SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome

OBJECTIVES:: The objectives of this study were to identify SIX1 gene mutations in a patient with branchio-oto syndrome (BO) and to clarify the relationship between SIX1 mutation and enlargement of the vestibular aqueduct (EVA). METHODS:: A genetic study and retrospective chart review for a patient in whom EYA1 mutation had already been excluded was conducted. We studied a Japanese patient who had autosomal-dominant mixed hearing loss, a unilateral ear pit and unilateral EVA, and who was previously diagnosed as having BO. We searched for SIX1 and SLC26A4 mutations using polymerase chain reaction and direct gene sequencing. RESULTS:: The patient carried a heterozygous A-->G mutation at nucleotide 386 within exon 1 of SIX1 that resulted in substitution of a cysteine for a tyrosine at codon 129 (Y129C) of the gene product. Y129C is a previously identified SIX1 mutation and was not detected in any of our 164 control chromosomes. No SLC26A4 mutations were identified. CONCLUSION:: Y129C mutation in SIX1 may cause EVA as well as BO.     

Labyrinthine fistula detection: the predictive value of vestibular symptoms and computerized tomography

A retrospective case record study of 20 patients in Oslo operated on for chronic otitis media with labyrinthine fistula between 1986 and 1999 was performed in order to estimate the incidence of, and identify predictors for, labyrinthine fistulas. The incidence of fistula was 0.3 per 100 000, with a median age at diagnosis of 37 years. The median duration of chronic otitis media prior to labyrinthine fistula detection was significantly correlated with age at surgery. Subjective hearing loss (90%), otorrhoea (65%) and dizziness (50%) were presenting symptoms. Modified canal-wall-down mastoidectomy was performed in all patients. Preoperative hearing levels could not predict postoperative hearing outcome. Positive signs of fistula were found in only 4 patients (20%). Correspondingly, computerized tomography (CT) diagnosed the fistula in 11 patients (55%). The seven patients presenting without dizziness and with a negative CT scan and fistula test were characterized by lower age, absence of previous middle ear surgery, lower preoperative pure-tone thresholds for bone conduction and better hearing outcome after surgery. In conclusion, the identification of a younger group of patients presenting with fewer symptoms indicates that fistulas should be suspected in all patients undergoing surgery for chronic middle ear and mastoid disease.     

Radiographic classification of the vestibular and cochlear aqueducts: the paired correlation between normal and abnormal vestibular aqueduct and cochlear aqueduct anatomy

Multidirectional tomography (MDT) can be useful in determining the caliber, shape, and course of the vestibular aqueduct (VA) and cochlear aqueduct (CA). Clinical decisions have been based on the findings from MDT. Unfortunately, the clinical utility of these observations has been confusing and controversial because similar MDT techniques were not used. This study will address some of the difficult questions and clinical controversies derived from MDT observations. This new perspective has evolved with the use of high resolution computed tomography (HRCT). An analysis of 750 petrous bones for the occurrence of the various types of VAs and CAs using Gado's classification, further vestibular aqueduct and a variation of Gado's classification for the cochlear classification is reported. The distribution of the possible paired types of VA and CA are evaluated. MDT results indicate that the paired analysis in patients with inner ear dysfunction is not useful, cost effective, diagnostic, or of prognostic value. MDT can provide clinically valid observations of periaqueductal and perilabyrinthine pneumatization which is helpful in anticipating the size and position of the endolymphatic sac at the time of surgery for those few patients who may benefit from endolymphatic system surgery. However, when a comparison is made between MDT and CT of 60 ears in those same patients, the clinical limitations of MDT for inner ear diagnosis and prognosis became apparent. The future for HRCT scanning with reformatting holds potential for clinically meaningful visualization of inner and middle ear structures previously expected from MDT imaging.     

Hearing loss associated with enlargement of the vestibular aqueduct: mechanistic insights from clinical phenotypes, genotypes, and mouse models

Enlargement of the vestibular aqueduct (EVA) is one of the most common inner ear malformations associated with sensorineural hearing loss in children. The delayed onset and progressive nature of this phenotype offer a window of opportunity to prevent or retard progression of hearing loss. EVA is not the direct cause of hearing loss in these patients, but rather is a radiologic marker for some underlying pathogenetic defect. Mutations of the SLC26A4 gene are a common cause of EVA. Studies of an Slc26a4 knockout mouse demonstrate that acidification and enlargement of the scala media are early events in the pathogenesis of deafness. The enlargement is driven by fluid secretion in the vestibular labyrinth and a failure of fluid absorption in the embryonic endolymphatic sac. Elucidating the mechanism of hearing loss may offer clues to potential therapeutic strategies.     

临床诊治大前庭水管综合征的思考与建议

18世纪CarloMondini在一例8岁先天性耳聋男孩的颞骨中观察到了前庭水管扩大现象。20世纪60年代，VaIvassori在7000余例耳聋患者的影像学检查中发现160例患者存在前庭水管扩大．几乎所有的前庭水管扩大患者均有感音性聋及前庭症状．并首次报道了前庭水管相关的梅尼埃样临床表型。     

Significance of tomography in Meniere's disease: visualization and morphology of the vestibular aqueduct

The revival of endolymphatic sac surgery has led to many investigations in Meniere's disease, including lateral tomography of the vestibular aqueduct. Contrary to recent literature, we found no difference in the presence and morphology of the vestibular aqueduct when assessed radiologically in a group of Meniere's patients and a control group. Our assessment of this information in regard to etiology and treatment of Meniere's disease is presented.     

大前庭水管综合征的诊治策略研究

目的研究和揭示大前庭水管综合征(LargevestibularaqueductSyndrome,LVAS)的临床诊治策略。方法对2003年5月—2005年12月收集的107例大前庭水管综合征患者进行系统的临床听力学特征分析、影像学分析及SLC26A4致病基因检测分析,以期发现大前庭水管综合征患者的系列特征。临床听力学特征性观察包括纯音听力中低频的气骨导差;听性脑干诱发电位检查时观察特征性的声诱发短潜伏期负反应(acousticallyevokedshortlatencynegativeresponse,ASNR);影像学检查包括对所有患者均行颞骨CT扫描或耳蜗水成像磁共振检查了解前庭水管、内淋巴囊及耳蜗的发育情况;病因学分析包括应用聚合酶链反应(PCR)的方法扩增SLC26A4基因的21个外显子,直接测序,DNAStar及BioEdit序列比对软件分析SLC26A4基因的突变位点。结果70.8%～83.7%LVAS患者在低频500Hz、250Hz存在显著的气骨导差,范围在15～95dBHL。75.7%的LVAS患者在常规ABR测试时发现ASNR,潜伏期为3.26±0.57ms。97.9%的LVAS患者发生了SLC26A4基因的突变,其中双等位基因突变占88.4%,单等位基因和未发现突变的家系分别占9.5%和2.1%。共发现38种突变形式,包括23种国际上尚未报道的突变,15种已报突变(五种仅报道于中国家系)。其中IVS7-2A>G突变是所有突变中最常见的突变,占所有突变者的78.9%,是中国人群中的特征性突变。影像学检查CT及磁共振是诊断LVAS的金标准。结论大前庭水管综合征具有特征性的纯音听力—低频气骨导差;具有特异性的ABR波形—ASNR;CT检查见前庭水管扩大,直径>1.5mm;具有特征性的MRI表现-扩大的内淋巴囊;具有特异和常见的SLC26A4基因突变谱。上述系列特征形成了对大前庭水管综合征的诊断依据。选择积极的治疗方案将有助于患者听力的保护与康复。     

Computer-aided three-dimensional reconstruction of the human vestibular aqueduct and the parvestibular canaliculus

The vestibular aqueduct (VA) and paravestibular canaliculus (PVC) were reconstructed using a computer-aided three-dimensional reconstruction system (SERSERS) from five series of the serial, histopathological sections of the human temporal bones without alignment markers. In order to align the serial sections, more than ten sectional tissue structure images on a section such as the cochlea, VA, PVC, semicircular canals, ossicles and facial canal were compared with those on the consecutive section and the position was determined where the deviation of each sectional image pair would be the minimum in every direction. Repeating this procedure throughout the series of the sections, we could perform the overall alignment of the sections. As the standard viewing axis of reconstruction, we used the modiolus and constructed a triplet of images; posteromedial view image viewing from posterior surface side of the pyramis parallel to the modiolus, superior view image viewing from anterior surface side of the pyramis perpendicularly to the modiolus, anteromedial view image viewing from the internal carotid artery side perpendicularly to the modiolus. The triplet images of the cochlea, VA and PVC presented us their three-dimensional configuration and the spatial relationship among them. Superior view showed that the angle between the plane of the proximal portion of the VA and that of the basal turn of cochlea varied in a wide range from 53 degrees to 68 degrees. Anteromedial view showed that the angle between the plane of the distal portion of the VA and that of the posterior semicircular canal also varied in a wide range from 22 degrees to 49 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)     

Size and growth rate of sporadic vestibular schwannoma: predictive value of information available at presentation.

BACKGROUND: The current study examines the hypothesis that tumor growth rate in sporadic vestibular schwannoma could be in part predicted by data available at diagnosis, such as tumor volume, patient age, laterality, and sex. METHODS: Tumor volumes and growth rates were calculated from serial magnetic resonance imaging data in a cohort of 50 patients (26 men and 24 women; mean age at presentation, 64.1 +/- 12.8 yr). Tumor volumes were measured using an algorithm that corrects for partial volume averaging errors and provides accurate estimates of tumor volume with known errors. RESULTS: Examination of presentation data showed no relationship between tumor size at diagnosis and patient age, sex, or tumor laterality. Two measurements of tumor growth--absolute growth per annum and tumor volume doubling time--were studied, and neither showed any relationship with tumor size at presentation, patient age, tumor laterality, or sex. CONCLUSION: The study represents a typical spectrum of patient ages and is of sufficient size in view of the distribution pattern of the variables to give a calculated statistical power in excess of 90% for each variable. This indicates that the clinical features available at presentation and diagnosis have no power to predict the expected behavior of sporadic vestibular schwannoma.     

Superior semicircular canal dehiscence: positive predictive value of high-resolution CT scanning

Patients with superior dehiscence (SCD) syndrome present with vertigo and oscillopsia evoked by loud sounds and changes in middle ear or intracranial pressure. The first objective of this retrospective cohort study is to demonstrate that thin-section computed tomography (CT) scans reformatted in the plane of the superior semicircular canal (SSC) overestimate this anomaly compared to pathologic studies. The second objective of this study is to re-evaluate the positive predictive value of temporal bone scanning. All temporal bone CT scans with 0.55-mm collimation and reconstruction in the SSC plane performed over a 1-year period were analysed at a tertiary referral centre. CT-positive cases had their clinical data reviewed and patients were re-examined, if available. A total of 581 temporal bone CT-scans were analysed. A dehiscent-appearing superior canal was seen in 4.0% of studies while published pathologic studies report that only 0.5% of temporal bones SSCs have a dehiscence (P < 0.001). Of the 21 patients with positive temporal bone CTs, only 1 presented with sufficient clinical dues to identify the syndrome. Three additional patients did not have symptoms consistent with the diagnosis, but had surgery for a dehiscence of the tegmen mastoideum. When our findings are added to published data, the positive predictive value of temporal bone CT-scanning drops from 93 to 57%. The prevalence of dehiscent-appearing superior canal on thin-section temporal bone scanning with reformation in the SSC plane is much higher than anticipated by pathologic studies. Even with 0.55 mm-collimated helical CT and reformation in the SSC plane, the risk of overdiagnosis is present.     

Estimation of the endolymphatic sac and vestibular aqueduct using magnetic resonance imaging

OBJECTIVE: To evaluate the diagnostic accuracy of magnetic resonance imaging for assessment of the endolymphatic sac and vestibular aqueduct. STUDY DESIGN: Imaging and histological study of the cadaver. METHODS: Five cadavers were studied by a 1.5-T magnetic resonance imaging system with a 3-inch-diameter surface coil. Magnetic resonance imaging scans were obtained with proton density-weighted and T2-weighted fast spin-echo sequences. Histological sections were made with an epoxy resin-embedding method and were compared with magnetic resonance imaging scans. RESULTS: The visibility of the endolymphatic sac on both sequences corresponded well to the presence of the endolymphatic sac on histological sections. On the histological sections, the width of the external aperture of vestibular aqueduct (endolymphatic sac including surrounding connective tissue) was 0.96 +/- 0.18 mm (mean +/- SD) and the width of lumen of endolymphatic sac at the same point was 0.47 +/- 0.17 mm. The width of the endolymphatic sac was 1.02 +/- 0.19 mm on proton density-weighted images and was 0.81 +/- 0.15 mm on T2-weighted images. The widths of endolymphatic sac measured on proton density-weighted image and those of vestibular aqueduct on histological section did not show statistically significant differences (P >.05). On the other hand, the endolymphatic sac as measured on T2-weighted image tended to be smaller than the vestibular aqueduct (P <.05) and tended to be larger than the lumen of the endolymphatic sac (P <.0005). CONCLUSION: Both sequences can precisely depict the endolymphatic sac; however, the proton density-weighted image is a more appropriate indicator of the actual anatomical configuration of the endolymphatic sac with surrounding connective tissue and vestibular aqueduct.     

利用螺旋CT三维图像对梅尼埃病患者前庭小管外口的研究

目的 通过螺旋CT三维重建技术观察梅尼埃病患者前庭小管外口，研究其宽度的大小与该病发生的内在联系。方法 分别观察比较梅尼埃病患者和正常受试者。对颞骨岩部范围进行容积扫描，采用后颅窝内面观、表面法进行三维重建。在三维方向上旋转切割后图像，直接测量前庭小管外口最大直径。结果 所有受试者三维图像上前庭小管外口均显示清晰，梅尼埃病患者前庭小管外口宽度与正常耳组间的差异具有非常显著性意义。单侧梅尼埃病患者病耳与非病耳前庭小管外口宽度的差异无显著性意义。结论 前庭小管发育不良为梅尼埃病的病理解剖学基础，并且常常累及双耳。