Intravenous Tirofiban With Intra-Arterial Urokinase and Mechanical Thrombolysis in Stroke

Background and Purpose— To evaluate preliminarily efficacy and safety of intravenous tirofiban combined with mechanical clot disruption and urokinase in patients with stroke attributable to major cerebral artery occlusion. Methods— Eleven consecutive patients with stroke attributable to acute occlusion of a major cerebral artery were treated with an intravenous bolus injection of the platelet glycoprotein IIb/IIIa antagonist tirofiban combined with heparin and by endovascular procedures including mechanical thrombolysis and locally delivered urokinase. Of the 11 cases, 9 involved angioplasty and 2 only microcatheter and microguidewire manipulation. Results— There were 7 patients with internal carotid or middle cerebral artery occlusion treated within 6 hours and 4 patients with basilar artery occlusion treated within 12 hours of symptom onset. Median National Institutes of Health Stroke Scale (NIHSS) score on admission was 20. After the interventional procedure, vessel recanalization was partial (thrombolysis in myocardial infarction grade flow 2 [TIMI 2]) in 7 patients and absent or insufficient in 4 patients. Twenty-four hours after the procedure, all the patients but 1 improved substantially, and on control angiography, the occluded vessel was totally patent (TIMI 3) in 10 of the 11 patients. One patient with partial recanalization did not improve and died 3 months later from pulmonary embolism. Neither a symptomatic intracerebral hemorrhage nor systemic bleedings requiring blood transfusion occurred in any patient. At discharge, median NIHSS score was 2. The 3-month outcome was excellent in 8 patients (modified Rankin Scale [mRS] 0 to 1), good in 2 patients (mRS 2), and poor in 1 patient (mRS 6). Conclusions— The combination of intravenous tirofiban with intra-arterial mechanical clot disruption and urokinase may be successful in reopening an occluded major cerebral vessel without increasing the hemorrhagic risk and with good functional outcome. This strategy cannot be recommended as the systematic treatment of stroke attributable to major cerebral artery occlusion until tested in a controlled study design

Small vessel disease and biomarkers of endothelial dysfunction after ischaemic stroke

Abstract Introduction: Although pathogenesis of small vessel disease is poorly understood, increasing evidence suggests that endothelial dysfunction may have a relevant role in development and progression of small vessel disease. In this crosssectional study, we investigated the associations between imaging signs of small vessel disease and blood biomarkers of endothelial dysfunction at two different time points in a population of ischaemic stroke patients. Patients and methods: In stroke patients treated with intravenous thrombolysis, we analysed blood levels of von Willebrand factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and vascular endothelial growth factor. Three reviewers independently assessed small vessel disease features using computed tomography. At baseline and 90 days after the index stroke, we tested the associations between single and combined small vessel disease features and levels of blood biomarkers using linear regression analysis adjusting for age, sex, hypertension, diabetes, smoke. Results: A total of 263 patients were available for the analysis. Mean age (SD) was 69 (13) years, 154 (59%) patients were male.We did not find any relation between small vessel disease and endothelial dysfunction at baseline. At 90 days, leukoaraiosis was independently associated with intercellular adhesionmolecule-1 (b¼0.21; p¼0.016) and vascular cell adhesionmolecule- 1 (b¼0.22; p¼0.009), and lacunes were associated with vascular endothelial growth factor levels (b¼0.21; p¼0.009) whereas global small vessel disease burden was associated with vascular endothelial growth factor (b¼0.26; p¼0.006). Discussion: Leukoaraiosis and lacunes were associated with endothelial dysfunction, which could play a key role in pathogenesis of small vessel disease

Unbalanced metalloproteinase-9 and tissue inhibitors of metalloproteinases ratios predict hemorrhagic transformation of lesion in ischemic stroke patients treated with thrombolysis: Results from the MAGIC study

Background Experimentally, metalloproteinases (MMPs) play a detrimental role related to severity of ischemic brain lesions. Both MMPs activity and function in tissues reflect the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We aimed to evaluate the role of MMPs/TIMPs balance in the setting of rtPA treated stroke patients Methods Blood was taken before and 24-hours after rtPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Delta median values of each MMP/TIMP ratio [(post rtPA MMP/TIMP-baseline MMP/TIMP)/(baseline MMP/TIMP)] were analyzed related to symptomatic intracranial hemorrhage (sICH) according to NINDS criteria, relevant hemorrhagic transformation (HT) defined as hemorrhagic infarction type 2 or any parenchimal hemorrhage, stroke subtypes (according to Oxfordshire Community Stroke Project) and 3-month death. The net effect of each MMP/TIMP ratio was estimated by a logistic regression model including major clinical determinants of outcomes Results Adjusting for major clinical determinants, only increase in MMP9/TIMP1 and MMP9/TIMP2 ratios remained significantly associated with sICH (odds ratio [95% confidence interval], 1.67 [1.17 – 2.38], p = 0.005; 1.74 [1.21 – 2.49], p=0.003 respectively). Only relative increase in MMP9/TIMP1 ratio proved significantly associated with relevant HT (odds ratio [95% confidence interval], 1.74 [1.17 – 2.57], p=0.006) with a trend towards significance for MMP9/TIMP2 ratio (p=0.007).Discussion Our data add substantial clinical evidence about the role of MMPs/TIMPs balance in rtPA treated stroke patients. These results may serve to generate hypotheses on MMPs inhibitors to be administered together with rtPA in order to counteract its deleterious effect

Aphasia predicts unfavorable outcome in mild ischemic stroke patients and prompts thrombolytic treatment

Background: Patients with an acute ischemic stroke rated as mild, and for this reason not submitted to thrombolysis, have an unfavorable outcome in a non-negligible proportion. Whether selective presentation features help identify those at risk of bad outcome, and whether it could be recommended to treat only patients with such features, is poorly elucidated.We report our experience based on retrospective evaluation of a consecutive series of patients scoring 6 or less on baseline National Institutes of Health Stroke Scale (NIHSS), some of whom received thrombolysis. Methods: From the prospective Careggi Hospital Stroke Registry, Florence, Italy, we selected a series of patients who fulfilled the following criteria: (1) screening for treatment within 3 hours of symptom onset; (2) mild symptoms, defined as a score of 6 or less on NIHSS, with or without rapid improvement; (3) no other reason for exclusion from thrombolysis; (4) no previous disability; and (5) admission to the stroke unit. We choose a modified Rankin scale score of less than 2 to define a good 3-month functional outcome.We studied as potential outcome predictors: age, baseline NIHSS score, isolated aphasia, motor impairment with or without aphasia, thrombolysis, previous stroke or transient ischemic attack, and interactions between each of these factors and thrombolysis. Results: Between February 2004 and June 2011, 128 patients fulfilled the selection criteria: 47 (36.7%) received tissue plasminogen activator, 81 (63.3%) did not. At 3 months, of the 81 patients not receiving tissue plasminogen activator, 14 (17.3%) had an unfavorable outcome, compared with 6 (12.8%) among the 47 treated. Hemorrhagic complications or death occurred in neither group. Adjusting for major confounders and for thrombolysis, the presence of aphasia on early assessment proved the only independent predictor of worse outcome. NIHSS score variation showed no effect. Conclusions: Aphasia is an early marker of unfavorable outcome in mild ischemic stroke patients. In these patients thrombolysis should be considered beyond the NIHSS scoring. Key Words: Aphasia—ischemic stroke—thrombolysis—mild symptoms

Translational Stroke Research Review: Using the Mouse to Model Human Futile Recanalization and Reperfusion Injury in Ischemic Brain Tissue

The approach to reperfusion therapies in stroke patients is rapidly evolving, but there is still no explanation why a substantial proportion of patients have a poor clinical prognosis despite successful flow restoration. This issue of futile recanalization is explained here by three clinical cases, which, despite complete recanalization, have very different outcomes. Preclinical research is particularly suited to characterize the highly dynamic changes in acute ischemic stroke and identify potential treatment targets useful for clinical translation. This review surveys the efforts taken so far to achieve mouse models capable of investigating the neurovascular underpinnings of futile recanalization. We highlight the translational potential of targeting tissue reperfusion in fully recanalized mouse models and of investigating the underlying pathophysiological mechanisms from subcellular to tissue scale. We suggest that stroke preclinical research should increasingly drive forward a continuous and circular dialogue with clinical research. When the preclinical and the clinical stroke research are consistent, translational success will follow

DYNAMAP – Development of low cost sensors networks for real time noise mapping

The Environmental Noise Directive (END) requires that regular updating of noise maps is implemented every five years to check and report about the changes occurred during the reference period. The updating process is usually achieved using a standardized approach, consisting in collating and processing information through acoustic models to produce the updated maps. This procedure is time consuming and costly, and has a significant impact on the budget of the authorities responsible for providing the maps. Furthermore, END requires that simplified and easy-to-read noise maps are made available to inform the public about noise levels and actions to be undertaken by local and central authorities to reduce noise impacts. To make the updating of noisemaps easier and more cost effective, there is a need for integrated systems that incorporate real-time measurement and processing to assess the acoustic impact of noise sources. To that end, a dedicated project, named DYNAMAP (DYNamic Acoustic MAPping), has been proposed and co-financed in the framework of the LIFE 2013 program, with the aim to develop a dynamic noise mapping system able to detect and represent in real time the acoustic impact of road infrastructures. In this paper, after a comprehensive description of the project idea, objectives and expected results, the most important steps to achieve the ultimate goal are described