Science for Patients: Lucinda Bateman (of Bateman Horne Center) 2015 interview with Dutch ME/cfs Association

Science for Patients

Lecture 68: Introduction and Diagnosis

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Web lecture by Dr. Lucinda Bateman, broadcast on 8 September 2015

I am Dr. Lucinda Bateman. I am a specialist in general internal medicine who has shifted the focus of her practice from primary care to the speciality of assessing and supporting patients with "chronic fatigue" and "pain".

Which diagnostic criteria for ME/CFS do you consider sufficient?

I think that the existing diagnostic criteria for ME/CFS have several weaknesses. They are not ideal and probably insufficient for both research and clinical medicine.

We need criteria that are very fine-grained, and therefore help us to identify every case of this condition. And we need criteria that are specific, so that we do not incorrectly diagnose other conditions as ME/CFS. In my view, there are examples of this throughout the case definitions.

For good diagnostic criteria, we will have to define subgroups of this broad illness. Whichever diagnostic criteria we use, they must be acceptable to scientific and medical institutions, so that they adopt and use the criteria and do justice to these illnesses.

The criteria must be reasonably simple and practical for doctors to use in their practice. Hopefully, there will be more objective criteria that make patients easier to recognise as such.

These diagnostic criteria will also have to recognise all stages of illness. Of course, it would be wonderful if we could minimise the need for an extensive differential diagnosis.

Instead of a diagnosis by exclusion, our diagnostic criteria should contain as many positively present elements as possible. 

What do you think of the current consensus to use the Canadian Criteria?

The criteria currently in general use are the M.E. criteria, the Canadian Consensus Criteria and the Fukuda CFS criteria. Each of those criteria has its strengths and weaknesses.

The Fukuda criteria were actually intended only as research criteria. They are therefore really not suitable and are far too broad to apply in a clinical setting.

The Canadian criteria and the International Consensus Criteria are probably a much more reliable description of the illness, clinically speaking.

The problem, in my opinion as a doctor, is that they are too complicated. They are mainly subjective and a doctor does not simply have them readily to hand. In the clinical setting, you have to be able to read all these criteria from paper.

So we need core criteria that are also as specific as possible to the illness, and they must be genuine findings related to the illness.

I think we can do better than we do now, and we have to, because science is advancing. We should develop criteria for subgroups in order to disentangle the differences in the presentation of the illness at different stages of illness.

Which diagnostic tools can be used?

At present, we actually have fairly good diagnostic tools, even without strong objective markers.

I think we have become a little lazy in the clinic. I can usually tell, largely through taking a careful medical history, what is going on with my patients; collecting subjective information, such as through a pain diagram, can help with this.

But when you discuss the initial symptoms, the nature of post-exertional malaise and other specific characteristics of ME/CFS, these subjective illness histories are very valuable. It is simply time-consuming.

So perhaps we need to develop tools to collect that information more quickly and efficiently, in a way that is consistent from case to case and from doctor to doctor.

Although we think that physical examination does not reveal very much, there is nevertheless a great deal that can be discovered.

Orthostatic intolerance and autonomic dysfunction can be identified from vital signs, heart rate, blood pressure and pulse while standing and lying down.

Look at the colour of the skin and the temperature of the skin and extremities.

You can see the fatigue. It may not be measurable in numbers, but an observant doctor can notice cognitive dysfunction and cognitive fatigue during the consultation. 

So we need to teach doctors how to notice these things, in order to perform better.

There are also usually subtle neurological symptoms that can be noticed during examination, such as myoclonus, poor balance, tremor and sensory changes.

Most of our laboratory evaluations are indirect and are used to exclude other illnesses. But I think we are going to start noticing a number of subtle signals statistically in such a way that we may later be able to learn more about them through laboratory tests.

I think one of the better diagnostic tests, which is not useful for everyone but is useful in some cases, is the cardiopulmonary exercise test.

Many patients will have abnormal values on the cardiopulmonary exercise test. At least two published studies showed reduced functioning on day two of consecutive cardiopulmonary exercise testing.

That could become an objective marker for making the diagnosis.

Science for Patients

Lecture 69: Autoimmunity in ME/CFS and Fibromyalgia

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Web lecture by Dr. Lucinda Bateman, broadcast on 22nd September 2015

Brief outline of autoimmunity in ME/CFS and fibromyalgia

There is increasing awareness of and interest in the possibility that autoimmunity plays an important role in ME, and also in related illnesses such as CFS and fibromyalgia.

Although fibromyalgia itself is generally not regarded as an autoimmune disease, some excellent articles have appeared over the past year showing that patients who meet the criteria for fibromyalgia may have small-fibre neuropathy. This has been demonstrated with skin biopsies.

These types of polyneuropathies are usually difficult to detect using other methods. EMG, nerve-conduction studies and even physical neurological examinations do not always reveal the abnormalities. It is, however, very important, because small-fibre neuropathies are usually either viral or autoimmune.

There have also been a few studies looking at the activation of glial cells, neuroimmune cells that form part of the brain's innate immunity, and at the role these cells may play in pain and fibromyalgia and what other functions they may have. These are some interesting studies in the field of pain.

We see that ME/CFS is often accompanied by many autoimmune diseases, such as Hashimoto's disease and coeliac disease. Also by peripheral and autonomic neuropathy, which we have only recently begun to understand better.

And personally, I am very interested in a study published this year in which autoimmune antibodies were found in patients with POTS, postural orthostatic tachycardia syndrome. This could explain the disturbed function of the alpha and beta receptors, and what role they play in patients with POTS.

They form an important subgroup in my clinic, particularly the younger patients who develop post-viral fatigue and subsequently, instead of recovering from their virus, develop dysautonomia.

That can be addressed and treated effectively, even if we do not directly treat the autoimmune disease. But hopefully, in the future, we will be able to target treatment more specifically at its autoimmune aspect.

What are the differences between ME/CFS and fibromyalgia?

Many people ask about the difference between M.E. and fibromyalgia. I do not see them so much as two separate conditions; they are case descriptions.

The criteria for fibromyalgia actually come closer to what I expect from good diagnostic criteria. Because they are easy to remember. Initially, the 1990 diagnostic criteria were simply the widespread pain and tenderness specified in them.

Patients with M.E. and ME/CFS meet the criteria for fibromyalgia if they have widespread chronic pain and tenderness. So the illnesses overlap and do not exclude one another.

But many people with widespread pain that is regarded as fibromyalgia are not as ill as M.E. patients. They suffer less from post-exertional malaise.

Many patients with fibromyalgia alone can exercise and increase their endurance. Their pain may worsen with exertion, but if they keep it within limits, they can normally improve their functioning and endurance.

And that really is different from what I regard as M.E. patients. So there is some overlap, but there is also some confusion about what the case descriptions and criteria actually mean.

Science for Patients

Lecture 70: Neuroinflammation and ME/CFS

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Web lecture by Dr. Lucinda Bateman, broadcast on 6nd October 2015

Has neuroinflammation been demonstrated in ME/CFS?

Neuroinflammation is an interesting issue because there is a conflict between the American criteria for CFS and other criteria that use M.E., because of the term ‘encephalomyelitis’.

Because technically ‘itis’ means inflammation, and previously we did not have really strong evidence for neuroinflammation. But in the last year or two, promising studies have been published in which neuroinflammation has been demonstrated with PET and MRI scans.

Small, but high-quality studies, which still need to be replicated. But I think they provide evidence that there is neuroinflammation in ME/CFS. 

Which part of the nervous system is usually affected?

Knowing which part of the nervous system is affected is a challenge in the absence of objective markers. But the research demonstrating neuroinflammation points to white-matter disease as the site of neuroinflammation. 

We do know, from autoantibodies, that the peripheral nervous system can be involved in our patients. The interaction between the peripheral and central nervous systems creates a cycle that is difficult to disentangle.

Is neuroinflammation the cause or consequence of other symptoms in ME/CFS?

Working out whether neuroinflammation is the cause or consequence of ME/CFS is going to be a challenge. I am not sure that we understand that at present.

We think that hereditary predisposition, infectious or viral triggers, physical injuries, exposures and other factors can lead to neuroinflammation. So it probably does not arise out of nowhere.

As I have said before, it is also possible that the peripheral nervous system becomes dysregulated, as in small-fibre polyneuropathy.

If those damaged peripheral nerves in the skin send abnormal signals to the brain, that can cause a series of reactions in the brain that changes something.

So there are a great many questions to answer about the interaction between the peripheral and central nervous systems, together with autoimmunity in the nerve endings and the neuroimmune mechanisms in the brain. 

Is neuroinflammation in ME/CFS treatable?

We actually have no treatments for neuroinflammation in ME/CFS at present.

In particular, no treatments that have been proven or tested. We may perhaps borrow medicines from other illnesses with neuroimmune mechanisms, but that remains to be seen.

There is an interesting treatment about which there are some published studies, and that is the use of naltrexone or very low doses of naltrexone, which might modulate glial-cell inflammation in such a way that at least part of the neuroinflammation is treated.

Perhaps the part that is more closely related to the amplification of pain. 

Science for Patients

College 71: ME/CFS and the Brain

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Web lecture by Dr. Lucinda Bateman, broadcast on 20th October 2015.

What are grey matter and white matter?

Let’s talk about M.E. and the brain. You will probably have heard of the terms grey matter and white matter.

The grey matter in the brain is the part of the brain containing most of the cell bodies, the neurons, and because of that it looks darker. This picture shows what this looks like.

Here is a cross-section of the brain, and you may be able to see that the outer part of the brain is grey and the inner part is white.

White matter is therefore the part located more towards the inside, and it looks white because of myelin. Myelin is the protective layer around the nerve fibres.

The thinking part of the brain is located more towards the outside. From there, the fibres of these neurons travel towards the centre and pass through some important areas in the midbrain, down to the spinal cord and onwards into the body.

Remarkably enough, it is the other way round in the spinal cord: the white matter is on the outside and the grey matter on the inside, because these are the pathways that extend out into the body.

The nerve pathways that communicate this and transmit the electrical signals are what constitute the white matter in the brain.

The interesting connection with M.E. is that the clinical picture of M.E. generally does not have a direct impact on cognition in the way that occurs in dementia.

There is more of a slowing or fatiguing aspect to cognition.

It seems as though the signals have to pass through the inflamed part of the brain. And the signal is slowed down or dysregulated as it passes through.

That is my way of explaining it.

But the white matter also includes the central area of the brain where pain, intense emotion, the autonomic nervous system and the neuroendocrine system are located, and this is extremely important for the functioning of the body.

And depending upon where the neuroinflammation is, you could have a different clinical presentation.

Abnormalities in grey and white matter: also in MS, Parkinson’s, RA and Alzheimer’s?

A number of diseases that we know about are probably also diseases involving neuroinflammation.

The three best known are multiple sclerosis, Parkinson’s and Alzheimer’s.

Rheumatoid arthritis is an autoimmune disease that is more peripheral, in contrast to the central nervous system involvement in neuroinflammation.

There are other things that can cause neuroinflammation, such as brain injury. Even the ageing process has been associated with progressive neuroinflammation.

It is a very important field, but each of these diseases has its own type, location or nature of neuroinflammation.

For example, multiple sclerosis is an autoimmune or neuroimmune attack on the myelin sheath, specifically in patches throughout the white matter. But we know how to identify it and we can identify those antibodies.

Parkinson’s disease has different stages. One of the principal stages is degeneration or damage to the substantia nigra cells that are responsible for the production of dopamine.

The disease manifests itself through dopamine deficiency as well as in other ways.

And then there is Alzheimer’s, which we do not yet completely understand. Abnormal functioning of glial cells in chronic inflammation is thought to be involved.

We have some ideas about the pathophysiology of these other diseases. But it is early days.

Do M.S., Parkinson’s, R.A. and Alzheimer’s present in the same way as ME/CFS?

The presentation of a neuroimmune disease depends upon the mechanism and the location where the neuroinflammation develops. And that, in turn, influences the clinical presentation.

In Alzheimer’s there is unmistakable cognitive decline; in Parkinson’s there are symptoms associated with low dopamine levels.

M.S. is somewhat random, depending upon where demyelination occurs in the white matter, including in the spinal cord.

I have just read a very interesting book entitled Brain on Fire. It was written by Susannah Cahalan and is her personal story of suddenly becoming severely mentally ill.

But while it was initially thought to be a mental illness, it developed into a severe neurological disease that would have led to death.

Fortunately, she was able to obtain a diagnosis.

Her disease was an autoimmune attack against a specific receptor in the nervous system: the NMDA receptors.

The area in which these NMDA receptors were located was the area of inflammation. Coincidentally, it was in the region that produced symptoms such as schizophrenia or bipolar illness.

Yet it was completely treatable and reversible.

She recovered and was able to come back and write the book.

The diagnosis of the disease was made by means of a brain biopsy.

Because she was going to die, and because she finally found the right person who could put the clinical picture of the disease together, determine the stages of the disease and take a good medical history, combine all this information and link it to NMDA-receptor function, and then perform the brain biopsy, he was then able to give the correct treatment.

Can abnormalities caused by neuroinflammation be treated with medication?

An important question is whether we have medicines or other forms of treatment to repair the damage caused by neuroinflammation.

The answer is that we probably have a number of treatments and the ability to develop others.

Some damage to the nervous system probably cannot be repaired, but the inflammation might possibly be reduced.

The severity of the damage that has occurred will determine how reversible the neurological component of this disease is.

That is the big question.

And the important area ahead of us is to gain a better understanding of neuroinflammation.

Science for Patients

Lecture 72: Gene Expression and Exercise

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Web lecture by Dr. Lucinda Bateman, broadcast on 3 November 2015.

Are the effects of exercise in ME/CFS visible through gene expression?

It was wonderful to work with Alan Light on research into gene expression. Because, as the clinical investigator, I was able to select the patients whom I thought showed the correct clinical picture and enrol them in the study.

The effects of exercise in M.E. can clearly be seen through gene expression. It directly changes the expression of the sensory receptors, the adrenergic receptors, and the immune and cytokine receptors that correspond to the clinical picture and to how patients describe their symptoms.

What are the negative effects of too much exercise?

The negative effects of too much physical exercise - actually, of any exertion in patients with M.E. - can be profound.

It leads to a clear deterioration: fatigue, pain and increased cognitive symptoms. I have seen patients who slept worse after exertion.

In fact, all symptoms can become worse after too much exertion.

What possibilities are there for exercise in ME/CFS?

Because deconditioning plays such an important role in the well-being of patients with M.E., I have spent a great deal of time teaching patients to do exercises to improve their illness.

I believe there are many possibilities for maintaining a certain degree of fitness. It depends upon the severity of the illness, and that sometimes changes within the same person.

So we try to focus on maintaining or improving muscle strength, flexibility and also some cardiovascular exercise, more through walking.

It is really about the fitness of your heart rather than the fitness of your muscles. Aerobic or cardiovascular exercise, and particularly upright activity, seem to be the most difficult.

We focus on very small improvements in muscle strength in different parts of the body, such as the trunk - the muscles you need every day in order to function.

And flexibility, so that patients do not become too stiff.

These things can be increased in very small steps, interspersed with periods of rest.

We also try to use exercises that minimise orthostatic stress. Particularly in people with greater orthostatic intolerance, exercises can be performed lying down or sitting.

Sometimes exercises can be done best of all in water. In water there is less stress on the joints, and water is a hydrostatic pressure tank. 

The deeper the water, the greater the pressure.

Patients sometimes tend to lie down in the water, so that there is less orthostatic stress.

But it is very difficult to get to the water. By the time ill patients have reached the water, they have already used up the exertion they are able to tolerate.

What are the exercise limitations in ME/CFS? For example, in bedridden patients?

The exercise limitations in M.E. are very individual.

The limit is the threshold that triggers post-exertional malaise.

That is the limit.

Understanding where that threshold lies is a constantly moving target and a major challenge.

In patients who are moderately ill, that threshold goes up and down. They have days when they can do a little more, and days when they need to rest and recover.

For patients who are so severely ill that they are bedridden, this threshold may be very low.

The point is not to remain exactly the same.

When patients say that they cannot exercise, I say:

“You can do one tiny thing more than you did.”

Because your level of conditioning will reflect the average level of activity you tolerate.

If you tense your muscles for thirty seconds, that will give you more strength. But it must be tailored to the patient and to their circumstances.

The most important thing with exercise is not to cause a relapse.

I tell my patients:

“Do nothing that makes you ill the next day.”

Whatever you do, you must be able to recover from it with a night's sleep.

If you have pain, nausea, fatigue, cognitive problems, or anything else the following day because of that extra exertion, then you should rest until it has passed and try again with something different.

Different activities have different effects on post-exertional malaise.

Muscle strengthening may perhaps be better tolerated. In my opinion, stretching exercises are tolerated best, followed by strength exercises and finally upright and aerobic exercises.

But that is actually the least important for development.

Science for Patients

College 73: FAQs from Clinical Practice - Part 1

All texts within the framework of the Science for Patients project may be distributed, but only with the explicit source attribution:

Web lecture by Dr. Lucinda Bateman, broadcast on 17th November, 2015.

Can I recover from this illness, ME/CFS?

One of the most common questions from patients who come to me for the first time is:

“Can I recover from this illness?”

This is a difficult question because, particularly now with the current diagnostics, perhaps at an already advanced stage of the illness, most studies show that by the time patients consult a specialist, they have a very small chance of recovering from their illness.

This may change when we are able to diagnose this illness earlier or when we develop other methods of treatment. But as things stand at present, the focus is not on recovery.

I do want to say that control, adaptation, stability and attempts at improvement can be achieved with good supportive care.

So patients should not ask:

“Can I recover?”

but:

“Am I doing everything I can to adapt, to treat my symptoms and to stabilise my condition, with perhaps small improvements?”

Are there treatments for ME/CFS?

At present, we actually have no direct curative treatments for ME/CFS.

But do not underestimate the usefulness of skilled management. I can tell you, and I think my patients can too, that we have many tools available in my medical practice.

So we focus on a few more manageable aspects of the illness.

We talked about deconditioning, which is one of them.

We have very good tools for manipulating and modulating pain. Particularly newer treatments for the modulation of pain, for increased pain sensitivity or for pain such as that associated with peripheral neuropathies or other forms of neuropathy.

We have treatments for sleep. It is a challenge, but we can improve the quality of sleep and add some quality of life.

And we also have treatments for cognitive impairment and for dysautonomia, for the autonomic aspects of the illness.

So we address as many aspects of the illness as possible and try to modulate the severity of those symptoms in order to improve quality of life, while waiting for direct treatments that intervene directly in the pathophysiology.

Is ME/CFS progressive? Can it be fatal?

A difficult question concerning ME/CFS is:

Is this a progressive illness and can this illness be fatal?

I do not know the answer to that.

Sometimes this illness can be progressive despite everything we do.

There are certainly cases with a fatal outcome in this illness. But these will often be patients who did not have access to good supportive care.

I think the secondary problems that develop around this illness are very serious and important, and because of them the morbidity and risk of death are much greater.

Some of those we might perhaps be able to prevent, and some we cannot.

That also includes deconditioning, weight gain and all the illnesses associated with them, problems in the end stages of sleep apnoea and diabetes.

I have patients whose principal problem is those overwhelming illnesses associated with their deconditioning and obesity, including young people.

We have problems with malnutrition and, of course, depression and despair, which arise partly from environmental stressors, but also from the severity of the illness.

And the lack of good care and direct treatment makes mortality in this illness much greater.

And there is much more that we can do about that.

Is ME/CFS contagious?

Another question I am frequently asked is whether this illness is contagious.

So far, there really are no studies or any evidence suggesting that this illness itself is contagious.

Sometimes we see it in a family setting. There may perhaps be something contagious that, at a particular stage in this illness, can make some people ill, but in a milder form.

But at present, the severe form does not appear to be contagious.

At least, not in the way that we think about contagiousness.

Science for Patients

College 74: FAQs from Clinical Practice - Part 2

All texts within the framework of the Science for Patients project may be distributed, but only with the explicit source attribution: 

Web lecture by Dr. Lucinda Bateman, broadcast on 1st December, 2015.

How can I explain to others what ME/CFS is?

One of the greatest challenges for patients is explaining this illness to others.

It is even difficult to understand it yourself. But my advice to patients is, first of all: educate yourself, because if you do not understand the illness, then it is difficult to explain it to others.

Develop a vocabulary to describe how the illness affects you and what your needs are. And learn to communicate about that. Educate yourself so that you learn as much as possible about the illness. That will enable you to talk about it better with others.

Secondly, you should only concern yourself with explaining this illness to the people who matter. That should be a very small circle. The people you depend upon, who love you, and whom you love.

Because there are an enormous number of people who will never understand this illness until we have more objective markers. And there is not enough energy to try to explain it.

There is no need to explain it to all those other people.

So I advise patients to invest their energy in their most important loved ones, and to leave the other people alone.

Compare it with a tortoise. The tortoise is the mascot for our patients, because it is patient and persistent.

And the tortoise also has a hard exterior. The tortoise learns to defend and protect itself and to be independent. It can pull its legs in when necessary.

But it is really important not to be overly concerned about the judgement of others.

Build that self-confidence, your own knowledge, and your own team around you.

Can I, as an ME/CFS patient, have and raise children?

Patients want to know whether they can continue with their normal activities when they have ME/CFS.

Can they marry, can they have children and start a family?

My advice to my patients is:

“You can probably do almost anything you want, but just a little less. So you may have to set priorities and it may require more resources.”

But I have many patients who choose to marry and, even when they are ill, to have children.

But be very realistic about the resources you will need in that situation. And if you plan in advance and provide for them, then you can do the things that make you glad and happy.

One of those is having children.

There are probably greater risks surrounding pregnancy and childbirth. And caring for children is very demanding and can worsen the illness.

But from a philosophical and medical point of view, on the other hand, I do not think there are reasons why it should not be possible for those who consider it one of their most important goals.

What hopeful developments are emerging in research?

Fortunately, many hopeful research developments are appearing on the horizon.

I am as optimistic as I have been throughout my entire career about what lies ahead.

I think one of the most important steps we need to take is the identification of subgroups.

And that should be possible through some of the studies currently under way: gene-expression studies, epigenetic studies, greater understanding of the autonomic aspects of this illness, the autoimmune aspects, and the neuroinflammatory changes.

I am also very interested in the neuroendocrine changes that may play a role in this illness.

We are on the threshold of really understanding much more about it.

That should lead to an explosion in research. Some of which is very much needed.

Another area of research that will become very important in the near future is a more consistent understanding of the post-exertional malaise that characterises this illness.

And because we do not even really have a way of describing that post-exertional malaise yet, we do not understand it yet.

I think these gene-expression studies are going to open the door to understanding what causes that relapse.

That is going to be the key, and I think it is going to become the focus of research in the near future.

What hopeful developments are taking place politically?

There is certainly a political side to this illness.

I cannot speak for what is happening outside the United States; people there will have to deal with the politics there.

But I have become quite involved in politics in the United States.

There is a great deal of controversy about this subject here.

I see positive developments.

One of them is the project by the Institute of Medicine to re-evaluate the evidence-based research and recommend diagnostic criteria for ME/CFS, and also make recommendations concerning the name.

I served on that committee.

I thought it was a wonderful experience and enjoyed doing it.

I feel that a great deal of work has been done.

And that will probably be released soon, early in 2015. Then the contract will expire and the report will be made public.

So that really is a major change.

It is going to change the picture of what we do, because ultimately we were asked to make changes in its evaluation.

How that will be received and implemented, I think we will have to wait and see.

The other major project under way is the NIH P2P workshop, or “Pathways to Prevention”, from December 2014.

The results of that will become available before the end of 2014.

Although there may be considerable disagreement about it, ideally the aim is nevertheless to weigh the existing evidence in order to identify gaps in the research and determine the next steps.

So hopefully, even if we think differently about the outcome, we can take that important final step of determining the next steps, as part of the mandate.

And that will move the research forward.

So I really think that, whatever happens, those two projects will put this entire field into a new position.

And hopefully that will become one of more research and much greater consensus within medicine about this illness.

So that patients do not remain on the periphery, where no attention is paid to them.

Science for Patients

Chat: Questions and Answers

On Friday 18th September 2015, questions could be put to Dr. Lucinda Bateman via our chat channel. 

The questions and answers are given below.

Q: In your webinar (68), you talk about the current diagnostic criteria and you do not think they are very good. Do you mean that the new SEID criteria, as recently proposed by the IOM committee, are not very good?

A: I think the new clinical diagnostic criteria (SEID) are better than those we had previously and they are intended for use by GP's and other specialists in clinical practice. The name SEID was only a proposal, but the criteria in the report are the most important part of it.

Q: Good diagnostic criteria should be both sensitive and specific. Are the SEID criteria sufficiently sensitive and specific in your opinion?

A: Time will tell. If doctors do their job in investigating patients for other illnesses, as they should, then the criteria should be very good. All newly proposed criteria need to be investigated and applied. The report states that everything in it should be re-evaluated before five years have passed.

Q: For me, it is very refreshing that the IOM committee proposed an ‘open end’, which means that the report should be looked at again completely if new research gives reason to do so!

A: Yes, that is important, and the report proposes that the US federal government should fund research to revise the IOM criteria.

Q: You talk about diagnostic criteria and biomarkers. The level of VIP (vasoactive intestinal polypeptide) hormones in the blood is sometimes regarded as a biomarker. In your practice, have you ever noticed a relationship between the level of VIP hormones and ME/CFS in a patient? VIP hormones regulate many things that do not function properly in ME/CFS patients.

A: I have never measured VIP hormones in the clinic.

Q: Are fasciculations common in certain illnesses?

A: Particularly in neurological illnesses.

Q: Can fasciculations ever occur IN the brain, generally speaking?

A: To me, fasciculations are twitching or small movements of the muscles. They are usually caused by a neurological signal, such as a damaged nerve or abnormal signals resulting from damage in the brain or spinal cord.

Q: Could you explain that to my neurologist?

A: I am still trying to explain this to my neurologist colleagues. Fortunately, there are some younger neurologists near me, at the University of Utah, who are interested in autoimmune and neuroimmune diseases of the nervous system.

College 68 chat - continued

Q: You talk about subgroups that can be distinguished within ME/CFS, with different phases in the course of the illness. Can you tell us more about that? Do you already have an idea which subgroups can be distinguished?

A: Yes, because my entire clinic is based on patients who meet the Fukuda CFS or fibromyalgia criteria. I can easily see the diversity and heterogeneity. I have my ideas about subgroups, but they need to be investigated with biomarkers that emerge or through their clinical presentation.

Q: Do these subgroups exist because of different causes of M.E., or because of different locations of, for example, neuroinflammation?

A: I would like to give an example. When I first worked with Alan Light on a study, I selected patients on the basis of the presence of exercise intolerance and PEM. The gene-expression results were excellent.

When gene expression was applied to a much larger group, the results became complex and non-specific. I think the subgroups can represent many things - including stage of illness, type of onset, secondary comorbidity, etc...

Q: Do you already sort your patients according to their symptoms, thereby creating hypothetical subgroups?

A: Perhaps we are dealing with a small number of illnesses that are unrelated to one another, or with a few rare illnesses that have been combined with the larger group.

When I examine patients, I make my best estimate of their possible ‘subgroup’. I then use the response to treatment to make further decisions about their subgroup.

For example, I rarely diagnose M.E. or CFS without the presence of PEM. I try to distinguish between the exercise response of FM (flaring pain) and the exercise response of ME/CFS. I also try to separate patients with POTS as a principal symptom because they often respond to treatment.

By the term ‘larger group’, I mean those who meet the CFS diagnosis and share the same diagnosis. I have patients who meet the criteria but whom I actually think have something else that I cannot determine. But I leave them in the group. That will be the minority.

Q: What kind of treatment works for POTS if you also have M.E.?

A: For POTS, you can use aggressive hydration, the addition of salt, compression stockings, specific exercises to strengthen the lower-leg muscles, behavioural changes and some medications.

The most important first step with POTS is diagnosis. Doctors do not routinely carry out the kind of investigation that demonstrates that complaint.

Q: What does strengthening the lower-leg muscles involve?

A: Strengthening the lower-leg muscles simply means developing stronger leg muscles. There are many ways to maintain muscle mass, tone and strength. It just takes some work. These muscles help return blood flow to the heart.

Q: If the results of the research by, for example, Mady Hornig on the possible stages of the illness had come earlier, would they have changed the results and recommendations of the IOM report?

A: I was part of the research group with Mady Hornig and was a co-investigator on that study. As clinicians, we all recognise that there are clinical differences between the early and late stages of the illness. The IOM report had to be based on large, published, high-quality studies. Unfortunately, there are none with clear data on the stage of the illness. Mady’s research is only one study with a small signal… we need much more.

Q: As an M.E. patient, I recognise myself most in the ICC because they describe all the different symptoms of M.E.. For me, it is quite disappointing that all these symptoms have been ‘reduced’ to a handful of diverse symptoms in the SEID criteria. Can you explain why this choice was made?

A: With the IOM criteria, the particular aim was to reduce the number of symptoms required to make a diagnosis. They are based on large datasets of patient-reported symptoms. We chose symptoms that were common, that could be objectively demonstrated by a doctor and that, in combination, would hopefully be relatively specific to this illness complex. The IOM criteria assume that doctors will carry out a differential diagnostic investigation. There are very few illnesses in which functioning is severely reduced, PEM is characteristic and sleep is unrefreshing, and which also show either clear cognitive impairment or measurable orthostatic intolerance.

Q: What do you think about SEID?

A: The term SEID was a consensus name. My personal preference is M.E.. I would add that not all of my patients have M.E.. - young people disabled by post-viral fatigue and POTS, for example, do not meet the M.E. criteria. But they do meet the CFS criteria.

Q: Do you mean those in whom a virus has been found? Because you believe in the theory of inflammation in the brain and spinal cord?

A: I prefer M.E. because I think we should all use one term and the US should not try to use terminology different from the rest of the world. 

I do not mind using SEID in association with the new clinical criteria, because those are not really the M.E. criteria. It really is all a mess.

Q: Do you know when the recommendations of the IOM report will be officially recognised? And who or which organisation is responsible for that recognition?

A: The recommendations in the IOM report for clinical diagnostic criteria are gradually being adopted. Use of the name ‘SEID’ is not widely supported. Unfortunately, there is no clear ‘boss’ in charge of these decisions. It is important to distinguish these two points - the diagnostic criteria and the name. I am beginning to get the feeling that the recommendations of the IOM report will never be ‘officially’ recognised. I think they will gradually be accepted. The controversy over the name of the illness will remain vague and confusing until we have objective diagnostic markers and begin naming subgroups on the basis of scientific data.

Q: Has the IOM committee been dissolved and does it no longer have anything to say about this matter?

A: Yes, the IOM committee no longer exists.

Q: Perhaps I was wrong, but I thought some organisation would give a final opinion on the recommendations.

A: The IOM committee was a working arrangement that brought people together from across the country on a one-off basis for a single product. It is up to the NIH to determine what to do with it. But the NIH is a huge, complex, broad organisation that never speaks with one voice. I probably should not say that the NIH ‘never’ speaks with one voice… but it rarely does. This illness is a tiny dot on the NIH landscape.

Q: So what can the M.E. community do to force the NIH to take action in this area?

A: The ME community needs to make itself heard in every possible way. That is happening now in the US. It is getting the attention of officials and the NIH. Things are happening behind the scenes here in the US at the moment. I think that will become apparent over the next year or so.

Q: Within the community there is an increasingly strong call to adopt the original Ramsay criteria. Is there a major difference between the IOM and Ramsay criteria?

A: I like the Ramsay criteria very much. They describe the severely ill very clearly. Perhaps we should regard this group as a subgroup, as an approach to studying the illness. 

(Bateman is claiming the patients, who actually have the diagnosis of M.E. are a subgroup, what of : 'CFS' criterias, of which... they are 'excluded')

The IOM criteria include people who meet the Ramsay criteria, but in my opinion they also include a larger group. I do not think we should try to insist upon a single case definition. That concept has not worked for twenty years.

Q: Have you ever considered that a disturbance in fat metabolism could be the main cause of the loss of energy and developing CFS? Or neurotransmitters?

A: I have never regarded fat metabolism as the central issue in this illness. I see many secondary illnesses associated with fat metabolism.

Q: I am personally convinced, and I think that once people have to burn their proteins simply for the strength to survive, they develop M.E..

A: I think there is some truth in that view. Many people have symptoms associated with carbohydrate intake.

Q: Is the requirement for ‘evidence-based’ evidence not setting the bar too high for consensus criteria, or should the term ‘evidence-based’ perhaps be interpreted less strictly? I mean, when several small studies demonstrate the same abnormalities, why are these not included in the diagnostic and clinical criteria instead of waiting for lengthy, double-blind, controlled, randomised studies? If their results turn out to differ, surely the criteria could still be adjusted afterwards?

A: The problem with small studies is that they do not always prove anything. Because of the small study group, or because of other aspects of the study design, they can turn out to be wrong.

Q: Do you think Lipkin has lost his interest?

A: I can say with certainty that Lipkin has not lost his interest. Quite the opposite. He is working behind the scenes to make further progress.

Q: Do you think there is one primary cause that ultimately results in all the different symptoms? Or are there probably multiple causes because of the different symptoms?

A: I think there is one primary cause in the majority of cases… and then there are people who meet the criteria who also have different causes. They are all lumped together.

Q: What research is most urgently needed to find the cause of M.E., in your opinion?

A: Everything. We need everyone in every field to investigate their part of this illness. At the moment there is considerable emphasis on genetic or genomic or epigenetic markers. And there is great interest in the microbiome and other immune markers. I think we should also place greater emphasis on the brain and the autonomic nervous system.

Q: Is there a worldwide exchange between research experts in all the fields involved?

A: The IACFS/ME has historically been the instrument for encouraging dialogue between researchers around the world. If their scientific conferences did not exist, that would not happen. The IACFS/ME needs more financial support.

Q: Why are you so convinced that we really are ill when most doctors are not?

A: I have assessed and treated more than a thousand patients. So: because I know more. Some patients I have followed for more than twenty years. 

Science for Patients

Chat: Questions and Answers

On Friday 9th October 2015, questions could be put to Dr. Lucinda Bateman via our chat channel. The questions and answers are given below.

Q: I would like to know what you think about swollen glands in the neck. Do they indicate inflammation in the brain, as some studies suggest?

A: The Fukuda criteria refer to ‘tender nodes’ rather than swollen [enlarged] nodes/glands. It is my experience, and this is supported by data, that most patients do not have enlarged nodes, and tender nodes occur only intermittently, perhaps during a flare.

I do not think they are directly related to brain inflammation. The brain inflammation that we expect to be present is much more difficult to demonstrate objectively.

Q: So tender glands are not caused by inflammation?

A: Tender glands are caused by inflammation, but not by brain inflammation.

Q: What investigations can my GP carry out to confirm a diagnosis of M.E.?

A: The best ‘test’ for M.E. is a professional physical examination to demonstrate signs of the illness: tender glands, appearing ill, neurological features of imbalance, blood pressure and irregularities in heart rate, particularly during orthostatic measurements (standing).

There are no laboratory tests at present.

Q: Regarding diagnostic tools: which blood tests can be done and how reliable are they? What about NK cells, B cells and T cells, etc.?

A: As part of the IOM report, we studied the immune literature. The only strong studies concerned NK cells.

Even the NK-cell literature has problems because studies are insufficiently replicated. Laboratories use a number of different tests and there is no consensus about them. There are many negative as well as positive studies.

At present, several studies are under way in the US to establish the role of NK cells in ME/CFS.

Q: What is the role of oxidants, such as Reactive Oxygen Species (ROS), in the neuroinflammatory aspect of ME/CFS?

A: The cause of neuroinflammation is not very well understood, but it is certainly complex. Microglial cells will be involved, as will the release of cytokines and other chemicals.

Other chemicals are released from other immune cells in the peripheral system, lymphocytes, etc., which damage cells. I do not have detailed specific knowledge about oxidants.

Q: Should ME/CFS patients take additional antioxidants such as flavonoids to reduce levels of inflammation?

A: That seems sensible, but I am not aware of evidence that it ultimately has an effect in the brain.

Q: Antioxidants do not necessarily have to affect the brain, but the question was actually whether they can have an influence on inflammation, if it is present.

A: I am not sure. Inflammation is a broad subject involving many cells, chemicals and interactions in different places in the body. Antioxidants may play a role in some of them.

Q: So you do not prescribe them and do not use them in your clinical practice?

A: I do not prescribe them, but many of them are readily available in food and supplement shops.

Q: There is no research being done on them as far as you know? Because almost all patients benefit from them. Free radicals are fairly well known in ME/CFS, aren't they?

A: Unfortunately, I do not know of research in the US concerning antioxidants specifically for the treatment of ME/CFS. It is interesting to hear. I would like to learn more from prescribers and patients who benefit from them.

I do not see it happening very much here. Doctors in the US have no training or experience with non-pharmaceutical medicines/supplements. There are many others who do provide them, such as naturopaths, etc...

Q: Shouldn't the two-day cardiopulmonary exercise test be mandatory when diagnosing the illness?

A: The two-day cardiopulmonary exercise test is a gruelling test that can cause many patients to relapse severely.

I therefore do not advocate it as a diagnostic test, except when there is an urgent need to prove the diagnosis.

I regard the two-day cardiopulmonary exercise test as a research tool for demonstrating the pathology, but I would not subject every patient to it in order to prove the diagnosis.

Q: Professor Visser (a Dutch cardiologist, quite knowledgeable about ME/CFS) has the same opinion. But isn't it nevertheless recommended in a research setting in the IOM criteria?

A: It is not recommended in the IOM criteria. It is used to support the concept of PEM in the report.

As part of the CDC multi-site study, we performed cardiopulmonary exercise tests on approximately twenty of our patients. Many of them did not recover for weeks.

Q: Surely enough patients could be found who would be willing to take the risk of a relapse in the interests of obtaining a clearer picture of ME/CFS.

A: Yes, I agree that many patients are interested and willing to undergo cardiopulmonary exercise testing.

I have patients who have to prove to the government that they are disabled. In those cases, it could be useful in securing their financial support.

A cardiopulmonary exercise test must be carried out by experienced technicians and interpreted with knowledge of the typical findings in ME/CFS.

Q: Is there a relationship between interstitial cystitis and M.E. and autoimmunity?

A: Yes, interstitial cystitis can occur on its own, but is very common in patients with M.E. and in patients with fibromyalgia (perhaps in any condition involving amplified pain in the central nervous system).

The cause is not clear. It is not clear how much of that condition (IC) is caused by inflammation of the bladder itself, damage to the peripheral nerves in the bladder, or a more central process of pain amplification.

Perhaps all three.

Q: Can you develop ME/CFS approximately ten years after interstitial cystitis?

A: Interstitial cystitis can occur before, or after M.E. or FM. 

Q: You mentioned stages of illness in ME/CFS. Could you elaborate on that? What are their characteristics?

A: As a clinician, I certainly see stages in the illness. I have patients who have been in my practice for 15-20 years.

Unfortunately, there is almost no longitudinal research to demonstrate what we see in practice.

Q: Not longitudinal, but didn't Alan [Light] show the different stages of illness in gene-expression markers? And how did Mady [Hornig] distinguish between them?

A: Although M.E. is defined by a sudden dramatic onset, I believe (as a clinician) that there are probably earlier warning signs and stages of illness that have never been diagnosed.

We should investigate that.

I also have patients who are much less ill for many years and then seem to deteriorate for various reasons. I also have severely ill patients who have improved to a more functional condition.

The gene-expression markers were dissected from a slice in time. They constitute a cross-section. We do not know whether they represent stages of illness, subsets of the illness, or different illnesses.

Q: Do you mean during childhood? Almost all patients had signs of a predisposition.

A: The cytokine study (Mady) simply compared the cytokine data of patients ill for <3 years and >3 years.

That was the same dataset that was used to refute XMRV, so it was specifically designed to include patients with an early onset of illness.

The cytokine data from the early and later stages are only a small signal. Much more extensive exploration with additional markers is needed.

The same group is preparing for a microbiome study. We hope to be able to include a substantial number of patients at an early stage of illness.

It is challenging because these patients often do not receive specialist care for many years.

Q: How large is the cohort?

A: My site is enrolling 25 ME/CFS patients and 25 healthy controls. I think there are 4-5 sites, but I am not sure how many enrolments they want in total.

Q: My M.E. became much worse after an infection. Are there things you can do to remain stable when you have an infection?

A: An M.E. relapse or deterioration can occur after almost any serious source of stress: trauma, pain, infection, sleep deprivation, emotional stress, etc.

I advise my patients who develop an infection to take things more slowly, receive supportive treatment and allow themselves an abundance of time for recovery.

If there is an available treatment for the infection, start it early. Shingles, for example, should be treated rigorously.

Q: I did all those things, so I suppose it is unpredictable because I remained stable after some other infections?

A: I suspect that some infections are more likely to cause problems with an M.E. relapse than others.

Q: Are you familiar with glutathione?

A: I am aware of the use of glutathione, but I do not prescribe it myself, so I do not have much clinical experience with which to discuss it.

Q: In your first webinar you say: we need criteria that are very sensitive. But one of the strongest criticisms of the IOM criteria is that they do not exclude psychiatric disorders. Was that danger anticipated when the IOM criteria were formulated?

A: There are some misconceptions about what ‘exclusions’ mean in the IOM criteria.

The IOM report encourages doctors to evaluate patients vigorously and continuously in order to discover and treat all other illnesses, including psychiatric disorders.

We simply decided not to include a list of exclusions in the diagnostic criteria.

That is another misconception. The IOM report does not propose a case definition, nor does it propose a case definition for research. 

It proposes 'diagnostic criteria'.

Those are the principal features of the illness that doctors should be able to recognise in their patients in order to make a diagnosis and treat the patient. The intention is for them to be used clinically.

Clinical practice teaches us that it is exceptional for a patient to turn out to have only one illness. Many ME/CFS patients have a number of additional conditions that contribute to their symptoms and disabilities.

The purpose of the report's diagnostic criteria is to encourage doctors to make the diagnosis of ME/CFS when M.E. is present, even when other conditions are also present. 

Q: ME/CFS has many associated illnesses. Do you generally find more than one comorbidity? And if you ‘peel away’ the comorbidities, is there anything left?

A: Exactly. In fact, this is how I make the diagnosis.

I ‘peel away’, or assess and treat, all the associated conditions, and if something terrible remains afterwards, it is usually ME/CFS.

I think it is easy to distinguish between a psychiatric diagnosis and ME/CFS.

Q: And can you describe that terrible thing? Is it the same in such cases?

A: In the terrible thing that remains, you see at least: severely reduced functioning, PEM, disturbed and unrefreshing sleep, cognitive impairments and orthostatic intolerance (the IOM core criteria), together with the possibility of many other symptoms.

Q: Now you say that it is easy to distinguish between a psychiatric diagnosis and ME/CFS. But that is precisely at the heart of the stigmatisation. So how do we get others to see that clear difference?

A: Anyone who seriously and thoroughly assesses patients can notice the difference. The clinicians in the US who know the difference best are psychologists!

Q: They can express the view in that sense that an ME/CFS patient has another illness, but generally they do not do that, do they? At least, they do not in Europe.

A: Yes, psychiatrists are best able to establish that, upon examination, their patient turns out to have more than a psychiatric problem.

Q: I think almost the entire American M.E. community would disagree with that.

A: I think the non-psychiatric providers make most of the mistakes. They are too quick to say that it is a psychiatric problem. Of course, that is not always true; I am generalising.

Q: That is at least everyday practice.

A: It actually does not matter if a psychologist feels that much more is going on, because they cannot refer patients to any doctor for further assessment anyway.

It is the shortage of doctors that creates the problem. Patients are sent from specialist to specialist until they really do become a little crazy!

Crazy = frustrated, anxious, depressed, humiliated, etc.

Q: What is a polyneuropathy?

A: Polyneuropathy is a term meaning that many different nerves are damaged.

As opposed to peripheral neuropathy (damage at the extremities) or mononeuropathy (a single nerve).

Q: How is it caused if it is viral? And how if it is autoimmune but not viral?

A: There are a number of causes.

A virus can damage the nerve, for example in shingles.

It is also possible for a number of factors to cause an autoimmune response that damages the nerve. That can be preceded by a virus, a physical injury, a bacterial infection, chemical damage, etc.

Any of these factors can damage the nerve directly, or indirectly by causing the autoimmune response.

Q: If one symptom or comorbidity in ME/CFS is treated, isn't there a danger that others will become severe? In severe ME/CFS, there seems to develop a kind of ‘illness-symptom balance’.

A: If a symptom or comorbidity is treated effectively, it should help.

There is always a chance that the treatment will cause more problems. One example is sleep medication that causes sedation or confusion.

It requires skill and experience to treat complex illnesses. And perhaps some luck.

I also regard input from patients as very important.

Q: Persistent viral infections, while the virus itself is gone, seem to be quite common in ME/CFS. Does treatment with antiviral drugs help in such cases?

A: Sometimes. For example, with (the whole family of) herpesviruses.

They are characterised by latent infection and a tendency to cause infection again under stressful circumstances or with ageing.

Treatment with antiviral drugs can, in this case, suppress reactivation of the virus. It requires 6-12 months or continuous treatment.

Fortunately, we have antiviral drugs that are active to some extent against some herpesviruses.

EBV is a herpesvirus, but it does not respond very well to the existing antiviral drugs, so it can be more difficult to control.

For example, there are no effective antiviral drugs for enteroviruses.

Q: Hopefully they will be developed. According to Byron [Hyde], they are major culprits.

A: And according to Dr. John Chia.