The biomechanical characteristics of human vestibular aqueduct: a numerical-based model construction and simulation.

Vestibular aqueduct is a precise structure embedded in the temporal bone and plays a key role in the physiological function of inner ear by maintaining the endolymphatic circulation and buffering the impact from intracranial pressure. Although the alterations on the morphology or volume of vestibular aqueduct result in variety of diseases, the approaches of evaluating the condition of vestibular aqueduct are still unsatisfing because the pathological sections utilized for the 3D construction model most likely undergoes morphological changes. In this study, the vestibular aqueduct images obtained by CT scanning were processed by finite element method to construct the 3D model. To assess if this numerical model reflects the actual biomechanical properties of vestibular aqueduct, the fluid-solid coupling calculation was applied to simulate the endolymphatic flow in the vestibular aqueduct. By measuring the dynamics of endolymphatic flow, and the pressure and displacement on round membrane under external pressure, we found the numerical 3D model recapitulated the biomechanical characteristics of the real vestibular aqueduct. In summary, our approach of 3D model construction for vestibular aqueduct will provide a powerful method for the research of vestibular aqueduct-related diseases.

Hearing loss without overt metabolic acidosis in ATP6V1B1 deficient MRL mice, a new genetic model for non-syndromic deafness with enlarged vestibular aqueducts.

Mutations of the human ATP6V1B1 gene cause distal renal tubular acidosis (dRTA; OMIM #267300) often associated with sensorineural hearing impairment; however, mice with a knockout mutation of Atp6v1b1 were reported to exhibit a compensated acidosis and normal hearing. We discovered a new spontaneous mutation (vortex, symbol vtx) of Atp6v1b1 in an MRL/MpJ (MRL) colony of mice. In contrast to the reported phenotype of the knockout mouse, which was developed on a primarily C57BL/6 (B6) strain background, MRL-Atp6v1b1vtx/vtx mutant mice exhibit profound hearing impairment, which is associated with enlarged endolymphatic compartments of the inner ear. Mutant mice have alkaline urine but do not exhibit overt metabolic acidosis, a renal phenotype similar to that of the Atpbv1b1 knockout mouse. The abnormal inner ear phenotype of MRL- Atp6v1b1vtx/vtx mice was lost when the mutation was transferred onto the C57BL/6J (B6) background, indicating the influence of strain-specific genetic modifiers. To genetically map modifier loci in Atp6v1b1vtx/vtx mice, we analysed ABR thresholds of progeny from a backcross segregating MRL and B6 alleles. We found statistically significant linkage with a locus on Chr 13 that accounts for about 20% of the hearing threshold variation in the backcross mice. The important effect that genetic background has on the inner ear phenotype of Atp6v1b1 mutant mice provides insight into the hearing loss variability associated with dRTA caused by ATP6V1B1 mutations. Because MRL-Atp6v1b1vxt/vtx mice do not recapitulate the metabolic acidosis of dRTA patients, they provide a new genetic model for nonsyndromic deafness with enlarged vestibular aqueduct (EVA; OMIM #600791).

Cochlear Implantation in Isolated Large Vestibular Aqueduct Syndrome: Report of Three Cases and Literature Review

Introduction Large vestibular aqueduct syndrome (LVAS) is characterized by the enlargement of the vestibular aqueduct associated with sensorineural hearing loss. It is the most common radiographically detectable inner ear anomaly in congenital hearing loss. LVAS may occur as an isolated anomaly or in association with other inner ear malformations. Objective To report three cases of isolated LVAS with a focus on preoperative assessment, surgical issues, and short-term postoperative follow-up with preliminary auditory habilitation outcomes. Resumed Report One girl and two boys with LVAS were assessed and cochlear implantation was performed for each. Various ways of intraoperative management of cerebrospinal fluid gusher and postoperative care and outcomes are reported. Conclusion Cochlear implantation in the deaf children with LVAS is feasible and effective.(AU)

Air-bone gap component of inner-ear origin in audiograms of cochlear implant candidates.

BACKGROUND: Experimental studies have shown that creating a window in the bony cover of the cochlea and vestibular parts of the inner ear, with preservation of membranous and middle-ear functions, induces an air-bone gap (ABG). This study sought to determine if a similar mechanism explains the ABG frequently observed in audiograms of cochlear implant candidates. METHOD: The study group included 47 candidates for a cochlear implant (94 ears) attending a university-affiliated tertiary medical center who had an ABG component in the audiogram in the absence of external or middle-ear abnormalities. Air- and bone-conduction thresholds on pure-tone audiometry were analyzed for 250 to 8,000 Hz and 250 to 4,000 Hz, respectively. In the 25 patients operated on during the study period, differences in the ABG and in cerebrospinal fluid (CSF) leak were compared between those with and without anomalies on computed tomography. RESULTS: Imaging revealed an abnormal inner-ear structure in 46% of cases, mostly a large vestibular aqueduct, alone or combined with other cochlear or vestibular malformations. ABG was evident over high and low frequencies and was significantly larger at low frequencies and in ears with structural anomalies. A high rate of CSF leak was observed in patients with an ABG and structural anomalies imaging as well as in those with an ABG and normal imaging findings. CONCLUSION: In cochlear implant candidates, the presence of a third window could cause an ABG because of stapes motion-induced shunting of acoustic energy outside the cochlear duct in response to air-conducted stimuli while bone conduction is preserved.

Molecular and functional characterization of human pendrin and its allelic variants.

Pendrin (SLC26A4, PDS) is an electroneutral anion exchanger transporting I(-), Cl(-), HCO(3)(-), OH(-), SCN(-) and formate. In the thyroid, pendrin is expressed at the apical membrane of the follicular epithelium and may be involved in mediating apical iodide efflux into the follicle; in the inner ear, it plays a crucial role in the conditioning of the pH and ion composition of the endolymph; in the kidney, it may exert a role in pH homeostasis and regulation of blood pressure. Mutations of the pendrin gene can lead to syndromic and non-syndromic hearing loss with EVA (enlarged vestibular aqueduct). Functional tests of mutated pendrin allelic variants found in patients with Pendred syndrome or non-syndromic EVA (ns-EVA) revealed that the pathological phenotype is due to the reduction or loss of function of the ion transport activity. The diagnosis of Pendred syndrome and ns-EVA can be difficult because of the presence of phenocopies of Pendred syndrome and benign polymorphisms occurring in the general population. As a consequence, defining whether or not an allelic variant is pathogenic is crucial. Recently, we found that the two parameters used so far to assess the pathogenic potential of a mutation, i.e. low incidence in the control population, and substitution of evolutionary conserved amino acids, are not always reliable for predicting the functionality of pendrin allelic variants; actually, we identified mutations occurring with the same frequency in the cohort of hearing impaired patients and in the control group of normal hearing individuals. Moreover, we identified functional polymorphisms affecting highly conserved amino acids. As a general rule however, we observed a complete loss of function for all truncations and amino acid substitutions involving a proline. In this view, clinical and radiological studies should be combined with genetic and molecular studies for a definitive diagnosis. In performing genetic studies, the possibility that the mutation could affect regions other than the pendrin coding region, such as its promoter region and/or the coding regions of functionally related genes (FOXI1, KCNJ10), should be taken into account. The presence of benign polymorphisms in the population suggests that genetic studies should be corroborated by functional studies; in this context, the existence of hypo-functional variants and possible differences between the I(-)/Cl(-) and Cl(-)/HCO(3)(-) exchange activities should be carefully evaluated.

Communication routes between intracranial spaces and inner ear: function, pathophysiologic importance and relations with inner ear diseases.

OBJECTIVE: There exist 3 communication routes between the intracranial space and the inner ear, the vestibular aqueduct, the cochlear aqueduct, and the internal auditory canal. They possess a key role in inner ear pressure regulation and fluid homeostasis and are related to inner ear diseases. REVIEW METHODS: Relevant literature was reviewed, and the current knowledge of the anatomy, physiologic importance, and relations to inner ear diseases were described. Pathologic communication routes such as semicircular canal dehiscence syndrome were highlighted as well. CONCLUSION: Abnormalities in all 3 communication routes may predispose or be the cause of distinct inner ear pathologic condition and involved in other cochlear and vestibular syndromes, in which their role is not completely clear. The increasing knowledge of the underlying mechanisms encourages promising approaches for possible intervention in the future.

The influence of vestibular and cochlear aqueducts on vestibular response to middle ear pressure changes in guinea pigs.

The responses of primary vestibular neurons and perilymphatic pressure changes to middle ear pressure were investigated in guinea pigs with obstructed vestibular or cochlear aqueduct (closed VA or closed CA group) in order to clarify the influence of VA and CA on pressure-induced vestibular response. Although the neural response rates and the amount of perilymphatic pressure change in the closed VA group resembled those in the control group, these values in the closed CA group were higher than in the control group. Patency of the CA had a more significant effect on the vestibular response to middle ear pressure change than patency of the VA.

Equilibrium of inner and middle ear pressure.

Global balance of inner and middle ear pressure is controlled by the cerebrospinal fluid inside and the atmospheric pressure outside. The cochlear and vestibular aqueducts and the Eustachian tube, connected by a one-way communication, provide a fine control over inner and middle ear pressure.

[Functional and morphologic changes in inner ear after experimental rupture of the round window membrane in the guinea pig].

The round window membrane of the guinea pig was perforated with a sharp instrument, and electrocochleography, vestibular function and histological changes of cochlea were studied in 1, 2, 4, 7, 14 and 28 days. It was found that the compound action potential (AP) threshold and the latency increased at 95 dB (spl) sound stimulus, and vestibular function decreased slightly, but histologic appearance of Corti's organ was normal in the early stage. Latency and threshold of AP and vestibular function gradually recovered to normal 2 weeks later. If no obvious histological change took place in inner ear, hearing loss would not appear. There was no significant difference of SP changes between the experimental and control ears.

Electrochemical composition of the cochlear fluids in the early experimental hydrops. Preliminary results.

The composition of endolymph and perilymph was studied in the guinea pig cochlea after 2 and 6 weeks of blockage of the vestibular aqueduct in an experimental model of hydrops. Compound action potential was monitored several times in the observation period. The endocochlear potential was measured and the endolymph was sampled at the first and third turns of the scala media. The Na, K, and Cl concentrations were determined in nanolitre aliquots of endolymph and of perilymph, the latter sampled from the basal scala vestibuli. After 2 weeks, no change in endolymphatic electrochemical composition was observed. After 6 weeks, endocochlear potential was decreased by 25% at both cochlear turns; K concentration was decreased in endolymph of the basal turn and Cl concentration was decreased in both turns; the calculated osmolality (Na + K + Cl) was decreased in both turns. These results indicate that the blockage of the vestibular aqueduct induced early auditory dysfunction whereas alterations of the electrochemical composition of endolymph occurred later after a time lag of more than 2 and less than 6 weeks.