Chronic fatigue syndrome or myalgic encephalomyelitis

None of the many spirited responses to the White et al editorial have
drawn attention to the urgent need to dissect ME from the all-embracing
concept of CFS.

It seems incomprehensible that there has been a multiplicity of guidelines
produced for the management of a disorder for which there is no accepted
aetiology or pathophysiology. Possibly, to a major extent, this simply
reflects the rejection of earlier concepts.

In the second edition of his book, Ramsay noted that the clinical identity
of the ME syndrome was based upon three distinct features.

"1. A unique form of muscle fatigability whereby even after a minor
degree of physical effort. three, four or five days, or longer, may elapse
before full muscle power is restored. (NB. Strenuous activity changes the
shape populations of red cells in both healthy and unwell subjects.)

2. Variability and fluctuations of both symptoms and physical findings
in the course of a day. (A blood sample taken during remission showed
normal features, but six hours later, after a relapse a blood sample was
grossly abnormal.)

3. An alarming tendency to become chronic.

Ramsay discussed the clinical features of ME under three headings.

1. Muscle phenomena. He noted, "...it is important to stress the fact
that cases of mild or even moderate severity may have normal muscle power
in a remission."

(NB It is rare for remissions to be mentioned let alone discussed and no
guideline provides an explanation of their happening. A short paper
titled, "The implications of remissions in ME," was quickly rejected by
the BMJ.)

2. Circulatory impairment. This was manifested as cold extremities and
facial pallor.

3. Cerebral dysfunction. The cardinal features were the impairment of
memory and the power of concentration, plus emotional lability.

It seems strange that Ramsay did not consider that the cerebral and muscle
dysfunction might be related causally to the circulatory impairment, as it
seems that this could be the key factor in the pathophysiology of ME. A
major problem relating to acceptance is that the problems concern altered
blood rheology - and blood rheology is not taught in medical schools.

My work indicates that ME is a dysfunctional state resulting from
inadequate rates of delivery of oxygen and nutrient substrates, due to
impaired capillary blood flow, to maintain normal tissue function. Some
of the background to this claim is summarised below.
In 1986 we reported that ME blood filtered poorly (1) and in the following
year reported similar findings with regard to MS blood. In addition MS
blood viscosity was increased and changed red cell shapes were observed by
scanning electron microscopy.(2) A study which showed that the red cells
of healthy animals and humans could be classified into six different shape
classes (3) was followed by a report that ME blood contained high levels
of cup forms, which would help to understand the poor filterability of ME
blood.(4) The results from a further 99 cases were presented at the
Cambridge Symposium in 1990. In 1992, New Jersey Medicine published an
article relating to idiopathic chronic fatigue in which I pointed out that
individuals who by chance had smaller than usual capillaries would be at
risk of developing chronic sickness after exposure to an agent which
changed the shape populations of red cells.(5)

The implications for ME were discussed in a 1997, invited paper titled,
"Myalgic encephalomyelitis (ME):a haemorheological disorder manifested as
impaired capillary blood flow."(6) In 2001 we reported the results from
red cell shape analysis of more than 2100 blood samples from members of ME
groups in four countries.(7)

It should be noted that SPECT scans show the expected effects of shape-
changed, poorly deformable red cells in reducing cerebral blood flow in
regions which by chance have smaller than usual capillaries.

It has been reported that SPECT scans in three different psychiatric
disorders showed reduced blood flow in different regions of the brain, so
it could be expected for psychological/psychiatric problems to emerge in
some ME people as a part of their dysfunctional state.

References.

1.Simpson LO et al. Pathology 1986;18:190-2.

2.Simpson LO et al. Pathology 1987;19: 51-5.

3.Simpson LO. Br J Haematol 1989;73:561-4.

4.Simpson LO. NZ Med J 1989;102:106-7.

5.Simpson LO. NJ Med 1992;89:211-6.

6.Simpson LO. J Orthomol Med 1997;12:69-76.

7.Simpson LO et al.J Orthomol Med 1997;12:221-6.

Competing interests:
None declared

The authors make reference to the PACE trial [1], a major trial in
the area. It seems particularly curious that this trial will use
actigraphy watches before the patients start the trial, but will not use
them again on the patients during or at the end of the trial. This would
give information on whether the patients are increasing their total
activity levels or simply doing the activity that is part of the trial in
the place of other activity they used to do, but which they have cut down
on or cut out altogether.

This is important given previous studies in the area. For example,
one study [2] "using a 26-session graded activity intervention involved
gradual increases in physical activity" found that "from baseline to
treatment termination, the patient’s self-reported increase in walk time
from 0 to 155 min a week contrasted with a surprising 10.6% decrease in
mean weekly step counts."

Another study [3], investigating CBT this time, is regularly quoted
as having showing the effectiveness of CBT for CFS. However if one
examines the actometer data from this study from the group given CBT, the
increases in activity were minimal [4]. For instance, the baseline average
was 67.9, which increased to 68.8 after treatment and to 72.2 at follow-
up. Approximately 4 points. Not unlike the medical care controls, who went
from 64.9 to 68.7 in the same period.

Given the costliness of the trial - over £3m (of UK taxpayers' money)
- it is disappointing that the PACE Trial is not using objective outcome
measures which were previously recommended in a review of CFS
interventions [5]:
"Outcomes such as "improvement," in which participants were asked to rate
themselves as better or worse than they were before the intervention
began, were frequently reported. However, the person may feel better able
to cope with daily activities because they have reduced their expectations
of what they should achieve, rather than because they have made any
recovery as a result of the intervention. A more objective measure of the
effect of any intervention would be whether participants have increased
their working hours, returned to work or school, or increased their
physical activities."

Perhaps it is not too late for this data to be collected from some
participants?

[1] White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; on behalf
of the PACE trial group. Protocol for the PACE trial: a randomised
controlled trial of adaptive pacing, cognitive behaviour therapy, and
graded exercise, as supplements to standardised specialist medical care
versus standardised specialist medical care alone for patients with the
chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC
Neurol 2007;7:6.
http://www.biomedcentral.com/1471-2377/7/6

[2]. Friedberg, F. Does graded activity increase activity? A case
study of chronic fatigue syndrome. Journal of Behavior Therapy and
Experimental Psychiatry, 2002, 33, 3-4, 203-215

[3]. Prins JB, Bleijenberg G, Bazelmans E, et al. Cognitive behaviour
therapy for chronic fatigue syndrome: a multicentre randomised controlled
trial. Lancet 2001; 357: 841-47.

[4]. Van Essen, M and de Winter, LJM. Cognitieve gedragstherapie by
het vermoeidheidssyndroom (cognitive behaviour therapy for chronic fatigue
syndrome). Report from the College voor Zorgverzekeringen. Amstelveen:
Holland. June 27th, 2002. Bijlage B. Table 2.

[5] Whiting P, Bagnall A.-M., Sowden AJ, Cornell JE, Mulrow CD,
Ramirez G (2001). Interventions for the Treatment and Management of
Chronic Fatigue Syndrome: A Systematic Review. JAMA 286: 1360-1368

Competing interests:
None declared

"The uncertainty inherent in making a diagnosis of chronic fatigue
syndrome (CFS) is reflected by the variety of names (such as myalgic
encephalomyelitis; ME)."

Many people who have responded, have mentioned the Canadian and
Australian guidelines; both were unfortunately not used by NICE at all. A
shame really, if you see what an excellent tick list they have produced to
enable doctors to (almost) rule this uncertainty or difficulty out. I say
almost, because there is no medical condition were we, as doctors, get the
diagnosis right all the time.

The other thing I am a bit surprised about, is that the Editorial is
written by a professor in psychiatry and the second article in the same
BMJ about ME and NICE was written by another professor. When I Google a
bit, this is what I find on his site about him:
"The Department of Health Sciences at the University of Leicester is a
research-led department with established strengths in epidemiology,
medical statistics, social science, public health, primary care, health
services research and PSYCHIATRY."

All really NICE, but why wasn't someone like Dr Speight the
Paediatrician, who has specialised in ME for more than twenty years, or Dr
Chaudhuri, the neurologist, who also specialises in ME (and a few other
neurological diseases) and who both acknowledge the fact that ME is a
neurological disease, as Classified by the WHO, not asked instead to write
about ME??? It would have given a much more balanced view if both a
Neurologist and a psychiatrist would have written about this subject which
is deemed by many as a controversial disease, just as we did with MS for
example, when it was still called Hysteria. Even though I, and many
others, think after reading the splendid psychiatric guidelines about ME
by Dr Stein, that the psychiatrist ONLY has a role in this chronic
neurological disease if patients develop a depression or so alongside
their ME.

Competing interests:
We as psychiatrists should spend more time helping patients with a mental health problem instead of wasting valuable time and resourches on a neurological illness.

Who is relieved by NICE? Probably the government and the other socio-political forces which do not see the usefulness of treating, or trying to
treat, these conditions.

In my opinion, the reasoning behind the guideline published by Nice
is contradictory.

First, NICE states that the causes which trigger these types of
syndromes are unknown.

Although this is true of many conditions, it does not stop doctors
from offering cures and treatments. The existence of a disease is not
subjected to doctors' will, neither is its cure, neither doctor’s
acceptance nor awareness of its existence. By now, after thousands of
years of the existence of doctors’ medicine, doctors should be aware that,
in medicine, today’s revealed truth is tomorrow’s heresy.

It seems that Nice guidelines were formulated under the this axiom
:

"E.M. does not exist, it is an imaginary illness, which exists only
in the minds of the E.M. / sufferers, and therefore any clinical
investigation is totally unnecessary. It is self-explanatory"

Then the guidelines suggest to proceed as follow:

1- To exclude all symptoms and all clinical findings, chemical
abnormalities etc., which can also be seen in other syndromes/conditions,
to exclude all infections, co-morbidity, etc. which can be present.

2- Also the clinicians will have to limit the clinical investigations
to a simple, basic, blood test and nothing else.

3- Then, after having excluded any symptom, any biological
abnormality, known to mankind, the clinicians should proceed with the
formulation of "mental illness" by using
mental descriptors listed in the appendix.

Comments about Nice guideline:

1 -Many symptoms and abnormal clinical findings are commonly present
a huge amount of diseases. To exclude a symptoms or a disease from the
differential diagnosis can be dangerous. To exclude "all" symptoms and
diseases from a hypothetical diagnosis, simply because they can be also
present in other conditions, also means to exclude the existence of
symptoms and conditions. Ultimately, this could mean that there are no
biological diseases.
Then, having denied the existence of certain biological diseases, simply
because they might have symptoms and biochemical abnormalities which, can
be found in other diseases, the doctors will have to formulate the
diagnosis of mental illness by applying mental "descriptors", which are
universal feelings, and they are present in all humans, all the time.

Therefore, when examining the biological aspect: Nice suggests to
eliminate all physical causes, chemical abnormalities, symptoms etc,
which can be also present in order physical conditions. This process
will excludes the physical condition of ME.

Then Nice suggests to apply at least two mental descriptors, which
are common and present every person, to establish that ME is indeed an
esclusively mental illness.
Therefore, two different and opposite type of considerations are used for
the diagnosis of ME.
A)Total exclusion of physical conditions/symptoms etc, of all biological
“descriptors” which can be found in other biological diseases.
B)Inclusion of universally common “mental” descriptors (but I would say
universally common human feelings) to ascertain with absolute certainty
the existence of ME as a mental disease. A disease which is only mental.
Point A contradicts B and vice-versa. This type of method is typical of
“Spanish Inquisitions”, which have pestered Europe during the Middle Ages.
NICEs approach has nothing to do with the scientific method.

Guidelines like this are neither scientific, nor doctrinal. At best
they are an example of the most hideous type of quackery.

In spite the fact that NICE et Al deny their biological existence,
M.E. diseases have been spreading all over the world in an epidemiological
pattern which seems to be more indicative of an infective nature, rather
than a mental one. Furthermore, it seems that this diseases are spreading
at increasing rates.

The very concept of mental disease varies from time to time in a
given society, and also from society to society.

Traditionally, in certain oriental societies the concepts of mental
disease, as it is construed in the West, did not exist. For instance, in
traditional Chinese Medicine “depression” is a dysfunction of the meridian
of the liver.

I would suggest to the NICE people to concentrate first on the
physical before focusing on the metaphysical.

For the metaphysical we already have priests.

Competing interests:
M.E Sufferer