Noise-induced hearing loss in the contralateral ear during otologic and neurotologic surgeries.

OBJECTIVE: Noise-induced hearing loss in the non-surgical ear during otologic/neurotologic surgery has not been well studied. The purpose of this study was to evaluate changes in hearing that may occur in the contralateral (i.e., non-surgical) ear after various otologic/neurotologic surgeries due to noise generated by drills. We hypothesized that otologic/neurotologic surgeries, longer in duration, would suggest longer drilling times and result in decreased hearing in the contralateral ear as evidenced by a change post-operative pure tone air conduction thresholds when compared to pre-operative thresholds. METHODS: A retrospective chart review at a tertiary referral center. Adult patients (18-75 years old) who underwent otologic/neurotologic surgeries from May 1, 2016 through May 1, 2021 were considered for inclusion. Surgeries included vestibular schwannoma resection (translabyrinthine, middle cranial fossa, or retrosigmoid approaches), endolymphatic sac/shunt and labyrinthectomy for Meniere's disease, and tympanomastoid surgery for middle ear pathology (e.g., cholesteatoma). Patient characteristics obtained through record review included age, sex, surgical procedure, pre-operative and post-operative audiometric thresholds and word recognition scores (WRS) for the contralateral ear, and duration of surgery. RESULTS: No significant differences were observed for change in audiometric thresholds in the contralateral ear for any surgery when considering individual frequencies. Additionally, no significant change in WRS was observed for any surgical approach. CONCLUSIONS: The risk of hearing loss in the non-surgical ear during various otologic/neurotologic surgeries appears to be minimal when measured via routine clinical tests.

Post-operative evaluation of computed tomography imaging following cochlear implantation.

PURPOSE: This study utilized an automated segmentation algorithm to assess the cochlear implant electrode array within the cochlea and investigate its impact on audiologic outcomes as measured by post-operative speech perception scores. Furthermore, manual evaluations of electrode placement were compared to automatic segmentation methods to determine their accuracy in predicting post-operative audiologic outcomes. MATERIALS AND METHODS: This retrospective chart review was conducted at a tertiary care referral center involving adult post-lingually deafened cochlear implant recipients implanted from 2015 to 2019. Patients with appropriate postoperative imaging and speech testing were included. Patients were excluded if non-English speaking, had a cognitive deficit, or a labyrinthine malformation. Automated and manual methods were used to analyze computed tomography (CT) scans and correlate the findings with post-operative speech perception scores and detection of electrode translocation. RESULTS: Among the 47 patients who met inclusion criteria, 15 had electrode translocations confirmed by automatic segmentation methods. Controlling for CI usage and pre-operative AzBio scores, patients with translocation exhibited significantly lower consonant-nucleus consonant (CNC) and AzBio scores at 6-months post-implantation compared to patients with ST insertions. Moreover, the number of translocated electrode contacts was significantly associated with post-operative CNC scores. Manual evaluations of electrode location were predictive but less sensitive to electrode translocations when compared with automated 3D segmentation. CONCLUSIONS: Placement of CI electrode contacts within ST without translocation into SV, leads to improved audiologic outcomes. Manual assessment of electrode placement via temporal bone CT, without 3D reconstruction, provides a less sensitive method to determine electrode placement than automated methods. LEVEL OF EVIDENCE: Level 4. LAY SUMMARY: This study investigated the impact of electrode placement on speech outcomes for cochlear implant recipients. Using advanced imaging techniques, the researchers compared automated and manual methods for evaluating electrode position and examined the relationship between electrode translocation and audiologic outcomes. The findings revealed that proper placement within the cochlea without translocation into inappropriate compartments inside the cochlea improves speech understanding. Manual evaluations were somewhat accurate but less sensitive in detecting translocations compared to automated methods, which offer more precise predictions of patient outcomes. These results contribute to our understanding of factors influencing cochlear implant success and highlight the importance of optimizing electrode placement for improved speech outcomes.

Subfascial dissection and extended temporal muscle detachment for middle fossa approach.

BACKGROUND: The soft tissue dissection for the middle fossa approach requires adequate management of the neuro, vascular, and muscular structures in order to maximize exposure and diminish morbidities. METHODS: An incision anterior to the tragus is performed, extending from the zygomatic process to the superior temporal line. The superior temporal artery is exposed, followed by a subfascial dissection of the frontalis nerve. The temporal muscle is dissected and released from the zygoma. All cranial landmarks are exposed for the 5 × 5 cm temporal fossa craniotomy. CONCLUSION: This novel approach provides a safe and adequate access to perform an extended middle fossa craniotomy.

Characterizing Electrophysiological Response Properties of the Peripheral Auditory System Evoked by Phonemes in Normal and Hearing Impaired Ears.

OBJECTIVE: This study aimed to characterize time and spectral domain characteristics of the phoneme-evoked electrocochleography (ECochG) response and explore potential associations between the ECochG spectral content, word recognition scores (WRSs), residual hearing, and aging in normal and hearing-impaired listeners. DESIGN: This was a prospective study with 25 adult participants. All participants underwent intraoperative ECochG testing and responses were recorded from the round window niche. Participants were divided into two groups based on their preoperative pure tone average: normal/mild sensorineural hearing loss and moderate/moderately-severe sensorineural hearing loss. Target stimuli were a 40 ms /da/ and an 80 ms /ba/ presented in alternating polarity (rarefaction/condensation). Waveform response patterns were analyzed including amplitude, latency, and spectra. Structural similarity index measure (SSIM) was used to determine similarity between the stimulus spectrum and that of the ECochG differential waveform. Correlation analyses were carried out among pure tone average, SSIM, age, and WRS. RESULTS: ECochG alternating waveform morphology evoked by the /da/ stimulus consisted of five prominent peaks labeled N 1 -N 5 . Its spectrum was dominated by the fundamental (F 0 ) frequency. The ECochG alternating response evoked by /ba/ consisted of nine prominent peaks labeled N 1 -N 9 and was also dominated by F 0 . Amplitudes and latencies were not statistically different between groups for both stimuli. Significant positive correlations were found between SSIM and WRS for responses evoked by /da/ (r = 0.56) and responses evoked by /ba/ (r = 0.67). High frequency pure tone average and the /ba/ SSIM were found to have a significant negative correlation (r = -0.58). CONCLUSIONS: Speech-like stimuli have become increasingly utilized in the assessment of auditory function. Here, we provided the groundwork for understanding how commonly employed syllable stimuli are encoded by the peripheral auditory system in regard to temporal and spectral characteristics. Expanding this work to include measurements of central auditory processing in conjunction with cochlear physiology is warranted to further understand the relationship between peripheral and central encoding of speech-like stimuli.

Intraoperative Electrocochleography in Subjects Affected by Vestibular Schwannoma and Ménière's Disease: Comparison of Results.

OBJECTIVES: Histologic reports of temporal bones of ears with vestibular schwannomas (VSs) have indicated findings of endolymphatic hydrops (ELH) in some cases. The main goal of this investigation was to test ears with VSs to determine if they exhibit electrophysiological characteristics similar to those of ears expected to experience ELH. DESIGN: Fifty-three subjects with surgically confirmed VS aged ≥18 and with normal middle ear status were included in this study. In addition, a second group of adult subjects (n = 24) undergoing labyrinthectomy (n = 6) or endolymphatic sac decompression and shunt (ELS) placement (n = 18) for poorly controlled vestibular symptoms associated with Meniere's disease (MD) participated in this research. Intraoperative electrocochleography (ECochG) from the round window was performed using tone burst stimuli. Audiometric testing and word recognition scores (WRS) were performed preoperatively. ECochG amplitudes, cochlear microphonic/auditory nerve neurophonic (ANN) in the form of the "ongoing" response and summation potential, were analyzed and compared between the two groups of subjects. In addition, to evaluate any effect of auditory nerve function, the auditory nerve score was calculated for each subject. Pure-tone averages were obtained using the average air conduction thresholds at 0.5, 1, and 2 kHz while WRS was assessed using Northwestern University Auditory Test No. 6 word lists. RESULTS: In the VS group the average pure-tone averages and WRS were 59.6 dB HL and 44.8%, respectively, while in the MD group they were 52.3 dB HL and 73.8%. ECochG findings in both groups revealed a reduced trend in amplitude of the ongoing response with increased stimulus frequency. The summation potential amplitudes of subjects with VS were found to be less negative than the MD subjects for nearly all test frequencies. Finally, the VS group exhibited poorer amounts of auditory nerve function compared to the MD group. CONCLUSIONS: The current findings suggest cochlear pathology (e.g., hair cell loss) in both groups but do not support the hypothesis that VSs cause ELH.

Relationship Between Electrocochleography, Angular Insertion Depth, and Cochlear Implant Speech Perception Outcomes.

OBJECTIVES: Electrocochleography (ECochG), obtained before the insertion of a cochlear implant (CI) array, provides a measure of residual cochlear function that accounts for a substantial portion of variability in postoperative speech perception outcomes in adults. It is postulated that subsequent surgical factors represent independent sources of variance in outcomes. Prior work has demonstrated a positive correlation between angular insertion depth (AID) of straight arrays and speech perception under the CI-alone condition, with an inverse relationship observed for precurved arrays. The purpose of the present study was to determine the combined effects of ECochG, AID, and array design on speech perception outcomes. DESIGN: Participants were 50 postlingually deafened adult CI recipients who received one of three straight arrays (MED-EL Flex24, MED-EL Flex28, and MED-EL Standard) and two precurved arrays (Cochlear Contour Advance and Advanced Bionics HiFocus Mid-Scala). Residual cochlear function was determined by the intraoperative ECochG total response (TR) measured before array insertion, which is the sum of magnitudes of spectral components in response to tones of different stimulus frequencies across the speech spectrum. The AID was then determined with postoperative imaging. Multiple linear regression was used to predict consonant-nucleus-consonant (CNC) word recognition in the CI-alone condition at 6 months postactivation based on AID, TR, and array design. RESULTS: Forty-one participants received a straight array and nine received a precurved array. The AID of the most apical electrode contact ranged from 341° to 696°. The TR measured by ECochG accounted for 43% of variance in speech perception outcomes (p < 0.001). A regression model predicting CNC word scores with the TR tended to underestimate the performance for precurved arrays and deeply inserted straight arrays, and to overestimate the performance for straight arrays with shallower insertions. When combined in a multivariate linear regression, the TR, AID, and array design accounted for 72% of variability in speech perception outcomes (p < 0.001). CONCLUSIONS: A model of speech perception outcomes that incorporates TR, AID, and array design represents an improvement over a model based on TR alone. The success of this model shows that peripheral factors including cochlear health and electrode placement may play a predominant role in speech perception with CIs.

Early Hearing Detection and Intervention: Timely Diagnosis, Timely Management.

OBJECTIVE: A quality improvement study was completed to assess the impact of three clinical practice changes on the timing of diagnosis and intervention for congenital hearing loss. DESIGN: A retrospective chart review was conducted for 800 infants evaluated for congenital hearing loss before and after implementing three clinical practice changes: the use of Kalman-weighted signal averaging for auditory brainstem response testing, a tone burst-prioritized testing protocol, and expediting scheduling of initial assessment. The impact of middle ear involvement on age at diagnosis and history of neonatal intensive care unit stay on age at treatment was also examined. RESULTS: The use of Kalman-weighted signal averaging for auditory brainstem response testing, a tone burst-prioritized testing protocol, and expedited scheduling of initial assessment each resulted in a decrease of age at diagnosis. Ultimately, the age at initial assessment was the only significant predictor related to decreased timeline for diagnosis. Middle ear pathology significantly increased age at diagnosis, while history of time in the neonatal intensive care unit significantly increased the age at provision of amplification as a treatment for permanent hearing loss. CONCLUSIONS: The technology used for assessment, clinical protocol, and timing of assessment of infants can impact the timeline for diagnosis and treatment of congenital hearing impairment. Given the significant sequelae of delayed or missed diagnosis of hearing loss in infancy, implementing clinical practice changes should be considered at pediatric diagnostic centers.

Intracochlear Electrocochleography: Response Patterns During Cochlear Implantation and Hearing Preservation.

OBJECTIVES: Electrocochleography (ECochG) obtained through a cochlear implant (CI) is increasingly being tested as an intraoperative monitor during implantation with the goal of reducing surgical trauma. Reducing trauma should aid in preserving residual hearing and improve speech perception overall. The purpose of this study was to characterize intracochlear ECochG responses throughout insertion in a range of array types and, when applicable, relate these measures to hearing preservation. The ECochG signal in cochlear implant subjects is complex, consisting of hair cell and neural generators with differing distributions depending on the etiology and history of hearing loss. Consequently, a focus was to observe and characterize response changes as an electrode advances. DESIGN: In 36 human subjects, responses to 90 dB nHL tone bursts were recorded both at the round window (RW) and then through the apical contact of the CI as the array advanced into the cochlea. The specific setup used a sterile clip in the surgical field, attached to the ground of the implant with a software-controlled short to the apical contact. The end of the clip was then connected to standard audiometric recording equipment. The stimuli were 500 Hz tone bursts at 90 dB nHL. Audiometry for cases with intended hearing preservation (12/36 subjects) was correlated with intraoperative recordings. RESULTS: Successful intracochlear recordings were obtained in 28 subjects. For the eight unsuccessful cases, the clip introduced excessive line noise, which saturated the amplifier. Among the successful subjects, the initial intracochlear response was a median 5.8 dB larger than the response at the RW. Throughout insertion, modiolar arrays showed median response drops after stylet removal while in lateral wall arrays the maximal median response magnitude was typically at the deepest insertion depth. Four main patterns of response magnitude were seen: increases > 5 dB (12/28), steady responses within 5 dB (4/28), drops > 5 dB (from the initial response) at shallow insertion depths (< 15 mm deep, 7/28), or drops > 5 dB occurring at deeper depths (5/28). Hearing preservation, defined as < 80 dB threshold at 250 Hz, was successful in 9/12 subjects. In these subjects, an intracochlear loss of response magnitude afforded a prediction model with poor sensitivity and specificity, which improved when phase, latency, and proportion of neural components was considered. The change in hearing thresholds across cases was significantly correlated with various measures of the absolute magnitudes of response, including RW response, starting response, maximal response, and final responses (p's < 0.05, minimum of 0.0001 for the maximal response, r's > 0.57, maximum of 0.80 for the maximal response). CONCLUSIONS: Monitoring the cochlea with intracochlear ECochG during cochlear implantation is feasible, and patterns of response vary by device type. Changes in magnitude alone did not account for hearing preservation rates, but considerations of phase, latency, and neural contribution can help to interpret the changes seen and improve sensitivity and specificity. The correlation between the absolute magnitude obtained either before or during insertion of the ECochG and the hearing threshold changes suggest that cochlear health, which varies by subject, plays an important role.

Residual Cochlear Function in Adults and Children Receiving Cochlear Implants: Correlations With Speech Perception Outcomes.

OBJECTIVES: Variability in speech perception outcomes with cochlear implants remains largely unexplained. Recently, electrocochleography, or measurements of cochlear potentials in response to sound, has been used to assess residual cochlear function at the time of implantation. Our objective was to characterize the potentials recorded preimplantation in subjects of all ages, and evaluate the relationship between the responses, including a subjective estimate of neural activity, and speech perception outcomes. DESIGN: Electrocochleography was recorded in a prospective cohort of 284 candidates for cochlear implant at University of North Carolina (10 months to 88 years of ages). Measurement of residual cochlear function called the "total response" (TR), which is the sum of magnitudes of spectral components in response to tones of different stimulus frequencies, was obtained for each subject. The TR was then related to results on age-appropriate monosyllabic word score tests presented in quiet. In addition to the TR, the electrocochleography results were also assessed for neural activity in the forms of the compound action potential and auditory nerve neurophonic. RESULTS: The TR magnitude ranged from a barely detectable response of about 0.02 µV to more than 100 µV. In adults (18 to 79 years old), the TR accounted for 46% of variability in speech perception outcome by linear regression (r = 0.46; p < 0.001). In children between 6 and 17 years old, the variability accounted for was 36% (p < 0.001). In younger children, the TR accounted for less of the variability, 15% (p = 0.012). Subjects over 80 years old tended to perform worse for a given TR than younger adults at the 6-month testing interval. The subjectively assessed neural activity did not increase the information compared with the TR alone, which is primarily composed of the cochlear microphonic produced by hair cells. CONCLUSIONS: The status of the auditory periphery, particularly of hair cells rather than neural activity, accounts for a large fraction of variability in speech perception outcomes in adults and older children. In younger children, the relationship is weaker, and the elderly differ from other adults. This simple measurement can be applied with high throughput so that peripheral status can be assessed to help manage patient expectations, create individually-tailored treatment plans, and identify subjects performing below expectations based on residual cochlear function.

Response Changes During Insertion of a Cochlear Implant Using Extracochlear Electrocochleography.

OBJECTIVES: Electrocochleography is increasingly being utilized as an intraoperative monitor of cochlear function during cochlear implantation (CI). Intracochlear recordings from the advancing electrode can be obtained through the device by on-board capabilities. However, such recordings may not be ideal as a monitor because the recording electrode moves in relation to the neural and hair cell generators producing the responses. The purposes of this study were to compare two extracochlear recording locations in terms of signal strength and feasibility as intraoperative monitoring sites and to characterize changes in cochlear physiology during CI insertion. DESIGN: In 83 human subjects, responses to 90 dB nHL tone bursts were recorded both at the round window (RW) and then at an extracochlear position-either adjacent to the stapes or on the promontory just superior to the RW. Recording from the fixed, extracochlear position continued during insertion of the CI in 63 cases. RESULTS: Before CI insertion, responses to low-frequency tones at the RW were roughly 6 dB larger than when recording at either extracochlear site, but the two extracochlear sites did not differ from one another. During CI insertion, response losses from the promontory or adjacent to the stapes stayed within 5 dB in ≈61% (38/63) of cases, presumably indicating atraumatic insertions. Among responses which dropped more than 5 dB at any time during CI insertion, 12 subjects showed no response recovery, while in 13, the drop was followed by partial or complete response recovery by the end of CI insertion. In cases with recovery, the drop in response occurred relatively early (<15 mm insertion) compared to those where there was no recovery. Changes in response phase during the insertion occurred in some cases; these may indicate a change in the distributions of generators contributing to the response. CONCLUSIONS: Monitoring the electrocochleography during CI insertion from an extracochlear site reveals insertions that are potentially atraumatic, show interaction with cochlear structures followed by response recovery, or show interactions such that response losses persist to the end of recording.

Is "no response" on diagnostic auditory brainstem response testing an indication for cochlear implantation in children?

OBJECTIVES: To compare the results of a "no response" (NR) result on auditory brainstem response (ABR) testing with those of behavioral pure-tone audiometry and ultimate clinical tracking to cochlear implantation (CI). DESIGN: Retrospective review of pediatric patients who underwent multifrequency ABR testing in a 5 year span. Total of 1143 pediatric patients underwent ABR testing during the study period and 105 (9.2%) were identified with bilateral NR based on absent responses to both click and tone burst stimuli. For the children with NR, various clinical parameters were evaluated as these children progressed through the CI evaluation process. Children were grouped based on whether they underwent ABRs for diagnostic or for confirmatory purposes. RESULTS: Of the 105 children who met inclusion criteria, 94 had sufficient follow-up to be included in this analysis. Ninety-one (96.8%) of 94 children with bilateral NR ABRs were ultimately recommended for and received a CI. Three (3.2%) children were not recommended for implantation based on the presence of multiple comorbidities rather than auditory factors. None of the children (0%) had enough usable residual hearing to preclude CI. For those who had diagnostic ABRs, the average time at ABR testing was 5.4 months (SD 6.2, range 1-36) and the average time from ABR to CI was 10.78 months (SD 5.0, range 3-38). CONCLUSIONS: CI should tentatively be recommended for children with a bilateral NR result with multifrequency ABR, assuming confirmatory results with behavioral audiometric testing. Amplification trials, counseling, and auditory-based intervention therapy should commence but not delay surgical intervention, as it does not appear to change the eventual clinical course. Children not appropriate for this "fast-tracking" to implantation might include those with significant comorbidities, auditory neuropathy spectrum disorder, and unreliable or poorly correlated results on behavioral audiometric testing.

Intraoperative round window electrocochleography and speech perception outcomes in pediatric cochlear implant recipients.

OBJECTIVES: The goal was to measure the magnitude of cochlear responses to sound in pediatric cochlear implant recipients at the time of implantation and to correlate this magnitude with subsequent speech perception outcomes. DESIGN: A longitudinal cohort study of pediatric cochlear implant recipients was undertaken. Intraoperative electrocochleographic (ECoG) recordings were obtained from the round window in response to a frequency series at 90 dB nHL in 77 children totaling 89 ears (12 were second side surgeries) just before device insertion. The increase in intraoperative time was approximately 10 min. An ECoG "total response" metric was derived from the summed magnitudes of significant responses to the first, second, and third harmonics across a series of frequencies. A subset of these children reached at least 9 months of implant use and were old enough for the phonetically balanced kindergarten (PB-k) word test to be administered (n = 26 subjects and 28 ears). PB-k scores were compared to the ECoG total response and other biologic and audiologic variables using univariate and multiple linear regression analyses. RESULTS: ECoG responses were measurable in almost all ears (87 of 89). The range of ECoG total response covered about 60 dB (from ~0.05 to 50 µV). Analyzing individual ECoG recordings in bilaterally implanted children revealed poor concordance between the measured response in the first versus second ear implanted (r = 0.21; p = 0.13; n = 12). In a univariate linear regression, the ECoG total response was significantly correlated with PB-k scores in the subset of 26 subjects who were able to be tested and accounted for 32% of the variance (p = 0.002, n = 28). Preoperative pure-tone average (PTA) accounted for slightly more of the variance (r = 0.37, p = 0.001). However, ECoG total response and PTA were significantly but only weakly correlated (r = 0.14, p = 0.001). Other significant predictors of speech performance included hearing stability (stable versus progressive) and age at testing (22 and 16% of the variance, respectively). In multivariate analyses with these four factors, the ECoG accounted for the most weight (ß = 0.36), followed by PTA (ß = 0.26). In a hierarchical multiple regression analysis, the most parsimonious models that best predicted speech perception outcomes included three variables: ECoG total response, and any two of preoperative PTA, age at testing, or hearing stability. The various three factor models each predicted approximately 50% of the variance in word scores. Without the ECoG total response, the other three factors predicted 36% of variance. CONCLUSIONS: Intraoperative round window ECoG recordings are reliably and easily obtained in pediatric cochlear implant recipients. The ECoG total response is significantly correlated with speech perception outcomes in pediatric implant recipients and can account for a comparable or greater proportion of variance in speech perception than other bio-audiologic factors. Intraoperative recordings can potentially provide useful prognostic information about acquisition of open set speech perception in implanted children.

The Relationship Between Cochleovestibular Orientation, Age, and Sensorineural Hearing Loss: Implications for Cochlear Implantation.

OBJECTIVES: To determine if spatial orientation of the cochlea within the temporal bone is related to age or sensorineural hearing loss (SNHL) and describe the implications for cochlear implantation. METHODS: Five angles of cochlear orientation were determined from computed tomography (CT) imaging of the temporal bones in adults with (n = 55) and without (n = 27) sensorineural hearing loss (SNHL) and children with (n = 45) and without (n = 12) SNHL: facial recess versus basal turn, posterior semicircular canal versus basal turn, round window versus basal turn (axial view), round window versus basal turn (coronal view), and the cochlear axis versus the mastoid facial nerve. RESULTS: All angles showed substantial variation between subjects and between ears. The angles between the round window and basal turn (coronal view) and the posterior semicircular canal and basal turn were significantly correlated with age for all subjects with SNHL (r = 0.22, P = .002 and r = 0.15, P = .03, respectively). Patients with SNHL had significantly more acute angles (46.6° vs 55.8°) between the round window versus basal turn (axial orientation) compared to controls (P < .001). CONCLUSIONS: Cochlear orientation within the temporal bone changes with age and the degree of SNHL. These results suggest that the approach to the round window for electrode insertion might differ between children and adults.

Distinguishing hair cell from neural potentials recorded at the round window.

Almost all patients who receive cochlear implants have some acoustic hearing prior to surgery. Electrocochleography (ECoG), or electrophysiological measures of cochlear response to sound, can identify remaining auditory nerve activity that is the basis for this residual hearing and can record potentials from hair cells that are no longer functionally connected to nerve fibers. The ECoG signal is therefore complex, being composed of both hair cell and neural signals. To identify signatures of different sources in the recorded potentials, we collected ECoG data across frequency and intensity from the round window of gerbils before and after treatment with kainic acid, a neurotoxin. Distortions in the recorded waveforms were produced by different sources over different ranges of frequency and intensity. In response to tones at low frequencies and low-to-moderate intensities, the major source of distortion was from neural phase-locking that was sensitive to kainic acid. At high intensities at all frequencies, the distortion was not sensitive to kainic acid and was consistent with asymmetric saturation of the hair cell transducer current. In addition to loss of phase-locking, changes in the envelope after kainic acid treatment indicate that sustained neural firing combines with receptor potentials from hair cells to produce the envelope of the response to tones. These results provide baseline data to interpret comparable recordings from human cochlear implant recipients.

Investigating Deferral Rates in Cochlear Implantation: How Often Do Candidates Defer and Why?

OBJECTIVE: Evaluate the rate at which cochlear implant (CI) candidates decline surgery and identify associated factors. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Four hundred ninety-three CI candidates from July 1989 to December 2020 with complete demographic and socioeconomic data. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Age, sex, race, marital and employment status, median household income percentile, distance-to-CI-center, and residence in a medically underserved county. RESULTS: Of the 493 CI candidates included, 80 patients (16.2%) declined surgery. Based on chart checking, the most common reason patients did not receive the implant was due to loss of follow-up (38%). African American patients were 73% less likely to undergo implantation compared with White patients (odds ratio [OR], 0.27 [0.11-0.68]; p = 0.005). Asian patients were 95% less likely to undergo implantation (OR, 0.05 [0.009-0.25]; p = 0.0003) compared with White patients. For every 1-year age increase, patients were 4% less likely to undergo implantation (OR, 0.96 [0.94-0.98]; p < 0.0001) and for every 10-year age increase, the patients were 33% less likely. Compared with their single counterparts, married patients were more likely to undergo implantation (OR, 1.87 [1.12-3.15]; p = 0.02). No differences were observed when comparing implanted and nonimplanted CI candidates in sex, employment status, distance-to-CI-center, or median family income percentile. A χ2 test of independence showed no association between receiving CIs and living in medically underserved counties ( χ2 = 2; N = 493; 0.3891; p = 0.53). CONCLUSIONS: Not infrequently, CI candidates decline surgery. Although demographic factors (race, age, and marital status) were associated with the cochlear implantation decision, socioeconomic factors (median family income and residence in a medically underserved community) were not. Perhaps cultural components of a patient's race have a larger impact on whether or not the patients get implanted.

Identifying Tumor Microenvironment Biomarkers in Adherent and Cystic Vestibular Schwannomas.

OBJECTIVE: A subset of vestibular schwannomas (VSs), including cystic tumors, have higher postoperative morbidity because of the presence of adhesions between the tumor, facial nerve (FN), and brainstem. We identify tumor microenvironment (TME) biomarkers to better classify these tumors and predict the degree of tumor adherence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary skull base referral center. METHODS: Adult patients with cystic and solid VS matched in tumor size who underwent surgical resection were included. Expressions of seven biomarkers of extracellular matrix remodeling and tumor immune response were quantified via immunohistochemistry. The distribution of CD45+ immune cells was evaluated in intratumoral and perivascular compartments. The degree of tumor adherence was categorized as none, adherent to FN, or adherent to both FN and brainstem. RESULTS: Twenty-eight patients were included. Cystic VSs were significantly more adherent than solid VSs ( p = 0.02). Patients with adherent VS had shorter duration of symptoms and were more likely to undergo subtotal resection. In solid tumors, matrix metalloproteinase (MMP)-2 expression ( p = 0.02) and CD163+ macrophage infiltration ( p = 0.007) were correlated with tumor size. Linear discriminant analyses (LDAs) demonstrated MMP-2, MMP-14, CD80, CD163, and perivascular CD45 to be individually predictive of the degree of tumor adherence (all p < 0.05), with perivascular CD45 being the best independent predictor ( p = 0.005). An LDA model including these biomarkers demonstrated 100% accurate discrimination of all three levels of tumor adherence ( p = 0.04). CONCLUSIONS: Adherent VS have a distinct proinflammatory TME characterized by elevated MMP expression, enrichment of tumor-associated macrophages, and perivascular immune cell infiltration.

Matrix metalloproteinase 9: An emerging biomarker for classification of adherent vestibular schwannoma.

Background: The progression of vestibular schwannoma (VS) is intricately linked with interactions between schwannoma cells and the extracellular matrix. Surgical resection of VS is associated with substantial risks as tumors are adherent to the brainstem and cranial nerves. We evaluate the role of matrix metalloproteinase 9 (MMP9) in VS and explore its potential as a biomarker to classify adherent VS. Methods: Transcriptomic analysis of a murine schwannoma allograft model and immunohistochemical analysis of 17 human VS were performed. MMP9 abundance was assessed in mouse and human schwannoma cell lines. Transwell studies were performed to evaluate the effect of MMP9 on schwannoma invasion in vitro. Plasma biomarkers were identified from a multiplexed proteomic analysis in 45 prospective VS patients and validated in primary culture. The therapeutic efficacy of MMP9 inhibition was evaluated in a mouse schwannoma model. Results: MMP9 was the most highly upregulated protease in mouse schwannomas and was significantly enriched in adherent VS, particularly around tumor vasculature. High levels of MMP9 were found in plasma of patients with adherent VS. MMP9 outperformed clinical and radiographic variables to classify adherent VS with outstanding discriminatory ability. Human schwannoma cells secreted MMP9 in response to TNF-α which promoted cellular invasion and adhesion protein expression in vitro. Lastly, MMP9 inhibition decreased mouse schwannoma growth in vivo. Conclusions: We identify MMP9 as a preoperative biomarker to classify adherent VS. MMP9 may represent a new therapeutic target in adherent VS associated with poor surgical outcomes that lack other viable treatment options.

A nomogram to predict long-term facial nerve function after vestibular schwannoma resection: a contemporary multi-institutional study.

OBJECTIVE: The objective of this study was to develop a nomogram to predict long-term facial nerve (FN) function after vestibular schwannoma (VS) resection. METHODS: A retrospective cohort study of two tertiary academic skull base referral centers was performed. Consecutive adults > 18 years of age with sporadic unilateral VS who underwent resection between September 2016 and May 2021 were included. FN function in the immediate postoperative period and at the most recent evaluation was measured. RESULTS: A total of 306 patients (mean age 49 years, 63% female) were included, with a mean follow-up of 18 months. The mean maximum tumor diameter was 19 mm (range 1-50 mm), and 80 (26.1%) tumors were > 25 mm. Overall, 85% of patients showed good immediate postoperative FN function (House-Brackmann [HB] grade I or II) and 89% maintained good FN function at > 12 months of follow-up. An intraoperative FN electromyographic (EMG) response ≥ 100 µV to 0.05 mA of stimulation (OR 18.6, p < 0.001) was the strongest predictor of good HB grade in the immediate postoperative period. EMG response ≥ 100 µV (OR 5.70, p < 0.001), tumor size ≤ 25 mm (OR 3.09, p < 0.05), and better immediate postoperative HB grade (OR 1.48, p = 0.005) predicted good long-term FN function on multivariable analysis. A point-of-care nomogram based on these data predicted long-term FN function with a sensitivity of 89% and specificity of 69%. CONCLUSIONS: Better immediate postoperative HB grade, intraoperative FN EMG response ≥ 100 µV, and tumor size ≤ 25 mm strongly predicted good long-term FN function after VS resection. A point-of-care nomogram based on these variables could serve as a useful tool for postoperative counseling and prognosis of long-term FN recovery.

Tumor biomechanical stiffness by magnetic resonance elastography predicts surgical outcomes and identifies biomarkers in vestibular schwannoma and meningioma.

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.

Comparison of Postoperative Outcomes in Cystic Versus Solid Vestibular Schwannoma in a Multi-institutional Cohort.

OBJECTIVE: Cystic vestibular schwannomas (cVSs) have more variable and less favorable clinical outcomes after microsurgical resection compared with solid VS (sVS). This study compares the preoperative presentation and postoperative outcomes between cVS and sVS. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary skull base referral centers. METHODS: Consecutive adult patients who underwent VS resection from 2016 to 2021 were included. Univariate and multivariate analyses compared differences in baseline symptoms and postoperative outcomes between cVS and sVS. RESULTS: There were a total of 315 patients (64% female; mean age, 54 yrs) and 46 (15%) were cystic. cVS were significantly larger than sVS (maximum diameter, 28 vs. 18 mm, p < 0.001) and had higher rates of dysphagia and dysphonia preoperatively (p < 0.02). cVSs were more likely to undergo translabyrinthine resection (76 vs. 50%, p = 0.001) and have a higher rate of subtotal resection (STR) compared with sVS (30 vs. 13%, p = 0.003). At latest follow-up, fewer cVS achieved good facial nerve (FN) outcome (House-Brackmann [HB] I/II) (80 vs. 90%, p = 0.048). Subanalysis of cVS and sVS matched in tumor size, and surgical approach did not show differences in the rate of STR or FN outcomes (HB I/II, 82 vs. 78%, p = 0.79). CONCLUSION: In this large multi-institutional series, cVSs represent a distinct entity and are characterized by larger tumor size and higher incidence of atypical symptoms. Although cVSs were more likely to undergo STR and portend worse FN outcomes than sVSs, this may be due to their larger tumor size rather than the presence of the cystic component.