stroke research, management, and care NAL-live 2021.2, v1.0, doi:10.34714/leopoldina_NAL-live_0002_01000 7 experimental research using animal models of disease has been essential for our understanding of stroke pathophysiology and identifying therapeutic targets (DIRNAGL and ENDRES 2014). Diagnosis Typical symptoms of stroke include sudden unilateral weakness and numbness of the face, arm (and leg), as well as altered speech. This has led to the acronym FAST (face, arm, speech, time to call ambulance) to aid prehospital stroke screening and public information campaigns. In essence, all brain functions can be affected by a stroke and indicate a specifically affected brain region – hence the quotation by stroke neurologist C. M. FISHER “we learn neurology stroke by stroke”. Other common symptoms include a sudden onset of non-orthostatic vertigo, visual loss, double vision, unsteady gait, swallowing difficulties, and confusion. Despite sharing a similar clinical presentation, acute treatment strategies for haemorrhagic and ischaemic stroke are fundamentally different. Therefore, a fast and reliable distinction between the two stroke types is paramount. Non-contrast cranial computed tomography (CT) can reliably detect fresh intracranial haemorrhage and remains the workhorse of acute stroke diagnosis. However, its sensitivity for revealing cerebral ischaemia is low for lesions which are recent, small, or in the lower posterior parts of the brain. Acute brain ischaemia can be detected in 90 % of patients with ischaemic stroke by diffusion weighted MRI. Fortunately, MRI also enables clinicians to estimate the onset of stroke in patients with an unclear time of occurrence, for instance when the stroke occurred while the patient was asleep, and thus permits the use of specific acute therapies (Fig. 4, THOMALLA et al. 2018). Fig. 4 Sample magnetic resonance (MR) images of an acute stroke using diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. (A) Time from stroke onset is likely to be <4.5 h in patients with mismatched DWI and FLAIR scans (i.e. hyperintense lesion on DWI is consistent with reduced diffusivity due to cytotoxic oedema but FLAIR images show no signal abnormality). (B) Time from stroke onset is likely to be >4.5 h in patients with visible lesions in both DWI and FLAIR MRI scans (i.e. hyperintense lesion on DWI is consistent with cytotoxic oedema induced by brain ischaemia and hyperintense signal on FLAIR, a sign of vasogenic oedema). DWI-FLAIR mismatch is commonly used in clinical trials to select patients for thrombolysis when the time of symptom onset is unknown. (Images courtesy of the Center for Stroke Research Berlin & the PRE-FLAIR study.) 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 8 Treatment When left untreated, about two out of three stroke patients are either deceased or dependent after six months; modern treatment options lower this rate to about 40 %. For ischaemic stroke, reduction in stroke mortality and long-term disability seen over the past two decades among high-income countries is almost entirely due to five interventions which have been shown to be effective in at least one properly designed, randomised controlled trial: (i) management of patients within a stroke unit (LANGHORNE et al. 1993), (ii) tissue plasminogen activator for intravenous thrombolysis within 4.5 hours of stroke onset (LEES et al. 2010), (iii) mechanical reopening of an occluded vessel with the help of vascular catheters, the so-called mechanical thrombectomy method, in particular for severely affected patients in whom a large brain vessel is blocked within 6 hours of stroke onset (BERKHEMER et al. 2015), (iv) aspirin within 48 hours of stroke onset (International Stroke Trial Collaborative Group 1997, JOHNSTON et al. 2018), and (v) decompressive surgery typically in younger patients with large middle cerebral artery (MCA) territory stroke (SCHWAB et al. 1998). Of these five treatments, the evidence is strongest for the long-term benefits of stroke unit treatment. Management within a stroke unit in the first days after stroke can be considered a complex organisational intervention. It comprises treatment by specialised multi-disciplinary staff, including specialised nursing and rehabilitation, as well as continuous monitoring of vital functions, fast access to imaging, and early initiation of secondary prevention (Fig. 5). Stroke unit treatment has been studied in randomised controlled trials since the 1990s and reduces death or dependency after one year by around 30 %. Fig. 5 Patient-centred model of specialised, interdisciplinary stroke unit care. 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 9 Tab. 2 Current treatment options of ischaemic stroke. The odds ratio represents the odds that death or dependency will occur given exposure to a particular treatment, compared to the odds of the outcome occurring in the absence of that exposure. The number needed to treat represents the average number of patients who need to be treated to prevent one additional bad outcome (e.g. the number of patients that need to be treated for one of them to benefit compared with a control in a clinical trial). n/a = not available Percentage of acute stroke patients that can be targeted by this