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Micro and nanoscale patterning of surface features and biochemical cues have emerged as tools to precisely direct neurite growth into close proximity with next generation neural prosthesis electrodes. Biophysical cues can exert greater influence on neurite pathfinding compared to the more well studied biochemical cues; yet the signaling events underlying the ability of growth cones to respond to these microfeatures remain obscure. Intracellular Ca2+ signaling plays a critical role in how a growth cone senses and grows in response to various cues (biophysical features, repulsive peptides, chemo-attractive gradients). Here, we investigate the role of inositol triphosphate (IP3) and ryanodine-sensitive receptor (RyR) signaling as sensory neurons (spiral ganglion neurons, SGNs, and dorsal root ganglion neurons, DRGNs) pathfind in response to micropatterned substrates of varied geometries. We find that IP3 and RyR signaling act in the growth cone as they navigate biophysical cues and enable proper guidance to biophysical, chemo-permissive, and chemo-repulsive micropatterns. In response to complex micropatterned geometries, RyR signaling appears to halt growth in response to both topographical features and chemo-repulsive cues. IP3 signaling appears to play a more complex role, as growth cones appear to sense the microfeatures in the presence of xestospongin C but are unable to coordinate turning in response to them. Overall, key Ca2+ signaling elements, IP3 and RyR, are found to be essential for SGNs to pathfind in response to engineered biophysical and biochemical cues. These findings inform efforts to precisely guide neurite regeneration for improved neural prosthesis function, including cochlear implants. [ABSTRACT FROM AUTHOR]

Cochlear implants (CI) represent incredible devices that restore hearing perception for those with moderate to profound sensorineural hearing loss. However, the ability of a CI to restore complex auditory function is limited by the number of perceptually independent spectral channels provided. A major contributor to this limitation is the physical gap between the CI electrodes and the target spiral ganglion neurons (SGNs). In order for CI electrodes to stimulate SGNs more precisely, and thus better approximate natural hearing, new methodologies need to be developed to decrease this gap, (i.e., transitioning CIs from a far-field to near-field device). In this review, strategies aimed at improving the neural-electrode interface are discussed in terms of the magnitude of impact they could have and the work needed to implement them. Ongoing research suggests current clinical efforts to limit the CI-related immune response holds great potential for improving device performance. This could eradicate the dense, fibrous capsule surrounding the electrode and enhance preservation of natural cochlear architecture, including SGNs. In the long term, however, optimized future devices will likely need to induce and guide the outgrowth of the peripheral process of SGNs to be in closer proximity to the CI electrode in order to better approximate natural hearing. This research is in its infancy; it remains to be seen which strategies (surface patterning, small molecule release, hydrogel coating, etc.) will be enable this approach. Additionally, these efforts aimed at optimizing CI function will likely translate to other neural prostheses, which face similar issues. [ABSTRACT FROM AUTHOR]

Cochlear implants (CI) have revolutionized the treatment of patients with severe to profound sensory hearing loss by providing a method of bypassing normal hearing to directly stimulate the auditory nerve. A further advance in the field has been the introduction of "hearing preservation" surgery, whereby the CI electrode array (EA) is carefully inserted to spare damage to the delicate anatomy and function of the cochlea. Preserving residual function of the inner ear allows patients to receive maximal benefit from the CI and to combine CI electric stimulation with acoustic hearing, offering improved postoperative speech, hearing, and quality of life outcomes. However, under the current paradigm of implant surgery, where EAs are inserted by hand, the cochlea cannot be reliably spared from damage. Robotics-assisted EA insertion is an emerging technology that may overcome fundamental human kinetic limitations that prevent consistency in achieving steady and slow EA insertion. This review begins by describing the relationship between EA insertion speed and generation of intracochlear forces and pressures. The various mechanisms by which these intracochlear forces can damage the cochlea and lead to worsened postoperative outcomes are discussed. The constraints of manual insertion technique are compared to robotics-assisted methods, followed by an overview of the current and future state of robotics-assisted EA insertion. [ABSTRACT FROM AUTHOR]

This study evaluates intracochlear electrocochleography (ECochG) for real-time monitoring during cochlear implantation. One aim tested whether adjusting the recording electrode site would help differentiate between atraumatic and traumatic ECochG amplitude decrements. A second aim assessed whether associations between ECochG amplitude decrements and post-operative hearing loss were weaker when considering hearing sensitivity at the ECochG stimulus frequency compared to a broader frequency range. Eleven adult cochlear implant recipients who were candidates for electro-acoustic stimulation participated. Single-frequency (500-Hz) ECochG was performed during cochlear implantation; the amplitude of the first harmonic of the difference waveform was considered. Post-operative hearing preservation at 500 Hz ranged from 0 to 94%. The expected relationship between ECochG amplitude decrements and hearing preservation was observed, though the trend was not statistically significant, and predictions were grossly inaccurate for two participants. Associations did not improve when considering alternative recording sites or hearing sensitivity two octaves above the ECochG stimulus frequency. Intracochlear location of a moving recording electrode is a known confound to real-time interpretation of ECochG amplitude fluctuations, which was illustrated by the strength of the correlation with ECochG amplitude decrements. Multiple factors contribute to ECochG amplitude patterns and to hearing preservation; these results highlight the confounding influence of intracochlear recording electrode location on the ECochG. [ABSTRACT FROM AUTHOR]

Background: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. Main text: 10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. Conclusion: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival. [ABSTRACT FROM AUTHOR]

Quantitative analysis of neurite growth and morphology is essential for understanding the determinants of neural development and regeneration, however, it is complicated by the labor-intensive process of measuring diverse parameters of neurite outgrowth. Consequently, automated approaches have been developed to study neurite morphology in a high-throughput and comprehensive manner. These approaches include computer-automated algorithms known as 'convolutional neural networks' (CNNs)—powerful models capable of learning complex tasks without the biases of hand-crafted models. Nevertheless, their complexity often relegates them to functioning as 'black boxes.' Therefore, research in the field of explainable AI is imperative to comprehend the relationship between CNN image analysis output and predefined morphological parameters of neurite growth in order to assess the applicability of these machine learning approaches. In this study, drawing inspiration from the field of automated feature selection, we investigate the correlation between quantified metrics of neurite morphology and the image analysis results from NeuriteNet—a CNN developed to analyze neurite growth. NeuriteNet accurately distinguishes images of neurite growth based on different treatment groups within two separate experimental systems. These systems differentiate between neurons cultured on different substrate conditions and neurons subjected to drug treatment inhibiting neurite outgrowth. By examining the model's function and patterns of activation underlying its classification decisions, we discover that NeuriteNet focuses on aspects of neuron morphology that represent quantifiable metrics distinguishing these groups. Additionally, it incorporates factors that are not encompassed by neuron morphology tracing analyses. NeuriteNet presents a novel tool ideally suited for screening morphological differences in heterogeneous neuron groups while also providing impetus for targeted follow-up studies. [ABSTRACT FROM AUTHOR]

Caldendrin is a Ca2+ binding protein that interacts with multiple effectors, such as the Cav1 L-type Ca2+ channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Cav1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Cav1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Cav1 channels to growth-inhibitory pathways in DRGNs of females but not males. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To determine the timing of acoustic hearing changes among hearing preservation Cochlear implant (CI) recipients. To determine differences in hearing outcomes based on device type and demographic factors. To determine if there is a relationship between the extent of early hearing loss after CI and the subsequent rate of continued hearing loss. Study Design: Prospective, single subject study. Methods: Two hundred and eleven subjects who received a hearing preservation CI were included in the study—80 Nucleus Hybrid L24 (Cochlear), 47 422/522 (Cochlear), 24 S8 (Cochlear), 14 S12 (Cochlear), 6 SRW (Cochlear), 21 SLIM J (Advanced Bionics), and 19 Flex (Med‐EL). Of these, 127 were included in the subsequent analyses. Audiometric thresholds (low frequency pure‐tone‐averages) were collected and compared pre and postoperatively. Results: Long‐term hearing preservation rates were 65% (52/80) for L24, 83% (20/24) for S8, 79% (11/14) for S12, 83% (5/6) for SRW, 54% (25/47) for 422/522, 91% (21/23) for SLIM J, and 84% (16/19) for Flex. Hearing loss was not related to device type (P =.9105) or gender (P =.2169). Older subjects (age ≥65) had worse hearing outcomes than younger subjects after initial device activation (age <65, P =.0262). There was no significant difference in rate of hearing loss over time between older and younger patients (P =.0938). Initial postoperative hearing loss was not associated with the rate of long‐term hearing loss. Conclusions: Long‐term low frequency hearing preservation is possible for CI recipients and is not associated with gender or device type. Rate of hearing loss over time is not dependent on patient age. Early hearing loss after CI does not predict the rate of long‐term hearing loss. Level of Evidence: 3 Laryngoscope, 132:2036–2043, 2022 [ABSTRACT FROM AUTHOR]

This report presents a case study of a patient who resumed bilateral hearing aid use after nearly four years of limited progress and subjective dissatisfaction with a hybrid cochlear implant device. Case study. One patient. The patient's post-operative objective and subjective abilities with bilateral hearing aids were better than with a hybrid cochlear implant and contralateral hearing aid. Although the benefits of combined acoustic and electric hearing have been well-documented, this report presents a solution for those with well-preserved hearing and poor hybrid cochlear implant performance: returning to bilateral hearing aid use. [ABSTRACT FROM AUTHOR]

Objective: Electrocochleography (ECochG) is increasingly being used during cochlear implant (CI) surgery to detect and mitigate insertion-related intracochlear trauma, where a drop in ECochG signal has been shown to correlate with a decline in hearing outcomes. In this study, an ECochG-guided robotics-assisted CI insertion system was developed and characterized that provides controlled and consistent electrode array insertions while monitoring and adapting to real-time ECochG signals. Study Design: Experimental research. Setting: A research laboratory and animal testing facility. Methods: A proof-of-concept benchtop study evaluated the ability of the system to detect simulated ECochG signal changes and robotically adapt the insertion. Additionally, the ECochG-guided insertion system was evaluated in a pilot in vivo sheep study to characterize the signal-to-noise ratio and amplitude of ECochG recordings during robotics-assisted insertions. The system comprises an electrode array insertion drive unit, an extracochlear recording electrode module, and a control console that interfaces with both components and the surgeon. Results: The system exhibited a microvolt signal resolution and a response time <100 milliseconds after signal change detection, indicating that the system can detect changes and respond faster than a human. Additionally, animal results demonstrated that the system was capable of recording ECochG signals with a high signal-to-noise ratio and sufficient amplitude. Conclusion: An ECochG-guided robotics-assisted CI insertion system can detect real-time drops in ECochG signals during electrode array insertions and immediately alter the insertion motion. The system may provide a surgeon the means to monitor and reduce CI insertion–related trauma beyond manual insertion techniques for improved CI hearing outcomes. [ABSTRACT FROM AUTHOR]

Understanding genetic causes of hearing loss can determine the pattern and course of a patient's hearing loss and may also predict outcomes after cochlear implantation. Our goal in this study was to evaluate genetic causes of hearing loss in a large cohort of adults and children with cochlear implants. We performed comprehensive genetic testing on all patients undergoing cochlear implantation. Of the 459 patients included in the study, 128 (28%) had positive genetic testing. In total, 44 genes were identified as causative. The top 5 genes implicated were GJB2 (20, 16%), TMPRSS3 (13, 10%), SLC26A4 (10, 8%), MYO7A (9, 7%), and MT-RNR1 (7, 5%). Pediatric patients had a higher diagnostic rate. This study lays the groundwork for future studies evaluating the relationship between genetic variation and cochlear implant performance. [ABSTRACT FROM AUTHOR]

Acoustic hearing can be preserved after cochlear implant (CI) surgery, allowing for combined electric-acoustic stimulation (EAS) and superior speech understanding compared to electric-only hearing. Among patients who initially retain useful acoustic hearing, 30–40 % experience a delayed hearing loss that occurs 3 or more months after CI activation. Increases in electrode impedances have been associated with delayed loss of residual acoustic hearing, suggesting a possible role of intracochlear inflammation/fibrosis as reported by Scheperle et al. (Hear Res 350:45–57, 2017) and Shaul et al. (Otol Neurotol 40(5):e518–e526, 2019). These studies measured only total impedance. Total impedance consists of a composite of access resistance, which reflects resistance of the intracochlear environment, and polarization impedance, which reflects resistive and capacitive properties of the electrode–electrolyte interface as described by Dymond (IEEE Trans Biomed Eng 23(4):274–280, 1976) and Tykocinski et al. (Otol Neurotol 26(5):948–956, 2005). To explore the role of access and polarization impedance components in loss of residual acoustic hearing, these measures were collected from Nucleus EAS CI users with stable acoustic hearing and subsequent precipitous loss of hearing. For the hearing loss group, total impedance and access resistance increased over time while polarization impedance remained stable. For the stable hearing group, total impedance and access resistance were stable while polarization impedance declined. Increased access resistance rather than polarization impedance appears to drive the increase in total impedances seen with loss of hearing. Moreover, access resistance has been correlated with intracochlear fibrosis/inflammation in animal studies as observed by Xu et al. (Hear Res 105(1–2):1–29, 1997) and Tykocinski et al. (Hear Res 159(1–2):53–68, 2001). These findings thus support intracochlear inflammation as one contributor to loss of acoustic hearing in our EAS CI population. [ABSTRACT FROM AUTHOR]

Objective: Radiation therapy is a mainstay in the treatment of numerous neoplasms. Numerous publications have reported good clinical outcomes for primary radiation therapy for Vestibular Schwannomas (VS). However, there are relatively few pathologic specimens of VSs available to evaluate post‐radiation, which has led to a relative dearth in research on the cellular mechanisms underlying the effects of radiation therapy on VSs. Methods: Here we review the latest literature on the complex biological effects of radiation therapy on these benign tumors—including resistance to oxidative stress, mechanisms of DNA damage repair, alterations in normal growth factor pathways, changes in surrounding vasculature, and alterations in immune responses following radiation. Results: Although VSs are highly radioresistant, radiotherapy is often successful in arresting their growth. Conclusion: By better understanding the mechanisms underlying these effects, we could potentially harness such mechanisms in the future to potentiate the clinical effects of radiotherapy on VSs. Level of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Changes in cochlear implant (CI) design and surgical techniques have enabled the preservation of residual acoustic hearing in the implanted ear. While most Nucleus Hybrid L24 CI users retain significant acoustic hearing years after surgery, 6–17 % experience a complete loss of acoustic hearing (Roland et al. Laryngoscope. 126(1):175-81. (2016), Laryngoscope. 128(8):1939-1945 (2018); Scheperle et al. Hear Res. 350:45-57 (2017)). Electrocochleography (ECoG) enables non-invasive monitoring of peripheral auditory function and may provide insight into the pathophysiology of hearing loss. The ECoG response is evoked using an acoustic stimulus and includes contributions from the hair cells (cochlear microphonic—CM) as well as the auditory nerve (auditory nerve neurophonic—ANN). Seven Hybrid L24 CI users with complete loss of residual hearing months after surgery underwent ECoG measures before and after loss of hearing. While significant reductions in CMs were evident after hearing loss, all participants had measurable CMs despite having no measurable acoustic hearing. None retained measurable ANNs. Given histological data suggesting stable hair cell and neural counts after hearing loss (e.g., Quesnel et al. Hear Res. 333:225-234. (2016)), the loss of ECoG and audiometric hearing may reflect reduced synaptic input. This is consistent with the theory that residual CM responses coupled with little to no ANN responses reflect a "disconnect" between hair cells and auditory nerve fibers (Fontenot et al. Ear Hear. 40(3):577-591. 2019). This "disconnection" may prevent proper encoding of auditory stimulation at higher auditory pathways, leading to a lack of audiometric responses, even in the presence of viable cochlear hair cells. [ABSTRACT FROM AUTHOR]

Background: Petrous apicitis (PA) is a serious infection involving the apical portion of the petrous temporal bone. The classic triad of purulent otorrhea, ipsilateral abducens nerve palsy and retroorbital pain is rarely seen due to early detection and widespread use of antibiotics. Medical management is the primary treatment modality with surgery reserved for cases of recalcitrant petrous apex abscess. Methods and Results: We presented a case of PA with previously untreated otitis media. After multidisciplinary evaluation, the patient was initially treated with intravenous antibiotics followed by drainage of the abscess using a combined transmastoid and middle cranial fossa (MCF) approach. The patient recovered well with no recurrence of the infection based on imaging and symptoms. Discussion: While a variety of different surgical approaches can be used in treatment of PA, we recommend the MCF approach in cases where access to the anterior petrous apex may be challenging via transcanal or transmastoid approach. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to explore the effect of the proneuronal transcription factor neurogenic differentiation 1 (Neurod1, ND1) on Schwann cells (SC) and schwannoma cell proliferation.Methods: Using a variety of transgenic mouse lines, we investigated how expression of Neurod1 effects medulloblastoma (MB) growth, schwannoma tumor progression, vestibular function, and SC cell proliferation. Primary human vestibular schwannoma (VS) cell cultures were transduced with adenoviral vectors expressing Neurod1. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) uptake.Study Design: Basic science investigation.Results: Expression of Neurod1 reduced the growth of slow-growing but not fast-growing MB models. Gene transfer of Neurod1 in human schwannoma cultures significantly reduced cell proliferation in dose-dependent way. Deletion of the neurofibromatosis type 2 (Nf2) tumor-suppressor gene via Cre expression in SCs led to increased intraganglionic SC proliferation and mildly reduced vestibular sensory-evoked potentials (VsEP) responses compared to age-matched wild-type littermates. The effect of Neurod1-induced expression on intraganglionic SC proliferation in animals lacking Nf2 was mild and highly variable. Sciatic nerve axotomy significantly increased SC proliferation in wild-type and Nf2-null animals, and expression of Neurod1 reduced the proliferative capacity of both wild-type and Nf2-null SCs following nerve injury.Conclusion: Expression of Neurod1 reduces slow-growing MB progression and reduces human SC proliferation in primary VS cultures. In a genetic mouse model of schwannomas, we find some effects of Neurod1 expression; however, the high variability indicates that more tightly regulated Neurod1 expression levels that mimic our in vitro data are needed to fully validate Neurod1 effects on schwannoma progression.Level Of Evidence: NA Laryngoscope, 131:E259-E270, 2021. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The use of a short 10-mm/10-electrode cochlear implant to preserve low-frequency residual hearing was investigated. This report describes the 12-month outcomes of this multicenter clinical trial.Study Design: Single-subject design.Methods: Twenty-eight subjects with low-frequency hearing at or better than 60 dB HL at 500 Hz and severe high-frequency hearing loss were implanted with a Nucleus Hybrid S12 implant in their poorer ear. Speech perception in quiet using Consonant-Nucleus-Consonant (CNC) words and sentences in noise using AzBio sentences was collected pre- and postoperatively at 3, 6, and 12 months. Subjective reporting using the Speech, Spatial, and Qualities of Hearing Scale (SSQ) questionnaire was also collected pre- and postoperatively.Results: Functional hearing preservation was accomplished in 96% of subjects. At 3 and 6 months, 86% of the 28 subjects had maintained functional hearing. By 12 months, 23 out of 27 subjects (85%) had maintained functional hearing (one subject with functional hearing at 6 months withdrew from the study prior to the 12-month visit). Speech perception results demonstrated that 81% of the participants on CNC words and 77% with AzBio sentences in noise had significant improvements using their everyday listening condition at 12 months compared to preoperative performance with bilateral hearing aids. Furthermore, preoperative to 12 months postoperative subjective ratings showed significant improvements for the SSQ.Conclusions: This study demonstrates that a high degree of hearing preservation enabling acoustic-electric hearing and improvement in speech understanding in quiet and in noise can be accomplished using a short-electrode 10-mm cochlear implant.Level Of Evidence: 2c Laryngoscope, 130:E548-E558, 2020. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between various electrodiagnostic modalities in acute facial palsy. Setting: Academic tertiary care center. Patients One‐hundred and six patients who presented with traumatic or non‐traumatic acute facial paralysis (House‐Brackmann, HB, grade 6/6) between 2008 and 2017 and underwent acute electrodiagnostic testing. Intervention: Electroneurography (ENoG) using nasolabial fold (NLF) or nasalis muscle (NM) methods, and volitional electromyography (EMG) in all patients. Main outcome measures: Percent degeneration of ipsilateral facial nerve compound muscle action potentials (CMAP) on NLF‐ and NM‐ENoG, presence or absence of muscle unit potentials (MUPs) on EMG. Results: Extent of facial nerve degeneration measured by NLF‐ and NM‐ENoG were highly correlated (r = 0.85, P <.01) on each test and on serial testing. NLF‐ and NM‐ENoG concordantly diagnosed ≥90% degeneration in 44 patients (80%), of whom 32 patients were diagnosed to have 100% degeneration by both methodologies. Absence of MUPs on EMG was 63% sensitive and 92% specific for ≥90% degeneration on ENoG, with a positive predictive value of 90%. For patients with Bell's palsy, percent degeneration on ENoG was also correlated to HB score at 1 year. Surgical decompression resulted in mean HB scores of 2.2 and 3.0 for patients with Bell's palsy and trauma, respectively. Conclusions: NM‐ENoG may be a valid and comparable method to NLF‐ENoG for predicting the recovery of facial nerve function in acute paralysis. Absence of MUPs on EMG is a specific measure of severe degeneration and highly predictive of candidacy for surgical decompression. Level of evidence: Level 3. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long-term audiometric outcomes, sound localization abilities, binaural benefits, and tinnitus assessment of subjects with cochlear implant (CI) after a diagnosis of unilateral severe-to-profound hearing loss.Method: The study group consisted of 60 (mean age 52 years, range 19-84) subjects with profound hearing loss in one ear and normal to near-normal hearing in the other ear who underwent CI. Data analysis included pre- and postoperative Consonant-Nucleus-Consonant (CNC) Word scores, AzBio Sentence scores, pure tone thresholds, sound localization, and Iowa Tinnitus Handicap Questionnaire scores.Results: Preoperative average duration of deafness was 3.69 years (standard deviation 4.31), with an average follow-up time of 37.9 months (range 1-87). CNC and AzBio scores significantly improved (both P < 0.001) postoperatively among the entire cohort, and there was much heterogeneity in outcomes with respect to deafness etiology subgroup analysis. Sound localization abilities tended to improve longitudinally in the entire cohort. Binaural benefits using an adaptive Hearing in Noise Test test showed a significant (P < 0.001) improvement with head shadow effect. Utilizing the Iowa Tinnitus Handicap Questionnaire, there was significant improvement in social, physical, and emotional well-being (P = 0.011), along with hearing abilities (P = 0.001).Conclusions: This case series is the largest cohort of CI SSD subjects to date and systematically analyzes their functional outcomes. Subjects have meaningful improvement in word understanding, and sound localization tends to gradually improve over time. Binaural benefit analysis showed significant improvement with head shadow effect, which likely provides ease of listening.Level Of Evidence: 4 Laryngoscope, 130:1805-1811, 2020. [ABSTRACT FROM AUTHOR]

Since a rapidly increasing number of neurostimulation devices are used clinically to modulate specific neural functions, the impact of electrical stimulation on targeted neural structure and function has become a key issue. In particular, the specific effect of electrical stimulation via a cochlear implant (CI) on inner hair cell (IHC) synapses remains unclear. Importantly, CI candidacy has recently expanded to include patients with partial hearing loss. Unfortunately, some CI recipients experience progressive hearing loss after activation of electrical stimulation. The mechanism(s) accounting for loss of residual hearing following electrical stimulation is unknown. Here normal‐hearing guinea pigs were implanted with customized CIs. Intracochlear electrical stimulation with an intensity equal to or above electrically evoked compound action potential (ECAP) threshold decreased the excitability of auditory nerve. Furthermore, the number of synapses between IHCs and the afferent spiral ganglion neurons (SGNs) also decreased after electrical stimulation with higher intensities. However, no significant change was observed in the packing density and perikaryal area of SGNs as well as the quantity of hair cells. These results carry important implications for use of CIs in patients with residual hearing and for an increasing number of patients treated with other neurostimulation devices. Notably, the results were based on acute electrical stimulation. Considering the complex interaction between CIs and targeted tissues, it is urgent to conduct further research to clarify whether the similar changes could be induced by chronic electrical stimulation. [ABSTRACT FROM AUTHOR]

Is Genetic Testing Indicated in a Pediatric Patient with Unilateral Hearing Loss or Single-Sided Deafness? Pediatric unilateral hearing loss (UHL), defined as hearing loss in one ear and normal hearing in the contralateral ear, can range in severity from mild to profound, with profound UHL referred to as single-sided deafness (SSD). In UHL patients, however, genetic testing should be considered if physical examination or imaging indicate a possible underlying syndrome.[3] A study looking at a large cohort of 1119 patients who underwent comprehensive clinical and genetic testing for hearing loss using targeted genomic enrichment and massively parallel sequencing reported diagnostic rates based on the hearing loss phenotype and ethnicity.[4] A genetic diagnosis was most likely in patients reporting a positive family history or when hearing loss was congenital and symmetric. [Extracted from the article]

Objective: To evaluate the postoperative facial nerve dysfunction, audiometric outcomes, and long-term quality-of-life outcomes of patients with idiopathic recurrent facial nerve paralysis (RFP) after middle cranial fossa (MCF) microsurgical decompression.Methods: Retrospective chart analysis of 11 (mean age 37.0 years, range 5 to 67) patients at an academic tertiary referral center who underwent MCF facial nerve decompression. Data analysis included evaluation of pre- and postoperative House-Brackmann (HB) score, pre- and postoperative pure-tone average (PTA), pre-and postoperative word recognition scores (WRS), and postoperative Facial Clinimetric Evaluation survey.Results: Mean number of preoperative facial paralysis episodes was 3.5 (range 2 to 6), and preoperative HB score was 4.5 (range 1 to 6). Postoperatively, 0 patients had further episodes of facial nerve paralysis at an average of 6.5 years (range 0.1 to 17.6) (P = 0.005), and the average postoperative HB score was 2.1 (range 1 to 3) (P = 0.011). Postoperative audiometry was stably maintained as assessed with PTA and WRS scores.Conclusion: Microsurgical facial nerve decompression for idiopathic RFP may be a reliable therapeutic modality to prophylactically decrease the number of facial nerve paralysis episodes and may also help to improve facial nerve functional status.Level Of Evidence: 4 Laryngoscope, 130:200-205, 2020. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Carcinomas of the temporal bone are rare, and appropriate treatment, staging, and survival data are limited. This study evaluates clinical characteristics and survival rates for patients with temporal bone carcinoma treated with resection at a single tertiary-care institution, with a focus on the outcomes of patients with locally advanced disease including skull base and/or dural invasion.Study Design: Retrospective chart review.Methods: Demographic, tumor-specific, and survival data were collected for patients with primary carcinomas of the external auditory canal with involvement of the temporal bone from 2003 to 2015. All patients were staged according to the modified Pittsburgh system. Kaplan-Meier and logistic regression analysis were used to calculate factor-specific survival outcomes.Results: Sixty-seven patients met inclusion criteria; 85% were male. There were 43 squamous cell carcinomas (64%) and 24 basal cell carcinomas (BCCs) (36%). Tumor stage was 24 (36%) T2, 12 (18%) T3, and 31 (46%) T4 tumors; 53% had recurrent disease. Surgical management included 49 lateral temporal bone resections and 18 subtotal temporal bone resections. Kaplan-Meier analyses revealed more favorable 5-year survival rates associated with BCC histology (P = .01), lateral temporal bone resection compared to subtotal temporal bone resection (P < .01), lack of immunocompromise (P = .04), and absence of perineural/lymphovascular invasion (P = .01). Multivariate regression analysis did not yield statistically significant results.Conclusions: Factors predictive of more favorable survival include lack of immunocompromise, BCC histology, absence of perineural/lymphovascular invasion, and disease extent amenable to lateral temporal bone resection. Dural invasion is not an absolute contraindication to surgery, with a subset of patients surviving >5 years.Level Of Evidence: 3 Laryngoscope, 130:E11-E20, 2020. [ABSTRACT FROM AUTHOR]

Objective: To report current knowledge on the topic of intracochlear fibrosis and the foreign body response following cochlear implantation (CI). Methods: A literature search was performed in PubMed to identify peer‐reviewed articles. Search components included "cochlear implant," "Foreign body response (FBR)," and "fibrosis." Original studies and review articles relevant to the topic were included. Results: Ninety peer‐reviewed articles describing the foreign body response or intracochlear fibrosis following CI were included. Conclusions: Intracochlear fibrosis following CI represents a significant limiting factor for the success of CI users. Several strategies have been employed to mitigate the foreign body response within the cochlea including drug delivery systems and modifications in surgical technique and electrode design. A better understanding of the FBR has the potential to improve CI outcomes and the next generation of cochlear prostheses. [ABSTRACT FROM AUTHOR]

Cochlear implantation has become the standard‐of‐care for adults and children with severe to profound hearing loss. There is growing evidence that qualitative as well as quantitative deficits in the auditory nerve may affect cochlear implant (CI) outcomes. Auditory neuropathy spectrum disorder (ANSD) is characterized by dysfunctional transmission of sound from the cochlea to the brain due to defective synaptic function or neural conduction. In this review, we examine the precise mechanisms of genetic lesions causing ANSD and the effect of these lesions on CI outcomes. Reviewed data show that individuals with lesions that primarily affect the cochlear sensory system and the synapse, which are bypassed by the CI, have optimal CI outcomes. Individuals with lesions that affect the auditory nerve show poor performance with CIs, likely because neural transmission of the electrical signal from the CI is affected. We put forth a nuanced molecular classification of ANSD that has implications for preoperative counseling for patients with this disorder prior to cochlear implantation. We propose that description of ANSD patients should be based on the molecular site of lesion typically derived from genetic evaluation (synaptopathy vs. neuropathy) as this has implications for expected CI outcomes. Improvements in our understanding of genetic site of lesions and their effects on CI function should lead to better CI outcomes, not just for individuals with auditory neuropathy, but all individuals with hearing loss. [ABSTRACT FROM AUTHOR]

Objectives: Cochlear implants provide an effective treatment option for those with severe hearing loss, including those with preserved low frequency hearing. However, certain issues can reduce implant efficacy including intracochlear tissue response and delayed loss of residual acoustic hearing. We describe a mouse model of cochlear implantation with chronic electric stimulation that can be used to study cochlear implant biology and related pathologies. Methods: Twelve normal hearing adult CBA/J mice underwent unilateral cochlear implantation and were evenly divided into one group receiving electric stimulation and one not. Serial impedance and neural response telemetry (NRT) measurements were made to assess implant functionality. Functionality was defined as having at least one electrode with an impedance ≤ 35 kOhms. Mouse cochleae were harvested for histology and 3D x-ray microscopy 21 days post-operatively, or, in case the implant was still functional, at a later time point when the implant failed. A separate experiment measured the hearing preservation rate in 7 adult CBA/J mice undergoing unilateral cochlear implantation with serial auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). Results: Implants maintained functionality for a mean of 35 days in the non-stimulated group and 19.8 days in the stimulated group. Reliable NRT and behavioral responses to electric stimulation were recorded. A robust intracochlear peri-implant tissue response with neo-ossification was seen in all cochleae. Six of seven mice maintained intact low frequency hearing up to 6 weeks following cochlear implantation. Conclusions: We demonstrate the feasibility of cochlear implantation and behaviorally significant electric stimulation in the mouse, with the potential for hearing preservation. This model may be combined with established mouse models of hearing loss and the large genetic and molecular research toolkit unique to the mouse for mechanistic and therapeutic investigations of cochlear implant biology. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The objectives of this study were to evaluate the diagnostic accuracy of constructive interference steady state (CISS) sequencing compared to gadolinium-enhanced T1 (GdT1) magnetic resonance imaging (MRI) to screen for small vestibular schwannomas (VSs), and to assess the overall diagnostic confidence of neuroradiologists in their ability to accurately diagnose or rule out VSs using CISS imaging compared to a GdT1 MRI STUDY DESIGN: Retrospective chart review.Methods: Chart review from 2011 to 2015 was performed for VS/benign cerebellopontine angle tumors. Two blinded, board-certified neuroradiologists each independently reviewed the axial CISS sequence and answered a set of questions that determined their confidence in diagnosis of VS. Next, each neuroradiologist independently reviewed the corresponding GdT1 MRI sequence and completed the same questionnaire.Results: The majority of the lesions were in the lateral internal auditory canal, with eight intralabyrinthine tumors. The overall sensitivity of CISS for both readers was 93.5%. All tumor locations had high sensitivities except for the intralabyrinthine location (62.3%). Four of the eight total intralabyrinthine lesions were missed by at least one reader. Each reader was highly confident in diagnosing VSs with CISS, which approximated that of GdT1 MRI.Conclusions: This study's results showed that CISS examinations for screening of small VS approximated that of GdT1. Neuroradiologists had high sensitivity, perfect specificity, and felt confident in ruling out a VS on CISS sequence while feeling extremely confident in diagnosing one on CISS. Intralabyrinthine lesions and lesions ≤3.0 mm are most at risk for not being detected on CISS examinations.Level Of Evidence: 4 Laryngoscope, 128:2128-2132, 2018. [ABSTRACT FROM AUTHOR]