Stroke Care and Application of Thrombolysis in Ibero-America: Report From the SITS-SIECV Ibero-American Stroke Register

Background and Purpose: Standardized registries may provide valuable data to further improve stroke care. Our aim was to obtain updated information about characteristics of stroke patients and management of stroke across the Ibero-American countries, using a common in-hospital registry (Safe Implementation of Treatments in Stroke­Sociedad Iberoamericana de Enfermedades Cerebrovasculares) as a basis for further quality improvement. Methods: Data for this study were entered into the Safe Implementation of Treatments in Stroke registry from September 2009 to December 2013 by 58 centers in 14 countries. Data included demographics, risk factors, onset-to-door time, National Institutes of Health Stroke Scale score, stroke subtype, ischemic stroke etiology, treatments, 3-month mortality, and modified Rankin Scale score. Time to treatment was also recorded for patients treated with thrombolysis. Results: Five thousand four hundred one patients were registered; median age, 65 years; 46% women; 3915 (72.5%) ischemic strokes; 686 (13.7%) hemorrhagic strokes; 213 (4.3%) subarachnoid hemorrhages; 414 (8.3%) transient ischemic attacks; and 31 (0.6%) cerebral vein thrombosis. The most prevalent risk factors were hypertension (71.3%), dyslipidemia (35.2%), and diabetes mellitus (23.6%). Atrial fibrillation was present in 15.1%. Three hundred one ischemic strokes were treated with intravenous thrombolysis (IVT; 7.7%). Patients undergoing IVT were more severely affected (median baseline National Institutes of Health Stroke Scale score, 11 versus 6). The rate of symptomatic intracerebral hemorrhages after IVT was 5.7%. At 3 months, 60.3% of IVT-treated patients and 59.1% of untreated patients were independent (modified Rankin Scale score, 0­2). Mortality was 11.4% in treated and 12.8% in untreated patients. Conclusions: Safe Implementation of Treatments in Stroke­Sociedad Iberoamericana de Enfermedades Cerebrovasculares is the largest registry of a general stroke population and the first study to evaluate the level of IVT use in Ibero-America. It provides valuable information that may help to improve the quality of stroke care in the Ibero-American region.

Safety of thrombolysis in stroke mimics: an observational cohort study from an urban teaching hospital in Sweden.

OBJECTIVES: Acute stroke management has changed dramatically over the recent years, where a timely assessment is driven by the expanding treatment options of acute ischaemic stroke. This increases the risk in treating non-stroke patients (stroke mimics) with a possibly hazardous intravenous thrombolysis treatment (IVT). SETTING: Patients of the thrombolysis registry of Södersjukhuset AB, a secondary health centre in Stockholm, were retrospectively studied to determine complications and outcome after IVT in strokes and stroke mimics. PARTICIPANTS: Consecutively, 674 recruited patients from 1 January 2008 to 1 December 2013 were analysed regarding demographics and outcome at 3 months after onset of symptoms. RESULTS: Ischaemic stroke was confirmed in 625 patients (93%), and 48 patients (7%) were stroke mimics. Patients with strokes were older than stroke mimics 72 (IQR: 64-81) vs 54 years (IQR 40-67), p<0.0001. Antihypertensive and antithrombotic treatment were more common in patients with stroke (p<0.0001 and p=0.006, respectively). National Institute of Health Stroke Scale did not differ at time of presentation. Excellent outcome defined as modified Rankin Scale score 0-1, at 3 months, was less common in stroke than in stroke mimics (50% vs 87.5%, p<0.0001). No stroke mimic had a symptomatic intracerebral haemorrhage. Age of less than 40 years may be a predictor for a patient to be a stroke mimic (OR: 8.7, 95% CI: 3.2 to 24.0, p<0.0001). CONCLUSIONS: Stroke mimics receiving IVT had a more favourable outcome compared with patients with stroke, and showed no haemorrhagic complications. Age below 40 years may be a predictor for stroke mimics.

Internal carotid dissection caused by an elongated styloid process (Eagle syndrome).

Eagle syndrome (symptoms associated with an elongated styloid process (SP)) is commonly divided into two presentations. First, the so-called classic Eagle syndrome where patients can present with unilateral sore throat, dysphagia, tinnitus, unilateral facial and neck pain and otalgia. Second, there is the vascular or stylocarotid form of Eagle syndrome in which the elongated SP is in contact with the extracranial internal carotid artery. We describe two cases of internal carotid artery dissection associated with an elongated SP. One is a patient with ischaemic stroke and another with transient ischaemic attacks caused by an elongated SP. A surgical resection of the SP was performed on the former patient. Both patients were treated with anticoagulation and recovered well. A literature search only revealed two prior descriptions of carotid dissection in the context of an elongated SP.

Long-term survival of ischemic cerebrovascular disease in the acute inflammatory stroke study, a hospital-based cohort described by TOAST and ASCO.

BACKGROUND: Ischemic cerebrovascular disease (ICVD) comprises multiple etiological phenotypes that share common clinical characteristics. Etiological classification of patients with ICVD is of major clinical interest to achieve optimal medical treatment and predict prognosis. The TOAST classification system has been widely used to describe stroke etiology but provides restricted phenotypic homogeneity within groups. The ASCO classification system has introduced a new approach in phenotypic classification, and aims to describe clinical characteristics without merging concurrent comorbidities. Inflammatory processes have been suggested to mediate stroke etiology and pathology. The Acute Inflammatory Stroke Study (AISS), a hospital-based cohort, is here introduced and described by TOAST and ASCO classification systems. The aim of this first analysis of AISS was to investigate long-term mortality in relation to ischemic stroke subtypes, and clinical and biochemical markers. METHODS: AISS consecutively follows patients on 6 occasions up to 1 year after stroke onset. Complete workup according to ASCO comprised CT or MRI of the head, ECG, duplex of the extracranial arteries or CT/MR angiography and ultrasound of the heart. Level 2 evidence was required in each domain to obtain a comparable system to TOAST (ASCO2). Clinical and biochemical characteristics and mortality rates were documented and compared by the two classification systems. RESULTS: Of 142 patients consecutively evaluated and recruited in the study, a total of 101 ICVD patients (ischemic stroke, n = 84; transient ischemic attack, n = 17) were included in the final analysis. Agreement between ASCO2 and TOAST was very good. During the mean observation period of 28 months, 26 patients died. The 1- and 4-year mortality rates were 0 and 4% for large artery atherosclerosis (LAA); 23 and 36% for cardioembolism (CE); 0% for small artery occlusion (SAO); 63 and 100% for the subtype with unknown etiology due to incomplete workup (Unknown), and 12 and 29% for the cryptogenic subtype. As for the ASCO2 groups, the 1- and 4-year mortality rates were 0 and 6% in LAA, 25 and 36% in CE, 0% in SAO, 0 and 14% in LAA + CE, 0% in SAO + CE, 16 and 36% in the subgroup with undetermined etiology despite complete workup, and 56 and 100% in Unknown. Regression analysis showed that age, white blood cell count, fibrinogen and bilirubin, but not etiological subgroup, were independent predictors of mortality. CONCLUSION: Our findings indicate that clinical and biochemical markers may differentiate phenotypically homogeneous etiological subtypes and predict long-term mortality. Further studies with larger patient numbers are needed to investigate possible causative mechanisms.

Hyperglycaemia in acute ischaemic stroke is associated with an increased 5-year mortality.

BACKGROUND: admission hyperglycaemia (HG) is associated with worse prognosis and higher mortality within 3 months after stroke. Reports on long-term mortality are inconsistent. OBJECTIVE: to evaluate the influence of admission HG [blood glucose (BG) levels >8 mmol/L] on long-term mortality after ischaemic stroke (IS) and transient ischaemic attack (TIA). METHODS: consecutive patients with IS or TIA, admitted from January 1997 until December 2002, were retrospectively screened. BG was measured within 3 days from onset of symptoms. Information on the date of death was obtained within 10 years after onset. RESULTS: a total of 509 patients (78% IS; 22% TIA) were included. Admission HG was present in 28% and 18% of the IS and TIA patients, respectively (P = 0.05). Mean admission BG was 7.6 +/- 3.2 mmol/L in the IS and 6.7 +/- 2.3 mmol/L in TIA (P = 0.002). During a mean observation of 66 +/- 35 months, the overall 1- and 10-year mortality rate was 12% and 51% in IS compared to 4% and 38% in TIA patients (P = 0.004). Normoglycaemic IS patients had a longer median survival than those with HG (113 vs 84 months, P = 0.04). Admission HG did not affect the mortality rates in TIA patients. CONCLUSION: admission HG is associated with greater mortality rates up to 5 years after stroke but does not influence the survival of TIA patients.

Bone marrow stromal cells control the growth of hepatic stellate cells in vitro.

Liver cirrhosis is characterized by hepatic dysfunction, with extensive accumulation of fibrous tissue in the liver. Hepatic stellate cells (HSCs) are the major source of fibrillar matrix proteins and play an important role in the progress of liver cirrhosis. In our study, the growth of HSCs is inhibited by bone marrow stromal cells (BMSCs). The inhibition is irreversible and is followed by apoptosis. The effect of BMSCs on the apoptosis of HSCs is possibly via the JNK pathway activated by nerve growth factor (NGF) and hepatocyte growth factor (HGF) secreted by BMSCs. Meanwhile, the apoptosis effect is enhanced by transforming growth factor-beta blocking.

Voriconazole into PLGA nanoparticles: improving agglomeration and antifungal efficacy.

This study is concerned with preparing PLGA nanoparticles loaded with voriconazole (PNLV), investigating the burst release and agglomeration of PNLV, and also evaluating antifungal efficacy of PNLV compared with voriconazole (VRC). The emulsion-solvent evaporation technique for nanoparticles and tests against fungi were completed. The amount of VRC in PNLV with sodium hexametaphosphate was 2.01+/-0.27%, and burst release of PNLV was reduced by about 33% using 20% ethanol solution (n=3). The mean D(50) of PNLV with or without this salt was 132.8 nm and 6.3 microm, respectively (n=5). In vitro; the fungal numbers treated with PNLV (3.5 mg/ml, equal amount calculated by VRC) and VRC (70 microg/ml) in tubes at the day 7 were 5.74 log(10) and 6.72 log(10), respectively (P<0.05). In vivo; the fungal burden treated with PNLV and VRC in tissue from mice kidneys at day 7 after administration was 0.64 log(10) and 2.61 log(10), respectively (5 mg/kg, P<0.001). The hematoxylin-eosin stain in mice kidney showed that the pathological lesions treated with PNLV were relieved in contrast with those with VRC. These results suggest that the emulsion-solvent evaporation process is feasible in preparing PNLV. Moreover, ethanol solution decreased burst release and Na-HMP inhibited agglomeration. PNLV could improve the VRC antifungal efficacy.

Interleukin-27 suppresses experimental autoimmune encephalomyelitis during bone marrow stromal cell treatment.

Interleukin (IL)-17 is a key inflammatory cytokine in autoimmune disease and may play an important role in the development of experimental autoimmune encephalomyelitis (EAE). In this study, we observed decreased IL-17 and increased IL-27 in EAE rats treated with bone marrow stromal cells (BMSCs). Neutralization of IL-27 resulted in recovery of the BMSCs effect. Adoptive transfer induction of EAE was poor by BMSC-stimulated MNCs, but could be induced by MNCs stimulated by BMSCs under blockade of IL-27 signaling. These results demonstrate that BMSCs may suppress the development of EAE, possibly via secretion of IL-27, which can inhibit IL-17 production or Th17 cell generation.

Dendritic cells are present in ischemic brain after permanent middle cerebral artery occlusion in the rat.

BACKGROUND AND PURPOSE: Cerebral ischemia is associated with inflammation involving accumulation of polymorphonuclear neutrophils. T cells have been suggested to contribute to the secondary progression of ischemic brain injury. Dendritic cells (DC) are potent regulators of immunity by activating and tolerizing T cells. DC have previously been detected in rat meninges and choroid plexus. Hypothesizing that DC are involved in inflammation associated with cerebral ischemia, we investigated DC in the brain of Sprague-Dawley rats after permanent middle cerebral artery occlusion (pMCAO) versus sham operation. METHODS: All experimental rats (n=24) had the right MCA permanently occluded by inserting a nylon monofilament through the right external carotid artery. Immunohistochemistry was used to detect DC (OX62(+)), microglia/macrophages (OX42(+)) that developed into DC, and activated DC expressing major histocompatibility complex class II (OX6(+)) in the brain hemispheres at 1 hour to 6 days after pMCAO or sham operation. RESULTS: Levels of DC were elevated at 1 hour in the ischemic versus sham hemispheres (P<0.001) and ischemic versus nonischemic hemispheres (P<0.001). Activated DC expressing major histocompatibility complex class II (OX62(+)OX6(+)) were still elevated at 6 days after pMCAO in the ischemic versus nonischemic hemispheres (P<0.01). The area of brain lesion correlated with numbers of OX62(+) DC per 100-mm2 brain tissue section (r=0.79; P<0.0001). CONCLUSIONS: Increased levels of DC in the brain after pMCAO and correlation between DC numbers and brain lesion area indicate a role for DC in cerebral ischemia. This observation could constitute a basis for further studies on the role of DC in inflammation related to cerebral ischemia.