Urs Fischer is a clinical researcher with a particular interest in the diagnosis, management, treatment, and outcome of patients with acute neurological diseases, especially of patients with acute ischaemic and haemorrhagic stroke. He is participating in multiple preventive, diagnostic and acute treatment trials and stroke registries. Here, he speaks to NeuroNews about his current research, his wish list in terms of the development of stroke therapy and his interests outside of medicine.
What drew you to neurology and stroke therapy in particular?
When I was in high school, I found it challenging to focus on a specific area or field because my interests were just too broad—I studied languages, I loved science and the arts, I played the cello in various orchestras and chamber music ensembles, among other things. Medical school was, therefore, the perfect choice for an indecisive person like me, since I could postpone the dilemma of whether I should study science or the arts. In my second year at medical school, I began to attend lectures in neuroanatomy and I immediately knew that neuroscience was a sphere about which I wanted to discover much more. Neuroscience—the interface between science and the arts—was the ideal field to combine my interests.
I wrote my medical doctoral thesis on neurophysiology and I realised that I wanted to work in a therapeutic rather than in a diagnostic domain of neurology. I then had the good fortune to meet Prof Heinrich Mattle, chair of the Stroke Center Bern (Switzerland), and a pioneer in endovascular stroke therapy. He offered me a position in his research group. This was in the early 2000s when endovascular stroke therapy was still in its experimental stages and evidence from randomised trials was lacking. We prospectively analysed clinical and imaging predictors of outcome in stroke patients treated with endovascular procedures and we saw a tremendous impact of recanalisation on the outcome—a finding that was later confirmed by the randomised trials after 2014.
Who were your mentors and what impact have they had on your career?
I was luckily supported by several mentors. Prof Heinrich Mattle was probably the most influential person in my professional career. Together with his research partners and team (Prof Gerhard Schroth, Prof Marcel Arnold and many others), he taught me to pursue a research idea and to focus on relevant scientific questions. During my research fellowship at the Stroke Prevention Research Unit at the University of Oxford, I had the privilege to be supported by Prof Peter Rothwell, one of the leading scientists in the field of stroke. He taught me the basic skills in epidemiology and statistics and he was a great mentor. He always tried to find the most relevant factor in stroke prevention with the biggest impact on outcome. Further important mentors were—and still are—Prof Valeria Caso, past president of the European Stroke Organisation (ESO), and Prof Claudio Bassetti, chair of the Department of Neurology at the University Hospital in Bern.
You have been practising for a number of years. How have you seen the field of neurology change and develop over that time?
Neurology has changed dramatically since I was in medical school: traditionally neurology was a diagnostic rather than a therapeutic domain. Today, many neurological diseases can be prevented and treated, and neurologists are working in emergency departments, on intensive care units, in acute neurological wards etc. The image of neurology has completely changed, and I strongly believe that neuroscience has become the “royal discipline” in medicine. However, there are more challenges than ever with the ageing populations. Many diseases, especially neurodegenerative ones cannot be prevented and treated yet.
In your opinion, what has been the most practice-changing advance in terms of treatment options and devices?
The changes in neurology are tremendous; however, the biggest breakthrough was in acute stroke management, especially endovascular stroke therapy with stent retrievers. There is almost no other intervention in the history of medicine with such a big effect. You have to treat only two patients with acute stroke due to a large vessel occlusion to prevent one major disabling or fatal event. Further practice-changing advances were treatment of stroke patients on dedicated units (i.e. stroke units), urgent investigation and treatment of patients with transient ischaemic attacks (TIAs) and minor strokes (i.e. TIA clinics), as well as carotid endarterectomy and stenting.
There have also been other major breakthroughs in neuroscience such as all the new treatment options for patients with multiple sclerosis, migraine, medical and surgical treatment of epilepsy, and deep brain stimulation in Parkinson’s disease to name but a few.
What has been the biggest disappointment—i.e. something that you thought would be practice-changing but was not?
In 2018, we still have no evidence-based treatment option for patients with intracerebral haemorrhage, a terrible condition that affects 15–20% of our stroke patients and is associated with high morbidity and mortality. The outcomes of previous trials such as FAST, STICH I and II, INTERACT, TICH II, etc. were all negative and the major breakthrough in prevention and management of intracerebral haemorrhage is not yet in sight. Our pathophysiological understanding of the manifold causes of intracerebral haemorrhage and their prevention is still insufficient. Therefore, prevention and treatment of intracerebral haemorrhage should become one of the main priorities for stroke research over the coming years. And there are many other disappointments: e.g. all the dementia trials to remove cerebral amyloid in Alzheimer’s patients failed and we still have no treatment option for other neurodegenerative diseases.
What is on your wish list in terms of the future development of stroke therapy?
My wish list is long, but before starting to develop new things, we should focus on the implementation of the current effective therapies in clinical practice. The top three priorities on my wish list are implementation, individualised treatment solutions and prevention of secondary brain damage.
Implementation: We have highly effective treatments for stroke patients with a very low number needed to treat, but, in many parts of the world, these treatments are still not available. This is why we have established the ESO ESMINT ESNR Stroke Winter School (www.strokewinterschool.ch) in order to train young physicians. We hope that, following the training, these young colleagues will implement acute stroke treatment strategies in their own hospitals. In 2019, we will organise the first Stroke Winter School in Asia.
Individualised treatment approaches: Randomised trials have shown the efficacy of interventions in well-defined populations. However, we are treating individuals. Further efforts should be made to establish more evidence for personalised treatment. As a clinician, I would like to be able to identify the patients who are most likely to benefit from a specific intervention, especially if the number needed to treat for that intervention is high and the number needed to harm is relevant. For instance, we should know, whether all patients with large vessel occlusion should be pretreated with intravenous thrombolysis prior to mechanical thrombectomy, or whether there is a subgroup (e.g. patients with carotid artery occlusion) which should better be treated with direct mechanical thrombectomy, given the low chances of recanalisation after thrombolysis and the relevant risk of bleeding complications. This is only one of many examples where we need more evidence, whether the same treatment strategy applies for all patients, or just for a certain subgroup. Population-based studies, randomised trials within cohorts, tailored randomised trials with stricter inclusion criteria and, eventually, advances in precision medicine should hopefully help to guide decisions on personalised treatment in the near future.
Prevention of secondary brain damage: Even though recanalisation rates in previous trials were very high, only about 50% of patients have regained their independence after three months and we now have to establish strategies to prevent secondary brain damage after the first hit. The ESCAPE NA1 trial is currently pursuing this aim and I am very keen to know whether this and other neuroprotection strategies will help us to further improve the outcome in addition to recanalisation strategies.
Finally yet importantly, many more efforts should be done to prevent strokes: it is much more (cost-) effective to prevent a stroke than to try to treat a stroke!
You are publishing a survey on stroke in Europe. What were the key findings?
Reliable data on access to and delivery of acute stroke treatment strategies (i.e. stroke unit treatment, intravenous thrombolysis [IVT] and endovascular stroke therapy[EVT]) throughout Europe are lacking. We therefore surveyed stroke experts from 44 of 51 European countries on rates of acute stroke unit care, IVT and EVT. We found major inequalities in acute stroke treatment, with many countries reporting rates that were far below the highest country rates. Another survey is currently underway assessing provision of secondary prevention services throughout Europe.
Were there any findings that were surprising or unexpected?
Even though I expected these inequalities, the numbers are alarming: more than 226,662 stroke patients in Europe could have been treated with IVT (339,929 instead of 113,267) and 67,347 with EVT (94,852 instead of 27,505), if best practice had been followed in all countries. Although these are still rather conservative estimates, this means that two-thirds of patients who would potentially be eligible for IVT and three-quarters of candidates for EVT did not receive adequate treatments in Europe. Globally these numbers could even be worse, but reliable data are lacking.
As part of the group who produced the Action Plan for Stroke in Europe 2018–2030, what effect do you hope the action plan will have?
The findings of our survey highlight the importance of the implementation of the current treatment options in clinical practice throughout Europe. The ESO, together with the patient organisation SAFE (Stroke Alliance for Europe) has therefore prepared a European Stroke Action Plan (www.eso-stroke.org/action-plan-stroke-europe-2018-2030-2) which has four overarching targets, namely:
– To reduce the absolute number of strokes in Europe by 10%
– To treat 90% or more of all patients with stroke in Europe in a dedicated stroke unit
– To have national plans for stroke encompassing the entire chain of care from primary prevention to life after stroke
– To fully implement national strategies for multisector public health interventions to promote and facilitate a healthy lifestyle, and reduce environmental, socioeconomic and educational factors that increase the risk of stroke.
What are your other current research interests?
I am passionate about all aspects of acute stroke management and the overarching “leitmotiv” of my research interests are the “unanswered questions” in acute stroke care, which I would like to answer with case–control studies and randomised controlled trials. Together with Prof Jan Gralla, chair of the Department of Neuroradiology, we are performing the SWIFT DIRECT trial (www.swift-direct.ch), addressing the impact of intravenous thrombolysis before thrombectomy in patients with large vessel occlusion. Furthermore, together with my colleagues from neurosurgery, we are currently analysing with the SWITCH trial, whether decompressive craniectomy improves the outcome in patients with intracerebral haemorrhage (www.switch-trial.ch). The ELAN trial addresses the question of when oral anticoagulation with novel oral anticoagulants can be restarted in ischaemic stroke patients with atrial fibrillation (www.elan-trial.ch). Lastly, we have started the EUROPEAN STROKE PROJECT, a prospective study to assess the status of stroke prevention and treatment within Europe.
What advice do you hope your mentees and students will always follow?
Good mentors feel responsible for the success of their mentees and empower them to develop their own strengths, beliefs and skills. I am very grateful for all the support I have received. Now that I am trying to become a good mentor myself, I realise how difficult a task this is. Apart from qualities such as knowledge, expertise and skills, you need a lot of time—time to analyse, time to listen, time to discuss, time to write and time to build trust, for example. I really hope that my students will focus their research projects on unanswered questions with a major impact on the outcome for our patients. I learned from Prof Peter Rothwell “Do the simple things first and right”, and I hope that my students and mentees will follow this advice as well.
What are your interests and hobbies outside of medicine?
Music has always been an important part of my life and I have been playing in the quartet “mit vier” for many years now. This offers a unique opportunity for me to dive into a completely different world and to meet people from outside the circle of medicine. And—most importantly—I love to spend as much time as possible with my family. Swimming in the river Aare in Bern in summer is a major highlight, which I try to do regularly with my wife and daughters after work! My kids love skiing with me and I go running on a regular basis. Spending time with friends is also very important. However, finding the right balance between family, friends, clinical and academic work is probably the biggest challenge.
