Study On The Pathogenesis Of Multiple Intracranial Aneurysms And Its Microanatomy Applications Of A Novel Operative Approaches

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 AneurysmsObjective 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 BranchesObjective 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 CasesObjective 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.