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.

血肿周围组织的代谢性损害 脑出血是一种具有高度社会影响的重要神经系统急症（Sunday 1994; Qureshi 2001; Broderick 2007）。脑出血的病理生理过程可分为两个阶段。第一阶段包括由于急性出血和早期出血性扩张导致出血核心中的脑细胞立即坏死。现在很清楚血肿扩大 会导致部分患者病情恶化Brott及其同事（1997）报告称，26%的患者在初次CT检查后1小时内出现血肿扩大，38%的患者在20小时内出现血肿扩大。这些发现与Kazui（1996）的研究结果雅阁，Kazui（1996）报道了其系列中的总体扩张率为20%。Mayer et al（2005）证明出血性扩张发生在发作后4小时内。虽然使用因素维拉 没有改善临床结局，出血性扩张减少（Mayer -美国神经病学学会会议口头报告，2007）。这可能是因为仅仅预防出血性扩张是不够的，并且由于水肿或其他机制， 必须减轻疼痛以改善治疗效果。 第二阶段是由于团块效应、兴奋性毒性水肿和铁、凝血酶、血液分解产物、自由基形成、蛋白酶活化和炎症引起的进行性神经毒性导致的血肿周围组织缓慢损伤（Gong 2000; Lee 1997; Wu 2002; Xi and霍夫2006）。 这些机制导致代谢窘迫和血肿周围组织的后续损伤，其随时间推移而进行（Gebel 2002 a，2002 b），可能是通过选定遗传途径的改变。我们假设，早期清除血液可以避免进行性脑水肿造成的后续损害， 发生在ICH后几天。 血肿周围组织的缓慢损害是复杂的，涉及多种机制，这些机制以一种或另一种方式与大量收集的血液和进行性水肿的存在有关。已经认识到血肿周围缺血本身并不存在于实验模型中（Qureshi 1999），然而，测量血流量、脑氧提取、氧消耗、 葡萄糖的利用和乳酸盐的产生已经证明血肿周围组织的代谢受到干扰（Nath 1987）。使用正电子发射断层扫描（PET）对人类进行的类似研究显示，在发病后7-28小时内成像的12名患者的两个半球的血流对称减少。（Zazulia and Diringer 2001）。在最近的一项研究中，Powers及其同事还证明，在14例急性ICH患者中， 平均动脉压降低15%。同一研究小组发现局灶性血肿周围CBF不成比例地降低，但氧提取分数没有局灶性增加，这表明低病灶周围CBF值反映了代谢功能障碍（Powers 2001），这已被线粒体 对活组织检查的人线粒体进行呼吸实验（Kim-Han 2006）。 我们的研究小组已经证实了两个独立的发现，即血肿周围组织由于血肿而处于代谢窘迫状态。第一种是在症状发作6小时内评价的患者亚组中，MRI发现血肿周围ADC值边缘降低（Kidwell 2001）。在我们最初的5年研究期间，我们证实了这些发现，证明30%的患者有ADC边缘降低（见下文的初步研究）。值得注意的是，这一边缘的组织生物能量妥协， 与局灶性血肿周围血流量减少相关，与血肿周围水肿的范围和严重程度无关。第二个发现是血肿周围的微透析谷氨酸和 乳酸/丙酮酸值在ICH后许多天升高。通过使用，减少血肿体积 立体定向溶栓，导致正常化的谷氨酸值，但不是乳酸/丙酮酸值。这 表明血肿清除术可以改善这种代谢性窘迫（米勒2006; Vespa 2006）。我们 已经验证了微透析乳酸/丙酮酸比率是氧化代谢受损的可靠标志物 （Vespa 2005）。我们在人脑微透析方面有相当丰富的经验， 这项技术在确定创伤后脑代谢顺序变化中的安全性和实用性 脑损伤和脑出血（Vespa 1998; Vespa 2003; Vespa 2006; Vespa 2007）。我们提出 内窥镜手术将改善瘤周区域的代谢状态，我们 本研究拟采用微透析和磁共振成像来测量这种反应。