颅内多发动脉瘤发病机制、新手术入路显微解剖及应用研究
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摘要
概述
颅内动脉瘤(intracranial aneurysm)是常见的危害人类健康的疾病,罹患率为2%～5%,其中破裂动脉瘤约占50%。动脉瘤破裂是导致蛛网膜下腔出血(subarachnoid hemorrhage,SAH)重要原因之一,其破裂出血后再次破裂出血、脑血管痉挛(cerebral vasospasm,CVS)、脑积水等是危及生命的并发症,具有较高的致死率和致残率。颅内动脉瘤以囊性动脉瘤(Intracranial Saccular Aneurysms,ISA)最常见,而颅内多发囊性动脉瘤(Multiple Intracranial Saccular Aneurysms,MISA)即通常所说颅内多发动脉瘤(Multiple Intracranial Aneurysms,MIA)占颅内囊性动脉瘤的20～30%,是较单发囊性动脉瘤更具威胁及治疗更具挑战性的疾病,严重危害人类健康。对于颅内多发囊性动脉瘤(MISA)方面的研究如发病机制、预防及治疗是当前的热门话题。
目前,由于对单发囊性动脉瘤的发病机制还不十分了解,因此,不但没有理想的预防手段。一直以来,人们认为主要由于脑动脉分叉处管壁中层缺少平滑肌和弹力纤维以及血流不断冲击而逐渐扩展形成了囊性动脉瘤。但MISA常呈双侧性地分布在Willis环及其主要分支、椎-基底动脉上。甚至,我们在临床工作中还发现囊性动脉瘤尤其多发动脉瘤还常位于颈内动脉海绵窦段、水平段、基底动脉等非分叉部,而且,并非所有的动脉主要分叉部都同时出现动脉瘤,因此,用血流动力学学说不能完全解释的发病机制。这一直是困扰着我们的一个问题。在对颅内单发囊性动脉瘤的细胞分子病理研究中发现,其具有瘤壁退行性变,在形态学改变方面集中在：多种因素参与的动脉管壁的一系列形态改变包括管壁中层缺陷,内弹力层碎裂、消失,平滑肌细胞减少或消失以及肌层变薄、内膜垫形成,细胞外基质(extracellular matrix,ECM)缺乏等。动态方面则是原有血管扩张、通透性增加、细胞外基质(extracellular matrix,ECM)的降解、内皮细胞增生、迁移等病理变化。进一步研究则表明,基质金属蛋白酶(matrix metalloproteinases,MMPs)、血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)在血管通透性增加、细胞外基质(ECM)的降解、内皮细胞增生、迁移中取着关键的作用。但对于MMPs以及VEGF在MISA发病机制方面的研究未见报道。
对于临床所有MISA均必需随诊、积极地治疗是目前较为一致的观点。对于MISA治疗方案多种多样,但是,尚没有一种方案可以安全可靠地治愈所有的动脉瘤。因此,神经外科医生必须熟悉各种治疗方法的特点和适应证,针对各种MISA制定最恰当的个性化的治疗方案。
MISA的治疗方法包括：血管内治疗、开颅夹闭术／孤立／包裹术。其中,开颅显微手术夹闭动脉瘤的瘤颈仍是治疗颅内动脉瘤的“金标准”。其中,对于不能夹闭的动脉瘤,暴露良好可以行包裹术,对于既不能夹闭又不能包裹的动脉瘤,必要时在病人侧枝循环允许情况下采用孤立(可能还需要辅以搭桥术)。
翼点入路是最常用的手术入路,术中尽可能一期手术处理完所有多发动脉瘤是其治疗原则。无疑,单一入路能够较好显露所有MISA是治疗的先决条件。单一入路及一次性手术不但可以减少患者手术次数,减少损伤,减轻患者的心理负担,而且也可预防未治疗动脉瘤在手术后血流动力学改变而发生破裂。但是,目前临床工作中往往不能实现。据统计约90%颅内动脉瘤多发生于Willis环近侧的大动脉上,虽然,通过一侧翼点入路不仅可以完成大部分同侧Willis环前部动脉瘤及大脑中动脉(median cerebral artery,MCA) M1-3及分支动脉瘤的手术,还可以完成少部分对侧颈内动脉床突上段内侧、远端及其分叉和M1段动脉瘤手术。但是,仍然有少部分同侧Willis环前部内侧动脉瘤、部分眼动脉瘤,大部分对侧颈内动脉床突上段外侧、远端及其分叉部,M1段动脉瘤手术及大部分后循环动脉瘤无法完成。MISA往往呈现双侧对称性生长是其一大特点,所在部位的分布的区域越广,要采取开颅手术治疗,就要采取多种手术入路或分期进行开颅术,这样对患者造成的损伤就大,患者心理及经济负担就更重。因此,探讨新的手术入路,更广泛暴露MISA好发部位,尽可能一次完成MISA夹闭具有重要意义。
血管内治疗MISA是发展较为迅速的领域。1973年前苏联Serbinenko用可脱性球囊闭塞动脉瘤开创了血管内治疗动脉瘤的先河,1991年Guglielmi发明电解脱铂弹簧圈(GDC)栓塞动脉瘤是一个革命性进展。方法有：单纯弹簧圈栓塞动脉瘤,支架辅助栓塞动脉瘤、球囊辅助栓塞动脉瘤、闭塞颈内动脉将动脉瘤孤立于循环系统之外等方法。其优点是：可以处理微导管可以到达任何部位的动脉瘤；而且只在血管内操作,不扰乱动脉瘤周围结构；部分患者可以在局麻下完成手术；可以使病人免受开颅手术之苦；特别对于那些病情严重,全身状况不良,动脉瘤夹闭困难和手术危险性大的病人更具有其独特的优势。例如治疗岩段及海绵窦段动脉瘤、眼动脉瘤及后循环动脉瘤治疗更具优势。但是其缺点是：脑血管痉挛严重、颈内动脉或者椎动脉严重狭窄、严重斑块形成、血管严重弯曲等可以导致不能进行血管内治疗。同时,操作时间长将会增加风险,尤其是在急性期易产生严重的而广泛的脑血管痉挛。这时血管内治疗MISA面临的另一难题。此外,栓塞材料的缺陷也限制了血管内治疗的开展；对于某些未破裂MISA尤其宽颈动脉瘤过度栓塞导致破裂出血是又一问题。2002年ISAT表明,经过长期随访,血管内治疗动脉瘤优于开颅手术。因此,随着介入材料的改进,血管内治疗MISA具有更广阔的前景。
对于不能一期处理的多发动脉瘤,也应优先处理破裂动脉瘤,而后二期(一般术后两个月左右)手术处理未破裂动脉瘤。而对分布于两侧颈内动脉系统的多发动脉瘤或者分别在颈内动脉和椎-基底动脉系统的多发动脉瘤,常常需仔细评估是一期还是二期治疗,采取一个入路还是两个入路,是选择开颅手术治疗还是血管内治疗MISA都必须考虑的因素,这,无疑是当前治疗MISA非常值得探讨的课题。
本课题旨在从三方面研究MISA:
第一部分：采用免疫组化S-ABC法检测单发、多发囊性动脉瘤瘤壁中基质金属蛋白酶2和9(matrix metalloproteinase-2,matrix metalloproteinase-9;MMP-2、9)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达状况,透射电镜观察单发、多发囊性动脉瘤瘤壁超微结构变化,初步从细胞、分子水平以及超级形态结构角度探讨ISA尤其囊性多发动脉瘤的表达及意义；
第二部分：对9例成人湿尸头标本先行9侧标准翼点入路开颅,用于显露Willis环及其主要分支,尤其基底动脉、对侧颈内动脉床突上段、大脑中动脉水平段(M1)。对传统额颞眶颧基础上进行改良,再行该9例同侧改良额颞颧入路开颅,暴露上述结构,探讨新的更广泛暴露Willis环及其主要分支的入路即改良额颞颧入路,为临床开颅手术治疗MISA提供解剖学参考；
第三部分：收集广州军区武汉总医院神经外科自2008年1月至2009年12月间收治的经规范治疗的MISA患者资料,初步探讨目前临床治疗MISA的有效方案。
第一部分MMP-2/9及VEGF在颅内囊性动脉瘤瘤壁的表达及意义
目的：初步探讨基质金属蛋白酶2和9(matrix metalloproteinase-2,matrix metalloproteinase-9;MMP-2、9)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)在颅内囊性动脉瘤表达及意义。方法：收集广州军区武汉总医院神经外科自2008年1月至2008年9月间经造影及手术证实的16例颅内多发动脉瘤患者标本作为实验组一,17例单发囊性动脉瘤标本作为实验组二,9例颅脑损伤患者标本作对照。实验组一共有39个囊性动脉瘤体标本,包括后交通动脉瘤20个,前交通动脉瘤11个,大脑中动脉瘤3个,脉络膜前动脉瘤4个,基底动脉-小脑上动脉动脉瘤1个。17例单发囊性动脉瘤包括后交通动脉瘤9个,前交通动脉瘤5个,大脑中动脉瘤3个。9例对照的重型颅脑损伤患者,脑血管的标本为手术需切除失活的脑组织的大脑中动脉一、二级分支。采用免疫组化S-ABC法检测正常脑血管和颅内单发、多发囊性动脉瘤中MMP-2、9及VEGF的表达情况,组间比较采用单向方差分析。通过透射电镜观察正常脑血管及颅内单发、多发囊性动脉瘤超微结构变化。结果：实验组颅内单发、多发囊性动脉瘤MMP-2、9及VEGF表达较对照组有统计学意义(P<0.05),而颅内单发囊性动脉瘤与多发囊性动脉瘤间MMP-2、9及VEGF表达差异没有统计学意义(P>0.05)。免疫阳性物质为棕黄色颗粒为主。阳性细胞形态呈长梭形或星形,类似异常增生的平滑肌细胞,主要分布于动脉瘤壁的中膜层尤其近内、外膜处。同时,实验组的内皮细胞变性脱落,胞浆内出现肿胀的线粒体和大小不等的空泡,瘤壁可见形态异常的平滑肌细胞和成纤维细胞,增多的胶原纤维排列紊乱。结论：MMP-2、9及VEGF表达明显增加可能与ECM的溶解、血管退行性变、颅内囊性动脉瘤的形成、进一步扩大乃至破裂有重要关系。这在颅内多发囊性动脉瘤的形成更具重要的临床意义。
第二部分改良额颞颧入路暴露Willis环及其主要分支的应用显微解剖学研究
目的：利用改良额颞颧弓(Modified Frontotemporal Zygomatic,FTZ)开颅,对Willis环及其主要分支显露进行显微解剖学研究,探讨其临床应用价值。方法：对9例成人湿尸头标本先行一侧标准翼点入路,显微磨钻充分磨除蝶骨嵴等骨质,在手术显微镜下显微暴露willis环及其主要分支,尤其是基底动脉、对侧颈内动脉床突上段、大脑中动脉水平段(M1)；而后在翼点入路基础上的同侧,对传统的额颞颧入路进行改良,务必暴露四分之三的前颅底并尽可能保护眼眶,形成改良FTZ开颅,利用手术显微镜充分暴露上述结构。利用配对资料t检验,比较两组手术入路所测上述结构长度。结果：改良FTZ入路较常规翼点入路具有更好暴露Willis环及其主要分支,尤其是基底动脉、对侧颈内动脉床突上段、M1。比较两组手术入路所测上述结构长度,差异具有统计学意义(P<0.05)。结论：改良FTZ入路较常规翼点入路具有更好暴露Willis环及其主要分支,尤其基底动脉、对侧颈内动脉床突上段、M1的优点。可用于处理Willis环及其主要分支的多发动脉瘤,值得进一步探讨。
第三部分颅内多发囊性动脉瘤的治疗方案探讨(附35例报道)
目的：探讨颅内多发囊性动脉瘤的治疗方案。方法：回顾分析广州军区武汉总医院神经外科2008年1月到2009年12月间的35例颅内多发动脉瘤病人的完整资料,根据患者具体情况,按实施治疗方案分手术、介入、手术加介入三组。术前患者评估内容包括：年龄、性别、动脉瘤数量、部位、侧别、大小、Hunt-Hess分级、Fisher分级。术后评估则以出院时GOS术后评分为准。单因素分析术前各因素、治疗方案对治疗效果的影响,多因素Logistic多元回归分析治疗效果与术前各因素、治疗方案的关系。结果：按GOS术后评分良好(4-5分)24例,差(1-2)11例。三组治疗效果比较差异没有统计学意义。通过统计学单因素分析,显示患者年龄、术前Hunt-Hess分级和Fisher分级与预后具有显著相关性(P<0.30,参考相关文献)。而多因素的Logistic多元回归分析结果显示患者年龄、术前Hunt-Hess分级和Fisher分级有没有显著相关性(P>0.05)。结论：患者年龄、术前Hunt-Hess分级和Fisher分级是影响颅内多发动脉瘤病人术后疗效的关键因素,根据病人的实际情况选择合理的治疗方案是提高颅内多发囊性动脉瘤疗效的关键,强调个性化治疗,可使手术、介入及手术+介入的治疗取得同样的效果,但仍然值得进一步探讨。
Intracranial aneurysm is a kind of common disease which is serious harm for human being health and it's attack rate was about 2%～5%,among these 50% of them occurred rupture approximately.Bleeding of ruptured intracranial aneurysms is one of the most important cause leading cause subarachnoid hemorrhage. And the much more important event occurred complications when rebleeding of ruptured intracranial aneurysms such as cerebral vasospasm, rebleeding,forming giant cerebral hematoma, encephalic infections,developing hydrocephalus and so on which will severely impact life-threatening.There is of high lethality rate and disability rate. Intracranial Saccular Aneurysms are the most common aneurysms, about 20-30% of these is Multiple Intracranial Aneurysms among them,which are much more serious harm for human being health than single saccular aneurysms thus,they are much more challenging disease.The study of pathogenesis and prevention and treatment for Multiple Intracranial Aneurysms is one of the hot issues.
However,there is no much more exact pathogenesis of single saccular aneurysms as yet,thus no ideal preventing methods and screening technique.The lack of smooth muscle in cerebral arteries tube wall middle layer and elastic fibers accepted occurring cerebral arteries bifurcation cause intracranial aneurysms complying with the continuous impact of the walls then gradually extended end to cause saccular aneurysms for a long time were accepted.But these Multiple Intracranial Aneurysms land bilaterally in willis artery circulations and its mainly branches including basilar artery,above on,they were find landing in the segments with non-main-bifurcation such as cavernous segment of the internal carotid artery, horizontal sections,basilar artery, etc.The hemodynamics can not elucidate what the pathogenesis of Multiple Intracranial Aneurysms is completely, which is perplexing us for a long time.Fewer scholars noticed that degeneration happened in aneurysmal tube wall is the most common by researching its cellular molecular pathological mechanism.showing morphological characteristics much like the structural defect in middle layer,the fragmentations or disappearance in internal elastic lamina,The lack and disappearance of smooth muscle,the thinning out of muscularis complying the formation of endometrial pad,the lack of extracellular matrix (ECM),etc.Dynamic pathological characteristics showing that vascular dilatation, permeability increasing, degradation of extracellular matrix,the proliferations and migrations of endothelia cell,etc. Further studies show that matrix metalloproteinases (MMPs)and vascular endothelial growth factor(VEGF)play a key role in these pathological characteristic formations.However, the investigations about why and how matrix metalloproteinases both vascular endothelial growth factor in the pathogenesis of Multiple Intracranial Aneurysms has not been reported.
There is a unified view about Multiple Intracranial Aneurysms when they are explored,that is they should de followed up clinic or positive therapied. None standard and ideal regimen could be chosen among these infinite variety therapeutic schemes.So,neurosurgeons have to familiar with therapeutic characteristics and indications to establish the perfect personalied therapeutic schemes aim to increase the efficacy of the Multiple Intracranial Aneurysms disease.Endovascular treatment and digging skull operation including clipping of intracranial aneurysm,surgery trapping and wrapped aneurysms are therapeutic methods can be picked up to therapy Multiple Intracranial Aneurysms disease. Performing open micro-craniotomy clip the neck of aneurysms is called golden standard still.Surgery trapping and wrapping aneurysms are used when clipping could not performed and by-passed will be applied.
Standard ptefional approach is the most commonly used approach to treat Multiple Intracranial Aneurysms,and the principles to follow is one-stage operate on these aneurysms as much as possible.A single operational approach must expose all aneurysms is precondition and only then could they been therapied.A single operation or one-off operation can reduce patients'operational times,less damages, relieve psychological pressure,and doing it can prevent the rupture by hemodynamics impacting on walls for those un-therapy aneurysms undoubtedly. Much of them can not be realized now and then, yet. About 90% Intracranial Aneurysms land in willis artery circulations and its mainly branches, neurosurgeon can therapy mostly ipsilateral anterior part of Aneurysms land in willis artery circulations, median cerebral artery 1 to 3 segment (M1-3) and its mainly branches.and a small part Aneurysms land in contralateral medial side,distal upper clinoid process segments of the internal carotid artery and 1st segment of median cerebral artery.There are a small part of aneurysms land in ipsilateral medial side anterior part of Aneurysms landing in willis artery circulations and some internal carotid artery ophthalmic arterysegmental aneurysm and mostly ipsilateral lateralisor distal and bifurcations anterior part of aneurysms land in upper clinoid process segments of the internal carotid artery and M1 and mostly aneurysms land in posterior circulation can not be treated perfectly make performing several operational approaches or staged operations because of Multiple Intracranial Aneurysms land bilaterally with distribution of extensive regions are total essential. But, all these will have to increase much more serious injury, psychological pressure and economic burden of the disease. It is of very important to investigate a new approach that can expose site where Multiple Intracranial Aneurysms landing for getting therapy these aneurysms well.
Endovascular treating Multiple Intracranial Aneurysms is the most dazzling fields with the rapid development.Since Serbinenko in Former Soviet occluse aneurysms using detachable balloon initiating advocated earlier of endovascular treating aneurysms in 1973 to Guglielmi invented electronic detachable coil leading to endovascular treating aneurysms revolutionary advances.The methods of endovascular treating aneurysms including when embolizate aneurysms by using simply spring coil embolization, aided by stents,aided by balloon, etc.Which isolate aneurysms whereabout blood circulatory system with peculiar advantages of treating all the aneurysms where micro-catheter can get,having no disturbs to its surrounding structures, performing under local anesthesia state, avoiding suffering from open craniotomy, working carries out smoothly when under severe condition and illness conditions with disabilities in clipping aneurysms.For example, it show has advantages when endovascular treating aneurysms landing rock section, cavernous segment, internal carotid artery ophthalmic artery segment and posterior circulation. However, it show disadvantages when cerebral vasospasm seriously internal carotid or vertebro-basilarartery stricture, plaque formation severely,curved configuration of vessel and so on will lead to failing to endovascular treating and operate too long time will increased risk inevitably, as cerebral vasospasm extensively and seriously during acute stage easily.
As is difficult problem faced by endovascular treating Multiple Intracranial Aneurysms, embolic materials have its own some defectiveness limiting the kind of therapy, too.Some of unruptured and wide neck Multiple Intracranial Aneurysms perform excessive embolization now and then will cause bleeding of these ruptured intracranial aneurysms moreover. International Subarachnoid Aneurysm Trial (ISAT) in 2002 show that endovascular treating aneurysm is superior toneurosurgical clipping them by followed up clinic for a long time. People believe in that endovascular treating Multiple Intracranial Aneurysms will possess more wide application with the developing of interventional materials.
There are some Multiple Intracranial Aneurysms that can not been got well therapy in one-stage operate, priority to treat ruptured aneurysms then follow up clinic for about two months before treating other ruptured aneurysms.Neurosurgeon must evaluate carefully what measures should be taken when Multiple Intracranial Aneurysms are very complicated landing in bilateral internal carotid artery,internal carotid or vertebro-basilarartery much like this one stage or two stages, a single or two approaches,.interventional or operative process.All these above are questions which are worth discussing at present undoubtedly.
The study is aim to research Multiple Intracranial Aneurysms including these 3 aspects:the first,To observe the expression and the significance of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9) and vascular endothelial growth factor(VEGF) in human Intracranial Saccular Aneurysms(ISA). by immunohistochemistry S-ABC method and transmission electron microscope technique respectively.Then got these viewpoint that MMP-2,MMP-9 and VEGF might play an primary role in the pathogenesis and rapture of ISA especial in multiple intracranial aneurysms in cellar and molecular level and super morphology aspect. Secondly, To research the exposure of Willis Circle and its Mainly Branch in a microscopic anatomy way by Modified Frontotemporal Zygomatie(FTZ) craniotomy Simultaneously posterior to standard ptefional craniotomies were performed on the same 9 sides of these cadaveric heads specimens, providing reference for clinical operate on Multiple Intracranial Aneurysms.Thirdly,To explore the good treatment of multiple intracanrial aneurysms and to improve its outcomes by collecting patients'data affected Multiple Intracranial Aneurysms in Center for Neurosurgery of PLA,Department of Neurosurgery,Wuhan General Hospital,Guangzhou Command PLA,from January 2008 to December 2009.
PartⅠThe Expression and Significance of Vascular Endothelial Growth Factor and Matrix Metalloproteinases-2,9 in Intracranial Saccular Aneurysms
Objective To observe the expression and the significance of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9) and vascular endothelial growth factor(VEGF) in human Intracranial Saccular Aneurysms(ISA).
Methods Sixteen patients'multiple intracanrial aneurismal sample were divided into group 1;including 20 cases PCoAAN,11 cases ACoA AN,3 cases MCA AN,4 cases AchA AN,1 case BA-SCA AN.Seventeen patients'single intracranial aneurismal sample were divided into group 2, including 9 cases PCoA AN,5 cases ACoA AN,3 cases MCA AN;Nine severely drain trauma patients'MCA or its main branches complying surgical excision of deactivated cerebral tissues.All which were collected in the Department of Neurosurgery, Wuhan General Hospital, Guangzhou Command of PLA, from January,2008 to September,2008.The expression of MMP-2,MMP-9, VEGF and super-microstructure changes were observed with immunohistochemistry and transmission electron microscope technique respectively.And the data were analyzed by chi-square test between groups.
Results MMP-2,MMP-9 and VEGF in ISA(groupland 2) were significantly higher than in MCA(group3)(P<0.05),and on significance between groupland 2(P>0.05).Immunoreactive substances were mainly brown-yellow granules. Immuno-positive cells were long fusiform or star types, looking like and smooth muscle cells hepatocyte,distributed mainly mediumfilm layer where near endometrium and outer membrane especially. Endothelial cells were degenerated and collaped.A number of vesicles and swollen mitochondria were present in the cytoplasm.These aneurysmal walls varied in thickness and were composed of regenerative smooth muscle cells and collagenous fibres.
Conclusions The over-expression of MMP-2, MMP-9 and VEGF might play an primary role in the pathogenesis and rapture of ISA especial in multiple intracranial saccular aneurysms.Playing a key role with degeneration happened in artery tube wall,degradation of extracellular matrix, gradual extension and rupture of saccular aneurysms.
Part II The Applied Micro-anatomical Study on Modified Frontotemporal Zygomatic Approach Exposure to Willis Circle and Its Mainly Branches
Objective To research the exposure of Willis circle and its mainly branches in a microscopic anatomy way by Modified Frontotemporal Zygomatic (FTZ) craniotomy,discussing its clinical application value.
Methods Standard ptefional approach craniotomies were performed on 9 sides of 9 adult wet cadaveric heads specimens,with the help of micro-grinding drill and surgical microscope,the sphenoid ridge and part of anterior clinoid process and sclerotin were removed to expose Willis Circle and its Mainly Branch.especially the basilar artery,the contralateral upper clinoid process segment of internal carotid artery and horizontal section of midge cerebral artery(M1);Simultaneously, Modified Frontotemporal Zygomatic (FTZ) approach craniotomies were performed on the same 9 sides of these cadaveric heads specimens, traditional frontotemporal orbitozygomatic were modified by exposing largely anterior skull base(75%)and protecting orbital walls, Comparing the two groups'lengths applied its own operational approaches analyzing by paired t test.
Results Modified FTZ approach could better expose Willis Circle and its Mainly Branch,especially the basilar artery(BA),contralateral supraclinoid segment of internal carotid artery(ICA)and horizontal section of midge cerebral artery(M1)compared to the standard pterional approach.Comparing the two groups' lengths applied its own operational approaches, there were statistical significance (P<0.05).
Conclusion Modified FTZ approach can be used to deal with the multiple aneurysms located in Willis Circle and its Mainly Branch compared to the standard pterional approach,and the craniotomy is an alternative to the standard pterional approach maybe, which is worth of furthermore investigate yet.
PartⅢThe discussion on therapeutic schemes of multiple intracranial aneurysms:A Report of 35 Cases
Objective To investigate the therapeutic schemes of multiple intracranial aneurysms.
Methods The clinical data of 35 patients with multiple intracranial aneurysms. ,who were treated in the Department of Neurosurgery, Wuhan General Hospital, Guangzhou Command of PLA, from January,2008 to December,2009,were analyzed retrospectively. They were divided into three groups operational group, interventional therapic group, operational both interventional therapic group by therapeutic schemes applied to these patients. Those factors before treatment that might influence the outcome were evaluated, including ages,gender,number of the aneurysms, the location of the aneurysms, lateral side the aneurysms, and size the aneurysms, preoperative Hunt-Hess grades,preoperative Fisher grades.The patients'outeome at discharge according to the Glasgow Outcome Scale was divided into two categories: favorable (4-5 grades)or unfavorable(1-3 grades).Chi-square test was applied to analysis preoperative factors that might influence the outcome respectively,and Logistic multivariable analysis of the factors related to the prognosis was performed in the patients with multiple intracranial aneurysms.
Results Favorable outcome in 24 cases,unfavorable in 11 cases, however. The preoperative patient's ages,Hunt-Hess grades and Fisher grades were predictors for the outcome by single factor analysis (P<0.30, referring to related literatures).The results of multiple Logistic regression analysis showed that no factor was predictors for the outcome (P>0.05).
Conclusions The prognosis in patients with MIA are significantly and negatively related to the patients ages, Fisher grade and Hunt-Hess grade before treatment.It is key to improve therapeutic effects with multiple intracranial aneurysms by selecting appropriate therapeutic schemes on the basis of the patients actual conditions, emphasizing personalization therapy.Which can get the same better effects by operation, interventional therapyor operation both interventional therapy any way And which are worth of the further discussing undoubtedly.
颅内动脉瘤(intracranial aneurysm)是常见的危害人类健康的疾病,罹患率为2%～5%,其中破裂动脉瘤约占50%。动脉瘤破裂是导致蛛网膜下腔出血(subarachnoid hemorrhage,SAH)重要原因之一,其破裂出血后再次破裂出血、脑血管痉挛(cerebral vasospasm,CVS)、脑积水等是危及生命的并发症,具有较高的致死率和致残率。颅内动脉瘤以囊性动脉瘤(Intracranial Saccular Aneurysms,ISA)最常见,而颅内多发囊性动脉瘤(Multiple Intracranial Saccular Aneurysms,MISA)即通常所说颅内多发动脉瘤(Multiple Intracranial Aneurysms,MIA)占颅内囊性动脉瘤的20～30%,是较单发囊性动脉瘤更具威胁及治疗更具挑战性的疾病,严重危害人类健康。对于颅内多发囊性动脉瘤(MISA)方面的研究如发病机制、预防及治疗是当前的热门话题。
目前,由于对单发囊性动脉瘤的发病机制还不十分了解,因此,不但没有理想的预防手段。一直以来,人们认为主要由于脑动脉分叉处管壁中层缺少平滑肌和弹力纤维以及血流不断冲击而逐渐扩展形成了囊性动脉瘤。但MISA常呈双侧性地分布在Willis环及其主要分支、椎-基底动脉上。甚至,我们在临床工作中还发现囊性动脉瘤尤其多发动脉瘤还常位于颈内动脉海绵窦段、水平段、基底动脉等非分叉部,而且,并非所有的动脉主要分叉部都同时出现动脉瘤,因此,用血流动力学学说不能完全解释的发病机制。这一直是困扰着我们的一个问题。在对颅内单发囊性动脉瘤的细胞分子病理研究中发现,其具有瘤壁退行性变,在形态学改变方面集中在：多种因素参与的动脉管壁的一系列形态改变包括管壁中层缺陷,内弹力层碎裂、消失,平滑肌细胞减少或消失以及肌层变薄、内膜垫形成,细胞外基质(extracellular matrix,ECM)缺乏等。动态方面则是原有血管扩张、通透性增加、细胞外基质(extracellular matrix,ECM)的降解、内皮细胞增生、迁移等病理变化。进一步研究则表明,基质金属蛋白酶(matrix metalloproteinases,MMPs)、血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)在血管通透性增加、细胞外基质(ECM)的降解、内皮细胞增生、迁移中取着关键的作用。但对于MMPs以及VEGF在MISA发病机制方面的研究未见报道。
对于临床所有MISA均必需随诊、积极地治疗是目前较为一致的观点。对于MISA治疗方案多种多样,但是,尚没有一种方案可以安全可靠地治愈所有的动脉瘤。因此,神经外科医生必须熟悉各种治疗方法的特点和适应证,针对各种MISA制定最恰当的个性化的治疗方案。
MISA的治疗方法包括：血管内治疗、开颅夹闭术／孤立／包裹术。其中,开颅显微手术夹闭动脉瘤的瘤颈仍是治疗颅内动脉瘤的“金标准”。其中,对于不能夹闭的动脉瘤,暴露良好可以行包裹术,对于既不能夹闭又不能包裹的动脉瘤,必要时在病人侧枝循环允许情况下采用孤立(可能还需要辅以搭桥术)。
翼点入路是最常用的手术入路,术中尽可能一期手术处理完所有多发动脉瘤是其治疗原则。无疑,单一入路能够较好显露所有MISA是治疗的先决条件。单一入路及一次性手术不但可以减少患者手术次数,减少损伤,减轻患者的心理负担,而且也可预防未治疗动脉瘤在手术后血流动力学改变而发生破裂。但是,目前临床工作中往往不能实现。据统计约90%颅内动脉瘤多发生于Willis环近侧的大动脉上,虽然,通过一侧翼点入路不仅可以完成大部分同侧Willis环前部动脉瘤及大脑中动脉(median cerebral artery,MCA) M1-3及分支动脉瘤的手术,还可以完成少部分对侧颈内动脉床突上段内侧、远端及其分叉和M1段动脉瘤手术。但是,仍然有少部分同侧Willis环前部内侧动脉瘤、部分眼动脉瘤,大部分对侧颈内动脉床突上段外侧、远端及其分叉部,M1段动脉瘤手术及大部分后循环动脉瘤无法完成。MISA往往呈现双侧对称性生长是其一大特点,所在部位的分布的区域越广,要采取开颅手术治疗,就要采取多种手术入路或分期进行开颅术,这样对患者造成的损伤就大,患者心理及经济负担就更重。因此,探讨新的手术入路,更广泛暴露MISA好发部位,尽可能一次完成MISA夹闭具有重要意义。
血管内治疗MISA是发展较为迅速的领域。1973年前苏联Serbinenko用可脱性球囊闭塞动脉瘤开创了血管内治疗动脉瘤的先河,1991年Guglielmi发明电解脱铂弹簧圈(GDC)栓塞动脉瘤是一个革命性进展。方法有：单纯弹簧圈栓塞动脉瘤,支架辅助栓塞动脉瘤、球囊辅助栓塞动脉瘤、闭塞颈内动脉将动脉瘤孤立于循环系统之外等方法。其优点是：可以处理微导管可以到达任何部位的动脉瘤；而且只在血管内操作,不扰乱动脉瘤周围结构；部分患者可以在局麻下完成手术；可以使病人免受开颅手术之苦；特别对于那些病情严重,全身状况不良,动脉瘤夹闭困难和手术危险性大的病人更具有其独特的优势。例如治疗岩段及海绵窦段动脉瘤、眼动脉瘤及后循环动脉瘤治疗更具优势。但是其缺点是：脑血管痉挛严重、颈内动脉或者椎动脉严重狭窄、严重斑块形成、血管严重弯曲等可以导致不能进行血管内治疗。同时,操作时间长将会增加风险,尤其是在急性期易产生严重的而广泛的脑血管痉挛。这时血管内治疗MISA面临的另一难题。此外,栓塞材料的缺陷也限制了血管内治疗的开展；对于某些未破裂MISA尤其宽颈动脉瘤过度栓塞导致破裂出血是又一问题。2002年ISAT表明,经过长期随访,血管内治疗动脉瘤优于开颅手术。因此,随着介入材料的改进,血管内治疗MISA具有更广阔的前景。
对于不能一期处理的多发动脉瘤,也应优先处理破裂动脉瘤,而后二期(一般术后两个月左右)手术处理未破裂动脉瘤。而对分布于两侧颈内动脉系统的多发动脉瘤或者分别在颈内动脉和椎-基底动脉系统的多发动脉瘤,常常需仔细评估是一期还是二期治疗,采取一个入路还是两个入路,是选择开颅手术治疗还是血管内治疗MISA都必须考虑的因素,这,无疑是当前治疗MISA非常值得探讨的课题。
本课题旨在从三方面研究MISA:
第一部分：采用免疫组化S-ABC法检测单发、多发囊性动脉瘤瘤壁中基质金属蛋白酶2和9(matrix metalloproteinase-2,matrix metalloproteinase-9;MMP-2、9)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达状况,透射电镜观察单发、多发囊性动脉瘤瘤壁超微结构变化,初步从细胞、分子水平以及超级形态结构角度探讨ISA尤其囊性多发动脉瘤的表达及意义；
第二部分：对9例成人湿尸头标本先行9侧标准翼点入路开颅,用于显露Willis环及其主要分支,尤其基底动脉、对侧颈内动脉床突上段、大脑中动脉水平段(M1)。对传统额颞眶颧基础上进行改良,再行该9例同侧改良额颞颧入路开颅,暴露上述结构,探讨新的更广泛暴露Willis环及其主要分支的入路即改良额颞颧入路,为临床开颅手术治疗MISA提供解剖学参考；
第三部分：收集广州军区武汉总医院神经外科自2008年1月至2009年12月间收治的经规范治疗的MISA患者资料,初步探讨目前临床治疗MISA的有效方案。
第一部分MMP-2/9及VEGF在颅内囊性动脉瘤瘤壁的表达及意义
目的：初步探讨基质金属蛋白酶2和9(matrix metalloproteinase-2,matrix metalloproteinase-9;MMP-2、9)及血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)在颅内囊性动脉瘤表达及意义。方法：收集广州军区武汉总医院神经外科自2008年1月至2008年9月间经造影及手术证实的16例颅内多发动脉瘤患者标本作为实验组一,17例单发囊性动脉瘤标本作为实验组二,9例颅脑损伤患者标本作对照。实验组一共有39个囊性动脉瘤体标本,包括后交通动脉瘤20个,前交通动脉瘤11个,大脑中动脉瘤3个,脉络膜前动脉瘤4个,基底动脉-小脑上动脉动脉瘤1个。17例单发囊性动脉瘤包括后交通动脉瘤9个,前交通动脉瘤5个,大脑中动脉瘤3个。9例对照的重型颅脑损伤患者,脑血管的标本为手术需切除失活的脑组织的大脑中动脉一、二级分支。采用免疫组化S-ABC法检测正常脑血管和颅内单发、多发囊性动脉瘤中MMP-2、9及VEGF的表达情况,组间比较采用单向方差分析。通过透射电镜观察正常脑血管及颅内单发、多发囊性动脉瘤超微结构变化。结果：实验组颅内单发、多发囊性动脉瘤MMP-2、9及VEGF表达较对照组有统计学意义(P<0.05),而颅内单发囊性动脉瘤与多发囊性动脉瘤间MMP-2、9及VEGF表达差异没有统计学意义(P>0.05)。免疫阳性物质为棕黄色颗粒为主。阳性细胞形态呈长梭形或星形,类似异常增生的平滑肌细胞,主要分布于动脉瘤壁的中膜层尤其近内、外膜处。同时,实验组的内皮细胞变性脱落,胞浆内出现肿胀的线粒体和大小不等的空泡,瘤壁可见形态异常的平滑肌细胞和成纤维细胞,增多的胶原纤维排列紊乱。结论：MMP-2、9及VEGF表达明显增加可能与ECM的溶解、血管退行性变、颅内囊性动脉瘤的形成、进一步扩大乃至破裂有重要关系。这在颅内多发囊性动脉瘤的形成更具重要的临床意义。
第二部分改良额颞颧入路暴露Willis环及其主要分支的应用显微解剖学研究
目的：利用改良额颞颧弓(Modified Frontotemporal Zygomatic,FTZ)开颅,对Willis环及其主要分支显露进行显微解剖学研究,探讨其临床应用价值。方法：对9例成人湿尸头标本先行一侧标准翼点入路,显微磨钻充分磨除蝶骨嵴等骨质,在手术显微镜下显微暴露willis环及其主要分支,尤其是基底动脉、对侧颈内动脉床突上段、大脑中动脉水平段(M1)；而后在翼点入路基础上的同侧,对传统的额颞颧入路进行改良,务必暴露四分之三的前颅底并尽可能保护眼眶,形成改良FTZ开颅,利用手术显微镜充分暴露上述结构。利用配对资料t检验,比较两组手术入路所测上述结构长度。结果：改良FTZ入路较常规翼点入路具有更好暴露Willis环及其主要分支,尤其是基底动脉、对侧颈内动脉床突上段、M1。比较两组手术入路所测上述结构长度,差异具有统计学意义(P<0.05)。结论：改良FTZ入路较常规翼点入路具有更好暴露Willis环及其主要分支,尤其基底动脉、对侧颈内动脉床突上段、M1的优点。可用于处理Willis环及其主要分支的多发动脉瘤,值得进一步探讨。
第三部分颅内多发囊性动脉瘤的治疗方案探讨(附35例报道)
目的：探讨颅内多发囊性动脉瘤的治疗方案。方法：回顾分析广州军区武汉总医院神经外科2008年1月到2009年12月间的35例颅内多发动脉瘤病人的完整资料,根据患者具体情况,按实施治疗方案分手术、介入、手术加介入三组。术前患者评估内容包括：年龄、性别、动脉瘤数量、部位、侧别、大小、Hunt-Hess分级、Fisher分级。术后评估则以出院时GOS术后评分为准。单因素分析术前各因素、治疗方案对治疗效果的影响,多因素Logistic多元回归分析治疗效果与术前各因素、治疗方案的关系。结果：按GOS术后评分良好(4-5分)24例,差(1-2)11例。三组治疗效果比较差异没有统计学意义。通过统计学单因素分析,显示患者年龄、术前Hunt-Hess分级和Fisher分级与预后具有显著相关性(P<0.30,参考相关文献)。而多因素的Logistic多元回归分析结果显示患者年龄、术前Hunt-Hess分级和Fisher分级有没有显著相关性(P>0.05)。结论：患者年龄、术前Hunt-Hess分级和Fisher分级是影响颅内多发动脉瘤病人术后疗效的关键因素,根据病人的实际情况选择合理的治疗方案是提高颅内多发囊性动脉瘤疗效的关键,强调个性化治疗,可使手术、介入及手术+介入的治疗取得同样的效果,但仍然值得进一步探讨。
Intracranial aneurysm is a kind of common disease which is serious harm for human being health and it's attack rate was about 2%～5%,among these 50% of them occurred rupture approximately.Bleeding of ruptured intracranial aneurysms is one of the most important cause leading cause subarachnoid hemorrhage. And the much more important event occurred complications when rebleeding of ruptured intracranial aneurysms such as cerebral vasospasm, rebleeding,forming giant cerebral hematoma, encephalic infections,developing hydrocephalus and so on which will severely impact life-threatening.There is of high lethality rate and disability rate. Intracranial Saccular Aneurysms are the most common aneurysms, about 20-30% of these is Multiple Intracranial Aneurysms among them,which are much more serious harm for human being health than single saccular aneurysms thus,they are much more challenging disease.The study of pathogenesis and prevention and treatment for Multiple Intracranial Aneurysms is one of the hot issues.
However,there is no much more exact pathogenesis of single saccular aneurysms as yet,thus no ideal preventing methods and screening technique.The lack of smooth muscle in cerebral arteries tube wall middle layer and elastic fibers accepted occurring cerebral arteries bifurcation cause intracranial aneurysms complying with the continuous impact of the walls then gradually extended end to cause saccular aneurysms for a long time were accepted.But these Multiple Intracranial Aneurysms land bilaterally in willis artery circulations and its mainly branches including basilar artery,above on,they were find landing in the segments with non-main-bifurcation such as cavernous segment of the internal carotid artery, horizontal sections,basilar artery, etc.The hemodynamics can not elucidate what the pathogenesis of Multiple Intracranial Aneurysms is completely, which is perplexing us for a long time.Fewer scholars noticed that degeneration happened in aneurysmal tube wall is the most common by researching its cellular molecular pathological mechanism.showing morphological characteristics much like the structural defect in middle layer,the fragmentations or disappearance in internal elastic lamina,The lack and disappearance of smooth muscle,the thinning out of muscularis complying the formation of endometrial pad,the lack of extracellular matrix (ECM),etc.Dynamic pathological characteristics showing that vascular dilatation, permeability increasing, degradation of extracellular matrix,the proliferations and migrations of endothelia cell,etc. Further studies show that matrix metalloproteinases (MMPs)and vascular endothelial growth factor(VEGF)play a key role in these pathological characteristic formations.However, the investigations about why and how matrix metalloproteinases both vascular endothelial growth factor in the pathogenesis of Multiple Intracranial Aneurysms has not been reported.
There is a unified view about Multiple Intracranial Aneurysms when they are explored,that is they should de followed up clinic or positive therapied. None standard and ideal regimen could be chosen among these infinite variety therapeutic schemes.So,neurosurgeons have to familiar with therapeutic characteristics and indications to establish the perfect personalied therapeutic schemes aim to increase the efficacy of the Multiple Intracranial Aneurysms disease.Endovascular treatment and digging skull operation including clipping of intracranial aneurysm,surgery trapping and wrapped aneurysms are therapeutic methods can be picked up to therapy Multiple Intracranial Aneurysms disease. Performing open micro-craniotomy clip the neck of aneurysms is called golden standard still.Surgery trapping and wrapping aneurysms are used when clipping could not performed and by-passed will be applied.
Standard ptefional approach is the most commonly used approach to treat Multiple Intracranial Aneurysms,and the principles to follow is one-stage operate on these aneurysms as much as possible.A single operational approach must expose all aneurysms is precondition and only then could they been therapied.A single operation or one-off operation can reduce patients'operational times,less damages, relieve psychological pressure,and doing it can prevent the rupture by hemodynamics impacting on walls for those un-therapy aneurysms undoubtedly. Much of them can not be realized now and then, yet. About 90% Intracranial Aneurysms land in willis artery circulations and its mainly branches, neurosurgeon can therapy mostly ipsilateral anterior part of Aneurysms land in willis artery circulations, median cerebral artery 1 to 3 segment (M1-3) and its mainly branches.and a small part Aneurysms land in contralateral medial side,distal upper clinoid process segments of the internal carotid artery and 1st segment of median cerebral artery.There are a small part of aneurysms land in ipsilateral medial side anterior part of Aneurysms landing in willis artery circulations and some internal carotid artery ophthalmic arterysegmental aneurysm and mostly ipsilateral lateralisor distal and bifurcations anterior part of aneurysms land in upper clinoid process segments of the internal carotid artery and M1 and mostly aneurysms land in posterior circulation can not be treated perfectly make performing several operational approaches or staged operations because of Multiple Intracranial Aneurysms land bilaterally with distribution of extensive regions are total essential. But, all these will have to increase much more serious injury, psychological pressure and economic burden of the disease. It is of very important to investigate a new approach that can expose site where Multiple Intracranial Aneurysms landing for getting therapy these aneurysms well.
Endovascular treating Multiple Intracranial Aneurysms is the most dazzling fields with the rapid development.Since Serbinenko in Former Soviet occluse aneurysms using detachable balloon initiating advocated earlier of endovascular treating aneurysms in 1973 to Guglielmi invented electronic detachable coil leading to endovascular treating aneurysms revolutionary advances.The methods of endovascular treating aneurysms including when embolizate aneurysms by using simply spring coil embolization, aided by stents,aided by balloon, etc.Which isolate aneurysms whereabout blood circulatory system with peculiar advantages of treating all the aneurysms where micro-catheter can get,having no disturbs to its surrounding structures, performing under local anesthesia state, avoiding suffering from open craniotomy, working carries out smoothly when under severe condition and illness conditions with disabilities in clipping aneurysms.For example, it show has advantages when endovascular treating aneurysms landing rock section, cavernous segment, internal carotid artery ophthalmic artery segment and posterior circulation. However, it show disadvantages when cerebral vasospasm seriously internal carotid or vertebro-basilarartery stricture, plaque formation severely,curved configuration of vessel and so on will lead to failing to endovascular treating and operate too long time will increased risk inevitably, as cerebral vasospasm extensively and seriously during acute stage easily.
As is difficult problem faced by endovascular treating Multiple Intracranial Aneurysms, embolic materials have its own some defectiveness limiting the kind of therapy, too.Some of unruptured and wide neck Multiple Intracranial Aneurysms perform excessive embolization now and then will cause bleeding of these ruptured intracranial aneurysms moreover. International Subarachnoid Aneurysm Trial (ISAT) in 2002 show that endovascular treating aneurysm is superior toneurosurgical clipping them by followed up clinic for a long time. People believe in that endovascular treating Multiple Intracranial Aneurysms will possess more wide application with the developing of interventional materials.
There are some Multiple Intracranial Aneurysms that can not been got well therapy in one-stage operate, priority to treat ruptured aneurysms then follow up clinic for about two months before treating other ruptured aneurysms.Neurosurgeon must evaluate carefully what measures should be taken when Multiple Intracranial Aneurysms are very complicated landing in bilateral internal carotid artery,internal carotid or vertebro-basilarartery much like this one stage or two stages, a single or two approaches,.interventional or operative process.All these above are questions which are worth discussing at present undoubtedly.
The study is aim to research Multiple Intracranial Aneurysms including these 3 aspects:the first,To observe the expression and the significance of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9) and vascular endothelial growth factor(VEGF) in human Intracranial Saccular Aneurysms(ISA). by immunohistochemistry S-ABC method and transmission electron microscope technique respectively.Then got these viewpoint that MMP-2,MMP-9 and VEGF might play an primary role in the pathogenesis and rapture of ISA especial in multiple intracranial aneurysms in cellar and molecular level and super morphology aspect. Secondly, To research the exposure of Willis Circle and its Mainly Branch in a microscopic anatomy way by Modified Frontotemporal Zygomatie(FTZ) craniotomy Simultaneously posterior to standard ptefional craniotomies were performed on the same 9 sides of these cadaveric heads specimens, providing reference for clinical operate on Multiple Intracranial Aneurysms.Thirdly,To explore the good treatment of multiple intracanrial aneurysms and to improve its outcomes by collecting patients'data affected Multiple Intracranial Aneurysms in Center for Neurosurgery of PLA,Department of Neurosurgery,Wuhan General Hospital,Guangzhou Command PLA,from January 2008 to December 2009.
PartⅠThe Expression and Significance of Vascular Endothelial Growth Factor and Matrix Metalloproteinases-2,9 in Intracranial Saccular Aneurysms
Objective To observe the expression and the significance of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9) and vascular endothelial growth factor(VEGF) in human Intracranial Saccular Aneurysms(ISA).
Methods Sixteen patients'multiple intracanrial aneurismal sample were divided into group 1;including 20 cases PCoAAN,11 cases ACoA AN,3 cases MCA AN,4 cases AchA AN,1 case BA-SCA AN.Seventeen patients'single intracranial aneurismal sample were divided into group 2, including 9 cases PCoA AN,5 cases ACoA AN,3 cases MCA AN;Nine severely drain trauma patients'MCA or its main branches complying surgical excision of deactivated cerebral tissues.All which were collected in the Department of Neurosurgery, Wuhan General Hospital, Guangzhou Command of PLA, from January,2008 to September,2008.The expression of MMP-2,MMP-9, VEGF and super-microstructure changes were observed with immunohistochemistry and transmission electron microscope technique respectively.And the data were analyzed by chi-square test between groups.
Results MMP-2,MMP-9 and VEGF in ISA(groupland 2) were significantly higher than in MCA(group3)(P<0.05),and on significance between groupland 2(P>0.05).Immunoreactive substances were mainly brown-yellow granules. Immuno-positive cells were long fusiform or star types, looking like and smooth muscle cells hepatocyte,distributed mainly mediumfilm layer where near endometrium and outer membrane especially. Endothelial cells were degenerated and collaped.A number of vesicles and swollen mitochondria were present in the cytoplasm.These aneurysmal walls varied in thickness and were composed of regenerative smooth muscle cells and collagenous fibres.
Conclusions The over-expression of MMP-2, MMP-9 and VEGF might play an primary role in the pathogenesis and rapture of ISA especial in multiple intracranial saccular aneurysms.Playing a key role with degeneration happened in artery tube wall,degradation of extracellular matrix, gradual extension and rupture of saccular aneurysms.
Part II The Applied Micro-anatomical Study on Modified Frontotemporal Zygomatic Approach Exposure to Willis Circle and Its Mainly Branches
Objective To research the exposure of Willis circle and its mainly branches in a microscopic anatomy way by Modified Frontotemporal Zygomatic (FTZ) craniotomy,discussing its clinical application value.
Methods Standard ptefional approach craniotomies were performed on 9 sides of 9 adult wet cadaveric heads specimens,with the help of micro-grinding drill and surgical microscope,the sphenoid ridge and part of anterior clinoid process and sclerotin were removed to expose Willis Circle and its Mainly Branch.especially the basilar artery,the contralateral upper clinoid process segment of internal carotid artery and horizontal section of midge cerebral artery(M1);Simultaneously, Modified Frontotemporal Zygomatic (FTZ) approach craniotomies were performed on the same 9 sides of these cadaveric heads specimens, traditional frontotemporal orbitozygomatic were modified by exposing largely anterior skull base(75%)and protecting orbital walls, Comparing the two groups'lengths applied its own operational approaches analyzing by paired t test.
Results Modified FTZ approach could better expose Willis Circle and its Mainly Branch,especially the basilar artery(BA),contralateral supraclinoid segment of internal carotid artery(ICA)and horizontal section of midge cerebral artery(M1)compared to the standard pterional approach.Comparing the two groups' lengths applied its own operational approaches, there were statistical significance (P<0.05).
Conclusion Modified FTZ approach can be used to deal with the multiple aneurysms located in Willis Circle and its Mainly Branch compared to the standard pterional approach,and the craniotomy is an alternative to the standard pterional approach maybe, which is worth of furthermore investigate yet.
PartⅢThe discussion on therapeutic schemes of multiple intracranial aneurysms:A Report of 35 Cases
Objective To investigate the therapeutic schemes of multiple intracranial aneurysms.
Methods The clinical data of 35 patients with multiple intracranial aneurysms. ,who were treated in the Department of Neurosurgery, Wuhan General Hospital, Guangzhou Command of PLA, from January,2008 to December,2009,were analyzed retrospectively. They were divided into three groups operational group, interventional therapic group, operational both interventional therapic group by therapeutic schemes applied to these patients. Those factors before treatment that might influence the outcome were evaluated, including ages,gender,number of the aneurysms, the location of the aneurysms, lateral side the aneurysms, and size the aneurysms, preoperative Hunt-Hess grades,preoperative Fisher grades.The patients'outeome at discharge according to the Glasgow Outcome Scale was divided into two categories: favorable (4-5 grades)or unfavorable(1-3 grades).Chi-square test was applied to analysis preoperative factors that might influence the outcome respectively,and Logistic multivariable analysis of the factors related to the prognosis was performed in the patients with multiple intracranial aneurysms.
Results Favorable outcome in 24 cases,unfavorable in 11 cases, however. The preoperative patient's ages,Hunt-Hess grades and Fisher grades were predictors for the outcome by single factor analysis (P<0.30, referring to related literatures).The results of multiple Logistic regression analysis showed that no factor was predictors for the outcome (P>0.05).
Conclusions The prognosis in patients with MIA are significantly and negatively related to the patients ages, Fisher grade and Hunt-Hess grade before treatment.It is key to improve therapeutic effects with multiple intracranial aneurysms by selecting appropriate therapeutic schemes on the basis of the patients actual conditions, emphasizing personalization therapy.Which can get the same better effects by operation, interventional therapyor operation both interventional therapy any way And which are worth of the further discussing undoubtedly.
引文
[1]Kaminogo M,Yonekura M,Shibata S.Incidence and outcome of mutip le intracranial aneurysmsin a defined population [J].stroke,2003; 34(1): 16-21.
[2]Boris Krischek Ituro Inoue. The genetics of intracranial aneurysms[J].J Hum Genet,2006; 5 (1):587-594
[3]Shojima M, Oshima M, Takagi K, et al.Magnitude and role of wall shear stress on cerebral aneurysm:computational fluid dynamic stud-y of 20 milddle cerebral artery aneurysms[J].Stroke,2004; 13(4):281-291.
[4]Caird J,Burke M,Roberts G,et al. Apolipoprotein(A)expression in intracranial aneurysms[J].Neurosurgery,2003; 52(4):854-859.
[5]Feng Y, Wada S,Tsubota K,et al.The application of computer simulation in the genesis and development of intracranial aneurysms[J].Technol Health Care.2005; 13(4):281-291.
[6]Futami K,Yamashita J,Higashi S.Do cerebral aneurysms originate at the site of medial defects? Experimental aneurysms at the fenestration of the anterior cerebral artery in rats[J].Surg Neurol,1998; 50(2):141-146
[7]Ferro JM,Canhao P,Peralta R.Update On subaraehnoid haemorrhage[J].J Neurol,2008; 255(4):465-479.
[8]Cheong JJ,Ghinea N,van Gelder JM. Estimating the annual rate of d e novo multiple aneurysms:three statistical approaches.Neurosurg Focus,2004; 1 7 (5):E8
[9]马廉亭.动脉瘤性蛛网膜下腔出血的诊治规范[J].中国现代神经疾病杂志,2004；4(1)：6-9.
[10]Clatterbuck RE, Tamargo RJ. Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery,2005; 57(1 Suppl):160-163
[11]B. G. Shinl,J. S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1): 33-38
[12]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases[J].J Neurosurg Sci.2006;50(1):1-8
[13]Wehman, J Christopher, Hanel, Ricardo A, et al.Giant Cerebral Aneurysms: Endovascular Challenges[J],Neurosurgery,2006; 59(5):125-138
[14]Solander S,ulhoa A,Vinuela,F etal.Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils[J],J Neurosurg, 1999;90(2):857-864.
[15]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko.2009;13(1):53-57
[16]Lawton Michael T,Quinones-Hinojosa, Alfredo Sanai, etal.Combined Microsurgical and Endovascular Management of Complex Intracranial Aneurysms[J],Neurosurgery,2003;52(2):263-275
[17]Hoh, Brian L, Carter, Bob S,Budzik, Ronald F,etal.Results after Surgical and Endovascular Treatment of Paraclinoid Aneurysms by a Combined Neurovascular Team[J],Neurosurgery,2001; 48 (1):78-90
[1]中华病理学杂志编辑委员会,《全国免疫组织化学技术与诊断标准化专题研讨会》会议记要.中华病理学杂志,1996；25(6)：326.
[2]Kassell NF, Torner JC,Haley EC Jr, et al.The international cooperative study on the timing of aneurysm surgery. Part 1.Overall management results[J].J Neurosurg,1990;73 (8):18-36.
[3]Weir B.Unruptured intracranial aneurysms:a review[J].J Neurosurg,2002;96 (26):3-42.
[4]赵刚,李铁林,王为民,等.胎儿脑动脉分叉部构筑发育的研究[J].中国神经精神疾病杂志,2002；28(6)：407-409.
[5]Kassell NF, Torner JC, Haley EC Jr, et al.The international cooperative study on the timing of aneurysm surgery. Part 1.Overall management results [J]. Neurosurg,1990;73 (6):18-36.
[6]Caird J,Burke M,Roberts G, etal.Apolipoprotein (A) expression in intracranial aneurysms [J].Neurosurgery,2003;52 (4):854-859
[7]Pearce WH,Shively VP.Abdominal aortic aneurysm as a complex multifactorial disease:interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs[J].Ann N Y Acad Sci,2006;1085 (22):117-132.
[8]Skirgaudas M,Awad IA,Kim J,et al.Expression of angiogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms [J].Neurosurgery,1996;39(3):537-547
[9]Sandalcioglu IE, Wende D, Eggert A,et al. VEGF plasma levels in non-ruptured intracranial aneurysms[J].Neurosurg Rev,2006;29(1):26-29.
[10]Krex D,Kotteck K,Konig IR,et al.Matrix metalloproteinase-9 coding sequence single-nucleotide polymorphisms in Caucasians with intracranial aneurysms[J].Neurosurgery,2004;55(1):207-212.
[11]Bergers G,Brekken R,McMaho G,et al.MMP and triggers the angiogenesis switch during carciobiogenesis [J].Nat Cell Biol,2000;2(10):737-744
[12]Kadirvel R, Dai D, Ding YH,etal.Endovascular treatment of aneurysms: healing mechanisms in a Swine model are associated with increased expression of matrix metalloproteinases, vascular cell adhesion molecule-1, and vascular endothelial growth factor, and decreased expression of tissue inhibitors of matrix metalloproteinases[J],Am J Neuroradiol,2007;28(5):849-856
[13]Perigny M, Bairati I, Harvey I, et al.Role of immunohistochemical overexp ression of matrix metallop roteinasesMMP-2 and MMP-9 in the p rognosis of death by ovarian cancer[J].Am J Clin Pathol,2008;129 (2):226-231
[14]廖旭兴,马廉亭,李俊,等.颅内囊性动脉瘤瘤壁的组织结构变化及其临床意义[J].中国临床神经外科杂志,2009；14(11)：669-672.
[15]Joo SP, Kim TS, Lee IK, et al.The role of collagen type I alpha2 polymorphisms:intracranial aneurysms in Koreans[J].Surg Neurol,2009; 72(1)：48-53.
[16]王嵘,齐巍,赵继宗,等.颅内囊性动脉瘤壁Ⅰ、Ⅲ型胶原分布的病理组织学研究[J].北京医学,2003；25(5)：12-16
[17]朱玉方,庞琦,栾立明,等.颅内动脉瘤Ⅲ型胶原蛋白α1链基因多态性检测分析[J].中华神经外科杂志,2009；25(2)：23-27
[18]华涛,张东,赵元立,等.COL3A1基因与颅内动脉瘤Ⅲ型胶原蛋白稳定性的关系[J].中华医学杂志,2008；88(7)：23-25
[19]M.G.亚萨吉尔著.显微神经外科学(Ⅰ卷)[M].凌锋主译.北京.中国科学技术出版社,2001：274-319.
[20]Proust F,G6rardin E,Chazal J.,Untuptttred intracranial aneurysm and microsurgieal exclusion:the need of a randomized study of surgery versus natural history[J].J Neuroradiol,2008;35(2):109-115.
[1]凌锋.显微神经外科学(Ⅰ卷)[M].北京：中国科学技术出版社,2001：274-319.
[2]田继辉,孙涛,于春江,等。额颞及额颞颧入路中面神经额颞支的保护[J],中华神经外科杂志,2004；20(4)：331-333.
[3]Kassell NF, Torner JC, Haley EC Jr, et al.The international cooperative study on the timing of aneurysm surgery. Part 1.Overall management results[J]. J Neurosurg,1990;73 (1):18-36
[4]Yamashiro S,Nishi T,Koga K,et al.Improvement of quality of life in patients surgically treated for asymptomatic unruptured intracranial aneurysms[J].J Neurol Neurosurg Psychiatry,2007;78 (5):497-500
[5]Bernhard Kis,Wwener Weber.Treatment of unruptured cerebral aneurysms do we have sufficient decision criteria[J]? Clin Neuroradiol,2007;17 (3):159-166
[6]Clatterbuck RE, Tamargo RJ.Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery.2005;57(1 Suppl):160-163
[7]B.G.Shinl,J. S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1):33-38
[8]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases[J].J Neurosurg Sci.2006;50(1):1-8
[9]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko.2009;Jan-Mar,(1):53-57
[10]Oshiro EM, RiniDA, Tamargo RJ.Contralateral app roaches to bilateral cerebral aneurysms:a microsurgical anatomical study[J].J Neurosurg,1997; 87 (2):163-169.
[11]M. Suzukil,H.Fujisawal,H.Ishiharal,etal.Side selection of pterional approach for anterior communicating artery aneurysms-surgical anatomy and strategy[J],Acta Neurochir (Wien) 2008;150(1):31-39
[12]周良辅.颅底外科浅论.中国神经精神疾病杂志[J],2008；34(3)：129-130
[1]Clatterbuck RE, Tamargo RJ.Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery,2005;57(1 Suppl):160-163
[2]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases [J],J Neurosurg Sci,2006;50(1):1-8
[3]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko,2009;Jan-Mar,(1):53-57.
[4]Ferro JM,Canhao P,Peralta R.Update On subaraehnoid haemorrhage[J].J Neurol,2008;255(4):465-479
[5]Kaminogo M,Yonekura M,Shibata S.Incidence and outcome of mutip le intracranial aneurysmsin a defined population [J],stroke,2003;34(1):16-21.
[6]MontalvemeF,Musaccio M,Tolentino V,et al.Endovascuar numagerment for intracranial ruptured aneurysms in elderly patients:outcome and technical aspects[J],Neuroradiology,2005;47(6):446-457
[7]Yoshimoto Y,Wakai s.Satoh A,et al.Intraparenchymal and intrasylvian haematomas secondary to ruptured middle cerebral artery aneurysms:prognostic factors and thempeutic considerations[J],Br J Neurosurg,1999;13 (1):18-24.
[8]MoccoJ,Ransom ER,Komotar RJ,et al.Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage [J].Neurosurgery,2006;59(3):529-538.
[9]B.G. Shinl,J.S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1): 33-38
[10]马廉亭.颅内动脉瘤治疗方法的选择[J].中国临床神经外科杂志,2001；6(2)：65.
[11]王芙昱,许百男,李宝民,等。颅内多发动脉瘤外科治疗的临床研究。临床神经外科杂志,2008；5(1)：9-12
[12]Proust F,G6rardin E,Chazal J.,Untuptttred intracranial aneurysm and microsurgieal exclusion:the need of a randomized study of surgery versus natural history[J],J Neuroradiol,2008;35(2):109-115.
[1]王忠诚.神经外科学(M).武汉：湖北科学技术出版社.1998：583-586.
[2]Boris Krischek Ituro Inoue. The genetics of intracranial aneurysms[J].J Hum Genet,2006;51(6):587-594
[3]Shojima M, Oshima M, Takagi K, et al.Magnitude and role of wall shear stress on cerebral aneurysm:computational fluid dynamic stud-y of 20 milddle cerebral artery aneurysms[J].Stroke,2004; 13 (4):281-291.
[4]Caird J,Burke M,Roberts G,et al.Apolipoprotein(A)expression in intracranial aneurysms[J].Neurosurgery,2003;52(4):854-859.
[5]Feng Y, Wada S,Tsubota K,et al.The application of computer simulation in the genesis and development of intracranial aneurysms[J].Technol Health Care,2005;13(4):281-91.
[6]Futami K,Yamashita J,Higashi S.Do cerebral aneurysms originate at the site of medial defects? Experimental aneurysms at the fenestration of the anterior cerebral artery in rats[J].Surg Neurol,1998;50(2):141-146
[7]Khasigovp Z, Podobed O V, Gracheva T S,et al.Role of matrixmetallo-proteinases and their inhibitors in tumor invasion and metastasis[J]. Biochemistry (Mosc),2003;68(7):711-717
[8]Rydlova M, Holubec L, Ludvikova M, et al.Biological activity and clinical imp lications of the matrixmetallop roteinases[J].Anticancer Res,2008; 28 (2B):1389-1397
[9]Ruigrok YM,Rinkel GJ, Wijmenga C.Genetics of Intracranial Aneurysms[J]. Lancet Neurol,2005;4(3):179-189.
[10]McMillanWD,Patterson BK, Keen RR, et al.In situ localization and quantification of seventy-two-kilodalton type Ⅳ collagenase in aneurysmal, occlusive and normal aorta[J].J Vasc Surg,1995;22 (3):295-305.
[11]Bruno G,Todor R,Lewis I,et al.Vascular extracellular matrix remodeling in cerebral aneurysms.J Neurosurg,1998;89(3):431-440.
[12]Chyatte D, Lewis I. Gelatinase activity and the occurrence of cerebral aneurysms [J].Stroke,1997;28(4):799-804.
[13]Mimata C, Kitaoka M, Nagahiro S,et al.Differential distribution and expressions of collagens in the cerebral aneurysmal wall.Acta Neuropathol. 1997;94(3):197-206.
[14]van den Berg JS,Pals G,Arwert F, Hennekam RC,et al.Type Ⅲ collagen deficiency in saccular intracranial aneurysms[J].Defect in gene regulation? 1999;30(8):1628-31.。
[15]Ruigrok YM, Rinkel GJ, Wijmenga C, et al.Association analysis of genes involved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort[J].cere brovasc Dis.2009;28 (2): 131-134.
[16]Veikkola T,Karkkainen M,Claesson-Welsh L,et al.Regulation of angiogenesis via vascular endothelial growth factor receptor[J].Cancer Res, 2000;60(2):202-212.
[17]Frosen J,Piippo A,Paetau A,et al.Remodeling of saccular cerebral artery aneurysm wall is associated with rupture:hislological analysis of 24 unruptured and 42 raptured cases[J].Stroke,2004,35(10):2287-2293.
[18]Fabrice Bonneville, Nader Sourour, Alessandra Biondi. Intracranial Aneurysms: an Overview [J].Neuroimaging Clinics of North America,2006; 16 (3): 371-382
[19]Ruigrok YM, Rinkel GJ. Genetics of intracranial aneurysms[J].Stroke, 2008;39(3):1049-55.
[1]Juvela S.Risk factors for multiple intracranial aneurysms[J].Stroke,2000; 31(2):392.
[2]F. Baumann, Nadia Khan Y.Yonekawa, et al.Patient and aneurysm characteristics in multiple intracranial aneurysms[J],Acta Neurochir Suppl,2008; 103 (1) 19-28.
[3]van der Wee N, Rinkel GJ, Hasan D, et al.Detection of subarachnoid haemorrhage on early CT:is lumbar puncture still needed after a negative scan? [J].J Neurol Neurosurg Psychiatry,1995;58(3):357-359.
[4]马廉亭.神经外科学血管内治疗[M].北京：人民军医出版社.1995；214-216.
[5]Brott T,Mandybur TI.Case-control study of clinical outcome after aneurismal subaraehnoid hemorhage[J].Neurosurg,1986;19(8):891-896.
[6]Venema HW,Hulsman FJ,Heeten GJ.CT angiography of the circle of wills and intracranial internal carotid arteries:maximum intensity projection with matched mask bone elimination feasibi-lity study[J].Radiology,2001;218(3): 898-902.
[7]SakamotO S.Kiura Y,Shibukawa M,et al.Subtracted 3D CT angiography for evaluation of intern al carotid artery aneurysms:comparison with conventional digital subtraction angiography.AJNR Am J Neumradiol[J], 2006;27(13):1332-337.
[8]Dehdashti AR,Binaghi S,Uske A,et al.Comparison of multi-slice computerized tomography and digital subtraction angiography in the postoperative evaluation of patients with clipped aneurysms[J].J Neurosurg,2006;104(23): 395-403.
[9]Davis CP,Ld ME,Romanweski BJ.Human aorta:preliminary results with virtual endoscopy based on three-dimensional MR imaging datasets [J].Radiology, 1996;199(1):37-40.
[10]Clatterbuck RE, Tamargo RJ.Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery,2005;57(1 Suppl):160-163
[11]11.B.G. Shinl,J.S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1):33-38
[12]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases[J].J Neurosurg Sci,2006;50(1):1-8
[13]廖旭兴,马廉亭,杨铭,等。扩大额颞颧弓入路暴露Willis环及其主要分支的应用显微解剖学研究[J].中国神经精神疾病杂志,2009；35(5)：304-306
[14]Wehman, J Christopher, Hanel, Ricardo A, et al.Giant Cerebral Aneurysms: Endovascular Challenges[J],Neurosurgery,2006;59 (5):125-138
[15]Solander S,ulhoa A,Vinuela F,et al.Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils[J].J Neurosurg, 1999;90(7):857-864.
[16]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko,2009;Jan-Mar,(1):53-57
[17]Hoh Brian L, Carter Bob S,Budzik Ronald F, et al.Results after Surgical and Endovascular Treatment of Paraclinoid Aneurysms by a Combined Neurovascular Team[J].Neurosurgery,2001;48 (1):78-90
[18]Lawton Michael T, Quinones-Hinojosa, Alfredo Sanai,et al.Combined Microsurgical and Endovascular Management of Complex Intracranial Aneurysms[J].Neurosurgery,2003;52(2):263-275
[2]Boris Krischek Ituro Inoue. The genetics of intracranial aneurysms[J].J Hum Genet,2006; 5 (1):587-594
[3]Shojima M, Oshima M, Takagi K, et al.Magnitude and role of wall shear stress on cerebral aneurysm:computational fluid dynamic stud-y of 20 milddle cerebral artery aneurysms[J].Stroke,2004; 13(4):281-291.
[4]Caird J,Burke M,Roberts G,et al. Apolipoprotein(A)expression in intracranial aneurysms[J].Neurosurgery,2003; 52(4):854-859.
[5]Feng Y, Wada S,Tsubota K,et al.The application of computer simulation in the genesis and development of intracranial aneurysms[J].Technol Health Care.2005; 13(4):281-291.
[6]Futami K,Yamashita J,Higashi S.Do cerebral aneurysms originate at the site of medial defects? Experimental aneurysms at the fenestration of the anterior cerebral artery in rats[J].Surg Neurol,1998; 50(2):141-146
[7]Ferro JM,Canhao P,Peralta R.Update On subaraehnoid haemorrhage[J].J Neurol,2008; 255(4):465-479.
[8]Cheong JJ,Ghinea N,van Gelder JM. Estimating the annual rate of d e novo multiple aneurysms:three statistical approaches.Neurosurg Focus,2004; 1 7 (5):E8
[9]马廉亭.动脉瘤性蛛网膜下腔出血的诊治规范[J].中国现代神经疾病杂志,2004；4(1)：6-9.
[10]Clatterbuck RE, Tamargo RJ. Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery,2005; 57(1 Suppl):160-163
[11]B. G. Shinl,J. S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1): 33-38
[12]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases[J].J Neurosurg Sci.2006;50(1):1-8
[13]Wehman, J Christopher, Hanel, Ricardo A, et al.Giant Cerebral Aneurysms: Endovascular Challenges[J],Neurosurgery,2006; 59(5):125-138
[14]Solander S,ulhoa A,Vinuela,F etal.Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils[J],J Neurosurg, 1999;90(2):857-864.
[15]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko.2009;13(1):53-57
[16]Lawton Michael T,Quinones-Hinojosa, Alfredo Sanai, etal.Combined Microsurgical and Endovascular Management of Complex Intracranial Aneurysms[J],Neurosurgery,2003;52(2):263-275
[17]Hoh, Brian L, Carter, Bob S,Budzik, Ronald F,etal.Results after Surgical and Endovascular Treatment of Paraclinoid Aneurysms by a Combined Neurovascular Team[J],Neurosurgery,2001; 48 (1):78-90
[1]中华病理学杂志编辑委员会,《全国免疫组织化学技术与诊断标准化专题研讨会》会议记要.中华病理学杂志,1996；25(6)：326.
[2]Kassell NF, Torner JC,Haley EC Jr, et al.The international cooperative study on the timing of aneurysm surgery. Part 1.Overall management results[J].J Neurosurg,1990;73 (8):18-36.
[3]Weir B.Unruptured intracranial aneurysms:a review[J].J Neurosurg,2002;96 (26):3-42.
[4]赵刚,李铁林,王为民,等.胎儿脑动脉分叉部构筑发育的研究[J].中国神经精神疾病杂志,2002；28(6)：407-409.
[5]Kassell NF, Torner JC, Haley EC Jr, et al.The international cooperative study on the timing of aneurysm surgery. Part 1.Overall management results [J]. Neurosurg,1990;73 (6):18-36.
[6]Caird J,Burke M,Roberts G, etal.Apolipoprotein (A) expression in intracranial aneurysms [J].Neurosurgery,2003;52 (4):854-859
[7]Pearce WH,Shively VP.Abdominal aortic aneurysm as a complex multifactorial disease:interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs[J].Ann N Y Acad Sci,2006;1085 (22):117-132.
[8]Skirgaudas M,Awad IA,Kim J,et al.Expression of angiogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms [J].Neurosurgery,1996;39(3):537-547
[9]Sandalcioglu IE, Wende D, Eggert A,et al. VEGF plasma levels in non-ruptured intracranial aneurysms[J].Neurosurg Rev,2006;29(1):26-29.
[10]Krex D,Kotteck K,Konig IR,et al.Matrix metalloproteinase-9 coding sequence single-nucleotide polymorphisms in Caucasians with intracranial aneurysms[J].Neurosurgery,2004;55(1):207-212.
[11]Bergers G,Brekken R,McMaho G,et al.MMP and triggers the angiogenesis switch during carciobiogenesis [J].Nat Cell Biol,2000;2(10):737-744
[12]Kadirvel R, Dai D, Ding YH,etal.Endovascular treatment of aneurysms: healing mechanisms in a Swine model are associated with increased expression of matrix metalloproteinases, vascular cell adhesion molecule-1, and vascular endothelial growth factor, and decreased expression of tissue inhibitors of matrix metalloproteinases[J],Am J Neuroradiol,2007;28(5):849-856
[13]Perigny M, Bairati I, Harvey I, et al.Role of immunohistochemical overexp ression of matrix metallop roteinasesMMP-2 and MMP-9 in the p rognosis of death by ovarian cancer[J].Am J Clin Pathol,2008;129 (2):226-231
[14]廖旭兴,马廉亭,李俊,等.颅内囊性动脉瘤瘤壁的组织结构变化及其临床意义[J].中国临床神经外科杂志,2009；14(11)：669-672.
[15]Joo SP, Kim TS, Lee IK, et al.The role of collagen type I alpha2 polymorphisms:intracranial aneurysms in Koreans[J].Surg Neurol,2009; 72(1)：48-53.
[16]王嵘,齐巍,赵继宗,等.颅内囊性动脉瘤壁Ⅰ、Ⅲ型胶原分布的病理组织学研究[J].北京医学,2003；25(5)：12-16
[17]朱玉方,庞琦,栾立明,等.颅内动脉瘤Ⅲ型胶原蛋白α1链基因多态性检测分析[J].中华神经外科杂志,2009；25(2)：23-27
[18]华涛,张东,赵元立,等.COL3A1基因与颅内动脉瘤Ⅲ型胶原蛋白稳定性的关系[J].中华医学杂志,2008；88(7)：23-25
[19]M.G.亚萨吉尔著.显微神经外科学(Ⅰ卷)[M].凌锋主译.北京.中国科学技术出版社,2001：274-319.
[20]Proust F,G6rardin E,Chazal J.,Untuptttred intracranial aneurysm and microsurgieal exclusion:the need of a randomized study of surgery versus natural history[J].J Neuroradiol,2008;35(2):109-115.
[1]凌锋.显微神经外科学(Ⅰ卷)[M].北京：中国科学技术出版社,2001：274-319.
[2]田继辉,孙涛,于春江,等。额颞及额颞颧入路中面神经额颞支的保护[J],中华神经外科杂志,2004；20(4)：331-333.
[3]Kassell NF, Torner JC, Haley EC Jr, et al.The international cooperative study on the timing of aneurysm surgery. Part 1.Overall management results[J]. J Neurosurg,1990;73 (1):18-36
[4]Yamashiro S,Nishi T,Koga K,et al.Improvement of quality of life in patients surgically treated for asymptomatic unruptured intracranial aneurysms[J].J Neurol Neurosurg Psychiatry,2007;78 (5):497-500
[5]Bernhard Kis,Wwener Weber.Treatment of unruptured cerebral aneurysms do we have sufficient decision criteria[J]? Clin Neuroradiol,2007;17 (3):159-166
[6]Clatterbuck RE, Tamargo RJ.Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery.2005;57(1 Suppl):160-163
[7]B.G.Shinl,J. S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1):33-38
[8]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases[J].J Neurosurg Sci.2006;50(1):1-8
[9]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko.2009;Jan-Mar,(1):53-57
[10]Oshiro EM, RiniDA, Tamargo RJ.Contralateral app roaches to bilateral cerebral aneurysms:a microsurgical anatomical study[J].J Neurosurg,1997; 87 (2):163-169.
[11]M. Suzukil,H.Fujisawal,H.Ishiharal,etal.Side selection of pterional approach for anterior communicating artery aneurysms-surgical anatomy and strategy[J],Acta Neurochir (Wien) 2008;150(1):31-39
[12]周良辅.颅底外科浅论.中国神经精神疾病杂志[J],2008；34(3)：129-130
[1]Clatterbuck RE, Tamargo RJ.Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery,2005;57(1 Suppl):160-163
[2]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases [J],J Neurosurg Sci,2006;50(1):1-8
[3]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko,2009;Jan-Mar,(1):53-57.
[4]Ferro JM,Canhao P,Peralta R.Update On subaraehnoid haemorrhage[J].J Neurol,2008;255(4):465-479
[5]Kaminogo M,Yonekura M,Shibata S.Incidence and outcome of mutip le intracranial aneurysmsin a defined population [J],stroke,2003;34(1):16-21.
[6]MontalvemeF,Musaccio M,Tolentino V,et al.Endovascuar numagerment for intracranial ruptured aneurysms in elderly patients:outcome and technical aspects[J],Neuroradiology,2005;47(6):446-457
[7]Yoshimoto Y,Wakai s.Satoh A,et al.Intraparenchymal and intrasylvian haematomas secondary to ruptured middle cerebral artery aneurysms:prognostic factors and thempeutic considerations[J],Br J Neurosurg,1999;13 (1):18-24.
[8]MoccoJ,Ransom ER,Komotar RJ,et al.Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage [J].Neurosurgery,2006;59(3):529-538.
[9]B.G. Shinl,J.S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1): 33-38
[10]马廉亭.颅内动脉瘤治疗方法的选择[J].中国临床神经外科杂志,2001；6(2)：65.
[11]王芙昱,许百男,李宝民,等。颅内多发动脉瘤外科治疗的临床研究。临床神经外科杂志,2008；5(1)：9-12
[12]Proust F,G6rardin E,Chazal J.,Untuptttred intracranial aneurysm and microsurgieal exclusion:the need of a randomized study of surgery versus natural history[J],J Neuroradiol,2008;35(2):109-115.
[1]王忠诚.神经外科学(M).武汉：湖北科学技术出版社.1998：583-586.
[2]Boris Krischek Ituro Inoue. The genetics of intracranial aneurysms[J].J Hum Genet,2006;51(6):587-594
[3]Shojima M, Oshima M, Takagi K, et al.Magnitude and role of wall shear stress on cerebral aneurysm:computational fluid dynamic stud-y of 20 milddle cerebral artery aneurysms[J].Stroke,2004; 13 (4):281-291.
[4]Caird J,Burke M,Roberts G,et al.Apolipoprotein(A)expression in intracranial aneurysms[J].Neurosurgery,2003;52(4):854-859.
[5]Feng Y, Wada S,Tsubota K,et al.The application of computer simulation in the genesis and development of intracranial aneurysms[J].Technol Health Care,2005;13(4):281-91.
[6]Futami K,Yamashita J,Higashi S.Do cerebral aneurysms originate at the site of medial defects? Experimental aneurysms at the fenestration of the anterior cerebral artery in rats[J].Surg Neurol,1998;50(2):141-146
[7]Khasigovp Z, Podobed O V, Gracheva T S,et al.Role of matrixmetallo-proteinases and their inhibitors in tumor invasion and metastasis[J]. Biochemistry (Mosc),2003;68(7):711-717
[8]Rydlova M, Holubec L, Ludvikova M, et al.Biological activity and clinical imp lications of the matrixmetallop roteinases[J].Anticancer Res,2008; 28 (2B):1389-1397
[9]Ruigrok YM,Rinkel GJ, Wijmenga C.Genetics of Intracranial Aneurysms[J]. Lancet Neurol,2005;4(3):179-189.
[10]McMillanWD,Patterson BK, Keen RR, et al.In situ localization and quantification of seventy-two-kilodalton type Ⅳ collagenase in aneurysmal, occlusive and normal aorta[J].J Vasc Surg,1995;22 (3):295-305.
[11]Bruno G,Todor R,Lewis I,et al.Vascular extracellular matrix remodeling in cerebral aneurysms.J Neurosurg,1998;89(3):431-440.
[12]Chyatte D, Lewis I. Gelatinase activity and the occurrence of cerebral aneurysms [J].Stroke,1997;28(4):799-804.
[13]Mimata C, Kitaoka M, Nagahiro S,et al.Differential distribution and expressions of collagens in the cerebral aneurysmal wall.Acta Neuropathol. 1997;94(3):197-206.
[14]van den Berg JS,Pals G,Arwert F, Hennekam RC,et al.Type Ⅲ collagen deficiency in saccular intracranial aneurysms[J].Defect in gene regulation? 1999;30(8):1628-31.。
[15]Ruigrok YM, Rinkel GJ, Wijmenga C, et al.Association analysis of genes involved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort[J].cere brovasc Dis.2009;28 (2): 131-134.
[16]Veikkola T,Karkkainen M,Claesson-Welsh L,et al.Regulation of angiogenesis via vascular endothelial growth factor receptor[J].Cancer Res, 2000;60(2):202-212.
[17]Frosen J,Piippo A,Paetau A,et al.Remodeling of saccular cerebral artery aneurysm wall is associated with rupture:hislological analysis of 24 unruptured and 42 raptured cases[J].Stroke,2004,35(10):2287-2293.
[18]Fabrice Bonneville, Nader Sourour, Alessandra Biondi. Intracranial Aneurysms: an Overview [J].Neuroimaging Clinics of North America,2006; 16 (3): 371-382
[19]Ruigrok YM, Rinkel GJ. Genetics of intracranial aneurysms[J].Stroke, 2008;39(3):1049-55.
[1]Juvela S.Risk factors for multiple intracranial aneurysms[J].Stroke,2000; 31(2):392.
[2]F. Baumann, Nadia Khan Y.Yonekawa, et al.Patient and aneurysm characteristics in multiple intracranial aneurysms[J],Acta Neurochir Suppl,2008; 103 (1) 19-28.
[3]van der Wee N, Rinkel GJ, Hasan D, et al.Detection of subarachnoid haemorrhage on early CT:is lumbar puncture still needed after a negative scan? [J].J Neurol Neurosurg Psychiatry,1995;58(3):357-359.
[4]马廉亭.神经外科学血管内治疗[M].北京：人民军医出版社.1995；214-216.
[5]Brott T,Mandybur TI.Case-control study of clinical outcome after aneurismal subaraehnoid hemorhage[J].Neurosurg,1986;19(8):891-896.
[6]Venema HW,Hulsman FJ,Heeten GJ.CT angiography of the circle of wills and intracranial internal carotid arteries:maximum intensity projection with matched mask bone elimination feasibi-lity study[J].Radiology,2001;218(3): 898-902.
[7]SakamotO S.Kiura Y,Shibukawa M,et al.Subtracted 3D CT angiography for evaluation of intern al carotid artery aneurysms:comparison with conventional digital subtraction angiography.AJNR Am J Neumradiol[J], 2006;27(13):1332-337.
[8]Dehdashti AR,Binaghi S,Uske A,et al.Comparison of multi-slice computerized tomography and digital subtraction angiography in the postoperative evaluation of patients with clipped aneurysms[J].J Neurosurg,2006;104(23): 395-403.
[9]Davis CP,Ld ME,Romanweski BJ.Human aorta:preliminary results with virtual endoscopy based on three-dimensional MR imaging datasets [J].Radiology, 1996;199(1):37-40.
[10]Clatterbuck RE, Tamargo RJ.Contralateral approaches to multiple cerebral aneurysms [J],Neurosurgery,2005;57(1 Suppl):160-163
[11]11.B.G. Shinl,J.S.Kiml,S.C.Hongl,et al.Single-stage operation for bilateral middle cerebral artery aneurysms[J],Acta Neurochir (Wien),2005; 147(1):33-38
[12]Santana Pereira RS,Casulari LA.Surgical treatment of bilateral multiple intracranial aneurysms[J].Review of a personal experience in 69 cases[J].J Neurosurg Sci,2006;50(1):1-8
[13]廖旭兴,马廉亭,杨铭,等。扩大额颞颧弓入路暴露Willis环及其主要分支的应用显微解剖学研究[J].中国神经精神疾病杂志,2009；35(5)：304-306
[14]Wehman, J Christopher, Hanel, Ricardo A, et al.Giant Cerebral Aneurysms: Endovascular Challenges[J],Neurosurgery,2006;59 (5):125-138
[15]Solander S,ulhoa A,Vinuela F,et al.Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils[J].J Neurosurg, 1999;90(7):857-864.
[16]Kheireddin AS,Filatov IuM, Iakovlev SB,et al.Stage-by-stage treatment of multiple cerebral aneurysms using endovascular and microsurgical techniques [J],Zh Vopr Neirokhir Im N N Burdenko,2009;Jan-Mar,(1):53-57
[17]Hoh Brian L, Carter Bob S,Budzik Ronald F, et al.Results after Surgical and Endovascular Treatment of Paraclinoid Aneurysms by a Combined Neurovascular Team[J].Neurosurgery,2001;48 (1):78-90
[18]Lawton Michael T, Quinones-Hinojosa, Alfredo Sanai,et al.Combined Microsurgical and Endovascular Management of Complex Intracranial Aneurysms[J].Neurosurgery,2003;52(2):263-275
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