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窘迫 脑出血是极其重要的神经急症，具有高度的社会影响（Sacco 1994；Qureshi 2001；Broderick 2007）。脑出血的病理生理学可以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扩张导致出血核心脑细胞立即坏死。目前已明确血肿扩大 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) 的研究结果一致，Kazui 在其系列中报道了 20% 的总体扩张率。 Mayer 等人 (2005) 证明，出血性扩张在发病后 4 小时内发生。而维拉的使用系数 并没有改善临床结果，出血性扩张减少（Mayer - 口头报告美国神经病学学会会议，2007 年）。可能是预防出血扩张不够，并且由于水肿或其他机制导致出血周围的代谢窘迫， 必须予以缓解才能改善结果。 第二阶段是由于铁、凝血酶、血液分解产物、自由基形成、蛋白酶激活和炎症引起的占位效应、兴奋性水肿和进行性神经毒性，对血肿周围组织造成缓慢的损害（Gong 2000；Lee 1997；Wu 2002； Xi 和 Hoff 2006）。 这些机制会导致血肿周围组织的代谢窘迫和随后的损伤，这种损伤会随着时间的推移而逐渐加重（Gebel 2002a，2002b），可能是通过改变选定的遗传途径来实现的。我们假设早期去除血液可以避免进行性脑水肿造成的后续损害。 发生在 ICH 之后的几天内。 血肿周围组织缓慢发生的损伤是复杂的，涉及多种机制，这些机制以某种方式与大量血液和进行性水肿的存在相关。人们认识到，实验模型中并不存在血肿周围缺血本身（Qureshi 1999），然而，复杂的动物研究测量了血流量、脑氧提取量、耗氧量、 葡萄糖利用和乳酸产生已证明血肿周围组织的新陈代谢受到干扰（Nath1987）。使用正电子发射断层扫描 (PET) 对人类进行的类似研究显示，12 名患者在发病 7 至 28 小时内成像，其两个半球的血流量对称减少。 （Zazulia 和 Diringer 2001）。在最近的一项研究中，Powers 及其同事还证明，14 名急性 ICH 患者在药物降压期间，CBF 的自动调节得以保留 平均动脉压降低15%。同一研究小组发现局灶性血肿周围 CBF 不成比例地减少，但氧提取分数没有局灶性增加，这表明病灶周围 CBF 值低反映了代谢功能障碍（Powers 2001），这已被线粒体证实。 对人体线粒体活检进行呼吸实验（Kim-Han 2006）。 我们的小组已经证明了两项独立的发现，即血肿周围组织因血肿而处于代谢窘迫状态。第一个是 MRI 发现，在症状出现 6 小时内评估的一部分患者中，血肿周围 ADC 值出现边缘下降 (Kidwell 2001)。在我们最初的 5 年研究期间，我们证实了这些发现，表明 30% 的患者有 ADC 降低的边缘（参见下面的初步研究）。值得注意的是，这种组织生物能妥协的边缘并不是 与局灶性血肿周围血流减少相关，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微透析谷氨酸和 ICH 后许多天，乳酸/丙酮酸值都会升高。通过使用减少血肿量 立体定向溶栓治疗导致谷氨酸值正常化，但乳酸/丙酮酸值没有正常化。这 表明血肿清除可以改善这种代谢窘迫（Miller 2006；Vespa 2006）。我们 已验证微透析乳酸/丙酮酸比率是氧化代谢受损的有力标志 （韦斯帕2005）。我们在人脑微透析方面拥有丰富的经验，并已证明 该技术在确定创伤后脑代谢的连续变化方面的安全性和实用性 脑损伤和脑出血（Vespa 1998；Vespa 2003；Vespa 2006；Vespa 2007）。我们建议 内窥镜手术将改善瘤周区域的代谢状态，我们 打算在本研究中使用微透析和 MRI 来测量这种反应。