Highest terrestrial 3He/4He credibly from the core.

The observation that many lavas associated with mantle plumes have higher 3He/4He ratios than the upper convecting mantle underpins geophysical, geodynamic and geochemical models of Earth's deep interior. High 3He/4He ratios are thought to derive from the solar nebula or from solar-wind-irradiated material that became incorporated into Earth during early planetary accretion. Traditionally, this high-3He/4He component has been considered intrinsic to the mantle, having avoided outgassing caused by giant impacts and billions of years of mantle convection1-4. Here we report the highest magmatic 3He/4He ratio(67.2 ± 1.8 times the atmospheric ratio) yet measured in terrestrial igneous rocks, in olivines from Baffin Island lavas. We argue that the extremely high-3He/4He helium in these lavas might derive from Earth's core5-9. The viability of the core hypothesis relaxes the long-standing constraint-based on noble gases in lavas associated with mantle plumes globally-that volatile elements from the solar nebula have survived in the mantle since the early stages of accretion.

Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke: results from the NOR-FIB Study.

BACKGROUND: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study. METHOD: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. RESULTS: In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7. CONCLUSION: Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.

Atrial fibrillation in cryptogenic stroke and TIA patients in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results.

Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA2DS2-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.

Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation.

BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Hydrothermal 15N15N abundances constrain the origins of mantle nitrogen.

Nitrogen is the main constituent of the Earth's atmosphere, but its provenance in the Earth's mantle remains uncertain. The relative contribution of primordial nitrogen inherited during the Earth's accretion versus that subducted from the Earth's surface is unclear1-6. Here we show that the mantle may have retained remnants of such primordial nitrogen. We use the rare 15N15N isotopologue of N2 as a new tracer of air contamination in volcanic gas effusions. By constraining air contamination in gases from Iceland, Eifel (Germany) and Yellowstone (USA), we derive estimates of mantle δ15N (the fractional difference in 15N/14N from air), N2/36Ar and N2/3He. Our results show that negative δ15N values observed in gases, previously regarded as indicating a mantle origin for nitrogen7-10, in fact represent dominantly air-derived N2 that experienced 15N/14N fractionation in hydrothermal systems. Using two-component mixing models to correct for this effect, the 15N15N data allow extrapolations that characterize mantle endmember δ15N, N2/36Ar and N2/3He values. We show that the Eifel region has slightly increased δ15N and N2/36Ar values relative to estimates for the convective mantle provided by mid-ocean-ridge basalts11, consistent with subducted nitrogen being added to the mantle source. In contrast, we find that whereas the Yellowstone plume has δ15N values substantially greater than that of the convective mantle, resembling surface components12-15, its N2/36Ar and N2/3He ratios are indistinguishable from those of the convective mantle. This observation raises the possibility that the plume hosts a primordial component. We provide a test of the subduction hypothesis with a two-box model, describing the evolution of mantle and surface nitrogen through geological time. We show that the effect of subduction on the deep nitrogen cycle may be less important than has been suggested by previous investigations. We propose instead that high mid-ocean-ridge basalt and plume δ15N values may both be dominantly primordial features.

Utstein recommendation for emergency stroke care.

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. CONCLUSIONS: Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability.

[Reduction of treatment time for children in the trauma room care : Impact of implementation of an interdisciplinary trauma room concept (iTRAPS)]. / Verkürzung der Versorgungszeit im Trauma-Schockraum für Kinder : Auswirkungen der Einführung eines interdisziplinären Schockraumkonzepts (iTRAPS).

INTRODUCTION: In addition to infrastructural and conceptual planning, smooth interdisciplinary cooperation is crucial for trauma room care of severely injured children based on time-saving management and a clear set of priorities. The time to computed tomography (CT) is a well-accepted marker for the efficacy of trauma management. Up to now there are no guidelines in the literature for an adapted approach in pediatric trauma room care. METHODS: A step-by-step algorithm for pediatric trauma room care (Interdisciplinary Trauma Room Algorithm in Pediatric Surgery, iTRAPS) was developed within the framework of an interdisciplinary team: pediatric surgeons, pediatric anaethesiologists, pediatric intensivists and pediatric radiologists. In two groups of patients from January 2014 to April 2015 (group 1) and from July 2015 to January 2017 (group 2) process quality was monitored by the time required for trauma room treatment until the CT scan was performed and used as a surrogate marker. Inclusion criteria were patients aged 0-16 years, who were evaluated in a level 1 pediatric trauma room with an injury severity score (ISS) ≥8 and the necessity for a CT scan. RESULTS: Before (group 1) and after (group 2) implementation of iTRAPS 16 patients were included in each group. There were no significant differences between the age and the ISS in the two groups of patients. The required time for trauma room treatment was significantly reduced from an average of 33.6 min before to 15.2 min after implementation of iTRAPS (p < 0.01). DISCUSSION: The required time for the trauma care room treatment could be significantly reduced by more than half after the implementation of iTRAPS. The reasons were the interdisciplinary organization of the trauma room leadership, reorganization of patient transfer and improved briefing by emergency doctors. CONCLUSION: Besides a well-organized trauma team, it is essential that the trauma room workflow is adapted to the specific structure of the hospital. Despite the limitations of the study the data demonstrate that the trauma room workflow enables an efficient management. By the interdisciplinary reorganization of the pediatric trauma room treatment with improved structures and standardized processes, patient care was more effective with a significant reduction in the time required for trauma room treatment. The suggested iTRAPS concept could be used as a framework to establish individualized workflows for pediatric trauma room treatment in other hospitals. This algorithm should be supplemented by standardized operating procedures (SOPs) for the differentiated radiological diagnostic procedures in areas of traumatic brain injury (TBI), thoracic and abdominal trauma in children.

The prognosis of stroke survivors primarily discharged to their homes.

OBJECTIVES: Stroke is one of the leading causes for nursing home placement (NHP). We have studied the prognosis and risk factors regarding NHP for stroke patients initially discharged to their homes. MATERIALS AND METHODS: All stroke patients in the municipality of Stavanger, Norway, between January 1, 1996, and March 31, 2004, were included and followed until death or May 31, 2012. Time intervals for NHP and death were compared to an age- and sex-matched, stroke-free control cohort. Logistic regression analysis was used to assess risk factors for NHP. RESULTS: A total of 452 patients were included. A total of 48 patients (10.6%) were directly placed in a nursing home, while 401 patients (88.7%) were discharged to their homes; 180 patients (44.7%) directly and 221 patients (55.3%) after temporary rehabilitation. Of the patients discharged to their homes, 29.7% needed NHP at a later time point as compared to 19.9% of the controls (P<.001). Logistic regression analysis showed that only age (P<.001) was a risk factor for NHP. Stroke patients discharged home and stroke patients admitted directly to nursing home were significantly younger at time of NHP; stroke patients discharged home died significantly earlier than the controls. CONCLUSIONS: Almost 90% of the stroke patients could be discharged to their homes, but they needed more often NHP in the long run than the stroke-free controls. Stroke patients discharged to their homes were younger at the time of NHP and death indicating that the stroke deficit may contribute to increased morbidity and mortality in this patient group.

Wake-up stroke-Amendable for thrombolysis-like stroke with known onset time?

Patients suffering an acute ischemic stroke can be treated with intravenous thrombolysis in the absence of contraindications. A known onset time is a prerequisite as treatment, according to guidelines, has to be started within 4.5 hours. In patients awakening with a stroke, the last time they were seen without a neurological deficit is assumed to be the time of onset. Thus, despite of lack of contraindications on initial brain imaging, these patients are largely excluded from therapy. This review discusses the underlying pathophysiological, clinical, and radiological evidence surrounding wake-up stroke and its consequences for making treatment decisions.

Radiological imaging in acute ischaemic stroke.

Patients who suffer acute ischaemic stroke can be treated with thrombolysis if therapy is initiated early. Radiological evaluation of the intracranial tissue before such therapy can be given is mandatory. In this review current radiological diagnostic strategies are discussed for this patient group. Beyond non-enhanced computed tomography (CT), the standard imaging method for many years, more sophisticated CT stroke protocols including CT angiography and CT perfusion have been developed, and additionally an increasing number of patients are examined with magnetic resonance imaging as the first imaging method used. Advantages and challenges of the different methods are discussed.

Children with cerebral palsy have uncharacteristic somatosensory cortical oscillations after stimulation of the hand mechanoreceptors.

Numerous clinical investigations have reported that children with cerebral palsy (CP) have tactile discrimination deficits that likely limit their ability to plan and manipulate objects. Despite this clinical awareness, we still have a substantial knowledge gap in our understanding of the neurological basis for these tactile discrimination deficits. Previously, we have shown that children with CP have aberrant theta-alpha (4-14 Hz) oscillations in the somatosensory cortices following tactile stimulation of the foot. In this investigation, we evaluated if these aberrant theta-alpha oscillations also extend to the hand. Magnetoencephalography was used to evaluate event-related changes in the theta-alpha and beta (18-34 Hz) somatosensory cortical oscillations in groups of children with CP and typically developing (TD) children following tactile stimulation of their hands. Our results showed that the somatosensory theta-alpha oscillations were relatively intact in children with CP, which is in contrast to our previous results for foot tactile stimulations. We suspect that these inter-study differences may be related to the higher probability that the neural tracts serving the lower extremities are damaged in children with CP, compared to those serving the upper extremities. This inference is plausible since the participating children with CP had Manual Ability Classification System (MACS) levels between I and II. In contrast to the theta-alpha results, children with CP did exhibit a sharp increase in beta activity during the same time period, which was not observed in TD children. This suggests that children with CP still have deficits in the computational aspect of somatosensory processing.

Evaluation of the recombinant tissue plasminogen activator pretreatment in acute stroke patients with large vessel occlusions treated with the direct bridging approach. Is it worth the effort?

BACKGROUND AND PURPOSE: The direct bridging concept in acute stroke treatment combines intravenous thrombolysis (IVT) and endovascular treatment (EVT). The frequency and extent of reperfusion obtained already due to IVT were evaluated. Additionally undesired events and the clinical outcome were analysed. METHODS: Fifty-seven acute stroke patients treated with direct bridging were analysed for this study. The response to IVT was evaluated according to the modified Thrombolysis in Cerebral Infarction scale (m-TICI). IVT responders (m-TICI ≥2B in digital subtraction angiography) were compared with IVT non-responders (m-TICI <2B in digital subtraction angiography) with respect to clinical outcome and occurrence of undesired events. RESULTS: Fourteen patients (25%) got a change from TICI 0 to ≥2B due to IVT alone. There were otherwise no differences between the IVT responders and IVT non-responders. CONCLUSIONS: Intravenous thrombolysis pretreatment in the context of the bridging approach contributes substantially to revascularization.

Helium and lead isotopes reveal the geochemical geometry of the Samoan plume.

Hotspot lavas erupted at ocean islands exhibit tremendous isotopic variability, indicating that there are numerous mantle components hosted in upwelling mantle plumes that generate volcanism at hotspots like Hawaii and Samoa. However, it is not known how the surface expression of the various geochemical components observed in hotspot volcanoes relates to their spatial distribution within the plume. Here we present a relationship between He and Pb isotopes in Samoan lavas that places severe constraints on the distribution of geochemical species within the plume. The Pb-isotopic compositions of the Samoan lavas reveal several distinct geochemical groups, each corresponding to a different geographic lineament of volcanoes. Each group has a signature associated with one of four mantle endmembers with low (3)He/(4)He: EMII (enriched mantle 2), EMI (enriched mantle 1), HIMU (high µ = (238)U/(204)Pb) and DM (depleted mantle). Critically, these four geochemical groups trend towards a common region of Pb-isotopic space with high (3)He/(4)He. This observation is consistent with several low-(3)He/(4)He components in the plume mixing with a common high-(3)He/(4)He component, but not mixing much with each other. The mixing relationships inferred from the new He and Pb isotopic data provide the clearest picture yet of the geochemical geometry of a mantle plume, and are best explained by a high-(3)He/(4)He plume matrix that hosts, and mixes with, several distinct low-(3)He/(4)He components.

Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture.

Cathepsin S is a cysteine protease that controls adipocyte differentiation and has been implicated in vascular and metabolic complications of obesity. Considering the inverse relation of osteoblasts and adipocytes and their mutual precursor cell, we hypothesized that cathepsin S may also affect osteoblast differentiation and bone remodeling. Thus, the fat and bone phenotypes of young (3 months old) and aged (12 or 18 months old) cathepsin S knock-out (KO) and wild-type (WT) mice were determined. Cathepsin S KO mice had a normal body weight at both ages investigated, even though the amount of subscapular and gonadal fat pads was reduced by 20%. Further, cathepsin S deficiency impaired adipocyte formation (-38%, p<0.001), which was accompanied by a lower expression of adipocyte-related genes and a reduction in serum leptin, IL-6 and CCL2 (p<0.001). Micro-CT analysis revealed an unchanged trabecular bone volume fraction and density, while tissue mineral density was significantly lower in cathepsin S KO mice at both ages. Aged KO mice further had a lower cortical bone mass (-2.3%, p<0.05). At the microarchitectural level, cathepsin S KO mice had thinner trabeculae (-8.3%), but a better connected trabecular network (+24%). Serum levels of the bone formation marker type 1 procollagen amino-terminal-propeptide and osteocalcin were both 2-3-fold higher in cathepsin S KO mice as was the mineralized surface. Consistently, osteogenic differentiation was increased 2-fold along with an increased expression of osteoblast-specific genes. Interestingly, serum levels of C-terminal telopeptide of type I collagen were also higher (+43%) in cathepsin S KO mice as were histological osteoclast parameters and ex vivo osteoclast differentiation. Thus, cathepsin S deficiency alters the balance between adipocyte and osteoblast differentiation, increases bone turnover, and changes bone microarchitecture. Therefore, bone and fat metabolisms should be monitored when using cathepsin S inhibitors clinically.

Alignment of D-state Rydberg molecules.

We report on the formation of ultralong-range Rydberg D-state molecules via photoassociation in an ultracold cloud of rubidium atoms. By applying a magnetic offset field on the order of 10 G and high resolution spectroscopy, we are able to resolve individual rovibrational molecular states. A full theory, using a Fermi pseudopotential approach including s- and p-wave scattering terms, reproduces the measured binding energies. The calculated molecular wave functions show that in the experiment we can selectively excite stationary molecular states with an extraordinary degree of alignment or antialignment with respect to the magnetic field axis.

[Technique of the urethral anastomosis in orthotopic neo-bladder following robot-assisted radical cystectomy (RARC)]. / Technik der urethralen Anastomose bei orthotopem Blasenersatz nach roboterassistierter radikaler Zystektomie (RARC).

The urethral anastomosis in extracorporeally constructed orthotopic neo-bladder following robot-assisted radical cystectomy (RARC) remains a challenge. In principle either pre-posi-tioned single sutures or robotic continuous suture techniques can be applied. In the literature the different techniques are most often not described in detail. In the present work one example for each technique is given and the advantages and disadvantages of both methods are discussed.

Acute ischemic stroke--from symptom recognition to thrombolysis.

OBJECTIVES: The understanding of stroke has changed in the recent years from rehabilitation to an emergency approach. We review existing data from symptom recognition to thrombolysis and identify challenges in the different phases of patient treatment. RESULTS: Implementation of treatment in dedicated stroke units with a multidisciplinary team exclusively treating stroke patients has led to significant reduction of stroke morbidity and mortality. Yet, first the introduction of treatment with intravenous rtPA (IVT) has led to the 'time is brain' concept where stroke is conceived as an emergency. As neuronal death in stroke is time dependent, all effort should be laid on immediate symptom recognition, rapid transport to the nearest hospital with a stroke treatment facility and diagnosis and treatment as soon as possible. The main cause of prehospital delay is that patients do not recognize that they suffered a stroke or out of other reasons do not call the Emergency Medical Services immediately. Educational stroke awareness campaigns may have an impact in increasing the number of patients eligible for rtPA treatment and can decrease the prehospital times if they are directed both to the public and to the medical divisions treating stroke. Stroke transport times can be shortened by the use of helicopter and a stroke mobile--an ambulance equipped with a CT scanner--may be helpful to decrease time from onset to treatment start in the future. Yet, IVT has several limitations such as a narrow time window and a weak effect in ischemic strokes caused by large vessel occlusions. In these cases, interventional procedures and the concept of bridging therapy, a combined approach of IVT and intraarterial thrombolysis or mechanical thrombectomy, might improve recanalization rates and patient outcome. CONCLUSIONS: As neuronal death in stroke patients occurs in a time-dependent fashion, all effort should be made to decrease time from symptom onset to treatment start with rtPA: major challenges are stroke recognition in the public, transport times to hospital and an efficient stroke triage in the hospital.