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[Changes of cochlear electrical activities in early experimental hydrolabyrinth].

Changes of endocochlear potential (EP), cochlear microphonic potential (CM) and summating potential (SP) were studied in guinea pig cochlea after four weeks blockade of the endolymphatic sac and duct. The EP, CM and SP were measured with a microelectrode through the spiral ligament of the first turn. EP was decreased by 15%. The minimum CM output produced by tone burst of six frequencies (0.5, 1, 2, 4, 5 and 8 KHz) had reduced by 83.1%, 82.4%, 84.5%, 84.2%, 47.2% and 54.2% respectively, and the maximum CM output had declined by 54.3%, 41%, 43.2%, 21.1%, 26% and 24% separately. The minimum SP output caused by 4, 5 KHz tone burst had declined by 62.4% and 70.5%, and the maximum SP output had decreased by 41.5%, 45.2% in the early experiments. These results indicate that EP, CM and SP all underwent decreases. The extent of CM declination at low frequencies was larger than that at the high frequencies in the early experiments. The mechanisms of influence on EP, CM and SP in early experimental endolymphatic hydrops are discussed.

Action Potentials↗

Comparison of WKB calculations and experimental results for three-dimensional cochlear models.

The WKB asymptotic method is applied to the calculation of cochlear models with square scala cross section, for which the fluid motion is fully three dimensional. The analysis begins with the exact solution for wave propagation in a duct with constant properties. This solution is somewhat tedious but straightforward, since it requires a Fourier series expansion across the duct. Then with the formulation of Whitham [Linear and Nonlinear Waves (Wiley, New York, 1974)], the approximate solution is readily generated for the duct with properties which vary slowly along the length. Numerical calculations are carried out for the experimental models of Cannel [Ph.D. thesis, Univ. of Warwick (1969)] and Helle [Dr.-Ing. disser., Technische Univ., Müchen (1974)] who furnish quantitative details of both "basilar membrane" response and model parameters. Without any free parameters for adjusting, the present WKB solution shows quite satisfactory agreement with the experimental model results. Computer time is reasonable; the calculation of displacement envelope and phase at a number of stations along the cochlea for a given frequency requires only one second of CPU time. Thus the credibility and practically of the approach is established for the investigation of yet more realistic and more elaborate cochlear models.

Cochlea↗

[Preoperative imaging of the inner ear prior to the implantation of a multichannel cochlear implant using computed and MR technology].

CT and MRT are now standard examinations prior to insertion of a cochlear implant. Both methods have advantages and disadvantages in terms of discovering potentially pathological structures in the inner ear. The aim of this study was to evaluate the pros and cons of using CT and MRT before cochlear implantation. CT is usually performed using axial planigraphic planes. Like MRT, bone-specific CT is helpful in the diagnosis of congenital and acquired changes within the inner ear. Congenital defects in the meatus acusticus internus, the endolymphatic duct and sac, the cochlea and the vestibulum can be diagnosed and also quantified. Infectious morphologic changes can be seen on CT images in their terminal residual state (sclerotic tissue). However, acute inflammation and fibrotic tissue is not visible on CT. T2-specific MRT images are very fluid sensitive and play a major role in preoperative cochlear implant diagnosis. This examination demonstrates fluid within the peri- and enolymphatic cave and permits the diagnostician to determine whether congenital or acquired diseases have destroyed such fluid-filled cavities. In order to demonstrate pathological changes in the temporal bone and neural structures in the inner ear, MRT is the preferred method. Displaying the modiolus and the cochlear nerve is extremely important because, in their absence, a cochlear implantation may be contra-indicated. MRT also demonstrates other neural structures such as the facial nerve. This information may be important for the surgeon, e.g. the state of the pneumatic system in the mastoid cavity (which is best visualised by bone-specific CT).

Cochlear Implantation↗

Selective vestibular ablation by KTP laser in endolymphatic hydrops.

OBJECTIVES AND HYPOTHESIS: Vertigo, the cause of disability in many patients with Ménière's disease, may be the result of the effects of endolymphatic hydrops on the semicircular canals. We hypothesize that intractable vertigo may be controlled by destruction of the semicircular canal neuroepithelium using visible light lasers without the need for extensive fenestration of the bony labyrinth. This study was designed to assess the cochlear effects of potassium titanyl phosphate (KTP) laser-assisted triple semicircular canal ablation (TSCA) in endolymphatic hydrops. STUDY DESIGN: Randomized, prospective, and controlled. METHODS: Forty-one adult guinea pigs underwent either a unilateral endolymphatic duct occlusion to induce hydrops or a sham procedure. Ten weeks after induction of the hydrops, a KTP laser-assisted TSCA or a sham surgery was performed. RESULTS: Electrocochleographic thresholds to clicks and tone-bursts (2-20 kHz) did not change significantly up to 4 weeks after TSCA in hydropic ears. Cross-sectional histology confirmed the presence of hydrops and the ablation of the semicircular canals. Cochlear whole-mounts for hair cell counts showed no significant loss of outer or inner hair cells in hydropic ears treated with TSCA. CONCLUSION: KTP laser-assisted TSCA can be performed in the guinea pig model of endolymphatic hydrops without significant loss of hearing. Evaluation of this technique may be warranted in patients with intractable Ménière's disease.

Animals↗

[Analysis of otoacoustic distortion products in a group of otosclerotic patients].

There is indication that middle ear pathologies can affect otoacoustic emissions (OAE) to varying degrees. In fact, since acoustic emissions are recorded in the outer ear duct, the energy transfer mechanisms both up and downstream of the middle ear must be intact. OAE distortion products (DP) enable one to analyze cochlear response by frequency and to verify the retrograde response as a function of frequency. In the present work this method was used to test otosclerosis patients. A group of 45 patients with otosclerosis was tested to determine whether the OAE-DP could be identified and measured. Subsequently the characteristics of these DPs were analyzed in a group of 18 subjects who had previously undergone stapedectomy. All the results obtained were compared with those from a control group of normal hearing subjects with normal emissions and free of any E.N.T. pathology. In approximately half of the cases (53%) in the otosclerosis patient group it was possible to detect clearly evident DPs. Obviously, the DP-Gram differed greatly and average amplitude was lower than those found in normal subjects. Indeed, there was no signal at all at the lower and middle frequencies reflecting a hearing loss typical of cases of otosclerosis. Most (58%) of the otosclerosis patients who had successfully undergone stapedectomy recorded valid DPs. The DP-Gram frequency range was much broader (750-4000 Hz) than in those who had not undergone surgery. Moreover the lower and mid frequency amplitudes were significantly better. The data obtained are quite encouraging and suggest that DP should be studied in depth in patients with otosclerosis.

Acoustic Impedance Tests↗

Expression of Math1 and HES5 in the cochleae of wildtype and Jag2 mutant mice.

The sensory epithelium within the mammalian cochlea (the organ of Corti) is a strictly ordered cellular array consisting of sensory hair cells and nonsensory supporting cells. Previous research has demonstrated that Notch-mediated lateral inhibition plays a key role in the determination of cell types within this array. Specificallly, genetic deletion of the Notch ligand, Jagged2, results in a significant increase in the number of hair cells that develop within the sensory epithelium, presumably as a result of a decrease in Notch activation. In contrast, the downstream mediators and targets of the Notch pathway in the inner ear have not been determined but they may include genes encoding the proneural gene Math1 as well as the HES family of inhibitory bHLH proteins. To determine the potential roles of these genes in cochlear development, in situ hybridization for Math1 and HES5 was performed on the cochleae of wild-type vs. Jagged2 mutants (Jag2deltaDSL). Results in wild-type cochleae show that expression of Math1 transcripts in the duct begins on E13 and ultimately becomes restricted to hair cells in the sensory epithelium. In contrast, expression of HES5 begins on E15 and becomes restricted to supporting cells in the epithelium. Results in Jag2 mutant cochleae suggest that Math1 transcripts are ultimately maintained in a larger number of cells as compared with wild-type, while transcripts for HES5 are dramatically reduced throughout the epithelium. These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1 in cochlear progenitor cells, possibly through the activity of HES5.

Aging↗

Endoscopy of the internal auditory canal during hearing conservation acoustic tumor surgery.

Hearing conservation acoustic neuroma surgery is technically demanding. This is attributable primarily to the formidable anatomic obstacles. The axis of the internal auditory canal (IAC) is oriented at an obtuse angle relative to the posterior petrous ridge. In addition, the labyrinth blocks the view of the lateral 2 to 3 mm of the IAC. These two factors prohibit an unobstructed view of the fundus of the IAC with a standard operating binocular microscope. However, angled rigid endoscopes (30 and 70 degrees) offer excellent views of the lateral portion of IAC. The facial nerve, cochleovestibular nerve, transverse crest, and vertical crest (Bill's bar) can be seen endoscopically. Neuroendoscopic examination is helpful to ensure complete tumor removal in the lateral IAC during acoustic tumor surgery. It is also helpful in visually verifying the continuity of the facial and cochlear nerves at the end of the operation.

Adult↗

Pressure transfer between the perilymph and the cerebrospinal fluid compartments in cats.

This is a review of our studies of the labyrinthine fluid pressure in cats subjected to pressure changes in the middle ear (implosive routes) and the cerebrospinal fluid compartment (explosive routes) as well as to changes in vascular and ambient pressures. The perilymph, cerebrospinal fluid (CSF), middle ear, venous and arterial pressures were measured with the cochlear aqueduct (CA) patent as well as surgically blocked. Experiments on explosive pressure changes revealed that the perilymph pressure was regulated by the CSF in case of CA patency. The CSF influence was dominant enough to obscure any direct effect on the labyrinth from other sources. With the CA obstructed the CSF influence on the labyrinth was apparently mainly via the endolymphatic sac and duct although limited and much delayed. Systemic arterial pressure changes had a pronounced influence on the perilymph pressure, but this effect was revealed only when the CSF influence was reduced by CA obstruction. Experiments on implosive and ambient pressure changes suggested that there was no fundamental difference in the perilymph response to equivalent levels of implosive versus hypobaric pressure. Three factors determined the effect of implosive and hypobaric pressure: the patency of the CA, the rate of the pressure change, and the eustachian tube function.

Air Pressure↗

Vestibular and cochlear efferent neurons in the monkey identified by immunocytochemical methods.

Attempts were made to identify vestibular (VEN) and cochlear (CEN) efferent neurons in the squirrel monkey using retrograde transport of horseradish peroxidase (HRP) and immunocytochemical methods. HRP implants in the ampulla of the lateral semicircular duct retrogradely labeled cells of VEN bilaterally and some cells of CEN. VEN located lateral to the rostral part of the abducens nucleus formed a compact collection of cells, all of which were immunoreactive only to antisera for choline acetyltransferase (ChAT). CEN, identified by immunoreactivity to ChAT were located at the hilus of the lateral superior olive (LSO), along the lateral border of the LSO and sparsely near lateral parts of the ventral trapezoid nucleus (VTN). A small number of cells and fibers near the border of the VTN and lateral to the LSO were immunoreactive for leucine enkephalin (L-ENK). Fibers immunoreactive for L-ENK also were identified in the hilus of the LSO. No cells of the superior olivary complex were immunoreactive for antisera to ChAT, L-ENK, substance P, gamma-aminobutyric acid or glutamic acid decarboxylase. Cells of VEN and CEN can be identified by their immunoreactivity to ChAT, and some cells and fibers of CEN also contain L-ENK.

Animals↗

Alternobaric oxygen therapy in long-term treatment of Ménière's disease.

Hyperbaric oxygen therapy (HBQ) has been used for several years as a treatment for Ménière's disease, particularly in Sweden. In this study continuous variations in pressure (from 1.7 to 2.2 ATA; alternobaric oxygen therapy: ABOT) were used to decrease endolymphatic hydrops, the typical histopathological substrate of Ménière's disease by increasing hydrostatic pressure and mechanical stimulation of the endolymphatic flow toward the duct and the endolymphatic sac, which produces a consequent increase in the dissolved O2 content in the labyrinth liquid, which should contribute to recovering cell metabolism and restoring cochlear electrophysiological function to normal. An experimental group of 20 patients suffering from unilateral Ménière's disease received a total of 15 ABOT treatment sessions during the acute episodes. Treatment foresaw two days without therapy every five days of application. Maintenance treatment consisted of one session per day for five consecutive days every month for one year. Thereafter, during the second, third, and fourth years of treatment, patients were submitted to one session per day for five consecutive days every three months. A control group of 18 patients suffering from Ménière's disease was treated with 10% glycerol i.v. (during the acute episodes) and with betahistine (8 mg x 3/day) in the periods in between. Mean pure tone average (PTA in dBHL) hearing thresholds at octave frequencies from 500 to 3,000Hz, and frequency of episodes of vertigo and tinnitus, both after 15 days of treatment and at the end of a four-year follow-up, were compared for both groups according to the 1995 Committee on Hearing and Equilibrium criteria. No statistically significant differences were found between the two groups at the end of the first 15 days of treatment. However, at the end of the follow-up period, patients treated with ABOT had significantly fewer vertiginous episodes and improved PTAs and tinnitus compared to the controls. The results support the use of ABOT as a valid alternative to drugs in the long-term treatment of Ménière's disease.

Adult↗

An evaluation of retrograde tracing methods for the identification of chemically distinct cochlear efferent neurons.

We have compared retrograde labelling of rat olivocochlear neurons after unilateral cochlear injections of wheatgerm agglutinin conjugated horseradish peroxidase (WGA-HRP) and free HRP. After cochlear injection of WGA-HRP, labelling of nerve cell bodies in the brainstem can be explained not only as conventional retrograde labelling resulting from uptake by efferent nerve terminals synapsing on or near hair cells, but also as spurious labelling originating from tracer leakage, through the periotic duct and over the eighth nerve sheaths, into the cerebral-spinal fluid. Depending on the length of survival time, spurious labelling can involve small portions of the nucleus of the trapezoid body or the entire auditory brainstem and other non-auditory centers. On the contrary, moderate amounts of free HRP delivered to the cochlea do not lead to spurious labelling. With free HRP as the tracer of choice, we found that cochlear efferent cells were located not only in the ipsilateral LSO body and bilaterally within MVPO and RPO as already described by White and Warr, but also surrounding the ipsilateral LSO and in the ipsilateral LVPO. The allocation of these newly described olivocochlear neurons to the medial large cell or lateral small cell system is uncertain because they are located laterally in the brainstem and project ipsilaterally but are large spherical to fusiform or multipolar cells. A zinc salicylate-formol fixative and a metal intensified DAB reaction were found to be effective in visualizing retrogradely transported HRP in neurons and allowed immunocytochemical staining of the same sections with antisera to glutamic acid decarboxylase and choline acetyltransferase. This double label protocol can be used to produce a neurochemical map of the OC systems.

Animals↗

Molecular mechanisms underlying inner ear patterning defects in kreisler mutants.

Prior studies have shown that kreisler mutants display early inner ear defects that are related to abnormal hindbrain development and signaling. These defects in kreisler mice have been linked to mutation of the kr/mafB gene. To investigate potential relevance of kr/mafB and abnormal hindbrain development in inner ear patterning, we analyzed the ear morphogenesis in kreisler mice using a paint-fill technique. We also examined the expression patterns of a battery of genes important for normal inner ear patterning and development. Our results indicate that the loss of dorsal otic structures such as the endolymphatic duct and sac is attributable to the downregulation of Gbx2, Dlx5 and Wnt2b in the dorsal region of the otocyst. In contrast, the expanded expression domain of Otx2 in the ventral otic region likely contributes to the cochlear phenotype seen in kreisler mutants. Sensory organ development is also markedly disrupted in kreisler mutants. This pattern of defects and gene expression changes is remarkably similar to that observed in Gbx2 mutants. Taken together, the data show an important role for hindbrain cues, and indirectly, kr/mafB, in guiding inner ear morphogenesis. The data also identify Gbx2, Dlx5, Wnt2b and Otx2 as key otic genes ultimately affected by perturbation of the kr/mafB-hindbrain pathway.

Animals↗

Meniere's disease: overview, epidemiology, and natural history.

Meniere's disease is a disease of the inner ear characterized by a triad of symptoms: vestibular symptoms, auditory symptoms, and pressure. The pathologic correlate of Meniere's disease is endolymphatic hydrops and the etiopathogenesis involves a deficiency in the absorption of endolymph. The pathophysiology of the symptoms is still disputed: membranous ruptures, pressure and mechanical displacement of the end organs, or obstruction followed by an abrupt clearance of the endolymphatic duct. The course of the disease may be progressive or nonprogressive and, in addition to the typical presentation of Meniere's disease, two variations of the disorder have been identified: cochlear Meniere's disease, and vestibular Meniere's disease. It can be further broken into two subsets: Meniere's syndrome, with a known and well-established cause, and Meniere's disease, in which the cause seems to be idiopathic. It is likely that there are racial (genetic) as well as environmental factors that influence differences in incidence among countries and among various sections of countries. The disease is much more common in adults, with an average age of onset in the fourth decade, the symptoms beginning usually between ages 20 and 60 years. Meniere's disease is (grossly) equally common in each sex, and right and left ears are affected with fairly equal frequency. The diagnosis of Meniere's disease is by exclusion, and a careful history is the most important guide to a correct diagnosis. Its medical treatment is largely empiric. Surgery can be considered when, even after medical therapy, the disease progresses and the symptoms become intractable. Surgery may be either conservative or destructive. Bilaterality must be considered when deciding the best surgical option for a patient with Meniere's disease. It is the authors' opinion that endolymphatic sac surgery is an extension of conservative treatment.

Adult↗

[Oxygen therapy in the long term treatment of Meniere's disease].

Endolymphatic hydrops is the hystopathological substrate characteristic of Ménière's disease. Besides the classical treatment with diuretics and/or osmotic drugs for some time, now treatment in a "pressure chamber" (OTI) has also been applied. The oxygen administered in the hyperbaric chamber can reduce the hydrops both by increasing the hydrostatic pressure and by mechanically stimulating the flow of endolymph toward the duct and endolymphatic sac. In addition, an increase is seen in the amount of O2 dissolved in the labyrinthine fluids and this contributes to recovering cell metabolism and restoring normal cochlear electrophysiological functions. Between 1992 and 1996 40 patients with monolateral Ménière's disease were studied: 15 underwent oxygen therapy at a constant pressure (2.2 ATA) (HOT), 25 with a continuous variation in pressure (from 1.7 to 2.2 ATA) (Alternobaric therapy, AOT). During the acute phase the patients underwent daily OTI treatment for 15 days in a row. The maintenance treatment called for one treatment cycle (one session a day for 5 days in a row) a month for 1 year, followed by for one treatment cycle (one session a day for 5 days in a row) every three months during the 2nd, 3rd and 4th years. The controls consisted of a group of 18 patients treated with 10% glycerol i.v. (during the acute phase) and betahystine (8 mg x 3/die) between episodes. A comparison was made of the average hearing threshold for the frequencies 500-3000 Hz (PTA), how frequently episodes of dizziness arose and extent of hearing loss in the three groups after the initial 15 days of treatment and at the end of the 4-year follow-up, in compliance with the criteria laid down by the Committee on Hearing and Equilibrium in 1995. At the end of the first 15 days of treatment, there were no statistically significant differences between the three groups. At the end of the follow-up, on the other hand, hyperbaric treatment, and in particular alternobaric therapy, enabled a significant reduction in the episodes of dizziness as compared to the control group. PTA and deafness also improved significantly in the patients who had undergone hyperbaric treatment. The results of the present work show that HOT, and in particular AOT, offer a valid alternative to drugs in the treatment of Ménière's disease.

Acute Disease↗

[Otoacoustic distortion products in infants and adults: a comparative study].

Distortion Products (DP) are otoacoustic emissions evoked by emitting two pure tones. The principle advantage of this method vs. transient evoked otoacoustic emissions is the specificness of frequency. The purpose of the present work was to determine whether this technique could be applied in objective study of cochlear function in infants. This was done by setting standard data for infants and comparing them with the data obtained in a control population of adults. The input/output functions of the DP and the DP audiograms for 8 f2 frequencies ranging from 696 to 6006 Hz were studied in a group of 15 healthy, full-term infants. The data obtained were statistically compared to the data taken from a control group of 8 normal hearing adults. The infants showed significantly more intense DPs in the intermediate frequencies, with a greater detection threshold and dynamic range. On the other hand, at the high frequencies the amplitude of infant DPs was the same or lower than (f2 = 5005) those found in the adults. These differences can partially be attributed to the fact that the outer auditory channel is smaller in infants thus the probe and the middle ear are better matched. There is significantly greater background noise in infant DPs, particularly at low frequencies. This may be due to the fact that the skin of the outer auditory duct--which acts as a low-pass filter allowing suction and movement of the cervical muscles to contaminate the tracing--is thinner in infants. In conclusion, the study of DPs has shown its potential in the study of cochlear function in infants because it is non invasive and objective, it can be performed quickly and shows frequency specificness. Unfortunately, it cannot be considered a valid method for determining cochlear function at the low frequencies.

Acoustic Stimulation↗

Comparison of ephrin-A ligand and EphA receptor distribution in the developing inner ear.

Members of the recently discovered Eph family appear to play important roles in a variety of developmental processes including tissue segmentation, cell migration and axonal guidance. To begin to understand the functions of the EphA subclass of receptors and their corresponding GPI-linked (ephrin-A) ligands in the inner ear, a developmental immunohistochemical analysis was completed. The results indicated that the ligands ephrin-A1 and ephrin-A2 were localized mainly at cellular boundaries in the inner ear. Ephrin-A1 was detected mainly in the epithelial cells lining the fluid filled ducts of the inner ear, whereas ephrin-A2 was prominently expressed in connective tissue regions. The receptor EphA4 was detected in vestibular hair cells. EphA5 and EphA7 were detected mainly in cochlear and vestibular supporting cells. These results suggest that these Eph molecules play a role in establishing the formation and cellular organization of the complex inner ear labyrinth. Additionally, all of the ligands and receptors evaluated were expressed in vestibular and cochlear neurons at various developmental stages, suggesting they may play a role in establishing or maintaining innervation to the inner ear.

Actins↗

Overlapping thin-section fast spin-echo MR of the large vestibular aqueduct syndrome.

PURPOSE: To evaluate a high-resolution, thin-section fast spin-echo MR imaging technique of the inner ear to identify the large vestibular aqueduct syndrome seen on temporal bone CT scans. METHODS: We retrospectively reviewed the temporal bone CT scans of 21 patients with hearing loss and enlarged bony vestibular aqueducts by CT criteria. High-resolution fast spin-echo MR imaging was then performed on these patients using dual 3-inch phased-array receiver coils fixed in a temporomandibular joint holder and centered over the temporal bones. MR imaging included axial and oblique sagittal fast spin-echo sequences. The diameter of the midvestibular aqueduct on CT scans and the signal at the level of the midaqueduct on MR images were measured on axial sequences, then compared. High-resolution MR imaging with the same protocol was performed in 44 control subjects with normal ears, and similar measurements were taken. RESULTS: The average size of the enlarged bony vestibular aqueduct on CT scans was 3.7 mm, and the average width of the signal from within the enlarged aqueduct on MR images was 3.8 mm. Statistical analysis showed excellent correlation. MR images alone displayed the enlarged extraosseous endolymphatic sac, which accompanies the enlarged aqueduct in this syndrome. Five ears in three patients with enlarged bony vestibular aqueducts on CT scans showed no evidence of an enlarged endolymphatic duct or sac on MR images. An enlarged endolymphatic sac was seen on MR images in one patient with a bony vestibular aqueduct, which had normal measurements on CT scans. MR imaging alone identified a single case of mild cochlear dysplasia (Mondini malformation). In the 88 normal ears studied, the average size of the endolymphatic sac at its midpoint between the common crus and the external aperture measured on MR images was 0.8 mm (range, 0.5 to 1.4 mm). In 25% of the normal ears, no signal was seen from within the vestibular aqueduct. CONCLUSION: Thin-section, high-resolution fast spin-echo MR imaging of the inner ear is complementary to CT in studying patients with the large vestibular aqueduct syndrome, as MR imaging better displays the soft tissue and fluid of the membranous labyrinth.

Adolescent↗

A cochlear vascular anomaly in a patient with hearing loss and tinnitus.

An unusual blood vessel in the cochlea of a patient is reported. The blood vessel derives from the osseous lamina spiralis and crosses straight through the scala tympani toward the lateral wall of the perilymphatic duct. In its course a branch derives from this vessel toward the other spiral vessel. In the region of this abberrant vessel a complete hair-cell loss is present. A high tone perceptive loss with a relative dip and tinnitus was found in the same ear during life. The possible cause and effects of this abberrant vessel are discussed.

Aged↗