Juan Francisco Arenillas: “If there is no regulation of protected research time, there will be less and less research”

Dr. Juan Francisco Arenillas has been continuously devoted to field of vascular neurology since he trained in neurology as a fellow at Barcelona’s Vall d’Hebron Hospital Stroke Unit (1998-2005) under José Álvarez Sabín and Carlos Molina.

A vascular neurologist at the Stroke Unit, Germans Trias i Pujol University Hospital in Barcelona, in 2008, he moved to Valladolid University Hospital (HCUV) to become Director of the Stroke Programme. In 2013, he became head of the Department of Neurology, and in July 2015, Associate Professor of Neurology at the University of Valladolid, obtaining full professorship in October 2022. During this period, the HCUV has become a regional reference centre for stroke treatment.

Dr. Arenillas is currently responsible for developing the Castile and Leon regional stroke plan. Intracranial atherosclerosis has been one of his main areas of research since his doctorate in 2003, and he is particularly interested in biomarkers, inflammation, progression of the disease from its asymptomatic onset stage, and characterisation of high-risk plaques using HRMRI vessel wall imaging.

What is intracranial atherosclerosis?

It’s atherosclerosis that affects the intracranial arteries within the brain, which until recently represented a great unknown. A large part of my research activities focus on this disease.

Twenty years ago, there were many myths and deep-seated preconceived ideas about this disease, but today’s reality is otherwise. The key has been the methods we have to study it better. These are imaging methods that take us directly to the intracranial arteries. What was the problem? These arteries are hidden inside the head, and we don’t have access to them, as we did, for instance, with coronary or carotid arteries or ones in the leg.

Ultimately, the conclusion you reach is that atherosclerosis is a systemic disease, which affects the whole body, and although we tend to compartmentalise, it is really not so different from atherosclerosis in other parts of the body as we thought 25 years ago.

So, for both prevention and treatment, we are getting closer to what has proved effective for atherosclerosis in general.

Is stroke a preventable disease?

The difficult thing about preventing a stroke is that, unlike what happens with ischaemic heart disease, which in 90-95% of cases is generated by atherosclerosis of coronary arteries, in the case of stroke, that percentage is lower. We have cardioembolic stroke, small vessel stroke, and stroke from other causes like artery dissection, inflammatory diseases, vasculitis, etc.

Although all of these manifest as a stroke eventually, the differential diagnosis is more complex.

There is another peculiarity, however, which is that in most cases of patients with vascular risk factors, several causes co-exist; for instance, the same person may have heart disease and small and large vessel disease. And although this is not the cause, what does it mean that a person simultaneously has small vessel disease and intracranial atherosclerosis apart from atrial fibrillation?

We’re seeing that what this usually means is that they are people at higher risk, who respond worse to treatment and have a worse prognosis because they present a cocktail of diseases, not a single causal disease.

The same thing happens with the distinction between what is neurodegenerative or vascular. We insist on compartmentalising. We’ve discussed this a lot, and almost come to verbal blows about it!

In the end, it’s been seen that we mustn’t compartmentalise, we are speaking about a spectrum where a person may be closer to one end or the other, but really various problems coexist. Each person is unique and so is their disease.

Each person is unique and so is their disease

The fact that atherosclerosis exists in arteries implies a risk of its presence in intracranial vessels too…

That’s right. The truth is that intracranial arteries have peculiarities, and that the intracranial territory is more protected, which means that when atherosclerosis eventually develops in intracranial arteries many protective mechanisms have failed. Which means that these patients are per se very high risk, since under normal conditions the intracranial territory should not develop atherosclerosis until a very advanced age.

We also see the influence of metabolic syndrome, insulin resistance, factors that accelerate the process of atherosclerosis at intracranial level.

Genetic predisposition is also a factor: there is a documented predominance among people of Asian ancestry, for whom intracranial atherosclerosis is the most frequent cause of stroke, but also among people of African or Hispanic ancestry. And we do not know if this is because of genetic or environmental factors, or even dynamic factors due to the different morphology of the head and arteries.

It is also associated with worse control of risk factors, extreme poverty and environmental contamination.

And the neurodegenerative/vascular “war”…

We used to argue about this a lot more 15 years ago. It’s probably related with how research is organised, how we obtain funding for research. It’s all about reasons that are more mundane.

I can clearly see a continuum; there are probably some people with a purely neurodegenerative component, but there is usually an overlap, and in some cases that is very clear, to the point of not knowing if there is vascular dementia or an Alzheimer’s dementia, not only from a clinical perspective but also from the neuroimaging abnormalities we see.

I think that the more we observe, with a flexible attitude and acceptance of what arises, the better for our research and the better for our patients.

I studied medicine with an investigative vocation: I wanted to be a doctor in order to research

In recent years we have been warned that strokes occur at younger ages. What are the causes?

Now, it’s not unusual to have patients in the stroke unit between the ages of 40 and 50, whereas until recently the age was 60 or 65.

Although this is not new, I had observed it during my training period in Barcelona, and since my move to Valladolid to develop the stroke programme, we have seen the trend increase.

The causes? The causes are probably to do with lifestyle, diet, toxic habits and other factors I think are important, like stress management.

What we eat, how we move and how we manage stress —which is the difference between what we expect and what happens, the difference between expectations and reality—, how each person manages that, makes them more or less unwell. Specifically cardiovascular and cerebrovascular disease is very susceptible to stress.

And in recent years, a final factor that we are considering is contamination, which probably influences the acceleration of all vascular damage.

Studies undertaken in large metropolitan areas have found that, curiously, the incidence of stroke increases in areas more exposed to the exits of city bypasses. We have our lifestyles, but we are also taking risks with our health.

What we eat, how we move and how we manage stress —which is the difference between what we expect and what happens, the difference between expectations and reality—, how each person manages that, makes them more or less unwell

Physician and researcher…

From an early age, I knew that’s what I wanted to do. I studied medicine with an investigative vocation: I wanted to be a doctor to research. I think what I said when I was little was, “I want to cure cancer”. And when I started in medicine, I realised that what really fascinated me was the nervous system, the brain. I specialised in neurology with a great vocation for research, but then I started clinical practice and I realised how difficult it is to be both a clinician and a researcher. It’s very complicated, particularly in a system like the Spanish one where there is no protected research time —the concept doesn’t exist— and all research activity is at the cost of your leisure time, personal and family life.

Ultimately, that limits the goals you can achieve in research because, if patients take up your time every day, you don’t have the energy you need.

Although it is true that being in contact with patients makes you more sensitive to problems and you have more ideas, when it comes to developing them, you don’t have the capacity.

And I see that now even more with younger doctors. This generation has a lot of good things but also has a more utilitarian, practical attitude to life. And what we did, devoting our free time to research… I think that either we regulate the concept of protected research time or there will be less and less research. I’m not judging which is better or worse.

It’s important to acknowledge that the system needs to change and understand that clinical researchers must have protected research time, as happens in more developed countries in Europe and North America. That means that a person does their healthcare work within a limited time and the rest of their time is devoted to research projects, which also involve a lot of responsibility, managing public funding, etc.

In Germany, for instance, you have working conditions, and you are oriented to scientific production, which is what you are assessed on at university. In the United States and Canada, you negotiate the amount of protected research time. They understand that you can’t do everything at night or during the weekend, with your children, even though that’s what happens in the end. There should be a more solid network for research.

And if you don’t research, you don’t get projects.

That’s right. You have to find a way to carry on doing all of those things. One solution is collaboration and working in a network. There are times when there is no time available to write an article, but you have a team who can do it.

There are five of us on the stroke team at the hospital and four at the university.

My goal is to have some protected research time so I can continue investigating.

Juan Francisco Arenillas gave the seminar “Unraveling Intracranial Atherosclerosis” at the invitation of M. Ángeles Moro.