Intraoperative Stereotactic CT Guided Endoscopic Surgery (ICES)

血肿周围组织的代谢障碍 脑出血是非常重要的神经急症，具有很高的社会影响(萨科1994；库雷希2001；布罗德里克2007)。脑出血的病理生理可分为两个阶段。第一阶段包括由于急性出血和早期出血扩大而导致出血核心脑细胞的即刻坏死。现在很明显，血肿扩大 会导致一部分患者的病情恶化。Brott和他的同事(1997)报告说，26%的患者在首次CT检查后1小时内血肿扩大，总体上，38%的患者在20小时内血肿扩大。这些发现与Kazui(1996)的发现是一致的，后者在他们的系列中报告了20%的总体扩张率。Mayer等人(2005)证明了出血性扩张发生在发病后4小时内。而使用率Vila 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)。可能是预防出血扩大不够，以及由于浮肿或其他机制导致的出血周围的代谢障碍， 必须松一口气才能改善结果。 第二阶段是血肿周围组织的缓慢损害，这是由于质量效应、兴奋性毒性水肿以及由铁、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进行性神经毒性(Gong 2000；Lee 1997；Wu 2002；Xi和Hoff 2006)。 这些机制导致血肿周围组织的代谢障碍和随后的损害，并随着时间的推移而进展(Gebel 2002a，2002b)，可能是通过选择的遗传途径的改变。我们假设，早期撤血可以避免随后进行性脑水肿造成的损害，即 发生在脑出血后的几天内。 慢慢地对血肿周围组织的损害是复杂的，涉及多种机制，这些机制以这样或那样的方式与收集的大量血液和进行性水肿的存在有关。人们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，复杂的动物研究测量了血流量、脑氧摄取、氧气消耗、 葡萄糖的利用和乳酸的产生已经证明血肿周围组织的新陈代谢受到干扰(Nath1987)。在人类中，使用正电子发射断层扫描(PET)的类似工作，在发病7-28小时内成像的12名患者中，显示出双侧大脑半球对称性血流减少。(Zazulia和Diringer，2001)。在最近的一项研究中，鲍尔斯和他的同事还证明了14名急性脑出血患者在药理性血压期间脑血流量的自动调节被保留下来 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，但没有局灶性氧摄取分数增加，这表明病灶周围低CBF值反映了代谢功能障碍，线粒体已经证实(Power 2001)。 对活组织的人线粒体进行呼吸实验(Kim-han 2006)。 我们小组已经证明了两个独立的发现，即血肿周围组织由于血肿而处于代谢窘迫状态。第一个是MRI发现，在症状出现后6小时内评估的一组患者中，血肿周围的ADC值呈边缘下降(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减少的边缘(参见下文的初步研究)。值得注意的是，这种组织生物能量妥协的边缘并不是 伴局灶性血肿周围血流量减少，与血肿周围水肿的程度和严重程度无关。第二个发现是血肿周围微透析谷氨酸和 脑出血后很多天乳酸/丙酮酸值升高。减少血肿量，通过使用 在立体定向溶栓中，谷氨酸值正常化，但乳酸/丙酮酸值不正常化。这 表明清除血肿可以改善这种代谢障碍(Miller 2006；Vespa 2006)。我们 已证实微透析乳酸/丙酮酸比率是氧化代谢受损的有力标志 (Vespa 2005)。我们在人脑微透析方面有相当多的经验，并证明了 这项技术在确定创伤后脑代谢序贯变化中的安全性和有效性 脑损伤和脑出血(VESPA1998；VESPA2003；VESPA2006；VESPA2007)。我们建议 内窥镜手术将改善瘤周区域的代谢状态，我们 在这项研究中，打算使用微透析和磁共振成像来测量这种反应。

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.