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Gentamicin and other ototoxic antibiotics for the transtympanic treatment of Menière's disease.

Severe unilateral cases of Menière's disease can be successfully treated with ototoxic antibiotics. Among them gentamicin sulfate gives the safest results. With the aid of a small syringe this antibiotic is introduced into the external auditory canal 5 times/day. From there it reaches the middle ear through a ventilating tube by using a Politzer bag. Gentamicin then penetrates the round and oval windows, where it influences inner ear function. Of 92 patients treated during the past 20 years, more than 90% have had no further attacks after therapy.

Auditory Threshold↗

Experimentally induced round window membrane lesions.

This investigation confirmed previous studies indicating that the middle and inner ear of the guinea pig have a pronounced tendency to healing. Middle ear hemorrhage of surgical origin appears to stop quickly in the guinea pig. A surgically created perforation of the round window with or without removal of perilymphatic fluid by suction resulted in a spontaneous healing of the round window membrane in 12/13 animals. Perilymphatic hemorrhage, associated with short post-surgical interval was found in a substantial number of cases. The origin of the perilymphatic hemorrhage is doubtful. Degeneration of the organ of Corti was found in four ears in three animals and appeared to be correlated to the perilymphatic hemorrhage. Electrophysiological measurements appeared to correlate well with the anatomical findings for one animal with very small changes and for three animals with pronounced middle and inner ear pathology. In three additional animals less agreement was observed. In general these animals showed a more pronounced decrease of function than would be expected by the anatomy.

Animals↗

Surgical anatomy of the singular nerve.

Rare cases of chronic persistent positional vertigo do not respond to physiotherapy. For the treatment of these cases Gacek suggested singular nerve neurectomy as a new surgical procedure. The aim of the present study was to investigate the surgical anatomy of the singular nerve in order to evaluate the exact topography. In 25 cadaver temporal bones the posterior ampullary ("singular") nerve was prepared. The topographical correlation between singular nerve, posterior semicircular canal, and the round window membrane was evaluated. The average length of the nerve was 4.2 mm, its diameter 0.6 mm. The shortest distance between singular nerve and round window membrane was 0.7 mm in average, the nerve could be detected at a depth of 1.3 mm. The transtympanal access was impossible in 7 of 25 cases either because of its close relation to the round window or its direct course towards the ampulla. In only 5 of 25 cases was the nerve located sufficiently inferior in the round window niche for neurectomy. Thus, transtympanal singular nerve neurectomy can be performed only in selected cases. The presented data are helpful for preoperative and intraoperative decisions.

Cadaver↗

The round window in acute hearing loss.

Sensorineural hearing loss has various etiologies. One of them is perilymphatic fistula, which is observed in (1) congenital malformation of the internal ear in children: (2) after operations on the oval window (stapedectomy, interposition); (3) in cases of head trauma, and (4) in acute hearing loss of unknown origin. The authors report 5 of 19 cases of acute hearing loss observed at the ORL Clinic in Kraków and operated on by exploratory tympanotomy. In 4 of them, rupture of the round window membrane (secondary tympanic membrane) was found. A hypothesis for the rupture mechanism is presented.

Adolescent↗

[The effects of Streptolysin-O and sodium hyaluronate on the permeability of the round window membrane in guinea pigs--an electrophysiologic study].

BACKGROUND: The round window membrane (RWM) acts like a barrier for topically applied substances into the middle ear preventing diffusion into the perilymphatic fluid compartment. MATERIAL AND METHOD: In an animal model, modulation of the permeability of the RWM was attempted using Streptolysin-O (SLO) in various concentrations and sodium hyaluronate. Thereafter, the effect of intratympanically applied Lidocain 2 % on hearing threshold measured by auditory brainstem response was tested for Lidocain 2 % and Lidocain 2 % in combination with SLO or sodium hyaluronate. RESULTS: The results show that both, SLO and sodium hyaluronate, influence the effect of Lidocain 2 % on hearing thresholds as an indirect sign for changes of the permeability of the RWM. However SLO by itself in low concentrations decreased auditory thresholds in some animals while this was never observed with sodium hyaluronate. CONCLUSIONS: Our findings preclude SLO and favor sodium hyaluronate as a modulator of RWM permeability in therapeutic trials.

Animals↗

Stress electrocochleography.

Electrocochleographic recordings after changes of middle-ear and intracranial pressure were studied in a group of otologically normal subjects and in patients with suspected Ménière's disease. Electrocochleography performed under these conditions was called stress electrocochleography. It was useful to distinguish among Ménière's disease, benign positional vertigo, and a round-window fistula. Changes of middle-ear pressure, whether positive or negative, always resulted in a rise of the SP/AP ratio. Raised intracranial pressure after Trendelenburg positioning showed fluctuations of the SP/AP ratio in both normal subjects and symptomatic patients. However, in normal subjects, a congruent pattern of these fluctuations was apparent, whereas symptomatic patients exhibited a discordant pattern. The discordant pattern, typical for Ménière's disease, showed an increase of the SP voltage, whereas the AP voltage decreased. In benign positional vertigo, the SP voltage decreased, and the AP voltage increased, once during Trendelenburg positioning and again at the end of the test when starting position was resumed. During raised intracranial pressure after the Queckenstedt maneuver, round-window fistulas showed an increase of the SP voltage, whereas the AP voltage decreased considerably. At our clinic, stress electrocochleography has become an important neurootological test in the differential diagnosis of Ménière's disease.

Action Potentials↗

Studies of inner ear blood flow in animals and human beings.

This article reviews current studies on inner ear blood flow, discusses their relevance to the maintenance of normal homeostasis of the inner ear, reports for the first time clear changes in fundamental properties of cochlear blood flow in the chronic hydropic ear, and describes the potential of applying laser Doppler flowmetry technology to the measurement of inner ear blood flow in human beings. Studies of the guinea pig in which perfusion pressure is varied demonstrate a broad range of autoregulatory capabilities of the inner ear vasculature. Gain factors range from 0.76 and higher for recovery for less than 1 minute of modified perfusion pressure. This is significantly greater than reports obtained for brain autoregulation. In a series of four investigations of cochlear blood flow in the hydropic ear in guinea pigs, a decreased responsiveness to electrical stimulation and direct stimulation of the superior cervical ganglia was found, indicating a change in sympathetic control of cochlear tone. Reduced vasomotion was observed, and autoregulatory capabilities were reduced. In human investigations, changes in cochlear blood flow were demonstrated with direct electrical stimulation of the round window and warm water irrigation of the ear canal, but not with carbogen breathing. Increased cochlear blood flow was observed with increased systemic blood pressure, and a remarkable decrease in cochlear blood flow was observed with the application of 1:10,000 epinephrine to the round window. These observations indicate the potential for development of laser Doppler flowmetry technology in the diagnosis and treatment of inner ear vascular disorders, and the animal investigations suggest that changes may occur in the chronic hydropic ear that compromise autoregulation and thus increase the sensitivity of the hydropic ear to other stress factors. Treatments can be found to modify such changes in vascular tone.

Animals↗

Results and perspectives with extracochlear round window electrodes.

The results obtained with implanted electrodes at the round window are comparable to results with electrodes in the scala tympani or in the hearing nerve in respect to frequency and amplitude resolution with pulsatile and sinusoidal stimulation (with considerable interpatient variations). Although the subjective quality of the perceived sounds is expected to vary depending on the stimulation site, it seems that timing effects of electrical stimulation may play a major role in pitch perception as required for voice and sound recognition or prosody identification. Our technique is a safe procedure involving only routine middle ear surgery to place the induction coil within the mastoid bone and to put an electrode at the round window margin. By an external stimulator, sounds are transformed to electrical stimuli suited to excite surviving fibers of the cochlear nerve. This helps the patient to communicate and provides some basic cues for speech discrimination.

Adult↗

Are inner or outer hair cells the source of summating potentials recorded from the round window?

The relative contribution of inner hair cells (IHCs) and outer hair cells (OHCs) to the production of the summating potential (SP) is unresolved in the literature. Since OHCs in the base of the cochlea have been reported to produce little dc receptor potential except at very high sound pressure levels [I. J. Russell and P. M. Sellick, J. Physiol (London) 284, 261-290 (1983)], the IHCs appear to be the dominant source of the SP. However, results of intracochlear recordings are conflicting, although deriving from measurements in different turns of the cochlea [e.g., I. J. Russell and P. M. Sellick, J. Physiol. (London) 284, 261-290 (1983) versus P. Dallos and M. A. Cheatham, Sensory Transduction (1992)]. To determine which type of hair cells is the dominant source of the SP recorded at the round window, we used carboplatin to selectively destroy IHCs or a combination of IHCs and OHCs in the chinchilla. Related work, using measurements of distortion product otoacoustic emissions and cochlear potentials to assess the functional status of the OHCs served to validate this animal model [Trautwein et al., Hearing Res. 96(1-2), 71-82 (1996)]. The SP, cochlear microphonic (CM), and compound action potential (CAP) were recorded from the round window, and cochleograms were determined using well-established histological methods. The results were reasonably distinctive among three groups of ears--control (from untreated normal chinchillas), IHC-loss (extensive IHC loss with minor or no loss of OHCs), and IHC-OHC loss (total IHC loss plus extensive loss of OHCs over the basal half of the cochlea). Ears of chinchillas in the IHC loss group had a decrease of over 50% in SP output compared to control ears with the exact reduction depending somewhat upon the stimulus conditions. Ears in the IHC + OHC loss group, nevertheless, showed even further reduction in SP output which was clearly attributable to destruction of OHCs in the cochlear base. It was concluded that, although the IHCs are responsible for a greater contribution of dc-receptor potential to the SP recorded at the round window, a significant contribution is made by the OHCs, as well. The results suggest, specifically, that the round window "sees" SP output roughly in inverse proportion to the IHC:OHC. Lastly, the complexity of SP production, as recorded from the round window, precludes a completely straightforward interpretation of the SP:CAP in clinical ECochG.

Acoustic Stimulation↗

Effect of intratympanic application of aminoglycosides on click-evoked myogenic potentials in Guinea pigs.

OBJECTIVES: Although numerous studies have identified damage to the cochlear and vestibular end organs as the primary site of aminoglycoside-induced ototoxicity, the effect on the saccule remains poorly understood, possibly due to lack of monitoring saccular function in experimental animals. Therefore, this study applied three kinds of aminoglycosides into the tympanic space of guinea pigs to examine their toxic impact on the saccule by way of click-evoked myogenic potential test coupled with morphologic assessment. DESIGN: Albino guinea pigs were treated with saline, gentamicin, tobramycin, or amikacin, with 10 animals assigned to each group. Each compound was injected directly overlying but not through the round window membrane on the left ear, with the right ear serving as a control. One week after injection, each animal underwent auditory brain stem response, caloric test, and click-evoked myogenic potential test. Animals were then killed for morphologic assessment through the use of light and electron microscopic examinations. RESULTS: The animals treated with saline, gentamicin, tobramycin, or amikacin exhibited abnormal auditory brain stem response in 0%, 30%, 100%, and 30% of cases; abnormal caloric responses were found in 0%, 100%, 40%, and 40% of cases; absent click-evoked myogenic potentials were found in 0%, 100%, 30%, and 40% of cases, respectively. Gentamicin and other groups differed significantly in abnormal rates of caloric responses and click-evoked myogenic potentials. Morphologic study of the gentamicin-treated animals confirmed that the absence of click-evoked myogenic potential originated from the lesion in the saccular macula. CONCLUSIONS: Gentamicin represents the dominant susceptibility of aminoglycoside-induced vestibulotoxicity for eliminating both semicircular canal and saccular functions. This study further confirms the findings of human studies in which the caloric and vestibular evoked myogenic potentials responses were monitored to assess the abolition of vestibular function in patients treated with intratympanic gentamicin injection.

Acoustic Stimulation↗

Reliability of the promontory stimulation test for the preoperative evaluation of cochlear implants: a comparison with the round window stimulation test.

The electrical stimulatory threshold of the preoperative promontory stimulation test (PST) was compared with the postoperative threshold of the electrode following cochlear implantation. Postoperative results from warble-tone audiometry, the vowel recognition test, the consonant recognition test, and the speech tracking test, which employed a speech processor, were similarly evaluated. In certain patients who responded insufficiently to the PST, an exploratory tympanotomy under local anesthesia was performed prior to cochlear implantation, and stimulatory threshold was measured with an electrode placed directly on the round window [round window stimulation test (RWST)]. No correlation was found between the PST results and the postoperative performance of the cochlear implant. The RWST was determined to be better than the PST in the evaluation of cochlear implant performance.

Adult↗

Selective lesions of the vestibular labyrinth.

In attempts to decrease gentamicin ototoxicity, the round windows of guinea pigs were covered with fat before gentamicin was given through the middle ear cavity. Although ototoxicity to the cochlea was reduced, the desired effect on the vestibular sense organs also was reduced, because of the oval window's resistance to drug penetration. In another series of guinea pigs, simple opening of the lateral semicircular canal and covering it with a pledget of Gelfoam soaked with gentamicin was an excellent method for producing a selective vestibular lesion. It is expected to reduce the function of all vestibular sense organs without impairing cochlear function.

Adipose Tissue↗

Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media.

Sensorineural hearing loss is a common sequela of acute and chronic otitis media, and the round window membrane (RWM) is currently being considered as a major route for noxious agents to pass from the middle ear cavity to the cochlea. Streptococcus pneumoniae, a major causative agent of otitis media, and Streptococcus pyogenes A produce molecularly related toxins, pneumolysin and streptolysin O (SLO), that form large pores in target membranes. In this study, we analyzed the effects of SLO on the permeability of the RWM. Resected RWMs from a total of 104 guinea pigs were embedded between two chambers of an in vitro system. One chamber was designated as the tympanal (cis) compartment, and the other was designated as the inner ear (trans) compartment. The permeability of normal and SLO-damaged RWMs towards Na+, [14C]mannitol, and proteins was investigated. SLO evoked permeability defects dose dependently in the RWM with fluxes of both Na+ and [14C]mannitol being demonstrable over a time span of up to 8 h. Serum proteins and radioiodinated SLO were also shown to pass through the damage RWM. Scanning electron microscopy revealed the morphological correlates to these results. We propose that damage to the RWM by potent pore-forming cytolysins leads to leakage of ions from the perilymph. Ionic disequilibrium and passage of noxious macromolecules to the cochlea could contribute to disturbances of the inner ear function.

Albumins↗

Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report).

Intratympanic instillation of Depo-Medrol (80 mg/cc), dexamethasone ophthalmic solution (1 mg/cc), or dexamethasone intravenous (4 mg/cc) solution produces improvement of cochlear function in certain patients with Meniere's disease, autoimmune inner ear disease and sudden sensorineural deafness. Tinnitus improved in 47%, most often in patients with Meniere's disease (9 of 15; 60%). The SRT improvement of greater than 10 dB or SD greater than 15% was documented in 41% (average improvement in SRT: 15 dB; SD: 24%). Patients with tinnitus and bilateral sensorineural hearing loss (i.e., presbycusis) did not benefit from the treatment. Prior to treatment with intratympanic medication, laser assisted tympanostomy with middle ear exploration, using otoendoscopy to determine the status of the round window niche and remove mucosal folds, helps in making the round window membrane accessible to local application of drops. Placing Gelfoam into the round window niche under direct vision, and using a Venturi Bobbin tube in the tympanic membrane, appears to be a satisfactory method for delivering medication to the inner ear fluids. The medication can be injected by the physician through the tube into the middle ear, or the patient can perform self-treatment at home, placing medication in the external auditory canal. A double-blind, cross-over study in patients with Meniere's disease is now in progress with Institutional Review Board (IRB) approval, which will be reported at a later date. This preliminary study has shown that intratympanic steroids may affect the symptoms of hearing loss and tinnitus in patients with various inner ear problems. Patients with Meniere's disease appear to respond in the highest percentage of cases. Hopefully, additional research will suggest the appropriate drugs which can be used to treat inner ear disease. Direct application of the drug to the round window membrane may increase the concentration in the inner ear fluids, thus avoiding the systemic effects.

Aged↗

Anteroposterior approach with split ear canal for cochlear implantation in severe malformations.

OBJECTIVE: To present an anteroposterior approach with split ear canal technique in severe malformed ears in which cochlear implantation is not possible through the standard facial recess approach. SETTING: The operation was performed at Hacettepe University Medical Faculty, which is a tertiary care center. STUDY DESIGN: Case report. PATIENT: A 4-year-old female patient with severe Mondini malformation whose facial nerve was completely dehiscent and overlying the stapes and round window. INTERVENTION: The anteroposterior approach was used, and the middle ear was entered after the tympanomeatal flap was elevated. The posterior wall of the ear canal was split longitudinally with a diamond drill. The electrode was inserted easily through the ear canal and then transferred into the mastoid. CONCLUSION: The anteroposterior approach with split ear canal method may be used if, during facial recess, the landmarks in the middle ear (stapes, stapedius tendon, round window, and promontory) cannot be identified clearly because of an abnormal facial nerve (coursing anteriorly, preventing the use of a drill). It is an alternative for the canal wall down procedure.

Abnormalities, Multiple↗

Electrocochleography in the presence and absence of perilymphatic fistula.

The purpose of the present study was to evaluate the effect of an acute perilymphatic fistula on the amplitude ratio (SP/AP) of the summating potential (SP) and action potential (AP). The effect of the acute fistula on AP threshold was also addressed. Electrocochleographic recordings were obtained before and immediately after surgical laceration of the round window membrane in 19 guinea pigs. Stimuli comprised clicks and 2,000-Hz and 8,000-Hz tone bursts, presented initially at 100 dB peak equivalent sound pressure level and in descending 10-dB steps. After fistula induction the SP/AP significantly increased for the click and 8,000-Hz tone burst stimuli but not for the 2,000-Hz tone burst stimuli. No significant change in AP threshold occurred. These findings suggest that the SP/AP may be sensitive to perilymphatic fistula, at least in guinea pigs. The changes in the SP/AP do not appear to be related to changes in threshold.

Action Potentials↗

Transtympanic gentamycin in the treatment of Ménière's disease.

Severe cases of Ménière's disease are successfully treated with ototoxic antibiotics. Gentamycin sulphate gives the best results. With the aid of a small syringe the drug is introduced into the external auditory canal 3-5 times per day. From there it is transported into the middle ear through a ventilating tube (Grommet) under slight pressure (Politzer bag). The liquid then penetrates the round and oval windows and influences inner-ear function. More than 90% of our patients in 25 years after therapy had no further attacks.

Ear, Middle↗

Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs.

Caroverine, an N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, has been shown to protect the inner ear from excitotoxicity and to be effective in the treatment of cochlear synaptic tinnitus. Local administration of caroverine on the round window membrane (RWM) could be a more effective means of administration to avoid systemic side/adverse effects. The present study investigates the pharmacokinetics of caroverine in the perilymph, cerebrospinal fluid (CSF) and plasma following intravenous and local applications at different dosages. High-performance liquid chromatography was used to determine the drug concentrations. Our results show much higher caroverine concentrations in the perilymph with lower concentrations in CSF and plasma following local applications compared with systemic administration. Auditory brainstem responses were measured to evaluate the changes in auditory function. The effects on hearing were transient and fully reversible 24 h after local caroverine applications. The findings suggest that local application of caroverine on the RWM for the treatment of excitotoxicity-related inner ear diseases, such as tinnitus and noise-induced hearing loss, might be both safe and more efficacious while avoiding high blood and CSF caroverine levels seen with systemic administration.

Animals↗