Interview with Milan Brázdil: Epilepsy and the Silent Epidemic of the Mind

Fifteen years ago, the World Health Organization warned that neurological diseases - from migraines to Alzheimer's disease - affect up to one billion of the world's population. Since then, our planet's population has increased by roughly the same number, and the average life expectancy has risen by two years. These facts, too, are mentioned in connection with the rise in neurodegenerative diseases, which, among other things, can be a trigger for epilepsy, which is one of the most common neurological disorders, not only in Europe. The International Epilepsy Day, a campaign launched by the International Bureau for Epilepsy and the International League Against Epilepsy, draws attention to its seriousness on the second Monday of February each year. The two awareness-raising organisations are also behind the joint Epilepsy Ambassador Award given for outstanding achievements in the field of epileptology. At the last award ceremony in 2021, Prof. Milan Brázdil, M.D., Ph.D., FRCP, received it as the fourth Czech. The head of the First Neurological Clinic of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University modestly waves his hand over the fact that he was recently included by Forbes magazine in the selection of the fifty best doctors and physicians in the Czech Republic. This year's thirty-year anniversary of the Centre for Epilepsy Brno, which he co-founded in 1993, last year's birth of the National Institute for Neurological Research or the aforementioned International Epilepsy Day have already been a slightly more compelling reason to commemorate the seriousness of neurological diseases...

13 Feb 2023 Václav Tesař

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Neurodegenerative diseases are sometimes referred to as the silent epidemic of recent years. How dramatic is such a claim?
For example, Alzheimer's disease currently affects around 55 million people worldwide, and this number will at least double by 2050; some estimates are as high as 139 million patients. The population is ageing, life expectancy is increasing dramatically and neurological diseases are becoming a global health priority. Their rise is so significant that all societies around the world will have problems with them.

Are you already seeing this rise in your clinic?
There isn't a diametrically higher number of neurological patients coming to our clinic than in the past, but if we talk about certain subpopulations such as patients with Alzheimer's disease, Parkinson's disease, or epilepsy, the increase is there. However, in our case, this is also related to the fact that our clinic has doctors who are highly specialised in these diseases, so patients naturally turn to us in large numbers.

I understand that neurodegenerative diseases are, by definition, diseases that are caused by certain wear and tear...
...that's what nobody knows yet! We know that in Alzheimer's dementia patients, certain pathological proteins accumulate in the tissue, causing nerve cell loss, i.e. neurodegeneration, but why these toxic proteins start to accumulate, we still don't know exactly.

So I mistakenly assumed that it happens as you get older?
The risk of that happening increases exponentially with age. But why, we don't know. For example, we are now finding that even in patients with temporal lobe epilepsy, the structure called the hippocampus, which is important for memory and where epileptic seizures begin, accumulates the pathological proteins mentioned above. And we don't know why.

Do you have any idea?
Recently, the so-called glymphatic system, which is a system that is supposed to remove all sorts of waste products from the spaces between neurons in the brain, has come to the fore in neurology. But if this system is damaged, it may be one of the causes of neurodegeneration. Interestingly, it was the Persian scholar Avicenna, who first coined the term 'epilepsy', who argued that the disease was caused by a disturbance in the flow of bodily fluids in the brain. This was a widely held hypothesis in its day, and although not entirely accurate, it is surprisingly close to the idea of a disrupted glymphatic system.

What is the impact on neurodegeneration of the 'age we live in', so to speak, a fast-paced, stress-filled, information-overload age? Personally, for example, I am very curious to see the first studies on the impact of social networks on the brain development of a generation that has been exposed to them since childhood...
That's a good question, but nobody really knows the exact answer yet. Maybe for the reason you mention, which is that social networks have not been with us that long. But otherwise, there's no doubt that stress affects the brain. We know that it can indeed lead to changes in memory structures, for example, in the hippocampus, which has already been mentioned, because in this case it is one of the parts of the brain where the formation of new nerve cells takes place throughout life.

“Today we know that the formation of nerve cells is lifelong. And in order to form and engage properly, they need to have a little rest. Stress can have a detrimental effect on neurogenesis.”

prof. MUDr. Milan Brázdil, Ph.D., FRCP

Isn't it true, as it used to be said, that a person is born with a certain amount of nerve cells and then they just die?
Today we know that this is not the case. There are two places in the brain where nerve cells are produced throughout life. We also know that they need to have a bit of a rest to form and engage properly. But they don't have that calm in times of stress, which can have a detrimental effect on this so-called neurogenesis. The second thing is the extent to which stress can also contribute to neuronal death. It is likely that it plays a role, but exactly how much is unknown.

But in general, we can say that the formation of new nerve cells can be positively influenced by lifestyle, am I right?
Exactly. In the case of neurodegenerative diseases, it is known that something like cognitive training, physical activity, sport and a healthy lifestyle can lead to their prevention.

If there are more and more patients with neurodegenerative diseases in the population, especially due to the ageing of the population, does this mean that despite all the progress, medicine is not responding to this trend?
It could be said that it is. Throughout the twentieth century, cancer and cardiovascular diseases have been at the forefront of interest. You could say that biology has focused primarily on genetics. And it was logical. It is only in the twenty-first century that biology's interest in neuroscience, in the biology of the mind, has increased significantly. And since we've neglected this area a little bit, we're surprised now.

Yet, many diseases, including some cancers, can now be successfully treated. But we hear everywhere how crucial prevention and early diagnosis are. Is there any way I can tell that I'm at risk for epilepsy?
If you think of a seizure, you won't be able to tell that it is somehow "in the making". But there are, of course, risk situations such as head injury where, if it is more severe, the risk of a seizure increases. It should be said, however, that while any pathology that happens in the central system in the brain can manifest itself in epileptic seizures, not all patients with epileptic seizures need to have structural brain damage. Thus, prevention of epilepsy is more about prevention of brain damage. And yes, once we have a patient with brain damage, we can estimate how much risk they are at for an epileptic seizure.

Management of First Neurological Department of St. Anne's University Hospital

Recently, there has been a lot of talk about the digitalisation of healthcare. How does it manifest itself within your field?
For us, it has manifested itself mainly in the form of telemedicine, where we experienced during covid that patients could not always come for a check-up and so we started using various video conferencing tools to stay in touch with them. The second thing related to digitalisation is patient and disease-specific registries, which are also supported at European level. Our Epilepsy Centre is part of the EpiCARE European Reference Network for Rare and Complex Diseases, where these registries are already in place and allow us to have better information on specific diseases.

But epilepsy is not such a rare disease, is it?
You are right, according to epidemiological studies, we know that it affects almost one percent of the population, about 50 million people worldwide. The interesting part is that epilepsy is not a single disease. There are different epilepsy syndromes, different types of epilepsy, whether they are congenital, whether they are after brain damage, after inflammation, after a brain haemorrhage, or whether they exist within a cancer. But even with this distinction, digitisation and registries can help.

Do you also work in epileptology with artificial intelligence, which is also becoming more and more popular in healthcare?
Yes, especially in the diagnosis and prediction of the effect of certain drugs or surgical procedures. For example, we are also conducting our own research, where we are using artificial intelligence and machine learning to process EEG signals and try to locate the part of the brain that is the site of the onset of epilepsy, which must be precisely defined in the surgical treatment so that we can safely and successfully remove it.

Which of these types of epilepsy is prevalent in the population? Are they the congenital ones?
They are the minority! The genetics of epilepsies is a big topic in epileptology at the moment. The number of known genes and mutations that underlie genetic epilepsies is constantly expanding, so that many of them can already be well diagnosed. Most of the time this is already in childhood, but even adult patients are often found to have genetic epilepsy. In the past, the cause of epilepsy was often sought in a complicated birth, in which case perinatal encephalopathy was cited as the cause. But then if you ask how the patient's birth went, you find that in many of them there was no pathology and the cause of the epilepsy is sometimes only revealed by genetic testing. However, in general, epilepsy is not a hereditary disease.

The year before last, you were honoured by two epileptology organisations as an Epilepsy Ambassador. How is Czech epileptology perceived abroad?
Well. Epileptology has a long tradition in the Czech Republic and there is quite a lot of interest in it even among young doctors in our country. I'm not surprised, because it is the most interesting part of medicine, of course. (smiles) Both in terms of the organisation of care, which has long been one of the priorities of the Czech League Against Epilepsy, and in terms of the availability of various therapeutic options (from drugs to different types of interventions), but also in terms of research, we are perceived very positively in the world.

“There are already attempts to continuously sense the brain's electrical activity with electrodes placed under the scalp and connected to a smartwatch, which could then theoretically signal an impending epileptic seizure.”

prof. MUDr. Milan Brázdil, Ph.D., FRCP

When you mention young doctors, how do you evaluate the cooperation with the Faculty of Medicine of Masaryk University? In an earlier interview, you expressed the general opinion that not enough space is given to communication in the field of clinical medicine, i.e. to the human factor. Has the situation improved in this respect?
Of course, I cannot judge how teaching is done in other clinics, but in our clinic, thanks to the expansion of neurology teaching from two weeks to three, we have more space for medics to spend more time among patients and learn by example from teachers and other doctors. So yes, I think the situation is improving. The crucial thing is that the lecturer themselves is passionate about the subject because then it is contagious. At the point where he himself would not be interested in neurology, then he would have a hard time convincing students that it is a very interesting field.

You obviously enjoy epileptology immensely. But at the same time, you once said that you are not exactly a prime example of what a medical career should look like. You've spent practically your entire life here at St. Anne's. Why is that?
I've had the advantage of a number of international placements, so it's not as if I haven't experienced any other workplaces. But yes, I've been here a long time. You have to be happy in a place, which I've always been. And maybe I'm even a little lazy to move somewhere. (laughs)

This year marks thirty years since the Centre for Epilepsy Brno was founded. What did the patient who came to the centre ninety-three years ago expect and what does his visit look like today?
What makes the difference is the availability of therapeutic options. Thirty years ago, there were, say, ten fewer epilepsy drugs than today, and the surgical treatment programme did not work at all. This only started in the ninety-fifth year, which I think was a very crucial moment for patients and for the centre. Unfortunately, for about a third of the patients, even if they follow all the regimes and take their medication honestly, we never achieve the disappearance of seizures, which is our goal. In such patients, the only option is to locate the site in the brain where the seizures originate and, if possible, remove it. But it is not always possible to locate the site. Some patients have more than one such lesion, or they are located in a place that cannot be removed with impunity, as it is important for speech or movement, for example. For these patients, we use the so-called neurostimulation method of treatment, which is vagal stimulation or vagus nerve stimulation, and if that does not help, deep brain stimulation of the anterior thalamic nuclei.

Neurological examination

What are some of the newest ever methods of taming epilepsy?
For example, in vagal stimulation, the older systems used to set the intervals at which it should take place - for example, half a minute of stimulation, then a minute without stimulation, and so on and so forth. Newer stimulators sewn into a subcutaneous pocket just outside the heart can register heart activity, and since we know that a significant proportion of patients experience an increase in heart rate at the onset of an epileptic seizure, the stimulator can sophisticatedly assess any change in heart rate and trigger extra stimulation outside the set mode. Something similar is already emerging in deep brain stimulation, where some systems register EEG from the brain and also trigger stimulation in this way "on demand".

How distant is the future when such systems will be so advanced that patients will be able to use them and carry them around, for example, in the form of a smartwatch?
There are already efforts to continuously sense just the electrical activity of the brain with electrodes placed under the scalp and linked to a smartwatch, which could then theoretically signal an impending seizure. So it's not that far in the future, although it doesn't quite work yet.

The National Institute for Neurological Research, of which you are the principal investigator, was set up last year as part of the National Recovery Plan. Eleven institutions in total are participating. What exactly is its purpose?
The aim is to create a national authority that would be a partner for ministries, for example, and would be involved in setting and promoting national policy and strategy for the future of excellent neuroscience research. For example, what research to support in national grant policy has often been determined by someone from the green table, someone without a strong mandate, and may have been disconnected from neuroscience research and practice. So the birth of such a national authority seems to me logical and appropriate. The purpose of the National Institute is to strengthen the efforts of the best teams in the country involved in neurological research, to link them together and to make their work more efficient, which may ultimately lead to significant savings in their resources.

What is the current agenda of the institute?
The Institute has three main pillars on which we focus our research. The first is neurodegeneration and cognitive disorders, particularly Alzheimer's disease; the second is neurodegeneration and movement disorders, such as Parkinson's disease; and the third is neurodegeneration and neurodevelopmental diseases. Because neurodegeneration seems to play a significant role in a number of diseases other than 'Alzheimer's' or 'Parkinson's', including, for example, multiple sclerosis. Within each of these pillars there are six work packages, and within these, in turn, several research groups. In total, there are about two hundred and fifty researchers whose publications are now being collected after six months of the Institute's existence. During February we should have a joint meeting of the research teams in Prague, and in mid-June we would like to organize the annual conference of the National Institute for Neurological Research in Brno, where we should present the best and most interesting things we are working on.

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