The effect of thrombolysis on short-term improvement depends on initial stroke severity

A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. In the present work we analyzed a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke with the aim of identifying independent predictors of the early clinical course. We used prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke admitted to our stroke unit and/or intensive care unit between 1 January 2003 and 12 December 2008 within 24h after last-well time were analyzed. Univariate and multivariate analyses were performed to identify significant associations with the National Institute of Health Stroke Scale (NIHSS) score at admission and 24h later. We also sought any interactions between the identified predictors. Of the 1,730 consecutive patients with acute ischemic stroke who were included in the analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the recommended time window. In multivariate analysis, the NIHSS score at 24h after admission was associated with the NIHSS score at admission (β=1, p<0.001), initial glucose level (β=0.05, p<0.002) and thrombolytic intervention (β=−2.91, p<0.001). There was a significant interaction between thrombolysis and the NIHSS score at admission (p<0.001), indicating that the short-term effect of thrombolysis decreases with increasing initial stroke severity. Thrombolytic treatment, lower initial glucose level and lower initial stroke severity predict a favorable early clinical course. The short-term effect of thrombolysis appears mainly in minor and moderate strokes, and decreases with increasing initial stroke severit

Acute seizures in acute ischemic stroke: does thrombolysis have a role to play?

Seizures appear at stroke presentation, during the acute phase or as a late complication of stroke. Thrombolysis has not been investigated as a risk factor despite its potential neurotoxic effect. We try to identify risk factors for seizures during the acute phase of ischemic stroke in a cohort including thrombolysed patients. We undertook a case-control study at a single stroke center using data from Acute Stroke Registry and Analyse of Lausanne (ASTRAL). Patients with seizure occurring during the first 7days following stroke were retrospectively identified. Bi-variable and multivariable statistical analyses were applied to compare cases and randomly selected controls. We identified 28 patients experiencing from seizures in 2,327 acute ischemic strokes (1.2%). All seizures occurred during the first 72h. Cortical involvement, thrombolysis with rt-PA, arterial recanalization, and higher initial NIHSS were statistically associated with seizures in univariated analysis. Backward linear regression identified cortical involvement (OR 7.53, 95% CI 1.6-35.2, p<0.01) and thrombolysis (OR 4.6, 95% CI 1.6-13.4, p=0.01) as being independently associated with seizure occurrence. Overall, 3-month outcome measured by the modified Rankin scale (mRS) was comparable in both groups. In the subgroup of thrombolysed patients, outcome was significantly worse at 3months in the seizure group with 9/12 (75%) patients with mRS ≥3, compared to 6/18 (33.3%) in the seizure-free group (p=0.03). Acute seizures in acute ischemic stroke were relatively infrequent. Cortical involvement and thrombolysis with rt-PA are the principal risk factors. Seizures have a potential negative influence on clinical outcome in thrombolysed patient

Beyond Conventional Event-related Brain Potential (ERP): Exploring the Time-course of Visual Emotion Processing Using Topographic and Principal Component Analyses

Recent technological advances with the scalp EEG methodology allow researchers to record electric fields generated in the human brain using a large number of electrodes or sensors (e.g. 64-256) distributed over the head surface (multi-channel recording). As a consequence, such high-density ERP mapping yields fairly dense ERP data sets that are often hard to analyze comprehensively or to relate straightforwardly to specific cognitive or emotional processes, because of the richness of the recorded signal in both the temporal (millisecond time-resolution) and spatial (multidimensional topographic information) domains. Principal component analyses (PCA) and topographic analyses (combined with distributed source localization algorithms) have been developed and successfully used to deal with this complexity, now offering powerful alternative strategies for data-driven analyses in complement to more traditional ERP analyses based on waveforms and peak measures. In this paper, we first briefly review the basic principles of these approaches, and then describe recent ERP studies that illustrate how they can inform about the precise spatio-temporal dynamic of emotion processing. These studies show that the perception of emotional visual stimuli may produce both quantitative and qualitative changes in the electric field configuration recorded at the scalp level, which are not apparent when using conventional ERP analyses. Additional information gained from these approaches include the identification of a sequence of successive processing stages that may not fully be reflected in ERP waveforms only, and the segregation of multiple or partly overlapping neural events that may be blended within a single ERP waveform. These findings highlight the added value of such alternative analyses when exploring the electrophysiological manifestations of complex and distributed mental functions, as for instance during emotion processin

CT angiography helps to differentiate acute from chronic carotid occlusion: the "carotid ring sign”

Introduction: Currently, there is no reliable method to differentiate acute from chronic carotid occlusion. We propose a novel CTA-based method to differentiate acute from chronic carotid occlusions that could potentially aid clinical management of patients. Methods: We examined 72 patients with 89 spontaneously occluded extracranial internal carotids with CT angiography (CTA). All occlusions were confirmed by another imaging modality and classified as acute (imaging 4weeks), based on circumstantial clinical and radiological evidence. A neuroradiologist and a neurologist blinded to clinical information determined the site of occlusion on axial sections of CTA. They also looked for (a) hypodensity in the carotid artery (thrombus), (b) contrast within the carotid wall (vasa vasorum), (c) the site of the occluded carotid, and (d) the "carotid ring sign” (defined as presence of a and/or b). Results: Of 89 occluded carotids, 24 were excluded because of insufficient circumstantial evidence to determine timing of occlusion, 4 because of insufficient image quality, and 3 because of subacute timing of occlusion. Among the remaining 45 acute and 13 chronic occlusions, inter-rater agreement (kappa) for the site of proximal occlusion was 0.88, 0.45 for distal occlusion, 0.78 for luminal hypodensity, 0.82 for wall contrast, and 0.90 for carotid ring sign. The carotid ring sign had 88.9% sensitivity, 69.2% specificity, and 84.5% accuracy to diagnose acute occlusion. Conclusion: The carotid ring sign helps to differentiate acute from chronic carotid occlusion. If further confirmed, this information may be helpful in studying ischemic symptoms and selecting treatment strategies in patients with carotid occlusion

TubeSpin bioreactor 50 for the high-density cultivation of Sf-9 insect cells in suspension

Here we present the TubeSpin bioreactor 50 (TubeSpins) as a simple and disposable culture system for Sf-9 insect cells in suspension. Sf-9 cells had substantially better growth in TubeSpins than in spinner flasks. After inoculation with 106cells/ml, maximal cell densities of 16×106 and 6×106cells/ml were reached in TubeSpins and spinner flasks, respectively. In addition the cell viability in these batch cultures remained above 90% for 10days in TubeSpins but only for 4days in spinner flasks. Inoculation at even higher cell densities reduced the duration of the lag phase. After inoculation at 2.5×106cells/ml, the culture reached the maximum cell density within 3days instead of 7days as observed for inoculation with 106cells/ml. Infection of Sf-9 cells in TubeSpins or spinner flasks with a recombinant baculovirus coding for green fluorescent protein (GFP) resulted in similar GFP-specific fluorescence levels. TubeSpins are thus an attractive option for the small-scale cultivation of Sf-9 cells in suspension and for baculovirus-mediated recombinant protein productio

Effect of transnasal insufflation on sleep disordered breathing in acute stroke: a preliminary study

Background and Purpose: Sleep disordered breathing (SDB) is frequent in acute stroke patients and is associated with early neurologic worsening and poor outcome. Although continuous positive airway pressure (CPAP) effectively treats SDB, compliance is low. The objective of the present study was to assess the tolerance and the efficacy of a continuous high-flow-rate air administered through an open nasal cannula (transnasal insufflation, TNI), a less-intrusive method, to treat SDB in acute stroke patients. Methods: Ten patients (age, 56.8 ± 10.7years), with SDB ranging from moderate to severe (apnea-hypopnea index, AHI, >15/h of sleep) and on a standard sleep study at a mean of 4.8 ± 3.7days after ischemic stroke (range, 1-15days), were selected. The night after, they underwent a second sleep study while receiving TNI (18L/min). Results: TNI was well tolerated by all patients. For the entire group, TNI decreased the AHI from 40.4 ± 25.7 to 30.8 ± 25.7/h (p = 0.001) and the oxygen desaturation index >3% from 40.7 ± 28.4 to 31 ± 22.5/h (p = 0.02). All participants except one showed a decrease in AHI. The percentage of slow-wave sleep significantly increased with TNI from 16.7 ± 8.2% to 22.3 ± 7.4% (p = 0.01). There was also a trend toward a reduction in markers of sleep disruption (number of awakenings, arousal index). Conclusions: TNI improves SDB indices, and possibly sleep parameters, in stroke patients. Although these changes are modest, our findings suggest that TNI is a viable treatment alternative to CPAP in patients with SDB in the acute phase of ischemic strok

A nonheme peroxo-diiron(iii) complex exhibiting both nucleophilic and electrophilic oxidation of organic substrates

The complex [Fe(III)(2)(μ-O(2))(L(3))(4)(S)(2)](4+) (L(3) = 2-(4-thiazolyl)benzimidazole, S = solvent) forms upon reaction of [Fe(II)(L(3))(2)] with H(2)O(2) and is a functional model of peroxo-diiron intermediates invoked during the catalytic cycle of oxidoreductases. The spectroscopic properties of the complex are in line with those of complexes formed with N-donor ligands. [Fe(III)(2)(μ-O(2))(L(3))(4)(S)(2)](4+) shows both nucleophilic (aldehydes) and electrophilic (phenol, N,N-dimethylanilines) oxidative reactivity and unusually also electron transfer oxidation

Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial

Introduction: Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset. Methods: Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria. Results: At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm3 in the treatment arm and 29 (8-105) cm3 in the placebo arm. Conclusions: This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be establishe