bleeding from expanding. In some cases, haemostatic drugs or surgery may also be useful. Recurrent strokes are best prevented by lifestyle changes along with control of high blood pressure, blood lipids, diabetes and smoking. Targeted interventions depend on the individual causes of the stroke. Possible interventions include blood-thinning medications, inhibiting blood clotting in atrial fibrillation, surgically restoring the patency of the carotid artery or inserting stents, and surgically closing an opening between the atria.. History The first description of a stroke by HIPPOCRATES over 2,400 years ago resembles today’s clinical description remarkably well. HIPPOCRATES described a sudden loss of speech, sensation, and power as if the person was “struck down by violence”. However, the biological cause of this dramatic and sudden loss of physical and mental function remained unknown for almost 2000 years. The term “stroke” was coined in the late 17th century by the physician William COLE. Around the same time, the anatomists Jacob WEPFER and Thomas WILLIS recognised that the occurrence of symptoms was related to a disturbed blood supply to the brain. In some stroke patients, they found an occlusion of large blood vessels supplying the brain, in others they observed bleeding into brain tissue. In 19th century Berlin, the pathologist Rudolf VIRCHOW distinguished between ischaemic stroke (Greek: ἴσχειν/ Emmrich, J. V., Knauss, S., Endres, M., Current advances, challenges, and opportunities in stroke research, management, and care NAL-live 2021.2, v1.0, doi:10.34714/leopoldina_NAL-live_0002_01000 2 is-chein ‘restrain’ + αἷμα/haima ‘blood’), which is caused by the occlusion of a blood vessel, and haemorrhagic stroke caused by blood vessel rupture and bleeding into the brain tissue (Greek: αἷμα/haima ‘blood’ + ῥῆξις/rhēxis ‘burst’). Definition Today, stroke is defined as an acute episode of focal dysfunction of the brain, retina, or spinal cord of a vascular origin if symptoms last longer than 24 hours or if computer tomography (CT), magnetic resonance imaging (MRI), or an autopsy show ischaemic brain injury or haemorrhage corresponding to the symptoms. Stroke is differentiated from a transient ischaemic attack (TIA) which is defined as transient neurological dysfunction without evidence of an ischaemic lesion in brain imaging for which symptoms typically last less than one hour and no more than 24 hours. Epidemiology Stroke is the second leading cause of death (after heart disease) worldwide. It accounts for more than 6.2 million deaths annually (World Health Organization 2020) with ~70 % of these deaths occurring in low- and middleincome countries (FEIGIN et al. 2015, JOHNSON et al. 2019). In high-income countries, nearly nine out of ten strokes are ischaemic strokes. Strokes are less frequently caused by haemorrhage (about 15 %). In Germany, the percentage of strokes caused by ischaemia, intracerebral haemorrhage, or subarachnoid haemorrhage (a bleeding into the subarachnoid space) is 84, 12, and 4 % respectively (EYDING et al. 2019). Globally, the incidence of haemorrhagic stroke (intracerebral haemorrhage and subarachnoid haemorrhage combined) is 30 %, indicating a higher incidence of haemorrhagic stroke in low- and middle-income countries (Institute for Health Metrics and Evaluation 2020). The global lifetime risk of stroke for men and women (at 25 years of age or older) is 25 % (The GBD 2016 Lifetime Risk of Stroke Collaborators 2018); the age-specific incidence increases exponentially with age, doubling for each decade after age 55 (ROGER et al. 2012). In people under 44 years of age, approximately 50 % of strokes are caused by ischaemia, 30 % by subarachnoid haemorrhage, and 20 % by intracerebral haemorrhage, indicating more diverse underlying pathogeneses and risk factors in this patient group (SINGHAL et al. 2013). Since 1990, the global age-standardised stroke incidence rate has slightly decreased, whereas the highest incidences of stroke are in East Asia, especially China, followed by Eastern Europe (JOHNSON et al. 2019). Strikingly, during the same period, the rate of deaths due to ischaemic and haemorrhagic stroke decreased by almost 40 % across all world regions except for sub-Saharan Africa (JOHNSON et al. 2019). However, as the world’s population increases and ages, and the low- and middle-income countries go through an epidemiological transition from infectious to non-communicable diseases, the overall burden of stroke in terms of the absolute number of people affected or disabled by stroke remains high and is steadily increasing (JOHNSON et al. 2019). In 2016, stroke-related disability was the second leading cause of disease burden worldwide, as measured in disabilityadjusted life years (DALYs – the sum of life years lost as a result of premature death and years lived in disability adjusted for severity (Fig. 1, JOHNSON et al. 2019)). In Germany, the social costs for treatment and loss of productivity resulting from stroke amount to around €18 billion a year, with treatment costs accounting for approximately 2 % of total health expenditures in 2017 (LUENGO-FERNANDEZ et al. 2019). Fig. 1 Stroke-related deaths and DALYs by development status based on the Socio-demographic Index (SDI). Countries with a high and highmiddle SDI are summarised under “developed”. Developing countries