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Recovery processes after stroke include restoration or compensation of function initially lost or newly acquired after injury. Therapeutic interventions can either directly improve these processes and/or inhibit processes that impede regeneration. Numerous experimental studies suggested a great opportunity for such treatments, but the results from recent large clinical trials with neuromodulators such as dopamine and fluoxetine have been rather disappointing. The reasons for this are manifold and involve the extrapolation of results from animal models to humans. Given the differences between animals and humans in genetic and epigenetic background, brain size and anatomy, cerebral vascular anatomy, immune system, as well as clinical function, and behavior, direct extrapolation is unlikely to work. Backward blockades include the incompatible adaption of clinical trial objectives and outcomes in clinical trials with regard to previous preclinical findings. For example, the clinical recovery trial design widely varies and has been characterized by the selection of different clinical endpoints, the inclusion a wide spectrum of stroke subtypes and clinical syndromes, and different time windows for treatment initiation after onset of infarction. This review will discuss these aspects based on the results of the recent stroke recovery trials with the aim to contributing to the development of a therapy that improves the functional outcome of a chronic stroke patient., Competing Interests: WRS ist Erfinder der Patentanmeldung „Hämatopoetische Faktoren zur Behandlung neurologischer Erkrankungen“, einschließlich Schlaganfall und anderer Krankheiten. Der Teil des Antrages (ALS) wurde erteilt. WRS übertrug seine Rechte an Sygnis und erhielt eine geringe finanzielle Entschädigung im Voraus. Im Falle der Wirksamkeit wird WRS in Form von Lizenzgebühren beteiligt. WRS besitzt oder erhält weder Aktien von Sygnis noch ist er direkt an dem Unternehmen beteiligt., (Thieme. All rights reserved.)

Intravenous thrombolysis (IVT) treatment with alteplase (rtPA) is an essential part of the routine treatment of patients with ischemic stroke since its introduction in the late 1990s. Rapid treatment is of essential importance. For patients with an unclear time window, various mismatch concepts have been established to identify salvageable brain tissue prior to IVT. Numerous official contraindications for rtPA are not evidence-based; for example, current data from observational studies show that systemic thrombolytic treatment is possible even in patients receiving direct oral anticoagulant (DOAC) treatment. Tenecteplase (TNK) is an alternative thrombolytic agent with some pharmacologic advantages. The most recent guidelines indicate that TNK is particularly advantageous over rtPA in patients treated in combination with endovascular stroke therapy (EST). The combination of IVT and EST should primarily be performed in the 4.5‑h time window in patients without contraindications; in the later time window EST alone is conceivable if it can be performed without delay., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be preferred over vitamin K antagonists (VKA) in this indication. This recommendation applies also to patients with VHF and concomitant chronic kidney disease (CKD). Real World Evidence (RWE), i. e., structured data from clinical practice, extends and confirms the clinical evidence generated in more formalized clinical trials with NOAC and VKA. In addition, RWE in respect to the indication showed that the superiority of NOAC versus the VKA warfarin can also be extrapolated to phenprocoumon, the commonly used VKA in Germany. Furthermore, data include evidence that the typical progression of CKD appears to be less pronounced in individuals treated with NOAC compared to those treated with VKA., Competing Interests: U.Z. hat in den vergangenen 3 Jahren Honorare für Arbeiten in Leitungsgremien von Studien, Beratungsboards und für Vorträge von Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Chiesi, Daiichi-Sankyo, Ferrer, GSK, Lilly, Novartis, MSD, Pfizer, Sanofi und Trommsdorff erhalten.H.B. hat in den vergangenen 3 Jahren Honorare für Arbeiten in Leitungsgremien von Studien, Beratungsboards und für Vorträge von Amgen, Bayer, BMS, Boehringer-Ingelheim, Chiesi, Daiichi-Sankyo, Novartis und Sanofi erhalten.C.W. hat in den vergangenen 3 Jahren Honorare für Arbeiten in Leitungsgremien von Studien, Beratungsboards und für Vorträge von Amgen, Actelion, Akebia, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Chiesi, Daiichi-Sankyo, FMC, GSK, GILEAD, Lilly, Novartis, MSD, Pfizer, Reata, Sanofi-Genzyme, Shire-Takeda, Tricida und Vifor erhalten.Das Institut Dr. Schauerte, München, erhielt ein Honorar der Bayer Vital GmbH für die redaktionelle Unterstützung der Autoren beim Erstellen des Manuskripts. Die Erstellung der Inhalte erfolgte nach Anweisung der Autoren., (Thieme. All rights reserved.)

In patients with intact kidney function and in patients with mild to moderate chronic kidney disease (CKD), strong evidence suggests the use of non-vitamin K dependent oral anticoagulants (NOAC) for preventing ischemic strokes and systemic thromboembolic events in patients with non-valvular atrial fibrillation (nvAF) and elevated thromboembolic risk. In contrast, less evidence is available on the risk-benefit ratio of oral anticoagulation (OAC) in patients with nvAF and severe CKD, particularly in dialysis patients. No large randomised study has tested whether OAC will reduce the risk of thromboembolic events in nvAF without prohibitively high bleeding risk, and whether NOACs or vitamin K antagonists are the superior strategy for OAC. Considering absence of strong evidence, the authors suggest that in dialysis patients with nvAF, in whom the treatment team sees the clear need to prevent thromboembolic events, the use of NOACs or left atrial appendage occlusion should be preferred over treatment with vitamin K antagonists. Any OAC treatment for dialysis patients with nvAF is not in-label in most European countries., Competing Interests: VB hat Honorare/Forschungsförderung bezogen von Bayer, BMS, Daiichi Sankyo, Pfizer.GHH hat keine persönlichen Honorare von Herstellern von NOAK oder VKA bezogen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Recurrent stroke is a frequent event and clinical trials that addressed the best secondary prevention are sparse. If patients take a thrombocyte aggregation inhibitor (TAI) before the recurrent stroke, clopidogrel can be chosen instead of aspirin or vice versa but evidence is lacking. A 3-week period of dual antiplatelet treatment might be a good alternative after acute reinfarction. The results of the recently published RESTART trial support resuming TAI treatment after a hemorrhagic stroke and showed that the intracerebral hemorrhage (ICH) rate is not elevated in comparison with a study group without TAI. Patients with ICH associated with oral anticoagulation (OAC) and atrial fibrillation should be restarted on novel OACs, if there are no relevant contraindications and the risk of ischemia is high. The anticoagulation treatment of patients with cerebral amyloid angiopathy is still a clinical dilemma as there is a high risk of recurrent ICH. These patients might be candidates for left appendage closure.

Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only. For the factor Xa inhibitors, an antidote is being investigated in clinical trials. To our best knowledge, there are no direct head-to-head studies between the NOACs. Therefore, none of them can be assumed to be superior and the decision for a specific NOAC should be based on the available scientific data from the NOAC trials considering the individual patient's characteristics and comorbidities., Competing Interests: C. Küpper hat an einer von Boehringer-Ingelheim organisierten und finanzierten Fortbildungsveranstaltung teilgenommen.L. Kellert erhielt Vortragshonorare und/oder Reiseunterstützung von Bayer Vital, Bristol Myers Squibb, Pfizer, Daiichy Sankyo und Boehringer Ingelheim.S. Tiedt hat an einer von Boehringer-Ingelheim organisierten und finanzierten Fortbildungsveranstaltung teilgenommen.FA. Wollenweber erhielt Vortragshonorare von Pfizer und Bayer Vital. Er war tätig als Berater für Daiichy Sankyo und Boehringer Ingelheim., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Upper limb spasticity is a common complication following stroke. Cohort studies found 19% of post-stroke patients had upper limb spasticity at 3 months and 38% of patients at 12 months. For focal spasticity, intramuscular injections of botulinum toxin are indicated. In Germany, it is assumed that patients with the described indication are undersupplied with botulinum toxin., Objective: The aim of the present study is to evaluate the medical care of patients with upper limb spasticity post-stroke with the focus on the use of botulinum toxin as one treatment option., Methods: A standardized questionnaire was developed and a postal survey of a representative national random sample of 800 neurologists to capture the actual medical care situation., Results: The response rate amounted to 37% (n = 292). 59% of the neurologists surveyed had never used botulinum toxin. In total, 87% of neurologists noticed barriers regarding the use of botulinum toxin, where the amount of the doctor's remuneration in 40% and the lack of reimbursement of costs in off-label use in 60% were the most commonly used answers. The achievement of an advanced training in using botulinum toxin was also stated as a general obstacle for resident neurologists., Discussion: Due to a response rate of 37% for the postal survey a selection bias cannot be excluded. Although botulinum toxin is recommended in the national treatment guidelines, many neurologists do not use botulinum toxin. The reasons can be seen from the barriers described.

The non-vitamin K antagonists (NOAC) are an integral component of our antithrombotic prevention and therapy. For four of the NOAC, their non-inferiority or even superiority versus vitamin K antagonists (VKA) has been proven. Thus, the management of special patient cohorts or the management of active bleeding complications is a focus of current discussion.In addition to prospective trials, numerous retrospective analyses of health insurers or public health provider data have been analyzed and published as "real life" or "real-world evidence" data. In almost all data sets the results of the NOAC approval trials were confirmed, demonstrating their non-inferiority or even superiority versus VKA. Attempts to compare the various NOAC with each other must be viewed critically since the real-world evidence (RWE) analysis provides very divergent results depending on the cohorts analyzed. Thus, a substantial prescriber-bias must be taken into account and never be excluded.In order to improve the management of bleeding complications, NOAC antidotes were developed. While the factors Xa antidote, andexanet alpha, a modified coagulation factor deleted of an intrinsic activity, will not be available before 2018, the dabigatran antidote idarucizumab is already in clinical use. Idarucizumab, a monoclonal antibody fragment directed against dabigatran, is able to completely antagonize the effect of dabigatran within minutes. Therefore, the drug has the potential to terminate life-threatening bleeding complications earlier and make emergency surgical or interventional procedures possible without an elevated bleeding risk.

Background: Monitoring non-vitamin K antagonist oral anticoagulants (NOAC) is usually not necessary; however, in some patients it may prove beneficial., Objectives: Patient subgroups who may profit from monitoring were identified, and methods of monitoring (including assessment of which coagulation parameters are affected by NOAC) are described., Materials and Methods: We searched the PubMed database for each of the search terms, "NOAC", "DOAC", "rivaroxaban", "dabigatran", and "apixaban", in combination with one of the terms, "monitoring", "measurement", "measuring", or "assessment". The results were compiled and reviewed., Results: Monitoring is most advantageous in emergency cases with severe bleeding where drug activity needs to be assessed. It can also help in deciding for or against lysis therapy after acute stroke in patients taking NOAC. Furthermore, it can also identify compliance problems and help in planning periprocedural management. There are quantitative measurement methods which measure plasma concentrations exactly and qualitative methods which only allow for a rough estimate or a general confirmation of drug activity. Recommended quantitative measurement methods are diluted thrombin time for dabigatran, and anti-factor Xa activity (calibrated) for rivaroxaban and apixaban., Conclusions: Several patient subgroups may profit from monitoring of NOAC plasma concentration. One should, however, take several issues into consideration before measurements, such as the objective of each individual measurement, possible consequences (e. g., dose adjustment), and which measurement method to pick.

Background: Elevated troponin levels are commonly found in patients with acute stroke and approximately 60 % of stroke patients suffer from an accompanying coronary artery disease. Troponin release can be caused either by an acute thrombotic myocardial infarction or by insufficient coronary perfusion due to neurocardiogenic causes like blood pressure or heart rate variability without thrombotic coronary occlusion. Due to the often unclear pathological cause of troponin release and the risk of secondary hemorrhage during dual antiplatelet therapy, the determination of the best time point for coronary diagnostics and therapy in stroke patients is a common challenge in clinical daily routine., Materials and Methods: Based on the current literature, we describe a potential diagnostic and therapeutic approach in stroke patients with increased troponin levels., Results: First, the probability of an acute thrombotic myocardial infarction should be evaluated based on clinical, laboratory, and electrocardiographic parameters. In case of suspected myocardial infarction, a diagnostic coronary angiography/CT angiography should be performed and dual antiplatelet therapy should be given depending on the intracranial bleeding risk. In patients with high risk of intracranial bleeding, thrombus aspiration and balloon dilatation should be considered., Conclusion: In patients with acute stroke and elevated troponin levels, a thorough diagnostic workup is necessary to estimate the probability for a thrombotic myocardial infarction and to prevent cardiac and neurologic complications.

Oral anticoagulation plays an essential role in the treatment of patients with atrial fibrillation as it is indicated for most patients to reduce the risk of stroke. It is prudent to assess the risks of stroke and bleeding using the CHA 2 DS 2 -VASc and HAS-BLED scores. Oral anticoagulation is indicated in general for all patients with valvular atrial fibrillation (atrial fibrillation in moderate to severe mitral stenosis or mechanical prosthetic valve) as well as for patients with a CHA 2 DS 2 -VASc-Score of 1 - 2 points or higher. The indication is irrespective of the form of atrial fibrillation: paroxysmal, persistent or permanent.Non-vitamin K antagonists (NOAK) are first-line therapy for many patients. The selection of the appropriate drug should be based on preference of patient and physician as well as other factors such as renal insufficiency, co-medication and bleeding risk.Percutaneous left atrial appendage closure is a therapeutic alternative especially for patients with a contraindication for oral anticoagulation., (© Georg Thieme Verlag KG Stuttgart · New York.)

The HOPE-3-Trial investigated the effect of primary prevention on cardio- and neurovascular events in patients without known atherosclerotic disease, but with intermediate risk. In a factorial design Rosuvastatin 10 mg, Candesartan 16 mg/HCT 12.5 mg or both were compared with placebo. Rosuvastatin effectively lowered LDL-cholesterol and the rate of cardio- and neurovascular complications with a NNT of approximately 500/year without detectable effect on mortalitiy. Candesartan 16 mg/HCT 12.5 mg did not influence any endpoint, however, the predefined subgroup of patients with hypertension level I had a benefit. Patients with systolic pressure <131 mmHg even trended towards a higher risk if treated. The combination of statin and blood pressure-lowering agents showed no additive effects. The benefit was solely the result of statin therapy alone. Primary prevention with Rosuvastatin can be recommended if the cardio- and neurovascular risk is 1-2%/year, independent of the initial LDL, although the NNT of 500-1400/year is high and mortalitiy is not decreased. Possibly there will be future studies with longer term follow up to verify a reduction in mortality. Therapy with Candesartan 16 mg/HCT 12,5 mg has a beneficial effect only in patients with hypertension. Further studies with different antihypertensives and more intensive blood pressure lowering are desirable. The approach of combining all three drugs within a poly-pill for primary prevention in an intermediate risk population without elevated blood pressure is not recommended., (© Georg Thieme Verlag KG Stuttgart · New York.)

In this third edition the secondary prevention of stroke will be discussed. After the acute phase in which recanalization of an occluded brain artery is in the focus, the risks for a recurrent stroke have to be minimized and rehabilitation should be started. A systematic workup, an extended evaluation of (non-) modifiable risk factors and the clinical-radiological findings are the source of an effective preventive therapy. Risk assessment of the major risk factors such as arterial hypertension, atrial fibrillation, diabetes and dyslipidemia is established. The obstructive sleep apnea syndrome and the complex atheromatosis with a complex structure are independent risk factors for stroke. The search for an etiology is usually a definition of probabilities. The most probable cause of stroke is assumed.

The results of previous studies on blood pressure in acute stroke therapy allow a few generally valid therapeutic recommendations. Efforts should be made to achieve a constant blood pressure level without major fluctuations. An antihypertensive therapy in the acute stage of stroke should be initiated only at highly elevated values. High blood pressure levels can be tolerated in patients with ischemic stroke unless thrombolytic comes into consideration. Should this be desired, the blood pressure must be quickly lowered to a target range of at least < 180 mmHg. In the case of intracerebral hemorrhage a blood pressure reduction appears to be beneficial. The ESO recommends a reduction to < 140 mmHg systolic within one hour, according to recommendations of the ESH and the EUSI but not more than 20 %., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Anticoagulation for the prevention of cardioembolic events is highly effective, but largely underused in frail older patients with atrial fibrillation or flutter (AF). This study aimed at identifying characteristics associated with anticoagulation use or non-use and the most frequent complications of this therapy., Methods: Hospitalized geriatric patients treated in a one-year interval were retrospectively studied for the presence of AF and use or non-use of anticoagulation. The risk of stroke and the indication for permanent anticoagulation were assessed using the CHA2DS2-VASc score., Results: In 451 of 1167 hospitalized patients (38.6%) there was a clear indication for anticoagulation. The most frequent indication for anticoagulation was AF in 381 patients (84.5% of 451 patients). Of these 381 patients, a strong indication for anticoagulation, based on CHA2DS2-VASc score, was identified in 379 patients. Of these patients, 200 (52.8%) did and 179 (47.2%) patients did not receive anticoagulation. 153 patients (40.4%) received antiplatelet therapy. 26 patients (6.7%) received neither anticoagulants nor antiplatelet therapy. The most common reason for non-implementation of anticoagulation was a high risk of falls in 93 patients (52%) of 179 patients without antocoagulation. The most frequent complications of anticoagulation were small hemorrhages without serious consequences in 8 cases. 4 patients suffered from serious bleedings., Conclusion: Almost half of our geriatric population did not receive anticoagulation despite a clear indication. Antiplatelet therapy use was associated with anticoagulation non-use., (© Georg Thieme Verlag KG Stuttgart · New York.)

The establishment of stroke networks is an approach to forward guideline driven stroke care to hospitals without full-time neurological service. Tele- stroke networks are evidence based for remote neurological support of acute stroke patients, administration of thrombolysis safely as well as increasing thrombolysis rates. Since 2011 the district hospital in Grabs was linked to the stroke center at the cantonal hospital St. Gallen which provided teleconsultations with full-scale audiovisual communication and access to brain images 24 hours per day 7 days per week. Regarding quality and safety issues the experiences were promising including the selection of patients for appropriate treatment with allocation to systemic thrombolysis or en dovascular reperfusion therapy. As perspective it may definitely contribute to better supply of rural areas with acute stroke therapy but also other specializations and neurological indications may benefit from telemedical support

Systemic thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) remains the only effective and approved medical treatment of acute ischemic stroke. Several studies have demonstrated the importance of rapid recanalization. The efficacy of thrombectomy has so far not been sufficiently shown in randomized clinical trials; therefore, inclusion of suitable patients in one of the currently ongoing randomized trials is of great importance. The early treatment with magnesium after acute ischemic stroke during the pre-hospital phase did not prove to be neuroprotective. Intermittent pneumatic compression of the lower extremities in immobilized stroke patients effectively prevents deep venous thrombosis and pulmonary embolism. In patients with lacunar stroke the combination of aspirin and clopidogrel is not superior to aspirin alone and causes more bleeding complications. The novel oral anticoagulants are superior to warfarin in secondary prevention and carry a lower risk of intracranial and systemic bleeding complications. New studies will investigate whether dabigatran or rivaroxaban are superior to aspirin in secondary prevention after cryptogenic stroke.

Background: This study aims at investigating ischaemic stroke therapy in Germany by using secondary data. The focus lies on the performance of thrombolysis., Methods: Statutory quality report data for 2010 were obtained. All hospitals (n = 1302) treating patients suffering from an ischaemic stroke either on a neurological, internal, geriatric or intensive care unit were analysed. The treatment situation, defined as the experience in performing thrombolysis, was displayed cartographically. Potential variables that may influence the thrombolysis rate were analysed., Results: 78 % of the 198,500 ischaemic stroke cases were treated on a ward specialised in the stroke treatment (i. e., a stroke unit). The mean thrombolysis rate in neurological departments was 9.1 %. Thrombolysis rates between departments ranged from 0 to 38 %. Significant factors influencing the thrombolysis rate were the total number of ischaemic strokes treated as well as the existence of a stroke unit., Discussion: In Germany, to date regional differences in the treatment of ischaemic stroke exist. Experience in the treatment of ischaemic stroke patients and the availability of a stroke unit both increase the thrombolysis rate. Data suggest that in Germany there is still room for improvement of appropriate ischaemic stroke treatment., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Recanalisation favourably influences outcome in acute stroke. Improved endovascular approaches seem to have higher recanalisation rates than systemic thrombolysis. Substantial efforts have been undertaken to increase the proportion of patients to whom these therapies can be applied. It is still unclear what rates can be realised in a clinical setting., Patients and Methods: This is a retrospective single-centre analysis of patients with acute ischaemic stroke and specific recanalisation therapy primarily admitted to our tertiary care centre from 1/2010 to 3/2012., Results: 20 % of patients received systemic thrombolysis, 20 % of these additional endovascular strategies. Pathological multimodal CT patterns were more common in patients not fulfilling the inclusion criteria for thrombolysis. Short-term clinical outcomes were similar in on-label and off-label applications., Conclusion: Structured clinical pathways including multimodal CT imaging are useful in identifying patients likely to profit from revascularisation therapies. Based upon our data, some realistic aims concerning therapy rates in patients with ischaemic stroke treated in everyday practice may be formulated (20/20 in 2020)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To reduce the time from symptom onset to treatment with tissue plasminogen activator (tPA) in ischemic stroke, an ambulance was equipped with a CT scanner. We analyzed process and image quality of CT scanning during the pilot study regarding image quality and safety issues., Materials and Methods: The pilot study of a stroke emergency mobile unit (STEMO) ran over a period of 12 weeks on 5 weekdays from 7a.m. to 6:30 p.m. A teleradiological service for the justifying indication and reporting was established. The radiographer was responsible for the performance of the CT scan on the ambulance. 64 cranial CT scans and 1 intracranial CT angiography were performed. We compared times from ambulance alarm to treatment decision (time of last brain scan) with a cohort of 50 consecutive tPA treatments before implementation of STEMO., Results: 62 (95%) of the 65 scans performed had sufficient quality for reading. Technical quality was not optimal in 45 cases (69%) mainly caused by suboptimal positioning of patient or eye lens protection. Motion artefacts were observed in 8 exams (12%). No safety issues occurred for team or patients. 23 patients were treated with thrombolysis. Time from alarm to last CT scan was 18 minutes shorter than in the tPA cohort before STEMO implementation., Conclusion: A teleradiological support for primary stroke imaging by CT on-site is feasible, quality-wise of diagnostic value and has not raised safety issues., (© Georg Thieme Verlag KG Stuttgart · New York.)

Patients waking up with stroke symptoms are generally excluded from intravenous thrombolysis. It was shown that magnetic resonance imaging (MRI) can identify patients within the time window for thrombolysis (≤  4.5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion-weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging. The WAKE-UP trial is an investigator initiated, European, randomized, double-blind, placebo-controlled trial designed to test efficacy and safety of MRI-based thrombolysis with alteplase (tPA) in stroke patients with unknown time of symptom onset, e.g. due to symptom recognition on awakening. A total of 800 patients showing MRI findings of a DWI-FLAIR-mismatch will be randomized to either tPA or placebo. The primary efficacy endpoint will be favourable outcome defined by a modified Rankin scale score 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin scale score 4-6 at 90 days. If positive the WAKE-UP trial is expected to change clinical practice and to make effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute treatment.

In selected stroke patients intravenous thrombolysis and/or endovascular therapies lead to a significant reduction of long term disabilities. In case of no contraindications, patients with acute ischemic stroke, which arrive within the time window on the emergency unit, should receive thrombolysis consequently and current data indicate that patients with a severe acute ischemic stroke and a proximal cerebral arterial vessel occlusion (i. e. main stem of the arteria cerebri media, posterior, maybe also anterior, arteria carotis interna and basilaris) should preferentially be treated endovascularly, patients with a peripheral cerebral arterial vessel occlusion (i. e. main branch of the arteria cerebri media, anterior and posterior) and mild symptoms with intravenous thrombolysis.

Stroke is heterogenous in its symptoms, which are also caused by various pathologies. Clinically the causing mechanism (bleeding or ischemia) of a new onset of neurological deficits can not reliably be distinguished. However, ischemia is four times more frequent than a bleeding causing neurological symptoms. Modern imaging technologies (computed assisted tomography or magnetic resonace imaging) and interventional techniques are a mainstay in diagnostics and management of acute onset of neurological symptoms. They can reliably distinguish between bleeding and stroke, especially taking newest technologies, such as perfusion studies and angiographies, into account. Neuroradiology with its interventional options has nowadays furthermore become an important tool in strokes and offers a local maneuver to retrieve the clotting pathology and even opens the therapeutic window for a delayed start of the therapy since symptom's onset beyong the conventional 4.5 hours window. Also risks of a therapy and which therapy option should be used can immediately be assessed.

For many decades Vitamin K antagonists were the standard orally given medication for primary and secondary prevention of thromboembolism in patients with atrial fibrillation and stroke. Three compounds, dabigatran, rivaroxaban, and apixaban, are now challenging this well established prescription, as they showed similar effect in preventing thromboembolism with a lower bleeding rate in recently published well designed, controlled randomised, non-inferiority trials. Their advantages of each are to have a fixed dosage, no need to monitor coagulation factors, and fewer interactions with food and other drug intake. The therapeutic effect is estimated overall similar between the three compounds. Who is a candidate for one of the new drugs: Patients with atrial fibrillation and the clear indication to get a future oral anticoagulation are potential candidates to receive one of the new drugs. Further this may be patients where the treatment with Vit K antagonists was difficult to optimise, patients who are not willing to have blood controls done regularly or where blood controls are difficult to obtain. This will also be an option in patients who had a stroke due to atrial fibrillation and had no history of cerebral bleeding. Who should not receive the new anticoagulants: patients who present stable blood coagulation values in the treatment range and no complications should not be merged to the new drugs. Patients with severe renal insufficiency or receiving a medication that interacts with the new drugs (e. g. ketoconazole) or with synthetic heart valves will not be candidates to receive the new drugs.

The only recommended therapy in the acute phase of ischemic stroke is thrombolysis within 4.5-(6) h after symptom onset. For secondary stroke prevention platelet inhibitors or, in cases of cardiac embolism, anticoagulants are used. However, these substances bear significant limitations: either they show only moderate efficacy (platelet inhibitors), or they are associated with a considerable bleeding risk (rt-PA, anticoagulants). Although the majority of strokes are caused by embolic or thrombotic vessel occlusion, strikingly little is known about the pathophysiological role of platelets and their local function in the brain vasculature. The recent development of novel transgenic mouse lines paved the way for the in-depth analysis of the different molecular steps of thrombus formation involving platelets and the plasma coagulation cascade in models of acute ischemic stroke. It was demonstrated that prevention of early platelet adhesion to the damaged vessel wall by blocking the platelet surface receptors GPIbα or GPVI dramatically protects against experimental stroke without increasing the frequency of intracranial hemorrhage. Moreover, the critical involvement of the blood coagulation factor XII (FXII)-driven intrinsic coagulation cascade in thrombus formation during the course of ischemic brain damage could be unraveled thereby disproving established concepts of hemostasis. Based on these findings novel pharmacological blockers of GPIbα and FXIIa were designed that likewise proved to be safe and effective in animal stroke studies. Those compounds now lay the groundwork for a novel and intriguing concept in ischemic stroke and other thromboembolic diseases: antithrombosis devoid of any bleeding complications. Further preclinical testing is currently ongoing.

Background: We wanted to compare the outcome following IV thrombolysis in our patients with ischemic stroke with the outcome reported from the phase 3 registration trials and other large trials., Patients and Methods: From January 2008 through December 2009 we treated 225 patients with ischemic stroke with IV thrombolysis. Retrospectively, we analyzed their clinical data upon admission, during their stay, and upon discharge with special reference to eligibility criteria for IV thrombolysis, symptomatic hemorrhage, and clinical outcome., Results: The average age of the patients was 74 years, with 34% being older than 80 years. The median time between stroke onset and initiation of treatment was 112 min. The initial median NIHSS was 11 points (Rankin score  ≥ 4 in 79% of patients). The rate of symptomatic hemorrhage was 3%. The median follow-up was 14 days. At the end of the observation period, clinical symptoms had improved in 73% of patients (Rankin score  ≤ 2 in 45% of patients). The mortality rate was 12%. In 55% of patients, IV thrombolysis was off label (age  > 80 years in 34% of patients)., Conclusion: The clinical results of IV thrombolysis in our stroke center are similar to the outcome reported from the registration trials and larger clinical series although we treated off label in more than half of the patients. Even larger studies have since shown that the age limit under 80 years for patients is not reasonable. The eligibility criteria should be adapted to reality at this point.

Ischemic stroke is a medical emergency and must be treated as quickly as possible according to the "time-is-brain" concept. At present, intravenous administration of recombinant tissue plasminogen activator (rt-PA) within the first 4.5 h from stroke onset is the only effective treatment but is currently still only approved within the first 3 h from onset of symptoms (0.9 mg/kg body weight, maximum dose 90 mg, 10% of the cumulative dose as bolus, remaining 90% subsequently infused within 60 min). The therapeutic effect of magnetic resonance imaging (MRI) based thrombolytic therapy beyond the 4.5 h time window remains to be proven. Proximal occlusions of the middle cerebral artery can be treated successfully within the first 6 h from stroke onset by catheter-based intra-arterial administration of plasminogen activator leading to a significant improvement of outcome. Acute basilar artery occlusion should be treated in specialized centres using intra-arterial application of urokinase, rt-PA or mechanical recanalization but intravenous thrombolysis beyond the 3 h window is an acceptable alternative.

Patients with a transient ischemic attack (TIA) or ischemic stroke are at high risk for a recurrent stroke. Platelet inhibitors can reduce this risk in patients with non-cardioembolic stroke or TIA. Aspirin is used for secondary prevention in patients with a low risk of recurrent stroke while the combination of aspirin and dipyridamole or clopidogrel is recommended in patients with a higher risk. Patients with atrial fibrillation have a five-fold increased risk of stroke. In comparison to placebo oral anticoagulation reduces the risk of stroke by 60-70% in primary and secondary stroke prevention. Aspirin can still reduce the relative stroke risk by 22% in patients with atrial fibrillation who have contraindications against anticoagulation. Given the limitations of oral anticoagulation with vitamin K antagonists a new generation of anticoagulants is currently being investigated which include factor Xa inhibitors and direct thrombin antagonists. Dabigatran has been shown to be as efficacious as warfarin given at a lower dose and significantly more efficacious when administered at a higher dosage. Both cerebral and intracranial hemorrhages were reduced by 60-80% in patients treated with dabigatran when compared to warfarin.

An optimised prehospital management is important for acute stroke patients. A structured admittance to a stroke centre increases the rate of thrombolysis four-fold. To achieve short door-to-needle-times (< 30 min) a multi-disciplinary approach is necessary. Elderly stroke patients benefit from stroke unit therapy as do the younger patients. Blood pressure management is important during the first 24 hours after thrombolysis. Systolic blood pressures between 140 - 150 mmHg correlate with low bleeding rates. A subgroup analysis of the ECASS III study shows that a broad range of patients can be treated safely and efficiently in the 3 - 4.5 hour time window. Endovascular recanalisation therapy achieves high recanalisation rates. Whether these will be responsible for a significantly better outcome has to be shown in future randomised trials., (© Georg Thieme Verlag KG Stuttgart · New York.)