Intraoperative Stereotactic CT Guided Endoscopic Surgery (ICES)

术中立体定向 CT 引导内窥镜手术 (ICES)

• 批准号: 7665612
• 负责人: Paul M Vespa
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7665612
• 关键词: Academy; Acute; American; Animals; Bioenergetics; Biological Markers; Biopsy; Blood; Blood Pressure; Blood Volume; Blood flow; Brain; Brain Edema; Brain Injuries; Brain hemorrhage; Cell Respiration; Cerebral hemisphere hemorrhage; Cerebrovascular Circulation; Cerebrum; Chemicals; Clinical; Complex; Core-Binding Factor; Deterioration; Diffusion; Distress; Edema; Excision; Experimental Models; Failure; Free Radical Formation; Functional disorder; Genetic; Genomics; Glucose; Glutamates; Hematoma; Hemorrhage; Hemostatic function; Homeostasis; Hour; Human; Image; Inflammation; Injury; Iron; Ischemia; Joints; Lead; Link; Lobar; Magnetic Resonance Imaging; Measures; Mechanics; Metabolic; Metabolic Marker; Metabolism; Methods; Microdialysis; Mitochondria; Necrosis; Neurological emergencies; Neurological outcome; Neurology; Operative Surgical Procedures; Oral; Outcome; Outcome Study; Oxygen; Oxygen Consumption; Pathogenesis; Pathway interactions; Patients; Peptide Hydrolases; Phase; Pilot Projects; Positron-Emission Tomography; Postoperative Period; Prevention; Procedures; Production; Prospective Studies; Protocols documentation; Pyruvate; Pyruvates; Randomized; Recurrence; Reporting; Research; Resolution; Respiration; Safety; Series; Serious Adverse Event; Severities; Signal Transduction; Spottings; Surface; Symptoms; Techniques; Testing; Thrombin; Time; Tissues; Trauma; Traumatic Brain Injury; Universities; Work; adjudicate; brain cell; brain metabolism; brain tissue; computerized; experience; improved; intraoperative imaging; irritation; meetings; minimally invasive; neurotoxicity; novel; pressure; research study; response; thrombolysis

Metabolic Distress in the perihematomal tissue Intracerebral hemorrhage is crucially important neurologic emergency with high societal impact (Sacco 1994; Qureshi 2001; Broderick 2007). The pathophysiology of intracerebral hemorrhage ca,n be considered to consist of two phases. The first phase includes immediate necrosis of the brain cells in the hemorrhage core due to the acute bleed and early hemorrhagic expansion. It is now clear that hematoma enlargement contributes to deterioration in a subset of patients. Brott and colleagues (1997) reported hematoma expansion in 26% of patients within 1 hour of the initial CT and overall in 38% of patients within 20 hours. These findings are in accord with those of Kazui (1996) who reported an overall expansion rate of 20% in their series. Mayer et al (2005) demonstrated that hemorrhagic expansion occurs within 4 hours of onset. While the use factor Vila did not result in improved clinical outcome, hemorrhagic expansion was reduced (Mayer - oral presentation American Academy of Neurology meeting, 2007). It may be that prevention of hemorrhagic expansion is not enough, and that the metabolic distress surrounding the hemorrhage, due to edema or other mechanisms, must be relieved in order to improve outcome. The second phase is the slowly ensuing damage to perihematomal tissue due to mass effect, excitotoxic edema, and progressive neurotoxicity resulting from iron, thrombin, blood breakdown products, free radical formation, protease activation and inflammation (Gong 2000; Lee 1997; Wu 2002; Xi and Hoff 2006). These mechanisms lead to metabolic distress and subsequent damage in the perihematomal tissue which is progressive over time (Gebel 2002a, 2002b), perhaps through alteratiion of selected genetic pathways. We hypothesize that early removal of blood avoids the subsequent damage from progressive brain edema that occurs in the days following ICH. The slowly ensuing damage to the perihematomal tissue is complex and involves multiple mechanisms that are in one way or another linked to the presence of the mass of collected blood and progressive edema. It is recognized that perihematomal ischemia per se does not exist in experimental models (Qureshi 1999), however, sophisticated animal studies measuring blood flow, cerebral oxygen extraction, oxygen consumption, glucose utilization, and lactate production have demonstrated that metabolism is disturbed in the perihematomal tissue (Nath1987). Similar work in humans, using positron emission tomography (PET), demonstrated symmetrically reduced blood flow in both hemispheres in 12 patients imaged within 7-28 hours of onset. (Zazulia and Diringer 2001). In a recent study, Powers and colleagues also demonstrated that autoregulation of CBF was preserved in 14 patients with acute ICH during pharmacologic blood pressure reductions of mean arterial pressure of 15%. The same research group found disproportionately reduced focal perihematomal CBF, but no focal increase in oxygen extraction fraction, suggesting that the low perilesional CBF values reflected metabolic dysfunction (Powers 2001), as has been confirmed by mitochondrial respiration experiments on biopsied human mitochondria (Kim-Han 2006). Our group has demonstrated two independent findings that the perihematomal tissue is in a state of metabolic distress due to the hematoma. The first is the MRI finding of a rim of perihematomal decrease in ADC values in a subset of patients evaluated within 6 hours of symptom onset (Kidwell 2001). In our initial 5- year study period, we confirmed these findings demonstrating that 30% of patients have a rim of ADC reduction (see Preliminary Studies below). Of note, this rim of tissue bioenergetic compromise was not associated with focal perihematomal decreased blood flow and was not associated with the extent and severity of perihematomal edema. The second finding is that perihematomal microdialysis glutamate and lactate/pyruvate values are elevated for many days after ICH. Reduction of hematoma volume, through the use of stereotactic thrombolysis, resulted in normalization of glutamate values but not lactate/pyruvate values. This suggests that evacuation of hematoma can improve this metabolic distress (Miller 2006; Vespa 2006). We have validated microdialysis lactate/pyruvate ratio to be a robust marker of impaired oxidative metabolism (Vespa 2005). We have a considerable experience with human cerebral microdialysis and have demonstrated the safety and utility of this technique in determining sequential changes in brain metabolism after traumatic brain injury and intracerebral hemorrhage (Vespa 1998; Vespa 2003; Vespa 2006; Vespa 2007). We propose that endoscopic surgery will result in improvement in the metabolic state of the perihmatomal region, and we intend to measure this response using microdialysis and MRI in this study.

近日成长组织的代谢困扰 脑出血是至关重要的神经系统紧急事件，具有很高的社会影响（Sacco 1994； Qureshi 2001； Broderick 2007）。脑出血Ca的病理生理，n被认为由两个阶段组成。第一阶段包括由于急性出血和早期出血性膨胀而导致出血核中脑细胞的立即坏死。现在很明显血肿肿大 在一部分患者中导致恶化。 Brott及其同事（1997年）在初始CT的1小时内报告了26％的患者血肿的膨胀，总体上有38％的患者在20小时内增加了血肿。这些发现符合Kazui（1996）的发现，他们在其系列赛中的总体扩张率为20％。 Mayer等人（2005年）证明，出血性扩张发生在发作后4小时内。而使用因子Vila 并未导致临床结果改善，减少了出血性扩张（Mayer-口腔介绍美国神经病学会会议，2007年）。可能是预防出血性扩张还不够，并且由于水肿或其他机制，周围的代谢困扰， 为了改善结果，必须放心。 第二阶段是由于质量效应，兴奋性水肿和进行性神经毒性引起的围栏围细胞增多症组织的损害缓慢，导致铁，凝血酶，血液崩溃产物，自由基形成，蛋白酶激活和炎症引起的进行性神经毒性（Gong 2000; Lee 1997; Wu 2002; XI and Hoff 2002; XI和Hoff 2006）。 这些机制会导致代谢困扰和随后的围栏组织组织的损害，这是随着时间的流逝而进行的（Gebel 2002a，2002b），也许是通过对选定遗传途径的改变。我们假设早期清除血液避免了渐进性脑水肿的随后损害， 发生在ICH之后的日子。 随之而来的对围围围栏组织的损害缓慢，并且涉及多种机制，这些机制与一种或另一种方式与收集的血液和进行性水肿的存在有关。众所周知，在实验模型中不存在近日并非存在性缺血本身（Qureshi 1999），但是，测量血液流动，脑氧气萃取，消耗氧，消耗，耗氧的精致动物研究， 葡萄糖利用和乳酸产生表明，新陈代谢在近核组织中受到干扰（NATH1987）。使用正电子发射断层扫描（PET）在人类中的类似工作表明，在发病后7-28小时内成像的12名患者中，两个半球的血流对称减少。 （Zazulia和Diringer 2001）。在最近的一项研究中，Powers及其同事还表明，在药理血压期间，CBF的自动调节保留在14例急性ICH患者中。 平均动脉压的降低15％。同一研究小组发现，局灶性围围CBF的局灶性局限性不成比例，但没有局灶性提取分数的局灶性增加，这表明较低的周围CBF值反映了代谢功能障碍（Powers 2001），正如线粒体界面所证实的那样 关于活检人类线粒体的呼吸实验（Kim-Han 2006）。 我们的小组证明了两个独立的发现，即由于血肿而导致的近日成amaTomatom组织处于代谢困扰状态。首先是MRI发现在症状发作后6小时内评估的一部分患者中，ADC值的围围围细胞膜降低的边缘（Kidwell 2001）。在我们最初的5年研究期内，我们证实了这些发现，表明30％的患者的ADC减少率（请参见下面的初步研究）。值得注意的是，组织生物能妥协的边缘不是 与局灶性围栏肿瘤降低血液流动有关，与近日杂附加成围骨水肿的程度和严重程度无关。第二个发现是围细胞周围微透析谷氨酸和 ICH后许多天多天，乳酸/丙酮酸值升高。通过使用减少血肿的体积 立体定向的溶栓分解，导致谷氨酸值的归一化，而不是乳酸/丙酮酸值。这 表明疏散血肿可以改善这种代谢困扰（Miller 2006； Vespa 2006）。我们 已经验证了乳酸/丙酮酸的微透析比为氧化代谢受损的强大标记 （Vespa 2005）。我们在人类脑微透析方面有丰富的经验，并证明了 这种技术在确定创伤后脑代谢的顺序变化方面的安全性和实用性 脑损伤和脑内出血（Vespa 1998; Vespa 2003; Vespa 2006; Vespa 2007）。我们建议 这种内窥镜手术将导致痛经区的代谢状态改善，我们 在这项研究中，打算使用微透析和MRI来衡量这一响应。