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Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial  [PDF]
Hendrik Harms, Konstantin Prass, Christian Meisel, Juliane Klehmet, Witold Rogge, Christoph Drenckhahn, Jos G?hler, Stefan Bereswill, Ulf G?bel, Klaus Dieter Wernecke, Tilo Wolf, Guy Arnold, Elke Halle, Hans-Dieter Volk, Ulrich Dirnagl, Andreas Meisel
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002158
Abstract: Background Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. Methods Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. Findings On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. Interpretation PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. Trial Registration Controlled-Trials.com ISRCTN74386719
Current Strategies To Prevent Ischemic stroke
Ashok P P
Annals of Indian Academy of Neurology , 2003,
Abstract: The very small numbers of acute ischemic stroke that can be effectively treated makes prevention of stroke a better option especially in a country like India. Hypertension is the commonest risk factor and control of even this is not effective. We are now looking at other options such as inflammatory drugs, ACE inhibitors, Statins, vitamins, new antiplatelet agents etc in a bid to prevent ischemic strokes.
Ischemic Stroke
Eleni Dokoutsidou,Konstantina Antoniou
To Vima tou Asklipiou , 2009,
Abstract: Stroke is currently the third leading cause of death, ranking after heart disease and cancer and causes 10% of deaths, worldwide.Aim: The aim of the present study was to review the literature about the types of stroke and the risk factors for ischemic stroke.The methodoly that was followed included bibliography review from the both the research and the review literature of Greek and international data base which referred to ischemic stroke.Results: Stroke, according to its’ underlying etiology, can be classified into two major categories, ischemic and hemorrhagic. 20% of stroke are of hemorrhagic type, whereas 80% are of ischemic type. Although, ischemic stroke is the most common type, its’ etiology differs. Ischemic stroke is categorized in thrombotic, embolic, lacunar, unknown etiology, transient and due to systematic low blood pressure. In the literature is cited that risk factors for stroke are classified in non-modifiable and modifiable. Non-modifiable risk factors are age, gender, ethnicity and heredity. The most important modifiable risk factors for stroke are high blood pressure and atrial fibrillation. Other modifiable risk factors include high blood cholesterol levels, diabetes mellitus, cigarette smoking (active and passive), carotid artery stenosis, heavy alcohol consumption, drug abuse, lack of physical activity, obesity and unhealthy diet.Conclusions: As it is supported by published evidence, ischemic stroke is of higher incidence compared to hemorrhagic stroke. Risk factor modification remains as the principal aspect of care for ischemic stroke prevention.
Ischemic stroke: impairment and disability
Soyuer, F.,?zarslan, M.,Soyuer, A.
Erciyes Medical Journal , 2004,
Abstract: Objective: To describe the association between impairment and disability in patients with acute ischemic stroke. Method: Totaly 100 patients with ischemic stroke were assessed at Erciyes University Hospital Department of Neurology. The Rivermead Motor Assessment (RMA) was used to measure impairment and the Functional Independence Measure (FIM) was used to measure disability. The assessments were made at 7-10 days and 3 months during poststroke period. Results: RMA correlated significantly with FIM at 7-10 days and 3 months. Conclusion: Stroke-related impairment and disability are significantly correlated with each other.
Chinese Ischemic Stroke Subclassification  [PDF]
S. Gao
Frontiers in Neurology , 2011, DOI: 10.3389/fneur.2011.00006
Abstract: Accurate classification of stroke has significant impact on patient care and conduction of stroke clinical trials. The current systems such as TOAST, SSS-TOAST, Korean TOAST, and A–S–C–O have limitations. With the advent of new imaging technology, there is a need to have a more accurate stroke subclassification system. Chinese ischemic stroke subclassification (CISS) system is a new two step system aims at the etiology and then underlying mechanism of a stroke. The first step classify stroke into five categories: large artery atherosclerosis (LAA), including atherosclerosis of aortic arch and intra-/extracranial large arteries, cardiogenic stroke, penetrating artery disease, other etiology, and undetermined etiology. The second step is to further classify the underlying mechanism of ischemic stroke from the intracranial and extracranial LAA into the parent artery (plaque or thrombosis) occluding penetrating artery, artery-to-artery embolism, hypoperfusion/impaired emboli clearance, and multiple mechanisms. Although clinical validation of CISS is being planned, CISS is an innovative system that offers much more detailed information on the pathophysiology of a stroke.
Isolation of inflammatory cells from rat brain tissue after stroke
Karoline M?ller, Tobias Stahl, Johannes Boltze, Daniel-Christoph Wagner
Experimental & Translational Stroke Medicine , 2012, DOI: 10.1186/2040-7378-4-20
Abstract: Cerebral stroke is still one of the main causes of death and acquired disabilities worldwide. The sole established therapeutic option is thrombolysis, which is severely limited by a narrow time window and several contraindications [1]. Cumulatively, only 5 - 13% of stroke patients benefit from clot lysis [2,3] whereas the remaining survivors have to be content with symptomatic and preventive treatments. The situation is even worse for patients suffering from hemorrhagic stroke where no causal treatment is available. Hence, numerous preclinical and clinical trials have been performed to test novel treatment options to ultimately reach more stroke patients [4].Amongst others, the modulation of inflammatory responses became a promising approach to treat cerebral ischemic and hemorrhagic stroke even days beyond the time window for thrombolysis [5]. The sterile inflammation after stroke was initially considered to be merely adverse and many pharmacological agents have been proposed to block this event [6]. However, recent evidence indicates a much more complex and partly conflicting picture [7]. Mostly by employing different knock-out mouse models, it has been emphasized that, in the early phase after stroke, T-cells act primarily detrimental [8,9] whereas B-cells seem to rather protect the injured brain [10]. The role of regulatory T-cells is still controversially discussed [11,12] and scarce knowledge is available about specific Th1, Th2 and Th17 responses [13] or the possible development of post-stroke autoimmunity and its sequelae [14].Hence it is clear that the identification and quantification of infiltrating inflammatory cells in animal models of stroke is critical for understanding the complex processes of post-stroke inflammation and for the identification of novel therapeutic targets. Multicolour flow cytometry has turned out to be the gold standard to achieve this goal since it allows the simultaneous identification and quantification of several immune cell su
Quantifying the Contribution of Risk Factors for Ischemic Stroke in Patients with a History of TIA  [PDF]
Duncan C. Ramsey,Mark G. Burnett,Matthew C. Cowperthwaite
ISRN Stroke , 2012, DOI: 10.5402/2012/976045
Abstract: Background. Patients with a history of transient ischemic attack (TIA) are known to be at higher risk for a stroke. We sought to investigate predictors of individual risk for an ischemic stroke within 30 days of a TIA. Methods and Results. A retrospective analysis of 57,585 TIA admissions was collected from 155 United States hospitals. Data describing each admission included demographic and clinical data, and information about the admitting hospital. Cerebrovascular disease was the primary readmission reason (19% of readmissions) in the TIA patient population. The prevalence of 30-day ischemic stroke readmissions was 11 per 1,000 TIA admissions; however, 53% of stroke readmissions occurred within one week. Hierarchal regression models suggested that peripheral vascular disease and hypertensive chronic kidney disease were significant individual stroke risk factors, whereas history of myocardial infarction, essential hypertension, and diabetes mellitus was not associated with significant stroke risk. Certified stroke centers were not associated with significantly lower stroke readmission rates. Conclusions. The results suggest that cardiovascular comorbidities confer the most significant risk for an ischemic stroke within 30 days of a TIA. Interestingly, certified stroke centers do not appear to be associated with significantly lower stroke-readmission rates, highlighting the challenges managing this patient population. 1. Introduction Annually, as many as 250,000 Americans may experience a transient ischemic attack (TIA); the annual worldwide incidence of TIA may exceed one million [1]. The 6-month mortality rate has been estimated to be as high as 8.3% in this patient population [2]. TIA is therefore associated with significant morbidity and mortality in the United States and globally. TIAs are significant risk factors for stroke with as many as 19% of acute strokes preceded by TIA [3, 4]. Several studies have identified risk factors for stroke in patients with history of TIA [2, 3, 5–7]; however, the contribution of these factors to a patient’s overall stroke risk has yet to be comprehensively studied. Identifying TIA patients at risk for a stroke is an important component of targeting preventive therapies. In the present study, we develop a risk-standardized model to (i) quantify the contribution of demographic and clinical factors to stroke risk and (ii) to identify TIA patients at high-risk for stroke. The model is also suitable for comparing stroke readmission rates across hospitals to gain insight into how hospitalization may affect stroke rates
Functional recovery in ischemic stroke
Paithankar M,Dabhi R
Neurology India , 2003,
Abstract: Functional outcome at three months was studied in 72 patients with ischemic stroke. The Canadian Neurological Scale was used to assess the severity of stroke at admission and functional outcome at 3 months was assessed using modified Rankin scale. The size and site of the infarct was noted from the initial CT. Risk factors like hypertension, diabetes, and serum cholesterol were analyzed. Initial neurological scoring at admission, and size and site of the infarct were significantly associated with functional recovery at 3 months.
Infections and Ischemic Stroke Outcome  [PDF]
Katarzyna Grabska,Gra?yna Gromadzka,Anna Cz?onkowska
Neurology Research International , 2011, DOI: 10.1155/2011/691348
Abstract: Background. Infections increase the risk of ischemic stroke (IS) and may worsen IS prognosis. Adverse effects of in-hospital infections on stroke outcome were also reported. We aimed to study the prevalence of pre- and poststroke infections and their impact on IS outcome. Methods. We analysed clinical data of 2066 IS patients to assess the effect of pre-stroke and post-stroke infections on IS severity, as well as short-term (up to 30 days) and long-term (90 days) outcome. The independent impact of infections on poor outcome (death, death/dependency) was investigated by use of logistic regression analysis. The effect of antibiotic therapy during hospitalization on the outcome was also assessed. Results. Pre-stroke infections independently predicted worse short-term outcome. In-hospital infections were associated with worse short-term and long-term IS prognosis. Antibacterial treatment during hospitalization did not improve patients' outcome. Conclusions. Prevention of infections may improve IS prognosis. The role of antibiotic therapy after IS requires further investigations. 1. Introduction Infections preceding the ischemic stroke (IS), as well as infections occurring in the acute phase of IS, are a frequent phenomenon [1, 2]. Chronic infections of both viral and bacterial etiology and coexistent vascular inflammatory state promote atherosclerosis, contributing to an increased cerebrovascular risk [3, 4]. The association of prestroke acute infectious events, in particular, respiratory tract infections, with increased risk of stroke [5], especially of cardioembolic and atherothrombotic etiology, was reported [2, 6]. Some authors suggest that prestroke infections are related not only to the risk but also to IS severity [7, 8]. On the other hand, stroke severity and lesion location are associated with the risk of in-hospital (post-stroke) infections. For example, patients with brainstem or diffuse cerebral lesions characterize with an increased risk of respiratory tract infection, that frequently results from dysphagia [9, 10]. It seems possible that post-stroke infectious events are favoured by the stroke-induced immunodepression [2]. The impact of post-stroke infections on IS outcome is the next important issue [11]. Some authors describe an association of post-stroke infections with poor patients’ outcome [12–14]. According to the presented data, a proper treatment of stroke-related infections may improve patients’ outcome. Until now some reports suggest that therapy with antibiotics in the acute phase of stroke (even in patients without the obvious
Pharmacological and Non-Pharmacological Recanalization Strategies in Acute Ischemic Stroke  [PDF]
Anita Frendl,László Csiba
Frontiers in Neurology , 2011, DOI: 10.3389/fneur.2011.00032
Abstract: According to the guidelines of the European Stroke Organization (ESO) and the American Stroke Association (ASA), acute stroke patients should be managed at stroke units that include well organized pre- and in-hospital care. In ischemic stroke the restoration of blood flow has to occur within a limited time window that is accomplished by fibrinolytic therapy. Newer generation thrombolytic agents (alteplase, pro-urokinase, reteplase, tenecteplase, desmoteplase) have shorter half-life and are more fibrin-specific. Only alteplase has Food and Drug Administration (FDA) approval for the treatment of acute stroke (1996). The National Institute of Neurological Disorders and Stroke (NINDS) trial proved that alteplase was effective in all subtypes of ischemic strokes within the first 3 h. In the European cooperative acute stroke study III trial, intravenous (IV) alteplase therapy was found to be safe and effective (with some restrictions) if applied within the first 3–4.5 h. In middle cerebral artery (MCA) occlusion additional transcranial Doppler insonication may improve the breakdown of the blood clot. According to the ESO and ASA guidelines, intra-arterial (IA) thrombolysis is an option for recanalization within 6 h of MCA occlusion. Further trials on the IA therapy are needed, as previous studies have involved relatively small number of patients (compared to IV trials) and the optimal IA dose of alteplase has not been determined (20–30 mg is used most commonly in 2 h). Patients undergoing combined (IV + IA) thrombolysis had significantly better outcome than the placebo group or the IV therapy alone in the NINDS trial (Interventional Management of Stroke trials). If thrombolysis fails or it is contraindicated, mechanical devices [e.g., mechanical embolus removal in cerebral ischemia (MERCI)- approved in 2004] might be used to remove the occluding clot. Stenting can also be an option in case of acute internal carotid artery occlusion in the future. An intra-aortic balloon was used to increase the collateral blood flow in the Safety and Efficacy of NeuroFlo? Technology in Ischemic Stroke trial (results are under evaluation). Currently, there is no approved effective neuroprotective drug.
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