*Reporter Note** : *
- ME is used where ME/CFS is meant.
- Prof. Dr. Evengard (Sweden) and Prof. Dr. Montagnier (France)
were scheduled to appear, but cancelled at the last moment.
*1. **Introduction: Prof. Dr. Maes (Belgium) : Organizer *
**
Dr. Maes emphasizes that the research of the last years clearly shows that
ME is a biological - or more precisely - an immunological illness. From the
lectures below, it will become clear that sufficient proof has been found
for this statement, and that viral/bacterial infections, "leaky gut
syndrome" and stress all play a role in possible causation. There are also
clear hereditary factors.
*2. Foreword: Mrs. Inge Vervotte, Minister of Families/Public Health and
Welfare *
**
The number of patients with chronic illnesses in Belgium and elsewhere in
the world has increased dramatically and the WHO's prognosis in this area is
bleak. The basis of current Belgian health policy is insufficient because it
mainly focuses on the individual needs of patients and not enough on quality
of life as a whole. The minister wants to incorporate the latter into her
new policy proposal. The minister clearly underlines that in ME quality of
life and human dignity are in danger and that basic medical care is
therefore insufficient.
ME-patients need a reliable healthcare system that adapts to patient needs
and that understands the important role played by their surroundings. The
core ideas in the policy with relation to ME will be: good flow of
information, motivation and support for patients, learning self-management
techniques and especially increased dialogue. The minister also underlined
the importance of a fast diagnosis for ME and the role general practitioners
must play in this. Finally, she recognized the importance of scientific
research; however she did not go into this further.
*3. Dr. Lucille Capuron: (France/USA): Department of Psychiatry & Behavioral
Medicine: Inflammation, fatigue and depression *
**
Dr. Capuron focused on the influence of cytokines (signaling compounds that
allow one cell to communicate with another) in ME and depression.
It is clear that cytokine activity is elevated in ME-patients as there is a
cytokine overproduction of interleukin 1 and 6 and interferon alpha. The
consequence of this activity and the associated inflammation processes
offers an explanation for the general flu-like feeling and the disturbed
activity of the HPA-axis and adrenal glands. This indirectly brings about
changes in the mechanism that is responsible for sugar metabolism and the
quantity and functioning of a number of regulating hormones such as ACTH,
dopamine, CRH, cortical and tryptophan. Healthy rats given cytokines or
better yet substances which increases the cytokine activity, display
sickness behavior. The same result occurs when cytokines are administered to
cancer patients; they then suffer from fatigue or depression. The same
mechanism is found in part in depression (primary or secondary) but also in
other illnesses such as cancer and cardiovascular disorders.
In other words, the changes in the immune system (immune
depression/inflammation processes) which have been caused by the raised
cytokine activity, can cause a ME-like or a depression-like syndrome and
this can be seen in both healthy and ill non-ME patients! Moreover, the
"depression" which is diagnosed in some ME-patients is actually a
consequence of this disturbed mechanism.
It is clear that the inflammation processes alone is sufficient for a
"fatigue syndrome" with its many symptoms.
* 4. Prof. Dr. Benjamin Natelson: (USA): The Pathophysiology of CFS. *
The research of Dr. Natelson and associates focuses primarily on the
classification of subgroups, potential differences between ME and
Fibromyalgia, brain deviations and neurological deviations.
Much research was done to classify ME-patients into subgroups to reduce the
large mixture in this population in hope of aiding the study of causation.
Another research field focuses on the possible differences between ME and
Fibromyalgia (FM) and if the disorders are at all the same. Research shows
that 43% of women with ME also have FM; in ME serotonin levels are raised,
while in FM they are reduced, therefore ME must be different from FM
according to Dr. Natelson.
From MRI scans and neurological research, it becomes clear that there are
abnormalities in the brain which offer an affirmation of reported diminished
cognitive functions in patients: the ability to think, to remember, etc.
And finally, research into the spinal cord fluid from a group of ME-patients
shows many abnormalities. No less than 30% of the examined patients had
abnormal values. Thus, inflammation process was clearly determined by the
increase in proteins and white blood cells.
*5. Prof. Dr. Kenny the Meirleir: Belgium: Immune disorders in ME/CFS *
**
*Reporter note: *Even for the doctors present Dr. De Meirleir's complex
recitation was hard to follow as it was given at an accelerated tempo in
order to make time for the two following participants - who had not
previously been announced. I have therefore tried to explain the most
critical information in an understandable language myself and added a lot of
other valuable information - that was not specifically mentioned at this
conference – but could be of interest to most ME-patients.**
Prof. Dr. De Meirleir spoke of the many immunological problems (PKR,
RNase-L,..) that are found in the blood of ME-patients and of the many
consequences of these impairments.
Two important enzyme systems - RNase-L and PKR - which play a key role in
the natural immune responses of the body, have been clearly disturbed: they
have been started but do never stop.
*A) RNase-L enzyme deficiency *
****
The enzyme RNase-L plays an important role in maintaining the normal defense
mechanism of viral, as well as bacterial, infections. If someone is infected
with a virus, interferon (a messenger substance) is activated and ensures
that RNase-L shoots into action. RNase-L then acts like a scissor and cuts
viruses into pieces and renders them harmless. The purpose of this is to
prevent the infection from spreading to the rest of the body and in this way
protects the body from viruses. The infected cell will be forced to destroy
itself and in this way keeps the viruses from multiplying further.
From research it has become clear that in ME-patients RNase-L is split into
a number of pieces. One piece of it -* the low Molecular
Weight*-*LMW-*causes a lot of damage in the body, with the result that
the genetic
material RNA ensures in an uncontrolled manner is demolished. Not only the
genetic material of the virus infected cell, but also the hereditary
material of normal cells is destroyed. Very simply explained, the
activation ofthis enzyme ensures that not only the proteins of the virus
are demolished, but also to a lesser degree human proteins. Because of this,
a large portion of normal immune cells are seriously damaged because they
commit suicide. This process is called *apoptosis.*
* *
*This causes the immune system to be weakened. The impact of this is that:*
** Opportunistic infections, such as Mycoplasma and Chlamydia*, which
normally have no chance in healthy people, are able to develop. Mycoplasmas
are very small microorganisms without cell walls. Because there are no cell
walls, they can easily penetrate other cells. When the immune system has
become much less efficient because of increased apoptosis - as is the case
with ME - they are free to multiply and cause extensive damage. Chlamydia is
frequently contagions in ME-patients. Chlamydia Pneumonia is the most common
form and can give sinus infections but also causes infections of the airways
of patients whose immune systems are functioning inadequately.
* A *reduced resistance to cancer can also arise*.
**Viral infections,* such as the* human herpes viruses (HHV),* are
frequently found in a portion of ME-patients. Herpes viruses occur when the
immune reaction is suppressed and there is chronic immune dysfunction. In
turn, a constant viral infection can ensure that the enzymes PKR and RNase-L
are over stimulated, with all impact for the body.
*Another consequence of the presence of abnormal RNase-L enzyme is the
disturbance of the ion transport.* An example of this is the ionenfluxen: no
normal transport can take place of the ions by the cell partition. This is
responsible for a number of the specific symptoms of ME: large fluctuations
in blood sugar, modified pain sensations, increased sensitivity to toxic
substances (abnormal evacuation of chemical substances mainly mercury and
nickel), etc.
*
* *B) Disturbed PKR*
**
A second important antiviral defense mechanism is PKR. PKR is also a protein
that is activated by viral infection. It will ensure that a number of
substances is released which will encourage the spontaneous cell death of a
virus-infected cell. Moreover it also starts inflammation processes in the
body which reduce the infection and afterwards ensure the disposal of it
from the body.
Part of the ME-population - and this in contrast to patients with MS - PKR
shows a continuously higher activity level. This leads to an early
destruction of the cells responsible for the defense and to a badly
functioning immune system, with for example, an increase of
allergies/intolerances.
*C) Disturbed NO-concentrations *
**
NO (Nitric Oxide) is a substance which is produced by the white blood cells.
Under normal circumstances NO is important for regulating certain
physiological responses. In ME-patients the NO-value often has been raised.
Raised concentrations of NO during a long time are toxic for the cells and
disturb the immune responses. A number of typical symptoms result: headache,
myalgia, low blood pressure.
*D) Disturbed Elastase *
**
Elastase is a substance which cuts RNase-L in pieces and in this way
disorganizes the RNase-L-system. Elastase however also acts on the
connective tissues. If there is an overload in the body - as is often the
case with ME - the connective tissue is split up. This could play a role in
back and joint pain because the joints have insufficient support to keep
them in place. The abnormal high activity of the enzyme elastase keeps in
every way a link with the incapacity of patients to carry out physical
activity. The performance during the bicycle test is partly determined by
the activity of elastase.
*E) Deviation in number and activity in **NK-cells*
**
One of the most occurring problems in the immune system of ME-patients is
the strongly reduced Natural Killer cell-activity. NK-cells are immune cells
which ensure the first defense against abnormal cells in the body (damaged
cells, cancer cells, infected cells). ME-patients frequently have a reduced
number of NK-cells and the NK-cells activity has often been strongly reduced
so that these cells are less able to carry out their function (reduced
cytotoxicity).
*F) Raised actine levels*
Actine is a protein that ensures the physical structure of the cell is
maintained and that cells can move properly. It is of critical importance
for immune cells to search for invaders so that these can be destroyed. In
the immune cells of ME-patients however actine is demolished or split up by
other enzymes (proteases). More actine in blood indicates elevated cell
death.
*
* *Some additional elements from the statement of Dr. De Meirleir:*
**
- Roughly three groups of ME can be distinguished: those with an MS-like
syndrome, those with a mild rheumatic like syndrome and those with a
syndrome with low cortisol levels and many symptoms.
- A clear difference to MS is the raised PKR activity (that is reduced in
MS)
- Not only the immune system has been damaged but also other systems, like
the hormonal system.
- Gene research in ME : Shows that there is a clear difference between
patients which became gradually or suddenly ill. Especially the genes
related to the immune system are different (in comparison with healthy
people): there is clearly an activation of genes which are related to immune
impairments.
*6. Mr. Marc Van Impe: (Belgium) : Freelance journalist and
ME-Lobbyist: Problems
surrounding ME in Belgium and elsewhere *
**
Marc van Impe has been a lobbyist for ME for many years. He also maintains
contact with top officials in politics and the insurance world. Mr. Van
Impe discusses the problems surrounding RIZIV, health insurance funding and
reference centers.
The Belgian government recently released a report evaluating the
ME-reference-centers. Note : This report was posted through Co-Cure in
English and French. The report was completely negative concerning the
functioning of the centers and the achieved goals. Less than 6% of
ME-patients appeared to respond well to the offered combination of Cognitive
Behavior Therapy and Graded Exercise Therapy. For your information: 6% is
the usual result expected to be generated by the "placebo effect". Thus,
the result of the treatment offered by the centers is effectively zero.
Another problem that was mentioned is that of the health insurance funders
and the RIZIV. They want to push ME in Belgium into the psychiatric corner,
as it is in some other European countries. This has to do with the
hospitalization and income insurance which they do not want to pay. However,
independent court cases are generally won. RIZIV and CM are supporters of
Cognitive Behavior Therapy (CBT). This CBT, which has existed for decades,
was taken out of the old box by the psychiatrists. They wanted to find a new
"consuming market" for the therapy. The proof from the centers that this
therapy produces few positive results reinforces what people in the ME-world
have been saying for a long time: That as a supportive therapy CBT can
sometimes be useful, as is the case in other illnesses, but no one has been
healed by learning how to deal better with their illness. In the world of
insurers ME is too often taken off as a "non objectification disorder" and
one speaks too easy about "illness benefit". Also the problem of the bad
information flow and the large shortage of good informed experts in courts
was briefly raised.
Finally Marc Van Impe underlined that the large discord which exists in
Belgium has an important negative impact. It appears that this is abused by,
for instance RIZIV, insurance companies and politicians for the conservation
of a status quo. It will be very important in the future to get everyone on
one line to increase battle strength also. The key to success will be
cooperation on all fronts.
*7. Mevr. Annette Whittemore: The Whittemore-Peterson Institute for
Neuro-Immune Disease: (USA): A new hopeful international project*
**
Mrs. Whittemore was the "surprise act" of the day with a new hopeful
international project. Together with Prof. Dr. Dan Peterson and Prof. Dr. De
Meirleir, she has founded a unique ME/CFS research centre in Reno, Nevada,
USA. Mr. and Mrs. Whittemore have been personally involved for many years in
the ME-business and are important lobbyists in the USA/Nevada.
The newly erected ME-centre will be integrated with the oncology research
department on the campus of the University of Nevada Center for Molecular
Medicine. With the cooperation between these three large entities they hope
to achieve better and faster results. Besides research they also want to
give support to patients and provide training for medical professionals. The
first objective is to stimulate ME-research so that there will be more
answers about biomarkers and treatment. They also hope to get more
governmental support with this ME-centre worldwide and to improve the
reaction speed of governmental agencies.
The centre is unique in its kind. It is the first institute for
neuro-immunological illnesses (such as ME) with a three-part target and at
university level (credibility). Moreover a structured cooperation will be
created between doctors in general and between foreign searchers in
particular. They also try, in a continuous way, to get subsidization for the
fundamental scientific research in ME.
Completion of this new international ME-centre is expected by 2009.
*8. Dr. M. Brack: France: Antioxidants and oxidative stress*
**
Both Dr. Brack and Dr. Maes consider oxidative stress OS an important factor
in ME.
*Note of reporter: *
**
Oxidative stress OS - the shaping of free radicals - is a normal biological
process and necessary for normal bodily functioning. Free radicals arise
more easily under the influence of poison, medicines, strong sunlight, air
clogging, radiation, cigarette smoke etc... OS steps on when the delicate
pro/antioxidant balance is disturbed (pro-oxidant status). When this process
happens accelerated - and therefore too much OS or free radicals form in the
body - sicknesses or health problems can arise. Thus Oxidative stress would
play a role in a lot of illnesses: cardiovascular disorders, metabolism -
and infectious diseases (e.g. AIDS), neurodegenerative illnesses (MS,
Parkinson), accelerated ageing and cancer. OS can damage fats, proteins,
organs and even DNA. From research becomes clear that because of the modern
living conditions there are more free radicals and oxidative processes in
the human body than ever before.
This process of OS can be positively influenced (slowed down) by taking
enough antioxidants from food or in the form of supplements. Antioxidant -
literally "against oxygen" – prevents the harmful free radicals to cause
damage by catching them and for this reason they are called free radical
catchers. Simply expressed the antioxidants reduce wear which is caused by
OS. The most important antioxidants are vitamin C and E and the minerals
selenium and zinc. Vegetables and fruit are rich in antioxidants and must
therefore be eaten sufficiently. However research show that vegetables and
fruits contain much less antioxidants then ever before. The reasons may have
to do with : too fast growing methods, in sere growing (too little
sunlight), pesticides abuse, preservation, too fast preparation (cook
etc.)."
Oxidative Stress to the mitochondrial (the cell's energy factory) plays an
important role in fatigue complaints like ME and Fibromyalgia. Chronic
infections – as occur in many ME-patients - can exhaust the
antioxidant-defense mechanisms which also increases OS. Research shows that
the most important intracellular antioxidant, glutathione, is greatly
reduced or exhausted in most ME- patients.
*Statement Dr. Brack*
The statement of Dr. Brack sufficiently dealt with the correct combination
and dose of antioxidants. He indicated that taking supplements is not to be
recommended without medical advice and that the incorrect use of
antioxidants can in itself cause OS. Nutrients work in synergy with each
other, and for this reason it is bad and even dangerous to take separate
supplements. Vitamin E research showed already the potential harm when taken
without real shortage. Dr. Brack suggests every patients to start with a
general lab status of antioxidants and work then in more detail on the
shortages that result from this. He suggests to start first with a general
complex and add later on the extra nutrients (antioxidants) that are needed
according to the tests.
*9. Prof. Dr. Maes: (Belgium-USA): ME*: *An inflammatory disorder with an
excess of oxidative stress*
External and internal stressors (stress, infections) cause changes in Nf-kB.
Nf-kB is a substance in the cells which is an important medium bug of OS and
inflammation processes. The increase of Nf-kB in ME explains the many
symptoms and could have an important impact on the increase in
OS/inflammation processes which can result in a leaking bowel (Leaky Gut).
Other causes of a leaking bowel are: use of pain-killers and antibiotics,
operations, food allergies, stress. The OS causes damage to mitochondria,
fats and proteins and acts - with the inflammation responses - that there
are auto-immunoreactions. Note: A large part of the ME-patients have these
auto immunoreactions. Each pathogenic germ which penetrates the body is
normally attacked by the body's defense mechanism and cleared in this way.
In autoimmune diseases the defense wrongly attacks an organ/cells from the
own body. That response is started by an underlying sickness process.
OS might also play a role in ME. This becomes clear from the shortages of a
number of essential antioxidants such as carnitine, DHEA and zinc. In Dr.
Maes' view this might be an important cause for ME. In his ME-treatment
omega-3 acids plays an important role. Omega-3 have inflammation inhibitor
properties and reduces raised prostaglandin (type hormones) and cytokine
activity in ME. A shortage of omega-3 is able to play a role in a number of
disorders other than ME. Note: In our Western society/diet the proportion
between Omega 3 and 6 is extremely disturbed with a surplus of Omega 6 and a
shortage of Omega 3. This is due to changing diet habits.
*10 Dr. Jonathan Kerr: UK: Genomics and proteomics of ME *
**
The British researcher who now receives the most attention is Dr. Johnathan
Kerr (London). He leads the largest study to the genetic basis of ME - a new
branch in ME-research. Dr. Kerr is also part of the international research
group of the Whittemore-Peterson Institute (USA).
As could be expected, a lot of defects were found in the genes of
ME-patients. The divergent gene activity relates for a large part to the
immune system and to a lesser degree to the mitochondria. The gene research
found no less than 78 genes which were hyperactive; only a few were
hypoactive. Moreover these deviations appear to lead to
overproduction/stimulation/low production of certain proteins (see research
Dr. De Meirleir).
Future research will have to determine which genes are specific for ME and
which are not. The research of Dr. Kerr is also important because it could
produce markers which can improve the diagnosis of the disorder. These
markers are expected in one or two years - the soonest. Dr. Kerr also
briefly mentioned the role of viral infections in ME (see statement Dr.
Capuron). Viral infections can increase the amount of cytokines - also in
the brain -and stimulate the immune system. Several viruses are found in ME:
acute viruses (EBV, enteroviruses, Mycoplasmas), chronic viruses and
reactive viruses (herpes viruses).
"Hope4All has translated this article which was posted (in Dutch) on
different ME-Fora in Belgium and the Netherlands by mid 2007' .
We would ask the government to avoid banning them completely, and still leave some opportunity for conventional bulbs to be purchased 