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Total deafness from aminoglycoside overdosage: histopathologic case study.

A 57-year-old patient became totally deaf two days after receiving excessive doses of the aminoglycosidic antibiotic lividomycin parenterally for 14 days; she died four and a half months later. Her temporal bones were examined by microdissection, surface preparation, and serial sectioning of the modiolus. Loss of inner and outer cochlear hair cells was virtually complete. Refractile concretions were scattered along the atrophic stria vascularis, especially in the middle turn. The distal half of the radial cochlear nerve fibers in the osseous spiral lamina had degenerated, but closer to the modiolus they appeared to be intact. The spiral ganglion in the basal turn showed partial loss of neurons. Scanning electron microscopy revealed hair cell loss from the vestibular end-organs, more severe in the ampullar cristae than in the utricular macula. The dark cells of the utricular wall appeared to be altered.

Chemical Phenomena↗

Some pathologies of sensory and neural hearing loss.

Recently surgical implantation of devices to stimulate the auditory nerve in man makes it apparent that sensory and neural pathologies of deafness need to be differentiated from each other. In this paper 10 exemplary cases are presented. In addition, an attempt is made to compile the information now available about sensory and neural pathologies in the various diseases that cause deafness. Superficially, it would appear that most such entities are sensory in nature and thus theoretically might be amenable to auditory nerve stimulation. However, loss of supporting cells seems to be associated with cochlear nerve fibre degeneration. Many individuals may, therefore, eventually develop combined pathology. The paucity of knowledge of pathology of the auditory pathways and their radiations in deaf persons is recognized as a limiting factor in attempts to predict which patients might benefit from auditory nerve stimulation. It is not within the scope of this paper to delineate the possible deleterious effects that cochlear implants might have on the auditory nerve.

Adult↗

Melatonin and other serotonin derivatives in the guinea pig membranous cochlea.

In mammals, the indolealkylamine melatonin is synthesized mainly in the pineal gland and to a lesser degree in a number of extrapineal sites. To obtain more information on its distribution, melatonin was measured in the membranous cochlea of the guinea pig. Moreover, melatonin and other serotonin derivatives were determined in organ cultures after incubation with 14C-labelled serotonin. The results show that melatonin is detectable in the organ of Corti and the basilar membrane, and to a lesser degree also in the cochlear nerve and stria vascularis, including the spiral ligament. In vitro studies reveal the occurrence of a number of radiolabelled serotonin derivatives indicating that two of the melatonin-forming enzymes, serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) are present in membranous cochlea. It is concluded that melatonin is synthesized in the guinea pig cochlea. Its role as modulator of hair cell function is dissolved.

Acetylserotonin O-Methyltransferase↗

Latency and amplitude compound action potential tuning curves for tonal stimuli with nontraditional envelopes.

To evaluate the influence of the acoustic context on the latency and amplitude tuning curves (TCs) of cochlear nerve compound action potentials (CAPs), tonal stimuli were generated with a variety of amplitude modulation envelopes. CAPs were produced by intensity increases (onsets) and decreases (offsets) from the low ambient sound level and by intensity changes from a preexisting tonal level. Onset CAPs from ambient levels generated V-shaped TCs. However, when simultaneous masking was used with onset CAPs which were produced by a 5- to 12-dB increase from preexisting levels of approximately 65 dB SPL, TCs were W-shaped and similar in appearance to those produced by simultaneous masking of offset CAPs. The forward masking of this same CAP resulted in a very sharp V-shaped TC. These data suggest that the preadaptation to 10 ms of a moderate level of a tonal stimulus can increase the tuning of ensembles of cochlear neurons to subsequent transient amplitude changes.

Acoustic Stimulation↗

Multichannel cochlear implants. Channel interactions and processor design.

Multichannel electrical stimulation of the cochlear nerve can generate complex interactions between the individual channels. Two types of channel interactions have been investigated: those that occur when two or more electrode channels are simultaneously stimulated and those that occur when the stimuli from each channel are not temporally coincident. Experiments with three human subjects, implanted with scala tympani electrode arrays, indicate that responses are a strong function of the spacing between the channels, the subject, and the electrode geometry (ie, bipolar or monopolar geometries).

Auditory Threshold↗

Nucleus 21-channel auditory brainstem implant in patients with previous tumour removal.

Three patients with neurofibromatosis type 2 who had undergone previous cochlear nerve tumour removal were implanted with the Nucleus 21-channel auditory brainstem implant (ABI). The time intervals between tumour removal and implantation were 4, 5, and 7 years, respectively. Total bilateral deafness was confirmed before implantation. One patient was also blind after acute intracranial hypertension. The translabyrinthine approach was used in all cases. The choice of side for implantation depended on pre-operative magnetic resonance imaging study, the facial nerve function, the presence of recurrent and/or other lesions, and the patient's preference. Although the scarring of prior surgical procedure largely changed the anatomical structures in the cerebello-pontine angle, various landmarks could be found to locate the foramen of Luschka, where the ABI electrode was inserted into the lateral recess of the fourth ventricle. During surgery, the electrically evoked auditory brainstem responses were recorded to confirm that the ABI stimulation activated the auditory system; the electromyogram of the 7th and 9th nerves was helpful in finding the landmarks and minimising the triggering of the cranial nerves with ABI stimulation. The number of active electrodes was 21, 7, and 4 in the three patients. All obtained meaningful pitch scaling and useful auditory sensations. One patient, with 21 activated electrodes, has achieved functional open-set speech understanding. The second patient, with 7 activated electrodes, has benefited from environmental sound awareness and improved lipreading. The last, blind, patient, with 4 electrodes activated, achieved only perception of environmental sounds.

Adult↗

Histopathologic features of the temporal bone in usher syndrome type I.

Temporal bones of 2 patients with Usher syndrome type I were examined using light microscopy. In both patients, findings from histopathologic examination of the cochlea were characterized by degeneration of the organ of Corti, which was most marked in the basal turn, atrophy of the stria vascularis, and a decrease in the number of spiral ganglion cells. The cochlear nerve appeared to be diminished. The sensory epithelium of the saccular and utricular maculae of patient 1 was normal for age. The left temporal bone of patient 2, classified as Usher syndrome genetic subtype USH1D or USH1F, demonstrated the typical signs of severe cochleosaccular degeneration. Present cases and cases from the literature were reviewed in search of an explanation for the above-described differences in histologic findings.

Aged↗

Prostaglandin synthesis by the cochlea.

The exogenous and endogenous syntheses of prostaglandins (PG's) by the cochlea of adult mongolian gerbils were studied in vitro. After incubation of the whole membraneous cochlea with [3H]-arachidonic acid (AA), syntheses of PGF2 alpha, 6-keto PGF1 alpha, PGE2, thromboxane (TX) P2 and PGD2 were evidenced in this order. The synthesis of radioactive PG's was almost completely inhibited by incubation with 10(-5) M indomethacin. No significant amounts of those PG's were detected by radioimmunoassay (RIA) in the cochlea obtained from animals killed by microwave irradiation at 5.0 kw for 0.8 sec. However, when the homogenate of the whole membraneous cochlea obtained from animals without microwave irradiation was incubated at 37 degrees C for 0-15 min, PGD2, PGE2, PGF2 alpha and 6-keto PGF1 alpha were found to be formed from endogenous AA in the cochlea by RIA. PG's were formed already at 0 time to considerable level (PGD2, PGF2 alpha and 6-keto PGF1 alpha, 90-120 pg/cochlea; PGE2, 370 pg/cochlea), reached to the maximum level (PGD2, PGF2 alpha and 6-keto PGF1 alpha, 170-200 pg/cochlea; PGE2, 500 pg/cochlea) at a 5-min incubation, and then gradually decreased. On the other hand, the amount of TXB2 was lower than the detection limit by RIA (less than 50 pg/cochlea) even after the incubation. The cochlea was dissected into three parts: organ of Corti + modiolus (OC + M), lateral wall (LW), and cochlear nerve (CN), and then PG's formed by these tissues were determined after a 5-min incubation of the homogenates. In the CN and OC + M, PGE2 was the major PG (100 and 160 pg/tissue, respectively), and the amounts of PGD2, PGF2 alpha and 6-keto PGF1 alpha were about 1/3 of those of PGE2. In the LW, the amounts of PGD2, PGE2, PGF2 alpha and 6-keto PGF1 alpha were about the same level (70-100 pg/LW).

6-Ketoprostaglandin F1 alpha↗

Permanent defects in rat peripheral auditory function following perinatal hypothyroidism: determination of a critical period.

Rats were treated with propylthiouracil (PTU) for 10-day periods beginning at different ages. Daily injections of L-thyroxine (T4) were administered concurrently with PTU to a group of rats which served as one control group. Peripheral auditory function was evaluated by the brainstem response audiometry (BSRA) technique performed at 12, 16, 25 and 120 days of age. PTU treatment significantly increased wave I latency (cochlear nerve compound action potential) in adult rats when administered from 3 days before delivery through 6 days of age, but was without permanent effect (wave I latencies and thresholds) when administered for 10 days starting at 10 days after birth. T4 replacement during the first 10 postnatal days prevented permanent abnormalities. These data suggest that the period of greatest vulnerability to thyroid hormone depletion in the peripheral auditory system extends from at least 3 days before delivery through between 5 and 10 days of age.

Animals↗

Temporal bone imaging in GJB2 deafness.

OBJECTIVE: To describe temporal bone findings on computed tomography (CT) imaging in GJB2-related hearing loss (HL). We asked whether evaluation of the temporal bone is required in individuals with biallelic GJB2 mutations. STUDY DESIGN: Randomized, blinded, controlled, prospective measurement. METHODS: Blood from 264 pediatric cochlear implant users was analyzed for mutations in the GJB2 gene. Thirty-six aspects of the temporal bone on CT imaging were evaluated in 53 individuals (106 ears) with biallelic disease causing GJB2 mutations. A subset of patients was age matched and compared with normally hearing individuals. Subjects with biallelic GJB2 mutations were tested for mutations in the SLC26A4 gene to rule out Pendred syndrome as a confounding cause of large vestibular aqueduct syndrome. RESULTS: Approximately 53% of ears of subjects (72% of subjects) with biallelic GJB2 mutations had at least one temporal bone anomaly. The most common findings were 1) dilated endolymphatic fossa (28%); 2) hypoplastic modiolus (25%); 3) large vestibular aqueduct (8%); 4) hypoplastic horizontal semicircular canal (8%); 5) hypoplastic cochlea (4%). Compared with normally hearing individuals, the GJB2 group had hypoplasia of the cochlear nerve canal, lateral semicircular canal vestibule, internal auditory canal (t tests, P < .001), and were 11 times more likely to have a hypoplastic modiolus. Dilated endolymphatic fossae were 1.4 times more common in the GJB2 group, and large vestibular aqueducts were 3 times more common in the GJB2 group, as compared with normally hearing controls. CONCLUSIONS: Temporal bone anomalies are common in GJB2-related HL, and imaging of the temporal bone should be included in routine evaluation of these individuals.

Child↗

Cochlear polyamines: markers of otitis media-induced cochlear damage.

High-performance liquid chromatography (HPLC) set to the femtomole [corrected] sensitivity level was used to identify and quantify the polyamines spermidine and spermine as well as the diamine putrescine in the different tissues of the inner ears of guinea pigs with experimentally induced otitis media. The tissues examined were the lateral wall (stria vascularis and the spiral ligament), the organ of Corti, and the cochlear nerve. The difference in polyamine profile in the different tissues of the control noninfected guinea pigs suggests a relation to the particular function of each of these tissues [see erratum notice re: preceding sentence]. The difference in polyamine profile in infected different inner ear tissues compared to controls encourages the assumption that the polyamines may be involved in a repair process of the inner ear after injury and that they may be considered as biochemical markers for inner ear damage secondary to acute otitis media.

Animals↗

Glucocorticoid receptor expression in the postnatal rat cochlea.

The glucocorticoid receptor (GR) expression in the neonatal rat cochlea was investigated by utilization of a polyclonal antibody against GR, the immunoreactivity of which exhibited a distinct, age-dependent developmental pattern in tissues of the spiral ligament (SL). Immunostaining of GR appeared initially at the 7th postnatal day (PND), increased rapidly between the 14th and 21st PND, and reached adult-like expression levels by the 21st PND. Less pronounced, developmentally regulated expression patterns of GR were observed in cells of the spiral limbus (SLi), spiral ganglion (SG), organ of Corti (OC), and cochlear nerve (CN). For example, high expression levels of GR were observed in the SLi, SG and OC at 3 PND; subsequently, GR immunoreactivity levels decreased from 7 to 14 PND, and then GR immunoreactivity intensified in these regions by 21 PND. No remarkable changes in GR expression were observed in stria vascularis (SV). These data indicate that GR expression in the inner ear is tissue and age-specific, and that GR expression parallels both Na,K-ATPase expression and endocochlear potential development.

Aging↗

Evidence that rapid vesicle replenishment of the synaptic ribbon mediates recovery from short-term adaptation at the hair cell afferent synapse.

We have employed both in vitro patch clamp recordings of hair cell synaptic vesicle fusion and in vivo single unit recording of cochlear nerve activity to study, at the same synapse, the time course, control, and physiological significance of readily releasable pool dynamics. Exocytosis of the readily releasable pool was fast, saturating in less than 50 ms, and recovery was also rapid, regaining 95% of its initial amplitude following a 200-ms period of repolarization. Longer depolarizations (greater than 250 ms) yielded a second, slower kinetic component of exocytosis. Both the second component of exocytosis and recovery of the readily releasable pool were blocked by the slow calcium buffer, EGTA. Sound-evoked afferent synaptic activity adapted and recovered with similar time courses as readily releasable pool exhaustion and recovery. Comparison of readily releasable pool amplitude, capture distances of calcium buffers, and number of vesicles tethered to the synaptic ribbon suggested that readily releasable pool dynamics reflect the depletion of release-ready vesicles tethered to the synaptic ribbon and the reloading of the ribbon with vesicles from the cytoplasm. Thus, we submit that rapid recovery of the cochlear hair cell afferent fiber synapse from short-term adaptation depends on the timely replenishment of the synaptic ribbon with vesicles from a cytoplasmic pool. This apparent rapid reloading of the synaptic ribbon with vesicles underscores important functional differences between synaptic ribbons in the auditory and visual systems.

Adaptation, Physiological↗

Albino and pigmented gerbil auditory function: influence of genotype and gentamicin.

Auditory function of albino and pigmented gerbils was examined before and after treatment with the ototoxic aminoglycoside antibiotic gentamicin. Auditory brainstem responses (ABRs) and cochlear nerve compound action potentials (CAPs) were measured in response to pure tones having frequencies between 2 and 32 kHz. Age-matched albinos had significantly lower CAP, but not ABR, thresholds than pigmented gerbils. Gentamicin treatment elevated CAP and ABR thresholds in both genotypes, but pigmented gerbils were less severely affected. Compared to the ABR, the CAP is a more sensitive measure of ototoxicity and pigmentation differences. CAP tuning curves (TCs) were another sensitive measure of genotypic differences in susceptibility to ototoxicity. TC tip thresholds from pigmented animals given gentamicin were not as elevated as the TC tip thresholds of albinos.

Animals↗

Mapping the VIIIth cranial nerve by electrical stimulation: methods for differentiating auditory from vestibular responses.

HYPOTHESIS: The goal of this study was to map the VIIIth cranial nerve by electrical stimulation. Specifically, the authors sought to 1) characterize auditory and vestibular evoked responses elicited by electrical stimuli delivered directly to the exposed surface of the VIIIth cranial nerve and 2) compare electrically evoked responses elicited in brainstem nuclei with extracranially recorded far-field potentials. BACKGROUND: Intraoperative monitoring of auditory brainstem responses is useful during cerebellopontine angle surgery. Identification of the vestibular portion of the VIIIth cranial nerve, which traditionally has been performed by physical characteristics and some electrophysiologic properties, is important because the vestibular subdivision in humans is indistinct in approximately 25% of cases. Positive identification of evoked responses emanating from the vestibular nerve would constitute a marked improvement over existing intraoperative techniques that use acoustic stimuli only. METHODS: Experiments were performed on 12 anesthetized cats. Electrical pulse stimuli were delivered using a bipolar electrode placed directly on the surface of the exposed VIIIth cranial nerve at several sites. Computer-averaged evoked responses were recorded from far-field electrodes placed on the scalp and from near-field electrodes stereotaxically positioned in or near the inferior colliculus and abducens nucleus. RESULTS: Latencies and morphologies of waves recorded in brainstem nuclei were compared with those of waves recorded extracranially. Direct electrical stimulation of the cochlear nerve elicited a four-wave, auditory brainstem response-like extracranial response, strong activity in the inferior colliculus, and weak activity in the abducens nucleus. Direct stimulation of the vestibular nerve produced a two-wave extracranial response, weak inferior colliculus activity, and strong abducens activation. Stimulation at the border of the cochlear and vestibular nerves produced intermediate responses that possessed both cochlear and vestibular characteristics. CONCLUSION: Direct electrical stimulation of the cochlear and vestibular subdivisions elicits evoked responses with distinctly different wave morphologies. Obtaining electrically evoked responses intraoperatively is feasible and may be of substantial value in the unambiguous identification of VIIIth cranial nerve subdivisions.

Animals↗

Intra-operative electrocochleography to monitor cochlear potentials during acoustic neuroma excision.

Intra-operative electrocochleography (ECochG) was used in an attempt to monitor the action potential of the cochlear nerve during acoustic neuroma surgery in 14 patients with useful pre-operative hearing. Five patients had ECochG potentials preserved and yet only three could hear when tested audiometrically later. Of those losing the potentials intra-operatively all were subsequently deaf and the pattern of waveform loss allowed determination of the probable cause of hearing loss. Complete excision of the tumour was achieved in each case regardless of the ultimate effect on the AP as it was not felt justified to risk subsequent recurrence. In common with other studies one of the best prognostic factors for these preservation of hearing was found to be the size of the tumour.

Adult↗

Analysis of spontaneous activity of auditory neurones in the spiral ganglion of the guinea-pig cochlea.

1. Spontaneous activity of single afferent neurones in the cochlea of the guinea-pig was studied by measurement of mean rates and computation of interspike interval histograms. 2. The shapes of interval histograms agreed with those found in cat cochlear nerve fibres. Modes of the histograms were less than 7 msec for all cells with mean rates ranging from 20 to 150 spikes/sec. 3. The distribution of mean rates showed higher maximum rates than those found in cat. Cells from animals with abnormally high thresholds showed lower mean rates than those from sensitive animals. 4. No correlation was found between mean spontaneous rate and sensitivity to acoustic stimulation. No discrete populations of cells could be discerned on any of the criteria used. 5. The simultaneous effects of hypoxia on cell thresholds, mean spontaneous rate and scala media potentials are reported. These and other results are discussed in relation to possible sites of generation of spontaneous activity in primary auditory afferents.

Action Potentials↗

Nimodipine ameliorates trauma-induced cochlear neuronal death.

Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)-activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration. A group of rats (n = 6) was pre-operatively treated with nimodipine for one week and compression injury was applied to the cerebellopontine angle portion of the cochlear nerve in a highly quantitative fashion. The rats from the compression with nimodipine treatment groups were post-operatively treated with nimodipine for 10 days and killed for histological examination. The histological analysis of the temporal bones revealed that the spiral ganglion cells in the basal turn of the cochlea where the magnitude of traumatic impact had been the least in our experimental condition were rescued in a statistically significant fashion in the compression with nimodipine treatment group. The results of the present study indicate that nimodipine may become an intra- and post-operative important adjunct to raise the rate of hearing preservation in vestibular schwannoma excision or other cerebellopontine angle surgical interventions.

Animals↗