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To identify the imaging characteristics associated with better hearing outcomes found in cochleovestibular nerve (CVN) abnormalities treated with hearing aids and/or cochlear implantation (CI).Retrospective review.A retrospective review was undertaken of 69 ears with CVN abnormalities seen on magnetic resonance imaging (MRI) treated at a tertiary referral academic center analyzing the clinical features, imaging characteristics, and hearing data. We searched for associations among the hearing and imaging data, hypothesizing that the imaging data was not a good indicator of hearing function.In univariable analysis of all those who underwent aided testing (hearing aid and CI), health status (P = .016), internal auditory canal (IAC) midpoint diameter (P .001), and number of nerves in the IAC (P .001) were predictors of positive hearing outcome. Modiolar abnormalities, cochlear aperture diameter, cochlear malformations, vestibular malformations, and nerves in the cerebellar cistern did not predict hearing outcome (P = .79, .18, .59, .09, .17, respectively). For patients who received CI, health status (P = .018), IAC midpoint (P = .024), and number of nerves in the IAC (P = .038) were significant. When controlling for health status, IAC midpoint diameter (P .001) and number of nerves in the IAC (P .001) remained significant. In our cohort, one out of the eight ears (13%) with Birman class 0 or 1 exhibited responses to sound compared to nine out of 13 ears (70%) with Birman class 2-4.Current imaging modalities cannot accurately depict the status of the cochleovestibular nerve or predict a child's benefit with a CI. Cochlear implantation should be considered in children with abnormal cochleovestibular nerves.3 Laryngoscope, 132:S1-S15, 2022.

Objectives/hypothesis To report a series of patients with neurofibromatosis type 2 (NF2), where each patient underwent both cochlear implantation and auditory brainstem implantation for hearing rehabilitation, and to discuss factors influencing respective implant success. Study design Retrospective case series. Methods Ten NF2 patients with both cochlear implantations and auditory brainstem implantations were retrospectively reviewed. Speech testing for auditory brainstem implants (ABIs) and cochlear implants (CIs) was performed separately. Scores at last follow-up were obtained for Iowa vowels and consonants, Northwestern University Children's Perception of Speech (NU-CHIPS), and City University of New York (CUNY) sentences. Results Mean age at time of implant was 37 years for cochlear implantation and 40 years for auditory brainstem implantation (P = .790, t test). Nine of 10 patients had a CI and ABI on contralateral sides, and one had both devices on the same side. Mean duration of deafness in the implanted ear was 4.3 years for both cochlear implantation and auditory brainstem implantation (P = .491, t test). Follow-up range was 1 to 28 years. CI performance on NU-CHIPS was 32% to 100%, and sound + lip-reading CUNY was 56% to 100%. Four patients experienced an eventual decline in CI function to unusable levels. ABI performance on NU-CHIPS was 40% to 80%, and sound + lip-reading CUNY was 38% to 94%. There was no notable decline in ABI function over time. Conclusions If the cochlear nerve is intact, cochlear implantation can be an effective strategy for hearing rehabilitation in NF2. However, a significant proportion experience a decline in CI performance related to growing vestibular schwannoma or tumor treatment. Auditory brainstem implantation remains the standard option for surgical hearing rehabilitation in NF2, but peak performance is generally lower than that achievable with cochlear implantation. Level of evidence 4. Laryngoscope, 128:2163-2169, 2018.

Objectives Facial nerve schwannomas (FNSs) and vestibular nerve schwannomas (VNSs) may occupy similar locations in the internal auditory canal (IAC). Risk factors for hearing loss in patients with FNS are unknown. Similar to VNSs, we hypothesize that the size and location of FNSs do not correlate with hearing loss. Study Design Retrospective cohort study and otopathology case review. Methods A single institution retrospective review of all patients diagnosed with FNS was performed. Demographic data, tumor size and location, severity and type of hearing loss, and facial nerve function were analyzed. Otopathologic review of a case of FNS was also performed. Results Thirty-three patients with FNS were identified. Mean age was 44 years, and 61% (n = 21) were female. Nine patients had tumors involving the IAC facial nerve, whereas 24 had distal tumors without IAC involvement. Eleven patients (33%) had hearing loss, and 55% of patients with sensorineural hearing loss (SNHL) had tympanic segment tumors without IAC involvement. The presence of SNHL was not associated with IAC tumor location (P = 0.21). Maximal dimensions of FNSs were 3 mm to 42 mm, without correlation between size and SNHL severity (r = −0.017, P = 0.926). Otopathologic review of an untreated 5-mm IAC FNS demonstrated disproportionate spiral ganglion and hair cell loss within the ipsilateral cochlea compared to the contralateral ear. Conclusion Tympanic segment FNS without IAC involvement may result in SNHL. Tumor size is not associated with the presence or severity of SNHL. Otopathologic review suggests degenerative cochlear changes in FNS. Mechanisms for SNHL in schwannomas are likely multifactorial and may be unrelated to cochlear nerve compression. Level of Evidence 4. Laryngoscope, 127:1676–1682, 2017

Objective Auditory brainstem implants (ABIs), which have previously been used to restore auditory perception to deaf patients with neurofibromatosis type 2 (NF2), are now being utilized in other situations, including treatment of congenitally deaf children with cochlear malformations or cochlear nerve deficiencies. Concurrent with this expansion of indications, the number of centers placing and expressing interest in placing ABIs has proliferated. Because ABI placement involves posterior fossa craniotomy in order to access the site of implantation on the cochlear nucleus complex of the brainstem and is not without significant risk, we aim to highlight issues important in developing and maintaining successful ABI programs that would be in the best interests of patients. Data Sources Especially with pediatric patients, the ultimate benefits of implantation will be known only after years of growth and development. These benefits have yet to be fully elucidated and continue to be an area of controversy. The limited number of publications in this area were reviewed. Review Methods Review of the current literature was performed. Results Disease processes, risk/benefit analyses, degrees of evidence, and U.S. Food and Drug Administration approvals differ among various categories of patients in whom auditory brainstem implantation could be considered for use. Conclusion We suggest sets of criteria necessary for the development of successful and sustaining ABI programs, including programs for NF2 patients, postlingually deafened adult nonneurofibromatosis type 2 patients, and congenitally deaf pediatric patients. Laryngoscope, 127:1909–1915, 2017

Objectives/hypothesis To describe the histopathologic findings and clinical presentation of arachnoid cysts (ACs) within the human temporal bone. Study design Retrospective cohort analysis. Methods An analysis of all medical records of patients diagnosed with an AC was performed. Temporal bones underwent standard processing for histologic examination. The slides were examined by light microscopy. The histologic findings were compared to premortem clinical data. Results Twenty-seven ACs were identified in 22 patients. Twenty ears (74%) had no identified risk factor for AC development. The median volume was 12.8 mm3 . The most prevalent location of the ACs was at the fundus (16 ACs) followed by the middle portion of the internal auditory canal (IAC) (six ACs). Nine ACs were asymptomatic. Among the 18 symptomatic ACs, the most common presentation was sensorineural hearing loss (SNHL) (94%), followed by tinnitus (22%). The most affected structure was the cochlear nerve (59%), followed by the vestibular nerve (41%). The average hearing threshold was of moderately severe SNHL and speech discrimination was in the range of 50% on monosyllabic word tests. The median time interval from initial presentation to death was 12 years. No correlation was found between duration of symptoms and AC volume. Conclusions AC of the IAC is not uncommon. Its presentation is variable, ranging from asymptomatic to SNHL, with poor speech discrimination, tinnitus, and vertigo. This diagnosis should be kept in the differential diagnosis of retrocochlear pathologies. Level of evidence 4 Laryngoscope, 129:1667-1674, 2019.

Objectives/Hypothesis To evaluate the correlation between a narrow bony cochlear nerve canal (BCNC) and facial nerve stimulation (FNS) after cochlear implantation (CI) and their underlying mechanisms and to predict the risk of FNS preoperatively. Study Design Retrospective cohort study. Methods A total of 64 pediatric cases that underwent CI were included. Among them, 32 cases experienced FNS after CI, and another 32 cases were selected from 817 pediatric implantees by stratified random sampling. The width of the BCNC, the status of the cochlear nerve (CN) and the internal auditory canal (IAC), T level, and C level were compared and analyzed. Strategies for eliminating FNS were also analyzed. Results The FNS group showed a narrower BCNC (1.09 ± 0.52 mm) than the control group (1.99 ± 0.61 mm; P < .01), a lower CN/facial nerve ratio (0.32 ± 0.36) than the control group (1.34 ± 0.76; P < .01), and narrower IAC diameter (4.06 ± 1.71 mm) than the control group (5.66 ± 1.36 mm; P < .01). The FNS group also showed higher T level (165.7 ± 28.3 μA) than the control group (142.2 ± 21.2 μA; P < .01). Adjustment of the C levels and/or pulse width and switching off offending electrodes were attempted to eliminate FNS, with a 75.0% success rate. The FNS group still showed low Categories of Auditory Performance scores (3.00 ± 1.90) compared with the control group (5.94 ± 1.41, P < .01) after adjustment. Conclusions A narrow BCNC could be a cause of FNS after CI. Therefore, careful selection of the side for CI and programming strategies are required to reduce FNS. Level of Evidence 4. Laryngoscope, 2015

Objectives/Hypothesis To examine the relationship between bony cochlear nerve canal (BCNC) width, degree of hearing loss, and speech discrimination in children with unilateral sensorineural hearing loss (USNHL). Study Design Retrospective chart review (case-control study). Methods Audiometric database was cross-referenced with radiologic database at pediatric tertiary care facility to identify children with USNHL and temporal bone computed tomography. BCNC widths were measured independently by two radiologists blinded to affected ear. Regression analyses investigated associations among variables. Results One hundred and sixty children with USNHL had temporal bone imaging. Mean BCNC width was significantly smaller in affected ears, P = 0.0001. Narrower width was associated with more severe hearing loss, P = 0.01. Among children who had narrower cochlear nerve canals in affected ears compared to unaffected ears, smaller width was associated with lower speech discrimination score, P = 0.03. Increasing asymmetry in BCNC width between affected and unaffected ears was associated with poorer discrimination scores, P = 0.02. Among ears with asymmetrically smaller cochlear nerve canals, a 1-mm reduction in cochlear canal width between the normal and affected ear was associated with 30.4% lower word recognition score percentage in the affected ear, P =

INTRODUCTION Over the past decade, indications for the auditory brainstem implant (ABI) have expanded to the pediatric population. The most common indications for ABI placement in children are severe cochlear nerve hypoplasia and cochlear nerve aplasia, as these patients (with some exceptions) have modest cochlear implant (CI) outcomes. Thus, in the workup of a child with congenital profound hearing loss, determining the presence and size of the cochlear nerve may predict whether CI or ABI is the more appropriate intervention. Magnetic resonance imaging (MRI) provides the most detailed view of the four nerves within the internal auditory canal (IAC) and is commonly used to assess potential ABI candidates. The acquisition technique of brain and temporal bone MRI is frequently along the axial plane, with additional views (parasagittal and coronal) created by reconstructing source images. These reconstructed images are usually adequate for assessment of neural structures, but they may become blurred within the confines of a bony environment, such as the IAC. The parasagittal view of the IAC provides an en face look at the cochlear, vestibular, and facial nerves, aiding in their differentiation. This is the critical view in the assessment of a patient’s suitability for a CI or ABI. Unfortunately, the quality of reconstructed MRI sequences within the IAC is variable, making it frequently difficult to determine the presence or absence of a cochlear nerve. As the decision for CI versus ABI largely rests on the presence or absence of the nerve, optimized image quality is essential for the otolaryngologist. At our institution, we have begun directly acquiring parasagittal MRI sequences (as opposed to reconstructed views obtained from the axial plane). The improved imaging modality has greatly assisted in determining the presence or absence of the cochlear nerve, and ultimately supports surgical decision-making. In this article, we provide our specific MRI protocol using directly acquired T2-weighted three dimensional (3D) turbo spin echo (TSE) with driven equilibrium radio frequency reset pulse (DRIVE) parasagittal images on a 3.0-Tesla scanner for optimal visualization of the IAC contents, including the cochlear nerve.

OBJECTIVES/HYPOTHESIS: The possibility that long-term mobile phone use increases the incidence of astrocytoma, glioma and acoustic neuroma has been investigated in several studies. Recently, our group showed that direct exposure (in a surgical setting) to cell phone electromagnetic fields (EMFs) induces deterioration of auditory evoked cochlear nerve compound action potential (CNAP) in humans. To verify whether the use of Bluetooth devices reduces these effects, we conducted the present study with the same experimental protocol. STUDY DESIGN: Randomized trial. METHODS: Twelve patients underwent retrosigmoid vestibular neurectomy to treat definite unilateral Ménière's disease while being monitored with acoustically evoked CNAPs to assess direct mobile phone exposure or alternatively the EMF effects of Bluetooth headsets. RESULTS: We found no short-term effects of Bluetooth EMFs on the auditory nervous structures, whereas direct mobile phone EMF exposure confirmed a significant decrease in CNAPs amplitude and an increase in latency in all subjects. CONCLUSIONS: The outcomes of the present study show that, contrary to the finding that the latency and amplitude of CNAPs are very sensitive to EMFs produced by the tested mobile phone, the EMFs produced by a common Bluetooth device do not induce any significant change in cochlear nerve activity. The conditions of exposure, therefore, differ from those of everyday life, in which various biological tissues may reduce the EMF affecting the cochlear nerve. Nevertheless, these novel findings may have important safety implications. LEVEL OF EVIDENCE: 4

Objectives/Hypothesis: To describe the clinical and audiometric characteristics of children with cochlear nerve dysplasia (CND). Study Design: Retrospective chart review of clinical database of children with inner ear anomalies treated at a tertiary care children's hospital. Methods: Institutional review board–approved retrospective review from June 30, 2006, to July 1, 2011; 18 children were identified with magnetic resonance imaging (MRI) evidence of CND defined as a cochlear nerve 50% smaller than the adjacent facial nerve. Results: Of the 18 patients, nine were girls and nine were boys. Average age at time of MRI diagnosis of CND was 4.6 years. Twelve children had cochlear nerve aplasia, and six had hypoplasia. Three were affected bilaterally: two with aplasia and one with hypoplasia. Unilateral dysplasia was found in 15 children; of these, 60% occurred on the left side. Other inner ear anomalies were found in 50%, including all patients with bilateral CND. Severe-to-profound hearing loss was found in the involved ear(s) in 14 of 18 patients, including all bilateral patients. Of the 18 patients tested, 13 (72%) had an audiometric profile of auditory neuropathy/dys-synchrony syndrome (auditory neuropathy spectrum disorder [ANSD]). Comorbid conditions were present in 56% of patients. Two patients were syndromic. Family history of hearing loss was present in 11% of patients. Conclusions: Many patients with CND have ANSD, and more than half have comorbidities. Approximately half of affected patients have other inner ear anomalies in the involved ears. Unilateral CND may be more common on the left side. Laryngoscope, 2013

Objectives/Hypothesis: An auditory brainstem implant (ABI) that stimulates the cochlear nucleus in the brainstem was initially designed for patients with neurofibromatosis type-2. Recently, promising surgical outcomes after ABI have been reported in nontumor patients with sensorineural hearing loss including those with cochlear nerve aplasia or ossified cochlea. We herein describe the surgical results and auditory outcomes of ABI in nontumor patients. Study Design: Retrospective case series at a tertiary hospital. Methods: Eleven deaf patients who received ABI from 2008 to 2010 were included in this study. The first group included eight patients with narrow internal auditory canals (IACs) and the second group consisted of three postlingually deaf adults with cochlear ossification. Pulsar CI100 ABI (Med-El Co., Innsbruck, Austria) was implanted via the suboccipital approach. Results: All eight patients with narrow IACs clearly demonstrated behavioral responses following initial stimulation using an ABI. The category of auditory performance (CAP) scores were progressively improved to reach auditory performances of CAP 4 in three patients, CAP 3 in two patients, CAP 2 in two patients, and CAP 1 in one patient. The three patients with ossified cochlea also reported auditory sensations when the ABI was activated. Two of them showed an auditory performance of CAP 4 or 5, but the third patient could not use the device due to nonauditory stimulation. Conclusions: Based on our experience, ideal nontumor candidates for ABI include congenitally deaf children who experienced failure after cochlear implantation owing to cochlear nerve deficiency and postlingually deaf adults with severe cochlear ossification. Laryngoscope, 121:2610–;2618, 2011

Objectives/Hypothesis: Compare outcomes among children with inner ear malformations and/or cochlear nerve deficiency (CND) who have received a cochlear implant (CI). Study Design: Individual retrospective cohort study from 1993 to 2010. Methods: A select cohort of 76 children was identified. Imaging characteristics, operative findings, complications, mapping parameters, and performance were assessed. Comparisons among the different groups were undertaken. Results: Surgery was mostly uncomplicated. Nearly all children demonstrated behavioral responses to CI stimulation irrespective of inner ear morphology or the presence of CND. Children with CND had higher pure tone averages (PTAs) and required greater charge for stimulation than other malformation types. Open-set speech perception was achieved in 100% of children with incomplete partition-enlarged vestibular aqueduct (IP-EVA), 50% of those with hypoplastic malformations, and 19% of CND cases. Robust responses on eighth nerve compound action potential (ECAP) testing through the implant was associated with higher levels of speech perception. Manually supplemented communication strategies were more common among children with hypoplastic malformations (69%) and CND (95%) than those with IP-EVA (18%). Conclusions: Children with IP-EVA malformations have an excellent prognosis for developing open-set speech perception and using oral communication modes following CI. On the contrary, children with severe malformations or CND may have elevated charge requirements for attaining sound detection alone. These children's prognosis for obtaining open-set speech understanding, using exclusive oral communication, and participating in mainstream education is more limited. These findings have important implications for considering alternative forms of intervention such as auditory brainstem implantation and/or supplementation with visually based communication strategies.

Objectives/Hypothesis: To analyze the value of preoperative diagnostic tools in predicting the status of the cochleovestibular nerve (CVN) in patients with narrow internal auditory canals (IAC). Study Design: Retrospective case series at a tertiary hospital. Methods: Eight profoundly deaf patients with narrow IACs who received auditory brainstem implantation were included in this study. The results of preoperative imaging, electrophysiologic, and auditory tests were correlated with the CVN status identified during auditory brainstem implantation. Results: Temporal bone computed tomography (CT) findings, including the patency of the bony cochlear nerve canal and the diameter of the IAC, were limited in accurately reflecting the status of the CVN. Magnetic resonance imaging (MRI) and preoperative auditory responses to either pure tone or environmental sounds were more accurate markers for detecting the presence of a CVN than CT; however, there were limitations in cases with a very thin CVN or combined severe mental retardation. Absence of promontory or intracochlear electrically evoked auditory brainstem responses were not always indicative of an absent CVN. Conclusions: Visualization on MRI and detection of auditory responses suggested the presence of a CVN in patients with narrow IACs; however, the possibility of the presence of a CVN should be considered even when there is no clear evidence of a CVN on preoperative evaluations. Therefore, physicians should be prudent when determining candidacy for cochlear implantation or auditory brainstem implantation in patients with narrow IACs.

Objectives/hypothesis Otoacoustic emissions (OAE) can be suppressed with activation of the medial olivocochlear neural pathway by stimulation of the contralateral ear. The primary objective of this study was to assess the feasibility of using olivocochlear mediated OAE suppression to test neonatal hearing with a novel device that detects changes in distortion product (DP)OAE level with high temporal resolution. The secondary objective was to investigate whether temporal parameters of the response can be determined with this technique and used in the assessment of neonates at risk of auditory neuropathy spectrum disorder (ANSD). Study design Prospective translational study of novel hearing assessment technique. Methods There were 46 neonates tested in a clinic or neonatal intensive care unit (NICU). DPOAE were recorded in real time with narrow band pass digital filtering (1 ms temporal resolution) during presentation of an intermittent contralateral broadband noise stimulus. Magnitude and latency of the contralateral suppression response were compared with hearing outcome (auditory brainstem response screen and clinical follow-up) and risk factors for hearing loss, particularly hyperbilirubinemia as a risk factor for ANSD. Results : Contralateral suppression was identified in all of 38 neonates with detectable DPOAE and normal hearing, most reliably at f(2) = 4.4 kHz (average values = 1 dB suppression from DP level of 14 dB SPL using 0.55 s contralateral stimulus at 50 dB SPL). Sensorineural hearing loss was identified in three cases (6.5%) and ANSD in five cases (11% of all neonates tested). Contralateral suppression was absent in two of the ANSD cases (one associated with cochlear nerve aplasia, the other with hyperbilirubinemia) and present in three. The median latency for onset of contralateral suppression was 60 ms and offset latency 83 ms. The latency for offset of suppression was longer in neonates who required treatment for hyperbilirubinemia at 123 ms (P = .02, Mann-Whitney rank sum test). Latency measurements were determined with high intraobserver reliability (Pearson product moment correlation coefficient > 0.96). Conclusions Contralateral suppression of real-time DPOAE can reliably be identified in neonates. This is likely a manifestation of olivocochlear activity, although middle ear muscle reflexes might contribute to suppression in some circumstances. The technique provides a feasible objective test of hearing in neonates that can be applied in the NICU setting without sedation. The presence of a response indicates detection of sound by the contralateral ear and effective brainstem transmission of neural signals, therefore providing a more sensitive test of hearing than OAE alone. The high temporal resolution of the technique allows measurement of latency of the response. These benefits help to identify neonates at risk of ANSD and have the potential to provide prognostic information that will assist in the management of this unpredictable disorder. Further development of the technique is indicated with regard to determination of hearing threshold, frequency specific testing, and automation of response detection.

Objectives: Deficient cochlear nerves (CN) have been associated with poor cochlear implant performance. Normative data on CN diameter based on radiographic imaging have not been published. The objectives of this study were to determine if CN diameter could be reproducibly measured on parasagittal constructive interference in steady state (CISS)-sequence magnetic resonance imaging (MRI) and to establish a normative range for CN diameter. Study Design: Retrospective review of MRI images by two independent blinded observers. Methods: Thirty patients (45 ears) with a CISS-sequence MRI done for auditory complaints in patients with normal hearing in one ear were included. CN diameters were measured in a parasagittal plane just medial to the internal auditory canal (IAC) fundus by two independent observers. Cross-sectional areas were calculated and interobserver agreement was evaluated. Results: The CN was identified in 100% of studied ears. In 93%, the diameters were able to be measured by both observers. In 7% of ears, the cochlear nerve was unable to be measured secondary to the proximity of the CN to IAC wall. The CN vertical diameter (1.4 mm ± 0.21 mm), horizontal diameter (1.0 mm ± 0.15 mm), and cross-sectional area (1.1 mum ± 0.26 mm 2 ) were normally distributed. There was good interobserver correlation for each measure. Conclusions: CN diameter can be reliably measured at the IAC fundus. This study establishes normative radiographic data for the CN diameter. These data may be used to evaluate the cause and treatment prognosis in patients with sensorineural hearing loss.

Objectives/Hypothesis: To determine the efficacy of prophylactic famciclovir to significantly reduce the percentage of patients experiencing postoperative delayed facial paresis. Study Design: Prospective evaluation of facial nerve grade for two groups (treated and untreated) with famciclovir before and after surgery. All procedures were conducted by the same group of experienced neurotologists. Methods: In a tertiary neurotologic private practice, the percentage of 1,023 patients with delayed facial paresis after undergoing microsurgical removal of unilateral acoustic tumor with no preoperative treatment was compared to the percentage of 530 patients with preoperative famciclovir treatment. Patients were prescribed famciclovir 500 mg BID for 3 days before surgery and 5 days postoperative. The House-Brackmann Facial Nerve Grade was assessed prospectively at preoperative, immediate postoperative, and discharge from the hospital in both groups. Results: Twenty-five percent of the no famciclovir group experienced delayed facial palsy compared to 20% in the famciclovir group, a statistically significant difference (P < .04). The famciclovir group undergoing translabyrinthine craniotomy showed a significantly greater decrease in percentage of patients with delayed facial palsy than those undergoing middle fossa craniotomies (P < .003). Conclusions: Famciclovir administered preoperatively and after craniotomies resulted in a smaller percentage of patients developing delayed facial weakness. We are continuing the routine use of famciclovir in perioperative acoustic tumor management and recommend that others do so.

Objectives: The mechanistic association between endolymphatic hydrops (ELH) and hearing loss (HL) is unclear. Although ELH severity has been shown to correlate in some studies with HL, injury of vital structures, including hair cells and the cochlear nerve, have failed to demonstrate correlation with ELH severity. The goal of this study is to evaluate the hypothesis that spiral ganglion cell degeneration is the principle pathologic site of ELH-related cochlear injury, correlates with ELH severity, and is most profound in the apical region. Study Design: Surgical induction of ELH in the guinea pig model was followed by histologic confirmation of ELH and subsequent correlation with segmental spiral ganglion cell densities. Methods: Guinea pigs (N = 14) were subjected to unilateral ELH induction and killed after 4 to 6 months. ELH severity and spiral ganglion densities were obtained using computer-aided morphometric analysis. Densities were normalized by calculating a spiral ganglion degeneration index (DI) for each animal. Results: The apical spiral ganglion demonstrated significantly greater degeneration than that noted in the basal spiral ganglion (DI: 1.93 vs. 1.13; P = .004). The degree of spiral ganglion degeneration in the apex correlates well with a total hydrops index (P = .006) and an apical hydrops index (P = .003). Basal spiral ganglion degeneration however, does not correlate well with hydrops severity (total hydrops index: P > .05; basilar hydrops index: P > .05). Conclusions: ELH-related pathology appears to focus initially on the apical spiral ganglion and the degree of deterioration correlates well with the severity of ELH. These findings mirror some reports in the human condition, and imply that the mechanism of cochlear injury in ELH and secondary dysfunction appears to be a neural toxicity that begins in the apex of the cochlea.

Objective: To evaluate the long-term hearing outcomes of neurofibromatosis type 2 (NF2) patients with cochlear implants. Methods: Retrospective analysis of cochlear implant performance in NF2 patients using open- and closed-set speech perception testing. Results: Patients with NF2-associated bilateral vestibular schwannomas frequently become profoundly deaf. The aim of surgical resection should be to preserve serviceable hearing in at least one ear; however, this goal can be difficult to achieve. Frequently, tumor size or poor preoperative hearing status can require a surgical approach that leaves the patient with a profound, bilateral sensorineural hearing loss. If the cochlear nerve is preserved anatomically after vestibular schwannoma surgery, and if promontory stimulation confirms the functionality of the cochlear nerve, then cochlear implantation is an excellent option to restore hearing. We present six cochlear implant patients with NF2 who attained a significant improvement in open- and closed-set speech understanding with a mean follow-up of 7.9 (range: 5–13) years after surgery. In all but one case, the hearing results did not deteriorate over the follow-up period. Conclusion: Early surgical intervention for vestibular schwannomas in NF2 patients when the cochlear nerve can be spared is an important consideration to allow for possible cochlear implantation. A 6- to 8-week recovery period for the anatomically intact cochlear nerve may be necessary to obtain a positive promontory stimulation response following tumor resection and should be performed prior to cochlear implantation.

The variability in speech perception between cochlear implant users is thought to result from the degeneration of the auditory nerve. Degeneration of the auditory nerve, histologically assessed, correlates with electrophysiologically acquired measures, such as electrically evoked compound action potentials (eCAPs) in experimental animals. To predict degeneration of the auditory nerve in humans, where histology is impossible, this paper reviews the correlation between speech perception and eCAP recordings in cochlear implant patients.PubMed and Embase.We performed a systematic search for articles containing the following major themes: cochlear implants, evoked potentials, and speech perception. Two investigators independently conducted title-abstract screening, full-text screening, and critical appraisal. Data were extracted from the remaining articles.Twenty-five of 1,429 identified articles described a correlation between speech perception and eCAP attributes. Due to study heterogeneity, a meta-analysis was not feasible, and studies were descriptively analyzed. Several studies investigating presence of the eCAP, recovery time constant, slope of the amplitude growth function, and spatial selectivity showed significant correlations with speech perception. In contrast, neural adaptation, eCAP threshold, and change with varying interphase gap did not significantly correlate with speech perception in any of the identified studies.Significant correlations between speech perception and parameters obtained through eCAP recordings have been documented in literature; however, reporting was ambiguous. There is insufficient evidence for eCAPs as a predictive factor for speech perception. More research is needed to further investigate this relation. Laryngoscope, 2016 127:476-487, 2017.

To evaluate the correlation between a narrow bony cochlear nerve canal (BCNC) and facial nerve stimulation (FNS) after cochlear implantation (CI) and their underlying mechanisms and to predict the risk of FNS preoperatively.Retrospective cohort study.A total of 64 pediatric cases that underwent CI were included. Among them, 32 cases experienced FNS after CI, and another 32 cases were selected from 817 pediatric implantees by stratified random sampling. The width of the BCNC, the status of the cochlear nerve (CN) and the internal auditory canal (IAC), T level, and C level were compared and analyzed. Strategies for eliminating FNS were also analyzed.The FNS group showed a narrower BCNC (1.09 ± 0.52 mm) than the control group (1.99 ± 0.61 mm; P.01), a lower CN/facial nerve ratio (0.32 ± 0.36) than the control group (1.34 ± 0.76; P.01), and narrower IAC diameter (4.06 ± 1.71 mm) than the control group (5.66 ± 1.36 mm; P.01). The FNS group also showed higher T level (165.7 ± 28.3 μA) than the control group (142.2 ± 21.2 μA; P.01). Adjustment of the C levels and/or pulse width and switching off offending electrodes were attempted to eliminate FNS, with a 75.0% success rate. The FNS group still showed low Categories of Auditory Performance scores (3.00 ± 1.90) compared with the control group (5.94 ± 1.41, P.01) after adjustment.A narrow BCNC could be a cause of FNS after CI. Therefore, careful selection of the side for CI and programming strategies are required to reduce FNS.4. Laryngoscope, 126:1433-1439, 2016.

Objectives/Hypothesis: Middle and external ear anomalies are well recognized in Down syndrome (DS, trisomy 21). Inner ear anomalies are much less frequently described. This study reviews inner ear morphology on imaging to determine the prevalence of cochlear and vestibular anomalies in children with DS. Study Design: The authors conducted a retrospective review of imaging features of (DS) inner ear structures. Methods: Fifty-nine sequential patients with DS with imaging of the inner ear were identified by a radiology report text search program. Quantitative biometric assessment of the inner ear was performed on patients with high-resolution computed tomography or magnetic resonance images of the petrous bone. Petrous imaging was performed for evaluation of inflammatory disease or hearing loss. Spinal imaging, which included petrous views, was performed in most cases to exclude C1 to 2 dislocation, a potential complication of DS. Measurements were compared with normative data. Results: Inner ear dysplasia is much more common in DS than previously reported. Inner ear structures are universally hypoplastic. Vestibular malformations are particularly common and a small bony island of the lateral semicircular canal (

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. Thirtysix 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. Key Words: Temporal bone, tomography, CT, GJB2, connexins, measure, Pendred, SLC26A4. Laryngoscope, 116:2178–2186, 2006

Objective: To report the feasibility of monitoring cochlear function during cochlear implantation. Study Design: Case report. Setting: Tertiary care referral center. Methods: A child with audiologic features typical of bilateral auditory neuropathy underwent cochlear implantation. The scala tympani was entered inferior and slightly anterior to the round window membrane margin and smooth electrode insertion was achieved. Using single polarity click stimuli, the cochlear microphonic was measured at several steps during surgery. Results: Cochlear microphonics were present at all stages during the implantation process and were clearly distinguished from neural responses by stimulus polarity inversion and constant latencies, despite changes in stimulus level. With the electrode in situ, amplitudes were smaller but persisted until the final measurement at 10 minutes after insertion. At follow-up 2 weeks after surgery, behavioral audiometry results indicated profound hearing loss in the operated ear. Conclusions: This paper demonstrates the feasibility of monitoring cochlear function during cochlear implantation. The routine surgical approach did not appear to adversely affect the functional measurements. Standard size, full electrode insertion did diminish the amplitude of the cochlear microphonics, possibly as a result of intracochlear mechanical impairment. Ultimately, profound hearing loss was documented, indicating that factors other than immediate changes induced by electrode insertion were likely responsible for the loss of cochlear function.

Objectives: The cochlea may be damaged by modern conventional radiotherapy (RT) for head and neck cancers when the ear is included in the radiation field. It is unclear however, if the retro-cochlear auditory pathways are affected as well, which has clinical significance in cochlear implantation. This study aims to investigate the integrity of the retro-cochlear auditory pathways in patients who had received RT for nasopharyngeal carcinoma. Study Design: Prospective study. Methods: Patients who were newly diagnosed with nasopharyngeal carcinoma and treated by RT alone were studied. Evoked response audiometry and PTAs were carried out prior to and after RT (at 3, 18, and 48 months postRT). In addition, evoked response audiometry was also performed during the 3rd, 5th, and 7th week of RT. Waves 1 to 5, 1 to 3, and 3 to 5 latencies were measured. The values recorded during and postRT were compared with those recorded before RT. In addition, a subset of ears that demonstrated postRT sensorineural hearing loss were identified so that their respective wave 1 to 5 interwave latencies could be similarly compared. Wilcoxon signed ranks test was used in the statistical analysis. To confirm that the cochlea and internal auditory meatus receive significant doses of radiation, the RT treatment plans of nine other nasopharyngeal carcinoma patients treated by the same RT technique were analyzed to derive dose-volume histograms of these structures. Results: Twenty-seven patients (20 males and 7 females) with a mean age of 51.2 (range 36–75) years participated in the study. There was no statistically significant difference in waves 1 to 5, 1 to 3, and 3 to 5 interwave latencies recorded during RT and postRT as compared with those recorded before RT (P > .05). Pre- and postRT wave 1 to 5 latencies of the 16 ears that had postRT hearing deterioration were also not statistically significant (P = .366). The mean radiation doses delivered to the cochlea and internal auditory meatus ranged from 24.1 to 62.2 Gy and 14.4 to 43.4 Gy, respectively. Conclusion: This study suggests in patients who have had RT for nasopharyngeal carcinoma, the retro-cochlear auditory pathways are functionally intact even in the longer term.

Objectives: This study was designed to compare the incidence and nature of facial nerve stimulation (FNS) in patients receiving cochlear implants (CI) manufactured by Cochlear Corporation, Advanced Bionics Corporation, and MedEl. Study Design: Retrospective chart review at a tertiary referral center. Methods: The charts of 600 patients who received CIs from 1993 to 2003 with at least 1 year of follow-up were reviewed for significant FNS (FNS on at least 1 channel at functional stimulation levels). Data collected included age, sex, etiology of deafness, device type, electrode, FNS onset after initial stimulation, number and location of electrode contacts causing FNS, and loudness level at which FSN occurred. Nucleus straight and perimodiolar electrodes were also compared. Results: Thirty-nine of 600 (6.5%) patients had FNS on at least one channel, (MedEl 3 of 43 [7.0%], Nucleus 29 of 440 [6.6%], and Clarion 7 of 117 [6.0%]). The incidence of FNS in Nucleus perimodiolar electrodes (16 of 250 [6.4%]) was similar to straight electrodes (13 of 190 (6.8%]), as was the mean number of electrodes causing FNS per patient (11 vs. 12). However, straight electrodes caused stimulation at significantly softer perceived loudness levels than perimodiolar electrodes (P

Objective: Hair cell regeneration in the avian cochlea is accompanied by frequency specific reinnervation and recovery of physiologic function. The molecular cues that guide ganglion cells to tonotopically appropriate new hair cells have not been identified. We investigated the potential of ephrin A2 in this process. Study Design: Ephrin A2 expression was characterized in acoustic ganglion cells of normal and gentamicin-treated early post hatch chicks. Methods: Ephrin A2 expression was determined by Western analysis of total protein isolated from acoustic ganglia in normal animals. Protein localization was characterized by fluorescence immunohistochemisty in sections of acoustic ganglia of normal and gentamicin treated animals. Patterns of ephrin A2 expression in acoustic ganglia were determined and quantified during hair cell regeneration. Results: Ephrin A2 expression was found in acoustic ganglia by Western analysis. Localization of this protein by immunofluoresence revealed its presence in acoustic ganglion cells in normal chicks. After gentamicin treatment, ephrin A2 expression was lost in a subset of acoustic ganglion cells. The spatial and temporal pattern of ephrin A2 loss coincides with the pattern of hair cell loss and regeneration. Conclusions: The changes in ephrin A2 immunoreactivity in acoustic ganglion cells during cochlear damage and regeneration suggests that ephrin A2 may be involved in the guidance of ganglion cells to tonotopically appropriate hair cell targets during regeneration. Ephrin A2 in hair cell regeneration.

Objectives/Hypothesis Auditory neuropathy is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses and normal cochlear outer hair cell function as measured by otoacoustic emission recordings. Many risk factors are thought to be involved in its etiology and pathophysiology. Four Chinese pedigrees with familial auditory neuropathy were presented to demonstrate involvement of genetic factors in the etiology of auditory neuropathy. Study Design Probands of the above-mentioned pedigrees, who had been diagnosed with auditory neuropathy, were evaluated and followed in the Department of Otolaryngology-Head and Neck Surgery, China People Liberation Army General Hospital (Beijing, China). Their family members were studied, and the pedigree maps established. Methods History of illness, physical examination, pure-tone audiometry, acoustic reflex, auditory brainstem responses, and transient evoked and distortion-product otoacoustic emissions were obtained from members of these families. Some subjects received vestibular caloric testing, computed tomography scan of the temporal bone, and electrocardiography to exclude other possible neuropathic disorders. Results In most affected patients, hearing loss of various degrees and speech discrimination difficulties started at 10 to 16 years of age. Their audiological evaluation showed absence of acoustic reflex and auditory brainstem responses. As expected in auditory neuropathy, these patients exhibited near-normal cochlear outer hair cell function as shown in distortion product otoacoustic emission recordings. Pure-tone audiometry revealed hearing loss ranging from mild to profound in these patients. Different inheritance patterns were observed in the four families. In Pedigree I, 7 male patients were identified among 43 family members, exhibiting an X-linked recessive pattern. Affected brothers were found in Pedigrees II and III, whereas in pedigree IV, two sisters were affected. All the patients were otherwise normal without evidence of peripheral neuropathy at the time of writing. Conclusion Patients with characteristics of nonsyndromic hereditary auditory neuropathy were identified in one large and three smaller Chinese families. Pedigree analysis suggested an X-linked, recessive hereditary pattern in one pedigree and autosomal recessive inheritances in the other three pedigrees. The phenotypes in the study were typical of auditory neuropathy; they were transmitted in different inheritance patterns, indicating clinical and genetic heterogeneity of this disorder. The observed inheritance and clinical audiological findings are different from those previously described for nonsyndromic low-frequency sensorineural hearing loss. This information should facilitate future molecular linkage analyses and positional cloning for the relative genes contributing to auditory neuropathy.

Objectives/Hypothesis Cochlear nerve stimulation using a linear array of electrodes, the cochlear implant, has become an accepted treatment for profound deafness. Major limitations of this technology are high threshold of stimulation, poor performance in a noisy background, cross-talk between electrodes, unsatisfactory channel selectivity, and variable reconstruction of frequency space. A novel auditory neuroprosthesis is proposed that is expected to overcome these problems by implanting an array of three-dimensional microelectrodes, the Utah Electrode Array, directly into the cochlear nerve. Study Design We have conducted acute, extending for up to 12 hours and semichronic, extending for up to 52 hours, electrophysiological experiments, radiologic and histologic studies in 12 cats. Methods The electrically evoked auditory brainstem response was used as a means to characterize the threshold, dynamic range, and stability of cochlear nerve stimulation through the implanted Utah Electrode Array neuroprosthesis. Plain film, computed tomographic, and histological studies were conducted to determine the result of the implant. Results The electrically evoked auditory brainstem response thresholds were approximately one to two orders of magnitude lower than those evoked with conventional cochlear implants. We were able to close the cochleostomy, bring the cat into normal anatomical position, and obtain stable electrically evoked auditory brainstem responses for up to 52 hours. Plain film and computed tomographic studies indicated that the Utah Electrode Array neuroprosthesis was in the intended position in the nerve. Histological studies did not reveal hemorrhage or significant damage to the nerve. Conclusion Because the presented stimulation paradigm appears to significantly mitigate some of the problems of conventional cochlear implants, it may offer a new therapeutic approach to profound deafness.

Objectives: The aim of this study is to determine the efficacy of L-N-acetyl-cysteine (L-NAC) as a protectant for inner ear auditory sensory cells against the toxic effects of cisplatin. Study Design: Prospective laboratory study of the otoprotective effect of L-NAC on auditory neurons and hair cells in vitro. Methods: The study has two arms. The first arm evaluated the neuroprotective effect of L-NAC on early postpartum auditory ganglion cell cultures. Two culture media were used. The two media differed in that one of them was enhanced by the addition of neurotrophins (neurotrophin type 3 and brain-derived neurotrophic factor) and a growth factor (transforming growth factor-β1). Then the survival of cisplatin-treated auditory neurons was studied before and after pretreatment with protective levels of L-NAC. The second arm of the study evaluated the effect of L-NAC on cisplatin damage initiated to auditory hair cells. Early-postpartum organ of Corti explants were grown in culture. Their rate of survival was studied after exposure to toxic levels of cisplatin. Then, survival of cisplatin-damaged hair cells was studied after they were pretreated with L-NAC. Results: Pretreatment of cultures with L-NAC protected both auditory neurons and hair cells from the effects of exposure to toxic levels of cisplatin. This observed otoprotective effect was dose dependent. Conclusions: Our in vitro studies have demonstrated that L-NAC protected both auditory neurons and hair cells from the toxic effects of cisplatin. Because it protects both of these inner ear structures, L-NAC may be potentially useful in protecting hearing, in general, from cisplatin-induced damage. In addition, L-NAC has low systemic and mucosal toxicity. It also has a low molecular weight that may allow it to readily cross the round window membrane. All these characteristics make it potentially suitable for transtympanic application for the prevention of the ototoxicity of cisplatin in vivo.

Distortion-product otoacoustic emissions (DPOAEs) have been shown to be ideally sensitive to interruptions of the cochlear blood flow. However, a 15- to 30-second latency typically occurs between cessation of circulation and measurable DPOAE level changes. DPOAEs can also be characterized by phase measures. The aim of the present study was to determine in 10 rabbits the effects on DPOAE phase of repetitively compressing the internal auditory artery. In contrast to the delays measured by DPOAE level, phase changes were detected 1 to 5 seconds after internal auditory artery compression. These data suggest that the essentially "real time" monitoring of cochlear function with DPOAE phase can be used to ensure hearing preservation during surgery involving the porus acousticus and skull base.

Objective: Direct implantation into the cochlear nerve can bypass the potential limitations of conventional cochlear implants. Implantable electrical arrays increase the number of stimulation sites, broaden frequency selectivity, require less activating current, and are not dependent on cochlear anatomy. Cochlear nerve implantation demands a unique surgical exposure to the modiolus. This study comprises an assessment of the risk of generating an intraoperative cerebrospinal fluid (CSF) leak using this approach. Methods: Five fresh cadavers were obtained for dissection. Using dyed normal saline as an indicator, the central nervous system was pressurized to physiological parameters. Surgical approaches to the cochlear nerve were initiated. Leakage of indicator fluid for each approach was quantitatively and qualitatively assessed. Indicator dye in the surgical field was considered a CSF breech. Indicator fluid was collected and quantified. Results: Eighty percent of the surgical approaches caused quantifiable leaks with rates ranging from 0.1 mL/minute to 6 mL/minute. For directly implanted microarrays, the utilization of a modified facial recess approach with cochleostomy and modiolar drillout carries significant risk for generating a CSF leak during the procedure.

Objective/Hypothesis Magnetic resonance imaging of the temporal bone has an important role in decision making with regard to cochlea implantation, especially in children with cochlear nerve deficiency. The purpose of this study was to evaluate the usefulness of the combination of an advanced high-resolution T2-weighted sequence with a surface coil in a 3-Tesla magnetic resonance imaging scanner in cases of suspected cochlear nerve aplasia. Study Design Prospective study. Methods Seven patients with cochlear nerve hypoplasia or aplasia were prospectively examined using a high-resolution three-dimensional variable flip-angle turbo spin-echo sequence using a surface coil, and the images were compared with the same sequence in standard resolution using a standard head coil. Three neuroradiologists evaluated the magnetic resonance images independently, rating the visibility of the nerves in diagnosing hypoplasia or aplasia. Results Eight ears in seven patients with hypoplasia or aplasia of the cochlear nerve were examined. The average age was 2.7 years (range, 9 months–5 years). Seven ears had accompanying malformations. The inter-rater reliability in diagnosing hypoplasia or aplasia was greater using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence (fixed-marginal kappa: 0.64) than with the same sequence in lower resolution (fixed-marginal kappa: 0.06). Conclusions Examining cases of suspected cochlear nerve aplasia using the high-resolution three-dimensional variable flip-angle turbo spin-echo sequence in combination with a surface coil shows significant improvement over standard methods. Level of Evidence NA. Laryngoscope, 124:751–754, 2014

Vestibular neuritis is a degenerative neuropathy of the peripheral vestibular system. The etiology of this condition is uncertain, although it is generally believed to be viral. A small percentage of patients with vestibular neuritis have chronic recurrent episodes of vertigo. Detailed cytologic descriptions of acute or chronic vestibular neuritis are lacking, and no previous studies have reported evidence of chronic inflammation in human temporal bone specimens. The authors of this study examined temporal bone specimens from three patients with a history of chronic recurrent vertigo of unknown cause. Varying degrees of inflammation and destruction were seen in the vestibular system, and mild involvement of the cochlear system was noted. These findings are consistent with postinfectious inflammatory changes of the cochlear-vestibular system analogous to a postinfectious syndrome involving the central nervous system.

Unilateral removal of Scarpa's ganglion and neurectomy of the peripheral vestibular nerve branches were compared in rats as methods to eliminate primary vestibular input. Ocular nystagmus was consistently observed after both types of lesion, but it completely disappeared within 4 to 7 days. Imbalance and rotation were more serious and prolonged after ganglionectomy than after peripheral neurectomy. Corresponding with these differences in symptoms were differences in terminal degeneration. After ganglionectomy, degenerated axons and terminals were distributed throughout all terminal regions of primary vestibular fibers on the lesioned side, while after peripheral neurectomy, the degeneration was more limited. The results of this study suggest that vestibular ganglionectomy is a more successful approach than peripheral vestibular neurectomy for removing the primary vestibular input.

Objectives/Hypothesis To evaluate whether there is a genetic contribution to the development of narrow bony cochlear nerve canal and analyze the differences between unilateral and bilateral narrow bony cochlear nerve canal. Study Design Retrospective review. Methods Patients diagnosed with unilateral (n=44) or bilateral (n=13) sensorineural hearing loss with narrow bony cochlear nerve canals from October 2004 to July 2011 were evaluated. The segregation ratio of hearing loss among siblings of probands was calculated. The differences in segregation ratio and other clinical characteristics were also compared. Results The segregation ratio of hearing loss in siblings of patients with unilateral narrow bony cochlear nerve canal was close to zero, whereas the ratio in siblings of patients with bilateral canals was 20%. Internal auditory canal narrowing was significantly more frequently combined in unilateral than bilateral narrow bony cochlear nerve canal cases. Cochlear nerve deficiency based on magnetic resonance imaging was found in 63.6% of bilateral narrow bony cochlear nerve canal cases. Milder hearing loss was exclusively detected in bilateral cases. Conclusions Narrow bony cochlear nerve canal is not likely to have a simple Mendelian inheritance pattern, especially in unilateral cases. The contribution of a Mendelian genetic etiology to bilateral narrow bony cochlear nerve canals remains elusive. More frequent coexistence of internal auditory canal narrowing among unilateral narrow bony cochlear nerve canal cases suggests that bilateral narrow bony cochlear nerve canals are not just a duplicate of the unilateral narrow bony cochlear nerve canal. Level of Evidence 4. Laryngoscope, 123:1996–2000, 2013

Objectives/Hypothesis: To describe cochlear nerve deficiency and abnormalities of the internal auditory canal (IAC) associated with CHARGE (coloboma, heart defects, atresia choanae, retardation of growth and/or development, genital hypoplasia, and ear anomalies and/or deafness) syndrome. Study Design: Case series. Methods: In a tertiary children's hospital, children with CHARGE syndrome were evaluated between 2006 and 2009. Morphology of the inner ear, IAC, and cochlear nerves was evaluated along with auditory-evoked brainstem response results. Results: Of the 17 patients with CHARGE diagnosis, 14 ears demonstrated profound sensorineural hearing loss (SNHL). The remaining ears had conductive hearing loss, mixed hearing loss, or mild to moderate SNHL. Computed tomography (CT) evaluation was refused in one case and delayed in one case due to parental decision. Of 30 ears evaluated with CT, 28 (93%) had substantial abnormalities of the inner ear including hypoplasia or aplasia of the semicircular canals and abnormalities of the cochlea and vestibule. CT evaluation revealed cochlear aperture narrowing or occlusion in 16 ears, one of which had normal hearing. The eight most recent patients with profound SNHL (six bilateral SNHL, two unilateral) underwent magnetic resonance imaging (MRI) of the IAC, and 13 of 14 ears with SNHL were noted to have absent or deficient cochlear nerves. CT scans in two ears with profound SNHL revealed normal cochlear apertures. Conclusions: The dysmorphic inner ear is well described in CHARGE patients; however, cochlear nerve deficiency has not been considered a common etiology for SNHL in these patients. Because of the implications of cochlear nerve deficiency in therapeutic decision making (i.e., cochlear implantation), MRI evaluation of the eighth nerve should be considered in CHARGE patients with profound SNHL. Laryngoscope, 2013

Objectives/Hypothesis: To assess the normative size of the cochlear nerve (CN) and facial nerve (FN) in normal-hearing ears and to determine whether nerve size varies with age. Study Design: Cross-sectional. Methods: We included 169 ears with normal hearing between 2005 and 2010. The height, width, and cross-sectional area (CSA) of the CN and FN in the middle of the internal auditory canal were measured on oblique sagittal images of 3.0-T magnetic resonance imaging. Results were compared by age. Young subjects were divided into three age groups, 0–5, 6–10, and 11–15 years. Subjects over age 40 years were divided into groups at 10-year intervals. Results: Mean age was 32.6 years (range, 0.75–79 years). We found that the CN had significantly greater vertical (1.10 ± 0.21 mm vs. 0.95 ± 0.21 mm) and horizontal (1.11 ± 0.20 mm vs. 1.03 ± 0.22 mm) diameters than the FN. The CSA of the CN was larger than that of the FN (0.98 ± 0.33 mm2 vs. 0.79 ± 0.31 mm2). Except for the CN vertical diameter, there were no significant differences between right and left ears. Sex did not affect the nerve size. Although the CN was not affected by age, the FN vertical diameter and CSA of children 5 years. The size of the two nerves did not differ among groups over age 40 years. Conclusions: The CN is not affected by age in normal-hearing ears. The FN vertical diameter and CSA of children

Compare outcomes among children with inner ear malformations and/or cochlear nerve deficiency (CND) who have received a cochlear implant (CI).Individual retrospective cohort study from 1993 to 2010.A select cohort of 76 children was identified. Imaging characteristics, operative findings, complications, mapping parameters, and performance were assessed. Comparisons among the different groups were undertaken.Surgery was mostly uncomplicated. Nearly all children demonstrated behavioral responses to CI stimulation irrespective of inner ear morphology or the presence of CND. Children with CND had higher pure tone averages (PTAs) and required greater charge for stimulation than other malformation types. Open-set speech perception was achieved in 100% of children with incomplete partition-enlarged vestibular aqueduct (IP-EVA), 50% of those with hypoplastic malformations, and 19% of CND cases. Robust responses on eighth nerve compound action potential (ECAP) testing through the implant was associated with higher levels of speech perception. Manually supplemented communication strategies were more common among children with hypoplastic malformations (69%) and CND (95%) than those with IP-EVA (18%).Children with IP-EVA malformations have an excellent prognosis for developing open-set speech perception and using oral communication modes following CI. On the contrary, children with severe malformations or CND may have elevated charge requirements for attaining sound detection alone. These children's prognosis for obtaining open-set speech understanding, using exclusive oral communication, and participating in mainstream education is more limited. These findings have important implications for considering alternative forms of intervention such as auditory brainstem implantation and/or supplementation with visually based communication strategies.

To determine the expression patterns of B ephrins and Ephs in the cochlea and identify functional consequences of disruption of ephrin B/Eph B interactions in both cultured spiral ganglion neurons and in the cochlea of live animals.The expression patterns of various B ephrins and Ephs were determined in mice with Lac-Z mutation. Mice with null function of individual B ephrin and Eph proteins and those with multiple knockouts were studied for cochlear innervation patterns.Mice with B ephrins and Ephs disrupted with the β-galactosidase gene were sacrificed at P6, and their cochleae isolated and processed for Lac-Z staining to determine expression of these proteins in cochlear tissue. Spiral ganglion cells from wild-type as well as ephrin B1 knockout mice were isolated and cocultured with Eph B2 expressing Cos1 cells and neurite lengths were determined. Fluorescent lipophillic dyes were used to label spiral ganglion cell nerve fibers to determine cochlear innervation patterns in wild-type and knockout mice.Eph B1, B2, and ephrin B2 but not B3 was expressed in the cochlea. Eph B2 inhibited outgrowth of spiral ganglion cell axons from wild-type mice, but not from ephrin B1 knockout mice in culture. Knockout mice with null function of ephrin B1 alone or Eph B1, Eph B2, Eph B3 in combination demonstrated abnormal innervation patterns in the organ of Corti.Disruption of B ephrins and Ephs results in functional consequences in spiral ganglion cells, suggesting that these proteins play a role in establishing normal innervation patterns in the cochlea.

One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory nerve is possible with a mid-infrared laser aimed at the spiral ganglion via the round window. However, these neurons must be driven at adequate rates for optical radiation to be useful in cochlear implants. We herein use single-fiber recordings to characterize the responses of auditory neurons to optical radiation.In vivo study using normal-hearing adult gerbils.Two diode lasers were used for stimulation of the auditory nerve. They operated between 1.844 μm and 1.873 μm, with pulse durations of 35 μs to 1,000 μs, and at repetition rates up to 1,000 pulses per second (pps). The laser outputs were coupled to a 200-μm-diameter optical fiber placed against the round window membrane and oriented toward the spiral ganglion. The auditory nerve was exposed through a craniotomy, and recordings were taken from single fibers during acoustic and laser stimulation.Action potentials occurred 2.5 ms to 4.0 ms after the laser pulse. The latency jitter was up to 3 ms. Maximum rates of discharge averaged 97 ± 52.5 action potentials per second. The neurons did not strictly respond to the laser at stimulation rates over 100 pps.Auditory neurons can be stimulated by a laser beam passing through the round window membrane and driven at rates sufficient for useful auditory information. Optical stimulation and electrical stimulation have different characteristics; which could be selectively exploited in future cochlear implants.

Anacusis following hearing preservation surgery for acoustic neuroma removal in which the cochlear nerve was preserved has been explained on the basis of neural or vascular compromise. In the absence of pathologic evidence for either theory, a physiologic model was chosen. Electrical promontory stimulation with monitoring of subjective and electrically evoked auditory brainstem responses was undertaken. A positive response to stimulation suggests a vascular impairment of the cochlea sparing the cochlear nerve and spiral ganglion. The absence of response suggests loss of neural integrity at the level of the spiral ganglion or cochlear nerve. Six patients who suffered anacusis following hearing preservation surgery for acoustic neuroma were studied. Data regarding electrical promontory stimulation, auditory brainstem responses, and implications of the possible role of cochlear implantation are discussed.

Deficient cochlear nerves (CN) have been associated with poor cochlear implant performance. Normative data on CN diameter based on radiographic imaging have not been published. The objectives of this study were to determine if CN diameter could be reproducibly measured on parasagittal constructive interference in steady state (CISS)-sequence magnetic resonance imaging (MRI) and to establish a normative range for CN diameter.Retrospective review of MRI images by two independent blinded observers.Thirty patients (45 ears) with a CISS-sequence MRI done for auditory complaints in patients with normal hearing in one ear were included. CN diameters were measured in a parasagittal plane just medial to the internal auditory canal (IAC) fundus by two independent observers. Cross-sectional areas were calculated and interobserver agreement was evaluated.The CN was identified in 100% of studied ears. In 93%, the diameters were able to be measured by both observers. In 7% of ears, the cochlear nerve was unable to be measured secondary to the proximity of the CN to IAC wall. The CN vertical diameter (1.4 mm +/- 0.21 mm), horizontal diameter (1.0 mm +/- 0.15 mm), and cross-sectional area (1.1 mm +/- 0.26 mm(2)) were normally distributed. There was good interobserver correlation for each measure.CN diameter can be reliably measured at the IAC fundus. This study establishes normative radiographic data for the CN diameter. These data may be used to evaluate the cause and treatment prognosis in patients with sensorineural hearing loss.

Objectives/Hypothesis: Auditory brainstem implants (ABIs) can provide excellent open set speech recognition in adults without auditory tumors. These favorable results prompted us to extend ABI indications to children with profound hearing loss (HL) who are not candidates for a cochlear implant (CI). This article reports on the auditory performance and cognitive development measured in children with ABIs. Study Design: This study quantifies the development of auditory perceptual and nonverbal cognitive abilities of children with profound HL undergoing ABI. From 2000 to 2006, 17 children aged 14 months to 16 years received an ABI for different tumor and nontumor diseases in our department in Verona, and nine children were operated in other countries. Six of the children had been previously fitted elsewhere with a CI with no auditory results. Fourteen children had multiple associated psychomotor handicaps. Methods: The retrosigmoid approach was used in all children. Intraoperative and postoperative electrically evoked auditory brainstem responses were performed in all children. Perceptual auditory abilities were evaluated with the Evaluation of Auditory Responses to Speech battery and the Category of Auditory Performance test. Cognitive evaluation was performed on 10 children using the Leiter International Performance Scale—Revised test. Results: All children consistently use their devices for 8 h/d at average and have environmental sound awareness and utterance of words and simple sentences. Their category of auditory performance test scores increased significantly with ABI use. Scores on two of the four subtests considered for cognitive evaluation in this study increased significantly (P < .05) during the first year of ABI use. Postimplant cognitive outcomes were positively related to the auditory results. Conclusions: The present investigation clearly indicates that children who are not candidates for CI fitted with ABI obtain significant development of their hearing ability and a significant improvement in some cognitive parameters. The outcomes of the present study suggest that children with cochlear or cochlear nerve abnormalities with associated cognitive deficits should not be excluded from ABI implantation.

Objective: The loss of spiral ganglion neurons (SGNs) is one of the major causes of profound sensorineural hearing loss (SNHL). Stem cell replacement therapy, which is still in its infancy, has the potential to treat or cure those who suffer from an array of illnesses and degenerative neurologic disorders, including sensorineural deafness (SNHL). Little is known about the potentials of mesenchymal stem cells (MSCs) and their ability to take on properties of SGNs. The two main purposes of this study were to evaluate the survival of mouse MSCs transplanted into normal and ouabain-treated gerbil cochleae and to determine the migratory patterns of MSCs with two differing injection methods. Subjects: Thirty-two Mongolian gerbils, 3 to 4 months old, were used as recipients, and four 6-week-old TgN(ACTbEGFP) mice that ubiquitously express green fluorescent protein (GFP) were used as donors. Design: The animals were deafened by ouabain, which damaged SGNs while leaving hair cell systems intact. After 4 weeks of recovery, the animals received an intraperilymphatic transplantation of 1.0 × 106 GFP-positive undifferentiated MSCs via two different injection methods: scala tympani injection and modiolar injection. Seven days after the transplantation, the survival of MSCs was evaluated by microscopic examination of frozen sections cut through the cochleae of the recipient animals. The number of profiles was counted on the five most central modiolar sections. One-way analyses of variance (ANOVA) were used to determine any significantdifferences among mean profile counts across the experimental conditions. Results: Our findings indicated that undifferentiated MSCs were able to survive in the modiolus both in the control and the ouabain-treated cochleae. The average number of profiles found in the modiolus was greater in the ouabain-treated cochleae than in the control cochleae. This difference was statistically significant (P < .01) as determined using a one-way ANOVA and an ad hoc Tukey-Kramer's test. With the scala tympani injection, there were no profiles found in the modiolus either in the control or ouabain-treated cochleae. This finding may indicate that donor MSCs need to be directly injected into the modiolus to replace injured SGNs. Finally, there was no evidence of hyperacute rejection in any of the gerbils despite the use of xenotransplantation. Conclusions: These findings may have important clinical implications as a means of delivering MSCs in the cochlea for stem-cell replacement therapy. Survival of transplanted MSCs into the modiolus of the cochlea may result in regeneration of damaged SGNs.

Objectives/Hypothesis: Although cochlear implants have been successfully used by many individuals with profound hearing impairment, limitations still remain with this approach to hearing restoration, including poor stimulation selectivity because of cross-talk between electrodes and poor low-frequency percepts. These limitations may be mitigated by direct intraneural stimulation of the auditory nerve by way of an array of penetrating microelectrodes. Such an approach should provide focal stimulation and selective activation of the nerve fibers, thereby minimizing cross-talk among implanted stimulating electrodes and evoking narrow-band frequency percepts. Study Design: We investigated the activation of primary auditory cortex evoked by such direct intraneural electrical stimulation of the auditory nerve. Methods: We implanted 11 penetrating microelectrodes in the cat auditory nerve, simulated the nerve by way of these electrodes, and recorded the evoked neuronal activity patterns in cat primary auditory cortex. We compared these activation patterns with acoustically evoked cortical activity patterns obtained in a different animal. Results: Our results showed that direct stimulation of the auditory nerve evoked localized activity patterns in primary auditory cortex similar in spatial extent to those evoked by acoustic stimulation and that the extent of cortical activation by both acoustic and electrical stimuli was graded with stimulus intensity. These results suggest that the implanted electrodes can excite independent and small populations of nerve fibers. Conclusion: This study demonstrates the functional feasibility of direct intraneural auditory nerve stimulation with an array of penetrating microelectrodes and that such an approach could form the foundation for an auditory prosthesis with improved frequency coding.

Objective/Hypothesis: Implantable hearing devices such as cochlear implants and auditory brainstem implants deliver auditory information through electrical stimulation of auditory neurons. The combination of microelectronic electrodes with auditory nerve cells may lead to further improvement of the hearing quality with these devices. Whereas several kinds of neurons are known to grow on semiconductor substrates, interactions of cochlear nucleus (CN) neurons with such materials have yet to be described. Materials and Methods: To investigate survival and growth behavior of CN neurons on different semiconductor materials. CN explants from postnatal day 10 Sprague-Dawley rats were cultured for 96 hours in Neurobasal medium on polished and unpolished silicon wafers (p-type Si {100} and p-type Si3N4{100}) as well as plastic surface. These surfaces had been coated with poly-L-lysine and laminin. Neuronal outgrowth was examined using image analysis software after immunohistologic staining for neurofilament. Neurite length and directional changes were quantified. Additionally, neurite morphology and adhesion to the semiconductor material was evaluated by scanning electron microscopy. Results: Although proper adhesion of CN explants was seen, no neurite growth could be detected on unpolished silicon wafers (Si and Si3N4). Compared with the other test conditions, polished, laminin-coated Si3N4 wafers showed best biocompatibility regarding neurite length and number per explant. CN explants developed a mean of eight neurons with an average length of 236 μm in 96 hours of culture on these wafers. Conclusion: The results of this study demonstrate the general possibility of CN neuron growth in culture on semiconductors in vitro. The differences in neuron length and number per explant indicate that the growth of CN neurons is influenced by the semiconductor substrate as well as extracellular matrix proteins, with laminin-coated p-type Si3N4{100} being a preferable material for future hybrid experiments on auditory-neuron semiconductor chips.

Objectives/Hypothesis: Aluminum (Al) is a neurotoxin in both human and animal models. Al accumulation is usually observed in patients with end-stage renal disease (ESRD). To clarify whether Al also exhibits toxic effects on the specified neural organ of inner ear, we recruited hemodialysis (HD) patients to investigate the effect of serum Al level on the auditory physiology. Study Design: Forty patients in maintenance HD as well as 40 age-matched healthy subjects without hearing complaints were enrolled. The auditory function tests, including pure-tone audiometry (PTA), distortion-product otoacoustic emissions (DPOAEs), and auditory brainstem response (ABR) were performed in all subjects. The serum Al levels determined within 3 months of auditory tests were used for analysis. Results: High-frequency hearing impairment was the predominant auditory dysfunction in HD patients who showed worse high-tone hearing level on PTA and diminished amplitudes of DPOAEs at 3 K and 4 K as compared with the controls (P < .001). Age was a significant factor determining the auditory dysfunction in both HD patients and control subjects. After age correction, serum Al level correlated reversely with the amplitude of DPOAEs-2 K (P = .002), but not with amplitudes of DPOAEs-3 K, -4 K, hearing levels on PTA, or wave latencies on ABR. Conclusion: High-frequency hearing impairment is a common presentation in HD patients. Serum Al level correlates reversely with the amplitude of DPOAEs-2 K but not those of DPOAEs-3 K, -4 K, hearing levels on PTA, and wave latencies on ABR. Possibly, the correlation between the Al level and the high-frequency OAE results was obscured by the significantly diminished amplitudes of DPOAEs-3 K, -4 K in ESRD patients. These results implicate that the effect of Al is mainly of cochlear origin rather than of retrocochlear origin.

Objective: High levels of bilirubin are neurotoxic and may result in deafness or auditory neuropathy/auditory dyssynchrony (AN/AD). The jaundiced (jj) Gunn rat animal model of kernicterus has electrophysiologic and neuroanatomic abnormalities of brainstem auditory nuclei with normal cochlear microphonic recordings. We examined morphologic changes in the cochlea, spiral ganglion, and auditory nerve and relate these findings to current understanding of AN/AD. Methods: At 15 days of age, jj and nonjaundiced (Nj) littermates were injected with sulfadimethoxine (sulfa) and killed 3 days later by transcardial perfusion. Sections were cut through decalcified temporal bones, cochlear nerves, and auditory brainstem and processed for light and electron microscopy and immunohistochemical localization of calbindin-D and parvalbumin. Results: Spiral ganglion neurons were severely degenerated with a paucity of myelinated axons in jj animals. Electron microscopy of the intramodilar auditory nerve revealed a lack of large caliber axons in jj-sulfa versus Nj-sulfa controls. Large diameter degenerating axons were characterized by an electron-dense atrophied axis cylinder resembling an axonopathy. Conclusions: Our findings of abnormal spiral ganglion cells and selective loss of large, myelinated auditory nerve fibers with no abnormalities in cochlear hair cells, support the sulfa-treated jj Gunn rat as a model for bilirubin induced AN/AD. The paucity of large caliber neurons undermines temporal coding of auditory information and neural synchrony and demonstrates that in addition to brainstem auditory nuclei, spiral ganglion neurons are selectively vulnerable to bilirubin toxicity.