110 results found
Wilson D, Ambler G, Lee K-J, et al., 2019, Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies, LANCET NEUROLOGY, Vol: 18, Pages: 653-665, ISSN: 1474-4422
Graf J, Schwitalla JC, Albrecht P, et al., 2019, Misdiagnoses and delay of diagnoses in Moyamoya angiopathy-a large Caucasian case series, JOURNAL OF NEUROLOGY, Vol: 266, Pages: 1153-1159, ISSN: 0340-5354
Wutzler A, Krogias C, Grau A, et al., 2019, Stroke prevention in patients with acute ischemic stroke and atrial fibrillation in Germany - a cross sectional survey, BMC Neurology, Vol: 19, ISSN: 1471-2377
BackgroundAtrial fibrillation (AF) is present in 15–20% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke.MethodsIn April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany.ResultsOverall, 154 stroke unit leads participated (response rate 52%). Anticoagulation in the acute phase of stroke is considered feasible in more than 90% of AF patients with ischemic stroke. Clinicians assume that about two thirds of all AF patients (range 20–100%) are discharged on oral anticoagulation. According to local preferences, acetylsalicylic acid is given orally in the majority of patients with delayed initiation of oral anticoagulation. A non-vitamin K-dependent oral anticoagulant (NOAC) is more often prescribed than a vitamin K-dependent oral anticoagulant (VKA). VKA is more often chosen in patients with previous VKA intake than in VKA naive patients. In the minority of patients, stroke unit leads discuss the prescription of a specific oral anticoagulant with the treating general practitioner. Adherence to medical stroke prevention after hospital discharge is not assessed on a regular basis in any patient by the majority of participating stroke centers.ConclusionsEarly secondary stroke prevention in AF patients in German stroke units is based on OAC use but prescription modalities vary in clinical practice.
Veltkamp R, Uhlmann S, Marinescu M, et al., 2019, Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction, Journal of Cachexia, Sarcopenia and Muscle, Vol: 10, Pages: 54-62, ISSN: 2190-6009
BackgroundStroke can lead to cardiac dysfunction in patients, but the mechanisms underlying the interaction between the injured brain and the heart are poorly understood. The objective of the study is to investigate the effects of experimental murine stroke on cardiac function and molecular signalling in the heart.Methods and resultsMice were subjected to filament‐induced left middle cerebral artery occlusion for 30 or 60 min or sham surgery and underwent repetitive micro‐echocardiography. Left ventricular contractility was reduced early (24–72 h) but not late (2 months) after brain ischaemia. Cardiac dysfunction was accompanied by a release of high‐sensitive cardiac troponin (hsTNT (ng/ml): d1: 7.0 ± 1.0 vs. 25.0 ± 3.2*; d3: 7.3 ± 1.1 vs. 52.2 ± 16.7*; d14: 5.7 ± 0.8 vs. 5.2 ± 0.3; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); reduced heart weight (heart weight/tibia length ratio: d1: 6.9 ± 0.2 vs. 6.4 ± 0.1*; d3: 6.7 ± 0.2 vs. 5.8 ± 0.1*; d14: 6.7 ± 0.2 vs. 6.4 ± 03; sham vs. 60 min. MCAO; mean ± SEM; *p < 0.05); resulting from cardiomyocyte atrophy (cardiomyocyte size: d1: 12.8% ± 0.002**; d3: 13.5% ± 0.002**; 14d: 6.3% ± 0.003*; 60 min. MCAO vs. sham; mean ± SEM; **p < 0.01; *p < 0.05), accompanied by increased atrogin‐1 and the E3 ubiquitin ligase murf‐1. Net norepinephrine but not synthesis was increased, suggesting a reduced norepinephrine release or an increase of norepinephrine re‐uptake, resulting in a functional denervation. Transcriptome analysis in cardiac tissue identified the transcription factor peroxisome proliferator‐activated rece
Tsivgoulis G, Wilson D, Katsanos AH, et al., 2018, Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage, ANNALS OF NEUROLOGY, Vol: 84, Pages: 694-704, ISSN: 0364-5134
Gill D, Georgakis MK, Laffan M, et al., 2018, Genetically determined FXI (Factor XI) levels and risk of stroke, Stroke, Vol: 49, Pages: 2761-2763, ISSN: 0039-2499
Background and Purpose—FXI (factor XI) is involved in thrombus propagation and stabilization. It is unknown whether lower FXI levels have a protective effect on risk of ischemic stroke (IS) or myocardial infarction. This study investigated the effect of genetically determined FXI levels on risk of IS, myocardial infarction, and intracerebral hemorrhage.Methods—Two-sample Mendelian randomization analysis was performed. Instruments and genetic association estimates for FXI levels were obtained from a genome-wide association study of 16 169 individuals. Genetic association estimates for IS and its etiological subtypes were obtained from a study of 16 851 cases and 32 473 controls. For myocardial infarction, estimates were obtained from a study of 43 676 cases and 123 504 controls and for intracerebral hemorrhage from a study of 1545 cases and 1481 controls.Results—After applying a Bonferroni correction for multiple testing, the Mendelian randomization analysis supported a causal effect of higher, genetically determined FXI levels on risk of any IS (odds ratio [OR] per 1-unit increase in natural logarithm-transformed FXI levels, 2.54; 95% CI, 1.68–3.84; P=1×10−5) but not myocardial infarction (OR, 1.01; 95% CI, 0.76–1.34; P=0.94) or intracerebral hemorrhage (OR, 1.81; 95% CI, 0.44–7.38; P=0.41). Examining IS subtypes, the main results supported an effect of higher, genetically determined FXI levels on risk of cardioembolism (OR, 4.23; 95% CI, 1.94–9.19; P=3×10−4) and IS of undetermined cause (OR, 3.44; 95% CI, 1.79–6.60; P=2×10−4) but not large artery atherosclerosis (OR, 2.73; 95% CI, 1.15–6.45; P=0.02) or small artery occlusion (OR, 1.19; 95% CI, 0.50–2.82; P=0.69). However, the statistically significant result for IS of undetermined cause was not replicated in all sensitivity analyses.Conclusions—We find Mendelian randomization evidence supporting FXI as a possible t
Van Mieghem NM, Unverdorben M, Valgimigli M, et al., 2018, Edoxaban Versus standard of care and their effects on clinical outcomes in patients having undergone Transcatheter Aortic Valve Implantation in Atrial Fibrillation-Rationale and design of the ENVISAGE-TAVI AF trial, AMERICAN HEART JOURNAL, Vol: 205, Pages: 63-69, ISSN: 0002-8703
Haeusler KG, Groeschel K, Koehrmann M, et al., 2018, Expert opinion paper on atrial fibrillation detection after ischemic stroke, CLINICAL RESEARCH IN CARDIOLOGY, Vol: 107, Pages: 871-880, ISSN: 1861-0684
Purrucker J, Wolf M, Haas K, et al., 2018, MICROBLEEDS IN ISCHEMIC VS. HEMORRHAGIC STROKES ON NOVEL ORAL ANTICOAGULANTS, INTERNATIONAL JOURNAL OF STROKE, Vol: 13, Pages: 84-84, ISSN: 1747-4930
Purrucker JC, Wolf M, Haas K, et al., 2018, Microbleeds in ischemic vs hemorrhagic strokes on novel oral anticoagulants, ACTA NEUROLOGICA SCANDINAVICA, Vol: 138, Pages: 163-169, ISSN: 0001-6314
Charidimou A, Shams S, Romero JR, et al., 2018, Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1), INTERNATIONAL JOURNAL OF STROKE, Vol: 13, Pages: 454-468, ISSN: 1747-4930
Hart RG, Sharma M, Mundl H, et al., 2018, Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 378, Pages: 2191-2201, ISSN: 0028-4793
Perera KS, Swaminathan B, Veltkamp R, et al., 2018, Frequency and features of embolic stroke of undetermined source in young adults, EUROPEAN STROKE JOURNAL, Vol: 3, Pages: 110-116, ISSN: 2396-9873
Kasner SE, Lavados P, Sharma M, et al., 2018, Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial, JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, Vol: 27, Pages: 1673-1682, ISSN: 1052-3057
Haeusler KG, Groeschel K, Koehrmann M, et al., 2018, Position Paper on Atrial Fibrillation Detection After Ischemic Stroke Working Group Heart and Brain of the German Cardiac Society (DGK) and the German Stroke Society (DSG), AKTUELLE NEUROLOGIE, Vol: 45, Pages: 93-106, ISSN: 0302-4350
Laible M, Schueler S, Veltkamp R, 2018, Preexisting cognitive impairment in intracerebral hemorrhage: Methodological issues Response, ACTA NEUROLOGICA SCANDINAVICA, Vol: 137, Pages: 371-371, ISSN: 0001-6314
Gill D, Sivakumaran P, Aravind A, et al., 2018, Temporal Trends in the Levels of Peripherally Circulating Leukocyte Subtypes in the Hours after Ischemic Stroke, JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, Vol: 27, Pages: 198-202, ISSN: 1052-3057
Charidimou A, Karayiannis C, Song T-J, et al., 2017, Brain microbleeds, anticoagulation, and hemorrhage risk Meta-analysis in stroke patients with AF, NEUROLOGY, Vol: 89, Pages: 2317-2326, ISSN: 0028-3878
Veltkamp R, Purrucker J, 2017, Management of Spontaneous Intracerebral Hemorrhage, CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, Vol: 17, ISSN: 1528-4042
Purpose of ReviewWe review the current evidence for medical and surgical treatments of spontaneous intracerebral hemorrhage (ICH).Recent FindingsTherapy with hemostatic agents (e.g. factor VIIa and tranexamic acid) if started early after bleeding onset may reduce hematoma expansion, but their clinical effectiveness has not been shown. Rapid anticoagulation reversal with prothrombin concentrates (PCC) plus vitamin K is the first choice in vitamin K antagonist-related ICH. In ICH related to dabigatran, anticoagulation can be rapidly reversed with idarucizumab. PCC are recommended for ICH related to FXa inhibitors, whereas specific reversal agents are not yet approved. While awaiting ongoing trials studying minimally invasive approaches or hemicraniectomy, the role of surgery in ICH remains to be defined. Therapies targeting downstream molecular cascades in order to prevent secondary neuronal damage are promising, but the complexity and multi-phased nature of ICH pathophysiology is challenging. Finally, in addition to blood pressure control, antithrombotic prevention after ICH has to consider the risk of recurrent bleeding as well as the risk of ischemic events.SummaryTreatment of acute ICH remains challenging, and many promising interventions for acute ICH await further evidence from trials.
Korompoki E, Filippidis FT, Nielsen PB, et al., 2017, Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation, NEUROLOGY, Vol: 89, Pages: 687-696, ISSN: 0028-3878
Objective: To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up.Methods: A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method.Results: Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27–0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29–0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79–2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45–1.90, p = 0.84).Conclusions: In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.
Marinescu M, Sun L, Fatar M, et al., 2017, Cerebral Microbleeds in Murine Amyloid Angiopathy Natural Course and Anticoagulant Effects, STROKE, Vol: 48, Pages: 2248-2254, ISSN: 0039-2499
Background and Purpose—Cerebral microbleeds (CMBs) predispose patients to intracerebral hemorrhage. Preclinical models to examine the effects of antithrombotic treatments on the development of clinically overt intracerebral hemorrhage are needed. We examined the natural course of CMB development and the effects of long-term anticoagulation with warfarin or dabigatran on cerebral micro- and macrohemorrhage in mice overexpressing the APP23 (amyloid precursor protein).Methods—Repeated susceptibility-weighted magnetic resonance imaging was performed in APP23 mice at the age of 18 and 21 months, respectively. After establishing stable long-term anticoagulation effects of warfarin and dabigatran on number and total volume of CMBs, the outcome parameters were compared with nonanticoagulated control.Results—CMBs were equally located in lobar and deep brain regions, and number and total volume of CMBs increased over time. Anticoagulation with either warfarin or dabigatran did not increase CMBs in APP23 significantly. Mice treated with warfarin numerically had a higher mortality (nonanticoagulated: 31%; dabigatran: 35% versus warfarin: 55%; P=0.21). In postmortem brains of prematurely dying animals warfarin caused significantly more frequently large intracerebral hemorrhage than control and dabigatran.Conclusions—Anticoagulation with warfarin or dabigatran for 3 to 4 months does not promote the formation of CMBs in aged APP23 mice. Nevertheless, warfarin but not dabigatran is associated with a higher risk of extensive intracerebral hemorrhage, suggesting that this model may allow preclinical safety evaluation of antithrombotic therapies.
Rizos T, Bartsch AJ, Johnson TD, et al., 2017, Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?, PLOS One, Vol: 12, ISSN: 1932-6203
ObjectiveAtrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke.MethodsPatients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke.Results582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF.ConclusionsIn the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations.
Purrucker JC, Rizos T, Haas K, et al., 2017, Coagulation testing in intracerebral hemorrhage related to non-vitamin K antagonist oral anticoagulants, Neurocritical Care, Vol: 27, Pages: 208-213, ISSN: 1556-0961
BACKGROUND: Intracerebral hemorrhage (ICH) is a life-threatening complication of non-vitamin K antagonist oral anticoagulants (NOAC). Little is known about the effect of intensity of anticoagulation on NOAC-ICH. We describe the current use of coagulation testing in the emergency setting and explore associations with baseline size and expansion of hematoma as determined in a previous study. METHODS: Data from the prospective multicenter RASUNOA registry were analyzed. Patients with NOAC-ICH were enrolled between February 2012 and December 2014. Frequency of local test performance of specific (anti-factor Xa tests, diluted thrombin time) and non-specific tests (international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time) was analyzed. The association of anticoagulation intensity at admission with hematoma volume and hematoma expansion was explored. RESULTS: In 61 NOAC-ICH patients enrolled at 21 centers, drug-specific coagulation testing was performed in 16 cases (26%), and only 29% of centers appeared to use drug-specific tests in NOAC-ICH at all. In some cases, INR and aPTT values were normal despite drug concentrations in the peak range. In patients with available drug-specific concentrations, 50% had drug levels in the peak range at admission. Higher intensity of anticoagulation was not associated with higher hematoma volume at admission or with subsequent hematoma expansion. CONCLUSION: Drug-specific tests are only infrequently used in NOAC-ICH. Normal results in non-specific coagulation do not reliably rule out peak range concentrations. Anticoagulation intensity at admission does not predict baseline hematoma volume or subsequent hematoma expansion.
Steiner T, Weitz JI, Veltkamp R, 2017, Anticoagulant-Associated Intracranial Hemorrhage in the Era of Reversal Agents, STROKE, Vol: 48, Pages: 1432-+, ISSN: 0039-2499
Wilson D, Seiffge DJ, Traenka C, et al., 2017, Outcome of intracerebral hemorrhage associated with different oral anticoagulants, Neurology, Vol: 88, Pages: 1693-1700, ISSN: 0028-3878
Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH).Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours.Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]).Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.
Elkins J, Veltkamp R, Montaner J, et al., 2017, Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial, LANCET NEUROLOGY, Vol: 16, Pages: 217-226, ISSN: 1474-4422
Uhlmann S, Mracsko E, Javidi E, et al., 2017, Genome-wide analysis of the circulating miRNome after cerebral ischemia reveals a reperfusion-induced microRNA cluster, Stroke, Vol: 48, Pages: 762-769, ISSN: 0039-2499
Background and Purpose—Circulating microRNAs (miRNAs) are emerging biomarkers for stroke because of their high stability in the bloodstream and association with pathophysiologic conditions. However, the circulating whole-genome miRNAs (miRNome) has not been characterized comprehensively in the acute phase of stroke.Methods—We profiled the circulating miRNome in mouse models of acute ischemic and hemorrhagic stroke by next-generation sequencing. Stroke models were compared with sham-operated and naive mice to identify deregulated circulating miRNAs. Top-ranked miRNAs were validated and further characterized by quantitative reverse transcription polymerase chain reaction.Results—We discovered 24 circulating miRNAs with an altered abundance in the circulation 3 hours after ischemia, whereas the circulating miRNome was not altered after intracerebral hemorrhage compared with sham-operated mice. Among the upregulated miRNAs in ischemia, the top-listed miR-1264/1298/448 cluster was strongly dependent on reperfusion in different ischemia models. A time course experiment revealed that the miR-1264/1298/448 cluster peaked in the circulation around 3 hours after reperfusion and gradually decreased thereafter.Conclusions—Alteration of the miRNome in the circulation is associated with cerebral ischemia/reperfusion, but not hemorrhage, suggesting a potential to serve as biomarkers for reperfusion in the acute phase. The pathophysiological role of reperfusion-inducible miR-1264/1298/448 cluster, which is located on chromosome X within the introns of the serotonin receptor HTR2C, requires further investigation.
Purrucker JC, Haas K, Wolf M, et al., 2017, Haernorrhagic transformation after ischaemic stroke in patients taking non-vitamin K antagonist oral anticoagulants, Journal of Stroke, Vol: 19, Pages: 67-76, ISSN: 2287-6391
J Stroke > Volume 19(1); 2017 > Article Original ArticleJournal of Stroke 2017;19(1):67-76.Published online: January 31, 2017DOI: https://doi.org/10.5853/jos.2016.00542Haemorrhagic Transformation after Ischaemic Stroke in Patients Taking Non-vitamin K Antagonist Oral AnticoagulantsJan C. Purruckera, Kirsten Haasb, Marcel Wolfc, Timolaos Rizosa, Shujah Khana, Peter Kraftd, Sven Polie, Rainer Dziewasf, Johannes Meyneg, Frederick Palmh, Sebastian Janderi, Markus Möhlenbruchc, Peter U. Heuschmannb,j, Roland Veltkampa,k, on behalf of the, RASUNOA investigatorsaDepartment of Neurology, Heidelberg University Hospital, Heidelberg, GermanybInstitute of Clinical Epidemiology and Biometry, University Würzburg, GermanycDepartment of Neuroradiology, Heidelberg University Hospital, Heidelberg, GermanydDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyeDepartment of Neurology, Tübingen University, Tübingen, GermanyfDepartment of Neurology, University Hospital Münster, GermanygDepartment of Neurology, University Hospital Schleswig-Holstein, Kiel, GermanyhDepartment of Neurology, Klinikum Ludwigshafen, Ludwigshafen, GermanyiDepartment of Neurology, Heinrich-Heine-University, Medical Faculty, Düsseldorf, GermanyjComprehensive Heart Failure Center, and Clinical Trial Center, University Hospital Würzburg, Würzburg, GermanykDepartment of Stroke Medicine, Imperial College London, London, United GermanyCorrespondence: Roland Veltkamp Department of Stroke Medicine, Imperial College London, Charing Cross Campus, 3 East 6, Fulham Palace Road, London, W6 8RF, United Kingdom Phone: +44-20-33130133, Fax: +44-20-83833309, E-mail: firstname.lastname@example.orgReceived June 16, 2016 Revised October 11, 2016 Accepted November 28, 2016Copyright © 2017 Korean Stroke SocietyThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://c
Mracsko E, Stegemann-Koniszewski S, Na S-Y, et al., 2017, A mouse model of post-stroke pneumonia induced by intra-tracheal inoculation with Streptococcus pneumoniae, Cerebrovascular Diseases, Vol: 43, Pages: 99-109, ISSN: 1015-9770
Background: Stroke-induced immunodeficiency increases the risk of infectious complications, which adversely affects neurological outcome. Among those, pneumonia affects as many as one third of stroke patients and is the main contributor to mortality in the post-acute phase of stroke. Experimental findings on post-stroke susceptibility to spontaneous pneumonia in mice are contradictory. Here, we established a mouse model inducing standardized bacterial pneumonia and characterized the impaired pulmonary cellular and humoral immune responses after experimental stroke. Methods: Bacterial pneumonia was induced by intra-tracheal inoculation with Streptococcus pneumoniae at different time points after transient middle cerebral artery occlusion (MCAO). Bacterial counts in lungs and blood, histological changes, and cytokine production in the lungs were assessed. Furthermore, we investigated the effect of pneumonia on stroke outcome. Results: Intra-tracheal inoculation resulted in reproducible pneumonia and bacteraemia, and demonstrated post-stroke susceptibility to streptococcal pneumonia developing with a delay of at least 24 h after MCAO. Higher bacterial counts in mice infected 3 days after stroke induction correlated with reduced neutrophil and macrophage infiltration in the lungs and lower levels of pro-inflammatory cytokines in the broncho-alveolar lavage compared to sham-operated animals. Pneumonia increased mortality without affecting brain-infiltrating leukocytes. Conclusions: In this standardized mouse model of post-stroke pneumonia, we describe attenuated leukocyte infiltration and cytokine production in response to bacterial infection in the lungs that has a profound effect on outcome.
Purrucker JC, Haas K, Rizos T, et al., 2016, Coagulation Testing in Acute Ischemic Stroke Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants, Stroke, Vol: 48, Pages: 152-158, ISSN: 0039-2499
Background and Purpose—In patients who present with acute ischemic stroke while on treatment with non–vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke.Methods—Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012–2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored.Results—In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%–44% [95% confidence interval 1%–69%]). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients.Conclusions—NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established.
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