Effect of an enlarged endolymphatic duct on bone conduction threshold.

An enlarged endolymphatic duct and sac (EDS) that makes contact with the cerebrospinal fluid­dural interface plays an important role in the pathway of bone conduction and enhances bone conduction at lower frequencies. Objectives. We investigated whether the bone conduction threshold was improved when the EDS was enlarged. Subjects and methods. Twenty-three patients (46 ears) with large vestibular aqueducts underwent standard pure tone audiometry (PTA) and magnetic resonance imaging (MRI) to investigate the relation between the diameter of the endolymphatic duct (ED) and the air or bone conduction threshold. We also investigated the relation between the volume of the EDS and the air or bone conduction threshold. Results. All ears had a mixed type hearing loss. The air­bone gaps were significantly larger at 250 and 500 Hz than at higher frequencies. The bone conduction thresholds were significantly lower at 250 Hz and 1000 Hz when the diameter of the ED was large, whereas there was no relation between the diameter of the ED and the air conduction threshold. In addition, there was no correlation between the volume of the EDS and air or bone conduction thresholds.

Lateral semicircular canal and vertigo in patients with large vestibular aqueduct syndrome.

OBJECTIVE: To evaluate the hypothesis that there are differences in the morphology of the lateral semicircular canal (LSCC) between patients with large vestibular aqueduct syndrome (LVAS) and control subjects and to investigate the clinical implications of these differences. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Nine patients (two male patients and seven female patients; age range, 8-54 yr) with LVAS (one patient had unilateral LVAS, and eight patients had bilateral LVAS). Five patients had vertigo, and four patients, including the one with unilateral LVAS, did not have vertigo. MAIN OUTCOME MEASURES: The area of the LSCC was traced on the magnetic resonance imaging console and compared between LVAS patients and 12 control subjects who did not have sensorineural hearing loss. The LSCC fluid-containing area was divided by the sum of the LSCC inner area and the LSCC fluid-containing area for evaluation of the degree of the LSCC dysplasia. RESULTS: The LSCC fluid-containing ratio was significantly larger in LVAS patients than in control subjects. Moreover, the LSCC fluid-containing ratio was significantly larger in the eight ears with vertigo than in the nine ears without vertigo. There was no relationship between hearing level and the LSCC fluid-containing ratio. CONCLUSION: Patients with LVAS may have disturbed morphogenesis of both membranous and bony labyrinths. Our results reveal that the morphology of semicircular canals is clinically associated with vertigo.

Distribution of pendrin in the organ of Corti of mice observed by electron immunomicroscopy.

The distribution of pendrin, which is encoded by the Pendred syndrome gene, has been investigated immunohistochemically in the inner ear. In the cochlea, pendrin has been found in the spiral prominence, external sulcus cells, Hensen's cells and Claudius cells, but its expression in the organ of Corti remains unclear. We examined whether pendrin localizes in the organ of Corti by postembedding immunogold analysis. In the organ of Corti, gold particles were clearly observed in outer and inner hair cells, including the stereocilia. The density of the particles was especially high in the cuticular plates of the hair cells. Gold particles were also detected in the external sulcus, in part of the spiral ligament adjacent to the external sulcus, in supporting cells, and in the spiral ganglion of the cochlea. Our study revealed that pendrin occurs in the organ of Corti. The role of pendrin in the organ of Corti and its association with the Cl- or pH regulation of neurotransmission require further study.

Hearing loss in patients with enlarged vestibular aqueduct: air-bone gap and audiological Bing test.

The Bing test is based on the principle that occlusion of the external auditory meatus improves the perception of bone-conducted sounds unless there is a conductive hearing impairment. An air-bone gap has been reported in patients with large vestibular aqueduct (LVA) syndrome without apparent middle ear dysfunction. We therefore performed the Bing test on nine patients with this syndrome to evaluate whether it is associated with an air-bone gap or middle ear dysfunction. Bone conduction thresholds did not change significantly during the Bing test in any patient. Because an air-bone gap is observed in patients with abnormal communication between the inner ear and cerebrospinal fluid through the LVA, dehiscent superior canal, or dilated inner ear meatus; we propose that a 'three windows' model (in which the abnormal communication provided by the enlarged endolymphatic duct and sac in LVA acts as the 'third window' for sound conductance) might explain the air-bone gap in such patients.

Long-term follow-up in patients with Pendred syndrome: vestibular, auditory and other phenotypes.

Fourteen patients with a Pendred syndrome gene (Pds) mutation and three patients without the mutation were studied to evaluate long-term vestibular and auditory manifestations among patients with bilateral enlarged vestibular aqueducts (EVA). Charts were reviewed retrospectively for age, gender, otological history, presence or absence of vertigo, results of magnetic resonance imaging, relevant gene mutations and perchlorate discharge test. A missense mutation, His 723 Arg (H723R), was identified in the homozygous state in six patients and in the heterozygous state in seven patients. Another missense mutation, Tyr 410 Met (T410 M), was identified in the heterozygous state in one patient. Patients with vertigo tended to have hearing fluctuation, compared with the patients without vertigo. Patients homozygous for H723R tended to have more episodes of vertigo than the heterozygous individuals. Only one patient who was homozygous for H723R had goiter. The long-term outcome of hearing level in patients with the H723R mutation was significantly better compared with published results for patients with a Pds mutation, but not for those with the H723R mutation. Whether environmental factors or a subtype of the Pds mutation H723R are related to the long-term outcome for these patients must be clarified.

The immunohistochemical analysis of pendrin in the mouse inner ear.

Pendred's syndrome (PS) is an autosomal recessive disorder characterized by deafness and goiter, which are caused by mutations in the Pendred's syndrome gene (PDS). PDS encodes a membrane protein named pendrin that is considered to act as an anion transporter. An expression pattern of the PDS ortholog (Pds) mRNA in the auditory and vestibular systems has been reported in mice, and the localization of pendrin has been reported recently. We generated antipeptide antibodies against human pendrin, and performed immunohistochemical analysis of mouse inner ears. We detected pendrin in the endolymphatic duct and sac, and the utricle, saccule, and external sulcus. In the endolymphatic duct and sac, the expression of pendrin was apparent at the apical membrane. In addition, we detected pendrin in the spiral ligament, Claudius cells, Deiter's cells, and the spiral ganglion of the cochlea. Our results are key to defining the role of pendrin in inner ear development and elucidating the pathogenic mechanisms underlying deafness in PS.

Enlarged endolymphatic duct and sac syndrome: relationship between MR findings and genotype of mutation in Pendred syndrome gene.

Pendred syndrome (PDS) is characterized by profound deafness in childhood, positive perchlorate challenge, and goiter. PDS is often associated with enlarged endolymphatic duct and sac (EEDS), and recently, PDS gene mutations have been reported even in those patients with EEDS without classic Pendred syndrome. In a previous report, the number of mutant alleles was correlated with the degree of subclinical thyroid abnormality, but not with hearing loss, in patients with missense mutation H723R. It also has been reported that the hearing loss in EEDS was not correlated with the EEDS volume, cochlear modiolar area, or signal intensity of the endolymphatic sac. We evaluated the correlations between the number of mutant alleles and these parameters in patients with EEDS to investigate the mechanisms underlying this condition. The study group was comprised of 16 Japanese patients with EEDS diagnosed by MR imaging. The H723R mutation was homozygous in six patients and heterozygous in six patients, with no mutation found in four patients. The modiolar area, EEDS volume, and signal intensity ratio (sac signal/cerebrospinal fluid signal) were not significantly correlated with the number of mutant alleles. PDS gene mutations may not be the only cause of EEDS, and the mechanisms underlying EEDS remain unclear.