About the name ME: Have inflammations of brain and spinal cord been demonstrated or not?

They have certainly been demonstrated. Dr. Natelson showed that 25 % of ME patients have a higher than normal white blood cell count in their cerebrospinal fluid. At autopsies also evidence of the presence of corpora amylacea was found, a kind of inflammatory infiltrate, but again only in a small percentage of patients. Then there are a number of other issues. Radiographic studies show deviations of the dorsal horn of the spinal cord, and also reduced grey matter was found. This reduction of grey matter is visible on a brain MRI.

Does a healthy lifestyle prevent the onset of ME?

In my opinion it’s not possible to prevent the onset of ME through a healthy lifestyle.

A number of other factors beyond ones control determine the onset of ME.

Is it possible to objectively assess exercise intolerance?

Exercise intolerance occurs primarily after physical exertion. The best way to measure this is by doing two peak exercise capacity tests separated by 24 hours. In healthy people work capacity will show no reduction after 24 hours. In ME patients on the other hand this capacity is reduced with an average of 22% after 24 hours.

Why does PEM (Post-Exertional Malaise) sometimes occur later on or delayed?

PEM stands for Post-Exertional Malaise, which means feeling unwell after a significant exertion or even - when you are seriously ill - after a minor physical strain. This is a result of a disruption of many body systems. The sympathetic nervous system, hormones controlled by the brain, the supply of all kind of substances needed for nutrition such as glucose - quite a few body systems are disrupted. It’s explicable that stress, like an exertion, can have more consequences in such patients.

Is POTS (Postural Orthostatic Tachycardia Syndrome) typical for ME?

POTS and its relationship with ME was discovered a long time ago. This was described then by researchers from Hopkins. POTS is also a disease that has several causes. But in my opinion a number of substances responsible for the expansion of the large blood vessels, such as hydrogen sulphide and NO, play a big role. When the larger blood vessels expand, there’s relatively less fluid present and this causes problems when standing upright. In reaction the smaller blood vessels contract and finally the blood flow to organs, such as muscles, diminishes. But it’s actually a complex condition in which also the nervous system is involved. A number of abnormal reactions arise, caused by a hidden inflammatory process.

What’s the relationship between POTS and cognitive impairment?

The relationship between this is a disrupted blood flow in the brain, caused by the underlying mechanisms of this disease. And the cerebral blood flow is better when one lies down than when one sits or stands upright.

There are pre-existing problems, but those are also present in the general population. So I don’t think that those are the main cause of ME. But a lot of problems arise later on in this disease, as a result of a malfunctioning immune system. And the immune system determines what happens in the intestines.

Does blood-brain barrier impairment play a role in the aggravation of ME?

In itself a weakening of the blood-brain barrier hasn’t been proven yet, but we very strongly suspect this is present. There are multiple factors in this disease that can provoke such a weakening.

What is the role of strain and (psychical) stress?

I don’t consider this to be a cause but rather a consequence of ME. That’s to say one becomes more stress prone. This is a result of all kinds of hormonal and neurological changes, which causes an ME patient to become more sensitive to stress. These changes have greater consequences than in normal people, so ones resistance decreases and one tries to avoid stressful situations.

Why are ME patients more susceptible to chronic infections?

ME patients are very susceptible to chronic infections, caused by a change in the immune system. Especially in a later stage of this disease, the TH-1 immunity diminishes, is less present, becomes less strong. There’s also a reduced natural killer cell activity, and a dysfunction of B- and T-cells, that’s to say they don’t function properly. So in fact one can say that it’s rather normal that some infections, such as intracellular infections, fungal infections and latent viruses present in our body, are reactivated.

How do you explain to your near ones why too much noise, light or impressions make you ill?

Many ME patients feel bad when they’re exposed to excessive sound or light, or when it’s too busy around them. This is a result of a number of neurotoxic substances present in their body. You can explain to your relations, that because of these neurotoxic substances your body is poisoned and the brain is overloaded.

Why are ME patients’ blood sugar levels often too low?

Low blood sugar levels often occur in ME patients. This is a consequence of the fact that ME patients absorb sugar more, absorb it faster, because there’s a shift to the so-called anaerobic metabolism. On the other hand there’s a problem with the mechanisms required for releasing sugar as soon as the blood sugar level drops. A number of hormonal systems, responsible for a stable blood sugar level, partially fail. And thirdly we know that in a subgroup of patients the production of insulin is too high, causing more sugar to be absorbed from the blood flow into the cells.

Which other groups of patients run the risk to be misdiagnosed with CFS?

Actually a wrongful diagnosis of CFS is a complicated concept. Because CFS is defined on the basis of a number of symptoms and exclusion of other disorders. But if you don’t look for these, the diagnosis ME/CFS is very easily made.

Many patients suffer from chronic infections or severe hormonal disorders, which may be regarded as secondary in this disease. For us it’s very difficult to debar a diagnosis of ME/CFS. Suppose that in additional examinations one delves really deep, and a number of pathological issues are found, at what point does one stop to call it CFS and ME, while in fact a different condition is being described?

What other deviations do you diagnose by which people eventually are excluded from ME? Does this occur often?

This is rather common. We should exclude for example Lyme disease and other chronic infections with clinical pictures similar to ME. I think this isn’t done often enough. Only a superficial examination by an internist is done, which subsequently leads to a diagnosis of ME. Thus, different diagnoses are hardly considered.

When do you diagnose that a patient has CFS and not ME?

People in whom we discover a chronic infection in an early stage, without the typical other pathologies seen with ME, are diagnosed with this infection. But when the clinical picture and complementary examinations point to the fact that there are a lot of effects which most likely are irreversible, a diagnosis of ME has to be held on to. It’s all about effects and irreversibility.

These last couple of years you have been testing ME/cfs patients for Lyme with improved tests.

What’s your experience with these? What’s the risk of being wrongly diagnosed with Lyme’s disease?

The last few years a lot of new tests did pop up, which give us a better understanding of intracellular infections. We have already found - for instance - quite a few patients with Brucella, chronic brucellosis; or Lyme disease, chronic borreliosis, or a chronic Bartonella infection. At present the count is approximately 50% of all ME patients. So the diagnosis ME is now seriously being questioned.

There’s an increasing number of ME patients who’re also afflicted with Bartonella (cat scratch disease). Yet in the second web seminar on November 10th you say we shouldn’t start from exclusions. So what’s the effect of co-morbidity in ME?

On this question, which actually implies Bartonella is found in patients, I would like to give some comments.

The Bartonella infection found in many ME patients is not cat scratch disease. Cat scratch disease is Bartonella Henselae, but in the meantime 32 other (sub)species of Bartonella have been discovered. We suspect very strongly that several other Bartonella infections are at stake and not Bartonella Henselae, as only in 3% of the patients antibodies against Bartonella Henselae are found.

We don’t know what the actual role of this infection is. It’s only been a year that people are being treated for this infection. Some people recover completely and others recover partially. In my opinion the diagnosis ME mustn’t be abandoned, but I think the impact of Bartonella is different in every patient.

What’s the relationship between IBS (PDS) and ME/cfs?

There’s a relationship between ME/cfs and IBS, Irritable Bowel Syndrome. A lot of people suffer from it, yet there are also many people who don’t have ME but do have IBS.

IBS has to do with abnormal intestinal bacteria, with an abnormal digestion, with an abnormal acidity in the intestines. This is something also found with a lot of ME patients. I personally think this has to do with changes stemming from the immune system, which caused different intestinal bacteria. Also a chronic low-grade inflammation causes changes in the peristaltic movement and an altered degree of acidity in different spots in the intestines.

What does a low number of natural killer cells imply?

in the blood of ME patients often a low number of natural killer cells is found. I have my personal opinion on this.

In my opinion the total number of natural killer cells within the body isn’t reduced, but they have actually moved to the tissues to help fight infections. As in Lyme disease, in which the number of CD57 positive lymphocytes is reduced, I suspect this to be an identical mechanism, which lowers the number of NK-cells in the blood, but makes us find a higher number of them in the tissues.

What does activation of the complement system imply?

Activation of the complement system is also to be found in ME patients. This activation occurs during an inflammation. In most ME patients a low-grade inflammation, a non-specific immunity is triggered. Complement is an aspect of the non-specific immunity. It’s a part of the recuperation process, but since the recuperation process is not complete, changes in the complement will remain present.

What’s the use of an MRI-scan, a Spect-scan or an EEG in ME/cfs?

Neurologists perform numerous tests on ME patients, among others an MRI of the brain. This MRI may demonstrate changes in the structures of the brain. For example, when the volume of grey matter is diminished, there will also be deeper grooves in white matter. Sometimes small areas of demyelination are present, where the myelin disappears. In English we call those UBO’s (Unidentified Bright Objects). Similar to MS these are small areas of 2 to 3 mm, but their location doesn’t correspond with MS and they are much smaller.

With a Spect scan, which is sometimes requested, one can detect the difference from depression. The blood flow disorders in ME patients are different from those in depression.

Another examination ordered by neurologists is an EEG. An EEG provides little information, unless it’s a quantitative EEG. Then often a form of micro epilepsy is seen. Waves are different from those in normal people, there’s an increased sensitivity of the brain.

What exactly is the problem with the mitochondria?

A number of people in the world are investigating the mitochondria in ME patients. They have determined a number of things, like the mitochondria producing less ATP. Mitochondria serve to generate basic energy, in the form of ATP. The actual cause for this malfunctioning disturbance, hasn’t been demonstrated yet. But in fact a number of neurotoxins like hydrogen sulphide that is released, are interfering with the mitochondria. Thus they cause the mitochondria to function less well. Also the release of abnormal proteins may interfere with the mitochondria and reduce their function. So there are a number of mechanisms known to be connected with a poor function of the mitochondria and with ME.

Is there a genetic connection between autism, MS and ME?

In this area only a few studies have been done. When one speaks about genetics and ME, we know there’s a number of issues concerning immunity. And also in the other body systems that cause a genetic predisposition for ME.

But this actually applies to any disease. There’s also a clear link between ME patients and families in which autism occurs. This connection becomes clearer and clearer. Autism is a disorder which is determined genetically as well as by environmental factors, and probably is also provoked by bacterial causes. It’s a wide-spectrum disorder, very diverse. A lot of research is needed to determine the actual relationship.

MS, Multiple Sclerosis and ME are also interlinked. There are families of which some members suffer from ME and others from MS. So there’s a clear genetic connection. More research on this is needed.

What’s the scientific explanation for patients feeling better in the evening than in the morning?

In my opinion, which is based on scientific research on ME patients feeling better in the evening and feeling worse in the morning, this has to do with the fact that their sleep isn’t invigorating. It’s actually of poor quality, because several hormones that should work and raise in level at night, don’t.

Cortisol levels, for instance, are relatively low, while normally in men the highest level of cortisol occurs at about 7 a.m. So ME patients have a different around the clock rhythm. Moreover there’s a serious problem with the release of melatonin. Melatonin makes you sleepy and apparently it isn’t produced at all or much later which causes a phase shift to occur.

These are just a few examples, In my opinion it’s much more complicated. But there’s clear scientific evidence for an abnormal circadian rhythm to occur in ME patients.

In web seminar 4, “ME and Sleep Disorders”, you say: “Patients go to sleep later and later”. Is this caused by the poor quality of sleep, or by lack of melatonin...?

Patients go to sleep later and later because the on/off switch within the brain doesn’t function well. They produce insufficient melatonin, resulting in going to sleep later and later and waking up much later during the day, which causes a total disturbance of their circadian rhythm. Unlike healthy people they aren’t adjusted to normal daylight anymore, and therefore their system gets disturbed and they go to sleep later and later.

What’s the cause of ME patients having so many nightmares? Is it neurochemical or psychological?

Many patients get nightmares and they can be entirely explained neurochemically. There are changes in the serotonin metabolism. Serotonin plays an important role in the brain. We know that especially in ME patients who have a co-morbidity, like a Bartonella or a Lyme-infection, many nightmares occur. Meanwhile we know the mechanism that causes less tryptophan to be converted into serotonin, causing a serotonin shortage in the brain. Personally I think this to play a role in causing those nightmares.

What’s the probable cause of pain?

Many ME patients suffer from diffuse pains, both headaches and muscle pains. In my view central pains also have to do with neurochemical activities, which are the result of neurotoxins and changes in neurotransmitters.

Peripheral pains, the pains in the extremities, to my opinion have to do with a deficient blood supply, which implies a more anaerobic metabolism, and more lactic acid to be produced, causing a shortage of energy and a toxic waste product called lactic acid.

Is it possible to objectify pain? Can you influence the pain by thinking differently?

As for pain traditional medications exist it can be treated with, once you understand the possible causes. There are of course other ways in which you can influence your brain too. But in my opinion these are not really helpful solutions when you suffer very severe pains. I think it’s possible to mentally influence a mild, dull, chronic pain. But if you really suffer pain which has organic roots, it will be very difficult to treat it without medication.

What’s the cause of the epileptic-like shocks within the bodies of ME patients?

Many ME-patients suffer from epileptic-like shocks or experience muscle fasciculations. These also have a neurochemical basis. It probably has to do with disturbances in the ion channels too, through loss of calcium, potassium etc. from the cell, causing an imbalance. This creates a mild form of epilepsy, sometimes perceptible and often not.

Web seminar by Prof. dr. K. de Meirleir, broadcast on March 1st, 2013

Oxygen treatment/therapy: what are the pro’s and cons?

Administration of oxygen has its advantages and disadvantages. Oxygen increases the release of free radicals, which can be harmful. On the other hand it can be very useful to help people with severe pain and with strong acidification.

The oxygen used at home, isn’t administered through oxygen cylinders anymore, like inhospital. It comes from a device that transforms air into almost 100% pure oxygen. So this doesn’t depend on the supply of oxygen cylinders.

Is the oxygen one gets in hospital akin to your oxygen treatment?

The oxygen administered through a so-called oxygenator, is almost equal to the pure oxygen administered in hospital through cylinders.

What do you expect from Rituximab?

For those who have never heard of Rituximab: Rituximab is an antibody against B-cells, used to treat cancer patients with B-cell lymphoma. Researchers from Norway found that people with ME temporarily improved while given this treatment. I consider this to be an excellent diagnostic study. It entirely confirms our hypothesis on ME.

But I don't consider this to be a long-term solution, because practically all patients relapse. So a new injection will be necessary after six or twelve months, which is extremely expensive, to replace these B-cells, which don’t function in a normal way, by young and healthy B-cells. Those young, healthy B-cells will function properly for some time, but will again become involved in the disease process. Therefore it isn’t a definitive solution. Due to the fact that we have few other drugs, this is at present a legitimate experiment.

Ampligen. Is it effective? For whom and for whom not? How does it work?

My experience with Ampligen dates from 1992 until 2001. We gave Ampligen to approximately 150 people then. So I can only speak from my own experience.

Ampligen partially works like Interferon and mainly combats the viral aspect of the disease. So those ME patients in whom the viral aspect of the disease is dominant, will

profit most from it. I think it’s possible it will become available on the market. That doesn’t depend on me and I don’t really have any insight into this, as it all happens in the USA.

Are you familiar with feces donation? Is this a useful approach?

We hear of some patients who choose to have a stool transplant. This means stool from the intestines is removed and replaced by stool from a healthier individual. I believe this also can give a temporary improvement as fewer toxins are released in the body, but again it’s no definitive solution. Because the problem isn't so much the intestines, but the immunity of the intestines. This abnormal flora will grow again. And after all such a stool transplant isn't an enjoyable treatment and must be repeated regularly.

The only indication for this concerns ME patients who have a very strong overgrowth of Clostridium. Clostridium is an extremely dangerous and toxic microbe. But the same applies to people with an overgrowth of Clostridium who don't have ME. I think that the academic hospitals who are doing this at this moment, both in the Netherlands and in other countries, do focus on patients with a dangerous overgrowth of Clostridium.

Heart-rate monitoring and pacing. Can you briefly explain what it implies? What do you expect from it?

Several researchers have established that ME patients have rather irregular heart rhythms, with major variations. This has to do with changes of the sympathetic nervous system, causing a less adequate control of the heart rhythm.

I do think all this can more or less help if one is in control of this. But again this isn't a treatment of the cause.

Pacing is applied in order to use less energy. That's to say to use the energy for things one absolutely wishes to do, to make it through the day in an acceptable and human way. Therefore I believe pacing is an alternative for people who are chronically ill and for whom few treatment options are left. They must learn to deal with the amount of energy they have left. That seems a possibility to me, but one that should be addressed only when the patient has tried all normal treatments.

Doesn’t long-term administering of antibiotics kill the colonic flora?

When one administers broad spectrum antibiotics for a very long time, then one destroys the colonic flora. But when one is very careful and uses narrow spectrum antibiotics to treat a specific infection, this will not happen. There are numerous examples, as for instance in tuberculosis, in which one administers antibiotics for eighteen months. But that's a very narrow spectrum antibiotic, therefore the colonic flora isn't seriously disturbed. If one uses antibiotics, in cases of very acute infection one chooses broad-spectrum antibiotics, like with any other individual. But when one is going to use long-term antibiotics to combat a very specific intracellular infection, one chooses a narrow spectrum antibiotic that has little effect on the colonic flora.

Web seminar by Prof. dr. K. de Meirleir, broadcast on March 15th, 2013

Is it possible for patients to recover just through their own powers?

And in that case should they be above a certain limit with regard to the severity of ME?

The only serious study that has been conducted in this area in the past is one by Dedra Buchwald, in which she questioned a large number of ME patients on the course of their disease. The conclusion was that after three years of illness only 3% of the people spontaneously recuperated. The only reservation that should be made here is that it was a study conducted via the telephone and not one which people registered for in a hospital or polyclinic.

What kind of research do you think will have the best chance of producing a biomarker for ME, following a successful replication study?

We suspect a number of biomarkers will be detected in 2013 or 2014, because a lot of research is being done in this field right now, based on tissue research and on deep sequencing.

“Deep sequencing” is a new technique used for DNA analysis. It will ultimately identify a number of things we previously weren’t able to identify. This research is in progress. This research is in full progress.

Could you describe a few recent discoveries?

A number of discoveries have been made recently. The first results of "deep sequencing" show that ME patients suffer from multiple infections, so they carry many chronic infections, many more than healthy people.

I believe this will be the evidence that the immune system, the defence system, isn’t functioning normally. I think that this will soon be published.

Do you notice a changing attitude among physicians?

A very gradual and slow shift in attitude is taking place, because publications continue to appear on the subject of the psychological model of this disease, continuing to create confusion. There’s a lot of criticism of these studies and about the way they’re performed, of their statistics, withholding of data, etc. But these publications are written by persons with influence and they continue to cause a stir in the medical world.

It's really difficult for people who focus on the biological basis of this disease to obtain and maintain credibility, when there are people who continue to make statements based on bad and unreliable studies.

There are patients who recover overnight. Does this mean that they didn't have ME?

Occasionally there are people who recover overnight from ME. The question is: what is the biological basis of ME? Until this is described, you can’t say that there was an overnight recovery.

There is probably some kind of disease process or mechanism present, which disappeared by chance, or as a result of treatment actually intended for something else. And all of a sudden all the symptoms just disappear. As long as there are no better evaluations of patients, based on biological research, it’s not possible to say that you can be cured of ME overnight.

Is there consensus among scientists, who, for example, are specialized in Lyme and ME-comorbidities, on the existence and criteria of ME?

At the moment I have a lot of contact with people who study Lyme disease and other chronic intracellular infections, such as chlamydia, Bartonella and so on. So a form of cooperation in the scientific field is developing.

The criteria overlap each other to a great extent, but I don't think that anyone has started to study this entire overlap yet. Currently we are working on a publication which compares ME patients with Bartonella to those without Bartonella and which looks at the differences in their symptoms. I expect these kinds of studies to take place more and more in the coming three to four years.