Implicació de la inflamació i la resposta immunitària en la lesió induïda per la isquèmia

El sistema nerviós central (SNC) i el sistema immunitari (SI) estan estretament connectats. Es produeixen nombroses alteracions en el sistema immunitari després de la isquèmia i la inflamació es reconeix com una de les principals causes de la progressió de la lesió isquèmica. És molt important determinar el paper de les diferents cèl•lules implicades en la resposta immunitària i inflamatòria després de la isquèmia i el perfil de citocines que s’alliberen. A partir de l’estudi de les diferents poblacions de leucòcits en sang circulant després de la isquèmia, hem determinat que la subpoblació de monòcits (CD43high/CD11bhigh) augmenta a 48h de manera proporcional al volum d’infart. Aquesta població està formada per dos subtipus descrits de monòcits, els no clàssics (CD43high/Ly6C-) i els intermedis (CD43high/Ly6Cdim), i sembla expressar un perfil de citocines anti-inflamatòries així com una major capacitat fagocítica. Per altra banda, observem la presència de CD43 en el cervell i la seva degradació a 4 dies després de la isquèmia. També s’observa l’aparició de la fracció soluble del CD43 en el parènquima cerebral després del trencament de la barrera hematoencefàlica. Addicionalment, hem estudiat com s’alteren els canvis a nivell immunològic en ratolins deficients en CD69 i hem observat una pitjor progressió del volum d’infart en els animals CD69KO. A més a més hem volgut esbrinar el paper dels limfòcits utilitzant ratolins RAG (-/-) que tenen infarts més petits que els WT, però quan aquests careixen de CD69, tenen infarts significativament més grans. En l’estudi del procés inflamatori en la isquèmica, hem treballat amb ratolins deficient en ApoE i IL10. Pel que fa als ratolins ApoE (-/-), observem que tenen un volum d’infart més gran a les 24h i que es manté fins als 4 dies, i proposem que NFkB pot tenir un paper molt rellevant en aquest procés. Pel que fa a la IL-10, els animals deficients en aquesta citocina presenten un volum d’infart major i una expressió de citocines proinflamatòries més alt. A més a més, els ratolins IL10 KO presenten uns nivells de IL-12 més elevats de manera basal, i proposem que això és degut a la falta de la IL-10 per a inhibir la via.

A new automated method versus continuous positive airway pressure method for measuring pressure-volume curves in patients with acute lung injury

Objective: To compare pressure–volume (P–V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with ALI or ARDS receiving mechanical ventilation. P–V curves were fitted to a sigmoidal equation with a mean R2 of 0.994 ± 0.003. Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with high intraclass correlation coefficients. Bias and limits of agreement for LIP, UIP and PMC obtained with the two methods in the same patient were clinically acceptable.

Effects of MRI scan acceleration on brain volume measurement consistency.

PURPOSE: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. MATERIALS AND METHODS: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. RESULTS: Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. CONCLUSION: The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.

Standardization of Stroke Perfusion CT for Reperfusion Therapy

With the advances in terms of perfusion imaging, the "time is brain" approach used for acute reperfusion therapy in ischemic stroke patients is slowly being replaced by a "penumbra is brain" or "imaging is brain" approach. But the concept of penumbra-guided reperfusion therapy has not been validated. The lack of standardization in penumbral imaging is one of the main contributing factors for this absence of validation. This article reviews the issues underlying the lack of standardization of perfusion-CT for penumbra imaging, and offers avenues to remedy this situation

Northern Ireland Chest Heart & Stroke - Research Grants for 2010 in Respiratory and Cardiovascular Disease

To download an Application Form, Guidance Notes and other information, please visit the website www.nichsa.com or contact Caoimhe Devlin, Research Assistant by email: cdevlin@nichsa.com or phone: 02890 266714 / 02890 320184 ext 248.

Northern Ireland Chest Heart and Stroke Association

The project will develop a relationship with the pharmacist in Bessbrook and Kilkeel. 3 sessions will be held in each area allowing time for 1-1 support for clients and carers.

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 24 h 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 24 h 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 24 h 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 severity.

Stroke initial severity and outcome relative to insurance status in a universal health care system in Switzerland

Contexte et but de l'étude :Le statut socio-économique est suspecté d'avoir une influence significative sur l'incidence des attaques cérébrales (AVC), sur les facteurs de risque cardio-vasculaire, ainsi que sur le pronostic. L'influence de ce statut socio-économique sur la sévérité de l'AVC et sur les mécanismes physiopathologiques sous-jacents est moins connue.Méthode :Sur une période de 4 ans, nous avons collecté de manière prospective (dans un registre) des données concernant tous les patients avec AVC aigus admis à l'Unité Cérébrovasculaire du CHUV. Les données comprenaient le statut assécurologique du patient (assurance privée ou générale), les données démographiques, les facteurs de risque cérébrovasculaires, l'utilisation de traitements aigus de recanalisation vasculaire, le délai avant l'admission à l'hôpital, ainsi que la sévérité et le pronostic de l'AVC en phase aiguë, à 7 jours et à 3 mois des symptômes. Les patients avec assurance privée ont été comparés à ceux avec assurance générale.Résultats :Sur 1062 patients avec AVC, 203 avaient une assurance privée et 859 avaient une assurance générale. Il y a avait 585 hommes et 477 femmes. Les deux populations étaient similaires en âge. Les facteurs de risque cardio-vasculaire, la médication préventive, le délai d'arrivée à l'hôpital, l'incidence du taux de thrombolyse et l'étiologie de l'AVC ne différaient pas dans les deux populations. Le score de gravité de l'AVC en phase aiguë, mesuré par le NIHSS, était significativement plus élevé chez les patients avec assurance générale. Un pronostic favorable, mesuré par le score de Rankin modifié (mRS), était plus fréquemment obtenu à 7 jours et à 3 mois chez les patients avec assurance privée.Commentaires :Un statut socio-économique bas est associé à une incidence plus élevée de maladies cérébrovasculaires ainsi qu'à un plus mauvais pronostic, comme cela a été démontré dans différents pays. Il a été suspecté que l'accès à une prise en charge spécialisée en phase aiguë ou en rééducation soit différent selon le statut socio-économique. Comme la Suisse a un système de santé universel, avec une couverture assécurologique obligatoire pour chaque habitant, il y a là une occasion unique de comparer l'influence de l'aspect socio-économique sur la sévérité et le pronostic de l'AVC. De plus, les patients ont été admis dans la même Unité Cérébrovasculaire et pris en charge par la même équipe médicale.Conclusion et perspectives :Le lien entre le statut assécurologique et le statut socio-économique a déjà été prouvé par le passé dans d'autres pays. Nous avons mis en évidence une sévérité plus importante et un plus mauvais pronostic chez les patients avec assurance générale dans la population étudiée. L'étiologie de cette différence dans un système de santé à couverture universelle comme celui de la Suisse reste peu claire. Elle devrait être étudiée à plus grande échelle.

Prediction of recanalization in acute stroke patients receiving intravenous and endovascular revascularization therapy.

BACKGROUND AND PURPOSE: The study aims to assess the recanalization rate in acute ischemic stroke patients who received no revascularization therapy, intravenous thrombolysis, and endovascular treatment, respectively, and to identify best clinical and imaging predictors of recanalization in each treatment group. METHODS: Clinical and imaging data were collected in 103 patients with acute ischemic stroke caused by anterior circulation arterial occlusion. We recorded demographics and vascular risk factors. We reviewed the noncontrast head computed tomographies to assess for hyperdense middle cerebral artery and its computed tomography density. We reviewed the computed tomography angiograms and the raw images to determine the site and degree of arterial occlusion, collateral score, clot burden score, and the density of the clot. Recanalization status was assessed on recanalization imaging using Thrombolysis in Myocardial Ischemia. Multivariate logistic regressions were utilized to determine the best predictors of outcome in each treatment group. RESULTS: Among the 103 study patients, 43 (42%) received intravenous thrombolysis, 34 (33%) received endovascular thrombolysis, and 26 (25%) did not receive any revascularization therapy. In the patients with intravenous thrombolysis or no revascularization therapy, recanalization of the vessel was more likely with intravenous thrombolysis (P = 0·046) and when M1/A1 was occluded (P = 0·001). In this subgroup of patients, clot burden score, cervical degree of stenosis (North American Symptomatic Carotid Endarterectomy Trial), and hyperlipidemia status added information to the aforementioned likelihood of recanalization at the patient level (P < 0·001). In patients with endovascular thrombolysis, recanalization of the vessel was more likely in the case of a higher computed tomography angiogram clot density (P = 0·012), and in this subgroup of patients gender added information to the likelihood of recanalization at the patient level (P = 0·044). CONCLUSION: The overall likelihood of recanalization was the highest in the endovascular group, and higher for intravenous thrombolysis compared with no revascularization therapy. However, our statistical models of recanalization for each individual patient indicate significant variability between treatment options, suggesting the need to include this prediction in the personalized treatment selection.

Safety and feasibility of NeuroFlo use in eight- to 24-hour ischemic stroke patients.

BACKGROUND: Acute treatment of ischemic stroke patients presenting more than eight-hours after symptom onset remains limited and largely unproven. Partial aortic occlusion using the NeuroFlo catheter can augment cerebral perfusion in animals. We investigated the safety and feasibility of employing this novel catheter to treat ischemic stroke patients eight-hours to 24 h following symptom onset. METHODS: A multicenter, single-arm trial enrolled ischemic stroke patients at nine international academic medical centers. Eligibility included age 18-85 years old, National Institutes of Health stroke scale (NIHSS) score between four and 20, within eight-hours to 24 h after symptom onset, and perfusion-diffusion mismatch confirmed by magnetic resonance imaging. The primary outcome was all adverse events occurring from baseline to 30 days posttreatment. Secondary outcomes included stroke severity on neurological indices through 90 days. This study is registered with ClinicalTrials.gov, number NCT00436592. RESULTS: A total of 26 patients were enrolled. Of these, 25 received treatment (one excluded due to aortic morphology); five (20%) died. Favorable neurological outcome at 90 days (modified Rankin score 0-2 vs. 3-6) was associated with lower baseline NIHSS (P < 0·001) and with longer duration from symptom discovery to treatment. There were no symptomatic intracranial hemorrhages or parenchymal hematomas. Asymptomatic intracranial hemorrhage was visible on computed tomography in 32% and only on microbleed in another 20%. CONCLUSIONS: Partial aortic occlusion using the NeuroFlo catheter, a novel collateral therapeutic strategy, appears safe and feasible in stroke patients eight-hours to 24 h after symptom onset.

Nava enhances ventilatory variability and diaphragmatic activity/tidal volume coupling

INTRODUCTION. Neurally Adjusted Ventilatory Assist (NAVA) is a new ventilatory mode in which ventilator settings are adjusted based on the electrical activity detected in the diaphragm (Eadi). This mode offers significant advantages in mechanical ventilation over standard pressure support (PS) modes, since ventilator input is determined directly from patient ventilatory demand. Therefore, it is expected that tidal volume (Vt) under NAVA would show better correlation with Eadi compared with PS, and exhibit greater variability due to the variability in the Eadi input to the ventilator. OBJECTIVES. To compare tidal volume variability in PS and NAVA ventilation modes, and its correlation with patient ventilatory demand (as characterized by maximum Eadi). METHODS. Acomparative study of patient-ventilator interaction was performed for 22 patients during standard PS with clinician determined ventilator settings; and NAVA, with NAVA gain set to ensure the same peak airway pressure as the total pressure obtained in PS. A 20 min continuous recording was performed in each ventilator mode. Respiratory rate, Vt, and Eadi were recorded. Tidal volume variance and Pearson correlation coefficient between Vt and Eadi were calculated for each patient. A periodogram was plotted for each ventilator mode and each patient, showing spectral power as a function of frequency to assess variability. RESULTS. Median, lower quartile and upper quartile values for Vt variance and Vt/Eadi correlation are shown in Table 1. The NAVA cohort exhibits substantially greater correlation and variance than the PS cohort. Power spectrums for Vt and Eadi are shown in Fig. 1 (PS and NAVA) for a typical patient. The enlarged section highlights how changes in Eadi are highly synchronized with NAVA ventilation, but less so for PS. CONCLUSIONS. There is greater variability in tidal volume and correlation between tidal volume and diaphragmatic electrical activity with NAVA compared to PS. These results are consistent with the improved patient-ventilator synchrony reported in the literature.