实验性蛛网膜下腔出血后的肿瘤坏死因子变化

目的：为探讨蛛网膜下腔出血（SAH）后的神经免疫学变化,采用动物实验方法对实验性SAH后不同时间内的TXB2和TNF－α的变化进行了观察。方法：选用Wistar大鼠做SAH实验模型,经颈骨钻孔往入自家血方法完成实验。对不同时间内的血浆TXB2及TNF－α水平做了放免学测定。结果：TXB2在实验后12h即有显著升高（实验前278．0±54．5mmol／L,12～36h间为2714．6±1248．8～3455．5±1496．9）,持续至36h后降至正常。TNF－α在实验后12h亦有显著增高,呈持续性（实验前4．6±1．7mmol／L实验后22．8±8．7mmom／L）,但在36h和5d有轻度下降,故增高呈双峰型。结论：实验性SAH后TNP有表达增高改变,其机制多与血管内皮损伤和神经组织受损后的合成增加有关,其作用过程与白细胞和血小板的激活过程相关联。TXB2和TNF早期增高的正相关改变提示TNF增高可能在促凝血和血管痉挛中起一定作用。     

大鼠蛛网膜下腔出血后白介素33的变化和可能的作用

目的：研究蛛网膜下腔出血（SAH）后,在大鼠脑组织中白介素33（IL-33）的变化情况并探讨IL-33在蛛网膜下腔出血后的可能作用。方法 SD大鼠被随机分为空白组与蛛网膜下腔出血后2 h、6 h、12 h、24 h、2 d、3 d组共7组,蛛网膜下腔出血模型采用视交叉前池注血模型,并用Western blot和免疫组化测定IL-33的表达,用RT-PCR检测IL-33和IL-1βmRNA的水平变化。结果蛛网膜下腔出血可以引起IL-33表达的升高,同时蛛网膜下腔出血后IL-33和IL-1β的mRNA变化水平有正相关。结论蛛网膜下腔出血可以提高IL-33的表达;IL-33有可能在蛛网膜下腔出血后的炎症反应中起重要作用。     

蛛网膜下腔出血后大鼠血清PDGF与脑血管痉挛关系的研究

目的探讨大鼠SAH(subarachnoid hemorrhage,SAH)后血清血小板源性生长因子(platelet-derivedgrowth factor,PDGF)与脑血管痉挛的关系,为临床治疗SAH后CVS(脑血管痉挛cerebral vasospasm)提供实验依据。方法 55只Sprague-Dawley大鼠随机分为三组:正常组,对照组(即SOR组,假手术组,Shamoperated rats,枕大池注入等量生理盐水)和SAH模型组。采用ELISA法测定血液中PDGF的水平;同时保存对应标本,观测大鼠基底动脉的形态学改变,测定血管壁厚度及血管内径。比较血清PDGF含量的变化与脑血管痉挛之间的关系。结果模型组基底动脉痉挛于第1 d就出现,第3d表现最为明显,第5,7d以后明显减轻,但仍比SOR组明显,第14 d基本正常。大鼠SAH后血清PDGF浓度于第1 d就明显升高,至第3 d达到顶峰,至第7天时仍高于SOR组,第14 d时基本正常。SAH后血清PDGF水平的变化与脑血管痉挛的变化是一致的。结论二次枕大池注血后,基底动脉发生了明显的细胞形态改变、管壁的增厚以及管腔的狭窄,提示SAH后有CVS的存在。SAH后血清PDGF水平的变化与脑血管痉挛的变化是一致的,呈正相关。提示PDGF可能参与了CVS的病理过程。     

Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH

The relation between angiographically determined cerebral vasospasm following a subarachnoid hemorrhage and regional cerebral blood flow (CBF) was studied in 63 investigations of 45 patients. The CBF was measured using the intra-arterial 133-Xe clearance technique within one hour of angiography. A positive correlation between regional CBF and diameter of major supplying vessel was observed. However, in the 13 cases with focal vasospasm the reduction in CBF was global and not restricted to the area of the spastic vessel. The cerebral oxygen extraction was reduced but independent of the degree of vasospasm, speaking against vasospasm as the cause for the reduction in CBF. The observed association between reduction in CBF and vasospasms could be caused by a common factor responsible for development of both. Thus, it is proposed that the amount of blood escaping at time of aneurysm rupture determines 1) the amount of reduction in cerebral oxygen uptake and thereby the reduction in CBF and 2) the degree of vasospasm. If so a correlation, yet not causal, between reduction in CBF and degree of vasospasm, will be observed.     

Value of repeat-angiography in cases of unexplained subarachnoid hemorrhage (SAH)

Purpose – To investigate the rate of false negative initial cerebral angiography in spontaneous SAH and to ascertain why aneurysms remain undetected. Furthermore to validate CCT in predicting the presence and site of an angiographically missed aneurysm. Methods – Forty-two patients with spontaneous SAH were investigated, in whom initial cerebral angiography did not reveal any bleeding cause. Repeat-angiography was performed in all patients 5 to 55 days (mean 15 days) after the bleeding event. All patients underwent CCT scans within 48h after the ictus. Results – In 8 of 42 patients (19%) repeat-angiography revealed an aneurysm missed on initial angiography. The aneurysms were located on the AcomA (n = 2), the MCA (n = 2), the ACA (n= 1), the PICA (n = 2) and the junction of ICA and PcomA (n = 1). Presumable reasons for missing an aneurysm were spasms detected in four of eight cases on initial angiography and thrombosis of the aneurysm found in two cases at surgery. In two cases, multiple additional views just revealed the aneurysm appearing different in size and shape on repeat-angiography. CCT blood distribution pattern in four cases indicated presence and site of an aneurysm, while blood distribution was non-specific in the other four cases. Conclusion – Repeat-angiography plays an important role in defining the site of an initially occult aneurysm and should be performed in all cases of unexplained SAH. It is of particular importance if vasospasm has compromised the initial angiogram or if one part of the vascular tree is not optimally seen.     

The impact of obstructive sleep apnoea severity on cardiac structure and injury

BackgroundObstructive sleep apnoea (OSA) is an important factor in the development and progression of heart failure (HF). The prevalence of OSA is higher in patients with HF than in the general population. We sought to test the hypothesis that OSA severity was predictive of ventricular function and cardiac injury [as assessed by high-sensitivity cardiac troponin I(hs-cTnI)].MethodsA total of 60 patients were recruited after evaluation for sleep disturbances using the Jenkins Sleep Questionnaire (JSQ) and Epworth Sleepiness Scale (ESS). Subsequently, they underwent polysomnography thus confirming the diagnosis of OSA and were equally divided into three groups according to OSA severity grade. Following polysomnography, the next morning patients underwent venous blood sampling and echocardiography.ResultsWe observed a statistically significant association (P = 0.009) between diastolic dysfunction grades and severity grades of OSA. All the three diastolic dysfunction variables E/A ratio, deceleration time and E/e’ ratio had a significant association(P < 0.05) with severity grades of OSA. There was a marginally significant positive correlation (ρ = 0.3244, p = 0.04) between AHI events per hour and mitral E/e’ ratio. There was a statistically significant association(P < 0.001) between hs-cTnI value among different severity grades of OSA.ConclusionsHere in our study, we found OSA a potential risk factor for development of myocardial injury and diastolic dysfunction. Severe grades of OSA are associated with higher grades of diastolic dysfunction and circulating levels of hs-cTnI. These data are consistent with the notion of a vicious cycle of frequent apnoea's or hypoxemia and recurrent myocardial injury, which could increase the risk of heart failure especially diastolic dysfunction in OSA.     

Organic psychiatric disorders after aneurysmal SAH: outcome and associations with age,bleeding severity,and arterial hypertension

OBJECTIVES: The Lindqvist & Malmgren's system was used to describe the outcome of organic psychiatric disorders (OPDs) after aneurysmal subarachnoid hemorrhage (aSAH) and their associations with age, bleeding severity, and pre-existing arterial hypertension (preAH). MATERIAL AND METHOD: OPDs were diagnosed at 3, 6, and 12 months after aSAH in a prospective cohort study (n=63). Reaction level (RLS85), World Federation of Neurological Surgeons Committee SAH scale (WFNS), Fisher, and hydrocephalus grades were assessed at admission. RESULTS: At 3/6/12 months, 60/49/38% had an Astheno-emotional disorder (AED), 4/5/5% had emotional-motivational blunting disorder (EMD) and 19/19/16% had Korsakoffs amnestic disorder (KAD). AED was associated with preAH, whereas EMD/KAD, but not AED, was associated with a higher mean age, worse median RLS85 levels, WFNS grades, and Fisher grades. CONCLUSIONS: OPDs were diagnosed in 59% of the patients at 12 months after aSAH. AED, the most common OPD, had the highest recovery rate and was associated with preAH. Use of organic psychiatric diagnoses for evaluation of outcome after aSAH and other brain injuries is encouraged.     

Neurovascular complications of cocaine

Use of cocaine in the USA, has reached epidemic proportions since 1983, when "crack" was introduced, its higher potency compared with cocaine HCl has been associated with a tremendous increase in the incidence of strokes. This study reports our experience with 55 cases of neurovascular events (25 ischemic and 30 hemorrhagic) related to cocaine use in 54 patients. Only 15 patients had other risk factors for stroke. Twenty six patients smoked "crack", 10 snorted cocaine and 12 injected it intravenously. Strokes occurred within 3 h of cocaine use in 15 patients with infarcts and 17 with hemorrhages. Ten infarcts occurred after an overnight binge. Of the hemorrhage group 9 were subarachnoid, 16 intracerebral (8 basal ganglia, 7 hemispheric and one brain stem) and 5 intraventricular. Computerized tomography (CT) showed an aneurysm of the anterior communicating artery, as well as one of the vein of Galen. Four aneurysms and 3 AVMs were identified on angiography. CT revealed 15 infarcts; it was normal in 7 patients with pure motor hemiparesis and in 3 with findings consistent with anterior spinal artery infarction. Several mechanisms may be responsible for the cerebrovascular complications. A sudden rise in systemic arterial pressure may cause hemorrhages, frequently in association with an underlying aneurysm or AVM. Vasospasm, arteritis, myocardial infarction with cardiac arrhythmias and increased platelet aggregation may provoke infarcts.     

自发性蛛网膜下腔出血预后的影响因素分析

目的 分析自发性蛛网膜下腔出血(SAH)患者预后的影响因素.方法 回顾性分析109例自发性SAH患者的临床资料,按发病后6个月的改良Rankin量表(mRS)评分分为转归良好组与转归不良组,采用多因素Logistic回归分析方法评估影响预后的因素.结果 迟发性脑血管痉挛(CVS)、发病早期的Glasgow昏迷评分(GCS)及既往卒中史是预后不良的影响因素.结论 预防CVS、使用合理的评估工具及做好卒中的预防是改善SAH预后的主要途径.     

The impact of neuropsychological functioning on treatment outcome in pediatric obsessive–compulsive disorder

Background: Scant research has examined the effect of neuropsychological (NP) functioning on treatment outcome in pediatric obsessive–compulsive disorder (OCD). This study sought to address this gap in existing research. Methods: A total of 63 youths were included in this study and asked to complete the Rey‐Osterrieth Complex Figure (ROCF) and specific subtests of the Wechsler Intelligence Scale for Children, Third Edition (WISC‐III). Results: Analyses suggest that 5 min recall accuracy (raw score) and percent recall from the ROCF, assessed before treatment may be predictors of treatment response among children with OCD. What is more, exploratory post hoc analyses indicated that performance on these ROCF tasks is particularly relevant among youths receiving cognitive‐behavior therapy (CBT) alone. These results may be driven by executive functioning ability. Additional analyses suggest a relationship between age, symptom severity, and NP functioning on select tasks from both the ROCF and WISC‐III. Conclusions: Although alternative explanations exist, these findings suggest that poorer performance on the ROCF and, in turn, poorer response to treatment, particularly among those youths receiving CBT alone, may be due to executive functioning difficulties. Clinicians and researchers should be sensitive to this fact and may warrant modification(s) to existing treatment protocols. Limitations to this study, however, suggest the need for replication and extension of these findings in the future. Depression and Anxiety, 2010. © 2009 Wiley‐Liss, Inc.     

脑梗死发生时间对动脉瘤性蛛网膜下腔出血患者临床结局的影响

目的探究脑梗死发生时间对动脉瘤性蛛网膜下腔出血患者(aSAH)临床结局的影响。方法纳入2010年3月至2016年6月来我院进行就诊的aSAH患者395例,其中发生早期脑梗死患者74例,迟发性脑梗死患者77例,两者并发患者29例。分析aSAH术后脑梗死患者临床特征;采用多因素Logistic回归分析术后脑梗死发生的独立危险因素和长期预后的独立危险因素。结果多因素Logistic回归分析显示Hunt～Hess≥Ⅲ级和手术夹闭术是早期脑梗死发生的独立危险因素(P0.05);Hunt～Hess≥Ⅲ级和血管痉挛是迟发性脑梗死发生的独立危险因素(P0.05);早期脑梗死是术后a SHA患者长期不良预后的独立危险因素(OR,2.43;95%CI,1.16～4.72;P0.001)。结论 Hunt～Hess≥Ⅲ级和手术夹闭术是aSAH患者术后并发早期脑梗死的独立危险因素,而Hunt～Hess≥Ⅲ级和血管痉挛则是迟发性脑梗死的独立危险因素。早期脑梗死比迟发性脑梗死更能预测aSAH患者术后的不良预后。     

The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages

Associations between the angiotensin II type 1 receptor (AGTR1) gene A1166C polymorphism and hypertension, aortic abdominal aneurysms (as a risk factor) as well as cardiovascular disorders (as a risk factor and an outcome predictor) have been demonstrated. We aimed to investigate the role of this polymorphism as risk factors and outcome predictors in primary intracerebral hemorrhage (PICH) and aneurysmal subarachnoid hemorrhage (aSAH).We have prospectively recruited 1078 Polish participants to the study: 261 PICH patients, 392 aSAH patients, and 425 unrelated control subjects. The A1166C AGTR1 gene polymorphism was studied using the tetra-primer ARMS-PCR method. Allele and genotype frequencies were compared with other ethnically different populations.The A1166C polymorphism was not associated with the risk of PICH or aSAH. Among the aSAH patients the AA genotype was associated with a good outcome, defined by a Glasgow Outcome Scale of 4 or 5 (p < 0.02). The distribution of A1166C genotypes in our cohort did not differ from other white or other populations of European descent.In conclusion, we found an association between the A1166C AGTR1 polymorphism and outcome of aSAH patients, but not with the risk of PICH or aSAH.     

Endothelial dysfunction in acute brain injury and the development of cerebral ischemia

Cerebral ischemia (CeI) is a major complicating event after acute brain injury (ABI) in which endothelial dysfunction is a key player. This study evaluates cellular markers of endothelial function and in vivo reactive hyperemia in patients with ABI and their relationship to the development of cerebral ischemia. We studied cellular markers of endothelial dysfunction and the peripheral reactive hyperemia index (RHI) in 26 patients with ABI at admission and after 6 and 12 days, and compared these with those of healthy volunteers (n = 15). CeI was determined clinically or by computer tomography. In patients with ABI, RHI at admission was significantly reduced compared with healthy subjects (P = 0.003), coinciding with a decrease in circulating endothelial progenitor cells (EPC; P = 0.002). The RHI recovered in eight patients without development of CeI, but failed to fully recover by day 12 in three of four patients who developed CeI. Despite recovery of the RHI within 12 days in these patients (P = 0.003), EPC count remained significantly lower after 12 days in patients with ABI (P = 0.022). CD31⁺ T cells and endothelial microparticles were not different between controls and patients. No differences were noted in cellular markers of endothelial dysfunction in patients developing CeI and those not. In conclusion, patients with ABI exhibit impaired microvascular endothelial function measured as RHI and a decreased circulating level of EPC. © 2015 Wiley Periodicals, Inc.     

动脉瘤性蛛网膜下腔出血及相关并发症的诊治

目的探讨动脉瘤性蛛网膜下腔出血（SAH）的血管内治疗及相关并发症处理。方法对动脉瘤性SAH患者早期诊断,采用血管内治疗并对其并发症进行处理。结论本组40例动脉瘤行栓塞治疗,其中栓塞达90%者26例,95%栓塞11例,完全栓塞3例。死亡4例,1例保守治疗后出院。结论动脉瘤性SAH的早期诊治及围手术期治疗极其重要,是降低死亡率及致残率的关键,介入治疗受血管痉挛的影响小。     

Molecular alterations in the hippocampus after experimental subarachnoid hemorrhage

Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.     

Clinical outcome of spontaneous non-aneurysmal subarachnoid hemorrhage in 108 patients

Background: The cause of spontaneous subarachnoid hemorrhage (SAH) is unknown in 15% of cases; idiopathic SAH has a better prognosis than aneurysmal SAH. When bleeding is confined to the perimesencephalic cisterns, SAH has an especially benign course. Methods: We retrospectively studied 108 patients admitted for spontaneous non‐aneurysmal SAH between 1991 and 2004. We divided patients into two groups according to the bleeding pattern at cranial CT: perimesencephalic pattern (n = 60) and aneurysmal pattern (n = 48). We included only patients in whom no source of bleeding was detected at angiography; patients with aneurysmal pattern underwent at least two angiographic examinations. Mean follow‐up was 5.5 years; follow‐up consisted of telephone interview in 84.7% of patients. Results: All but one patient with perimesencephalic pattern were classified as grade I or II on the Hunt and Hess scale; the exception was the only patient in this group with a complication (hydrocephalus), who was classified as grade IV. Three‐quarters of the patients with aneurysmal pattern were classified as grade I or II on the Hunt and Hess scale; 5 patients presented with hydrocephalus that required drainage and 2 with vasospasms without repercussions. No rebleeding or long‐term complications were observed in either group. Conclusions: Non‐aneurysmal SAH with a perimesencephalic pattern of bleeding has a benign course and excellent short‐term and long‐term prognosis. Patients with non‐aneurysmal SAH with an aneurysmal pattern of bleeding have more complications, and the initial clinical situation has a significant impact on their prognosis.     

Genetic elimination of eNOS reduces secondary complications of experimental subarachnoid hemorrhage

Delayed complications of subarachnoid hemorrhage (SAH) such as angiographic vasospasm, cortical spreading ischemia, microcirculatory dysfunction, and microthrombosis are reported in both patients and animal models of SAH. We demonstrated previously that SAH is associated with increased oxidative stress in the brain parenchyma, and that this correlates with dysfunction of endothelial nitric oxide synthase (eNOS) (homodimeric uncoupling). Uncoupling of eNOS exacerbated oxidative stress and enhanced nitric oxide (NO) depletion, and was associated with multiple secondary complications such as microthrombosis, neuronal apoptosis, and release of reactive oxygen species. Thus, we hypothesized that genetic abbrogation of eNOS would confer a beneficial effect on the brain after SAH. Using a prechiasmatic injection model of SAH, we show here that eNOS knockout (KO) significantly alleviates vasospasm of the middle cerebral artery and reduces superoxide production. Endothelial nitric oxide synthase KO also affected other nitric oxide synthase isoforms. It significantly increases neuron nitric oxide synthase expression but has no effect on inducible nitric oxide synthase. Endothelial nitric oxide synthase KO decreases Zn²⁺ release after SAH, reduces microthrombi formation, and prevent neuronal degeneration. This work is consistent with our findings where, after SAH, increased oxidative stress can uncouple eNOS via Zn²⁺ thiolate oxidation, or theoretically by depletion or oxidation of tetrahydrobiopterin, resulting in a paradoxical release of superoxide anion radical, further exacerbating oxidative stress and microvascular damage.     

蛛网膜下腔出血时脑脊液检查的意义

５２５例ＳＡＨ患者６８７次腰穿所得ＣＳＦ理化检查表明：ＳＡＨ后早期ＣＳＦ呈浓血性者死亡率达２０．９％压力高于１．９６ｋＰａ者死亡率达２８．４％；血性ＣＳＦ维持最长者到病后１８天，ＣＳＦ黄变的高峰是在病后２～３周。黄变延续时间最长可到病后５７天；ＣＳＦ中含噬铁颗粒的白细胞可存子病后的第十周。因此。ＳＡＨ急性期治疗以到病后３～４周为宜。ＣＳＦ检查对ＳＡＨ诊断、预后判断有价值。