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Interview with Dr. Diego Borreguero Director of the Sleep Research Institute, Spain

February 22, 2018

Dr. Diego Borregero_capa 2

“ In the broad field of movement disorders during sleep, the most frequent of all of them, the most important in terms of the consequences for health, is the restless legs syndrome…”

I am a neurologist, psychiatrist, and sleep specialist. I started working in the latter when I finished my doctorate studies and specialization at the Max-Planck Institute in Munich (Germany) and I then completed a sub-specialty in sleep medicine in the United States where for five years I was working at the National Institutes of Health of Bethesda and at Georgetown University. I then came back to Spain, where I directed the Sleep Unit of Fundación Jiménez Díaz for ten years. And then, since 2005, I created the Instituto de Investigaciones del Sueño. My investigation field is focused on movement disorders during sleep, a field in which we are leaders among the most recognized centers in the world. From the care standpoint, we are the main private sleep center of Spain. We conduct more than two thousand polysomnographies every year and we have a broad base of patients within the private sector in Madrid.

NN: Your career, both in the academic and in the professional fields, includes important experiences in several countries, in Europe, North America and Asia, countries in which you have participated in events and conferences. What´s your opinion on the progress of sleep medicine studies worldwide? Is there a more outstanding country in this area?

There is a certain dispute over the place where sleep medicine began. Europeans think of themselves as the innovators. The United States also think of themselves as the first in sleep medicine. They both tell the story as if from inception. In actuality, it probably started in many places at the same time. The point is that sleep medicine went from being something in which only scholars – that is, people only interested in research – were interested in. Sleep medicine experienced an important shift towards the end of the ‘70s. The concept of sleep medicine centers as institutions that initially were exclusively devoted to treating respiratory disorders during sleep was developed for mainly sleep apnea.

However, with time in sleep research, more attention was devoted to the fact that there was a variety of pathologies which could have overall repercussions on health. REM sleep behavior disorder was discovered towards the end of the ‘80s, and after that it has been discovered that this condition is an early marker for the likeliness to suffer from Parkinson´s Disease, which is a neurological disorder which 1% of the population suffers from. I am talking about REM sleep behavior disorder, a condition which had not been discovered up until the mid-‘80s. I am giving this as an example of how there is still a lot to be discovered in sleep medicine. There are still entire conditions to be discovered, researched, and cared for, that require treatment.

Concerning the most outstanding country, the country that sets the norm for the rest of the world is the United States. This is something that depends on the amount of resources devoted to this, and on the amount of resources devoted to research. In Europe, there are great developments in sleep medicine, particularly in Germany, and not far from this country, France, Spain, and Italy. But sleep medicine is in constant progress all over Western Europe.

NN: Movement disorders are one of the main references during sleep. What are the most common disorders patients are suffering from? Are there significant differences among continents?

Clearly, within the broad field of movement disorders during sleep, the most frequent among them – epidemiologically speaking, the most important one in terms of the consequences for health, is the restless legs syndrome (RLS). Yes, there are various differences among the continents, but these depend on ethnic characteristics.

Among the white population, restless legs syndrome can be seen in up to 5% to 7% of adults. In other regions of Europe, it may be seen in up to 3% of adults, which is a high figure. However, in non-white populations, frequency clearly decreases. We know that the prevalence of this condition in Japan is between 1% and 4% of the population. There are more studies stating that it is more toward the 1% figure han toward the 4% one, and in black people the restless legs syndrome is not as frequent. This means there is certainly an ethnic racial element linked to the presence or absence of certain genes which are risks of polymorphism that increase the chance of this condition being present.

NN: Specifically, regarding the restless legs syndrome, a topic in which you have specialized, when does a patient need to go see a doctor, and how is a diagnosis reached?

oday, diagnosis is clinical. This is something that has been decided should be treated in this way. There are of course great doubts on whether diagnosis is enough, but the consensus is that the diagnosis must be conducted clinically, and that sleep laboratory testing should only be used when there are doubts in the diagnostics. This is likely to change in the future. Based on what I just said, patients are advised to seek medical assistance whenever this condition alters night sleep or their quality of life. This should never prevent them from going on trips, or to the theater, et cetera – that is, to be in situations of relaxed wakefulness – but this is purely a clinical criterion. All of this is likely to change as we have more and more information telling us that the restless legs syndrome is a cardiovascular risk. There are various prospective studies investigating this matter more fully, but it is perfectly possible that in the future, when this relation has been established sufficiently, we place the consultation point with the doctor in a different place. This means that it is possible that from a certain number of periodical leg movements during sleep or during wakefulness we have biological markers to signal the level of seriousness of the disease in a more appropriate way than purely clinical criteria. When we reach that point, we stop worrying so much about the clinical aspect and start being more interested in these types of biological markers as the starting point for defining treatment.

NN: Which are the most recent studies, and how have treatments against the restless legs syndrome evolved in the latest years?

The restless legs syndrome currently has various important investigation lines. One of them related to its cause, the connection between brain iron and the appearance of the disease itself, is reaching an important development and is in fact opening a way to one of the most effective forms of treatment in the last years, this being administering iron intravenously as a direct way to fill those brain deposits which are depressed. On the other hand, there is a whole line of genetic research being done. An article stating there are up to 19 risk polymorphisms has been recently published. We are talking about genes, which, depending on the variants of those genes in the genotype, will determine whether we are at a higher or lower risk of developing the condition. The function of these genes is barely known; generally speaking, however, we see some of them are involved in the embryonic development of the central nervous system. The third line is related to what causes the disease. As to this issue, we are working jointly with a center in the United States, the National Institutes of Health in Bethesda, on the physiopathology, which was mainly centered on dopamine. Dopamine are the mechanisms related to adenosine as a regulator, which in the end produces an increase in the functioning of the glutamatergic system and an increase in the dopaminergic system. This opens a new vision to the condition´s physiopathology and it is mostly giving way to the first treatment options that are not at all related to glutamic acid or dopamine.

 NN: In a world that works 24/7, there are many people working at night and who can only sleep during the day. Is this habit harmful? What would you recommend to them?

The biggest problem, as far as we are currently concerned, is that sleeping during the day is not really harmful as long as it is done under environmental conditions of noise, light, and the lack of interruptions similar to the ones at night. However, what is more and more frequent in modern society is working in shifts. That is, we sleep during the day some days; we sleep during the night some other days. This variation in schedules is the most novel characteristic. The human body is trained to change the circadian cycles for us to adapt to a life rhythm in which we sleep during the day and work at night, but always in a constant manner. The problem is, this rarely happens. This variation in the circadian cycle of sleeping three days in the morning, three days in the afternoon, three days at night, is something our nervous system has not been trained for, and in the long term, this produces an increase in morbidity, at least cardiovascular morbidity. This may be the biggest issue. Research at the moment is somehow directed at seeking new ways of using light therapy to influence those circadian rhythms while the patient is doing other activities. This can even occur when the patient is asleep, so other light frequencies are being researched. Frequencies that can even be used with workers of night shifts.

NN: How did you know about Neurovirtual?

I knew this brand through Dr. Thomas Penzel, who is a friend and colleague and prominent doctor in sleep medicine in Germany. He put me in touch with this brand and with the company´s staff. At that moment, I needed to buy a new device. We currently have three devices from Neurovirtual. We were the first ones in Spain to acquire them. Basically two things caught my attention. The software is tremendously easy to use. It´s flexible and robust. This characteristic I defined in three terms: It´s tremendously easy to use, flexible, and solid. The second element which is essential to me is technical support. Any brand can offer excellent products, but if tech support is not efficient enough, we are going to have problems sooner or later. Neurovirtual is different. They offer 24- hour service in Spanish and English, a great advantage for the staff in my laboratory. We even take advantage of the time difference between Spain and America, because it allows us to have support during the hours in which sleep studies are being conducted in Spain. Staff there assists patients in the evening. Neurovirtual´s tech support is probably the best I have ever seen. It is the fastest. They work sending parts and giving solutions online, almost to the minute, and we have seen that ourselves from the time we have been working with them. The Instituto del Sueño currently has plans for expansion. We are going to start activities in a new center in Santiago de Chile and Panama City. We count on Neurovirtual for all these centers. They will be our brand of reference.

NN: Would you recommend Neurovirtual products to your colleagues in neurology and sleep medicine?

Clearly, the best recommendation I can give now is the one I just gave to you. All the expansion our center is going to have throughout 2018 is going to be done with Neurovirtual. The experience we have had in 2017 has convinced us enough to make them our brand of reference from now on.

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