急性脑梗死患者血清超敏-C反应蛋白水平变化及其与TOAST分型关系的研究

目的观察急性脑梗死(ACI)患者超敏-C反应蛋白(hs-CRP)水平变化,及其与急性卒中治疗低分子肝素试验(TOAST)病因分型的关系。方法采用免疫散射比浊法对152例住院ACI患者进行血清hs-CRP水平测定,并按照TOAST标准分为5大亚型,分析TOAST各亚型与hs-CRP水平的关系。结果本组TOAST各亚型构成比为:不明原因型41·45%,小动脉闭塞型34·87%,心源性栓塞型5·26%,大动脉粥样硬化型15·79%,其他明确病因型2·6%。心源性栓塞型hs-CRP水平(11·60±7·85)mg/L、hs-CRP阳性率(87·50%)最高,阳性者hs-CRP水平(25·14±5·12)mg/L亦最高;其余依次为大动脉粥样硬化型(10·77±4·27)mg/L、其他明确病因型(6·45±3·25)mg/L、不明原因型(4·09±5·65)mg/L,而小动脉闭塞型(3·99±0·56)mg/L最低。经Logistic回归多因素分析:年龄、收缩压、胆固醇、三酰甘油、空腹血糖、纤维蛋白原与血清hs-CRP值呈显著正相关(r=0·1640、0·2489、0·2066、0·1866、0·3029、0·2224,均P<0·05)。结论ACI患者血清hs-CRP水平随TOAST亚型的不同而变化,hs-CRP可能在ACI的发生发展中起一定作用。血清hs-CRP水平增高可作为病情评估的指标之一。     

Synergistic neuroprotective effects of combined treatment with olmesartan plus azelnidipine in stroke‐prone spontaneously hypertensive rats

An angiotensin 2 type 1 receptor blocker, olmesartan, and a calcium channel blocker, azelnidipine, possess not only an antihypertensive effect but also an antioxidative effect and other beneficial effects. In the present study, we examined the efficacy of olmesartan and azelnidipine monotherapy (2 mg/kg or 10 mg/kg each) and their combination therapy (1 mg/kg each) on stroke‐prone spontaneously hypertensive rats (SHR‐SP) in relation to oxidative stress, inflammation, and the neurovascular unit. In comparison with the vehicle group, body weight, regional cerebral blood flow, and motor function were preserved, whereas systolic blood pressure and diastolic blood pressure decreased in the five drug‐treatment groups. Spontaneous infarct volume decreased with the low‐dose combination of olmesartan plus azelnidipine and with the high‐dose olmesartan, with a further decrease in the high‐dose azelnidipine group. In addition, these drugs dose‐dependently reduced oxidative stresses, proinflammatory molecules, and well‐preserved components of the neurovascular unit. The low‐dose combination of olmesartan plus azelnidipine showed a better effect than the low‐dose olmesartan or azelnidipine monotherapy. The present study shows that the low‐dose combination of olmesartan plus azelnidipine demonstrates a greater synergistic benefit than monotherapy with a low‐dose of olmesartan or azelnidipine in SHR‐SP for preventing spontaneous infarct volume, reducing oxidative stresses and proinflammatory molecules, and imparting neurovascular protection. In addition, a high‐dose of olmesartan showed a greater benefit without the lowering of blood pressure, probably because of the antioxidative and anti‐inflammatory effects. A high dose of azelnidipine showed the best benefit, probably because of the two effects mentioned above related to the lowering of blood pressure. © 2014 Wiley Periodicals, Inc.     

超选择动脉溶栓治疗80岁以上脑梗死的安全性及疗效评估-两中心研究

目的 探讨80岁以上高龄脑梗死患者超选择动脉溶栓治疗的安全性、可行性及治疗效果.方法 回顾性分析86例超选择动脉溶栓治疗的脑梗死患者的临床资料,根据年龄不同分为高龄组(≥180岁,21例)和普通年龄组(<80岁,65例),并设对照组(同时期≥80岁未行动脉溶栓治疗患者,50例).评估患者动脉溶栓术后血管良好再通率、早期临床改善率,以及各组症状性脑出血发生率、较好转归率及死亡率.结果 接受动脉溶栓治疗的两组患者血管良好再通率、早期临床改善率及症状性脑出血发生率比较差异无统计学意义(P=0.528,P=0.102,P=0.353).高龄组症状性脑出血发生率明显高于对照组,比较差异有统计学意义(P=0.034).高龄组较好转归率为42.9%,低于普通年龄组(50.8%),但高于对照组(16%),差异有统计学意义(P=0.042,P=0.017).高龄组死亡率与对照组比较差异无统计学意义(23.8%vs 28%,P=0.816),但高于普通年龄组,差异有统计学意义(23.8%vs 10.8%,P=0.034).结论 80岁以上高龄脑梗死患者超选择动脉溶栓治疗具有较高的安全性、可行性和临床疗效,高龄不是脑梗死动脉溶栓治疗的禁忌因素.

Abstract：

Objective To evaluate the feasibility, safety and efficacy of intra-arterial thrombolytic therapy on elderly patients (≥ 80 years old) with acute ischemic stroke. Methods The clinical data of 86 patients with acute ischemic stroke, received intra-arterial thrombolytic therapy, were retrospectively analyzed; according to age differences, these patients were divided into advanced age group (≥80 years old, n=21) and common age group (<80 years old, n=65); and control group (≥80 years old, not receiving thrombolytic therapy, n=50) was established. The recanalization rate and early clinical improvement rate, and the incidence, recover rate and death rate of symptomatic intracerebral hemorrhage were evaluated in these patients after treatment. Results No significant differences in the favorite recanalization rate and short-term outcome, and the incidence of symptom intracranial hemorrhage were noted between the advanced age group and common age group (P=0.528, P=0.102,P=0.353). The incidence of symptom intracranial hemorrhage in the advanced age group was obviously higher than that in the control group (P=0.034); the recover rate of symptom ntracranial hemorrhage in the advanced age group (42.9%) was obviously lower than that in the common age group (50.8%), but significantly higher than that in the control group (16%, P=0.042, P=0.017). The mortality of the advanced age group was similar to that of the control group (23.8% versus 28%, P=0.816), but higher than that of common age group (23.8% versus 10.8%, P=0.034). Conclusion Relatively high feasibility, safety and efficacy of intra-arterial thrombolytic therapy are noted in elderly patients (≥80 years old) with acute ischemic stroke, demonstrating that the use of intra-arterial thrombolytic therapy in very elderly patients should not be avoided but pursued advisably.     

Solar term peak of onset and death in 1 597 patients with acute ischemic stroke Circular statistical analysis

BACKGROUND： Previously, time data were analyzed by using constituent ratio or relative ratio; however, circular statistical analysis could exactly provide average peak phase of diseases. OBJECTIVE： To investigate the correlation of solar term peak with onset and death of acute ischemic stroke. DESIGN： Retrospective case analysis. SETTINGS： Emergency Department of Foshan Municipal Hospital of Traditional Chinese Medicine; Department of Science and Education, the Second People＇s Hospital of Foshan. PARTICIPANTS： A total of 1 597 patients with acute ischemic stroke were selected from Emergency Room, Department of Neurology, Foshan Municipal Hospital of Traditional Chinese Medicine from 1994 to 2002. There were 875 males and 722 females, and their ages ranged from 33 to 97 years. All cases met the diagnostic criteria of acute cerebral infarction modified by the Second National Cerebrovascular Disease Academic Meeting; meanwhile, they were diagnosed with CT/MRI test. Patients and their relatives provided the confirmed consent. METHODS： Solar term of onset was retrospectively analyzed in 1 597 patients with acute ischemic stroke; among them, solar term of death in 90 cases were analyzed by using circular statistical analysis to calculate peak phase of onset and death of acute ischemic stroke and investigate the correlation of solar term with onset and death of acute ischemic stroke. MAIN OUTCOME MEASURES： Onset and death time of patients with acute ischemic stroke. RESULTS： Solar term of onset in 1 597 patients, especially solar term of death in 90 patients, was not concentrated （P 〉 0.05）, and specific peak phase was not found out. Acute ischemic stroke low attacked from vernal equinox to summer begins, but death caused by acute ischemic stroke high attacked from grain buds to autumn begins. CONCLUSION： Patients with acute ischemic stroke do not have specific solar term peak of onset and death.     

脑梗死患者动脉粥样硬化与OCSP分型关系的研究

目的 探讨脑梗死患者动脉粥样硬化所致的颈动脉颅外段狭窄与OCSP分型各亚型的关系。方法 对161例急性脑梗死（ACI）患者进行OCSP分型,并对其中配合检查的156例以及54例单纯高血压患者和43例健康正常人进行颈动脉彩色多普勒超声检测颈动脉颅外段的狭窄程度,并探讨OCSP各亚型与颈动脉狭窄的关系。结果 脑梗死组颈动脉颅外段狭窄发生率为75％,较高血压组35．19％,和正常对照组27．91％明显升高（P〈0．01）。脑梗死组OCSP各亚型构成比为：腔隙性梗死49．1％,部分前循环梗死37．9％,和后循环梗死7．5％,完全性前循环梗死5．6％。OCSP各亚型急性脑梗死患者之间的颈动脉狭窄阳性率无显著性差异（P〉0．05）。前循环和后循环梗死中重度的血管狭窄明显高于腔隙性梗死。结论 脑梗死同颈动脉颅外段的狭窄明显相关,OCSP分型不能提示脑梗死患者动脉粥样硬化病因。     

脑微出血与不同亚型缺血性脑卒中的关系及预后分析

目的探讨脑微出血(CMBs)与不同亚型缺血性脑卒中的关系及预后。方法收集2014年3月~2016年5月期间就诊我院,并确诊为缺血性脑卒中的患者116例,根据中国缺血性脑卒中亚型(CISS)标准分为5种亚型,即大动脉粥样硬化型卒中(LAA)、心源性卒中(CS)、其他病因型(OE)、穿支动脉疾病型(PAD)和病因不确定型(UE)。每个亚型分为CMBs组和非CMBs组,比较各组血清相关指标,采用Logistic回归分析每种亚型伴CMBs的影响因素,采用NIHSS评分评价每种亚型伴CMBs的预后情况。结果 PAD组同型半胱氨酸(Hcy)水平(23.32±2.79)μmol/L,明显高于LAA(20.64±3.11)μmol/L、CS(20.7±2.63)μmol/L、OE(18.92±2.91)μmol/L和UE(17.63±3.06)μmol/L,差异具有统计学意义(P0.05)。OE组和LAA组糖化血红蛋白(Hb A1)水平(7.60±0.25和7.11±0.32)明显高于CS组(5.03±0.11)、PAD组(5.10±0.11)和UE组(4.99±0.12),差异具有统计学意义(P0.05);而OE和LAA两组间、CS、PAD和UE三组间Hb A1水平差异不明显(P0.05)。长期饮酒是CS和PAD伴CMBs的独立危险因素;Hcy是每种亚型伴CMBs的独立危险因素;Hb A1是PAD、LAA伴CMBs的独立危险因素。结论 Hcy、Hb A1和长期饮酒是缺血性脑卒中伴CMBs的独立危险因素。不同亚型缺血性脑卒中伴CMBs的预后差异不明显。     

The clinical spectrum of intracerebral hematoma, hemorrhagic infarct, non-hemorrhagic infarct, and non-lesional venous stroke in patients with cerebral sinus-venous thrombosis

Background and purpose: The clinical spectrum of different neuroradiological features of cerebral sinus–venous thrombosis (CSVT) varies considerably. We sought the relationship between different neuroradiological aspects and clinical presentations in these patients. Methods: The diagnosis of cerebral sinus–venous thrombosis has been confirmed by conventional angiography, MRI combined with MR venography following established diagnostic criteria. We analyzed clinical data, symptoms and signs, imaging findings, location and extent of the thrombus, and parenchymal lesions, retrospectively. Results: There were 220 consecutive patients with cerebral sinus–venous thrombosis; 98 (45%) had non‐lesional sinus–venous thrombosis (NL CSVT), 51 (23%) had non‐hemorrhagic infarct (NHI), 45 (20%) had hemorrhagic infarct (HI), and 26 (12%) had intracerebral hemorrhage (ICH). In patients with hemorrhagic lesion (HI+ICH), advanced age, headache (99%), behavioral disturbances (55%), consciousness disturbances (35%), seizures (41%), and language deficits (42%) were significantly higher than the other patients (NL+NHI) (P < 0.001). High blood pressure at admission, puerperium, sigmoid and straight sinus thrombosis, multiple sinus and vein involvement were more frequent in patients with hemorrhagic lesion than those with non‐hemorrhagic lesion. Patients with hemorrhagic lesion were more dependent or died (32%) than the other patients (12%) (P < 0.001), and most of the patients with NL and NHI had no disability compared with the other patients at the 3 month of follow‐up (96% and 65%; P < 0.001). Conclusion: Headache, convulsion, behavioral disorder, seizures, and speech disorders were the most frequent clinical symptoms of patients with hemorrhagic CSVT. Specific risk factors, including pregnancy/puerberium, early and extended thrombosis of large sinus, and presence of high blood pressure at admission, are associated with hemorrhagic lesion and unfavorable outcome.     

Social interaction plays a critical role in neurogenesis and recovery after stroke

Stroke survivors often experience social isolation. Social interaction improves quality of life and decreases mortality after stroke. Male mice (20–25 g; C57BL/6N), all initially pair housed, were subjected to middle cerebral artery occlusion (MCAO). Mice were subsequently assigned into one of three housing conditions: (1) Isolated (SI); (2) Paired with their original cage mate who was also subjected to stroke (stroke partner (PH-SP)); or (3) Paired with their original cage mate who underwent sham surgery (healthy partner (PH-HP)). Infarct analysis was performed 72 h after stroke and chronic survival was assessed at day 30. Immediate post-stroke isolation led to a significant increase in infarct size and mortality. Interestingly, mice paired with a healthy partner had significantly lower mortality than mice paired with a stroke partner, despite equivalent infarct damage. To control for changes in infarct size induced by immediate post-stroke isolation, additional cohorts were assessed that remained pair housed for three days after stroke prior to randomization. Levels of brain-derived neurotrophic factor (BDNF) were assessed at 90 days and cell proliferation (in cohorts injected with 5-bromo-2′-deoxyuridine, BrdU) was evaluated at 8 and 90 days after stroke. All mice in the delayed housing protocol had equivalent infarct volumes (SI, PH-HP and PH-SP). Mice paired with a healthy partner showed enhanced behavioral recovery compared with either isolated mice or mice paired with a stroke partner. Behavioral improvements paralleled changes in BDNF levels and neurogenesis. These findings suggest that the social environment has an important role in recovery after ischemic brain injury.     

脑梗死大鼠神经功能缺损评分与脑梗死体积的相关性研究

目的:研究经典线栓法制备局灶性脑梗死模型大鼠的神经功能评分与脑梗死面积的相关性。方法:采用Zea Longa法制作大鼠局灶性脑梗死模型,在不同时间段对脑梗死大鼠进行神经功能缺损评分,并用2%TTC(氯化三苯基四氮唑)溶液对脑组织染色,计算脑梗死面积及梗死体积百分比。结果:线栓法制备局灶性脑梗死模型的大鼠24～48 h内神经功能评分降低,但脑梗死体积却增大,神经功能缺损评分与脑梗死体积百分比之间无相关性(r=-0.3762;P=0.88999)。结论:经典线栓法制备的局灶性脑梗死模型(大脑中动脉栓塞)中,尚不能认为大鼠的肢体运动功能与脑梗死体积有相关性。     

髓鞘碱性蛋白免疫治疗对出血性卒中大鼠的保护作用研究

目的研究髓鞘碱性蛋白(myelin basic protein,MBP)主动免疫,对大鼠出血性卒中的保护作用,探讨其预防继发性脑损害的可能机制。方法SD大鼠84只,采用随机数字表法,分为MBP、卵白蛋白(Ovalbumin,VOA)、PBS和空白对照四组(n=21)。制备脑出血模型后24小时内,用不完全福式佐剂(Incom-plete Freund's Adjuvant,IFA)乳化的MBP、VOA、PBS分别免疫三组大鼠,对照组只做脑出血模型,在相应时间点行为学评分,并标本取材,行胶质纤维酸性蛋白(Glial fibrillary acid protein,GFAP)和神经微丝蛋白200(Neurofilament protein,NF200)免疫染色,电镜观察血肿周围脑组织的超微结构变化。结果(1)MBP组免疫后第1～3天行为学评分明显优于其它三组(P<0.05);(2)出血免疫后第1～5天,MBP组GFAP阳性细胞数与其它三组相比有显著性差异(P(0.05),后三组相比无统计学意义(P>0.05)。(3)MBP组NF200阳性细胞数在免疫后第3～14天与后三组相比有显著性差异(P(0.05),后三组之间相比无明显差异(P>0.05)。(4)免疫后第7天,MBP组神经元亚细胞器较丰富,神经微丝排列整齐,其他三组亚细胞器变形或消失,神经微丝排列紊乱。结论MBP免疫治疗能阻断出血性卒中的继发性脑损害,促进神经症状的改善,即血肿周围神经元的恢复。     

Severity of cerebral white matter lesions and infarcts in patients with transient or moderately disabling cerebral ischaemia: reproducibility of grading by neurologists

Diffuse or multifocal ischaemic white matter lesions increase the risk of intracranial haemorrhage in patients using oral anticoagulants for secondary prevention after cerebral ischaemia of arterial origin. We studied whether neurologists could reliably assess the presence of these white matter abnormalities. As part of the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), the severity of white matter lesions and presence of ischaemic lesions were twice assessed in a consensus meeting of three neurologists (from a pool of nine) as absent, moderate or severe, in a sample of 126 randomly selected CT or MRI scans. The neurologists were not aware of the duplicate grading. The degree of agreement between the first and second observation was calculated with kappa statistics. The kappa value for agreement between the first and second assessment of white matter lesions was 0.58 (95% CI 0.40–0.76). The kappa value for the presence of clinically relevant and/or irrelevant ischaemic lesions was 0.68 (95% CI 0.58–0.78). Clinicians can assess the presence of white matter lesions with sufficient reliability. Such assessment may prevent unnecessary risk with oral anticoagulation in secondary prevention after cerebral ischaemia of arterial origin, of which the efficacy is currently being assessed in ESPRIT.     

Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct

Stereotactic transplantation of bone marrow stromal cells (BMSCs) enables efficient delivery to the infarct brain. This study was aimed to assess its optimal timing and cell dose for ischemic stroke. The BMSCs were harvested from the green fluorescent protein‐transgenic rats and were labeled with quantum dots. The BMSCs (1 × 10⁵ or 1 × 10⁶) were stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion at 1 or 4 weeks post‐ischemia. Motor function was serially assessed. Using in vivo near infrared (NIR) fluorescence imaging, the engrafted BMSCs were visualized at 3 weeks post‐transplantation. Immunohistochemistry was performed to evaluate their fate. Functional recovery was significantly enhanced when both low and high doses of BMSCs were transplanted at 1 week post‐ischemia, but such therapeutic effects were observed only when the high‐dose BMSCs were transplanted at 4 weeks post‐ischemia. Both optical imaging and immunohistochemistry revealed their better engraftment in the peri‐infarct area when the high‐dose BMSCs were transplanted at 1 or 4 weeks post‐ischemia. These findings strongly suggest the importance of timing and cell dose to yield therapeutic effects of BMSC transplantation for ischemic stroke. Earlier transplantation requires a smaller number of donor cells for beneficial effects.     

Predictors of survival and functional outcome in acute stroke patients admitted to the stroke intensive care unit

Multivariate models have not been widely used to predict the outcome of acute stroke patients admitted to the intensive care unit (ICU). The purpose of this study was to determine potential measures observed in the first 12 h post-stroke that predict early mortality and functional outcomes in ICU-admitted stroke patients. Eight hundred and fifty acute stroke patients (ischemic stroke, 508; intracerebral hemorrhage, 342) were included in this analysis between November 2002 and December 2006. Measures of interest were obtained in the first 12 h after onset of stroke were analyzed for three types of outcome: 3-month mortality, 3-month mortality or institutional care, and poor functional outcomes at discharge. Poor functional outcomes were defined as a Barthel index <80 or a Rankin scale >2. Multivariate regression models were used to determine the predictive value of the observed measures. After 3 months, 17% of patients had died; 21% were alive but being cared for in institutional settings; and 62% were alive and living at home. Functional status at discharge indicated 16% of patients had died, poor function in 50%, and good function in 34% of patients. Initial stroke severity, measured by National Institute of Health Stroke Scale, and dependence on a ventilator predicts 3-month mortality and poor outcome in all stroke patients. In addition, old age, previous stroke, and total anterior circulatory infarct were associated with poor outcome in ischemic stroke patients; old age, low body mass index and the presence of intraventricular hemorrhage were associated with poor outcomes in intracerebral hemorrhage patients. In conclusion, early stroke mortality and outcome at discharge can be predicted in the first few hours following an acute stroke for moderate to severe ICU-admitted stroke patients.