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http://www.meactionuk.org.uk/Essential_investigations_for_people_with_ME.htm
Essential investigations for people with ME/CFS?
Margaret Williams
16th January 2008
On 14th January 2008 Fred Springfield drew attention on Co-Cure to a Review
Article associated with inflammation in medically ill patients
("Identification and treatment of symptoms associated with inflammation in
medically ill patients"; Robert Dantzer et al; Psychoneuroendocrinology
2008:33:18-29). The Review was the result of a meeting on 28th and 29th May
2007 in Bordeaux, France, on inflammation, psychiatry, neurosciences and
psychoneuroimmunology, attended by experts from the US, France, the UK and
Israel.
As noted by Fred Springfield, whilst not relating specifically to ME/CFS,
the Review may nevertheless be of interest to the ME/CFS community, whose
members may be aware that there is evidence of low-grade (but still
important) inflammation in ME/CFS -- see, for example, "Low grade
inflammation and arterial wave reflection in patients with CFS"; VA Spence
et al, Clin Sci 2007, Epub ahead of print: doi:10.1042/CS20070274, which
contains 54 references and demonstrates that, despite the recent reporting
that markers of post-infective fatigue syndromes are not sustained into the
chronic phase of the illness and play no role in persisting symptoms, hsCRP
levels in (ME)CFS are indeed indicative of chronic, low-grade, sub-clinical
inflammation. (Within the last ten years, researchers have developed a high
sensitivity immunoassay known as hsCRP, which is a much better assay and a
more sensitive marker than CRP, as it can measure levels below 10mg/L.
Whilst some clinicians may still regard low levels as unimportant,
nevertheless at these levels, measurement of conditions indicative of
chronic, low-grade inflammation are now possible).
The Review recommends testing for a standardised set of inflammatory
biomarkers, but the NICE Guideline on "CFS/ME" issued in August 2007
specifically proscribes such tests.
The following are quotations that might be relevant for people with ME/CFS:
"The most harmful and costly health problems in the Western World are
originating from a few diseases (and) in addition to the specific symptoms
that are characteristic of each of these conditions, most patients
experience non-specific symptoms that are similar in all these conditions
and include depressed mood, altered cognition, fatigue, and sleep disorders".
"The possibility that immune-to-brain communication pathways represent the
main biological mechanism for symptom burden experienced by medically ill
patients has now gained credibility in the medical community".
"This meeting brought together clinicians and basic scientists with a common
interest in understanding inflammation and associated symptoms in medically
ill patients (and it) focused on: (a) predominant symptoms associated with
inflammation, (b) markers of inflammation at the periphery, (c) possible
markers of brain inflammation associated with low-grade peripheral
inflammation in humans, (d) animal models of inflammation-associated
symptoms, and (e) domains of intervention for controlling
inflammation-associated symptoms".
"Among the myriad of questionnaires that are available to categorise or
assess fatigue, sleep disorders, altered cognition and pain, none
specifically refers to inflammation-associated neurobehavioural alterations".
"The diagnostic tools that are favoured by psychiatrists are clearly not the
best ones. As pointed out by Joel Dimsdale (San Diego, CA), the concept of
somatisation that is used for characterising symptoms in the absence of any
detectable disease is of little operational value, if not misleading".
"For instance, the enduring fatigue experienced by the vast majority of
breast cancer survivors could easily be labelled as somatisation disorder
according to the 4th Edition of the Diagnostic and Statistical Manual of
Mental Disorders".
"Making fatigue a somatisation disorder overlooks the fact that fatigue has
both mental and physical components, thereby denying a possible organic
aetiology to explain such fatigue".
"Furthermore, this emphasis on the lack of an organic basis favours missed
diagnoses (e.g. fatigue and thyroid abnormalities, or fatigue and
inflammation)".
"Inflammation is not a stable condition. In a given individual it can
fluctuate rapidly according to a number of environmental factors (e.g.
stressors) and internal variables (e.g. diurnal variation of cortisol)".
"Basic aspects of diagnosis of behavioural disorders remain controversial
and lack solid scientific foundations".
"In order to provide consistency, all studies examining the potential impact
of inflammatory pathways should include a standard set of inflammatory
biomarkers (which should include) the acute phase proteins, CRP, sialic acid
and hatoglobin; the inflammatory mediators, prostaglandins E2 and C3A and
the innate immune cytokine IL-6 as measured by the high sensitivity
(hs)-enzyme-linked immunosorbent assay (ELISA) in plasma. These biomarkers,
especially hs-CRP and IL-6, have been found to reproducibly identify the
presence of an activated immune response in a number of disorders. Most of
these assessments can be run in certified commercial or hospital
laboratories".
"There have been significant advances in imaging techniques during the past
ten years (and) a variety of imaging techniques have enabled inflammation in
the brain to be viewed in real time. However, except in conditions of
severe systemic inflammation, signalling of systemic inflammation to the
healthy brain does not involve structural damage".
"It is important to highlight the distinction between signalling by
molecules typically associated with inflammation and an inflammatory
response per se. During systemic inflammation there is induction of IL-1b
and other proinflammatory cytokines, but there is no inflammatory response
in the brain. It is of interest that microinjection of IL-1b into the brain
at concentrations that would typically give rise to inflammation in
peripheral tissues does not lead to typical inflammation within the brain
parenchyma. This indicates that the biological significance of IL-1b in the
brain parenchyma is different from that in other tissues".
"Although we have the necessary tools to image inflammation in the brain, it
seems we do not have sufficiently sensitive tools to image signalling in the
brain consequent to a systemic inflammatory response".
"Proinflammatory cytokines induce the production of several downstream
inflammatory mediators, such as prostaglandins and nitric oxide.
Proinflammatory cytokines and other inflammatory mediators are produced by
accessory immune cells, such as macrophages and monocytes in the periphery,
and microglia within the central nervous system. Targeting cell trafficking
into the central nervous system is unlikely to be a very useful approach
since symptoms of sickness are dependent on the activation of brain cytokine
signalling independently of any blood cell recruitment".
"Peripheral infections can sensitise or exaggerate existing brain
inflammatory processes (and) elevated cytokine levels in blood have the
potential to reverberate and activate central nervous inflammatory systems".
The Conclusions of the Review note the intense discussion at the meeting
that resulted in a series of recommendations for improving understanding of
the relationship between inflammation and subjective health complaints.
These recommendations note that because inflammation-associated sickness
symptoms are a major impediment to human health, research on the mechanisms
and treatment of such symptom burden in physically ill patients should be
strongly encouraged; that clinical tools for assessing
inflammation-associated symptoms should be standardised; that there should
be a minimum set of inflammatory biomarkers; that brain neuroimaging
techniques should be used for revealing the brain structures that are
influenced by peripheral inflammatory processes and whose ability to process
information is impaired by excessive amounts of interoceptive stimuli
(caused, it seems, not - as asserted by Wessely School psychiatrists -- by
aberrant focusing on normal bodily sensations or by "remembered illness" but
by inflammatory processes), and that the high presence of
inflammation-associated symptoms in physically ill patients provides a
background against which it is possible to test alleviating effects of
therapies targeting immune-to-brain communication pathways.
The Review notes that despite major advances in the understanding of the
immune-to-brain communication pathways that underlie the pathophysiology of
symptoms in inflammatory conditions, little has been done to translate this
knowledge to the clinics.
As NICE is now in the process of contacting selected people asking for their
input on the advisability of it producing guidance on the use of Ampligen in
"CFS/ME",might NICE also be persuaded to seek the input of experienced
vascular biologists on the advisability of it recommending specific testing
for inflammation in ME/CFS?
___________________________________
http://www.meactionuk.org.uk
* * *
I eventually had the CRP test, years after being told "all tests are normal", and was told the results were "off the charts". How much distress and disability could have been avoided if that test had been done initially and proper treatment initiated, instead of years of being told "it's all in your head, take these anti-depressants"?
Oh, yeah, THAT would have required the doctor to accept that he was wrong and that CFS really is a biological disease, not just "another name for depression".
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