The Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+): rationale and methodology.

Venous thromboembolism (VTE) is common and has a high impact on morbidity, mortality, and costs of care. Although most of the patients with VTE are aged ≥65 years, there is little data about the medical outcomes in the elderly with VTE. The Swiss Cohort of Elderly Patients with VTE (SWITCO65+) is a prospective multicenter cohort study of in- and outpatients aged ≥65 years with acute VTE from all five Swiss university and four high-volume non-university hospitals. The goal is to examine which clinical and biological factors and processes of care drive short- and long-term medical outcomes, health-related quality of life, and medical resource utilization in elderly patients with acute VTE. The cohort also includes a large biobank with biological material from each participant. From September 2009 to March 2012, 1,863 elderly patients with VTE were screened and 1003 (53.8 %) were enrolled in the cohort. Overall, 51.7 % of patients were aged ≥75 years and 52.7 % were men. By October 16, 2012, after an average follow-up time of 512 days, 799 (79.7 %) patients were still actively participating. SWITCO65+ is a unique opportunity to study short- and long-term outcomes in elderly patients with VTE. The Steering Committee encourages national and international collaborative research projects related to SWITCO65+, including sharing anonymized data and biological samples.

Comparison of results of intravenous infusion of anistreplase versus streptokinase in acute myocardial infarction.

This randomized study compares the coronary perfusion rate in patients with acute myocardial infarction (AMI) treated with 2 different intravenous thrombolytic agents: streptokinase 1.5 million U given over 60 minutes and anisoylated human plasminogen streptokinase activator complex (anistreplase) administrated as a bolus of 30 U over 5 minutes. One hundred seventy-five patients (149 men and 26 women, mean age 54 years) have been included in this study. Eighty-nine patients were treated with anistreplase and 86 patients with streptokinase. AMI was inferior in 54 patients (61%) in the anistreplase group and in 54 patients (63%) in the streptokinase group. It was anterior in 35 (40%) and 32 (37%) patients, respectively. Coronary angiography and ventriculography were performed at a mean time (+/- SEM) of 207 +/- 11 minutes after the beginning of thrombolysis in 170 patients. A perfusion score grade of 2 or 3 according to the Thrombolysis in Myocardial Infarction trial was found in 63 patients (72%) in the anistreplase group and in 56 patients (68%) in the streptokinase group (p = NS). Severe bleeding occurred in 7 patients (8%) after anistreplase and in 6 patients (7%) after streptokinase. No cerebral hemorrhage occurred. Nine patients (5%) died during their hospital stay: 6 after anistreplase and 3 after streptokinase. It is concluded that intravenous administration of anistreplase or streptokinase is efficient and safe. Coronary patency 207 minutes after fibrinolysis, incidence of adverse events and mortality are similar in both groups.

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.

Extent of hypoattenuation on CT angiography source images in basilar artery occlusion: prognostic value in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). METHODS: BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0-3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0-2). RESULTS: Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS≥8. Patients with a pc-ASPECTS≥8 more often had a favorable outcome than patients with a pc-ASPECTS<8 (crude RR, 1.7; 95% CI, 0.98-3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8-2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5-0.98) and functional independence (RR, 2.0; 95% CI, 1.1-3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2-7.5). CONCLUSIONS: pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.

Improving prediction of recanalization in acute large-vessel occlusive stroke.

BACKGROUND: Recanalization in acute ischemic stroke with large-vessel occlusion is a potent indicator of good clinical outcome. OBJECTIVE: To identify easily available clinical and radiologic variables predicting recanalization at various occlusion sites. METHODS: All consecutive, acute stroke patients from the Acute STroke Registry and Analysis of Lausanne (2003-2011) who had a large-vessel occlusion on computed tomographic angiography (CTA) (< 12 h) were included. Recanalization status was assessed at 24 h (range: 12-48 h) with CTA, magnetic resonance angiography, or ultrasonography. Complete and partial recanalization (corresponding to the modified Treatment in Cerebral Ischemia scale 2-3) were grouped together. Patients were categorized according to occlusion site and treatment modality. RESULTS: Among 439 patients, 51% (224) showed complete or partial recanalization. In multivariate analysis, recanalization of any occlusion site was most strongly associated with endovascular treatment, including bridging therapy (odds ratio [OR] 7.1, 95% confidence interval [CI] 2.2-23.2), and less so with intravenous thrombolysis (OR 1.6, 95% CI 1.0-2.6) and recanalization treatments performed beyond guidelines (OR 2.6, 95% CI 1.2-5.7). Clot location (large vs. intermediate) and tandem pathology (the combination of intracranial occlusion and symptomatic extracranial stenosis) were other variables discriminating between recanalizers and non-recanalizers. For patients with intracranial occlusions, the variables significantly associated with recanalization after 24 h were: baseline National Institutes of Health Stroke Scale (NIHSS) (OR 1.04, 95% CI 1.02-1.1), Alberta Stroke Program Early CT Score (ASPECTS) on initial computed tomography (OR 1.2, 95% CI 1.1-1.3), and an altered level of consciousness (OR 0.2, 95% CI 0.1-0.5). CONCLUSIONS: Acute endovascular treatment is the single most important factor promoting recanalization in acute ischemic stroke. The presence of extracranial vessel stenosis or occlusion decreases recanalization rates. In patients with intracranial occlusions, higher NIHSS score and ASPECTS and normal vigilance facilitate recanalization. Clinical use of these predictors could influence recanalization strategies in individual patients.

Neurologie [News in neuroloey 2014].

In 2014, breastfeeding during maternal antiepileptic therapy seems to be safe for the children and can be recommended. Intravenous thrombolysis by Alteplase improves the outcome after a stroke if administered within 4.5 hours and it is also recommended in elderly population over 80 years. ProSavin genic therapy for Parkinson disease is under investigation. The Transcranial Magnetic Stimulation (TMS) has an analgesic effect in neuropathic pain as well as an antidepressant effect. Antagonists of calcitonin gene-related peptide can have a beneficial role in migraine prevention. Diagnostic biomarker panels for Alzheimer disease are under investigation. Oral teriflunomide and dimethyl fumarate (BG-12) for relapsing multiple sclerosis treatment are now available in Switzerland.

Usefulness of Clinical Scores for Patient Risk Stratification in Non-ST Elevation Acute Coronary Syndrome: Any Role for Serum Markers of Inflammation?

Risk stratification of patients with unstable angina or non ST-segment elevation myocardial infarction (UA/NSTEMI) is problematic given the heterogeneous presentation of the condition and clinical characteristics of patients. We sought to compare, in acute coronary syndrome patients, the prognostic value of two frequently used risk scores (RS): the Thrombolysis in Myocardial Infarction (TIMI) and the physician’s risk assessment (PRA). We also assessed whether serum biomarkers can increase the prognostic accuracy of clinical RS.

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial.

BACKGROUND: Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials.Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. DESIGN: BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0-3. DISCUSSION: The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755).

Neuroprotection in cerebral ischemia with XG-102, a new peptide inhibitor of JNK

Abstract Stroke or cerebrovascular accident, whose great majority is of ischemic nature, is the third leading cause of mortality and long lasting disability in industrialised countries. Resulting from the loss of blood supply to the brain depriving cerebral tissues of oxygen and glucose, it induces irreversible neuronal damages. Despite the large amount of research carried out into the causes and pathogenic features of cerebral ischemia the progress toward effective treatments has been poor. Apart the clot-busting drug tissue-type plasminogen activator (tPA) as effective therapy for acute stroke (reperfusion by thrombolysis) but limited to a low percentage of patients, there are currently no other approved medical treatments. The need for new therapy strategies is therefore imperative. Neuronal death in cerebral ischemia is among others due to excitotoxic mechanisms very early after stroke onset. One of the main involved molecular pathways leading to excitotoxic cell death is the c-Jun NH2-terminal kinase (JNK) pathway. Several studies have already shown the efficacy of a neuroprotective agent of a new type, a dextrogyre peptide synthesized in the retro inverso form (XG102, formerly D-JNKI1), which is protease-resistant and cell-penetrating and that selectively and strongly blocks the access of JNK to many of its targets. A powerful protection was observed with this compound in several models of ischemia (Borsello et al. 2003;Hirt et al. 2004). This chimeric compound, made up of a 10 amino acid TAT transporter sequence followed by a 20 amino acids JNK binding domain (JBD) sequence from JNK inhibitor protein (JIP) molecule, induced both a major reduction in lesion size and improved functional outcome. Moreover it presents a wide therapeutic window. XG-102 has proved its powerful efficacy in an occlusion model of middle cerebral artery in mice with intracérebroventricular (i.c.v.) injection but in order to be able to consider the development of this drug for human ischemic stroke it was therefore necessary to determine the feasibility of its systemic administration. The studies being the subject of this thesis made it possible to show a successful neuroprotection with XG-102 administered systemically after transient mouse middle cerebral artery occlusion (MCAo). Moreover our data. provided information about the feasibility to combine XG-102 with tPA without detrimental action on cell survival. By combining the benefits from a reperfusion treatment with the effects of a neuroprotective compound, it would represent the advantage of bringing better chances to protect the cerebral tissue. Résumé L'attaque cérébrale ou accident vasculaire cérébral, dont la grande majorité est de nature ischémique, constitue la troisième cause de mortalité et d'infirmité dans les pays industrialisés. Résultant de la perte d'approvisionnement de sang au cerveau privant les tissus cérébraux d'oxygène et de glucose, elle induit des dommages neuronaux irréversibles. En dépit du nombre élevé de recherches effectuées pour caractériser les mécanismes pathogènes de l'ischémie. cérébrale, les progrès vers des traitements efficaces restent pauvres. Excepté l'activateur tissulaire du plasminogène (tPA) dont le rôle est de désagréger les caillots sanguins et employé comme thérapie efficace contre l'attaque cérébrale aiguë (reperfusion par thrombolyse) mais limité à un faible pourcentage de patients, il n'y a actuellement aucun autre traitement médical approuvé. Le besoin de nouvelles stratégies thérapeutiques est par conséquent impératif. La mort neuronale dans l'ischémie cérébrale est entre autres due à des mécanismes excitotoxiques survenant rapidement après le début de l'attaque cérébrale. Une des principales voies moléculaires impliquée conduisant à la mort excitotoxique des cellules est la voie de la c-Jun NH2terminal kinase (JNK). Plusieurs études ont déjà montré l'efficacité d'un agent neuroprotecteur d'un nouveau type, un peptide dextrogyre synthétisé sous la forme retro inverso (XG-102, précédemment D-JNKI1) résistant aux protéases, capable de pénétrer dans les cellules et de bloquer sélectivement et fortement l'accès de JNK à plusieurs de ses cibles. Une puissante protection a été observée avec ce composé dans plusieurs modèles d'ischémie (Borsello et al. 2003;Hirt et al. 2004). Ce composé chimérique, construit à partir d'une séquence TAT de 10 acides aminés suivie par une séquence de 20 acides aminés d'un domaine liant JNK (JBD) issu de la molécule JNK protéine inhibitrice. (JIP), induit à la fois une réduction importante de la taille de lésion et un comportement fonctionnel amélioré. De plus il présente une fenêtre thérapeutique étendue. XG-102 a prouvé sa puissante efficacité dans un modèle d'occlusion de l'artère cérébrale moyenne chez la souris avec injection intracerebroventriculaire (i.c.v.) mais afin de pouvoir envisager le développement de ce composé pour l'attaque cérébrale chez l'homme, il était donc nécessaire de déterminer la faisabilité de son administration systémique. Les études faisant l'objet de cette thèse ont permis de montrer une neuroprotection importante avec XG-102 administré de façon systémique après l'occlusion transitoire de l'artère cérébrale moyenne chez la souris (MCAo). De plus nos données ont fourni des informations quant à la faisabilité de combiner XG-102 et tPA, démontrant une protection efficace par XG-102 malgré l'action nuisible du tPA sur la survie des cellules. En combinant les bénéfices de la reperfusion avec les effets d'un composé neurooprotecteur, cela représenterait l'avantage d'apporter des meilleures chances de protéger le tissu cérébral.

Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study.

BACKGROUND: Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO. METHODS: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes. FINDINGS: 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22). INTERPRETATION: Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial. FUNDING: Department of Neurology, University Medical Center Utrecht.

Recanalization and Collaterals Predict Outcome in Proximal MCA Occlusion, but neither Penumbra nor Core of Stroke

Data on new predictors of outcome include penumbra core or collaterals.Objective: To test the predictive value of recanalization, collaterals, penumbra and core of ischemia for functional outcome in a large group of patients with MCA occlusion. Method: Consecutive events included prospectively in the Acute Stroke Registry and Analysis of Lausanne from April 2002 to April 2009 with an acute stroke due to proximal MCA occlusion (M1) were considered for analysis. Acute CTA were reviewed to grade the collaterals (dichotomized in poor __50% or good _50% compared to the normal side) and localization of M1 occlusion (proximal or mid-distal). Acute CTP were reviewed and reconstructed to determine penumbra, core and stroke index (penumbra/penumbra_core) of brain ischemia. Good outcome was defined by mRS 0-2 at 3 months.Results: Among 242 events (115 male, mean NIHSS 18.1, SD 5.8, mean age 66, SD 15), 42% were treated with intravenous thrombolysis, and 3% with intraarterial thrombolysis. Collateral status was rated as poor in 53% of events and proximal M1 occlusion was present in 64%. Recanalization determined at 24 hours with CTA was complete in 26% events and partial/absent in 54%.CTP was available for 212 events. Mean penumbra was 88.6 cm3 (median 84.4, SD 53.8), mean core was 54.1 cm3 (median 46.2, SD 45.7) and stroke index was 64% (median 68%, SD 25%). Good outcome was observed in 87 events (36%) and was associated in multivariate logistic regression with thrombolysis (p_0.02, OR_2.5, 95% CI 1.2-5.4), recanalization (p_0.001, OR_4.1, 95% CI 1.9-8.9), lower NIHSS (p_0.001, OR_0.84, 95% CI 0.78-0.91), male gender (p_0.01, OR_2.8, 95% CI 1.3-5.9), mRS prior to stroke (p_0.02, OR_0.5, 95% CI 0.28-0.9) and good collateral status (p_0.005, OR_3, 95% CI 1.4-6.4). Nor penumbra, nor core, nor stroke index were significant in the multivariate model, even if an association was present in the univariate model between good functional outcome and penumbra (p_0.004, OR_1.008, 95% CI 1.003-1.01), core (p_0.001, OR_0.98, 95% CI 0.976-0.99) and strokeindex (p_0.001, OR_16.7, 95% CI 4.6 59.9).Conclusion: MCA recanalization is the best predictor for good functional outcome, followed by collateral status. CTP data did not predict the functional outcome in our large group of M1 occlusion. Author Disclosures: C. Odier: None. P. Michel: Research Grant; Significant; Paion, Lundbeck. Speakers; Modest; Boehringer-Ingelheim. Consultant/Advisory Board; Modest; Boehringer- Ingelheim. Consultant/Advisory Board; Significant; Servier, Lundbeck.

Differences Between Posterior and Anterior Acute Ischaemic Circulation Strokes in 1449 Consecutive Patients

Background: The current data comparing posterior and anterior circulation strokes with regards to clinical, etiological, radiological and outcome factors are conflicting. We searched for distinguishing features between both territories in 1'449 consecutive acute ischemic stroke patients. Methods: All consecutive patients with acute ischemic stroke admitted to a single stroke unit from January 2003 to July 2008 were included in a prospective registry. Territory of acute stroke was determined by a combination of neuroimaging (MRI and / CT / CTP) and clinical symptoms and signs. Patients with uncertain localisation and patients with simultaneous strokes in the anterior and posterior circulation were excluded from this analysis. Results: Of a total of 1728 patients, 466 (17.0%) had had posterior, 983 (56.8%) anterior, 136 (7.9%) unknown territory, and 43 (2.5%) simultaneous posterior and anterior territory stroke. Of 39 variables that were compared, 29 differed significantly in univariate analysis, including less dependency (OR_0.50) and mortality (OR_0.56) at 3 months in posterior stroke. In multivariate analysis (see table), male gender, lacunar mechanism, arterial dissection and endovascular recanalisation were more frequent in posterior stroke, and admission NIHSS and IV-thrombolysis rate were lower. Significant acute arterial pathology (_50% stenosis) was less frequently found on acute imaging in posterior stroke (OR_0.33). Of 633 patients with significant arterial pathology, it was more frequently present intracranially in posterior (OR_1.62) and extracranially in anterior stroke (OR _ 0.87). In 610 patients where recanalisation was assessed at 24 hours, intracranial (OR_0.26), extracranial (OR_0.25) and overall recanalisation (OR_0.34) was less frequent in the posterior circulation. Conclusions: Acute posterior strokes are less severe and recover better, despite lower IV thrombolysis and recanalisation rates. They are more frequently due to lacunes and dissections and have less arterial pathology burden then anterior circulation strokes.

Early major worsening in ischemic stroke: predictors and outcome.

INTRODUCTION: We aimed to investigate the characteristics and outcome of patients suffering early major worsening (EMW) after acute ischemic stroke (AIS) and assess the parameters associated with it. METHODS: All consecutive patients with AIS in the ASTRAL registry until 10/2010 were included. EMW was defined as an NIHSS increase of ≥8 points within the first 24 h after admission. The Bootstrap version of the Kolmogorov-Smirnov test and the χ(2)-test were used for the comparison of continuous and categorical covariates, respectively, between patients with and without EMW. Multiple logistic regression analysis was performed to identify independent predictors of EMW. RESULTS: Among 2155 patients, 43 (2.0 %) had an EMW. EMW was independently associated with hemorrhagic transformation (OR 22.6, 95 % CI 9.4-54.2), cervical artery dissection (OR 9.5, 95 % CI 4.4-20.6), initial dysarthria (OR 3.7, 95 % CI 1.7-8.0), and intravenous thrombolysis (OR 2.1, 95 % CI 1.1-4.3), whereas a negative association was identified with initial eye deviation (OR 0.4, 95 % CI 0.2-0.9). Favorable outcome at 3 and 12 months was less frequent in patients with EMW compared to patients without (11.6 vs. 55.3 % and 16.3 vs. 50.7 %, respectively), and case fatality was higher (53.5 vs. 12.9 % and 55.8 vs. 16.8 %, respectively). Stroke recurrence within 3 months in surviving patients was similar between patients with and without EMW (9.3 vs. 9.0 %, respectively). CONCLUSIONS: Worsening of ≥8 points in the NIHSS score during the first 24 h in AIS patients is related to cervical artery dissection and hemorrhagic transformation. It justifies urgent repeat parenchymal and arterial imaging. Both conditions may be influenced by targeted interventions in the acute phase of stroke.

Behandlung des akuten Hirninfarktes [Treatment of acute stroke -- an overview]

This paper provides an overview on the actual state of acute therapy in patients with ischemic stroke. The discussion focusses on intravenous and intraarterial thrombolysis, antithrombotic therapy, and the treatment of medical and neurological complications, and therapy recommendations are presented. Finally ongoing studies, particularly those concerning thrombolysis with glycoprotein IIb/IIIa receptor blockers and ultrasound-assisted thrombolysis, are presented.

Age-related differences in the use of guideline-recommended medical and interventional therapies for acute coronary syndromes: a cohort study.

OBJECTIVES: To compare the use of guideline-recommended medical and interventional therapies in older and younger patients with acute coronary syndromes (ACSs). DESIGN: Prospective cohort study. SETTING: Fifty-five hospitals in Switzerland. PARTICIPANTS: Eleven thousand nine hundred thirty-two patients with ACS enrolled between March 1, 2001, and June 30, 2006. ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA). MEASUREMENTS: Use of medical and interventional therapies was determined after exclusion of patients with contraindications and after adjustment for comorbidities. Multivariate logistic regression models were used to calculate odds ratios (ORs) per year increase in age. RESULTS: Elderly patients were less likely to receive acetylsalicylic acid (OR=0.976, 95% confidence interval (CI)=0.969-0.980) or beta-blockers (OR=0.985, 95% CI=0.981-0.989). No age-dependent difference was found for heparin use. Elderly patients with STEMI were less likely to receive percutaneous coronary intervention (PCI) or thrombolysis (OR=0.955, 95% CI=0.949-0.961). Elderly patients with NSTEMI or UA less often underwent PCI (OR=0.943, 95% CI=0.937-0.949). CONCLUSION: Elderly patients across the whole spectrum of ACS were less likely to receive guideline-recommended therapies, even after adequate adjustment for comorbidities. Prognosis of elderly patients with ACS may be improved by increasing adherence to guideline-recommended medical and interventional therapies.