation may be an additional symptom of (ME)CFS.  Moreover, they
suggest the presence of a biological link between fatigue and the autonomic
nervous system. 
The (ME)CFS group had less vagal power than the controls at
every stage (and also) during the first stage of recovery. These results
indicate that vagal power responses in patients with (ME)CFS are different
from healthy controls. A common complaint in (ME)CFS is that patients are
unable to exert themselves for prolonged periods due to a lack of energy.
Our findings might explain this
.  It is possible that reduced vagal power
might interfere with the normal recovery process that follows bouts of
exertion.  This interference might exacerbate fatigue immediately or for
several days following exertion, a common complaint in (ME)CFS.  Decreases
in vagal power have been identified in several medical conditions, including
congestive heart failure. Our data suggest that (ME)CFS may involve a
primary neurological abnormality.  (ME)CFS patients also show dysfunction in
complex auditory processing that is of the same magnitude as that found in
patients with multiple sclerosis. Other data show that patients with ME/CFS
(sic) had significantly lower brain stem perfusion ratios than either
healthy or depressed controls
"  (DL Cordero, BH Natelson et al. Clinical
Autonomic Research 1996:6:329-333).


"The aim of this study was to investigate the role of the autonomic nervous
system in (ME)CFS.  Autonomic signs and symptoms have appeared frequently in
reports of CFS, also called myalgic encephalomyelitis. The three criteria
used to determine autonomic symptoms eligibility were (1) dizziness upon
standing and rapid heart beat; (2) dizziness upon standing and either
nausea, diarrhoea, constipation and night sweats and (3) rapid heart beat
and either nausea, diarrhoea, constipation or night sweats. Recent reports
have documented neurocardiogenic syncope in patients, again suggesting
autonomic dysfunction in (ME)CFS.
Several autonomic function test results
were significantly different in the (ME)CFS group when compared to controls.
Our study found that neither depression nor anxiety correlated with any of
the measures of autonomic dysfunction. Deconditioning alone did not explain
these autonomic abnormalities
. 89% of patients in this study reported that
the onset of fatigue was preceded by (an infectious illness), a history
typical of patients with (ME)CFS. Our results provide evidence for an
association between an autonomic neuropathy and (ME)CFS. An exercise
programme, alone and in combination, cannot now be generally recommended for patients with (ME)CFS
"  (R Freeman, AL Komaroff.  Am J Med


"Spatial and temporal parameters of gait were collected from (ME)CFS
patients by using instrumentation of movement analysis. Interestingly,
abnormalities were present from the beginning of the gait, which indicates
that they are unlikely to be caused by the rapidly increasing fatigue. This
strengthens the hypothesis of a direct involvement of the central nervous
in the onset of the disease" (R Saggini et al. Journal of the
Neurological Sciences 1998:154:18-25).


"A substantial body of clinical evidence now supports an association between
various forms of hypotension and (ME)CFS. Features that exacerbated
(patients') fatigue included physical exertion, a hot shower, prolonged
standing (such as waiting in line at the grocery store) and a warm
environment. Importantly, all (ME)CFS patients but none of the controls
developed orthostatic symptoms (during testing), suggesting that orthostatic
intolerance may be a defining feature of the illness
.  Virtually all (ME)CFS
patients have their symptoms provoked by the simple process of assuming an
upright posture. There is a high prevalence of allergic disease among those
with (ME)CFS (and) one would expect to find a mechanism by which allergic
disease increases the activation of the NMH reflex pathway. Undem et al have
shown that both viral infection and allergic reactions to food antigens
enhance the excitability of mechanically sensitive vagal afferents in the
airway (which provides a link between these clinical situations).
Investigations into the high prevalence of neurally mediated hypotension and
other forms of autonomic dysfunction among those with (ME)CFS should improve
our understanding of this disorder" (Peter C Rowe and Hugh Calkins. Am J Med


"The fatigue in (ME)CFS is similar to that found in disorders of the central
nervous system such as multiple sclerosis, Parkinson's disease and multiple
system atrophy. It is now clear that (ME)CFS patients differ from patients
with major depression
in their symptoms (and) biologic markers such as
steroid metabolism. We propose dysfunctional ion channels in the cell
membranes as the key abnormality in (ME)CFS which may also be responsible
for the altered neuroendocrine functions reported in this condition.
Associated symptoms that are common in (ME)CFS include paroxysmal attacks of
angina-like chest pain (Syndrome X), nocturnal attacks of sweating and
palpitations, irritable bowel syndrome, vertigo or dysequilibrium,
photophobia (and) daily migraine-like headaches. Autonomic dysfunction in
(ME)CFS is well-recognised. One of the most characteristic features of the
illness is the fluctuation in symptoms which can be induced by physical
and/or mental stress. Acquired ion channel abnormalities in myocardium could
explain the pathogenesis of Syndrome X.  Acquired mutations of a similar
nature may form the basis of the cardiac dysfunction seen in Syndrome X and
(ME)CFS.  The role of abnormal ionophores governing both Syndrome X and
(ME)CFS assume importance in the light of the fact that a highly significant
proportion of (ME)CFS patients have cardiomyopathy. (ME)CFS is an episodic
neurological disorder with a basic mechanism of disease involving abnormal
ion channel functions" (Abhijit Chaudhuri et al. Hum Psychopharmacol Clin
Exp 1999:14:7-17).


In 2000, the CFIDS Association of America produced a 24 page document
entitled "Neurological Findings in (ME)CFS: A Survey of the Research"
containing 175 references.  It is available from the CFIDS Association of
America, email:


A quantitative assessment of cerebral ventricular volumes in (ME)CFS
patients found that volumes were larger than in the control groups. "The
results of this study provide further evidence of pathophysiological changes
in the brains of participants with (ME)CFS"
(Lange G, Natelson BH et al.
Appl Neuropsychol 2001:8(1):23-30).


Research at the Salk Institute, La Jolla, California, identified a gene that
may link certain pesticides and chemical weaponry to a number of
neurological disorders.  The finding, published in the 17 March online
version of Nature Genetics, was the first to demonstrate a clear genetic
link between neurological disorders and exposure to organophosphate (OP)
chemicals.  OPs include household pesticides as well as the nerve gas sarin.
The research showed that OPs inhibit the activity of a gene called
neuropathy target esterase (NTE). Some of the neurological problems echoed
many of the symptoms of Gulf War Syndrome.

This is important because the Proceedings of The National Academy of Science
(PNAS) published evidence that NTE is inhibited by several OP pesticides,
chemical warfare agents, lubricants and plasticisers, leading to OP-induced
delayed neuropathy in more than 30,000 human cases (PNAS
2003:100:13:7983-7987). It is highly significant in ME/CFS, because gene
expression research has demonstrated 16 genes as having an expression
profile associated with (ME)CFS.
  These genes can be grouped according to
immune, neuronal and mitochondrial functions. A neuronal component was
identified that is associated with central nervous system hypomyelination,
and the researchers specifically noted the association of organophosphates
and chemical warfare agents: "A neuronal component is suggested by
up-regulation of NTE.  NTE is a target for organophosphates and chemical
warfare agents, both of which may precipitate (ME)CFS" (N Kaushik,  ST
Holgate, JR Kerr et al. J Clin Pathol 2005:58:826-832).  Stephen Holgate is
MRC Clinical Professor of Immunopharmacology at the University of
Southampton and this is top-rank research, not mere hypothesis.

"The purpose of this study was to determine whether brain activity of
(ME)CFS patients during voluntary motor actions differs from that of healthy
controls. Fifty-eight channels of surface EEG were recorded simultaneously
from the scalp.  Major findings include (1) Motor performance of the (ME)CFS
patients was poorer than the controls (2) Relative power of EEG theta
frequency band  during performance of tasks was significantly greater in
(ME)CFS than in the control group (3) The amplitude of MRCP (motor
activity-related cortical potential) negative potential for tasks was higher
in (ME)CFS than the control group.  These results clearly show that (ME)CFS
involves altered central nervous system signals in controlling voluntary
muscle activities, especially when the activities induce fatigue
. Physical
activity-induced EEG signal changes may serve as physiological markers for
more objective diagnosis of (ME)CFS" (Siemionow V et al. Clin Neurophysiol

It is worth noting once again that such investigations for these patients in
the UK are proscribed by NICE.


In 2004, The Lancet published a Review entitled "Fatigue in neurological
disorders" by Abhijit Chaudhuri et al (Lancet 2004:363:978-988). It included
(ME)CFS as a neurological disease and it contained 94 references.


In a study looking at gray matter volume reduction in (ME)CFS, researchers
found significant reductions in global gray matter volume in (ME)CFS
patients compared with matched controls: "Moreover, the decline in gray
matter volume was linked to the reduction in physical activity, a core
aspect of (ME)CFS.  These findings suggest that the central nervous system
plays a key role in the pathophysiology of (ME)CFS and point to an objective
and quantitative tool for clinical diagnosis of this disabling disorder
" (FP
de Langea et al. NeuroImage 2005:26:3:777-781).

The persistence of the Wessely School's ignoring of the biomedical evidence

Following the publication of the NICE Guideline, the Wessely School's
determination to promote their own model and to force the implementation of
the Guideline's recommendations continues unabated.

In July 2008, the same Systematic Review team at the Centre for Reviews and
Dissemination at York which produced the alleged "evidence-base" upon which
the GDG relied to support its behavioural interventions for "CFS/ME" (the
advisers to the team being members of the Wessely School) published another
Systematic Review, this time of alleged risk factors for the development of

This latest Systematic Review was funded by NICE. The authors state: "The
work forms part of the independent (sic) synthesis of research evidence to
support the development of these guidelines".

The authors specifically acknowledge the input of members of the CG53
Clinical Guideline GDG, and they acknowledge assistance from"two anonymous

Of the 27 references cited, no less than 16 are from the Wessely School.

Unsurprisingly therefore, the conclusion states: "Significantly associated
with the development of CFS/ME in the final predictive model were being
female, presence of anxiety disorder, mood disorder, emotional instability,
sick certification after viral illness, no sport in spare time at 10 years
old, visits to GP" and it mentions "psychological characteristics".
The authors concede that: "Not all studies seem to have excluded CFS/ME
defining factors for the prediction of CFS/ME, which makes the studies
difficult to compare"  (Risk factors for chronic fatigue syndrome / myalgic
encephalomyelitis: A systematic coping review of multiple predictor studies.
Hempel S, Chambers D, Bagnall A-M, Forbes C. Psychological Medicine July

It is disturbing that no attention seems to have been paid by the Systematic
Review team or its advisers to the existing scientific evidence: "We found
that the best predictor for (ME)CFS was the intensity of the initial
infectious disease.  There were no other factors, psychological or
biological, that held up under thorough analysis"
(Dr Williams Reeves, Chief
of Chronic Viral Diseases Branch, Centres for Disease Control, USA: November
2006:   and
"The syndrome was predicted largely by the severity of the acute illness
rather than by demographic or psychological factors"
(I Hickie et al. BMJ

It is curious indeed that the Wessely School repeatedly asserts the need for "evidence-based medicine" in "CFS/ME", yet pays no heed to it.


Throughout these illustrations there have been repeated calls for further
investigation of patients with (ME)CFS.

The fact that in the UK, the NICE Guideline proscribes such investigations and recommends only mind-altering interventions that are designed to disabuse patients of the notion that they are physically sick, together with
incremental aerobic exercise, might be construed as State-sponsored abuse of extremely sick people.

* * *
Like the NICE Guidelines, the CDC information on CFS also states that the very tests that would be abnormal in CFS patients are "not necessary" in making the diagnosis.
As Margaret notes, these objective findings date back more than 20 years.  Yet, they are disregarded by both the US and UK government, and many doctors are still unaware of them.  My doctors had no idea what they should be testing for; they gave me the basic first-round blood tests and when those were normal (as they should be) didn't look any further before concluding there was nothing physically wrong. In fact, the assertion of "no objective evidence" was based on not doing the tests that would have provided the objective evidence; the correct tests would have been abnormal. 
A later blood test was described to me as "off the charts", but was one of many tests that wasn't done before the false pronouncement that there was nothing physically wrong.  As shown in Margaret's history of the research, the symptoms of CFS are compatible with an ongoing viral infection; that test showed I had a severe infection of some sort, e.g., a virus for which I had not yet been specifically tested.  And at the point that test was done, showing levels exponentially higher than normal, I had gotten some medical help and was feeling much better than I had when the first series of tests that were all normal -- at that point, I actually had it in me to venture to a doctor at the other end of the county instead of barely making it to one four blocks from home..
People see and hear what they want to see.  Someone who wants to see depression will focus only on the symptoms that support that diagnosis.  (See "How Doctors Think" by Dr. Jerome Groopman.)  When symptoms and test results come up that are inconsistent with depression, they're shoved to the side. 
It is clear that the authors of the NICE guidelines did the same thing -- disregarded any evidence that CBT and GET are not the solutions to a biological/neurological disease, in order to reach their pre-determined conclusion.