Thrombolytic treatment of acute cerebral infarction

Stroke is a common cause of death and disability throughout the world. Acute neurologic deficits due to ischemic injury deserve rapid recognition and diagnosis in order to provide effective therapy. Intravenous tissue plasminogen activator (t-PA) provided to carefully selected patients that can be treated within 3 hours of stroke onset results in improved outcome in these patients. Intra-arterial administration of t-PA within a 6-hour window is performed at several academic centers in patients with middle cerebral and other intracranial artery occlusions based on results of one randomized clinical trial and numerous case reports. Although acute therapy of ischemic stroke has received much attention since the approval of intravenous t-PA, only a small percentage of individuals suffering a stroke actually receive t-PA. This article will review the optimal management of the acute stroke patient and discuss thrombolytic clinical trials that have been completed as well as those that are in progress.     

Neues in der Akuttherapie des ischämischen Schlaganfalls

Stroke is one of the major causes of mortality and the most important cause of disability in the industrialized world. About 85?% of all strokes are caused by acute occlusion of a cerebral vessel and are, therefore, classified as ischemic stroke. Acute stroke care has seen substantial improvements in the last 20 years with the introduction of specialized acute care units (stroke units) and the implementation of intravenous thrombolysis with rtPA, which can be administered up to 4.5 h after symptom onset. According to recent evidence, even patients with age over 80 years, history of diabetes and stroke, wake up stroke, pretreatment with vitamin K antagonists, or one of the new oral anticoagulants could benefit from rtPA under specific conditions. A new therapeutic option for patients with a severe ischemic stroke could be the combined use of intravenous and intraarterial thrombolysis together with mechanical thrombectomy.     

Endovaskuläre Therapie des akuten ischämischen Schlaganfalls

Endovascular therapy of acute ischemic stroke represents a supplementary or (in cases of contraindications to systemic lysis) alternative therapy option to intravenous thrombolysis for patients with severe clinical deficits and proximal vascular obstruction. Currently, (in cases with no contraindications to systemic lysis) the combination with mechanical thrombectomy in the form of so-called stent retrievers has proven to be effective and safe. Until superiority over intravenous thrombolysis alone has been proven in certain patient groups, patients who have received endovascular therapy should be carefully documented in register-based studies.     

脑卒中诊治观念转变的思考

脑卒中是一种常见病,伴有较高的病死率和致残率。近年来脑卒中诊治方面取得了不少进展,许多有关脑卒中的诊治的观念发生了巨大的转变,如卒中后血压的控制,高血压脑出血的止血治疗,急性脑梗死的溶栓治疗,卒中单元以及卒中的预防等方面。从这些转变中渗透着许多哲学观点,如否定之否定规律,科学假说与理论之间的关系,系统论的应用等。运用哲学的观点认识脑卒中的诊断治疗的转变,对日后的临床和科研有着一定的指导意义。     

高尿酸血症与急性脑梗死患者病情严重程度和预后的相关性研究

文章探讨高尿酸血症与急性脑梗死患者病情严重程度和预后的相关性.选择急性脑梗死患者198例,男性115例,女性83例,以前瞻性病例对照的研究方法,分析高尿酸血症与急性脑梗死患者入院时、住院10天时的病情严重程度和90天预后的相关性.高尿酸血症与急性脑梗死患者入院时病情严重程度无关（P＆gt;0.05）,与住院10天时病情严重程度呈负相关（P=0.003）,与10天时的美国国立卫生研究院卒中量表（NIHSS）转归分数呈正相关（P=0.002）,与90天预后呈正相关（P=0.001）.笔者认为高尿酸血症与急性脑梗死患者住院10天时的病情严重程度和90天预后具有独立的相关性.     

阿司匹林在高血压治疗中的应用与意义

高血压,即使是经过了治疗,仍较正常人有较高的心血管并发症的发生。高血压有关的并发症对患者的生活质量及预后有较大的影响。其首要死亡原因是缺血性事件。阿司匹林是经过大量安慰剂对照、随机临床试验证实、可降低首次心肌梗死及缺血性脑卒中危险的抗血小板药物。近年来有关阿司匹林在防治缺血性心血管病方面的循证医学证据逐渐增多,国内及国际的心血管病防治指南均推荐应用阿司匹林。随着卒中预防领域内几项关键性的临床试验（ESPRIT、CHARISMA及WHS）的公布,美国心脏协会／美国卒中协会写作委员会对2006版指南的内容进行了更新。本文结合新的临床试验的证据,对阿司匹林在高血压治疗中的意义进行了分析,以期能更适当地应用阿司匹林,减少与高血压有关的缺血事件,提高人口的生存质量及寿命。     

Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat

Physical activity impacts functional recovery following stroke in humans, however its effects in experimental animals submitted to chronic cerebral hypoperfusion have not been investigated. The aim of this study was to evaluate the therapeutic potential of exercise, as assessed by cognitive activity in the Morris water maze and the brain oxidative status, through measurement of macromolecules damage, TBARS levels and total cellular thiols, as well as antioxidant enzymes in hippocampus, striatum and cerebral cortex. Adult male Wistar rats were submitted to the modified permanent bilateral occlusion of the common carotid arteries (2VO) method, with right common carotid artery being first occluded, and tested 3 months after the ischemic event. The effects of three different exercise protocols were examined: pre-ischemia, post-ischemia and pre+post-ischemia. Physical exercise consisted of sessions of 20-min, 3 times per week during 12 weeks (moderate intensity). Rats were submitted to cognitive assessment, in both reference and working spatial memory and after the last testing session were sacrificed to have oxidative stress parameters determined. Hypoperfusion caused a significant cognitive deficit in both spatial water maze tasks and this effect was reversed in rats receiving exercise protocol post and pre+post the ischemic event. Moreover, forced regular treadmill exercise regulated oxidative damage and antioxidant enzyme activity in the hippocampus. These results suggest that physical exercise protects against cognitive and biochemical impairments caused by chronic cerebral hypoperfusion.     

Neuroprotection and the ischemic cascade

Brain ischemia is a process of delayed neuronal cell death, not an instantaneous event. The concept of neuroprotection is based on this principle. Diminished cerebral blood flow initiates a series of events (the "ischemic cascade") that lead to cell destruction. This ischemic cascade is akin to a spreading epidemic starting from a hypothesized core of ischemia and radiating outward. If intervention occurs early, the process may be halted. Interventions have been directed toward salvaging the ischemic penumbra. Hypothermia decreases the size of the ischemic insult in both anecdotal clinical and laboratory reports. In addition, a wide variety of agents have been shown to reduce infarct volume in animal models. Pharmacologic interventions that involve thrombolysis, calcium channel blockade, and cell membrane receptor antagonism have been studied and have been found to be beneficial in animal cortical stroke models. Human trials of neuroprotective therapies have been disappointing. Other than thrombolytics, no agents have shown an unequivocal benefit. The future of neuroprotection will require a logical extension of what has been learned in the laboratory and previous human trials. A sensible approach to the use of multiple-agent cocktails used in combination with thrombolytics is likely to offer the highest chance for benefit.     

Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients. Here, we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke. We hypothesized that tDCS applied to the left superior temporal gyrus (Wernicke’s area) or the right Wernicke’s area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke. Participants included right-handed subacute stroke patients with global aphasia due to ischemic infarct of the left M1 or M2 middle cerebral artery. Patients were randomly divided into three groups: patients who received anodal tDCS applied to the left superior temporal gyrus, patients who received cathodal tDCS applied to the right superior temporal gyrus, and patients who received sham tDCS. All patients received conventional speech and language therapy during each period of tDCS application. The Korean-Western Aphasia Battery (K-WAB) was used to assess all patients before and after tDCS sessions. After intervention, all patients had significant improvements in aphasia quotients, spontaneous speech, and auditory verbal comprehension. However, auditory verbal comprehension improved significantly more in patients treated with a cathode, as compared to patients in the other groups. These results are consistent with the role of Wernicke’s area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke, suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke.     

Post-stroke depression as a predictor of caregivers burden of acute ischemic stroke patients in China

Our aim was to explore the independent attribution of Post-stroke depression (PSD) to caregiver burden of acute ischemic stroke patients. A cross-sectional survey was performed with 271 acute ischemic stroke patients in the Huai-He Hospital and First People’s Hospital of Kaifeng City in China. PSD was assessed by Self-rating Depressive Scale, and caregiver burden was assessed by Zarit Caregiver Burden Interview. Clustered logistic regression was applied to identify the impact of PSD on caregiver burden. As results, female patients, normal muscle strength and PSD were associated with caregiver burden. PSD correlated with an independent influence of 17.2% on the risk of caregiver burden, The independent influence of PSD on caregiver burden was smaller than that of social-demographics of caregivers and clinical factors of stroke patients This study suggests that PSD may have a modest influence on caregiver burden.     

急性脑干梗死的治疗进展

脑干梗死为脑梗死中较为少见的一种,病死率和残疾率均较其他部位高。近年来,随着医学的不断发展,尤其是循证医学证据的增多,急性脑干梗死的治疗方法有了许多新的进步。本文就近年来国内外急性脑干梗死治疗方面的最新进展进行综合性介绍,内容涉及静脉溶栓、动脉溶栓、动静脉联合溶栓、超声辅助溶栓、抗血小板治疗、抗凝治疗、脑保护治疗、卒中单元等,以期为-临床医生的治疗决策提供参考。     

Stimulated release of tissue plasminogen activator from artery wall sympathetic nerves: implications for stress-associated wall damage

Recurrent stress is clinically associated with early onset hypertension and coronary artery disease. A mechanism linking emotion to pathogenic remodeling of the artery wall has not been identified. Stress stimulates acute regulated release of tissue plasminogen activator (t-PA) into the circulation, which is presently attributed to the vascular endothelium. Sympathetic neurons also synthesize t-PA and axonally transport it to the arterial smooth muscle. Unlike release by the endothelium, a stress-stimulated sympathetic discharge would potentially accelerate degradation of the wall matrix by plasmin. To assess whether sympathetic axons are the principal source of acute stress-induced arterial release of t-PA, we compared the output from small densely innervated and large sparsely innervated isolated artery segments before and after sympathetic stimulation, and after ablations. Following phenylephrine infusion densely-innervated microvessels in uveal eyecups were released over 60-fold greater amounts of active t-PA per milligram than the sparsely innervated aorta; and ten-fold more than carotid artery segments. Mesenteric artery release was 4.8-fold greater than release by the carotid artery. In vivo, uveal release of t-PA increased more than three-fold within one minute following superior cervical sympathetic ganglion electrical stimulation, and after phenylephrine, or nicotine infusions of the anterior chamber. Circulating levels of t-PA fell 70% following chemical sympathectomy. We propose that sympathetic nerves are the primary source of stress-induced release of t-PA into and from the densely innervated resistance arteries and arterioles, where dysregulated plasmin-induced proteolysis could damage the wall matrix.     

尿微量白蛋白与急性缺血性脑卒中的关系研究

探讨尿微量白蛋白（MA）与急性缺血性脑卒中（AIS）的关系。选取2012年1月1日～2014年3月31日于大连大学附属新华医院神经内科住院的缺血性脑卒中患者175例为研究对象。分为试验组：A1S患者103例;对照组：非AIS患者72例。比较两组的一般资料和MA阳性率情况。结果试验组的MA阳性率为41．75％,显著高于对照组MA的阳性率20．83％（P〈0．05）。MA与AIS可能有相关性,MA可能是AIS的危险因素。     

Hypercoagulable states and stroke: a selective review

Blood disorders have been implicated in approximately 5% to 10% of ischemic stroke, with an increased frequency in younger patients. Most disorders are associated with an increased thrombotic tendency and, therefore, an increased risk of ischemic stroke. Less commonly, a bleeding diathesis may predispose a patient to intracranial hemorrhage. While many conditions predisposing to thrombosis have been associated with stroke, there are relatively few prospective, epidemiological studies addressing hypercoagulable states and arterial stroke compared with the number of studies on the genetic thrombophilias, which are predominantly associated with venous thrombosis. When ordering tests of coagulation in stroke patients, one should keep in mind whether the results will influence therapy and/or patient outcome. It is generally not advocated to screen all stroke patients for a "hypercoagulable workup". Typically, patients to be screened for coagulation defects will have a prior history of one or more unexplained thromboembolic events. The yield for diagnosing a hypercoagulable state is typically greatest for young stroke patients or those with a family history of thrombosis and who have no other explanations for their stroke (cryptogenic stroke). The yield in typically low in unselected ischemic stroke patients and older patients. Treatment of a first stroke with a documented hypercoagulable state is typically long-term or indefinite duration warfarin, although there is a paucity of clinical trial data supporting this clinical approach.     

Testing conclusions from functional imaging of working memory with data from acute stroke

Functional imaging studies indicate that the left hemisphere mediates verbal working memory, while the right hemisphere mediates both verbal and spatial working memory. We evaluated acute stroke patients with working memory tests and imaging to identify whether unilateral dysfunction causes deficits in spatial and/or verbal working memory deficits. While left cortical stroke patients had verbal working memory impairments (p<0.003), right cortical stroke patients had both verbal p<0.007) and spatial working memory (p<0.03) impairments, confirming functional imaging results. Patients with transient ischemic stroke and patients with non-cortical stroke did not have significant deficits in working memory in either modality.     

Motor performance improved by exercises in cerebral ischemic rats

Physical exercise may induce neuroprotective effects against brain damage after stroke. The authors aimed to investigate the effects of various exercises on motor function, striatal angiogenesis, and infarct volume in cerebral ischemic rats. Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion and randomly assigned to 1 of the 4 groups: Rota-rod training, lower speed treadmill training, higher speed treadmill training, or no exercise control. Motor function, striatal angiogenesis, and infarct volume were evaluated before or after motor training. After training, motor function and striatal angiogenesis changed significantly in Rota-rod and higher speed treadmill training groups as compared with the control group. Improvement in motor function significantly correlated with striatal angiogenesis after motor training. Infarct volumes were significantly decreased in lower and higher speed treadmill training groups. The results indicated that both motor training procedures can be used as effective training programs in stroke rehabilitation.     

Diagnosis and prevention of atherosclerotic cerebral infarction

Atherosclerotic disease accounts for approximately 25% of ischemic strokes. Atherosclerotic stroke is caused mainly by embolic events from the carotid artery bifurcation or the aortic arch, although intracranial thrombosis can occur, more often in African Americans, Asians, and diabetes patients. Primary prevention of stroke is critical for patients with risk factors for atherosclerosis, including hypertension, diabetes, smoking and hypercholesterolemia. Stroke can be prevented in patients with established atherosclerotic disease by identification and management of patients with carotid artery stenosis by non-invasive testing. Particular attention must be paid to patients with transient symptoms of brain ischemia.     

Hyperperfusion syndromes: insight into the pathophysiology and treatment of hypertensive encephalopathy

Hypertensive encephalopathy is one of the manifestations of a hypertensive crisis. It is not the absolute value of the blood pressure that causes the encephalopathy, rather the presence of an abrupt rise in pressure. In terms of clinical and radiographic findings, there are many similarities among a group of entities, including hypertensive encephalopathy, eclampsia, and immunosuppressant neurotoxicity. Hyperperfusion syndromes may represent these clinical disease states that may share the same pathophysiology. Magnetic resonance imaging fluid attenuated inversion recovery sequences have recognized the prominent cortical involvement of the disease that had been previously missed on computed tomography. Studies have found cortical involvement in 94% of their patients, particularly in mild cases. Animal models demonstrate endothelial damage and enhanced pinocytosis in the cortex as reasons why edema may begin in that region of the brain. Patients diagnosed with hypertensive encephalopathy should be diagnosed and treated promptly in order to avoid further neurological complications. The mean arterial pressure should be lowered by 20% to 25% within the first hour of patient presentation, followed by further gradual reduction in blood pressure over the following 24 hours. Hypertensive emergency in acute ischemic stroke should be managed with more caution. According to the 2003 American Stroke Association treatment guidelines, for patients with ischemic stroke not eligible for thrombolytic therapy, target blood pressures are a diastolic blood pressure <120 mmHg and systolic blood pressure <220 mmHg. The systolic pressure must be <185 mmHg and diastolic pressure <110 mmHg at all times if eligible for thrombolytic therapy.     

Demand characteristics and self-report measures of imaginary audience sensitivity: implications for interpreting age differences in adolescent egocentrism.

Self-consciousness during early adolescence has been explained as an outcome of adolescent egocentrism, in which adolescents create an imaginary audience (IA) of attentive, critical peers. The possibility that such self-consciousness might result from contact with peers who are more attentive and critical than those encountered during childhood or adulthood has not been considered. Study 1 tested whether young adults, who are not theoretically susceptible to IA, could be made to receive high scores on IA and self-consciousness measures by having them complete a procedure in 1 of 3 laboratory conditions-a critical audience, a noncritical audience, or no audience. However, participants in the critical-audience condition received significantly lower IA and self-consciousness scores than participants in the no-audience condition did. Study 2 tested whether the directions given to Study 1 participants might have been responsible for the unexpected findings. Results indicated that participants instructed to give mature-sounding responses received lower IA/self-consciousness scores than did those asked to report their honest opinions. Together, the results of Studies 1 and 2 indicated that survey measures of IA are subject to demand characteristics and highlighted the need to interpret with caution age differences in IA as traditionally assessed.     

Etiology of strokes in children with sickle cell anemia

The most devastating complication of sickle cell anemia is cerebral infarction, affecting approximately 30% of all individuals with sickle cell anemia. Despite being one of the most common causes of stroke in infants and children, the mechanism of cerebral infarction in this population has not been extensively studied and is poorly understood. Multiple, synergistic factors are important in the pathogenesis of stroke including the hemodynamic effects of cerebral arterial occlusive disease, viscosity, chronic and acute anemia and acute medical events. This review focuses on the relationship between these factors in order to provide a foundation for further study of the etiology of strokes in this high-risk population.