Circulating mesenchymal stem cells microparticles in patients with cerebrovascular disease

Preclinical and clinical studies have shown that the application of CD105(+) mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke. In addition, circulating microparticles are reportedly functional in various disease conditions. We tested the levels of circulating CD105(+) microparticles in patients with acute ischemic stroke. The expression of CD105 (a surface marker of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating microparticles was evaluated by flow cytometry of samples from 111 patients and 50 healthy subjects. The percentage of apoptotic CD105 microparticles was determined based on annexin V (AV) expression. The relationship between serum levels of CD105(+)/AV(-) microparticles, stromal cells derived factor-1α (SDF-1α), and the extensiveness of cerebral infarcts was also evaluated. CD105(+)/AV(-) microparticles were higher in stroke patients than control subjects. Correlation analysis showed that the levels of CD105(+)/AV(-) microparticles increased as the baseline stroke severity increased. Multivariate testing showed that the initial severity of stroke was independently associated with circulating CD105(+)/AV(-) microparticles (OR, 1.103 for 1 point increase in the NIHSS score on admission; 95% CI, 1.032-1.178) after adjusting for other variables. The levels of CD105(+)/CXCR4(+)/AV(-) microparticles were also increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS score on admission), but were decreased with time after stroke onset (r = -0.204, p = 0.036). Risk factor profiles were not associated with the levels of circulating microparticles or SDF-1α. In conclusion, our data showed that stroke triggers the mobilization of MSC-derived microparticles, especially in patients with extensive ischemic stroke.     

Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke

Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke.     

The Role of Tryptophan Catabolism along the Kynurenine Pathway in Acute Ischemic Stroke

Post-stroke inflammation may induce upregulation of the kynurenine (KYN) pathway for tryptophan (TRP) oxidation, resulting in neuroprotective (kynurenic acid, KA) and neurotoxic metabolites (3-hydroxyanthranillic acid, 3-HAA). We investigated whether activity of the kynurenine pathway in acute ischemic stroke is related to initial stroke severity, long-term stroke outcome and the ischemia-induced inflammatory response. Plasma concentrations of TRP and its metabolites were measured in 149 stroke patients at admission, at 24 h, at 72 h and at day 7 after stroke onset. We evaluated the relation between the KYN/TRP ratio, the KA/3-HAA ratio and stroke severity, outcome and inflammatory parameters (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and neutrophil/lymphocyte ratio (NLR)). KYN/TRP but not KA/3-HAA correlated with the NIHSS score and with the infarct volume. Patients with poor outcome had higher mean KYN/TRP ratios than patients with more favourable outcome. The KYN/TRP ratio at admission correlated with CRP levels, ESR and NLR. The activity of the kynurenine pathway for tryptophan degradation in acute ischemic stroke correlates with stroke severity and long-term stroke outcome. Tryptophan oxidation is related to the stroke-induced inflammatory response.     

Admission C – reactive protein after acute ischemic stroke is associated with stroke severity and mortality: The 'Bergen stroke study'

Background

There is growing evidence that inflammation plays an important role in atherogenesis. Previous studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. It is not clear whether this is due a direct dose-response effect or rather an epiphenomenon. We studied the effect of CRP measured within 24 hours after stroke onset on functional outcome, mortality and future vascular events.

Methods

We prospectively studied 498 patients with ischemic stroke who were admitted within 24 hours after the onset of symptoms. CRP and NIH stroke scale (NIHSS) were measured at the time of admission. Short-term functional outcome was measured by modified Rankin scale (mRS) and Barthel ADL index (BI) 7 days after admission. Patients were followed for up to 2.5 years for long-term mortality and future vascular events data.

Results

The median CRP at admission was 3 mg/L. High CRP was associated with high NIHSS (p = 0.01) and high long-term mortality (p < 0.0001). After adjusting for confounding variables, high CRP remained to be associated with high NIHSS (p = 0.02) and high long-term mortality (p = 0.002). High CRP was associated with poor short-term functional outcomes (mRS > 3; BI < 95) (p = 0.01; p = 0.03). However, the association was not significant after adjusting for confounding variables including stroke severity (p = 0.98; p = 0.88). High CRP was not associated with future vascular events (p = 0.98).

Conclusion

Admission CRP is associated with stroke severity and long-term mortality when measured at least 24 hours after onset. There is a crude association between high CRP and short-term functional outcome which is likely secondary to stroke severity. CRP is an independent predictor of long-term mortality after ischemic stroke.     

Relevance of Distinct Monocyte Subsets to Clinical Course of Ischemic Stroke Patients

Background and Purpose

The most common strategy for treating patients with acute ischemic stroke is thrombolytic therapy, though only a few patients receive benefits because of the narrow time window. Inflammation occurring in the central nervous system (CNS) in association with ischemia is caused by immune cells including monocytes and involved in lesion expansion. If the specific roles of monocyte subsets in stroke can be revealed, they may become an effective target for new treatment strategies.

Methods

We performed immunological examinations of 36 consecutive ischemic stroke patients within 2 days of onset and compared the results with 24 age-matched patients with degenerative disorders. The stroke patients were repeatedly tested for the proportions of monocyte subsets in blood, and serum levels of pro- and anti-inflammatory cytokines immediately after admission, on days 3-7 and 12-16 after stroke onset, and on the day of discharge. In addition, immunological measurements were analyzed for relationships to stroke subtypes and complications, including progressive infarction (PI) and stroke-associated infection (SAI).

Results

Monocyte count was significantly increased from 0–16 days after stroke as compared to the controls (p<0.05). CD14^highCD16^- classical and CD14^highCD16⁺ intermediate monocytes were significantly increased from 0-7 and 3-16 days after stroke, respectively (p<0.05), whereas CD14 ^dimCD16^high non-classical monocytes were decreased from 0–7 days (p<0.05). Cardioembolic infarction was associated with a persistent increase in intermediate monocytes. Furthermore, intermediate monocytes were significantly increased in patients with PI (p<0.05), while non-classical monocytes were decreased in those with SAI (p<0.05). IL-17A levels were positively correlated with monocyte count (r=0.485, p=0.012) as well as the percentage of non-classical monocytes (r=0.423, p=0.028), and negatively with that of classical monocytes (r=-0.51, p=0.007) during days 12-16.

Conclusions

Our findings suggest that CD14^highCD16⁺ intermediate monocytes have a role in CNS tissue damage during acute and subacute phases in ischemic stroke especially in relation to cardioembolism.     

Seasonal variation of admission severity and outcomes in ischemic stroke – a consecutive hospital-based stroke registry

Different morbidities and mortalities of ischemic stroke may occur among seasons. For detecting the seasonal variations of severity after stroke onset and prognosis, we employed a retrospective analysis on a prospective regional hospital-based stroke registry and included a total of 1039 consecutive patients with onset date from January 2014 to December 2015. Patients were divided into four groups according to the onset seasons. Baseline characteristics, stroke subtypes, admission National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score in 90 d were recorded and compared. Ordinal logistic regression was used to evaluate the association of seasons and severity or outcomes. Higher proportion of cardiac embolisms appeared in spring and winter (p < 0.001). The median admission NIHSS score was 5 in spring, 3 in summer, 4 in fall and 4 in winter (p = 0.036). After 90 d from onset, 40.5% of patients in spring suffered poor outcome (mRS 3–6), while 24.6% in summer, 33.9% in fall and 40.1% in winter (p < 0.001). After adjusted for age, sex, stroke subtypes and other covariates, patients in spring and winter had 1.76 times (95%CI 1.14–2.70, p = 0.010) and 1.53 times (95%CI 1.08–2.18, p = 0.017) the risk of suffering higher severity category than patients in summer, respectively. Compared with summer group, risk of worse outcomes at 90 d increased to 2.30 times in spring (95%CI 1.53–3.45, p < 0.001), 1.57 times in fall (95%CI 1.14–2.16, p = 0.006) and 2.09 times in winter (95%CI 1.50–2.91, p < 0.001), respectively. In conclusion, onset seasons were associated with severity and outcomes in ischemic stroke, and patients admitted in spring and winter had more severity and worse outcomes than patients in summer.     

CT perfusion and noncontrast CT in acute ischemic stroke diagnosing--is there influence on early thrombolytic therapy outcome?

The objective of this study was to compare noncontrast computed tomography (NCCT) and computed tomography perfusion (CTP) in early diagnosis of acute ischemic stroke and to define influence of these diagnostic procedures on early outcome of thrombolytic therapy (TLTH). The study included 45 patients, 35 patients submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score we compared early outcome of patients who received TLTH after NCCT only (group 1) with the early outcome of patients who received TLTH following NCCT and CTP (group 2). Statistically significant difference was found in acute stroke diagnosing between CTP and NCCT (p = 0.002). There were no statistically significant differences in TLTH early outcome between group 1 and group 2. In conclusion, CTP should be done regulary in patients presenting with acute ischemic stroke symptoms. More research needs to be done in defining exact influence of CTP implementation on the TLTH outcome.     

Effects of vitamin C and aspirin in ischemic stroke-related lipid peroxidation: results of the AVASAS (Aspirin Versus Ascorbic acid plus Aspirin in Stroke) Study

A condition of oxidative stress is known to occur in ischemic stroke, the current therapeutic intervention of which is largely limited to thrombolysis. To assess the effect of vitamin C - in conjunction to aspirin - in ischemic stroke-related lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes F2alpha-VI (8,12-iPF2alpha-VI) and activities and levels of a broad spectrum of antioxidant enzymes and micronutrients in stroke patients randomized to receive, from stroke onset and up to three months, either vitamin C (200 mg/day) plus aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week, patients treated with vitamin C plus aspirin had higher vitamin C levels (p = 0.02) and lower 8,12-iPF2alpha-VI levels (p = 0.01) than patients treated with aspirin alone. The significance was maintained for the increase of vitamin C after three months of therapy (p < 0.01). The clinical functional outcome for both groups of patients similarly ameliorated after three months of treatment. We conclude that vitamin C, at the dose of 200 mg/day and in conjunction with aspirin, significantly decreases ischemic stroke-related lipid peroxidation in humans. Further studies are warranted to clarify whether the use of vitamin C may add clinical long-term beneficial effects in patients with stroke.     

Quantification of volume of tissue damage in stroke using T2- weighed MRI images

We have developed a quantitative technique for scoring of the severity of ischemic damage of the brain using quantitative data of the T2-weighted MRI images of brain in stroke. The principle of the method is the assumption that T2 signal increases proportionally to the severity of ischemic damage of cerebral tissue up to the level equal to intraventricular liquor signal in the case of postinfarction cystic degeneration. Depicting the mean T2-signal from the intraventricular liquor region as Iliq, the signal from ischemic brain area as Iinsult, and from the intact brain as Inorm, obviously, the volume quota of damaged tissue in the total volume of the stroke region is represented by the ratio (Iinsult - Inorm)/(Iliq - Inorm). The total volume of damaged tissue (VDT, cub.cm) in the stroke region is then the following sum taken over all slices i, where the stroke damage can be: VDT = sigma i d.Si.[(Iinsult - Inorm)/(Iliq - Inorm)]i, where d is the slice thickness, Si--area of the ischemic region in the slice i. The quota of damaged tissue in the physical volume of the stroke region is henceforth the following ratio: Q = [sigma i d.Si.[(Iinsult - Inorm)/(Iliq - Inorm)]i]/[sigma i d.Si]. The technique was applied in retrospective analysis of routine MRI studies in 15 patients referred because of acute ischemic stroke. The studies were performed using low-field MRI tomograph Magnetom-Open (Siemens Medical) with field strength 0.22 T. In patients studied during the first day after occurrence of ischemic insult with the minimal degree of acute neurologic deficit, who later have demonstrated clinically full recovery, the VDT was below 20 cm3, and Q was below 10%. In cases with VDT > 25 cm3 and Q > 20% the full regress was not observed in any patient. Henceforth, the quantification of cerebral damage in stroke using quantitative indices based on measurement of T2-parameters over ischemic and intact zones of the brain are of independent prognostic clinical value and improve clinical usefulness of the MRI in ischemic brain stroke.     

老年H型高血压合并急性缺血性脑卒中患者血清omentin-1、Irisin水平与病情及预后的关系研究

目的:探讨老年H型高血压合并急性缺血性脑卒中患者血清网膜素-1(omentin-1)、鸢尾素(Irisin)水平与病情及预后的关系。方法:选择2017年6月-2019年9月我院收治的老年H型高血压合并急性缺血性脑卒中患者92例,记作合并脑卒中组,根据美国国立卫生研究院卒中量表(NIHSS)评分将患者分为轻症组28例(NIHSS评分≤4分)、中症组39例(5分≤NIHSS评分≤20分)和重症组25例(NIHSS评分>20分),根据改良Rankin量表(mRS)评分将患者分为预后不良组28例(mRS评分>2分)和预后良好组64例(mRS评分≤2分)。另选择同期我院收治的单纯老年H型高血压患者90例作为单纯H型高血压组,分析合并脑卒中组患者血清omentin-1、Irisin水平及omentin-1、Irisin与NIHSS评分、mRS评分的相关性,并应用ROC曲线分析血清omentin-1、Irisin水平对患者预后的预测价值。结果:合并脑卒中组血清omentin-1、Irisin水平显著低于单纯H型高血压组(P<0.05),随脑卒中神经缺损严重程度的升高,H型高血压合并急性缺血性脑卒中患者血清omentin-1、Irisin水平逐渐降低(P<0.05),预后不良组血清omentin-1、Irisin水平显著低于预后良好组(P<0.05)。老年H型高血压合并急性缺血性脑卒中患者血清omentin-1、Irisin水平与NIHSS评分及mRS评分均呈负相关(P<0.05)。omentin-1最佳临界值为105.36 ng/ml,敏感度为78.23%,特异度为83.44%;Irisin最佳临界值为90.77 ng/L,敏感度为71.00%,特异度为61.43%。结论:老年H型高血压合并急性缺血性脑卒中患者血清omentin-1、Irisin水平异常降低,其水平与神经缺损程度和预后呈负相关,血清omentin-1、Irisin对老年H型高血压发生急性缺血性脑卒中的预后评估具有一定价值。     

Intravenous thrombolysis for acute ischemic stroke--our experiences

Intravenous (i.v.) thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the only available pharmacological therapy to improve the outcome of acute ischemic stroke. We compared 71 patients presenting with ischaemic stroke and given intravenous rt-PA (0.9 mg/kg total dose) within 3 h with 71 patients who present to the hospital more than 3 hours after stroke symptom onset. The primary endpoint was the modified Rankin scale (mRS) at 90 days, dichotomised for favourable and unfavourable (score 2-6). Outcome measures were symptomatic intracerebral haemorrhage within 36 h (haemorrhage associated with National Institutes of Health Stroke Scale [NIHSS] > or = 4 points deterioration), and mortality at 3 months. More patients had favourable outcome with the rt-PA-treated group than with the control group (64.79% vs. 22.54%; p = 0.0001). The greater proportion of patients left with minimal or no deficit 90 days after rt-PA treatment, as compared with the control group. In the treated group symptomatic intracranial hemorrhage occurred in 1 patient who recovered to a level of functional independence, and asymptomatic intracranial hemorrhage was observed in 2 patients. Our experience of an acute stroke thrombolysis service shows that we are able to provide this treatment safely and in accordance with established treatment guidelines. We recommend thrombolytic treatment in acute ischemic stroke for selected population.     

Comparative evaluation of treatment with low-dose aspirin plus dipyridamol versus aspirin only in patients with acute ischaemic stroke

ABSTRACT: BACKGROUND: Previous studies have suggested that pre-stroke treatment with low-dose aspirin (A) couldreduce the severity of acute ischaemic stroke, but less is known on the effect of pre-stroketreatment with a combination of aspirin and dipyridamole (A + D) and post-stroke effects ofthese drugs. The aim of the present study was to evaluate the effect of this drug combinationon acute and long-term prognosis of ischaemic stroke. METHODS: Patients without atrial fibrillation admitted to the stroke unit with acute ischaemic stroke (n =554) or TIA (n = 108) were studied during acute hospital care and up to 12 months afterdischarge from hospital. RESULTS: Prior to acute stroke 62 patients were treated with A + D while 247 patients were treated withA only. No beneficial effects of the combination A + D compared to A only were noted onstroke severity and/or acute in-hospital mortality. However, survival analysis by Coxproportionalhazard model demonstrated lower 12-months all-cause mortality in patientsdischarged with A + D (n = 275) compared with patients on A only (HR, 0.52; CI, 0.32-0.86;p = 0.011; n = 262) after adjusting for age, baseline NIHSS, previous stroke, previousmyocardial infarction and type 2 diabetes. We also noted a tendency towards lower all-causemortality at 3 months with use of A + D, but this was not statistically significant (p = 0.12). CONCLUSIONS: Pre-stroke treatment with a combination of low-dose A + D does not reduce the severity ofacute stroke, nor does it reduce the acute in-hospital mortality. However, treatment with A +D at discharge from hospital is seemingly associated with lower long-term mortalitycompared with A only, contrary to the results from previous randomised studies. However,our results must be interpreted with extreme caution considering the non-randomised studydesign.     

Mobilisation of hematopoietic CD34+ precursor cells in patients with acute stroke is safe--results of an open-labeled non randomized phase I/II trial

Background

Regenerative strategies in the treatment of acute stroke may have great potential. Hematopoietic growth factors mobilize hematopoietic stem cells and may convey neuroprotective effects. We examined the safety, potential functional and structural changes, and CD34⁺ cell–mobilization characteristics of G-CSF treatment in patients with acute ischemic stroke.

Methods and Results

Three cohorts of patients (8, 6, and 6 patients per cohort) were treated subcutaneously with 2.5, 5, or 10 µg/kg body weight rhG-CSF for 5 consecutive days within 12 hrs of onset of acute stroke. Standard treatment included IV thrombolysis. Safety monitoring consisted of obtaining standardized clinical assessment scores, monitoring of CD34⁺ stem cells, blood chemistry, serial neuroradiology, and neuropsychology. Voxel-guided morphometry (VGM) enabled an assessment of changes in the patients'' structural parenchyma. 20 patients (mean age 55 yrs) were enrolled in this study, 5 of whom received routine thrombolytic therapy with r-tPA. G-CSF treatment was discontinued in 4 patients because of unrelated adverse events. Mobilization of CD34⁺ cells was observed with no concomitant changes in blood chemistry, except for an increase in the leukocyte count up to 75,500/µl. Neuroradiological and neuropsychological follow-up studies did not disclose any specific G-CSF toxicity. VGM findings indicated substantial atrophy of related hemispheres, a substantial increase in the CSF space, and a localized increase in parenchyma within the ischemic area in 2 patients.

Conclusions

We demonstrate a good safety profile for daily administration of G-CSF when begun within 12 hours after onset of ischemic stroke and, in part in combination with routine IV thrombolysis. Additional analyses using VGM and a battery of neuropsychological tests indicated a positive functional and potentially structural effect of G-CSF treatment in some of our patients.

Trial Registration

German Clinical Trial Register DRKS 00000723     

Dimethylarginine Levels in Cerebrospinal Fluid of Hyperacute Ischemic Stroke Patients are Associated with Stroke Severity

We hypothesise that asymmetric and symmetric dimethylarginine (ADMA, SDMA) are released in cerebrospinal fluid (CSF) due to ischemia-induced proteolysis and that CSF dimethylarginines are related to stroke severity. ADMA and SDMA were measured in CSF of 88 patients with ischemic stroke or TIA within 24 h after stroke onset (mean 8.6 h) and in 24 controls. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission. Outcome was evaluated by institutionalization due to stroke and the modified Rankin scale. Dimethylarginine levels were higher in patients with stroke than in TIA patients, who had higher levels than controls and correlated with the NIHSS. Logistic regression analysis confirmed that dimethylarginines were independently associated with stroke severity. The SDMA/ADMA ratio did not differ significantly between controls and stroke patients. CSF dimethylarginine levels are increased in hyperacute ischemic stroke and are associated with stroke severity. R. Brouns is a research assistant of the Fund for Scientific research Flanders (FWO-Vlaanderen).     

缺血性脑梗死与颈动脉斑块、嗜酸性粒细胞、血小板CD62p水平的临床相关性研究

目的探讨急性缺血性脑梗死初发与再发与颈动脉斑块、嗜酸性粒细胞水平与血小板活化水平之间的相关性。 方法本研究选取50例被诊断为急性缺血性脑梗死的患者,患者均进行颈部血管超声检查,根据有无颈动脉斑块分为2组,均进行嗜酸性粒细胞、血小板活性CD62p水平等指标检测。两组间比较采用t检验。 结果有颈动脉斑块形成的急性缺血性脑梗死患者,其嗜酸性粒细胞计数低于无颈动脉斑块患者（P < 0.05）,而其血浆CD62p水平高于无颈动脉斑块患者（P < 0.05）,1年随访中复发率更高（P < 0.05）。 结论急性缺血性脑梗死患者的初发与复发与颈动脉斑块存在,嗜酸性粒细胞计数及CD62p水平密切相关。     

Asymmetry of Deep Medullary Veins on Susceptibility Weighted MRI in Patients with Acute MCA Stroke Is Associated with Poor Outcome

Background and Purpose

Due to its sensitivity to deoxyhemoglobin, susceptibility weighted imaging (SWI) enables the visualization of deep medullary veins (DMV) in patients with acute stroke, which are difficult to depict under physiological circumstances. This study assesses the asymmetric appearance of prominent DMV as an independent predictor for stroke severity and outcome.

Materials and Methods

SWI of 86 patients with acute middle cerebral artery (MCA) stroke were included. A scoring system from 0 (no visible DMV) to 3 (very prominent DMV) was applied for both hemispheres separately. A difference of scores between ipsi- and contralateral side was defined as asymmetric (AMV+). Occurrence of AMV+ was correlated with the National Institute of Health Stroke Scale (NIHSS) Score on admission and discharge, as well as the modified Rankin Scale (mRS) at discharge. Ordinal regression analysis was used to evaluate NIHSS and mRS as predictors of stroke severity, clinical course of disease and outcome.

Results

55 patients displayed AMV+ while 31 did not show an asymmetry (AMV–). Median NIHSS on admission was 17 (11–21) in the AMV+ group and 9 (5–15) in the AMV– group (p = 0.001). On discharge median NIHSS was 11 (5–20) for AMV+ and 5 (2–14) for AMV– (p = 0.005). The median mRS at discharge was 4 (3–5) in the AMV+ group and 3 (1–4) in AMV– (p = 0.001). Odds ratio was 3.19 (95% CI: 1.24–8.21) for AMV+ to achieve a higher mRS than AMV– (p = 0.016).

Conclusion

The asymmetric appearance of DMV on SWI is a fast and easily evaluable parameter for the prediction of stroke severity and can be used as an additional imaging parameter in patients with acute MCA stroke.     

Association between Statin Use and Short-Term Outcome Based on Severity of Ischemic Stroke: A Cohort Study

Background

Statins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity.

Methods

A total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0–5) at 3 months after onset using multivariable logistic regression models.

Results

A total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38–0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81–1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31–0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57–0.92) at 3 months in the non-minor stroke group.

Conclusions

Statin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.     

Temporal Evolution of Ischemic Lesions in Nonhuman Primates: A Diffusion and Perfusion MRI Study

MethodsPermanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10–21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1–6, 48, and 96 hours post occlusion and validated with H&E staining.ResultsThe stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1–6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion.ConclusionThe infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.     

Acute phase proteins and oxidised low-density lipoprotein in association with ischemic stroke subtype, severity and outcome

Objectives: The goal of our study was to investigate the associations of oxidized LDL (apoB100 aldehyde-modified form) and acute phase proteins (fibrinogen, CRP) with acute ischemic stroke severity and outcome.

Materials and Methods: The study included 61 ischemic stroke patients and 64 controls. Strokes were subtyped according to TOAST criteria, the severity and outcome of stroke (at 1 year) were measured.

Results: The mean triglyceride, fibrinogen, CRP and glucose values were significantly higher among cases. The median oxLDL value for patients with large artery atherosclerosis (LAA) type of stroke was significantly higher than for other subtypes. The oxLDL values did not correlate with age, stroke severity and outcome.

Conclusions: Inflammatory markers (fibrinogen and CRP) predicted the stroke severity and outcome whereas elevation of oxLDL levels did not. Our data refer to possibility that there may exist some links between the LAA subtype of stroke and elevated oxLDL (apoB100 aldehyde-modified form).     

Nonvalvular atrial fibrillation: evidence for a prothrombotic state

OBJECTIVE: To determine whether patients with nonvalvular atrial fibrillation (NVAF) have prothrombotic changes compared with patients in sinus rhythm. DESIGN: Cross-sectional study. Hemostatic function compared in NVAF patients without prior embolic event (transient ischemic attack or embolic stroke) and control subjects without prior thrombotic stroke, and in NVAF patients with prior embolic event and control subjects with prior thrombotic stroke. SETTING: Internal medicine outpatient group practice and anticoagulation clinic in 2 teaching hospitals. PATIENTS: A total of 75 NVAF patients (50 without and 25 with prior embolic event) and 42 control patients (31 without and 11 with prior thrombotic stroke) recruited concurrently over 18 months during 1990-91. OUTCOME MEASURES: Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and plasma levels of hemoglobin, fibrinogen, von Willebrand factor antigen, factor VIII, fibrin D-dimer, antithrombin III, protein C, protein S, fibrinopeptide A and prothrombin fragment F1+2. All statistical analyses were performed after adjustments for age and sex. RESULTS: The NVAF patients without a prior embolic event had significantly higher mean hemoglobin and fibrinogen levels (p < 0.001 and p = 0.05, respectively) than the control subjects without prior thrombotic stroke. The 29 NVAF patients not taking warfarin (none had had an embolic event) had significantly lower mean protein C and protein S levels (p = 0.012 and p < 0.001, respectively) and a significantly higher fibrinopeptide A level (p = 0.03, after exclusion of outliers) than the control subjects without prior stroke. The NVAF patients with a prior embolic event had alterations in the hemostatic variables similar to those seen in the control patients with a prior thrombotic stroke. The latter had significantly higher fibrinogen, von Willebrand factor antigen and factor VIII levels (p = 0.04, 0.002 and 0.002, respectively) and significantly lower protein S levels (p = 0.02) than the control subjects without prior stroke. CONCLUSIONS: NVAF patients without a history of an embolic event show evidence of a prothrombotic state compared with patients in sinus rhythm who have not had a thrombotic stroke. NVAF patients with a history of an embolic event show evidence of a prothrombotic state similar to that of patients in sinus rhythm who have had a thrombotic stroke. Prospective studies are needed to determine whether these abnormalities predict higher risk of stroke in individual NVAF patients.