安定对前庭功能及前庭代偿影响的研究进展

本文复习安定的应用药理学，就其对前庭功能及前度代偿的影响进行综述。指出安定对前庭功能有一定的抑制作用，对前庭代偿过程可产生不同的影响，认为研究结果的差异与多种因素有关。     

组胺与前庭功能

组胺作为中枢神经递质参与前庭功能的调控。本文就中枢组胺能系统的解剖生理特点、组胺与前庭功能、组胺与前庭代偿的相关研究作一综述。     

1个DFNA5家系临床遗传学特点及听力学特征分析

目的:对1个DFNA5大家系的临床遗传学特点及听力学特征进行分析.方法:通过整理分析家系资料,确定该家系的遗传方式为常染色体显性遗传,对家系成员的临床特点进行分析,对比研究该家系成员听力受损与年龄增长之间的关系.结果:该家系是一个分布于5代、成员共42例(包括已故和配偶)的常染色体显性遗传性聋家系,听力学特征表现为早期以高频损失为主,听力曲线多呈"Z"型,随着年龄增长,逐渐演变为斜坡形听力曲线.最终导致全频听力逐渐下降.结论:该家系是一个常染色体显性遗传的DFNA5大家系,听力学具有早期高频听力下降并逐渐累积全频的特征,这一特征与年龄相关性听力损失的频率特性很相似,因此具备该类听力特点的遗传性聋应考虑到DFNA5基因突变的可能.     

中国一家系凝血因子C同源物基因新突变携带者听力学及前庭功能特点

目的分析携带凝血因子C同源物（coagulation factor C homology，COCH）基因新突变的中国常染色体显性遗传非综合征型聋（autosomal dominant non-syndromic sensorineural hearing loss，DFNA）9家系成员的听力学及前庭功能特点。方法对家系成员进行纯音测听、听性脑干反应、耳蜗电图等听力学及计算机动态姿势描记、前庭诱发性肌源性电位、视眼动、前庭眼动等前庭功能检查。结果听力学检查提示该家系患者20～50岁出现以高频下降为主的进行性感音神经性聋，60～70岁进展为重至极重度全频听力损失。前庭功能检查提示随意抽取的家系中耳聋患者计算机动态姿势描记、视眼动、温度试验正常；前庭诱发性肌源性电位检查提示耳聋患者耳石功能异常；速度阶梯试验时间常数异常、正弦谐波试验增益和相位异常，提示耳聋患者水平半规管功能减弱。结论中国DFNA9家系的所有耳聋患者均无前庭功能损害的主诉，通过详尽的前庭功能检查提示位于COCH非胶原结构糖蛋白A型2结构域上的突变所导致的前庭功能损害明显轻于位于LCCL结构域上的突变。中国DFNA9家系的临床资料分析首次表明DFNA9存在基因型和表现型的相关性。     

前庭性偏头痛患者前庭功能的临床研究

目的通过实验室检查来评估前庭性偏头痛(vestibular migrain,VM)患者的前庭功能,探寻该疾病的前庭功能特点。方法对37例确诊为前庭性偏头痛的患者及30例健康志愿者分别行冷热试验(caloric test)、摇头试验(head-shaking nystagmus,HNS)、速度阶梯试验及颈肌性前庭诱发电位(cervical Vestibular-Evoked Myogenic Potentials,cVEMP)检查,对两组冷热试验、摇头试验及速度阶梯试验的异常结果进行分析,对100dB的短音刺激情况下cVEMP不对称性进行分析。结果前庭性偏头痛患者水平半规管功能的异常率显著高于对照组,差异有统计学意义(P<0.05)。37例VM患者中,有11例(29.7%)出现冷热试验异常,14例(37.8%)出现摇头试验异常,7例(18.9%)出现速度阶梯试验异常。30例健康志愿者中,有2例(6.7%)出现冷热试验异常,1例(3.3%)出现摇头试验异常,无患者出现速度阶梯试验异常。总体而言,28例(76%)VM患者至少在一个水平半规管功能试验中出现异常,异常率最高的是摇头试验,其次是冷热试验和速度阶梯试验。前庭性偏头痛患者的cVEMP异常率(21.6%)要显著高于对照组(3.3%),差异有统计学意义(P<0.05)。结论 76%的前庭性偏头痛患者被发现存在前庭功能异常,在冷热试验的基础上加用摇头试验和旋转试验,可以提高VM患者前庭功能异常的检出率。前庭性偏头痛患者显示的cVEMP结果,反映了球囊功能的异常及VM患者在球囊-颈反射通路上有所损害。前庭性偏头痛患者存在不同程度的前庭功能异常。     

听力学及前庭功能检查在桥小脑角肿瘤诊断中的意义

目的 :探讨听力学及前庭功能检查在桥小脑角肿瘤诊断中的意义。方法 :回顾性分析 2 0例 (2 1耳 )桥小脑角肿瘤患者的听力学及前庭功能资料。结果 :2 0例 (2 1耳 )纯音测听、听觉诱发电位均异常 ,19例镫骨肌声反射及前庭功能异常。结论 :听力学及前庭功能检查有助于桥小脑角肿瘤的诊断。     

大前庭水管综合征患者的听力学特点

目的探讨大前庭水管综合征(large vestibular aqueduct syndrome,LVAS)患者的听力学特点。方法对19例(38耳)LVAS患者进行了纯音听阈测试、盖莱氏试验、声导抗测试及颞骨高分辨CT检查。结果19例(38耳)患者CT检查均为单纯前庭水管扩大。纯音测听34耳为混合性聋,低频骨气导差较大,中高频骨气导差较小。28耳鼓室导抗图均为A型,20耳可引出声反射,声反射阈与听阈之差平均为28 dB HL。28耳进行了共振频率测试,中耳共振频率为652±175 Hz,较正常耳低(P<0.01)。18耳进行了盖莱氏试验,均为阳性。结论LVAS患者可表现为感音神经性聋,也可表现为混合性聋。混合性聋患者在听力较好时可引出声反射,是该病的特征性表现。另外,该病呈混合性聋时,还可能意味着病变的可逆性。     

中国前庭康复现状与前庭康复继续教育

前庭康复是前庭功能损伤后缓解症状与功能恢复的基础。国际上,前庭康复系统化的工作标志是前庭康复专著的出版。中国前庭康复工作起步较晚,推进比较缓慢。目前,国内前庭康复工作的开展基本是以“眩晕中心”为依托,医生在患者就诊时给予康复指导,并进行随访,还缺乏康复科专业的大夫进行眩晕的前庭康复治疗。随着耳科学的发展,眩晕在中国受到前所未有的关注,本文通过了解前庭康复的理论、现状及其教育,指导相关医生掌握康复培训基础与临床的专业技能,以特殊的评价技术和治疗技术积极推进前庭康复,使国内前庭康复工作能够健康发展。     

单侧前庭功能低下患者前庭康复治疗前后前庭自旋转试验的动态变化

目的:观察前庭自旋转试验（vestibular autorotation test,VAT）在单侧前庭功能低下（unilateral vestibular hypo function,UVH）患者前庭康复治疗前后的动态变化。方法:回顾性研究2019年1月至2021年1月就诊于华中科技大学同济医学院附属协和医院耳鼻咽喉科...     

糖尿病患者前庭功能的变化特点

目的　了解糖尿病对前庭功能的影响。方法  通过视频眼震图（videonystagmography,VNG）描记法,分析120例Ⅱ型糖尿病患者前庭功能的特点。根据病程分 组,A组：糖尿病病程≤5年者;B组：糖尿病病程5～10年者;C组：糖尿病病程＞10年者。3个组间进行前庭中枢和外周功能比较。结果　①前庭功能异常97例（80.8%）,其中前庭外周功能异常64例（66.0%）,前庭中枢功能异常16例（16.5%）,外周合并前庭中枢功能异常17例（17.5%）。②不同病程组间比较：前庭中枢功能异常在不同病程组间比较有显著性差异（P＜0.05）,组间两两比较均有显著性差异（P＜0.017）。结论　研究提示随着糖尿病病程进展,视跟踪、视动性眼动异常反应发生率同步增高。     

Clinical characterization of a novel COCH mutation G87V in a Chinese DFNA9 family

Objectives

To characterize the clinical features of a Chinese DFNA9 family associated with a novel COCH mutation and to confirm the proposed genotype–phenotype correlation of COCH.

Methods

Mutation screening of 79 deafness genes was performed in the proband by targeted next-generation sequencing. Co-segregation of the disease phenotype and the detected variants was confirmed in all family members by PCR amplification and Sanger sequencing. The progression of hearing impairment in affected family members was followed and the concomitant vestibular dysfunction was verified by the caloric vestibulo-ocular reflex test.

Results

A novel COCH mutation p.G87V was identified in the family segregating with late-onset, progressive sensorineural hearing impairment and consistent vestibular dysfunction.

Conclusion

The p.G87V mutation leads to a very similar phenotype as a previously reported p.G87W mutation of COCH. Our study suggested that the G87 residue is critical for function of COCH and further confirms a previously proposed genotype–phenotype correlation for DFNA9.     

Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): a follow‐up study of a family

Hereditary cochleovestibular dysfunction due to a COCH gene mutation (DFNA9): a follow‐up study of a family Cochleovestibular impairment was evaluated, in relation to age, in a longitudinal follow‐up study on a Dutch family with a DFNA9 trait caused by a Pro51Ser mutation in the COCH gene on chromosome 14q12‐q13. Fourteen cases were genotyped. The onset age of progressive impairment reported by the mutation carriers was between age 35 and 45 years. Pure‐tone thresholds deteriorated by about 2–7 dB per year (mean 3.8 dB per year) in a variable, often asymmetrical, fashion. One mutation carrier developed recurrent episodes of vertigo accompanied by nausea and vomiting, resembling Ménière's disease. Two others developed special susceptibility for motion sickness and appeared to have a hyperactive vestibulo‐ocular reflex. More advanced stages of vestibular impairment, i.e. vestibular hyporeflexia and complete vestibular areflexia, were eventually found in a number of cases. DFNA9/COCH should be considered as a possible cause in patients developing combined progressive cochlear and vestibular impairment, or suspected hereditary Ménière‐like disease, from around middle age.     

Extralabyrinthine Manifestations of DFNA9

DFNA9 is an autosomal dominant cause of non-syndromic adult-onset sensorineural hearing loss with associated variable vestibular dysfunction caused by mutations in the COCH gene. DFNA9 has previously been characterized by the presence of unique histopathologic features limited to the cochlear and vestibular labyrinth. This report describes newly discovered extralabyrinthine findings within the middle ear in DFNA9 and discusses their implications. The histopathologic anatomy of extralabyrinthine structures was reviewed in 12 temporal bones from seven individuals with DFNA9 and compared with age-matched controls. All temporal bones with DFNA9 had abnormal deposits within the tympanic membrane, incudomalleal joint, and incudostapedial joint. Hematoxylin and eosin stain and Movat’s pentachrome stain both revealed different staining patterns of the extralabyrinthine deposits compared with the intralabyrinthine deposits suggesting that the composition of the deposits varies with location. The deposits within the tympanic membrane resembled cartilage morphologically and stained positively for aggrecan, an extracellular matrix protein found in cartilage. However, the cellular component of the tympanic membrane deposits did not stain with immunomarkers for chondrocytes (s100 and connective tissue growth factor). These novel findings in DFNA9 have implications for the phenotypic expression of the disorder and the clinical workup of adult-onset sensorineural hearing loss.     

KCNN4及KPTN基因在中国DFNA4型耳聋中的突变检测

目的应用位置候选基因法了解中国DFNA4型耳聋家系定位区域内的两个基因KCNN4、KPTN与该家系耳聋表型的相关性。方法对一个6代相传、全基因组扫描连锁分析定位于DFNA4座位的常染色体显性遗传性耳聋中国家系成员,针对候选基因KCNN4、KPTN的全部编码序列设计引物,应用PCR扩增反应、产物纯化后直接测序的方法进行突变或多态性位点的检测与鉴定。结果两种基因的各对引物均有较好的扩增效果,直接测序结果与标准序列比对分析显示在KCNN4基因的所有编码区未检测到突变;在KPTN基因外显子10的编码区鉴定出一处同义突变（2154G／A,P302P）,该突变不与家系的耳聋表型共分离,为已报道的单核苷酸多态性（SNP）位点（rs2293424）。结论该中国DFNA4家系的耳聋表型不是由其定位区域内的KCNN4、KPTN基因编码区的突变所导致,但这两个基因仍是极好的耳聋候选基因,其与遗传性耳聋的相关性有待进一步研究。     

DFNA9 is a progressive audiovestibular dysfunction with a microfibrillar deposit in the inner ear

OBJECTIVES: Several mutations in the COCH gene were recently identified in American and European families with DFNA9, an autosomal dominant progressive sensorineural hearing loss with onset in high frequencies. Our preliminary vestibular studies in one American family indicated progressive vestibular dysfunction. More complete vestibular studies in European families have shown vestibular abnormalities in the affected individuals. Our temporal bone studies on two families with DFNA9 revealed, in addition to neurosensory degeneration, a unique acidophilic deposit in the membranous labyrinths of the affected individuals. The purposes of this study were 1) to further investigate the vestibular abnormalities in members of one American family for the purposes of genotype-phenotype correlation and 2) to investigate the electron microscopic structure of the acidophilic deposit to obtain further insights into the pathogenesis of DFNA9. STUDY DESIGN: Prospective analysis. METHODS: Extensive vestibular testing was performed in some unaffected and affected members of a family with DFNA9. One temporal bone was analyzed by electron microscopy of celloidin-embedded tissue. RESULTS AND CONCLUSIONS: The findings indicate progressive vestibular dysfunction in many of the patients affected with hearing loss. Thus, despite different mutations in the COCH gene, the American and European families manifest auditory and vestibular dysfunction. Electron microscopic analysis shows the spiral ligament to be enriched for a highly branched non-banded microfibrillar substance that is decorated with glycosaminoglycan granules. Additionally, the spiral ligament lacks the 67-nm-thick straight periodically banded bundles of type II collagen that are normally abundant in this structure. A speculative pathogenetic model is proposed for this unique disease and its relationship with other late-onset or adult-onset audiovestibular diseases and Meniere's disease is investigated.     

Cochlear implants for DFNA17 deafness

BACKGROUND: Nonsyndromic autosomal-dominant, adult-onset sensorineural hearing loss resulting from DFNA17 was described in a single American kindred in 1997, and the causative gene was subsequently identified as MYH9. OBJECTIVE: The objective of this study was to report clinical and genetic analyses of an Australian family with nonsyndromic adult-onset sensorineural hearing loss. METHODS: The clinical presentation of the family was detailed and identification of the causative gene was conducted by SNP genotyping and direct sequencing. RESULTS: Sequence analysis of the MYH9 gene revealed the same missense mutation as in the original DFNA17 family. We are not aware of a link between the two kindreds, making the present one only the second DFNA17 family to be reported. CONCLUSIONS: One important point of clinical relevance is the excellent outcome with cochlear implants in the Australian family compared with a "poor" response in the American family. Thus, cochlear implants should be strongly considered for clinical management of patients with DFNA17 deafness.     

Audiological Evaluation of Affected Members from a Dutch DFNA8/12 (<Emphasis Type="Italic">TECTA</Emphasis>) Family

In DFNA8/12, an autosomal dominantly inherited type of nonsyndromic hearing impairment, the TECTA gene mutation causes a defect in the structure of the tectorial membrane in the inner ear. Because DFNA8/12 affects the tectorial membrane, patients with DFNA8/12 may show specific audiometric characteristics. In this study, five selected members of a Dutch DFNA8/12 family with a TECTA sensorineural hearing impairment were evaluated with pure-tone audiometry, loudness scaling, speech perception in quiet and noise, difference limen for frequency, acoustic reflexes, otoacoustic emissions, and gap detection. Four out of five subjects showed an elevation of pure-tone thresholds, acoustic reflex thresholds, and loudness discomfort levels. Loudness growth curves are parallel to those found in normal-hearing individuals. Suprathreshold measures such as difference limen for frequency modulated pure tones, gap detection, and particularly speech perception in noise are within the normal range. Distortion otoacoustic emissions are present at the higher stimulus level. These results are similar to those previously obtained from a Dutch DFNA13 family with midfrequency sensorineural hearing impairment. It seems that a defect in the tectorial membrane results primarily in an attenuation of sound, whereas suprathreshold measures, such as otoacoustic emissions and speech perception in noise, are preserved rather well. The main effect of the defects is a shift in the operation point of the outer hair cells with near intact functioning at high levels. As most test results reflect those found in middle-ear conductive loss in both families, the sensorineural hearing impairment may be characterized as a cochlear conductive hearing impairment.     

进行性非综合征型聋家系临床表型及遗传学分析

目的分析一个连续五代常染色体显性遗传性非综合征型聋家系的临床表型及遗传学特征。方法对该耳聋家系成员进行病史采集、全身及听力学检查,绘制遗传图谱并进行遗传学特征分析。应用微卫星标记连锁分析方法及外显子序列分析对常染色体显性遗传(DFNA)23个基因的22个位点进行初步筛查。结果该耳聋家系共五代,现存家系成员44人,参与本研究的39人中耳聋患者16人,除1人为语前聋外,其他患者均表现为迟发性、渐进性听力下降,发病年龄介于14～40岁,早期以中频听力下降为主,逐渐累及高频,随着年龄的增长,呈全频听力下降。除DFNA5外,各DFNA位点连锁分析所得LOD值均<-2,提示该家系的致聋基因与这些位点均不连锁。对家系中2例患者和2例正常者DFNA5的所有外显子进行测序分析,未发现突变。结论该家系遗传方式符合常染色体显性遗传规律,表现为以中高频听力下降为主的感音神经性聋;对已知耳聋基因位点进行筛查,未发现明确的阳性位点;通过新一代测序技术进行全外显子组分析可能发现新的感音神经性聋致病基因。