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Developmental expression of a voltage-dependent potassium channel (Kv3.1) in auditory neurons without cochlear input.

Kv3.1, a voltage-dependent potassium channel, has two forms, -a and -b, which differ in expression during development and at the onset of function in the auditory system. To determine whether cochlear nerve input could affect the expression of these two forms, cultures of the developing cochlear nucleus were explanted in the absence of the cochlear nerve at the beginning of cell migration (Hamburger-Hamilton stage 28-30), while neuroblasts continued to migrate onto the culture substrate. After 8, 15, and 22 days in vitro (three survival groups), cultures were immunostained with antibodies recognizing either both forms of Kv3.1 or only the -b form. Only young and newly migrated nerve cells were sampled. In the three survival groups, all nerve cells expressed Kv3.1, among which only 50% or less expressed the -b form. Some of the more differentiated multipolar cells expressed the -b form, but most were labeled with the antibody that recognizes both forms. Thus, in the absence of peripheral input, both forms of Kv3.1 appear at stages very early in development, although not all cells necessarily coexpress both forms. These results agree with other observations in the chick embryo in situ. They are consistent with previous work implicating Kv3.1 in cell migration during early development.

Age Factors↗

Neurostimulation as a new treatment for severe tinnitus: a pilot study.

BACKGROUND: Tinnitus is an uncomfortable symptom for the patient and an embarrassing one for the consulted physician. So far, there is no treatment that can be considered well established in terms of providing long-term reduction of tinnitus in excess of placebo effects. There is considerable evidence of pathophysiological similarity between tinnitus and chronic pain. Some forms of chronic pain can be treated by neurostimulation. OBJECTIVE: This study was designed to investigate the feasibility of neurostimulation of the cochlear nerve in order to reduce tinnitus. STUDY DESIGN: Pilot study. SETTING: Tertiary referral center. PATIENTS: Five patients with therapeutically refractory tinnitus were selected for this study. INTERVENTION: Placing a stimulation lead around the cochlear nerve through the suboccipital approach and connecting the stimulation lead to a pulse generator. MAIN OUTCOME MEASURES: The patients experienced 1) an absence of major or minor complications, such as death, meningitis, cranial nerve deficit, and vestibular problems; 2) tolerance of the procedure as considered by the patient; 3) relief of tinnitus in at least one patient. RESULTS: Implantation of the neurostimulation system was accomplished in each patient without any difficulty. None of the patients considered the treatment unbearable. No major or minor complications occurred in this study. Subjective tinnitus reduction was accomplished in four patients. CONCLUSION: Our preliminary data show that neurostimulation of the cochlear nerve is feasible, is bearable for the patient, and is a safe treatment modality without major complications. The effects on tinnitus are promising.

Aged↗

Enhanced MRI in patients with Ramsay-Hunt's syndrome.

Enhanced MRI was performed in 14 patients with Ramsay-Hunt's syndrome to investigate the pathogenesis of this syndrome. All MRI studies were performed on a 0.5T superconductivity MRI system using a head coil with Gd-DTPA. Enhancement was observed in the areas of the distal internal auditory canal and labyrinthine segment in many patients, and was especially prominent in patients suffering from vertigo, tinnitus, and hearing loss. In some patients it involved not only the facial nerve of the internal auditory canal but also the cochlear nerve and vestibular nerves. Since histological changes of the facial nerve in patients with Ramsay-Hunt's syndrome are assumed to occur in the distal internal auditory canal and labyrinthine segment, which is more proximal than the geniculate ganglion, and the possibility is suggested that inflammation may spread to the vestibular and cochlear nerve via the internal auditory canal.

Aged↗

The magnetless Clarion cochlear implant in a patient with neurofibromatosis 2.

We present our experience using the Clarion magnetless multichannel cochlear implant with a woman profoundly deafened following bilateral acoustic neuromata as a consequence of neurofibromatosis 2 (NF2). The right neuroma had been previously removed without an attempt at neural preservation. On the left, however, a posterior fossa approach had been taken with the aim of preserving hearing. Although the left cochlear nerve appeared to be undamaged at the end of the operation, no hearing thresholds could be elicited on post-operative audiometry, because of damage either to the cochlear nerve or to the blood supply to the cochlea. Round window electrical stimulation subsequently produced a perception of sound, confirming that the cochlear nerve was capable of functioning and that a cochlear implant would be effective. Because she would need regular magnetic resonance imaging (MRI) to monitor existing and future NF2 lesions, it was decided to use a magnetless Clarion implant, which has been shown to be MRI compatible. We report our experience of using the device in this case and discuss some of the issues related to the provision of cochlear implants to patients with NF2.

Adult↗

[Failure to preserve hearing in acoustic neuroma surgery: experiences after introduction of MRI].

This report elucidates our experiences on acoustic neuroma surgery, in which auditory function was lost postoperatively, although conservation of hearing had been intended preoperatively. Five ears from four patients (two ears: unilateral, three ears from bilateral acoustic neuromas) were operated on via standard retromastoid route, with monitoring of auditory evoked potentials. Abolition of ABR occurred when surgical manipulations were performed within the internal auditory canal. Pulling tumor tissue away from the cochlea toward the brain stem has proved to be a hazardous procedure. Recognizing the condition of tumor tissue within the internal auditory canal is prerequisite for hearing preservation. For this purpose, MRI is very useful because tumor tissue within the internal auditory canal can be clearly visualized. The preoperative criteria in selecting candidates for hearing preservation operations should be more strict because most acoustic neuromas with a diameter of more than 10mm cannot be resected without causing loss of hearing, and, even in such small tumors, the cochlear nerves are infiltrated by tumor cells. Most ABR changes during operations seem to be explicable from avulsion of the cochlear nerve fibers and/or the internal auditory artery from the fundus of the internal auditory canal-the tractus spiralis foraminosus. Postoperative recordings of ABR indicated that progression of degeneration of the cochlear nerve fibers occurred after surgery. This phenomenon may explain postoperative delayed hearing loss observed clinically.

Adolescent↗

Auditory evoked responses under total spinal anesthesia in rats.

In order to investigate the function of the auditory pathway from the cochlea to the brain stem under total spinal anesthesia, the auditory brain stem response (ABR), compound action potential of the cochlear nerve (CAP), and cochlear microphonics (CM) were simultaneously recorded in rats. Total spinal anesthesia was induced by infusion of 2% lidocaine hydrochloride at a constant rate of 0.10 mL/min into the cerebrospinal fluid through the rats' skulls. The ABR completely disappeared within 1.5 to 4 minutes. After cessation of the injection, the ABR reappeared, starting from wave I and progressing through waves II and III to wave IV. The latency change of the CAP throughout the recording period was quite similar to that of wave I of the ABR. A reduction in amplitude of the CM was observed, but the CM did not disappear during the recording period. Disappearance of the ABR was due, not to loss of cochlear function, but to anesthetic effects on the acoustic nerve and the brain stem. Monitoring of the ABR provided information on the level of neural activity in the brain stem under total spinal anesthesia.

Action Potentials↗

Axogenesis in the human fetal auditory system, demonstrated by neurofilament immunohistochemistry.

Morphological, electrophysiological and behavioral evidence indicates that the onset of rapid, synchronized conduction of auditory impulses occurs in the human brainstem during the 28th-29th fetal weeks. This implies that axonal connections in the brainstem auditory pathway are generated prior to this time. In order to investigate the sequence of axogenic events in the human brainstem pathway, we employed immunohistochemical techniques and an antibody to neurofilament protein. Immunostaining for axonal neurofilaments in an age-graded series of fetal brains demonstrates that a small number of cochlear nerve axons have invaded the ventral cochlear nucleus by the 16th fetal week. By this same time point, a limited number of trapezoid body-lateral lemniscus axons have reached the superior olivary complex and inferior colliculus. Between gestational weeks 16 and 26, there is marked expansion and collateralization of the ascending pathway from cochlear nerve to inferior colliculus. By week 26, ascending axons have begun to form plexuses of terminal neuropil within all of the brainstem auditory nuclei. Beginning in week 22, there is development of commissural axons (dorsal commissure of the lateral lemniscus and commissure of the inferior colliculus) and descending projections (descending collicular axons and olivocochlear bundle). This early establishment of a mature pattern of axonal connections presumably forms the basis for the appearance of myelin, acousticomotor reflexes and recordable brainstem responses by fetal week 29.

Auditory Pathways↗

Projections of cochlear root neurons, sentinels of the rat auditory pathway.

In certain rodents, the root of the cochlear nerve contains a population of large neurons, known as cochlear root neurons (CRNs), an essential element of the primary acoustic startle pathway. To characterize the projections of the CRNs, we made stereotaxically guided, iontophoretic injections of biotinylated tracers into the cochlear nerve root of albino rats. CRN axons, which are remarkably thick, enter the trapezoid body, cross the midline, and ascend in the rostral aspect of the lateral lemniscus to reach the upper levels of the midbrain. As a group, CRN axons produce a characteristic pattern of profusely ramified collaterals that innervate specific brainstem regions. The main target of CRN axons is the contralateral pontine reticular formation, where collaterals terminate in the caudal pontine reticular nucleus (PnC) and, to a lesser degree, in the ventrolateral tegmental area, the oral pontine reticular nucleus, and the rostral and medial paralemniscal regions. Other targets of CRN axons include the lateral paragigantocellular nucleus of both sides, the ipsilateral facial motor nucleus and PnC, and the contralateral intercollicular tegmentum and superior colliculus. Notably, CRNs apparently do not innervate any of the nuclei of the auditory brainstem, as usually defined, even though their axons pass through or in close proximity to them. The fact that CRNs innervate several reticular and tectal structures that mediate auditory alerting and escape behaviors suggests that they are "early warning neurons," i.e., true sentinels of the auditory pathway.

Animals↗

Preservation of hearing in patients undergoing excision of acoustic neuromas and other cerebellopontine angle tumors.

Microsurgical techniques have made it possible to identify and preserve the cochlear nerve from its origin at the brain stem and along its course through the internal auditory canal in patients undergoing removal of small or medium-sized acoustic neuromas or other cerebellopontine angle (CPA) tumors. In a consecutive series of 100 patients with such tumors operated on between 1975 and 1981, an attempt was made to preserve the cochlear nerve in 23. The decision to attempt to preserve hearing was based on tumor size and the degree of associated hearing loss. In cases of unilateral acoustic neuroma, the criteria for attempted preservation of hearing were tumor size (2.5 cm or less), speech reception threshold (50 dB or less), and speech discrimination score (60% or greater). In patients with bilateral acoustic neuromas or tumors of other types, the size and hearing criteria were significantly broadened. All patients were operated on through a suboccipital approach. Hearing was preserved postoperatively in six (31.6%) of the 19 patients with unilateral acoustic neuromas, although the cochlear nerve was preserved in 16. Of the six patients with postoperative hearing, three retained excellent hearing, and the other three had only sound awareness and poor discrimination. Hearing was preserved in three cases with other CPA tumors, including an epidermoid cyst and small petrous meningiomas in the internal auditory canal. Of the two cases with bilateral tumors, hearing was preserved in one. Of the 23 patients in whom hearing preservation was attempted, nine (39.1%) had some postoperative hearing, which in six was equal to or better than the preoperative level. Thus, it is worthwhile to attempt hearing preservation in selected patients with CPA tumors.

Brain Neoplasms↗

Electrode interaction in pediatric cochlear implant subjects.

Multielectrode cochlear implants rely on differential stimulation of the cochlear nerve for presenting the brain with the spectral and timing information required to understand speech. In implant patients, the degree of overlap among cochlear nerve fibers stimulated by the different electrodes constitutes the electrode interaction. Electrode interaction degrades the spectral resolution of the implant's stimulus. We sought to define electrode interaction in a cohort of pediatric cochlear implant subjects as a function of both stimulus intensity and electrode location along the array. The 27 pediatric subjects that completed the study were implanted with either the Clarion Hi-Focus array with or without positioner, the Nucleus 24 Contour array, or the Nucleus 24 Straight array. All but two of the patients had congenital hearing loss, and none of the patients had meningitis prior to the onset of deafness. The cochlear nerve response was measured with the electrically evoked compound action potential (ECAP). A forward masking protocol was used such that a probe stimulus electrode remained fixed while a preceding masker was moved across the array. Electrode interaction was estimated by measuring the unmasked probe response minus the masked probe response. Three probe locations and three probe intensities were examined for each subject. At all probe locations, electrode interaction increased as probe intensity increased (p < 0.05). Interaction at the basal probe was less than that at either the middle or apical probe locations (p < 0.05), and significant correlation found between probe distance from the basal end of the array and electrode interaction (p < 0.001). These results demonstrate that in this cohort of pediatric subjects, electrode interaction depended on both stimulus intensity and probe location. Implications of these findings on future implant array design and current implant fitting strategies are discussed. The impact of electrode interaction on implant performance is yet to be elucidated.

Artifacts↗

Temporal bone pathology of acoustic neuroma correlating with presence of electrocochleography and absence of auditory brainstem response.

The temporal bone pathology of a 74-year-old female affected by vestibular schwannoma was compared with findings of auditory brainstem response and electrocochleography. At age 71, she complained of hearing loss in the left ear in which pure tone audiometry revealed threshold elevation in the middle- and high-frequency range. Temporal bone CT scanning revealed a medium-sized cerebellopontine angle tumour in the left ear. ABR showed no response in the left ear, but the electrocochleography showed clear compound action potentials. Three years later, at age 74, she died of metastatic lung cancer and sepsis. The left temporal bone pathology consisted primarily of a large vestibular schwannoma occupying the internal auditory meatus. The organ of Corti was well preserved in each turn. In the modiolus, the numbers of spiral ganglion cells and cochlear nerve fibres in each turn were decreased. These histological findings suggest that clear compound action potentials were recorded from the distal portion of the cochlear nerve in spite of the presence of the vestibular schwannoma, but ABR could not be detected because of the blockade of the proximal portion of the cochlear nerve by the vestibular schwannoma.

Aged↗

A developmental gradient of dendritic loss in the avian cochlear nucleus occurring independently of primary afferents.

Cochlear nerve axons and their target neurons in nucleus magnocellularis (NM) of the chicken undergo extensive parallel structural transformations during development. Between embryonic days 12 and 17 (E12-E17), each immature highly branched axon condenses into a mature calyxlike ending applied to a single NM neuron. Simultaneously, NM neurons are transformed from multipolar cells with many long dendrites into spherical unipolar neurons with only an axon. We tested the hypothesis that cochlear nerve input is necessary for the transformation of NM cells by surgically destroying one otocyst on E3, thereby preventing formation of the nerve. Nucleus magnocellularis neurons from embryos at E11-E12, E13-14, and E17-18 were stained by horseradish peroxidase injected into their axons or by a Golgi-Hortega method. In camera lucida drawings, the number of dendrites on each cell was counted and the cell's position along the posterior-to-anterior and lateral-to-medial axes of the nucleus quantified. At E11-12, neurons throughout NM on both the deafferented and normally innervated sides of the brain have about ten dendrites. At E13-14, there is a steep spatial gradient in dendritic number bilaterally; cells at anteromedial positions have about two dendrites, while cells in posterolateral positions have an average of nine dendrites. By E17-18, only 14% of the neurons on either side have a dendrite, and these cells are evenly distributed throughout the nucleus. We conclude that cochlear nerve axons are not required for normal spatio-temporal gradients of dendritic loss, even though the absence of these axons causes severe atrophic changes in NM.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Frequency selectivity of central auditory neurons without inner ear.

A group of neurons in the inferior colliculus (IC) of the chicken displayed frequency selectivity after surgical removal of both cochleae. Characteristic neuronal frequencies were evident in the following three measures. i) The cells fired spontaneously with discrete preferred interspike intervals; ii) Impulse responses of these neurons to electrical stimuli of cochlear nerves displayed oscillations at the preferred frequencies; iii) When the cochlear nerves were stimulated with a random pulse sequence, a reverse correlation analysis showed that the cells preferred the same frequencies in the stimulus input. Preferred frequencies observed thus far covered over 4 octaves of the auditory range. These "oscillating cells" were found only in a small rostromedial area in the IC. Neuronal frequency selectivity may serve a temporal analysis of sound and underlie sound identification with certain cochlear implants. It may also support interaural crosscorrelation necessary for directional hearing.

Animals↗

Quantitative analysis of nerve fibre densities in the cochlea of the house mouse (Mus musculus).

Transverse sections of the cochlear nerve, silver-stained surface preparations of the cochlea, and silver- and osmium-stained tangential sections of the cochlea of the house mouse were made to determine the number and density of nerve fibres entering the organ of Corti and their distribution to inner and outer hair cells along the cochlear spiral. A number of 12,578 +/- 819 fibres was counted within the cochlear nerve, which is almost equal to the total number of 12,350 +/- 810 fibres entering the organ of Corti. The 12,350 fibres divide into 9,780 (= 79%) fibres running to the inner hair cells, 703 (= 6%) basilar (afferent) fibres and 1,867 (= 15%) upper tunnel radial (efferent) fibres innervating the outer hair cells. About 93% of all afferent fibres are connected to the inner hair cells, and only 7% innervate outer hair cells. The density of fibres running to the inner hair cells varies considerably and has a significant (p less than 0.01) absolute and relative maximum 3.7 mm and 2.9 mm from the apex respectively (total length: 6.84 mm) and decreases toward apex and base. The density of afferent fibres running to the outer hair cells shows a slow increase up to 2 mm from the apex, and remains on a constant low level (5.5 fibres per 40 micrometer) down to the base. The density of efferent fibres running to the outer hair cells increases linearly up to about 2 mm from the apex, remains rather constant (10 fibres per 40 micrometer) from 2 mm to 4 mm, and then decreases toward the base. Generally, the outer hair cells show a convergent innervation pattern, the inner hair cells a divergent one. The significance of the present measurements is discussed in relation to respecitve results from other mammals and in relation to auditory thresholds.

Animals↗

Occurrence of vestibular and facial nerve injury following cerebellopontine angle operations.

To elucidate how surgery in the cerebellopontine (CP) angle may cause vestibular and facial nerve injury, the 7th and 8th cranial nerves of dogs were manipulated as in human surgery along with monitoring of auditory evoked brain stem responses. Postoperatively, histological examinations were performed to investigate the effect of the surgical manipulations. We found that the occurrence of vestibular, facial and cochlear nerve injury was dependent on the direction of the excessive movement of the nerves in the cerebellopontine (CP) angle. Caudal-to-rostral shift of the nerve trunk most effectively avulsed the vestibular nerve. Haemorrhages were revealed between the vestibular ganglion and the fundus of the internal auditory canal. This caudal-to-rostral retraction could also damage the facial nerve in its intrapetrous labyrinthine portion. This was likely to be one of the pathophysiological mechanisms responsible for postoperative facial nerve palsy occasionally observed in human cases. Rostral-to-caudal retraction of the cerebellum damaged the cochlear nerve selectively. Although caudal-to-rostral retraction, instead of lateral-to-medial one, has been recommended to protect the cochlear nerve, this retraction was shown to be dangerous to the vestibular nerve if excessive. The clinical significance of the fragility of the vestibular nerve was discussed and the importance of preserving the vestibular nerve function is stressed.

Animals↗

Glutamate neurotoxicity in rat auditory system: cochlear nuclear complex.

In other systems such as the hypothalamus and hippocampus, it has been shown that cells postsynaptic with respect to glutamatergic inputs degenerate when exposed to large doses of glutamate ("glutamate neurotoxicity"). We have shown that large doses of glutamate administered intraperitoneally are toxic to spiral ganglion cells in the inner ear of the rat. In the present study, we have investigated whether similar levels of glutamate cause alterations in the neurons of the cochlear nuclei. Specifically, we have studied the morphology and size of the cochlear nuclear complex and its subdivisions as well as the size and density of cochlear nucleus neurons following administration of glutamate. The morphological evidence indicates that glutamate caused severe anatomical alteration of the cochlear nuclei. The changes were most pronounced in the anteroventral cochlear nucleus, especially in the neurons that receive terminals of the end bulbs of Held from the cochlear nerve. This could be a direct effect of glutamate in the cochlear nuclei or secondary to degeneration of cochlear nerve fibers in the inner ear.

Animals↗

Differential expression of N-methyl-D-aspartate receptor in the cochlear nucleus of the mouse.

Glutamate is used in the cochlear nucleus as a neurotransmitter by cochlear nerve synapses and by local circuits of granule cell axons. In the present study, immunocytochemistry and in situ hybridization were used to identify different types of neurons expressing N-methyl-D-aspartate receptor subunit I (NMDAR1) in the mouse cochlear nucleus. N-Methyl-D-aspartate receptor subunit 1 was expressed in most neuronal types, but granule cells in the dorsal cochlear nucleus had little, if any, expression, unlike their heavily labeled counterparts in the small cell shell and cerebellum. The findings do not support an analogy between the dorsal cochlear nucleus and the cerebellar cortex. In the cochlear nucleus the most heavily labeled structures were dendrites in the small cell shell and superficial dorsal cochlear nucleus, including the fusiform cell apical dendrites, which are targets of granule cell axons. However, fusiform cell basal dendrites, which are the synaptic sites of cochlear nerve fibers, did not express N-methyl-D-aspartate receptor subunit 1. Thus different parts of the fusiform cells can have different subunits in their glutamate receptors. Also branches of the same cochlear nerve axons projecting to the octopus, stellate, and bushy cells of the ventral cochlear nucleus can use N-methyl-D-aspartate receptor, while their branches to fusiform cells cannot. Each cochlear nucleus neuron type has a characteristic level of N-methyl-D-aspartate receptor subunit 1 expression. Each type differs in its auditory response properties, which may depend on synaptic activities requiring different glutamate subunit patterns.

Animals↗