President of the European Stroke Organisation (ESO) Bart van der Worp emphasises the need for additional treatment options for patients with acute ischaemic stroke, next to reperfusion strategies. Still hoping that these options could come from the field of neuroprotection, he tells NeuroNews about the important trial results he is awaiting this year, as well as his plans for the future of the society and his interests outside of medicine.
What drew you to neurology and stroke therapy in particular?
Alongside a long-standing interest in the functioning of the brain, two professors of neurology at my university had excellent teaching skills and convincingly conveyed the importance of carefully taking the patient’s history and performing a detailed but focused neurological examination. Professor Jan van Gijn, who was also a renowned clinical investigator in the field of stroke, served as a role model to me; later convincing me to choose neurology early in the 1990’s. I had a strong interest in the pathophysiology of ischaemic stroke and was impressed by the impact of stroke on the lives of the patients and their families, and by the lack of treatment options at that time. I decided to commit myself to improving treatment options, which proved to be more difficult than I expected when I was young.
Did anyone else influence your career?
In addition to Jan van Gijn, I quietly admired frontrunners in the field of experimental stroke, including Bo Siesjö and Uli Dirnagl, as well as Werner Hacke, who specialised in acute stroke treatment. They (and others) managed to persuade the medical field that stroke could be a treatable condition.
You have been practising for a number of years. How have you seen the field of neurology change and develop over that time?
It will come as no surprise that I am extremely happy with major therapeutic developments in the past 20 years, not only in the field of stroke, but also for multiple sclerosis, for example. These really have a great impact on the lives of many patients with diseases that often had a very poor prognosis at the time I started working in neurology.
You are a member of CAMARADES. Why has this group been established and what does it set out to achieve?
CAMARADES has been founded because of the observed huge and unacceptable failure of most animal experiments to translate to the clinic. CAMARADES has identified sources of bias in animal work; developed recommendations for improvements in the design and reporting of animal studies, and improved meta-analysis methodology to be able to apply this better to animal studies. We hope this will lead to more methodological rigour in animal experiments, fewer animals that are “wasted”, and ultimately a better translation of animal experiments to the clinic.
What has been the biggest disappointment? I.e., something that you thought would be practice-changing but was not?
In the 1990s, neuroprotection for patients with acute stroke was really hot—based on new insights in the pathophysiology of stroke and the positive results of thousands of animal studies. I was among many who strongly believed that this was the way forward. Unfortunately, the very large majority of findings in animal studies could not be reproduced in clinical trials, and only reperfusion therapies have convincingly shown to improve outcomes in selected patients with acute ischaemic stroke. Furthermore, only a minority of the patients with acute stroke are eligible for intravenous thrombolysis or endovascular treatment, and the risk of a poor outcome is still considerable even when treated. Additional treatment options are therefore strongly needed.
My biggest disappointment so far is the lack of evidence of benefit for hypothermia in patients with acute stroke. Hypothermia (or cooling) has an unchallenged benefit in animal models of acute ischaemic stroke, and has therefore been coined as the “gold standard” for neuroprotection. Unfortunately, results of animal studies have not yet been replicated in clinical trials despite major efforts, including one American and one European phase III clinical trial. These trials seriously failed to recruit to target and at least the European trial was severely hampered by regulatory hurdles and practical problems to achieve a modest temperature reduction in patients. I hope that the ongoing PRECIOUS trial, which assesses the effect of the prevention of infections and fever with simple, safe, and inexpensive drugs, will show that even a modest temperature reduction can be of benefit in patients with acute stroke.
What are your current research interests?
I still have not left the field of neuroprotection, and next to exploring the effects of temperature reduction in PRECIOUS, I co-lead the MR ASAP trial, which assesses whether glyceryl trinitrate started within three hours of stroke onset will preserve brain tissue better before reperfusion therapies (IVT or EVT) are started. I also co-chair the phase II secondary prevention trial APACHE-AF, which assesses the optimal antithrombotic strategy in patients with atrial fibrillation who had an intracerebral haemorrhage during treatment with an anticoagulant. Finally, I carry out research in the field of end-of-life decisions and palliative care.
What are the most important trial results that you are awaiting in the near-future?
One of several large stroke trials that will be presented at ESOC 2019 is RESTART, a randomised trial for adults surviving spontaneous intracerebral haemorrhage who had taken an antithrombotic drug before the haemorrhage. This trial has tested whether a policy of starting antiplatelet drugs results in a net reduction of all serious vascular events during follow-up, compared with a policy of avoiding antiplatelet drugs. The results of this trial will hopefully inform difficult decisions in these patients in daily clinical practice.
As president of the ESO since 2018, what have you achieved, and what are your hopes for the future?
The work in ESO is obviously performed in collaboration with colleagues from all over Europe and even from elsewhere. The organisation has grown considerably over the past five years, in part thanks to the start of our own conference (ESOC) in 2015. The conference has become a huge success, with the presentation of results of ground-breaking trials in the field of stroke, and numbers of participants increasing each year (4,500 in 2018). In addition, ESO now has its own successful journal, which will hopefully be indexed in PubMed shortly, and an increasing number of guidelines, among many other activities. My primary aim is to consolidate these successes and to make these even greater where possible. However, we are also working on getting stroke higher on the political agenda in Europe; implementing the recently published Stroke Action Plan for Europe in all European countries, and on making the society “greener”.
What are the highlights of the 2019 annual meeting?
To be honest, highlights are difficult to select because of the wealth of research data from all over the world that will be presented, alongside high-quality state-of-the-art lectures by renowned experts. However, many people may consider the presentation of the results of at least seven major stroke trials among the highlights.
What is your key message to young neurologists?
For their own careers: follow your passion, and believe that everything is possible until the opposite is proven. For patient care: the truth is at the bedside!
What are your interests and hobbies outside of medicine?
I love good food and do my best to improve my own cooking skills through membership of a cooking club, but my main hobby since a left the city for a house in a village a few years ago is gardening. This might also be my greatest talent, so perhaps I took the wrong turn many years ago…