Altered mapping of sound frequency to cochlear place in ears with endolymphatic hydrops provide insight into the pitch anomaly of diplacusis.

A fundamental property of mammalian hearing is the conversion of sound pressure into a frequency-specific place of maximum vibration along the cochlear length, thereby creating a tonotopic map. The tonotopic map makes possible systematic frequency tuning across auditory-nerve fibers, which enables the brain to use pitch to separate sounds from different environmental sources and process the speech and music that connects us to people and the world. Sometimes a tone has a different pitch in the left and right ears, a perceptual anomaly known as diplacusis. Diplacusis has been attributed to a change in the cochlear frequency-place map, but the hypothesized abnormal cochlear map has never been demonstrated. Here we assess cochlear frequency-place maps in guinea-pig ears with experimentally-induced endolymphatic hydrops, a hallmark of Ménière's disease. Our findings are consistent with the hypothesis that diplacusis is due to an altered cochlear map. Map changes can lead to altered pitch, but the size of the pitch change is also affected by neural synchrony. Our data show that the cochlear frequency-place map is not fixed but can be altered by endolymphatic hydrops. Map changes should be considered in assessing hearing pathologies and treatments.

Early Detection of Endolymphatic Hydrops using the Auditory Nerve Overlapped Waveform (ANOW).

Endolymphatic hydrops is associated with low-frequency sensorineural hearing loss, with a large body of research dedicated to examining its putative causal role in low-frequency hearing loss. Investigations have been thwarted by the fact that hearing loss is measured in intact ears, but gold standard assessments of endolymphatic hydrops are made postmortem only; and that no objective low-frequency hearing measure has existed. Yet the association of endolymphatic hydrops with low-frequency hearing loss is so strong that it has been established as one of the important defining features for Ménière's disease, rendering it critical to detect endolymphatic hydrops early, regardless of whether it serves a causal role or is the result of other disease mechanisms. We surgically induced endolymphatic hydrops in guinea pigs and employed our recently developed objective neural measure of low-frequency hearing, the Auditory Nerve Overlapped Waveform (ANOW). Hearing loss and endolymphatic hydrops were assessed at various time points after surgery. The ANOW detected low-frequency hearing loss as early as the first day after surgery, well before endolymphatic hydrops was found histologically. The ANOW detected low-frequency hearing loss with perfect sensitivity and specificity in all ears after endolymphatic hydrops developed, where there was a strong linear relationship between degree of endolymphatic hydrops and severity of low-frequency hearing loss. Further, histological data demonstrated that endolymphatic hydrops is seen first in the high-frequency cochlear base, though the ANOW demonstrated that dysfunction begins in the low-frequency apical cochlear half. The results lay the groundwork for future investigations of the causal role of endolymphatic hydrops in low-frequency hearing loss.

Cochlear compound action potentials from high-level tone bursts originate from wide cochlear regions that are offset toward the most sensitive cochlear region.

Little is known about the spatial origins of auditory nerve (AN) compound action potentials (CAPs) evoked by moderate to intense sounds. We studied the spatial origins of AN CAPs evoked by 2- to 16-kHz tone bursts at several sound levels by slowly injecting kainic acid solution into the cochlear apex of anesthetized guinea pigs. As the solution flowed from apex to base, it sequentially reduced CAP responses from low- to high-frequency cochlear regions. The times at which CAPs were reduced, combined with the cochlear location traversed by the solution at that time, showed the cochlear origin of the removed CAP component. For low-level tone bursts, the CAP origin along the cochlea was centered at the characteristic frequency (CF). As sound level increased, the CAP center shifted basally for low-frequency tone bursts but apically for high-frequency tone bursts. The apical shift was surprising because it is opposite the shift expected from AN tuning curve and basilar membrane motion asymmetries. For almost all high-level tone bursts, CAP spatial origins extended over 2 octaves along the cochlea. Surprisingly, CAPs evoked by high-level low-frequency (including 2 kHz) tone bursts showed little CAP contribution from CF regions ≤ 2 kHz. Our results can be mostly explained by spectral splatter from the tone-burst rise times, excitation in AN tuning-curve "tails," and asynchronous AN responses to high-level energy ≤ 2 kHz. This is the first time CAP origins have been identified by a spatially specific technique. Our results show the need for revising the interpretation of the cochlear origins of high-level CAPs-ABR wave 1. NEW & NOTEWORTHY Cochlear compound action potentials (CAPs) and auditory brain stem responses (ABRs) are routinely used in laboratories and clinics. They are typically interpreted as arising from the cochlear region tuned to the stimulus frequency. However, as sound level is increased, the cochlear origins of CAPs from tone bursts of all frequencies become very wide and their centers shift toward the most sensitive cochlear region. The standard interpretation of CAPs and ABRs from moderate to intense stimuli needs revision.

Direct administration of 2-Hydroxypropyl-Beta-Cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements.

2-Hydroxypropyl-Beta-Cyclodextrin (HPßCD) can be used to treat Niemann-Pick type C disease, Alzheimer's disease, and atherosclerosis. But, a consequence is that HPßCD can cause hearing loss. HPßCD was recently found to be toxic to outer hair cells (OHCs) in the organ of Corti. Previous studies on the chronic effects of in vivo HPßCD toxicity did not know the intra-cochlear concentration of HPßCD and attributed variable effects on OHCs to indirect drug delivery to the cochlea. We studied the acute effects of known HPßCD concentrations administered directly into intact guinea pig cochleae. Our novel approach injected solutions through pipette sealed into scala tympani in the cochlear apex. Solutions were driven along the length of the cochlear spiral toward the cochlear aqueduct in the base. This method ensured that therapeutic levels were achieved throughout the cochlea, including those regions tuned to mid to low frequencies and code speech vowels and background noise. A wide variety of measurements were made. Results were compared to measurements from ears treated with the HPßCD analog methyl-ß-cyclodextrin (MßCD), salicylate that is well known to attenuate the gain of the cochlear amplifier, and injection of artificial perilymph alone (controls). Histological data showed that OHCs appeared normal after treatment with a low dose of HPßCD, and physiological data was consistent with attenuation of cochlear amplifier gain and disruption of non-linearity associated with transferring acoustic sound into neural excitation, an origin of distortion products that are commonly used to objectively assess hearing and hearing loss. A high dose of HPßCD caused sporadic OHC losses and markedly affected all physiologic measurements. MßCD caused virulent destruction of OHCs and physiologic responses. Toxicity of HPßCD to OHC along the cochlear length is variable even when a known intra-cochlear concentration is administered, at least for the duration of our acute studies.

Brain stem and inner ear abnormalities in children with auditory neuropathy spectrum disorder and cochlear nerve deficiency.

BACKGROUND AND PURPOSE: Cranial abnormalities, including CND, are common in children with ANSD. The purpose of this study was to assess whether CND is associated with brain or inner ear abnormalities in a cohort of children with ANSD. MATERIALS AND METHODS: Two neuroradiologists retrospectively reviewed cranial MR imaging examinations in 103 children with ANSD. Brain, cochlear nerve, and temporal bone abnormalities were described and tabulated. Findings were stratified on the basis of the presence and laterality of CND, and differences in the presence of associated inner ear or intracranial abnormalities were assessed by using 2-tailed Fisher exact tests. RESULTS: CND was identified in 33.0% of children and 26.9% of ears with ANSD. Significantly more patients with bilateral CND had intracranial abnormalities than those with unilateral CND (60.0% versus 15.8%; P = .012). Forty percent of patients with bilateral CND, 0% of patients with unilateral CND, and 10.1% of those without CND demonstrated hindbrain malformations. Patients with bilateral CND were more likely to demonstrate hindbrain malformations than patients with normal nerves (P = .01) or unilateral CND (P = .004). Labyrinthine abnormalities were significantly more common in patients with bilateral CND than in those without CND (P ≤ .001). Cochlear anomalies were more common in patients with bilateral versus unilateral CND (P = .01). IAC and cochlear aperture stenosis were more common in those with unilateral and bilateral CND than those without CND (both P < .001). CONCLUSIONS: Cochlear and hindbrain abnormalities are significantly more common among patients with ANSD with bilateral CND compared with those with at least 1 intact cochlear nerve.

Cochlear implantation in the irradiated temporal bone.

OBJECTIVE: To demonstrate the feasibility and complexities of cochlear implantation in the setting of bilateral temporal bone osteoradionecrosis. STUDY DESIGN: Case report. SETTING: Tertiary care referral centre. CASE DESCRIPTION: A 66-year-old woman with bilateral temporal bone osteoradionecrosis and profound hearing loss, following treatment for tonsillar cancer, underwent cochlear implantation. Prior canal wall down mastoidectomy and subsequent temporal bone resection with free flap reconstruction had been performed on the implanted ear. The contralateral ear received a canal wall down mastoidectomy. A completely dehiscent mastoid segment of the facial nerve and extensive fibrosis were evident in the implanted ear. Only minimal fibrous reaction was found within the cochlea, allowing for full electrode insertion. At three months, speech recognition testing documented a consonant-nucleus-consonant (CNC) word score of 54 per cent. CONCLUSIONS: This report demonstrates the feasibility of cochlear implantation after temporal bone surgery and free flap reconstruction in the setting of diffuse osteoradionecrosis. The patient's excellent open-set speech understanding using the cochlear implant implies that radiation did not severely damage the central auditory pathways. Thus, some patients with radiation-induced hearing loss may be appropriate cochlear implant candidates. Special attention should be paid to surgical planning, as complications related to wound healing, electrode insertion and facial nerve injury may be more likely.

Safety and efficacy of topical mitomycin C in myringotomy patency.

OBJECTIVE: To develop an alternative method for prolonged middle ear ventilation using topical mitomycin C. STUDY DESIGN AND SETTING: Twenty guinea pigs with normal ears had bilateral myringotomies performed using the argon laser. After myringotomy, either mitomycin C (0.4 mg/mL) or saline pledgets were applied topically. Monitoring consisted of otomicroscopy and distortion-product otoacoustic emissions. RESULTS: Before myringotomy, all tympanic membranes were intact, and distortion-product otoacoustic emissions were measurable. After myringotomy, none (0%) of the saline-treated myringotomies were patent at day 7 as compared with 100% of the mitomycin C-treated myringotomies. At day 42, 10 (52.6%) of 19 mitomycin-treated myringotomies remained patent and 4 (28.6%) of 14 were patent at 131 days. Five (13.1%) ears developed purulent otorrhea; 3 were mitomycin C-treated and 2 were treated with saline solution.- Distortion-product otoacoustic emissions testing did not document any evidence of ototoxicity. CONCLUSION: Topical mitomycin C appears to be safe and effective at prolonging the duration of myringotomy patency in the guinea pig. SIGNIFICANCE: Mitomycin C may be useful as an adjunct for preventing myringotomy closure.

Influenza A virus infection of human middle ear cells in vitro.

HYPOTHESIS: Human-derived normal middle ear mucosal cells can be harvested and cultured and will support influenza A virus (INF A) infection. STUDY DESIGN: Protocols for the collection and in vitro culture of middle ear mucosal cells were developed and used to investigate the effects of INF A infection as it relates to the pathogenesis of otitis media. MATERIALS AND METHODS: Middle ear mucosa was harvested during surgeries that opened the normal middle ear. Middle ear mucosal cells were plated and grown in collagen-coated dishes. Cells were characterized before and after INF A exposure using phase-contrast and immunofluorescence microscopy as well as reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokeratin 18 gene expression and INF A. RESULTS: Primary cultures of human middle ear epithelial cells were established. Prolonged growth of middle ear cells yielded a second cell type that failed to stain for cytokeratin on immunofluorescence but continued to produce positive RT-PCR results on cytokeratin 18 analysis. After INF A exposure, cytological changes and immunofluorescence staining showed cellular infection. RT-PCR analysis using INF A-specific primers showed positive results for up to 72 hours after viral exposure. CONCLUSIONS: Primary cultures of human middle ear mucosal cells have been established. Two distinctly different cell culture systems have been developed: 1) middle ear epithelial cells and 2) either dedifferentiated epithelial cells or fibroblasts. Exposure of both cell types to INF A demonstrates that each can support cellular infection and viral replication. These models should be useful for studies of the pathogenesis of virus-mediated otitis media.

Tumor-associated hemorrhage in patients with acoustic neuroma.

OBJECTIVE: To describe the clinical significance of tumor-associated hemorrhage in patients with acoustic neuromas. STUDY DESIGN: Retrospective chart review. SETTING: University-based, tertiary care teaching hospital. PATIENTS: Three patients with acoustic neuromas who experienced symptomatic tumoral bleeding. INTERVENTIONS: Radiographic imaging, surgical removal of tumors, and pathologic analysis. MAIN OUTCOME MEASURES: Patient histories, radiologic characteristics, surgical results, and pathologic findings. RESULTS: Tumoral hemorrhage can occur in patients with acoustic neuromas. These three cases and a review of the world literature suggest that tumor size may be the most important risk factor for tumor-related hemorrhage. CONCLUSION: These findings have implications for those patients with acoustic neuromas who choose not to have surgical removal.

Comparison of argon and CO2 laser stapedotomy in primary otosclerosis surgery.

PURPOSE: The primary use for the laser in otosclerosis surgery is to create a stapes footplate fenestration that obviates the need for mechanical footplate removal. Experimental studies that evaluate the potential safety of visible (argon and potassium-titanyl-phosphate [KTP]) and invisible (CO2) light laser systems in stapes surgery report conflicting results. The purpose of this study is to compare the clinical safety and efficacy of the CO2 and argon laser systems when used for primary laser stapedotomy. MATERIALS AND METHODS: A retrospective case review of 124 primary laser stapedotomies using either the argon (n = 59) or CO2 (n = 65) laser was performed. Data consisted of pre- and postoperative air and bone conduction audiometry, speech discrimination scores (SDS), intraoperative findings, and postoperative complications. Between group differences (argon v CO2) were sought using standard statistical methodology. RESULTS: The argon and CO2 laser groups were comparable with regards to age, sex, preoperative air-bone gap, and laterality. Mean preoperative air and bone conduction pure-tone average (PTA) and SDS were somewhat higher in the CO2 laser group (P < .05). Postoperatively, both groups showed similar results in mean change in air conduction PTA, air-bone gap, and SDS, as well as in the frequency of complications. There were no anacoustic ears in either group. CONCLUSIONS: The results suggest that the argon and CO2 laser systems are comparable with regards to safety and efficacy when used by experienced surgeons for stapedotomy.

Acoustic tumor growth: implications for treatment choices.

BACKGROUND: Knowledge of acoustic neuroma (AN) growth is essential for treatment planning. METHODS: A retrospective analysis of 119 patients with AN (mean age, 65 years; range, 37-84 years) followed with interval magnetic resonance imagings (MRIs) was performed. Change in maximum tumor dimension as a function of follow-up period was analyzed. RESULTS: Overall, maximum tumor dimension increased >2 mm in only 30% of patients. Of those that grew, the mean growth rate was 3.8 mm/year (maximum, 25 mm/year). Age, gender, and laterality did not predict growth. Most tumors that grew (86.1 %) were <20 mm at presentation. However, tumors >20 mm were statistically more likely to grow (71%, p =0.028). CONCLUSIONS: Most ANs followed with periodic MRIs do not grow. Available clinical information usually cannot predict growth. Serial MRIs are advocated for all patients treated with observation.

Cochlear implants in the geriatric population: benefits outweigh risks.

Cochlear implantation has become widely accepted as an effective means of hearing rehabilitation in severely and profoundly deaf individuals. In the elderly, cochlear implantation involves a number of unique issues that can affect patient outcomes. These factors include age-related changes in the auditory system, prolonged durations of deafness, diminished communication abilities, and coexisting medical and psychosocial problems. In general, the results of cochlear implantation in the elderly have been comparable with those of younger adults. Perioperative attention to medical and surgical details allows for safe insertion and a minimum of postoperative complications. Patients older than 65 have obtained excellent results by both audiologic and quality-of-life measures.

Effects of nasal obstruction on Eustachian tube function and middle ear pressure.

To evaluate the relationship between nasal obstruction and otitis media, 10 ferrets were studied before and after either unilateral (E = 5) or bilateral (n = 5) nasal obstruction. Observations included otomicroscopic assessments of middle ear status, tympanometric recordings of middle ear pressure and forced-response, inflation-deflation and continuous monitoring tests of Eustachian tube function. During the 6 8 week post-obstruction follow-up period no animal developed evidence of otitis media. Abnormal positive middle ear pressures lasting for the period of follow-up occurred only in the animals with bilateral nasal obstruction. Eustachian tube function test results showed these pressures to be generated during swallowing. No changes in the passive function of the tube were documented in either group, but changes in active function consistent with alterations in the pressure gradient between the middle ear and the nasopharynx were observed in both groups.

Intraoperative corticosteroids in acoustic tumor surgery.

BACKGROUND: Corticosteroids are frequently used for the prevention and treatment of neural edema. Although perioperative steroid therapy has been used in patients undergoing acoustic neuroma removal, the efficacy of such therapy has not been previously documented. METHODS: A retrospective review of 169 patients who underwent acoustic neuroma surgery with (n = 75) or without (n = 94) a single dose of intraoperative corticosteroids was performed. Tumor size ranged from 0.4 cm to 6 cm (mean, 2.1; SD, 1.0) The translabyrinthine approach was used in 85% of the patients, and the middle cranial fossa approach was used in 13%. Data were analyzed for differences in postoperative facial function and complication rates. RESULTS: After controlling for differences in tumor size, no significant effects of steroid therapy were found for any of the outcome variables. CONCLUSIONS: This retrospective study showed no apparent benefit from intraoperative steroid use in acoustic neuroma surgery. A prospective, randomized, placebo-controlled trial should be performed to confirm these findings.

Beta-2 transferrin assay in the identification of perilymph.

HYPOTHESIS: Western blot assay for beta-2 transferrin protein is a clinically useful method for the detection of human perilymph and should be used for the diagnosis of perilymph fistulas (PLFs). BACKGROUND: Considerable controversy exists regarding the diagnosis of PLF. Recent studies suggest that the detection of beta-2 transferrin protein may be useful in the identification of perilymph. METHODS: To evaluate the usefulness of the beta-2 transferrin assay for identifying human perilymph, paired perilymph samples and negative controls were collected on Gelfoam pledgets from 20 patients who had surgery that opened the inner ear. Blinded immunoelectrophoretic assay (Western blot) for beta-2 transferrin was performed on each specimen. RESULTS: Only one (5%) of the known perilymph samples and none of the control specimens were definitely positive for beta-2 transferrin. Combined with historical data, this assay has 29% sensitivity, 100% specificity, 100% positive predictive value, and 31% negative predictive value. CONCLUSIONS: These findings suggest that the beta-2 transferrin protein assay may not be a reliable method for detecting human perilymph when performed using this technique.

Alternative to endoscopic sinus surgery in the management of pediatric chronic rhinosinusitis refractory to oral antimicrobial therapy.

We determined the safety, feasibility, and efficacy of a treatment regimen consisting of maxillary sinus aspiration and irrigation with or without adenoidectomy, followed by culture-directed intravenous antibiotics and oral prophylaxis, for children with chronic rhinosinusitis refractory to oral antimicrobial therapy. Twenty-seven children (age 1-12 years, mean 6.7 years) with symptomatic (mean duration 16 months) and computed tomography-proven sinus disease, which persisted despite at least 1 month of oral antibiotics, were treated. Twenty-four patients (89%) had complete resolution of their presenting symptoms after intravenous therapy; in 3 (11%), intravenous therapy failed and endoscopic sinus surgery was required. Follow-up data were available for 26 of the children (96%); 23 of them had initial complete resolution. At last follow-up (mean 282 days, range 26-1095 days), 10 of these 23 patients (44%) remained asymptomatic, and 13 (57%) had had at least one other episode of sinusitis (mean 1.0, range 1-3) treated with oral antibiotics, with resolution. Treatment-related complications included superficial thrombophlebitis (7%), diarrhea (7%), intravenous catheter guide-wire kink requiring venotomy (4%), and serum sickness-like syndrome (4%). These preliminary results suggest that this treatment plan is relatively safe and feasible and that it may be a reasonable alternative to endoscopic sinus surgery in children with chronic rhinosinusitis unresponsive to orally administered antimicrobial therapy.

Illness and otological changes during upper respiratory virus infection.

OBJECTIVES: Upper respiratory virus infection is associated with the expression of symptoms and signs of illness, and with the development of complications in anatomically contiguous structures. In most epidemiological studies, the frequency of the various complications is expressed as a fraction of the total population judged to be ill by report, signs, or symptoms. Because not all infected subjects become ill and because infected non-ill subjects may develop complications, such risk estimates could be inaccurate. The objective of this study was to estimate the magnitude of the presentation bias during controlled, experimental infections. STUDY DESIGN: This was a prospective, experimental study of the relationship between illness and otological complications during experimental upper respiratory virus infection in 316 adult volunteers. METHODS: The data for illness and for abnormal middle ear underpressure in adult (18-54 y) volunteers experimentally infected with one of three viruses (rhinovirus type 39, rhinovirus strain hanks, influenza A virus) were analyzed and expressed as the relative frequencies of infected subjects reporting illness, developing abnormal middle ear pressure, and developing abnormal middle ear pressure in the absence of illness. RESULTS: For all three viruses, illness was documented in approximately 50% of the infected subjects. While the frequency of persons developing abnormal middle ear underpressure was greater in the infected-ill subjects, approximately one third of all infected subjects developing that complication did not report illness. CONCLUSIONS: These results support a large presentation bias in epidemiological surveys of viral upper respiratory infections, and infer that those surveys underestimate the true frequency of complications resulting from such infections.

Prechallenge antibodies moderate disease expression in adults experimentally exposed to rhinovirus strain hanks.

This double-blind study determined the influence of serum neutralizing antibody titers on the rate of infection and magnitude of disease expression after experimental exposure of adult volunteers to rhinovirus strain Hanks (RV-H). A total of 133 healthy volunteers were tested for antibody status, cloistered for a 6-day period, and challenged with RV-H at the end of the first cloister day. On these days, response to viral challenge is assessed with symptom diaries and physical examinations. The low-titer infected group was significantly different from the intermediate-titer infected and the uninfected groups in terms of postchallenge nasal and throat symptoms, expelled secretion weights, nasal mucociliary clearance rates, and frequency of negative middle ear pressures. A similar trend held for the infected high-titer vs. low-titer group comparisons. These data show that high homotypic serum neutralizing antibody titers are associated with protection from infection and lessened signs and symptoms following experimental RV-H exposure.