Direct measurement of cochlear parameters for automatic calculation of the cochlear duct length.

BACKGROUND: Cochlear morphology and cochlear duct length (CDL) play important roles in the selection of appropriate electrodes. Cochlear parameters such as diameter (A value) and width (B value) are used as inputs for calculating the CDL. Current measurements of these parameters are inefficient and time consuming. Recently developed otological planning software (OTOPLAN) allows surgeons to directly measure these parameters and then automatically calculate the CDL. OBJECTIVES: The primary objective was to validate this new software for measuring the cochlear parameters and CDL. The secondary aim was to investigate the correlation between each cochlear parameter with the calculated CDL. DESIGN: Retrospective. SETTINGS: Ear specialist hospital. PATIENTS AND METHODS: The measurement of cochlear diameter (A value) was chosen as the validation parameter. To do this, the A value was measured by a neurotologist on the new OTOPLAN planning software and was validated to the one measured on the currently used DICOM viewer. Upon the validation of the OTOPLAN software, the other two cochlear parameters, namely width (B value) and height (H value) were measured, and CDL was automatically calculated. Finally, the correlation of all parameters with the CDL was statistically analyzed. MAIN OUTCOME MEASURES: Validation of OTOPLAN and CDL estimation. SAMPLE SIZE: 88 ears. RESULTS: There was no significant difference between the A-value measured on the DICOM viewing software and that on the new planning software by the two independent neurotologists (P=.27). Both A-and B-values showed a high positive correlation to the CDL. However, the B-value showed a stronger correlation to the CDL than the A-value (r=0.63 for A, and r=0.96 for B). CONCLUSION: The direct measurement of cochlea parameters and automatic calculation of the CDL could improve the efficiency of clinical workflow and make otology surgeons more independent. Moreover, the cochlear width (B) has a strong correlation to the CDL. Thus, we suggest using the combination of A and B to accurately estimate the CDL rather than using only one. LIMITATIONS: Single center and small sample size. CONFLICT OF INTEREST: None. No relationship with manufacturers.

CT-scan contouring technique allows for direct and reliable measurements of the cochlear duct length: implication in cochlear implantation with straight electrode-arrays.

OBJECTIVES: The advent of hybrid electro-acoustic implants requires precise positioning of the electrode-array (EA) within the cochlea. The cochlea size, that is, the length of the cochlear scala tympani, is often indirectly estimated from distance A by Escudé's method. This technique has been confirmed by anatomical studies, in a bunch of cadaveric specimens, but it is not yet widely established in the field of computed tomography (CT). We compared cochlear duct length obtained by Escudé's method to those directly acquired on CT images. MATERIALS AND METHODS: The lengths of cochlear scala tympani were directly measured on CT scans by contouring the external cochlear wall (contouring technique-CoT). In fifteen patients implanted with a straight EA, the length of the EA and the measured length of the cochlea by the CoT were compared, to check the reliability of the CoT. Then, in 200 CT-scans, the length of the cochlear duct was measured by the CoT then compared to Escudé's method. RESULTS: In the 200 CT-scans which served for cochlear length measurements, a significant variability between the cochleae were observed, as expected. At 360°, the correlation between the measurements of the length of the cochlear scala tympani between the two techniques differed, with a difference of 0.2 ± 0.7 mm at 360° (extreme: 2 mm; p < 0.001) and 2.2 ± 1.2 mm at 540° (extreme: 5.6 mm; p < 0.001). CONCLUSION: The CoT can predict with accuracy the length of EA-insertion depth, more precisely than estimation methods such as Escudé's.

Malformaciones del oído interno: una aproximación diagnóstica práctica / Inner ear malformations: a practical diagnostic approach

La hipoacusia neurosensorial pediátrica es una causa mayor de discapacidad. Pese a que solo en el 20-40% de los casos se identifica una malformación del oído interno, su detección es de vital importancia para el tratamiento de estos pacientes. En este artículo se repasan la anatomía y la embriogénesis del oído interno. Se valora el papel de la neuroimagen en la hipoacusia neurosensorial pediátrica y en el estudio preimplante coclear. Se destaca la necesidad de la utilización de un sistema universal de clasificación de las malformaciones del oído interno con implicaciones pronósticas y terapéuticas. Por último, se describen e ilustran de forma concisa los hallazgos radiológicos clave de cada tipo de malformación. La tomografía computarizada y la resonancia magnética desempeñan un papel crucial en la caracterización de las malformaciones del oído interno y permiten la valoración de las estructuras anatómicas que posibilitan la selección del tratamiento y del abordaje quirúrgico idóneos (AU)

Pediatric sensorineural hearing loss is a major cause of disability; although inner ear malformations account for only 20-40% of all cases, recognition and characterization will be vital for the proper management of these patients. In this article relevant anatomy and development of inner ear are surveyed. The role of neuroimaging in pediatric sensorineural hearing loss and cochlear preimplantation study are assessed. The need for a universal system of classification of inner ear malformations with therapeutic and prognostic implications is highlighted. And finally, the radiological findings of each type of malformation are concisely described and depicted. Computed tomography and magnetic resonance imaging play a crucial role in the characterization of inner ear malformations and allow the assessment of the anatomical structures that enable the selection of appropriate treatment and surgical approach (AU)

Evaluation of Cochlear Duct Length Computations Using Synchrotron Radiation Phase-Contrast Imaging.

HYPOTHESIS: Evaluation of cochlear duct length (CDL) using novel imaging techniques will help improve the accuracy of existing CDL equations. BACKGROUND: Various relationships relating A value measured from a patient's computed tomography scan and CDL have been proposed to aid in preoperative electrode selection and frequency mapping. METHODS: Ten cadaveric temporal bones were scanned using synchrotron radiation phase-contrast imaging. Reference CDL values were calculated by placing points representing the organ of Corti (OC), lateral wall (LW), and electrode location (I) on the synchrotron radiation phase-contrast imaging slices along the length of the cochlea. The CDL estimates from the existing three equations (OC, LW, I) in addition to two newly proposed equations (OC and LW) were compared with reference CDL values at each respective location. RESULTS: When compared with reference CDL values, the new OC equation improved the CDL estimates from a 6.2% error to a 5.1% error while the new LW equation improved the CDL estimate error from 3.9 to 3.6%. Bland-Altman plots revealed both new equations increased similarity to reference values and brought more samples to within clinically significant ranges. Validation of the original electrode location equation to the reference values showed a 4.6% difference. CONCLUSION: The newly proposed equations for LW and OC provided an improvement over past equations for determining CDL from the A value by showing improved agreement with reference values. Therefore, these equations can provide quick and accurate preoperative estimates of CDL for improving customized frequency mapping.

Hair cell regeneration or the expression of related factors that regulate the fate specification of supporting cells in the cochlear ducts of embryonic and posthatch chickens.

Hair cells in posthatch chickens regenerate spontaneously through mitosis or the transdifferentiation of supporting cells in response to antibiotic injury. However, how embryonic chicken cochleae respond to antibiotic treatment remains unknown. This study is the first to indicate that unlike hair cells in posthatch chickens, the auditory epithelium was free from antibiotic injury (25-250 mg gentamicin/kg) in embryonic chickens, although FITC-conjugated gentamicin actually reached embryonic hair cells. Next, we examined and counted the cells and performed labeling for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) (triple or double labeling) in the injured cochlea ducts after gentamicin treatment at 2 h (h), 15 h, 24 h, 2 days (d), 3 d and 7 d after BrdU treatment in posthatch chickens. Our results indicated that following gentamicin administration, proliferating cells (BrdU+) were labeled for Atoh1/Math1 in the damaged areas 3d after gentamicin administration, whereas hair cells (PV+) renewed through mitosis (BrdU+) or direct transdifferentiation (BrdU-) were evident only after 5 d of gentamicin administration. In addition, Sox2 expression was up-regulated in triggered supporting cells at an early stage of regeneration, but stopped at the advent of mature hair cells. Our study also indicated that p27(kip1) was expressed in both hair cells and supporting cells but was down-regulated in a subgroup of the supporting cells that gave rise to hair cells. These data and the obtained dynamic changes of the cells labeled for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) are useful for understanding supporting cell behaviors and their fate specification during hair cell regeneration.

Fatiga auditiva / Auditory fatigue

Introducción y objetivos: Ante posibles pérdidas de audición a causa de sobrecargas sonoras y la escasa referencia de procedimientos objetivos para su estudio, aportamos una técnica que suministra datos precisos sobre el perfil audiométrico y el factor reclutamiento. El objetivo del estudio es la determinación de la fatiga auditiva temporal a través de la respuesta microfónica coclear ante estímulos de sobrecarga de presión sonora y medida del tiempo de recuperación. Material y método: Instrumentación específica para el estudio de microfónicos cocleares, más un generador que nos proporciona estímulos sonoros de diversa intensidad y componente armónico. Utilizamos ratas Wistar. Medimos la respuesta microfónica normal y después el efecto que sobre ella ha ejercido la aportación de sobrecarga acústica. Resultados: Utilizando un tono puro a 60 dB obtenemos una respuesta microfónica. Fatigando de inmediato con 100 dB en la misma frecuencia, a los 15 min obtenemos una pérdida de 11 dB, a partir de los cuales el deterioro se lentifica y no supera los 15 dB. Mediante sonidos de banda compleja aleatoria o ruido blanco no se produce fatiga ni a niveles de 100 dB durante una hora de sobreestímulo. Conclusiones: No existe fatiga a nivel de los receptores sensoriales. El deterioro de la respuesta mediante intenso sobreestímulo posiblemente se deba a alteraciones bioquímicas de desensibilización por agotamiento. La fatiga auditiva en pruebas clínicas subjetivas afecta a tramos supracocleares. Las pruebas de fatiga auditiva encontradas no coinciden con las obtenidas subjetivamente en clínica ni en psicoacústica (AU)

Introduction and objectives: Given the relevance of possible hearing losses due to sound overloads and the short list of references of objective procedures for their study, we provide a technique that gives precise data about the audiometric profile and recruitment factor. Our objectives were to determine peripheral fatigue, through the cochlear microphonic response to sound pressure overload stimuli, as well as to measure recovery time, establishing parameters for differentiation with regard to current psychoacoustic and clinical studies. Material and method: We used specific instruments for the study of cochlear microphonic response, plus a function generator that provided us with stimuli of different intensities and harmonic components. In Wistar rats, we first measured the normal microphonic response and then the effect of auditory fatigue on it. Results: Using a 60 dB pure tone acoustic stimulation, we obtained a microphonic response at 20 dB. We then caused fatigue with 100 dB of the same frequency, reaching a loss of approximately 11 dB after 15 minutes; after that, the deterioration slowed and did not exceed 15 dB. By means of complex random tone maskers or white noise, no fatigue was caused to the sensory receptors, not even at levels of 100 dB and over an hour of overstimulation. Conclusions: No fatigue was observed in terms of sensory receptors. Deterioration of peripheral perception through intense overstimulation may be due to biochemical changes of desensitisation due to exhaustion. Auditory fatigue in subjective clinical trials presumably affects supracochlear sections. The auditory fatigue tests found are not in line with those obtained subjectively in clinical and psychoacoustic trials (AU)

Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss.

Nonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least 60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G mitochondrial mutation play a major role worldwide in causing deafness, but there is a high degree of genetic heterogeneity and many genes involved in deafness have not yet been identified. Therefore, there remains a need to search for new causative mutations. In this study, a combined strategy using both linkage analysis and sequencing identified a new mutation causing hearing loss. Linkage analysis identified a region of 40 Mb on chromosome 5q13 (LOD score 3.8) for which exome sequencing data revealed a mutation (c.7873 T>G leading to p.*2625Gluext*11) in the BDP1 gene (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) in patients from a consanguineous Qatari family of second degree, showing bilateral, post-lingual, sensorineural moderate to severe hearing impairment. The mutation disrupts the termination codon of the transcript resulting in an elongation of 11 residues of the BDP1 protein. This elongation does not contain any known motif and is not conserved across species. Immunohistochemistry studies carried out in the mouse inner ear showed Bdp1 expression within the endothelial cells in the stria vascularis, as well as in mesenchyme-derived cells surrounding the cochlear duct. The identification of the BDP1 mutation increases our knowledge of the molecular bases of Nonsyndromic Hereditary Hearing Loss and provides new opportunities for the diagnosis and treatment of this disease in the Qatari population.

Changes in auditory brainstem response (ABR) in Kanamycin-induced auditory disturbance model rats.

This study was designed to evaluate changes in auditory brainstem response (ABR) in the course of auditory disturbance in rats induced by Kanamycin (KM). KM was administered subcutaneously to 12 CD (SD) male rats aged 6 weeks for 10 days at a dose of 800 mg/kg. Death was observed in one male on day 8 and 2 males on day 10. It was thought that kidney damage was the cause of death from histopathological findings. ABR was recorded before KM treatment and on days 4, 8, 10 and 11 after KM treatment. The ABR changes after KM treatment in rats were as follows. On day 4, 6 rats showed an increase in amplitude of waves I and/or II and on day 8, among those, 4 rats still showed a high amplitude of waves I and/or II. On day 8, 2 rats showed an elevation of ABR threshold (15-40 dB SPL) and a decrease in amplitude of wave I and increase in amplitude of wave II at the same time. On day 11, 7 rats showed a decrease in amplitude of wave I. In addition, ABR threshold shifts (10-70 dB SPL) were observed in those rats. In ABR recording, KM-induced auditory disturbance model rats showed an increase in amplitude of waves I and/or II earlier than an ABR threshold shift. By analyzing temporal alteration of amplitude of the ABR components, we could detect precursory phenomenon of the auditory disturbance at an early phase of treatment. By following the pathway of click-ABR and tone pip-ABR examination, the auditory disturbance of low- frequency to high-frequency range could be analyzed at an early date in detail.

A targeted Coch missense mutation: a knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction.

Mutations in COCH (coagulation factor C homology) are etiologic for the late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. We introduced the G88E mutation by gene targeting into the mouse and have created a Coch(G88E/G88E) mouse model for the study of DFNA9 pathogenesis and cochlin function. Vestibular-evoked potential (VsEP) thresholds of Coch(G88E/G88E) mice were elevated at all ages tested compared with wild-type littermates. At the oldest ages, two out of eight Coch(G88E/G88E) mice had no measurable VsEP. Auditory brainstem response (ABR) thresholds of Coch(G88E/G88E) mice were substantially elevated at 21 months but not at younger ages tested. At 21 months, four of eight Coch(G88E/G88E) mice had absent ABRs at all frequencies tested and two of three Coch(G88E)(/+) mice had absent ABRs at three of four frequencies tested. Distortion product otoacoustic emission amplitudes of Coch(G88E/G88E) mice were substantially lower than Coch(+/+) mice and absent in the same Coch(G88E/G88E) mice with absent ABRs. These results suggest that vestibular function is affected beginning as early as 11 months when cochlear function appears to be normal, and dysfunction increases with age. Hearing loss declines substantially at 21 months of age and progresses to profound hearing loss at some to all frequencies tested. This is the only mouse model developed to date where hearing loss begins at such an advanced age, providing an opportunity to study both progressive age-related hearing loss and possible interventional therapies.

Sensory cell regeneration and stem cells: what we have already achieved in the management of deafness.

BACKGROUND/OBJECTIVE: Genetic manipulation of the cell-cycle exit, induction of new hair cells (HCs) through gene modification therapy, and introduction of stem cells (SCs) into damaged cochleas potentially offer exciting new strategies in treating sensorineural hearing loss. MATERIALS AND METHODS: Literature review from Medline and database sources. STUDY SELECTION: Ex vivo models, animal studies, in vitro studies, and review articles. DATA SYNTHESIS: Embryonic SCs, neural SCs, or bone marrow SCs survive in the mammalian inner ear after transplantation. The scala media and the modiolus seem more functionally appropriate injection sites. The clear evidence that transplanted neural SCs can adopt the morphologic phenotypes of HCs was the most significant milestone achieved in the related research. The normal cytoarchitecture in the organ of Corti may also be restored through mouse atonal homologue 1 transgene expression and transduction of the nonsensory cells, producing clinically measured improvement in hearing thresholds. Embryonic SC-derived neurons have the potential for synapse formation with auditory HCs and reinnervation of the auditory epithelia. However, fluctuations in survival rates, functional recovery of the spiral-ganglion neurons, integration to the host tissue, and potential immune barriers are also areas of utmost importance. CONCLUSION: There is an already exciting progress in the fields of sensory cell regeneration and SC research in an attempt to restore hearing or prevent deafness. However, further understanding of the underlying mechanisms of auditory genetics, continuing investigation of the human genome, refinement of the delivering techniques, and specification of the therapeutic strategies have to be developed before functional regeneration of the cochlea can be achieved in clinical practice.

Spiral ganglion degeneration patterns in endolymphatic hydrops.

OBJECTIVES: The mechanistic association between endolymphatic hydrops (ELH) and hearing loss (HL) is unclear. Although ELH severity has been shown to correlate in some studies with HL, injury of vital structures, including hair cells and the cochlear nerve, have failed to demonstrate correlation with ELH severity. The goal of this study is to evaluate the hypothesis that spiral ganglion cell degeneration is the principle pathologic site of ELH-related cochlear injury, correlates with ELH severity, and is most profound in the apical region. STUDY DESIGN: Surgical induction of ELH in the guinea pig model was followed by histologic confirmation of ELH and subsequent correlation with segmental spiral ganglion cell densities. METHODS: Guinea pigs (N = 14) were subjected to unilateral ELH induction and killed after 4 to 6 months. ELH severity and spiral ganglion densities were obtained using computer-aided morphometric analysis. Densities were normalized by calculating a spiral ganglion degeneration index (DI) for each animal. RESULTS: The apical spiral ganglion demonstrated significantly greater degeneration than that noted in the basal spiral ganglion (DI: 1.93 vs. 1.13; P = .004). The degree of spiral ganglion degeneration in the apex correlates well with a total hydrops index (P = .006) and an apical hydrops index (P = .003). Basal spiral ganglion degeneration however, does not correlate well with hydrops severity (total hydrops index: P > .05; basilar hydrops index: P > .05). CONCLUSIONS: ELH-related pathology appears to focus initially on the apical spiral ganglion and the degree of deterioration correlates well with the severity of ELH. These findings mirror some reports in the human condition, and imply that the mechanism of cochlear injury in ELH and secondary dysfunction appears to be a neural toxicity that begins in the apex of the cochlea.

Pólipo-quiste del seno esfenoidal como hallazgo casual en paciente con hipoacusia brusca severa retrococlear / Sphenoidal sinus-cyst as casual finding in a patient with severe and audden retrocochlear hearing loss

Presentamos el caso de una mujer de 56 años controlada en nuestro servicio de ORL, a causa de acúfenos y vértigo de aparición brusca. La exploración endoscópica fue normal. La audiometría mostraba una hipoacusia neurosensorial severa y los potenciales evocados auditivos (PEATC) confirmaron la citada hipoacusia apuntando un origen retrococlear de la misma. Como pruebas de imagen se solicitarion TC y RMN óticocraneal, en la que se informaba de la presencia de una lesión quística versus pólipo en seno esfenoidal de 15 por 10 mm sin otras alteraciones o patología significativa

We present the case of a 56 years old female controlled in our ENT Department because of right suden hearing loss, tinnitus and vertigo. The endoscopic exam was normal. Audiogram showed a severe neurosensorial hypoacusia and PEATC confirmed the so called hypoacusia suggesting a retrocochlear origin of it. As imaging tests and otic-craneal CT and IRM were asked for, which informed of the presence of a cystic lesion versus polyp in sphenoidal sinus of 15 x 10 mm without other alterations or significant pathology

Impact of electrode insertion depth on intracochlear trauma.

OBJECTIVE: To assess the effect of cochlear implant (CI) insertion depth and surgical technique on intracochlear trauma. STUDY DESIGN AND SETTING: Twenty-one fresh human temporal bones were implanted with CI electrodes and underwent histologic processing and evaluation. Specimens were grouped into 3 categories: 1) soft implantation technique and standard electrode; 2) soft implantation technique and flexible prototype array; 3) forceful implantations and standard electrode. Based on the grading system (1 to 4), 2 numeric values were calculated indicating the overall severity of cochlear damage (trauma indices). RESULTS: Mean trauma index values were 13.8, 36.3, and 59.2 for group 1, 2, and 3, respectively. Differences in cochlear trauma (trauma index) were nonsignificant between specimens in groups 1 and 2 but were significant between groups 1 and 3. CONCLUSION: This study gives evidence that intracochlear trauma increases with deep insertions. Thus, in cases where cochlear integrity might be important, limited insertions should be achieved.

Presbycusic neuritic degeneration within the osseous spiral lamina.

OBJECTIVE: To describe a neglected anatomic variant occurring with presbycusis. STUDY DESIGN: Retrospective temporal bone histopathology study. METHODS: Quantitative analysis of peripheral hair cells, neurites, neurons, and the stria vascularis in temporal bones from individuals who had presbycusis. Fifty-three patients aged 65 years or older and with a down-sloping audiogram and clinical diagnosis of presbycusis were reviewed. Nine cases had normal hair and ganglion cell populations but reduced peripheral processes (neuritic presbycusis). These were compared with five normal-hearing controls on measurements of anterior middle and basal turn fiber bundle diameter and the ratio of basal to middle diameters. RESULTS: Thresholds at 4 and 8 kHz were significantly poorer in the neuritic presbycusis group than in the control group (p

Recruitment en la presbiacusia / Recruitment in presbycusis

La presbiacusia se caracteriza por una hipoacusia neurosensorial, sobre todo de los agudos, simétrica y progresiva, y una mala inteligibilidad. El recruitment, típico de las hipoacusias cocleares estaría presente en los casos de presbiacusia sensorial que cursan primariamente con cocleopatía. Analizamos en 241 pacientes presbiacúsicos varias variables y las posibles interrelaciones con el recruitment

Presbycusis is characterised by a sensori neural hearing loss mainly in high frequencies, symmetrical and progressive and poor understanding. Recuritment, typical in cochlear hearing loss, would be present in cases of sensorial presbycusis which runs mainly in cochlear pathologies. We analyse variables and their possible interrelations with recruitment in 241 presbycusic patients

Paget disease and sensorineural hearing loss associated with spiral ligament degeneration.

HYPOTHESIS: Previously unreported cystic degeneration of the spiral ligament in cases of Paget disease. BACKGROUND: About 70% of cases of Paget disease involve the skull, with hearing affected in approximately 50% of these. The hearing impairment may be sensorineural, mixed, or, rarely, only conductive. The etiology and pathogenesis of the hearing loss are not yet understood, and reports in the literature are inconsistent regarding the pathologic changes responsible for sensorineural hearing loss. Of six pairs of temporal bones from patients with Paget disease in the temporal bone collection of a research institution, two pairs have abnormalities not previously associated with sensorineural hearing loss or Paget disease. We report the histopathologic findings in these temporal bones. METHODS: The temporal bones were fixed in formalin, decalcified in ethylenediaminetetraacetic acid, embedded in celloidin, and sectioned in the horizontal plane at a thickness of 20 microm. Every 10th section was stained with hematoxylin-eosin and mounted on glass slides. The sections were examined by light microscopy. RESULTS: Cystic degeneration of the spiral ligament, primarily in the basal segment, was found in both cases. Endolymphatic hydrops and a small endolymphatic sac with calcification of the perisaccular tissue were found in one case. CONCLUSIONS: Cystic degeneration of the spiral ligament has not been previously reported and may be unique to Paget disease. This is consistent with recent literature showing a previously unsuspected role of the spiral ligament in sensorineural hearing loss.

Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on hearing level.

OBJECTIVE: To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization. INTERVENTION: Audiography. MAIN OUTCOME MEASURES: Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques. RESULTS: Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent. CONCLUSION: These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.

Effects of hyperbaric therapy on function and morphology of Guinea pig cochlea with endolymphatic hydrops.

OBJECTIVE: The objective of this study was to investigate the effect on experimental endolymphatic hydrops in guinea pigs after hyperbaric therapy. BACKGROUND: The histopathologic character of Ménière's disease is the presence of endolymphatic hydrops. Endolymphatic hypertension could be one of the factors resulting from endolymphatic hydrops. Some treatments of Ménière's disease are aimed toward preventing the endolymphatic hypertension. Exposure to pressure change has risen in recent years. METHODS: Thirty-two guinea pigs were operated on the right ears to induce endolymphatic hydrops by obliterating the endolymphatic sac through an extradural posterior cranial fossa approach. After 5 weeks' survival, 12 guinea pigs were put into a chamber with an absolute atmospheric pressure of 2.2 for 3 weeks (90 minutes once a day 5 times a week). We observed the morphologic and functional changes in guinea pig cochleae of the pressure group, 4-week hydrops group (n = 10), 8-week hydrops group (n = 10), and the normal group (n = 10). We measured the hearing threshold of the auditory brainstem response, the 70-dB SPL action potential (AP) latency, the ratio of 70-dB SPL summating potential magnitude to action potential magnitude (-SP/AP) of the electrocochleogram, and the maximum scala media area (SMA) ratio, respectively. RESULTS: The average 70-dB SPL-SP/AP magnitude of right ears (0.29 +/- 0.09) and the average maximum SMA ratio (2.23 +/- 0.20) in the pressure group were significantly less than that in the 8-week hydrops group (0.69 +/- 0.15 and 4.04 +/- 0.52, respectively) with the same survival time (p < 0.05). The results in the pressure group were almost as similar as that in the 4-week hydrops group (0.29 +/- 0.13 and 2.22 +/- 0.20, respectively) (p > 0.05). The average hearing threshold of ABR of right ears in the pressure group (36.67 +/- 14.30-dB SPL) was lower than that of the 8-week hydrops group (44 +/-1 4.30-dB SPL), but the difference was insignificant (p > 0.05). The average 70-dB SPL AP latency of right ears in the pressure group was not significantly different from those of the 8-week hydrops group, the 4-week hydrops group, or the normal group (p > 0.05). CONCLUSIONS: Our findings suggest hyperbaric therapy can significantly suppress the development of endolymphatic hydrops and improve cochlear function in guinea pigs. This study provided strong evidence for the development of pressure treatment of Ménière's disease without destroying the inner ear.

The role of Pax2 in mouse inner ear development.

The paired box transcription factor, Pax2, is important for cochlear development in the mouse inner ear. Two mutant alleles of Pax2, a knockout and a frameshift mutation (Pax21Neu), show either agenesis or severe malformation of the cochlea, respectively. In humans, mutations in the PAX2 gene cause renal coloboma syndrome that is characterized by kidney abnormalities, optic nerve colobomas and mild sensorineural deafness. To better understand the role of Pax2 in inner ear development, we examined the inner ear phenotype in the Pax2 knockout mice using paint-fill and gene expression analyses. We show that Pax2-/- ears often lack a distinct saccule, and the endolymphatic duct and common crus are invariably fused. However, a rudimentary cochlea is always present in all Pax2 knockout inner ears. Cochlear outgrowth in the mutants is arrested at an early stage due to apoptosis of cells that normally express Pax2 in the cochlear anlage. Lack of Pax2 affects tissue specification within the cochlear duct, particularly regions between the sensory tissue and the stria vascularis. Because the cochlear phenotypes observed in Pax2 mutants are more severe than those observed in mice lacking Otx1 and Otx2, we postulate that Pax2 plays a key role in regulating the differential growth within the cochlear duct and thus, its proper outgrowth and coiling.

[Quantification of endolymphatic hydrops in experimental animal model].

OBJECTIVE: To investigate a method of quantification of the endolymphatic hydrops in experimental animal model. METHODS: Thirty guinea pigs were divided into three groups at random. In control group, there were ten guinea pigs without operation on both ears. Endolymphatic hydrops was induced by endolymphatic sac obliteration through extradural posterior cranial fossa approach in right ear, including 4-week postoperative group(n = 10) and 8-week postoperative group(n = 10). The area of scala vestibuli (SV) and scala media(SM) of each turn on both cochlear midmodiolar sections was measured, respectively, using auto computer aided design(AutoCAD R14) software combined with digital camera, and then the maximum scala media area(SMA) ratio was calculated and compared. RESULTS: No endolymphatic hydrops was observed in all non-operated ears, however, variety degree of hydrops was present in all operated ears. The average maximum SMA ratio in the 4-week group (2.2231 +/- 0.1996) was greater than that in the control group (1.0971 +/- 0.0644). The average maximum SMA ratio of the 8-week group (4.0142 +/- 0.5218) was greater than that in the 4-weekgroup. There was significant difference between the two groups(P < 0.05). CONCLUSION: It is convenience and reliable to be used to quantify the experimental endolymphatic hydrops with the present method. This study provides a reliable methodological base for the experimental study of Meniere's disease.