【作者】 陈亮；

【导师】 周良辅； 毛颖； 钟平； 宋冬雷； 张荣；

【作者基本信息】 复旦大学 ， 外科学， 2007， 博士

【摘要】 第一部分硬脑膜动静脉瘘的形成机制研究目的探讨硬脑膜动静脉瘘的发病机制，特别是促血管生长因子和脑慢性低灌注对硬膜新生血管形成的作用。材料和方法120只大鼠随机分为4组，A组(n=25)为假手术组，B组(n=25)诱发上矢状窦血栓形成，C组(n=35)采用大鼠右侧颈总动脉的近心端与颈外静脉的远心端端端吻合，同时结扎对侧横窦出颅处导致颅内静脉高压，D组(n=35)兼行B、C组操作。分别于术前、术后即刻监测血压、静脉窦压、动脉血气、脑血流等生理指标，C、D组静脉窦压低于20mmHg者排除。术后1、2、4、12周分批处死，免疫组化检测VEGF在基底节、皮层、蛛网膜和硬膜的分布，术后12周行头颈部MR证实吻合口通畅，上矢状窦血栓仍存在，行磁共振灌注成像了解脑灌注情况。用Western-blot法检测硬膜VEGF和MMP9的含量。结果C、D组在术后即刻均出现血压下降、静脉窦压升高，后者达28.55±4.92mmHg，4周后稳定在22.34±3.24mmHg。左侧横窦末端血氧饱和度在血管吻合前后变化明显，C组分别为58.02+3.58％和93±3.18％，D组分别达57.74±3.34％和95.58±1.72％，计算动静脉分流量分别占左侧横窦末端总血流量的89.51％和96.29％。C、D组术后即刻出现皮层血流的显著性下降，右侧枕叶最明显。左侧在术后2周基本恢复正常，右侧恢复到85％-90％水平，此后不再恢复，直至12周实验结束。磁共振灌注成像见右侧枕部与左侧相比，脑血容量升高、平均通过时间延长。C、D组VEGF染色基底节区在术后1周即达高峰，在2周后转为阴性或弱阳性，枕叶皮层和蛛网膜血管呈持续阳性表达。枕部矢状窦及周围硬膜在术后早期呈弱阳性，在4周至12周呈持续阳性表达。术后12周硬膜微血管明显增加，管腔扩张。A、B组均为阴性或弱阳性，微血管计数无明显改变。Western Blotting分析硬膜VEGF蛋白表达量D组＞C组＞B组=A组，硬膜MMP9蛋白表达量D组＞C组＞B组＞A组结论DAVF形成的关键在于静脉窦压力升高，静脉窦血栓是促使静脉窦压力升高的危险因素。脑慢性低灌注是静脉窦高压导致皮层返流前的早期表现，能促进VEGF和MMP9的表达，从而促使硬膜异常血管新生，因而脑慢性低灌注是从静脉窦高压到DAVF形成过程中的重要一环。第二部分小脑幕的解剖和手术入路研究目的研究小脑幕的解剖特征和多种手术入路的显露差异，提出合适的小脑幕动静脉瘘手术入路。材料和方法尸头标本15例30侧，观察小脑幕静脉窦数量、粗细、起源和分布；另取标本15例，在神经导航指引下，分别经侧裂、颞下和前岩骨等前外侧入路，经枕下和幕下小脑上等后方入路，观察小脑幕显露范围，并做好导航标记；结果粗大的小脑幕静脉窦集中分布于小脑幕后内侧，来自幕下桥静脉，后外侧静脉窦源于颞枕的桥静脉，游离缘静脉可来自深静脉属支或岩静脉。前外侧入路以前岩骨入路显露范围最大，可完全显露同侧的小脑幕游离缘，并且可以同时显露幕上和幕下表面；颞下入路便于显露小脑幕外侧部。后方入路便于显露小脑幕后部和内侧部，对内侧游离缘和松果体区的显露以枕叶下入路最为宽广。若切开双侧小脑幕和大脑镰，可以显露整个松果体区。结论小脑幕的不同部位桥静脉及其形成的小脑幕静脉窦引流区域有一定规律，据此可将小脑幕分为游离缘区、后内侧区和后外侧区。小脑幕DAVF应根据瘘口在小脑幕上下表面的不同位置，选择不同的手术入路。游离缘型采用前岩骨入路，内侧型和外侧型分别采用颞下和后方入路。第三部分硬脑膜动静脉瘘的诊断和治疗目的探讨硬脑膜动静脉瘘的临床特征、诊断和治疗方法。材料和方法回顾性分析从2001年7月到2006年6月收治的54例颅内DAVF患者资料，包括临床表现、影像学特征、治疗经过和结果。瘘口位于小脑幕14例(25.9％)，横、乙状窦或窦汇7例(13.0％)，前颅底6例(11.1％)，上矢状窦6例(11.1％)，枕大孔区2例(3.7％)，蝶底窦1例(1.9％)。瘘口位于海绵窦者不包括颈动脉海绵窦瘘，为18例(33.3％)；根据Borden分级标准，Ⅰ型16例(29.6％)，Ⅱ型16例(29.6％))，Ⅲ型22例(40.7％)。表现颅内出血13例，进行性脑功能障碍15例，慢性颅高压7例。采用血管内介入治疗22例。其中经动脉途径栓塞治疗15例，经静脉途径治疗8例。直接开颅手术22例，栓塞后开颅手术8例。结果术后DSA检查41例(74.5％)，影像学痊愈25例(61.0％)，好转13例(31.7％)，复发或加重3例(7.3％)。临床随访47例，平均随访时间32.5个月。随访期内无脑内或蛛网膜下腔出血发生，术后症状消失并基本恢复正常生活29例(61.7％)，颅内杂音、偏瘫等症状缓解11例(23.4％)，症状无缓解4例(8.5％)，复发需再次治疗或放弃治疗3例(6.4％)。结论静脉高压是引起DAVF严重症状的主要原因。根据病变部位，治疗方法的选择有所不同。海绵窦DAVF以血管内介入治疗首选，前颅底、小脑幕DAVF开颅手术仍为首选的治疗方法。小脑幕DAVF宜根据瘘口的部位分为游离缘型、内侧型和外侧型三类，并据此选择合适的手术入路。对其中的复杂病例，往往需要介入和手术的联合，目前疗效仍欠佳。更多还原

【Abstract】 Part OneEtiological Research of Intracranial Dural Arteriovenous FistulasObjectTo investigate the pathogenesis of intracranial dural arteriovenous fistula, withspecial concern on the role of angiogenic factors and chronic brain hypoperfusion.Methods120 Sprague-Dawley rats were randomly assigned to 4 groups: 1) Group A（n=25）,sham operation; 2) Group B（n=25）, thrombosis of the sagittal sinus; 3) GroupC（n=35）, anastomosis of the right common carotid artery（CCA） to the external jugularvein（EJV） and occlusion of the proximate-cardiac end of the transverse sinus on theleft; 4) Group D（n=35）, procedures done as Group C and added thrombosis of thesagittal sinus. Mean arterial pressure, sinus pressure, blood gas from the artery andjugular vein, blood flow of the brain were monitered during the operation. Animals ofgroup C and D with its sinus pressure below 20mmHg were excluded from the study.Mean arterial pressure, sinus pressure and blood flow of the brain were again tested 1,2, 4, 12 weeks after operation in subgroups of animals. Histological examination andWestern blotting analysis were used to test the distribution and concentration ofVEGF and MMP-9 in dura mater, arachnoid membrane, cortex and basal ganglia.Perfusion MR of the brain was done to compare blood flow in different site of thebrain.ResultsIn group C and D, the mean blood pressure went down soon after operation, and thesinus pressure elevated to 28.55±4.92mmHg and kept stable at 22.34±3.24mmHg 4weeks later. The SO₂ of the vein draining the left transverse sinus changedsignificantly from 58.02±3.58% to 93±3.18% in group C and from 57.74±3.34 %to 95.58±1.72% in group D after CCA-EJV anastomosis. The blood flow of the brainwent down significantly after operation in group C and D, with the right occipital lobemore significantly than any of the other sites. Two weeks later the blood flow hadretumed to the normal level in the left side but stayed abnormal in the right occipitallobe. Perfusion MR found higher blood volume and longer mean time to enhance in the right occipital lobe, comparing with its contralateral side. Immunohistologicalstain of VEGF was positive in basal ganglia, right occipital lobe and arachnoidmembrane one week after operation, but weakened in basal ganglia two weeks later.VEGF expression was weak in dura mater one week after operation, but becamestrongly positive from the 4th to 12th week after operation. The angiogenesis wasprominent in the dura mater 12 weeks after operation in group C and D but negativeor abscure in group A and B. Western blotting analysis of the protein of dura mater 12weeks after operation realized the expression of VEGF as D＞C＞B=A, andexpression of MMP-9 as D＞C＞B＞A.ConclusionsSinus high pressure was the main reason for angiogenesis of dura mater and wascritical for DAVF formation. Sinus thrombosis is a risk factor for elevation of sinuspressure. Chronic brain hypoperfusion is an early sign of venous hypertension. It willpromote the expression of VEGF and MMP-9, so as enhance abnormal angiogenesisof the dura mater. Chronic brain hypoperfusion is an important step from theprogression of venous hypertension to DAVF formation, so maybe helpful forjudgment of the prognosis of DAVF before venous reflex.Part TwoAnatomy and Surgical Approaches of the TentoriumObjectTo investigate the anatomic features of the tentorium, compare the difference ofvarious approaches to this region and to select the proper approach for the lesions ator around the tentoriam.Methods15 cadaver heads were used to observe the number, shape, derivation and afflux ofthe tentorial sinuses. Under the direction of neuronavigation, another 15 cadaverheads were used to modify surgical approaches. The anteriolateral approachesincluded trans-sylvian approach, subtemporal approach and trans-anterior petrousapproach. The posterior approaches included suboccipital transtentorium approachand subtentorium-supercerebellar approach. The exposed realm of the tentorium andsurrounding structures were labeled with navigation system.ResultsMain tentorial sinuses located at the posteriomedial part of the tentorium, deriving from the bridge veins of the superior verrnis and medial part of the cerebellum.Tentorial sinuses at the posteriolateral part of the tentorium derived from the bridgeveins of the temporal and occipital lobe. Veins at the tentorial edge were frombranches of deep venous system or the petrous vein. The trans-anterior petrousapproach had the best view to tentorium, comparing with other anteriolateralapproaches. Ipsolateral tentorial edge and superficies inferia at the petrous apex couldbe fully visualized. The lateral part of the tentorium could be better visualized viasubtemporal approach and the posterio-medial part of the tentorium could be betterexposed via posterior approaches. The suboccipital transtentorium approach had thebest view of the medial tentorial edge and the pineal region. After incision of thebilateral tentorium and the falx, we could get a total view of the pineal region.ConclusionsRegular pattem of the tentorial sinus was summarized. Different approaches couldexpose different realm of the tentorium. Accordingly, tentorial dural arteriovenousfistula could be classfied into the marginal type, the medial type and the lateral type.Appropriate surgical approaches should be be chosen based on the fistula site at thetentorium.Part ThreeDiagnosis and Therapy of Intracranial Dural Arteriovenous FistulasObjectTo summarize the clinical characters, diagnostic and therapeutic ways of theintracranial DAVF.MethodsA review of 54 patients with intracranial DAVFs treated in our hospital from July2001 to June 2006 was conducted, including the clinical manifestation, imagingcharacters, therapeutic procedure and results. The fistula located at thetentorium（n=14, 25.9%）, transverse or sigrnoid sinus（n=7, 13.0%）, anterior cranialfossa（n=6, 11.1%）, superior sigittal sinus（n=6, 11.1%）, foramen magnum（n=2, 3.7%）and sphenobasic sinus（n=1, 1.9%）. There were 18 cavernous sinus DAVF（33.3%）.According to Borden classification, there were typeⅠ16 cases（29.6%）, typeⅡ16cases（29.6%） and typeⅢ22 cases（40.7%）. Clinical manifestation includedintracranial hemorrhage（n=13）, progressive neurological defesits（n=15）, chronicintracranial hypertension（n=7）, etc. 22 cases underwent intravascular embolization, including 15 via arterial pathway and 8 via the venous way. 22 cases underwenttranscranial operation without embolization and 8 cases was treated with thecombination of vascular embolization and microsurgery.ResultsPostoperative DSA was performed in 41 cases（74.5%）, demonstrating the cure in25 cases（61.0%）, relief in 13（31.7%） and recurrence in 3 cases（7.3%）. 47 cases werefollowed up for a mean time of 32.5 months. No one had intracranial hemorrhageduring follow up period. 29 cases（61.7%） returned to normal life without neurologicaldeficits. Symptoms relieved in 11 cases（23.4%） and resumed in 4 eases（8.5%）. 3 casesrecurred and need further therapy.ConclusionsVenous hypertension was the main cause of severe symptoms. Therapeutic methodswere different according to the site of fistula. Intravascular therapy was preferred forcavernous sinus DAVF, while microsurgery was the first choice for DAVF of theanterior cranial fossa and tentorium. Tentorial DAVF could be divided into themarginal type, medial type and lateral type according to the fistula site at thetentorium. Appropriate approaches were chosen accordingly. Combination ofintravascular therapy and microsurgery was recommended for complex ones, and theresults remained unsatisfactory.更多还原