Four-Point Impedance: A Potential Biomarker for Residual Hearing After Cochlear Implantation.

INTRODUCTION: Preservation of residual hearing after cochlear implantation allows for electroacoustic stimulation, which leads to better music appreciation, noise localization, and speech comprehension in noisy environments. Real-time intraoperative electrocochleography (rt-ECochG) monitoring has shown promise in improving residual hearing rates. Four-point impedance (4PI) is being explored as a potential biomarker in cochlear implantation that has been associated with fibrotic tissue response, hearing loss, and dizziness. In this study, we explore whether monitoring both rt-ECochG intraoperatively and postoperative 4PI improves predictions of the preservation of residual hearing. METHODS: This was a prospective cohort study. Adults with residual acoustic hearing underwent cochlear implantation with intraoperative intracochlear electrocochleography (ECochG) monitoring. The surgeon responded to a drop in ECochG signal amplitude of greater than 30% by a standardized manipulation of the electrode with the aim of restoring the ECochG. At the end of the procedure, the ECochG signal was categorized as being maintained or having dropped more than 30%. 4PI was measured on 1 day, 1 week, and 1 and 3 months after cochlear implantation. Residual hearing was measured by routine pure-tone audiogram at 3 months postoperatively. The ECochG category and 4PI impedance values were entered as factors in a multiple linear regression predicting the protection of residual hearing. RESULTS: Twenty-six patients were recruited. Rt-ECochG significantly predicted residual hearing at 3 months (t test; mean difference, 37.7%; p = 0.002). Inclusion of both 1-day or 3-month 4PI in a multiple linear regression with rt-ECochG markedly improved upon correlations with residual hearing compared with the rt-ECochG-only model (rt-ECochG and 1-d 4PI model, R2 = 0.67; rt-ECochG and 3-mo 4PI model, R2 = 0.72; rt-ECochG-only model, R2 = 0.33). CONCLUSIONS: Both rt-ECochG and 4PI predict preservation of residual hearing after cochlear implantation. These findings suggest that the biological response of the cochlea to implantation, as reflected in 4PI, is an important determinant of residual hearing, independent of the acute effects on hearing during implant surgery seen with rt-ECochG. We speculate that 4PI relates to inflammation 1 day after implantation and fibrosis at 3 months.

Intra-cochlear Flushing Reduces Tissue Response to Cochlear Implantation.

INTRODUCTION: Intraoperative trauma leading to bleeding during cochlear implantation negatively impacts residual hearing of cochlear implant recipients. There are no clinical protocols for the removal of blood during implantation, to reduce the consequential effects such as inflammation and fibrosis which adversely affect cochlear health and residual hearing. This preclinical study investigated the implementation of an intra-cochlear flushing protocol for the removal of blood. METHODS: Three groups of guinea pigs were studied for 28 days after cochlear implantation; cochlear implant-only (control group); cochlear implant with blood injected into the cochlea (blood group); and cochlear implant, blood injection, and flushing of the blood from the cochlea intraoperatively (flush group). Auditory brainstem responses (ABRs) in addition to tissue response volumes were analyzed and compared between groups. RESULTS: After implantation, the blood group exhibited the highest ABR thresholds when compared to the control and flush group, particularly in the high frequencies. On the final day, the control and blood group had similar ABR thresholds across all frequencies tested, whereas the flush group had the lowest thresholds, significantly lower at 24 kHz than the blood and control group. Analysis of the tissue response showed the flush group had significantly lower tissue responses in the basal half of the array when compared with the blood and control group. CONCLUSIONS: Flushing intra-cochlear blood during surgery resulted in better auditory function and reduced subsequent fibrosis in the basal region of the cochlea. This finding prompts the implementation of a flushing protocol in clinical cochlear implantation. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1410-1416, 2024.

Intraoperative Measured Electrocochleography and Fluoroscopy Video to Detect Cochlea Trauma.

HYPOTHESIS: Gross electrode movements detected with intraoperative, real-time X-ray fluoroscopy will correlate with fluctuations in cochlear output, as measured with intraoperative electrocochleography (ECochG). BACKGROUND: Indications for cochlear implantation (CI) are expanding to include patients with residual hearing; however, implant recipients often lose residual hearing after CI. The objective of this study was to identify probable traumatic events during implantation by combining electrophysiological monitoring of cochlear function with simultaneous X-ray monitoring. The surgical timing of these apparently traumatic events was then investigated. METHODS: For 19 adult patients (21 surgeries, 2 bilateral), the ECochG responses were measured during implantation of a cochlear nucleus slim modiolar electrode (CI532/CI632, Cochlear Ltd Australia Nucleus slim modiolar). Simultaneous fluoroscopy was performed, as well as a postoperative cone-beam computed tomography (CT) scan. For all patients, pre- and postoperative audiograms were recorded up to 1 year after surgery to record the loss of residual hearing. RESULTS: Electrode insertions for 21 surgeries were successfully monitored. A drop in ECochG response was significantly correlated with reduced hearing preservation compared with patients with preserved responses throughout. Drops in the ECochG response were measured to occur during insertion, because of movement of the array after insertion was complete, including while sealing of the electrode array at the round window or coiling of the array lead within the mastoid cavity. In some patients, a reduction in cochlear output, resulting in poor ECochG response, was inferred to occur before the beginning of implantation. CONCLUSION: The combination of perioperative ECochG measurements, microscope video, fluoroscopy, and postoperative CT scan may inform on what causes the loss of residual hearing after implantation. These findings will be used to improve the surgical procedure in future.

Using Four-Point Impedance to Detect and Locate Blood during Cochlear Implantation.

Biosensing technologies are emerging as an important consideration when designing implantable medical devices. For cochlear implants, biosensors may help preserve the natural hearing a patient has prior to implantation by detecting blood in the cochlea during insertion. If blood enters the cochlea, it creates a hostile environment leading to further hearing loss and reduced device function. Here we present four-point impedance, measured directly from a commercial cochlear implant, as a biosensor for real-time detection of blood in the cochlea. The four-point impedance of different concentrations of whole blood in saline were measured using the impedance-measuring capabilities of a cochlear implant with a square-wave stimulation. Impedance derived from a cochlear implant succeeded in differentiating concentrations of blood in saline with results from a sensitivity analysis showing the lowest concentration the system could detect was between 12 % to 21 % of whole blood. In a subsequent in-vitro study, continuous four-point impedance was measured from a cochlear implant while it was inserted into a 3D printed cochlear model, followed by an injection of blood to emulate surgical events. These results demonstrated four-point impedance from a cochlear implant can instantaneously detect the addition of blood within the cochlea and localize it along the electrode array. The adaptation of a biosensing tool using a cochlear implant provides more information that can be relayed to the surgeon intraoperatively to potentially enhance hearing outcomes with the implant.Clinical Relevance - Using the cochlear implant itself to detect intra-cochlear bleeding may open therapeutic avenues to prevent further hearing loss.

Four-Point Impedance and Utricular Dysfunction Is Associated with Postoperative Dizziness after Cochlear Implantation.

INTRODUCTION: Postimplantation dizziness is common, affecting approximately 50% of patients. Theories for dizziness include utricular inflammation, endolymphatic hydrops, and loss of perilymph. Four-point impedance (4PI) is a novel impedance measurement in cochlear implantation that shows potential to predict hearing loss, inflammation, and fibrotic tissue response. Here, we associate 4PI with dizziness after implantation and explore the link with utricular function. METHODS: Subjective visual vertical (SVV) as a measure of utricular function was recorded preoperatively as a baseline. 4PI was measured immediately postinsertion. Ongoing follow-up was performed at 1 day, 1 week, and 1 month, postoperatively. At each follow-up, 4PI, SVV, and the patients' subjective experience of dizziness were assessed. DISCUSSION: Thirty-eight adults were recruited. One-day 4PI was significantly higher in patients dizzy within the next week (254 Ω vs 171 Ω, p = 0.015). The optimum threshold on receiver operating characteristic curve was 190 Ω, above which patients had 10 times greater odds of developing dizziness (Fisher exact test, OR = 9.95, p = 0.0092). This suggests that 4PI varies with changes in the intracochlear environment resulting in dizziness, such as inflammation or hydrops. SVV significantly deviated away from the operated ear at 1 day (fixed effect estimate = 2.6°, p ≤ 0.0001) and 1 week (fixed effect estimate 2.7°, p ≤ 0.001). CONCLUSION: One-day 4PI is a potentially useful marker for detecting postoperative dizziness after cochlear implantation. Of the current theories for postoperative dizziness, inflammation might explain the findings seen here, as would changes in hydrostatic pressure. Future research should focus on detecting and exploring these labyrinthine changes in further detail.

Speech-in-noise performance in objectively determined cochlear implant maps, including the effect of cognitive state.

OBJECTIVE: Cochlear Implant (CI) programming based on subjective psychophysical fine-tuning of loudness scaling involves active participation and cognitive skills and thus may not be appropriate for difficult-to-condition populations. The electrically evoked stapedial reflex threshold (eSRT) is an objective measure that is suggested to provide clinical benefit to CI programming. This study aimed to compare speech reception outcomes between subjective and eSRT objectively determined CI maps for adult MED-EL recipients. The effect of cognitive skills on these skills was further assessed. METHODS: Twenty-seven post lingually hearing-impaired MED-EL CI recipients were recruited, 6 with mild cognitive impairment (MCI- 4 male, 79 years ± 5), 21 with normal cognitive function (5 male, 63 years ± 12). Two MAPs were generated: a subjective MAP and an objective MAP in which eSRTs determined maximum comfortable levels (M-Levels). Participants were randomly divided into two groups. Group A trialled the objective MAP for two weeks before returning for outcome assessment. During the following two weeks, Group A trialled the subjective MAP before returning for outcome assessment. Group B trialled MAPs in reverse. Outcome measures included the Hearing Implant Sound Quality Index (HISQUI), Consonant-Nucleus-Consonant (CNC) word test, and Bamford-Kowal-Bench Speech-in-Noise (BKB-SIN) test. RESULTS: eSRT based MAPS were obtained in 23 of the participants. A strong relationship was demonstrated between global charge between eSRT-based and psychophysical-based M-Levels (r = 0.89, p < .001). The Montreal Cognitive Assessment for the Hearing Impaired (MoCA-HI) testing identified 6 CI recipients with MCI (MoCA-HI total score ≤23). The MCI group was older (63, 79 years), but were not otherwise different in sex, duration of hearing loss or duration of CI use. For all patients, no significant differences were found for sound quality or speech in quiet scores between eSRT-based and psychophysical-based MAPs. However, psychophysically determined MAPs showed significantly better speech-in-noise reception (6.74 vs 8.20-dB SNR, p = .34). MoCA-HI scores showed a significant, moderate negative correlation with BKB SIN for both MAP approaches (Kendall's Tau B, p = .015 and p = .008), with no effect on the difference between MAP approaches. CONCLUSION: Results indicate eSRT-based methods provide poorer outcomes than psychophysical-based method. While speech-in-noise reception is correlated with MoCA-HI score, this affected both behaviourally and objectively determined MAPs. The results suggest fair confidence in the eSRT-based method as a guide for setting M-Level for difficult-to-condition CI populations in simple listening conditions.

Characteristics of the Summating Potential Measured Across a Cochlear Implant Array as an Indicator of Cochlear Function.

OBJECTIVES: The underlying state of cochlear and neural tissue function is known to affect postoperative speech perception following cochlear implantation. The ability to assess these tissues in patients can be performed using intracochlear electrocochleography (IC ECochG). One component of ECochG is the summating potential (SP) that appears to be generated by multiple cochlear tissues. Its qualities may be able to detect the presence of functional inner hair cells, but evidence for this is limited in human cochleae. This study aimed to examine the IC SP characteristics in cochlear implantation recipients, its relationship to preoperative speech perception and audiometric thresholds, and to other IC ECochG components. DESIGN: This is a retrospective analysis of 113 patients' IC ECochG recordings across the array in response to a 500 Hz tone burst stimulus. Responses to condensation and rarefaction stimuli were then subtracted from one another to emphasize the cochlear microphonic and added to one another to emphasize the SP, auditory nerve neurophonic, and compound action potential. Patients were grouped based on their maximum SP deflection being large and positive (+SP), large and negative (-SP), or minimal (0 SP) to further investigate these relationships. RESULTS: Patients in the +SP group had better preoperative speech perception (mean consonant-vowel-consonant phoneme score 46%) compared to the -SP and 0 SP groups (consonant-vowel-consonant phoneme scores 34% and 36%, respectively, difference to +SP: p < 0.05). Audiometric thresholds were lowest for +SP (mean pure-tone average 50 dB HL), then -SP (65 dB HL), and highest for 0 SP patients (70 dB HL), but there was not a statistical significance between +SP and -SP groups ( p > 0.1). There were also distinct differences between SP groups in the qualities of their other ECochG components. These included the +SP patients having larger cochlear microphonic maximum amplitude, more apical SP peak electrode locations, and a more spatially specific SP magnitude growth pattern across the array. CONCLUSIONS: Patients with large positive SP deflection in IC ECochG have preoperatively better speech perception and lower audiometric thresholds than those without. Patterns in other ECochG components suggest its positive deflection may be an indicator of cochlear function.

Electrocochleographic Patterns Predicting Increased Impedances and Hearing Loss after Cochlear Implantation.

OBJECTIVES: Different patterns of electrocochleographic responses along the electrode array after insertion of the cochlear implant electrode array have been described. However, the implications of these patterns remain unclear. Therefore, the aim of the study was to correlate different peri- and postoperative electrocochleographic patterns with four-point impedance measurements and preservation of residual hearing. DESIGN: Thirty-nine subjects with residual low-frequency hearing which were implanted with a slim-straight electrode array could prospectively be included. Intracochlear electrocochleographic recordings and four-point impedance measurements along the 22 electrodes of the array (EL, most apical EL22) were conducted immediately after complete insertion and 3 months after surgery. Hearing preservation was assessed after 3 months. RESULTS: In perioperative electrocochleographic recordings, 22 subjects (56%) showed the largest amplitude around the tip of the electrode array (apical-peak, AP, EL20 or EL22), whereas 17 subjects (44%) exhibited a maximum amplitude in more basal regions (mid-peak, MP, EL18 or lower). At 3 months, in six subjects with an AP pattern perioperatively, the location of the largest electrocochleographic response had shifted basally (apical-to-mid-peak, AP-MP). Latency was analyzed along the electrode array when this could be discerned. This was the case in 68 peri- and postoperative recordings (87% of all recordings, n = 78). The latency increased with increasing insertion depth in AP recordings (n = 38, median of EL with maximum latency shift = EL21). In MP recordings (n = 30), the maximum latency shift was detectable more basally (median EL12, p < 0.001). Four-point impedance measurements were available at both time points in 90% (n = 35) of all subjects. At the 3-month time point, recordings revealed lower impedances in the AP group (n = 15, mean = 222 Ω, SD = 63) than in the MP (n = 14, mean = 295 Ω, SD= 7 6) and AP-MP groups (n = 6, mean = 234 Ω, SD = 129; AP versus MP p = 0.026, AP versus AP-MP p = 0.023, MP versus AP-MP p > 0.999). The amplitudes of perioperative AP recordings showed a correlation with preoperative hearing thresholds ( r2 =0.351, p = 0.004). No such correlation was detectable in MP recordings ( r2 = 0.033, p = 0.484). Audiograms were available at both time points in 97% (n = 38) of all subjects. The mean postoperative hearing loss in the AP group was 13 dB (n = 16, SD = 9). A significantly larger hearing loss was detectable in the MP and AP-MP groups with 28 (n = 17, SD = 10) and 35 dB (n = 6, SD = 13), respectively (AP versus MP p = 0.002, AP versus AP-MP p = 0.002, MP versus AP-MP p = 0.926). CONCLUSION: MP and AP-MP response patterns of the electrocochleographic responses along the electrode array after cochlear implantation are correlated with higher four-point impedances and poorer postoperative hearing compared to AP response patterns. The higher impedances suggest that MP and AP-MP patterns are associated with increased intracochlear fibrosis.

Four-Point Impedance Changes After Cochlear Implantation for Lateral Wall and Perimodiolar Implants.

OBJECTIVE: Monitor four-point impedance in cochlear implant recipients over time and determine if implant type, surgical approach, and electrode positioning affected impedance measurements. STUDY DESIGN: Prospective observational. SETTING: Hospital. PATIENTS: Adult cochlear implant recipients implanted with a perimodiolar or lateral wall cochlear implant. MAIN OUTCOME MEASURES: Mean values for four-point impedances were calculated for all electrode contacts at perioperative and 3 months after surgery. Linear mixed models were applied to the impedance data to compare between implant types and time points. The angular insertion depth and electrode position relative to the medial and lateral wall, commonly termed the Intracochlear Position Index (ICPI), were collected and compared with impedance measurements. RESULTS: Perioperatively, the four-point impedance was similar between implant types, with perimodiolar implants having marginally higher impedance values in the basal region. At 3 months after surgery, impedances significantly increased in the basal half of the electrode array for both implants, with higher impedance values for CI532 implants. There were no significant differences in insertion angle depth between implant types. The ICPI values for the seven most basal electrodes were similar for both implants; however, CI532 arrays were significantly more medially placed along the remaining apical portion of the array, which is expected. ICPI values did not correlate with impedance measurements for either implant. CONCLUSIONS: Four-point impedance increases at 3 months after surgery may reflect fibrous tissue formation after cochlear implantation. The higher impedance values in perimodiolar implants may reflect a more extensive fibrosis formation as a result of surgical approaches used, requiring drilling of the cochlea bone.

Four-point Impedance Changes in the Early Post-Operative Period After Cochlear Implantation.

OBJECTIVE: Monitoring four-point impedance changes after cochlear implantation with comparison to conventional impedance measurements. Four-point impedance provides information regarding the bulk biological environment surrounding the electrode array, which is not discernible with conventional impedances. STUDY DESIGN: Prospective observational. SETTING: Hospital. PATIENTS: Adult cochlear implant recipients with no measurable hearing before implantation and implanted with a perimodiolar cochlear implant. MAIN OUTCOME MEASURES: Mean values for four-point and common ground impedances were calculated for all electrode contacts at intra-operative, 1 day, 1 week, 4 to 6 weeks, and 3 months post implantation. Linear mixed models were applied to the impedance data to compare between impedances and time points. Furthermore, patients were divided into groups dependent on the normalized change in four-point impedance from intra-operative to 1 day post-operative. The normalized change was then calculated for all other time points and compared across the two groups. RESULTS: Significant increases in four-point impedance occurred 1 day and 3 months after surgery, particularly in the basal half of the array. Four-point impedance at 1 day was highly predictive of four-point impedance at 3 months. Four-point impedance at the other time points showed marginal or no increases from intra-operative. Patients with an average increase higher than 10% in four-point impedance from intra-operative to 1 day, had significantly higher values at 3 months ( p = 0.012). These patterns were not observed in common ground impedance. CONCLUSION: This is the first study to report increases in four-point impedance within 24 hours of cochlear implantation. The increases at 1 day and 3 months align with the natural timeline of an acute and chronic inflammatory responses.

Automatic analysis of cochlear response using electrocochleography signals during cochlear implant surgery.

Cochlear implants (CIs) provide an opportunity for the hearing impaired to perceive sound through electrical stimulation of the hearing (cochlear) nerve. However, there is a high risk of losing a patient's natural hearing during CI surgery, which has been shown to reduce speech perception in noisy environments as well as music appreciation. This is a major barrier to the adoption of CIs by the hearing impaired. Electrocochleography (ECochG) has been used to detect intra-operative trauma that may lead to loss of natural hearing. There is early evidence that ECochG can enable early intervention to save natural hearing of the patient. However, detection of trauma by observing changes in the ECochG response is typically carried out by a human expert. Here, we discuss a method of automating the analysis of cochlear responses during CI surgery. We establish, using historical patient data, that the proposed method is highly accurate (∼94% and ∼95% for sensitivity and specificity respectively) when compared to a human expert. The automation of real-time cochlear response analysis is expected to improve the scalability of ECochG and improve patient safety.

Electrocochleography triggered intervention successfully preserves residual hearing during cochlear implantation: Results of a randomised clinical trial.

BACKGROUND: Preservation of natural hearing during cochlear implantation is associated with improved speech outcomes, however more than half of implant recipients lose this hearing. Real-time electrophysiological monitoring of cochlear output during implantation, made possible by recording electrocochleography using the electrodes on the cochlear implant, has shown promise in predicting hearing preservation. Sudden drops in the amplitude of the cochlear microphonic (CM) have been shown to predict more severe hearing losses. Here, we report on a randomized clinical trial investigating whether immediate surgical intervention triggered by these drops can save residual hearing. METHODS: A single-blinded placebo-controlled trial of surgical intervention triggered when CM amplitude dropped by at least 30% of a prior maximum amplitude during cochlear implantation. Intraoperative electrocochleography was recorded in 60 adults implanted with Cochlear Ltd's Thin Straight Electrode, half randomly assigned to a control group and half to an interventional group. The surgical intervention was to withdraw the electrode in ½-mm steps to recover CM amplitude. The primary outcome was hearing preservation 3 months following implantation, with secondary outcomes of speech-in-noise reception thresholds by group or CM outcome, and depth of implantation. RESULTS: Sixty patients were recruited; neither pre-operative audiometry nor speech reception thresholds were significantly different between groups. Post-operatively, hearing preservation was significantly better in the interventional group. This was the case in absolute difference (median of 30 dB for control, 20 dB for interventional, χ² = 6.2, p = .013), as well as for relative difference (medians of 66% for the control, 31% for the interventional, χ² = 5.9, p = .015). Speech-in-noise reception thresholds were significantly better in patients with no CM drop at any point during insertion compared with patients with a CM drop; however, those with successfully recovered CMs after an initial drop were not significantly different (median gain required for speech reception score of 50% above noise of 6.9 dB for no drop, 8.6 for recovered CM, and 9.8 for CM drop, χ² = 6.8, p = .032). Angular insertion depth was not significantly different between control and interventional groups. CONCLUSIONS: This is the first demonstration that surgical intervention in response to intraoperative hearing monitoring can save residual hearing during cochlear implantation.

The Effect of Different Round Window Sealants on Cochlear Mechanics Over Time.

BACKGROUND: This project investigated the effects of round window membrane (RWM) sealants after surgical incision, with a focus on audiological thresholds, ossicular mechanics, and the impact upon cochlear function and pathology. METHODS: Twenty-eight guinea pigs were randomly allocated to one of three sealant groups (muscle, n = 7; fascia, n = 7, Tisseel, n = 8) or an unsealed control group (n = 6). Preoperative hearing was measured using auditory brainstem responses (ABRs). The ossicular chain and RWM were exposed surgically, and Laser Doppler Vibrometry (LDV) measurements were obtained from the long process of the incus. The RWM was incised then sealed (or left unsealed) according to group. ABR testing and LDV measurements were repeated 4 and 12 weeks after surgery. At 12 weeks all cochleae were harvested. RESULTS: ABR thresholds deteriorated over time in all groups. Overall, group was not statistically significant (p = 0.064). There was no significant effect by group on LDV measurements (p = 0.798). Histopathological analyses of the RWM showed that the fascia group had more extensive fibrosis than other groups (Independent-Samples Median Test, p = 0.001). However, there were minimal differences in the outer hair cell counts between the different intervention groups. CONCLUSIONS: All the interventions appeared to be safe while none affected the cochlear mechanics or hearing thresholds in a statistically significant manner.

Real Time Monitoring During Cochlear Implantation: Increasing the Accuracy of Predicting Residual Hearing Outcomes.

OBJECTIVES: Real-time electrocochleography (rt-ECochG) is a method to detect intracochlear potential changes during cochlear implantation (CI). Steep amplitude drops of the cochlear microphonic (CM) signal (so called "ECochG events") have been correlated with worse residual hearing outcomes. However, the sensitivity and specificity of monitoring CM amplitude on its own are too low to use it as a biomarker. The aim of this article was to establish if additional signal components would help to better predict postoperative hearing outcomes. DESIGN AND SETTING: Single-center, prospective cohort study at a tertiary referral hospital. PARTICIPANTS AND INTERVENTIONS: Between 2017 and 2020, we included 73 adult patients receiving a lateral wall cochlear implant electrode. During electrode insertion, rt-ECochG measurements were performed. MAIN OUTCOMES: We calculated a multiple regression analysis for patients with one ECochG event. The dependant variable was the relative acoustic hearing result 4 weeks after surgery. Independent variables were CM latency, a ratio of the auditory nerve neurophonic to the CM (the ANN/CM index) as well as CM signal recovery. RESULTS: The change of the ANN/CM index linearly correlated with acoustic hearing outcomes 4 weeks after surgery. Adding this factor led to a statistically significant increase in the variance accounted for by the regression model. CONCLUSIONS: When monitoring the implantation process with rt-ECochG, prediction of postoperative hearing thresholds is improved by addition of the ANN/CM index to a model that includes CM amplitude fluctuation.

Toward a Better Understanding of Electrocochleography: Analysis of Real-Time Recordings.

OBJECTIVES: Real-time electrocochleography (ECochG) has been used as a monitoring tool during cochlear implantation (CI), whereby, amplitude drops have been correlated with postoperative acoustic hearing results. However, no consensus has been reached as to how a single event of an amplitude drop should be characterized. The aim of this study was to identify ECochG events that predict loss of hearing 1 month after surgery. DESIGN: Fifty-five patients were included in this prospective cohort study. Real-time ECochG measurements were performed during CI electrode insertion. Single ECochG events were characterized according to their amplitude loss and slope steepness. RESULTS: Using receiver operating characteristic analyses, the most efficient cut-off criterion for a relative hearing loss of 25% was an amplitude loss of 61% at a fixed slope steepness of 0.2 µV/sec. Three-quarters of our population had at least one such event during implantation. Most events occurred shortly before full insertion. With increasing number of events, median residual hearing thresholds deteriorated for all frequencies. Larger amplitude drops trended toward worse hearing preservation. Signal recovery after an ECochG event could not be correlated to acoustic hearing outcomes. CONCLUSIONS: Our data suggest that amplitude drops exceeding 61% of the ongoing signal at a slope steepness of 0.2 µV/sec are correlated with worse acoustic hearing preservation. Clearly defined ECochG events have the potential to guide surgeons during CI in the future. This is essential if a fully automated data analysis is to be employed or benchmarking undertaken.

Cochlear microphonic latency predicts outer hair cell function in animal models and clinical populations.

As recently reported, electrocochleography recorded in cochlear implant recipients showed reduced amplitude and shorter latency in patients with more severe high-frequency hearing loss compared with those with some residual hearing. As the response is generated primarily by receptor currents in outer hair cells, these variations in amplitude and latency may indicate outer hair cell function after cochlear implantation. We propose that an absence of latency shift when the cochlear microphonic is measured on two adjacent electrodes indicates an absence or dysfunction of outer hair cells between these electrodes. We test this preclinically in noise deafened guinea pigs (2 h of a 124 dB HL, 16-24 kHz narrow-band noise), and clinically, in electrocochleographic recordings made in cochlear implant recipients immediately after implantation. We found that normal hearing guinea pigs showed a progressive increase in latency from basal to apical electrodes. In contrast, guinea pigs with significantly elevated high-frequency hearing thresholds showed no change in cochlear microphonic latency measured on basal electrodes (located approximately at the 16-24 kHz location in the cochlea).. In the clinical cohort, a significant negative correlation existed between cochlear microphonic latency shifts and hearing thresholds at 1-, 2-, & 4 kHz when tested on electrodes located at the relevant cochlear tonotopic place. This reduction in latency shift was such that patients with no measurable hearing also had no detectable latency shift (place assessed by CT scan, r's of -.70 to -.83). These findings suggest that electrocochleography can be used as a diagnostic tool to detect cochlear regions with functioning hair cells, which may be important for defining cross-over point for electro-acoustic stimulation.

Four-point impedance as a biomarker for bleeding during cochlear implantation.

Cochlear implantation has successfully restored the perception of hearing for nearly 200 thousand profoundly deaf adults and children. More recently, implant candidature has expanded to include those with considerable natural hearing which, when preserved, provides an improved hearing experience in noisy environments. But more than half of these patients lose this natural hearing soon after implantation. To reduce this burden, biosensing technologies are emerging that provide feedback on the quality of surgery. Here we report clinical findings on a new intra-operative measurement of electrical impedance (4-point impedance) which, when elevated, is associated with high rates of post-operative hearing loss and vestibular dysfunction. In vivo and in vitro data presented suggest that elevated 4-point impedance is likely due to the presence of blood within the cochlea rather than its geometry. Four-point impedance is a new marker for the detection of cochlear injury causing bleeding, that may be incorporated into intraoperative monitoring protocols during CI surgery.

Nanomechanical mapping reveals localized stiffening of the basilar membrane after cochlear implantation.

Cochlear implantation leads to many structural changes within the cochlea which can impair residual hearing. In patients with preserved low-frequency hearing, a delayed hearing loss can occur weeks-to-years post-implantation. We explore whether stiffening of the basilar membrane (BM) may be a contributory factor in an animal model. Our objective is to map changes in morphology and Young's modulus of basal and apical areas of the BM after cochlear implantation, using quantitative nanomechanical atomic force microscopy (QNM-AFM) after cochlear implant surgery. Cochlear implantation was undertaken in the guinea pig, and the BM was harvested at four time-points: 1 day, 14 days, 28 days and 84 days post-implantation for QNM-AFM analysis. Auditory brainstem response thresholds were determined prior to implantation and termination. BM tissue showed altered morphology and a progressive increase in Young's modulus, mainly in the apex, over time after implantation. BM tissue from the cochlear base demonstrated areas of extreme stiffness which are likely due to micro-calcification on the BM. In conclusion, stiffening of the BM after cochlear implantation occurs over time, even at sites far apical to a cochlear implant.

Glucocorticoid for Hearing Preservation After Cochlear Implantation: A Systemic Review and Meta-analysis of Animal Studies.

OBJECTIVES: To conduct systematic review and meta-analyses of preclinical studies describing the efficacy of glucocorticoids administered via different routes for hearing preservation after cochlear implantation. DATA SOURCES: A literature search was performed in PubMed to identify peer-reviewed articles published before December 31, 2017, with no language restrictions. Search components were "Cochlear implant," "Glucocorticoids," and "Hearing preservation." The results were specified for animal studies. STUDY SELECTION: Original studies in which glucocorticoids were administered before or during cochlear implantation in animal models and hearing threshold shifts were measured using auditory brainstem response. DATA EXTRACTION: Quality of included studies was assessed using the SYstematic Review Centre for Laboratory animal Experimentation protocol. Threshold Shift reduction between the "study" and "control" groups at 1-month postimplantation was the parameter used to evaluate hearing preservation. DATA SYNTHESIS: The random-effects models were used to combine the results of selected studies. Separate meta-analyses were performed for drug-eluting electrodes, systemic, and local administration. CONCLUSIONS: Administering either systemic or topical glucocorticosteroids had a significant effect on preserving low and high-frequency hearing. Topical administration was equally effective across a range of concentration levels and provided maximal hearing preservation when applied 120 minutes before implantation. The effect of systemic treatment was achieved with high doses, equivalent to 26 mg of dexamethasone per day in humans. No significant effect was found with the use of drug-eluting electrodes and more studies are needed to characterise the utility and efficacy of this administration method.

Electrical Impedance as a Biomarker for Inner Ear Pathology Following Lateral Wall and Peri-modiolar Cochlear Implantation.

OBJECTIVES/HYPOTHESIS: Spikes in cochlear implant impedance are associated with inner ear pathology after implantation. Here, we correlate these spikes with episodes of hearing loss and/or vertigo, with a comparison between lateral wall and peri-modiolar electrode arrays. METHODS: Seven hundred seventy recipients of Cochlear's slim-straight, lateral wall electrode (CI422), or peri-modiolar (CI512) electrode were investigated for impedance spikes. Impedance fluctuations were defined as a median rise of ≥ 4 kΩ across all intracochlear electrodes from baseline measurements taken 2 weeks after switch-on. Medical records were analyzed from 189 of the 770 patients. RESULTS: The slim straight, lateral wall electrode was found to spike in impedance at a significantly higher rate than the peri-modiolar array (17% vs 12%). The peri-modiolar electrode tended to spike in impedance earlier than the slim-straight electrode. Impedance spikes were found to significantly correlate with medical events (hearing loss, vertigo, or tinnitus). Overall, in the "spike" group, 42 of 75 patients (56%) demonstrated a clinical event during the impedance spike, whereas 26 of 114 patients (22%) of the "non-spike" group had a clinical event. This significant difference existed with both implant types. CONCLUSION: These results demonstrate a small, but significant increase in impedance spikes in lateral wall electrodes, and support the relationship between spikes in cochlear implant impedances and postoperative inner-ear events, including the loss of residual hearing and vertigo. Monitoring cochlear implant impedance may be a method for early detection, and so the prevention, of these events in the future.