内耳畸形HRCT影像学研究及SNHL家系耳聋相关基因的检测
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摘要
研究背景
感音神经性聋是导致语言交流障碍的主要原因,严重影响耳聋患者的生存质量,一直是国内外耳科学及其相关领域的一个研究热点和难点。先天性内耳畸形是儿童感音神经性聋的重要原因之一,可由于遗传、染色体变异、外部环境因素等引起,畸形可发生在单耳,亦可罹患双耳,形式多样。由于内耳畸形的确诊直接影响治疗,作为完整评估感音神经性聋的组成部分,影像学检查具有重要意义。自上世纪八十年代以来,高分辨率CT(HRCT)在颞骨的影像诊断学中得到广泛的应用。HRCT具有良好的密度分辨力,图像清晰,采用薄层扫描及骨算法重建,可清晰显示耳部的正常细微解剖结构及病变形态变化,有助于内耳畸形的确定,具有很高的临床应用价值。但由于内耳结构精细,从影像学检查中发现内耳畸形需要依靠影像学家的经验,尤其一些细小的病变,临床医师对此检查认识不足,临床上对先天性内耳畸形漏诊误诊时有发生。
研究表明(Kelley等,1998),每1000个新生儿中有1至3名听力障碍儿童,其中至少一半与遗传因素有关。另外在大量的迟发性听力下降患者中,亦有许多患者由自身的基因缺陷致病,或由于基因缺陷和多态性造成对致聋环境因素易感性增加而致病。人类基因组计划的完成,促进了遗传学与耳科学的紧密结合和遗传性聋的研究。在欧美遗传性耳聋人群中,已发现数个耳聋重点基因,如由GJB2基因突变导致的耳聋及PDS基因突变导致的Pendred综合症,Kelley等研究发现,GJB2(Connexin26)基因突变是造成全球一半以上的中、重度先天性耳聋的原因。此两项基因检测已被美国哈佛大学儿童医院以及Iowa大学医学中心列为常规临床检测项目。在我国,自1998年夏家辉教授成功克隆GJB3(Connexin31)耳聋基因之后,越来越多的中国人遗传性耳聋基因被定位和克隆。研究表明(Prezant等,1993),在应用氨基甙类抗生素导致的药物性耳聋病例中有很大比例与线粒体基因A1555G突变有关。由于感音神经性聋的治疗效果并不理想,因此耳聋的预防更为重要,这就迫切需要相关技术进行基因突变的筛查或用药前检测。另外,在我国很多耳聋家庭希望通过再次生育拥有健听的后代,他们需要知道发生耳聋的准确病因,并需要相应的产前诊断技术来确保再次生育成功,耳聋的基因诊断对产前诊断,防止神经性耳聋的纵向传递具有重要意义。聋病的基因研究为探索感音神经性聋的根本原因开辟了一个新的研究领域,应用基因诊断技术探讨耳聋发病的真正原因,开放基因治疗,为最终解决感音神经性聋的治疗难题带来了希望。
正常听力是儿童学习言语的基本保证,6岁以前发生听力障碍,势必影响言语能力,因此早期诊断耳聋患儿并对其实施干预,对减少聋哑残疾的发生起着重要作用。人工耳蜗植入术近年来国内发展较快,已成为双耳极重度感音神经性聋听觉康复的有效的治疗手段,术前影像学评估也是人工耳蜗植入术前检查的一项重要内容。随着人工耳蜗植入技术的发展,耳蜗植入候选者选择标准和手术适应证在拓宽,近年来不断有耳蜗畸形患者成功进行人工耳蜗植入的病例,某些耳蜗畸形不再是手术的完全禁忌,但耳蜗畸形和耳蜗骨化会影响电极插入深度及放置的位置,从而增加手术难度或影响术后效果,导致术中出现并发症,如井喷,面神经损伤等的风险增加。听力重建、人工耳蜗植入等临床治疗技术的发展,需要对各种病变或解剖变异进行全面评估,为临床准确地选择手术适应症、正确地制定术式、径路提供可靠依据。
本论文分三部分:
第一部分通过对临床表现为不同程度感音神经性聋患者的HRCT影像资料进行分析,在CT工作站通过对内耳结构的三维图像重建,进一步分析内耳畸形的影像特征,并对接受人工耳蜗植入手术治疗患者的临床资料进行总结,探讨HRCT及后处理技术对先天性内耳畸形的诊断价值及其对人工耳蜗植入手术的指导意义;结合重建图像,在大前庭导水管患者颞骨轴位CT外半规管层面上,对外半规管中央骨岛进行定量测量,对大前庭导水管合并的半规管畸形进行定量分析。
第二部分对临床遇到的寻求遗传咨询的感音神经性耳聋家系进行不同方法耳聋相关基因突变的检测,建立方便实用的耳聋基因诊断方法路线,以便于进一步开展耳聋基因临床诊断工作。
第三部分通过对采用半规管阻塞技术治疗的16例(16耳)胆脂瘤型中耳炎并发迷路瘘管的临床资料进行回顾性分析,对半规管阻塞技术治疗迷路瘘管的安全性及手术效果进行探讨。
第一部分感音神经性聋伴内耳畸形的HRCT影像学研究及内耳畸形患者人工耳蜗植入
目的:
1.探讨HRCT及MPR、VRT等多种后处理技术对先天性内耳畸形的诊断价值,加强对内耳畸形的认识。
2.对临床常见前庭导水管扩大畸形患者的CT资料进行分析,结合MPR重建图像,通过对大前庭导水管患者颞骨轴位CT外半规管层面上,外半规管中央骨岛的定量测量,对大前庭导水管合并的外半规管畸形进行定量分析。
3.总结先天性内耳畸形患者行人工耳蜗植入的临床资料,探讨先天性内耳畸形患者人工耳蜗植入的有关问题。
材料与方法:
1.对112例临床表现为不同程度感音神经性聋患者的临床资料及数字化保存的颞骨HRCT资料进行回顾性分析。
2.在CT工作站利用多种图像后处理技术(MPR、MIP、VR),进行内耳结构的三维重建。
3.结合MPR重建图像,在颞骨轴位CT外半规管层面上,应用电子测量工具对前庭导水管扩大患者外半规管中央骨岛进行测量,对大前庭导水管合并的半规管畸形进行定量分析。
4.总结接受人工耳蜗植入患者的临床资料,包括病史调查、体格检查、手术记录、术后听力康复效果及满意度。
结果:
1.112例患者中语前聋97例,语后聋15例。有先天性耳聋家族史2例,均为男性,其中1例其父、母均为先天性耳聋,另一例其同胞姐姐为先天性聋,其余病例无明确病因。
2.HRCT表现为内耳畸形34例(68耳),其余78例颞骨HRCT内耳结构未见异常。34例内耳畸形患者中:前庭导水管扩大20例,其中单侧扩大1例,其余均为双侧;Michel畸形1例(2耳);IP-Ⅰ型1例(2耳);IP-Ⅱ型(Mondini型)3例(6耳);前庭-半规管畸形3例(6耳);单纯半规管畸形4例,内听道狭窄1例(2耳);X-连锁隐性遗传性聋1例(2耳)。
3.多数病例病变累及多个内耳结构,少数病例为单个结构受损。其中1例IP-Ⅰ型伴有前庭及半规管畸形,不伴前庭导水管扩大;3例IP-Ⅱ型患者均合并有前庭扩大及前庭导水管扩大;3例前庭畸形患者耳蜗发育正常,但均合并外半规管畸形。无单纯耳蜗或单纯前庭畸形病例。单个结构受损的病例只见于半规管畸形及前庭导水管扩大。其中单纯半规管畸形表现为双侧上、后半规管裂。
4.HRCT轴位图像和MPR图像、VRT图像均可以清晰的显示畸形的部位和程度,其中VRT图像可以直观、立体地显示畸形的空间形态结构。
5.定量测量结果显示:前庭导水管扩大畸形患者颞骨CT轴位外半规管骨岛测量值普遍＜3mm,与正常对照比较差异有显著性意义(P＜0.05),前庭导水管扩大患者外半规管中央骨岛测量值明显小于对照组测量值。
6.86例极重度感音神经性聋患者成功进行单耳人工耳蜗植入,其中78例颞骨HRCT内耳骨性结构无异常,8例为HRCT提示内耳畸形患者,包括6例大前庭导水管、1例IP-Ⅰ型及1例IP-Ⅱ(Mondini型)内耳畸形。全部病例一次植入成功,无严重术中、术后并发症。
7.术后耳蜗位X线摄片示电极位置良好,术后NRT测试,IP-Ⅰ型患者各电极均未能引出明确的NRT反应,但给予刺激后出现听觉反应;Mondini型内耳畸形患者NRT测试可引出正常波形,但电极阻抗及刺激阈值高于无内耳畸形患儿;大前庭导水管患者NRT阈值与内耳结构正常患儿无差异,平均随访18个月,患者家庭均对结果表示满意。
结论:
1.临床上对原因不明的双侧感音神经性聋儿童患者进行评估时,要充分考虑到内耳畸形的可能,颞骨HRCT扫描作为首选的影像学检查方法,结合后处理技术可更加准确的对内耳骨迷路畸形的部位和程度做出诊断,对内耳畸形具有重要诊断价值。
2.HRCT图像结合定量测量有助于内耳畸形的诊断,本组病例测量结果提示:大前庭导水管患者外半规管中央骨岛测量值明显小于对照组测量值,差异有显著性意义(P＜0.05)。本研究结果提示EVA患者普遍存在半规管的发育异常,对阐明大前庭导水管耳聋发病机制有重要意义。
3.内耳畸形耳蜗植入候选者的选择更应重视残余听力评估,听神经-听觉通路完整性评估,以避免无意义人工耳蜗植入。颞骨CT的主要优势在于清晰显示颞骨的骨性结构,但对于膜迷路、耳蜗神经及中枢神经系统的病变的评估受到很大限制,耳蜗畸形患者人工耳蜗植入术前的影像学评估需结合CT及MRI综合分析。
4.双耳重度、极重度聋伴大前庭导水管、IP-Ⅰ及IP-Ⅱ内耳畸形,不是人工耳蜗植入的绝对禁忌,根据畸形的类型决定手术策略,术中采用适当的术式,内耳畸形的人工耳蜗植入可以达到满意的效果。对重度、极重度听力损失的大前庭水管综合征患者进行人工耳蜗植入效果是肯定的。而IP-Ⅰ畸形及Mondini内耳畸形人工耳蜗植入效果有一定不确定性,术前应考虑及此点,并告知候选者使其具有适当的期望值
第二部分感音神经性耳聋家系耳聋相关基因突变的检测
目的:
采用多种基因检测方法,对临床遇到的寻求遗传咨询的糖尿病伴感音神经性聋家系及大前庭导水管家系进行耳聋相关基因突变检测,为基因诊断和遗传咨询的临床应用提供科学依据。
材料与方法:
1.收集临床遇到的寻求遗传咨询的耳聋家系资料,包括2个糖尿病伴感音神经性耳聋家系及3个大前庭导水管伴神经性耳聋核心家系相关资料,调查患者的性别、年龄、发病年龄、家系内患病情况,所有耳聋患者均行耳科专科检查、听力学检查,排除耳毒性药物应用史、噪声暴露史、耳科疾病史等获得性病因,大前庭导水管患者行颞骨CT及MRI检查确诊。所有糖尿病患者均符合糖尿病的诊断标准。
2.采集患者及家系中其他成员外周血,采用DNA提取试剂盒提取DNA,用提取的DNA作为模板,利用聚合酶链反应(PCR)扩增目的基因。
3.PCR产物提纯后测序:应用遗传性聋基因芯片检测试剂盒对所有家系样本进行GJB2基因、PDS基因及线粒体12SrRNA基因突变筛查;应用PDS基因检测试剂盒配合PAGE银染法对大前庭导水管家系样本进行针对SLC26A4基因IVS7-2 A＞G突变的检测;应用限制性核酸内切酶方法对糖尿病耳聋家系进行线粒体基因3243位点基因突变检测。
4.采用直接测序法,对所有测序结果进行测序验证。
结果:
1.在两个糖尿病伴感音神经性耳聋家系耳聋患者及家系中其他成员均未发现线粒体基因3243位点突变及GJB2基因、PDS基因及线粒体12SrRNA基因突变。
2.三个大前庭导水管核心家系中,先天性感音神经性聋先证者均为子代,均经颞骨HRCT或MRI诊断为大前庭导水管,而三个家庭的父、母亲均听力正常。测序结果:其中一个家庭为父亲及女儿存在SLC26A4基因IVS7-2 A＞G杂合突变,另一家庭为母亲及儿子存在SLC26A4基因IVS7-2 A＞G杂合突变。在三个大前庭导水管核心家系中均未发现GJB2基因及线粒体12SrRNA基因的阳性突变。
结论:
1.在2个糖尿病伴感音神经性耳聋家系中未检测到线粒体3243位点突变及GJB2基因突变,本研究结果初步排除线粒体基因3243位点突变或GJB2基因突变致该家系出现遗传性感音神经性耳聋的可能性。
2.研究结果证实有2个大前庭导水管家系存在SLC26A4基因IVS7-2 A＞G杂合突变,研究结果可为两个大前庭导水管家庭耳聋的遗传咨询及再生育指导提供依据。
第三部分半规管阻塞技术在胆脂瘤型中耳炎并发迷路瘘管治疗中的应用
目的:
探讨半规管阻塞技术治疗胆脂瘤型中耳炎并发迷路瘘管的安全性及手术效果。
材料与方法:
回顾性分析16例(16耳)胆脂瘤型中耳炎并发迷路瘘管的临床资料。所有病人术前均行颞骨HRCT检查,对病人的临床表现、术前术后听力学变化,手术记录资料进行回顾性分析。
结果:
1.全部病例胆脂瘤母质均一期在手术显微镜下彻底消除,采用外半规管阻塞技术一期修复迷路瘘管。根据术中探查所见病变情况,14例行开放式乳突根治术加鼓室成形术;1例存在鼓室硬化,镫骨足板固定,二期鼓室成形;1例病变耳术前听力为全聋行开放式乳突根治术。
2.手术证实全部瘘管位于外半规管,术前HRCT检查与术中所见符合。合并面神经骨管骨质缺损7例(其中2例术前已有病变侧周围性面瘫)、乙状窦表面骨质缺损2例、鼓室及乳突天盖缺损3例。
3.全部病例均获干耳,术后短期内有眩晕发作,经休息及药物治疗均获缓解,术后随访6～36个月,平均随访15个月,眩晕症状均有效控制。除1耳术前听力为全聋者外,其余患者均无明显骨导听力下降,纯音听阈检查,比较手术前后骨导变化,差异无显著性意义(P＞0.05)。
结论:
1.颞骨高分辨CT结合MPR图像重建对迷路瘘管的术前诊断有重要价值。
2.胆脂瘤型中耳炎并发迷路瘘管手术方式的选择,需根据不同患者病变的性质、程度和范围决定术式及否分期,提倡个体化治疗方案。
3.外半规管迷路瘘管可一期彻底清除瘘管区病变,半规管阻塞技术为有效修补瘘孔,控制眩晕,保存听力的安全术式。
Background
Profound congenital hearing impairment is the most frequently occurring birth defect, with an estimated incidence of approximately 1-3:1000 births in the US.Deafness has many recognized genetic and environmental causes,many previous studies have suggested that about 50%of profound deafness is genetic in etiology,with the remainder of cases attributed to environmental causes such as congenital infection,fetal ototoxic drug exposure and trauma.
The advance of Human Genome has brought along the epoch of molecular medicine, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment.The American College of Medical Genetics has recommended that all infants with confirmed hearing loss,who are identified in newborn screening programs, should be referred to a geneticist for clinical evaluation,the performance of indicated genetic tests,and counseling.Previous reports have described that mutations in GJB2, or connexin 26,encoding gap junction beta 2 protein are responsible for the commonest form of non-syndromic recessive deafness in many populations.A specific genetic diagnosis can sometimes be of great clinical importance,as in the case of the mitochondrial A1555G mutation which causes gene carriers to be exquisitely sensitive to the ototoxic effects of amino-glycosides.
Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling, it is expected that new diagnostic techniques could be adopted to prevent part of the environmental and hereditary deafness by molecular genetic tests and genetic counseling.In addition,genetics can provide empowering knowledge to many deaf couples to know whether their children will be hearing or deaf even before they are conceived.
Inner ear malformations may be associated with sensorineural hearing loss(SNHL), imaging examination plays a crucial role in the diagnosis of inner ear malformations, and so in the assessment of SNHL,detailed images with high resolution are mandatory for the demonstration of small pathological processes.With the development of HRCT in the 1980s,HRCT became the first line recommended method of choice in the evaluation and management of hearing impairment,malformations and destructive processes in the middle and inner ear.Because of the detailed display of soft tissue and bony structures,small bony pathologies can be well visualized.With special software, the acquired data allowed the reconstruction of three-dimensional images of missing sections,with this method,loss of information was compensated for by a lower radiation dose.Identification of obvious morphogenetic malformations is not difficult. However,the recognition of these less severe anomalies is dependent on the clinical experience of the clinician and nearly one-third of less severe inner ear anomalies may be missed.
Children affected by SNHL before 6 years of age may leads to deficits in speaking and communication abilities,which,in turn,negatively affect the child's social and educational development.Importance of the early diagnosis and intervention of hearing loss has been increasingly valued.Cochlear implant is considered an effective procedure to treat patients with severe(between 70 and 90 dB) to profound(＞90dB) bilateral SNHL,and that have not benefited from conventional sound amplification hearing aids.In the last years,cochlear implantation has gained widespread acceptance in the Chinese profoundly deaf patients.Evaluation by imaging methods is critical in the preoperative care of cochlear implant(CI) surgery,providing safety to surgeons when indicating and performing this procedure.As demands for Cochlear implant increase,surgeons should be aware of what key points they have to check before implanting patients.HRCT has been of high value in clinical application of analysis of each inner ear malformations and help to guide proper treatment of each patient. However,there has been little written about the correlation of specific inner ear malformations with their clinical presentation and management.
This paper is composed of three parts as follows:
The aim of the first study was to analyze the HRCT imaging features in patients with SNHL and discussed the clinical values of HRCT in diagnosis of congenital inner ear malformations and preoperative evaluation for cochlear implantation by correlating preoperative radiological signs with surgical findings.In the second study we screened GJB2,PDS gene mutations in patients of SNHL using direct sequencing analysis,for the purpose of accumulating the experience and samples for the new technique of the detection of gene mutation and collection basic information for the clinical application of genetic diagnosis and genetic counseling of SNHL.The popurse of the third study was to evaluate the effect of semicircular canal occlusion on hearing in the treatment of labyrinthine fistula caused by cholesteatoma.
Part one HRCT Analysis and Cochlear Implantation in Patients with Inner Ear Malformation
Objective:
1.To investigate the HRCT findings in children with SNHL and discuss it's clinical values in the diagnosis of congenital inner ear malformations and preoperative evaluation for cochlear implantation.
2.Using standardized measurements of central bony island width within the LSCC to investigate the lateral semicircular canal(LSCC) anomalies and the coexistence of other inner ear anomalies on HRCT imaging that occur in association with LVAS.
3.To analyze the surgical indications,prevention of complication and surgical difficulty of cochlear implant in patients with congenital inner ear malformations.
Methods:
1.One hundred and twelve children with SNHL performed HRCT scan,the digitally stored temporal bone multi-slice spiral CT imaging of the inner ear structures were reviewed and the 3-dimensional reconstructions and multiplanar reformation(MPR) were performed using the volume-rendering technique(VRT) on the workstation.
2.The measurements of the central bony island width within the LSCC on axial imaging at the level of LSCC from the children with LVAS were performed on the workstation.
3.The cochlear implantations were performed in 86cases of our patients,routine transmastoid facial recess approach was performed in these Cases.The medical records of all patients undergoing CI surgery were studied.
Results:
1.Among 112 patients,78 patients were normal and 34 patients(68ears) were congenital inner ear malformations.The malformations were as follows:Michel deformity one case(two ears Fig.2),incomplete partition typesⅠone case(IP-Ⅰ,two ears,accompanyied by vestibule lateral semicircular canal dysplasia),incomplete partition typesⅡ3 cases(IP-Ⅱ,Mondini deformity,6 ears,accompanied by dilation of lateral semicircular canal and vestibule,enlarged vestibular aqueduct),vestibule and lateral semicircular canal dysplasia 3cases(6ears),isolated semicircular canal abnormality 4 cases(8ears), narrow internal auditory canal one case(two ears),X-linked inherited deafness one case(two ears),enlarged vestibular aqueduct 20 cases(39ears).
2.The axial,MPR and VRT reconstruction images can display the site and degree in the ears with inner ear malformations.The VRT reconstruction images can display the malformations of inner ear three-dimensionally and intuitively.
3.In all cases the diagnosis of inner ear malformation was made by CT imaging. Combined deformities were found in all of the patients with cochlear or vestibule dysplasia in our sieries,and the single structure abnormalities were found only in isolated semicircular canal dysplasia or isolated enlarged vestibular aqueduct.
4.The measurements of the central bony island width within the LSCC showed:A small bony island of the LSCC(＜3mm in diameter) appears highly typical in patients with LVAS.Coexistent inner ear anomalies are common in LVAS.
5.Eighty-six patients received a cochlear implant.The cochlear implantations were performed in 8 patients with the malformation of inner ear.In this series,there were 6cases of large vestibular aqueduct syndrome(LVAS),1 cases of incomplete partition typesⅠ,and 1 cases of Mondini malformation.
Conclusion:
1.HRCT allows a comprehensively assessing various congenital inner ear malformations through high quality MPR and VRT reconstructions.It is very useful to the cochlear implantation.
2.Measurement of the inner ear structures,in conjunction with visual inspection of CT images,will increase recognition of subtle inner ear abnormalities.
3.For the patients with inner ear malformations,it is important to accurately assess the extent of abnormalities in the inner ear and accompanied malformations before operation,and to evaluate the full extent of difficulties of the operation in order to minimize the risk of CSF leakage.
4.Inner ear malformations can not be a contraindication to implantationfor cochlear implantation in children,but it is important to be aware of the various aspects of the surgical management and to attempt to minimize the risks of complications.Cochlear implant is potentially a good functional solution for patients suffering from large vestibular aqueduct syndrome.
Part two Detection of Heredity Deafness Gene Mutations in Chinese Family Suffered from SNHL
Objective:
To identify the prevalence of deafness related gene mutations in patients with SNHL, for the purpose of accumulating the experience and samples for the new technique of the detection of gene mutation and collection basic information for the clinical application of genetic diagnosis and genetic counseling of SNHL.
Methods:
Two Chinese families suffered from SNHL accompanied by diabetes mellitus and three Chinese families suffered from SNHL associated with enlarged vestibular aqueduct(EVA) were collected.Genomic DNA was extracted from peripheral blood cells of all patients and the others of their pedigree.All the coding exons and their flanking sequences of the testing gene were amplified by polymerase chain reaction (PCR).The products were analyzed totest the PDS gene,GJB2 gene and Mt 3243 gene mutations in these families.
Results:
There are no GJB2 and Mt 3243 gene mutations found in the two Chinese family suffered from SNHL accompanied by diabetes mellitus.SLC26A4 gene mutation was found in two of the three Chinese families suffered from SNHL associated with enlarged vestibular aqueduct.
Conclusion:
The mutations of GJB2 are not likely to be the cause of SNHL accompanied by diabetes mellitus in our siries.More studies are needed.SLC26A4 mutations were found in the family with EVA.Genetic test for this mutation is necessary for prenatal diagnosis of these two families,and genetic testing can provide efficient information about hearing condition of their offsprings.
Part three Lateral Semicircular Canal Plugging for Treatment of Labyrinthine Fistula Caused by Cholesteatoma
Objective:
To evaluate the effect of semicircular canal occlusion on hearing in the treatment of labyrinthine fistula caused by cholesteatoma
Methods:
Retrospective study based on 16 cases of labyrinthine fistula caused by cholesteatoma. The preoperative symptoms,incidence of labyrinthine fistula,type of surgery and preoperative and postoperative hearing function and intraoperative findings were analyzed.Preoperative high resolution computed tomography(HRCT) scans and the MPR reconstruction were performed on all patients,
Results:
1.All patients were detected to be with labyrinthine fistula in preoperative HRCT imaging.During the operation the lateral semicircular canal was found in all of the cases.
2.During surgery the matrix over the fistula was removed in all cases.Occlusion of the lateral semicircular canal for the treatment of labyrinthine fistula was performed in all cases.Postoperative change of bone conduction threshold was not significantly different compared with preoperative bone conduction threshold(P＜0.05).
3.The patients were followed up for an average time of 15 months,dizziness disappeared completely in all cases and the preservation of the bone conduction threshold was obtained when semicircular canal occlusion surgical technique is used.
Conclusion:
1.Preoperative HRCT scan and MPR reconstruction technique is useful in diagnosis of labyrinthine fistula.but it s limitations should also be recognized.The verification of a labyrinthine fistula can be definitively established only at the time of surgery.
2.The current study confirmed that careful manipulation of the labyrinthine fistula is safe to preserve hearing functions for these patients.
3.Hearing preservation can be obtained when semicircular canal occlusion surgical technique is used.
感音神经性聋是导致语言交流障碍的主要原因,严重影响耳聋患者的生存质量,一直是国内外耳科学及其相关领域的一个研究热点和难点。先天性内耳畸形是儿童感音神经性聋的重要原因之一,可由于遗传、染色体变异、外部环境因素等引起,畸形可发生在单耳,亦可罹患双耳,形式多样。由于内耳畸形的确诊直接影响治疗,作为完整评估感音神经性聋的组成部分,影像学检查具有重要意义。自上世纪八十年代以来,高分辨率CT(HRCT)在颞骨的影像诊断学中得到广泛的应用。HRCT具有良好的密度分辨力,图像清晰,采用薄层扫描及骨算法重建,可清晰显示耳部的正常细微解剖结构及病变形态变化,有助于内耳畸形的确定,具有很高的临床应用价值。但由于内耳结构精细,从影像学检查中发现内耳畸形需要依靠影像学家的经验,尤其一些细小的病变,临床医师对此检查认识不足,临床上对先天性内耳畸形漏诊误诊时有发生。
研究表明(Kelley等,1998),每1000个新生儿中有1至3名听力障碍儿童,其中至少一半与遗传因素有关。另外在大量的迟发性听力下降患者中,亦有许多患者由自身的基因缺陷致病,或由于基因缺陷和多态性造成对致聋环境因素易感性增加而致病。人类基因组计划的完成,促进了遗传学与耳科学的紧密结合和遗传性聋的研究。在欧美遗传性耳聋人群中,已发现数个耳聋重点基因,如由GJB2基因突变导致的耳聋及PDS基因突变导致的Pendred综合症,Kelley等研究发现,GJB2(Connexin26)基因突变是造成全球一半以上的中、重度先天性耳聋的原因。此两项基因检测已被美国哈佛大学儿童医院以及Iowa大学医学中心列为常规临床检测项目。在我国,自1998年夏家辉教授成功克隆GJB3(Connexin31)耳聋基因之后,越来越多的中国人遗传性耳聋基因被定位和克隆。研究表明(Prezant等,1993),在应用氨基甙类抗生素导致的药物性耳聋病例中有很大比例与线粒体基因A1555G突变有关。由于感音神经性聋的治疗效果并不理想,因此耳聋的预防更为重要,这就迫切需要相关技术进行基因突变的筛查或用药前检测。另外,在我国很多耳聋家庭希望通过再次生育拥有健听的后代,他们需要知道发生耳聋的准确病因,并需要相应的产前诊断技术来确保再次生育成功,耳聋的基因诊断对产前诊断,防止神经性耳聋的纵向传递具有重要意义。聋病的基因研究为探索感音神经性聋的根本原因开辟了一个新的研究领域,应用基因诊断技术探讨耳聋发病的真正原因,开放基因治疗,为最终解决感音神经性聋的治疗难题带来了希望。
正常听力是儿童学习言语的基本保证,6岁以前发生听力障碍,势必影响言语能力,因此早期诊断耳聋患儿并对其实施干预,对减少聋哑残疾的发生起着重要作用。人工耳蜗植入术近年来国内发展较快,已成为双耳极重度感音神经性聋听觉康复的有效的治疗手段,术前影像学评估也是人工耳蜗植入术前检查的一项重要内容。随着人工耳蜗植入技术的发展,耳蜗植入候选者选择标准和手术适应证在拓宽,近年来不断有耳蜗畸形患者成功进行人工耳蜗植入的病例,某些耳蜗畸形不再是手术的完全禁忌,但耳蜗畸形和耳蜗骨化会影响电极插入深度及放置的位置,从而增加手术难度或影响术后效果,导致术中出现并发症,如井喷,面神经损伤等的风险增加。听力重建、人工耳蜗植入等临床治疗技术的发展,需要对各种病变或解剖变异进行全面评估,为临床准确地选择手术适应症、正确地制定术式、径路提供可靠依据。
本论文分三部分:
第一部分通过对临床表现为不同程度感音神经性聋患者的HRCT影像资料进行分析,在CT工作站通过对内耳结构的三维图像重建,进一步分析内耳畸形的影像特征,并对接受人工耳蜗植入手术治疗患者的临床资料进行总结,探讨HRCT及后处理技术对先天性内耳畸形的诊断价值及其对人工耳蜗植入手术的指导意义;结合重建图像,在大前庭导水管患者颞骨轴位CT外半规管层面上,对外半规管中央骨岛进行定量测量,对大前庭导水管合并的半规管畸形进行定量分析。
第二部分对临床遇到的寻求遗传咨询的感音神经性耳聋家系进行不同方法耳聋相关基因突变的检测,建立方便实用的耳聋基因诊断方法路线,以便于进一步开展耳聋基因临床诊断工作。
第三部分通过对采用半规管阻塞技术治疗的16例(16耳)胆脂瘤型中耳炎并发迷路瘘管的临床资料进行回顾性分析,对半规管阻塞技术治疗迷路瘘管的安全性及手术效果进行探讨。
第一部分感音神经性聋伴内耳畸形的HRCT影像学研究及内耳畸形患者人工耳蜗植入
目的:
1.探讨HRCT及MPR、VRT等多种后处理技术对先天性内耳畸形的诊断价值,加强对内耳畸形的认识。
2.对临床常见前庭导水管扩大畸形患者的CT资料进行分析,结合MPR重建图像,通过对大前庭导水管患者颞骨轴位CT外半规管层面上,外半规管中央骨岛的定量测量,对大前庭导水管合并的外半规管畸形进行定量分析。
3.总结先天性内耳畸形患者行人工耳蜗植入的临床资料,探讨先天性内耳畸形患者人工耳蜗植入的有关问题。
材料与方法:
1.对112例临床表现为不同程度感音神经性聋患者的临床资料及数字化保存的颞骨HRCT资料进行回顾性分析。
2.在CT工作站利用多种图像后处理技术(MPR、MIP、VR),进行内耳结构的三维重建。
3.结合MPR重建图像,在颞骨轴位CT外半规管层面上,应用电子测量工具对前庭导水管扩大患者外半规管中央骨岛进行测量,对大前庭导水管合并的半规管畸形进行定量分析。
4.总结接受人工耳蜗植入患者的临床资料,包括病史调查、体格检查、手术记录、术后听力康复效果及满意度。
结果:
1.112例患者中语前聋97例,语后聋15例。有先天性耳聋家族史2例,均为男性,其中1例其父、母均为先天性耳聋,另一例其同胞姐姐为先天性聋,其余病例无明确病因。
2.HRCT表现为内耳畸形34例(68耳),其余78例颞骨HRCT内耳结构未见异常。34例内耳畸形患者中:前庭导水管扩大20例,其中单侧扩大1例,其余均为双侧;Michel畸形1例(2耳);IP-Ⅰ型1例(2耳);IP-Ⅱ型(Mondini型)3例(6耳);前庭-半规管畸形3例(6耳);单纯半规管畸形4例,内听道狭窄1例(2耳);X-连锁隐性遗传性聋1例(2耳)。
3.多数病例病变累及多个内耳结构,少数病例为单个结构受损。其中1例IP-Ⅰ型伴有前庭及半规管畸形,不伴前庭导水管扩大;3例IP-Ⅱ型患者均合并有前庭扩大及前庭导水管扩大;3例前庭畸形患者耳蜗发育正常,但均合并外半规管畸形。无单纯耳蜗或单纯前庭畸形病例。单个结构受损的病例只见于半规管畸形及前庭导水管扩大。其中单纯半规管畸形表现为双侧上、后半规管裂。
4.HRCT轴位图像和MPR图像、VRT图像均可以清晰的显示畸形的部位和程度,其中VRT图像可以直观、立体地显示畸形的空间形态结构。
5.定量测量结果显示:前庭导水管扩大畸形患者颞骨CT轴位外半规管骨岛测量值普遍＜3mm,与正常对照比较差异有显著性意义(P＜0.05),前庭导水管扩大患者外半规管中央骨岛测量值明显小于对照组测量值。
6.86例极重度感音神经性聋患者成功进行单耳人工耳蜗植入,其中78例颞骨HRCT内耳骨性结构无异常,8例为HRCT提示内耳畸形患者,包括6例大前庭导水管、1例IP-Ⅰ型及1例IP-Ⅱ(Mondini型)内耳畸形。全部病例一次植入成功,无严重术中、术后并发症。
7.术后耳蜗位X线摄片示电极位置良好,术后NRT测试,IP-Ⅰ型患者各电极均未能引出明确的NRT反应,但给予刺激后出现听觉反应;Mondini型内耳畸形患者NRT测试可引出正常波形,但电极阻抗及刺激阈值高于无内耳畸形患儿;大前庭导水管患者NRT阈值与内耳结构正常患儿无差异,平均随访18个月,患者家庭均对结果表示满意。
结论:
1.临床上对原因不明的双侧感音神经性聋儿童患者进行评估时,要充分考虑到内耳畸形的可能,颞骨HRCT扫描作为首选的影像学检查方法,结合后处理技术可更加准确的对内耳骨迷路畸形的部位和程度做出诊断,对内耳畸形具有重要诊断价值。
2.HRCT图像结合定量测量有助于内耳畸形的诊断,本组病例测量结果提示:大前庭导水管患者外半规管中央骨岛测量值明显小于对照组测量值,差异有显著性意义(P＜0.05)。本研究结果提示EVA患者普遍存在半规管的发育异常,对阐明大前庭导水管耳聋发病机制有重要意义。
3.内耳畸形耳蜗植入候选者的选择更应重视残余听力评估,听神经-听觉通路完整性评估,以避免无意义人工耳蜗植入。颞骨CT的主要优势在于清晰显示颞骨的骨性结构,但对于膜迷路、耳蜗神经及中枢神经系统的病变的评估受到很大限制,耳蜗畸形患者人工耳蜗植入术前的影像学评估需结合CT及MRI综合分析。
4.双耳重度、极重度聋伴大前庭导水管、IP-Ⅰ及IP-Ⅱ内耳畸形,不是人工耳蜗植入的绝对禁忌,根据畸形的类型决定手术策略,术中采用适当的术式,内耳畸形的人工耳蜗植入可以达到满意的效果。对重度、极重度听力损失的大前庭水管综合征患者进行人工耳蜗植入效果是肯定的。而IP-Ⅰ畸形及Mondini内耳畸形人工耳蜗植入效果有一定不确定性,术前应考虑及此点,并告知候选者使其具有适当的期望值
第二部分感音神经性耳聋家系耳聋相关基因突变的检测
目的:
采用多种基因检测方法,对临床遇到的寻求遗传咨询的糖尿病伴感音神经性聋家系及大前庭导水管家系进行耳聋相关基因突变检测,为基因诊断和遗传咨询的临床应用提供科学依据。
材料与方法:
1.收集临床遇到的寻求遗传咨询的耳聋家系资料,包括2个糖尿病伴感音神经性耳聋家系及3个大前庭导水管伴神经性耳聋核心家系相关资料,调查患者的性别、年龄、发病年龄、家系内患病情况,所有耳聋患者均行耳科专科检查、听力学检查,排除耳毒性药物应用史、噪声暴露史、耳科疾病史等获得性病因,大前庭导水管患者行颞骨CT及MRI检查确诊。所有糖尿病患者均符合糖尿病的诊断标准。
2.采集患者及家系中其他成员外周血,采用DNA提取试剂盒提取DNA,用提取的DNA作为模板,利用聚合酶链反应(PCR)扩增目的基因。
3.PCR产物提纯后测序:应用遗传性聋基因芯片检测试剂盒对所有家系样本进行GJB2基因、PDS基因及线粒体12SrRNA基因突变筛查;应用PDS基因检测试剂盒配合PAGE银染法对大前庭导水管家系样本进行针对SLC26A4基因IVS7-2 A＞G突变的检测;应用限制性核酸内切酶方法对糖尿病耳聋家系进行线粒体基因3243位点基因突变检测。
4.采用直接测序法,对所有测序结果进行测序验证。
结果:
1.在两个糖尿病伴感音神经性耳聋家系耳聋患者及家系中其他成员均未发现线粒体基因3243位点突变及GJB2基因、PDS基因及线粒体12SrRNA基因突变。
2.三个大前庭导水管核心家系中,先天性感音神经性聋先证者均为子代,均经颞骨HRCT或MRI诊断为大前庭导水管,而三个家庭的父、母亲均听力正常。测序结果:其中一个家庭为父亲及女儿存在SLC26A4基因IVS7-2 A＞G杂合突变,另一家庭为母亲及儿子存在SLC26A4基因IVS7-2 A＞G杂合突变。在三个大前庭导水管核心家系中均未发现GJB2基因及线粒体12SrRNA基因的阳性突变。
结论:
1.在2个糖尿病伴感音神经性耳聋家系中未检测到线粒体3243位点突变及GJB2基因突变,本研究结果初步排除线粒体基因3243位点突变或GJB2基因突变致该家系出现遗传性感音神经性耳聋的可能性。
2.研究结果证实有2个大前庭导水管家系存在SLC26A4基因IVS7-2 A＞G杂合突变,研究结果可为两个大前庭导水管家庭耳聋的遗传咨询及再生育指导提供依据。
第三部分半规管阻塞技术在胆脂瘤型中耳炎并发迷路瘘管治疗中的应用
目的:
探讨半规管阻塞技术治疗胆脂瘤型中耳炎并发迷路瘘管的安全性及手术效果。
材料与方法:
回顾性分析16例(16耳)胆脂瘤型中耳炎并发迷路瘘管的临床资料。所有病人术前均行颞骨HRCT检查,对病人的临床表现、术前术后听力学变化,手术记录资料进行回顾性分析。
结果:
1.全部病例胆脂瘤母质均一期在手术显微镜下彻底消除,采用外半规管阻塞技术一期修复迷路瘘管。根据术中探查所见病变情况,14例行开放式乳突根治术加鼓室成形术;1例存在鼓室硬化,镫骨足板固定,二期鼓室成形;1例病变耳术前听力为全聋行开放式乳突根治术。
2.手术证实全部瘘管位于外半规管,术前HRCT检查与术中所见符合。合并面神经骨管骨质缺损7例(其中2例术前已有病变侧周围性面瘫)、乙状窦表面骨质缺损2例、鼓室及乳突天盖缺损3例。
3.全部病例均获干耳,术后短期内有眩晕发作,经休息及药物治疗均获缓解,术后随访6～36个月,平均随访15个月,眩晕症状均有效控制。除1耳术前听力为全聋者外,其余患者均无明显骨导听力下降,纯音听阈检查,比较手术前后骨导变化,差异无显著性意义(P＞0.05)。
结论:
1.颞骨高分辨CT结合MPR图像重建对迷路瘘管的术前诊断有重要价值。
2.胆脂瘤型中耳炎并发迷路瘘管手术方式的选择,需根据不同患者病变的性质、程度和范围决定术式及否分期,提倡个体化治疗方案。
3.外半规管迷路瘘管可一期彻底清除瘘管区病变,半规管阻塞技术为有效修补瘘孔,控制眩晕,保存听力的安全术式。
Background
Profound congenital hearing impairment is the most frequently occurring birth defect, with an estimated incidence of approximately 1-3:1000 births in the US.Deafness has many recognized genetic and environmental causes,many previous studies have suggested that about 50%of profound deafness is genetic in etiology,with the remainder of cases attributed to environmental causes such as congenital infection,fetal ototoxic drug exposure and trauma.
The advance of Human Genome has brought along the epoch of molecular medicine, genetic testing has emerged as an invaluable tool in the assessment of hearing impairment.The American College of Medical Genetics has recommended that all infants with confirmed hearing loss,who are identified in newborn screening programs, should be referred to a geneticist for clinical evaluation,the performance of indicated genetic tests,and counseling.Previous reports have described that mutations in GJB2, or connexin 26,encoding gap junction beta 2 protein are responsible for the commonest form of non-syndromic recessive deafness in many populations.A specific genetic diagnosis can sometimes be of great clinical importance,as in the case of the mitochondrial A1555G mutation which causes gene carriers to be exquisitely sensitive to the ototoxic effects of amino-glycosides.
Establishing the etiology of congenital hearing impairment can significantly improve treatment for certain causes of hearing loss and facilitates genetic counseling, it is expected that new diagnostic techniques could be adopted to prevent part of the environmental and hereditary deafness by molecular genetic tests and genetic counseling.In addition,genetics can provide empowering knowledge to many deaf couples to know whether their children will be hearing or deaf even before they are conceived.
Inner ear malformations may be associated with sensorineural hearing loss(SNHL), imaging examination plays a crucial role in the diagnosis of inner ear malformations, and so in the assessment of SNHL,detailed images with high resolution are mandatory for the demonstration of small pathological processes.With the development of HRCT in the 1980s,HRCT became the first line recommended method of choice in the evaluation and management of hearing impairment,malformations and destructive processes in the middle and inner ear.Because of the detailed display of soft tissue and bony structures,small bony pathologies can be well visualized.With special software, the acquired data allowed the reconstruction of three-dimensional images of missing sections,with this method,loss of information was compensated for by a lower radiation dose.Identification of obvious morphogenetic malformations is not difficult. However,the recognition of these less severe anomalies is dependent on the clinical experience of the clinician and nearly one-third of less severe inner ear anomalies may be missed.
Children affected by SNHL before 6 years of age may leads to deficits in speaking and communication abilities,which,in turn,negatively affect the child's social and educational development.Importance of the early diagnosis and intervention of hearing loss has been increasingly valued.Cochlear implant is considered an effective procedure to treat patients with severe(between 70 and 90 dB) to profound(＞90dB) bilateral SNHL,and that have not benefited from conventional sound amplification hearing aids.In the last years,cochlear implantation has gained widespread acceptance in the Chinese profoundly deaf patients.Evaluation by imaging methods is critical in the preoperative care of cochlear implant(CI) surgery,providing safety to surgeons when indicating and performing this procedure.As demands for Cochlear implant increase,surgeons should be aware of what key points they have to check before implanting patients.HRCT has been of high value in clinical application of analysis of each inner ear malformations and help to guide proper treatment of each patient. However,there has been little written about the correlation of specific inner ear malformations with their clinical presentation and management.
This paper is composed of three parts as follows:
The aim of the first study was to analyze the HRCT imaging features in patients with SNHL and discussed the clinical values of HRCT in diagnosis of congenital inner ear malformations and preoperative evaluation for cochlear implantation by correlating preoperative radiological signs with surgical findings.In the second study we screened GJB2,PDS gene mutations in patients of SNHL using direct sequencing analysis,for the purpose of accumulating the experience and samples for the new technique of the detection of gene mutation and collection basic information for the clinical application of genetic diagnosis and genetic counseling of SNHL.The popurse of the third study was to evaluate the effect of semicircular canal occlusion on hearing in the treatment of labyrinthine fistula caused by cholesteatoma.
Part one HRCT Analysis and Cochlear Implantation in Patients with Inner Ear Malformation
Objective:
1.To investigate the HRCT findings in children with SNHL and discuss it's clinical values in the diagnosis of congenital inner ear malformations and preoperative evaluation for cochlear implantation.
2.Using standardized measurements of central bony island width within the LSCC to investigate the lateral semicircular canal(LSCC) anomalies and the coexistence of other inner ear anomalies on HRCT imaging that occur in association with LVAS.
3.To analyze the surgical indications,prevention of complication and surgical difficulty of cochlear implant in patients with congenital inner ear malformations.
Methods:
1.One hundred and twelve children with SNHL performed HRCT scan,the digitally stored temporal bone multi-slice spiral CT imaging of the inner ear structures were reviewed and the 3-dimensional reconstructions and multiplanar reformation(MPR) were performed using the volume-rendering technique(VRT) on the workstation.
2.The measurements of the central bony island width within the LSCC on axial imaging at the level of LSCC from the children with LVAS were performed on the workstation.
3.The cochlear implantations were performed in 86cases of our patients,routine transmastoid facial recess approach was performed in these Cases.The medical records of all patients undergoing CI surgery were studied.
Results:
1.Among 112 patients,78 patients were normal and 34 patients(68ears) were congenital inner ear malformations.The malformations were as follows:Michel deformity one case(two ears Fig.2),incomplete partition typesⅠone case(IP-Ⅰ,two ears,accompanyied by vestibule lateral semicircular canal dysplasia),incomplete partition typesⅡ3 cases(IP-Ⅱ,Mondini deformity,6 ears,accompanied by dilation of lateral semicircular canal and vestibule,enlarged vestibular aqueduct),vestibule and lateral semicircular canal dysplasia 3cases(6ears),isolated semicircular canal abnormality 4 cases(8ears), narrow internal auditory canal one case(two ears),X-linked inherited deafness one case(two ears),enlarged vestibular aqueduct 20 cases(39ears).
2.The axial,MPR and VRT reconstruction images can display the site and degree in the ears with inner ear malformations.The VRT reconstruction images can display the malformations of inner ear three-dimensionally and intuitively.
3.In all cases the diagnosis of inner ear malformation was made by CT imaging. Combined deformities were found in all of the patients with cochlear or vestibule dysplasia in our sieries,and the single structure abnormalities were found only in isolated semicircular canal dysplasia or isolated enlarged vestibular aqueduct.
4.The measurements of the central bony island width within the LSCC showed:A small bony island of the LSCC(＜3mm in diameter) appears highly typical in patients with LVAS.Coexistent inner ear anomalies are common in LVAS.
5.Eighty-six patients received a cochlear implant.The cochlear implantations were performed in 8 patients with the malformation of inner ear.In this series,there were 6cases of large vestibular aqueduct syndrome(LVAS),1 cases of incomplete partition typesⅠ,and 1 cases of Mondini malformation.
Conclusion:
1.HRCT allows a comprehensively assessing various congenital inner ear malformations through high quality MPR and VRT reconstructions.It is very useful to the cochlear implantation.
2.Measurement of the inner ear structures,in conjunction with visual inspection of CT images,will increase recognition of subtle inner ear abnormalities.
3.For the patients with inner ear malformations,it is important to accurately assess the extent of abnormalities in the inner ear and accompanied malformations before operation,and to evaluate the full extent of difficulties of the operation in order to minimize the risk of CSF leakage.
4.Inner ear malformations can not be a contraindication to implantationfor cochlear implantation in children,but it is important to be aware of the various aspects of the surgical management and to attempt to minimize the risks of complications.Cochlear implant is potentially a good functional solution for patients suffering from large vestibular aqueduct syndrome.
Part two Detection of Heredity Deafness Gene Mutations in Chinese Family Suffered from SNHL
Objective:
To identify the prevalence of deafness related gene mutations in patients with SNHL, for the purpose of accumulating the experience and samples for the new technique of the detection of gene mutation and collection basic information for the clinical application of genetic diagnosis and genetic counseling of SNHL.
Methods:
Two Chinese families suffered from SNHL accompanied by diabetes mellitus and three Chinese families suffered from SNHL associated with enlarged vestibular aqueduct(EVA) were collected.Genomic DNA was extracted from peripheral blood cells of all patients and the others of their pedigree.All the coding exons and their flanking sequences of the testing gene were amplified by polymerase chain reaction (PCR).The products were analyzed totest the PDS gene,GJB2 gene and Mt 3243 gene mutations in these families.
Results:
There are no GJB2 and Mt 3243 gene mutations found in the two Chinese family suffered from SNHL accompanied by diabetes mellitus.SLC26A4 gene mutation was found in two of the three Chinese families suffered from SNHL associated with enlarged vestibular aqueduct.
Conclusion:
The mutations of GJB2 are not likely to be the cause of SNHL accompanied by diabetes mellitus in our siries.More studies are needed.SLC26A4 mutations were found in the family with EVA.Genetic test for this mutation is necessary for prenatal diagnosis of these two families,and genetic testing can provide efficient information about hearing condition of their offsprings.
Part three Lateral Semicircular Canal Plugging for Treatment of Labyrinthine Fistula Caused by Cholesteatoma
Objective:
To evaluate the effect of semicircular canal occlusion on hearing in the treatment of labyrinthine fistula caused by cholesteatoma
Methods:
Retrospective study based on 16 cases of labyrinthine fistula caused by cholesteatoma. The preoperative symptoms,incidence of labyrinthine fistula,type of surgery and preoperative and postoperative hearing function and intraoperative findings were analyzed.Preoperative high resolution computed tomography(HRCT) scans and the MPR reconstruction were performed on all patients,
Results:
1.All patients were detected to be with labyrinthine fistula in preoperative HRCT imaging.During the operation the lateral semicircular canal was found in all of the cases.
2.During surgery the matrix over the fistula was removed in all cases.Occlusion of the lateral semicircular canal for the treatment of labyrinthine fistula was performed in all cases.Postoperative change of bone conduction threshold was not significantly different compared with preoperative bone conduction threshold(P＜0.05).
3.The patients were followed up for an average time of 15 months,dizziness disappeared completely in all cases and the preservation of the bone conduction threshold was obtained when semicircular canal occlusion surgical technique is used.
Conclusion:
1.Preoperative HRCT scan and MPR reconstruction technique is useful in diagnosis of labyrinthine fistula.but it s limitations should also be recognized.The verification of a labyrinthine fistula can be definitively established only at the time of surgery.
2.The current study confirmed that careful manipulation of the labyrinthine fistula is safe to preserve hearing functions for these patients.
3.Hearing preservation can be obtained when semicircular canal occlusion surgical technique is used.
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25 Park HJ,Lee SJ,Jin HS,et al.Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans.Clin Genet.2005 Feb;67(2):160-5.
26 Campbell C,Cucci RA,Prasad S,et al.Pendred syndrome,DFNB4,and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.Hum Mutat.2001 May;17(5):403-411.
27 戴扑,韩东一,冯勃,等.大前导水管综合征的基因诊断和SLC26A4基因突变分析.中国耳鼻咽喉头颈外科,2006,13:303-307.
28 Ballinger SW,Shoffner JM,Hedaya EV,et al.Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.Nat Genet.1992Apr;1(1):11-15.
29 van den Ouweland JM,Lemkes HH,Ruitenbeek W,et al.Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type Ⅱ diabetes mellitus and deafness.Nat Genet.1992 Aug;1(5):368-371.
30 Reardon W,Ross RJ,Sweeney MG,et al.Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA.Lancet.1992 Dec 5;340(8832):1376-1379.
31 项坤三,陆惠娟,吴松华,等.线粒体tRNAleu(UUR)基因突变糖尿病的基因诊断(一个中国人).中华医学志,1995,75:2162219.
32 Hosszufalusi N,Karcagi V,Horvath R,et al.A detailed investigation of maternally inherited diabetes and deafness(MIDD) including clinical characteristics,C-peptide secretion,HLA-DR and -DQ status and autoantibody pattern.Diabetes Metab Res Rev.2009 Feb;25(2):127-135.
33 Bergamin CS, Rolim LC, Dib SA, et al. Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10. Arq Bras Endocrinol Metabol. 2008 Nov; 52(8): 1345-1349.
34 Maassen JA, 't Hart LM, Janssen GM, et al. Mitochondrial diabetes and its lessons for common Type 2 diabetes. Biochem Soc Trans. 2006 Nov; 34(Pt 5):819-823.
35 Friedman TB, Griffith AJ. Human nonsyndromic Sensorineural deafness. Annu Rev Genomics Hum Genet. 2003; 4:341-402.
1 Minor LB.Labyrinthine fistulae:pathobiology and management.Curr Opin Otolaryngol Head Neck Surg.2003 Oct;11(5):340-346.
2 Gersdorff MC,Nouwen J,Decat M,et al.Labyrinthine fistula after cholesteatomatous chronic otitis media.Am J Otol.2000 Jan;21(1):32-35.
3 张天宇,王正敏,迟放鲁,等.慢性化脓性中耳炎并发全聋的临床研究.临床耳鼻咽喉科杂志,2002,16(7):336-337.
4 Soda-Merhy A,Betancourt-Suarez MA.Surgical treatment of labyrinthine fistula caused by cholesteatoma.Otolaryngol Head Neck Surg.2000 May;122(5):739-742.
5 Ahmad I,East DM.Hearing preservation in patients with labyrinthine fistulae.Rev Laryngol Otol Rhinol(Bord).2002;123(1):49-52.
6 Busaba NY.Clinical presentation and management of labyrinthine fistula caused by chronic otitis media.Ann Otol Rhinol Laryngol.1999 May;108(5):435-439.
7 Sanna M,Zini C,Bacciu S,et al.Management of the labyrinthine fistula in cholesteatoma surgery.ORL J Otorhinolaryngol Relat Spec 1984;46:165-172.
8 Kobayashi T,Sato T,Toshima M,et al.Treatment of labyrinthinefistula with interruption of the semicircular canals.Arch Otolaryngol Head Neck Surg 1995;121:469 -475.
9 Seo T,Hashimoto M,Saka N,et al.Hearing and vestibular functions after plugging surgery for the posterior semicircular canal.Acta Otolaryngol.2008 Dec 30:1-5.
10 殷善开,沈平江,鲁文莺,等.半规管阻塞技术的初步临床应用.中国耳鼻咽喉头颈外科,2003,1 0(5):263-265.
11 Carey JP,Migliaccio AA,Minor LB.Semicircular canal function before and after surgery for superior canal dehiscence.Otol Neurotol.2007 Apr;28(3):356-364.
12 Agrawal SK,Parnes LS.Transmastoid superior semicircular canal occlusion.Otol Neurotol.2008 Apr;29(3):363-7.
13 Chen Z,Yu D,Yin S,Wang J.Horizontal semicircular canal occlusion in a patient with benign paroxysmal positional vertigo.J Otolaryngol Head Neck Surg.2008Jun;37(3):E69-72.
14 Yin S,Chen Z,Yu D,et al.Triple semicircular canal occlusion for the treatment of Meniere's disease.Acta Otolaryngol.2008 Jul;128(7):739-743.
15 Jang CH,Merchant SN·Histopathology of labyrinthine fistula in chronic otitis media with clinical implications[J].Am J Otol' 1997,18(1):15-25.
16 Gersdorff MC,Nouwen J,Decat M,et al.Labyrinthine fistula after cholesteatomatous chronic otitis media[J].Am J Otol,2000,21(1):32-35.
17 Quaranta N,Liuzzi C,Zizzi S,et al.Surgical treatment of labyrinthine fistula in cholesteatoma surgery.Otolaryngol Head Neck Surg.2009 Mar;140(3):406-11.
18 Magliulo G,Celebrini A,Cuiuli G,Parrotto D.Surgical management of the labyrinthine fistula complicating chronic otitis media with or without cholesteatoma.J Otolaryngol Head Neck Surg.2008 Apr;37(2):143-147.
19 吴雅琴,殷善开,时海波,等.半规管阻塞技术治疗迷路瘘管初步报告.上海交通大学学报(医学版),2007,27(9):1056-1057
20 Hara M,Kimura RS.Morphology of the membrana limitans.Ann Otol Rhinol Laryngol.1993 Aug;102(8 Pt 1):625-30.
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1 Kelley PM, Harris DJ, Comer BC, et al. Novel mutations in the Connexin 26 gene (GJB2) that cause autosomal recessive(DFNBl) hearing loss. Am J Hum Genet. 1998 Apr; 62(4):792-799.
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4 Kelsell DP, Dunlop J, Stevens HP,et al. Connexin 26 mutations in hereditary non-syndromic Sensorineural deafness. Nature. 1997 May 1; 387(6628):80-83.
5 Smith RJ, Robin NH. Genetic testing for deafhess-GJB2 and SLC26A4 as causes of deafness. J Commun Disord. 2002 Jul-Aug;35(4):367-377.
6 Prezant TR, Agapian JV, BoMman MC, et al. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and nonsyndromic deafness. Nat Genet, 1993, 4(3): 289-294.
7 Reid FM, Vernham GA, Jacobs HT. Complete mtDNA sequence of a patient in a maternal pedigree with Sensorineural deafness. Hum Mol Genet. 1994 Aug; 3 (8): 1435-6.
8 Casano RA, Johnson DF, Bykhovskaya Y, et al. Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity andclinical implications. Am J Otolaryngol. 1999 May-Jun; 20(3): 151-156.
9 van den Ouweland JM, Lemkes HH, Trembath RC, et al. Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes. 1994 Jun; 43(6):746-751.
10 Maassen JA, 't Hart LM, Janssen GM, et al. Mitochondrial diabetes and its lessons for common Type 2 diabetes. Biochem Soc Trans. 2006 Nov; 34(Pt 5):819-823.
11 戴朴,于飞,康东洋,等.线粒体DNAl555位点和GJB2基因及SLC26A4基因的诊断方法及临床应用.中华耳鼻咽喉头颈外科杂志,2005,40(10):769-773.
12 王秋菊,韩东一,郭玉芬,等.遗传性耳聋资源收集保存及基因定位克隆.中国耳鼻咽喉头颈外科,2006,13(10):661-665.
13 Albert S,Blons H,Jonard L,et al.SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations.Eur J Hum Genet.2006 Jun;14(6):773-779.
14 Todt I,Hennies HC,Basra D,et al.Vestibular dysfunction of patients with mutations of Connexin 26.Neuroreport.2005 Aug 1;16(11):1179-1181.
15 Thomas MA,Der Kaloustian VM,Tewfik TL.Connexin mutation testing of children with nonsyndromic,autosomal recessive sensorineural hearing loss.J Otolaryngol.2004 Jun;33(3):189-192.
16 Avraham KB.Deafness.Sounds from the cochlea.Nature.1997 Dec 11;390(6660):559-560.
17 Cryns K,Orzan E,Murgia A,et al.A genotype-phenotype correlation for GJB2(connexin 26) deafness.J Med Genet.2004 Mar;41(3):147-154.
18 Sugata A,Fukushima K,Sugata K,et al.High-throughput screening for GJB2mutations--its clinical application to genetic testing in prelingual deafness screening for GJB2 mutations.Auris Nasus Larynx.2002 Jul;29(3):231-239.
19 Estivill X,Fortina P,Surrey S,et al.Connexin-26 mutations in sporadic and inherited sensorineural deafness.Lancet.1998 Feb 7;351(9100):394-398.
20 Everett LA,Glaser B,Beck JC,et al.Pendred syndrome is caused by mutations in a putative sulphate transporter gene(PDS).Nat Genet.1997 Dec;17(4):411-22.
21 Usami S,Abe S,Weston MD,et al.Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations.Hum Genet.1999 Feb;104(2):188-92.
22 陈东野,陈晓巍,金昕,等.伴内耳畸形的人工耳蜗植入患者SLC26A4(PDS)基因突变分析.中华医学杂志,2007,87(40):2820-2824.
23 Fitoz S,Sennaroglu L,Incesulu A,et al.SLC26A4 mutations are associated with a specific inner ear malformation.Int J Pediatr Otorhinolaryngol.2007 Mar;71(3):479-86.
24 Park H J,Shaukat S,Liu XZ,et al.Origins and frequencies of SLC26A4(PDS)mutations in east and south Asians:global implications for the epidemiology of deafness.J Med Genet.2003 Apr;40(4):242-248.
25 Park HJ,Lee SJ,Jin HS,et al.Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans.Clin Genet.2005 Feb;67(2):160-5.
26 Campbell C,Cucci RA,Prasad S,et al.Pendred syndrome,DFNB4,and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.Hum Mutat.2001 May;17(5):403-411.
27 戴扑,韩东一,冯勃,等.大前导水管综合征的基因诊断和SLC26A4基因突变分析.中国耳鼻咽喉头颈外科,2006,13:303-307.
28 Ballinger SW,Shoffner JM,Hedaya EV,et al.Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.Nat Genet.1992Apr;1(1):11-15.
29 van den Ouweland JM,Lemkes HH,Ruitenbeek W,et al.Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type Ⅱ diabetes mellitus and deafness.Nat Genet.1992 Aug;1(5):368-371.
30 Reardon W,Ross RJ,Sweeney MG,et al.Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA.Lancet.1992 Dec 5;340(8832):1376-1379.
31 项坤三,陆惠娟,吴松华,等.线粒体tRNAleu(UUR)基因突变糖尿病的基因诊断(一个中国人).中华医学志,1995,75:2162219.
32 Hosszufalusi N,Karcagi V,Horvath R,et al.A detailed investigation of maternally inherited diabetes and deafness(MIDD) including clinical characteristics,C-peptide secretion,HLA-DR and -DQ status and autoantibody pattern.Diabetes Metab Res Rev.2009 Feb;25(2):127-135.
33 Bergamin CS, Rolim LC, Dib SA, et al. Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10. Arq Bras Endocrinol Metabol. 2008 Nov; 52(8): 1345-1349.
34 Maassen JA, 't Hart LM, Janssen GM, et al. Mitochondrial diabetes and its lessons for common Type 2 diabetes. Biochem Soc Trans. 2006 Nov; 34(Pt 5):819-823.
35 Friedman TB, Griffith AJ. Human nonsyndromic Sensorineural deafness. Annu Rev Genomics Hum Genet. 2003; 4:341-402.
1 Minor LB.Labyrinthine fistulae:pathobiology and management.Curr Opin Otolaryngol Head Neck Surg.2003 Oct;11(5):340-346.
2 Gersdorff MC,Nouwen J,Decat M,et al.Labyrinthine fistula after cholesteatomatous chronic otitis media.Am J Otol.2000 Jan;21(1):32-35.
3 张天宇,王正敏,迟放鲁,等.慢性化脓性中耳炎并发全聋的临床研究.临床耳鼻咽喉科杂志,2002,16(7):336-337.
4 Soda-Merhy A,Betancourt-Suarez MA.Surgical treatment of labyrinthine fistula caused by cholesteatoma.Otolaryngol Head Neck Surg.2000 May;122(5):739-742.
5 Ahmad I,East DM.Hearing preservation in patients with labyrinthine fistulae.Rev Laryngol Otol Rhinol(Bord).2002;123(1):49-52.
6 Busaba NY.Clinical presentation and management of labyrinthine fistula caused by chronic otitis media.Ann Otol Rhinol Laryngol.1999 May;108(5):435-439.
7 Sanna M,Zini C,Bacciu S,et al.Management of the labyrinthine fistula in cholesteatoma surgery.ORL J Otorhinolaryngol Relat Spec 1984;46:165-172.
8 Kobayashi T,Sato T,Toshima M,et al.Treatment of labyrinthinefistula with interruption of the semicircular canals.Arch Otolaryngol Head Neck Surg 1995;121:469 -475.
9 Seo T,Hashimoto M,Saka N,et al.Hearing and vestibular functions after plugging surgery for the posterior semicircular canal.Acta Otolaryngol.2008 Dec 30:1-5.
10 殷善开,沈平江,鲁文莺,等.半规管阻塞技术的初步临床应用.中国耳鼻咽喉头颈外科,2003,1 0(5):263-265.
11 Carey JP,Migliaccio AA,Minor LB.Semicircular canal function before and after surgery for superior canal dehiscence.Otol Neurotol.2007 Apr;28(3):356-364.
12 Agrawal SK,Parnes LS.Transmastoid superior semicircular canal occlusion.Otol Neurotol.2008 Apr;29(3):363-7.
13 Chen Z,Yu D,Yin S,Wang J.Horizontal semicircular canal occlusion in a patient with benign paroxysmal positional vertigo.J Otolaryngol Head Neck Surg.2008Jun;37(3):E69-72.
14 Yin S,Chen Z,Yu D,et al.Triple semicircular canal occlusion for the treatment of Meniere's disease.Acta Otolaryngol.2008 Jul;128(7):739-743.
15 Jang CH,Merchant SN·Histopathology of labyrinthine fistula in chronic otitis media with clinical implications[J].Am J Otol' 1997,18(1):15-25.
16 Gersdorff MC,Nouwen J,Decat M,et al.Labyrinthine fistula after cholesteatomatous chronic otitis media[J].Am J Otol,2000,21(1):32-35.
17 Quaranta N,Liuzzi C,Zizzi S,et al.Surgical treatment of labyrinthine fistula in cholesteatoma surgery.Otolaryngol Head Neck Surg.2009 Mar;140(3):406-11.
18 Magliulo G,Celebrini A,Cuiuli G,Parrotto D.Surgical management of the labyrinthine fistula complicating chronic otitis media with or without cholesteatoma.J Otolaryngol Head Neck Surg.2008 Apr;37(2):143-147.
19 吴雅琴,殷善开,时海波,等.半规管阻塞技术治疗迷路瘘管初步报告.上海交通大学学报(医学版),2007,27(9):1056-1057
20 Hara M,Kimura RS.Morphology of the membrana limitans.Ann Otol Rhinol Laryngol.1993 Aug;102(8 Pt 1):625-30.
21 孙建军,倪道凤.提高中耳乳突炎的诊断与外科治疗水平.中华耳鼻咽喉科杂志,2007,42(7):481-482.
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