Research progress on incomplete partition type 3 inner ear malformation.

PURPOSE: This review aims to provides a comprehensive overview of the latest research progress on IP-III inner ear malformation, focusing on its geneticbasis, imaging features, cochlear implantation, and outcome. METHODS: Review the literature on clinical and genetic mechanisms associated with IP-III. RESULTS: Mutations in the POU3F4 gene emerge as the principal pathogenic contributors to IP-III anomalies, primarily manifesting through inner ear potential irregularities leading to deafness. While cochlear implantation stands as the primary intervention for restoring hearing, the unique nature of the inner ear anomaly escalates the complexity of surgical procedures and postoperative results. Hence, meticulous preoperative assessment to ascertain surgical feasibility and postoperative verification of electrode placement are imperative. Additionally, gene therapy holds promise as a prospective treatment modality. CONCLUSIONS: IP-III denotes X-linked recessive hereditary deafness, with cochlear implantation currently serving as the predominant therapeutic approach. Clinicians are tasked with preoperative assement and individualized postoperative rehabilitation.

Vestibular function and hearing preservation in children following a minimally invasive cochlear implantation.

PURPOSE: This retrospective cohort study aimed to investigate the effect of minimally invasive cochlear implantation (CI) on the vestibular function (VF) and residual hearing (RH) as well as their relationship in pediatric recipients before and after surgery. METHODS: Twenty-four pediatric patients with preoperative low frequency residual hearing (LFRH) (250 or 500 Hz ≤ 80 dB HL) who underwent minimally invasive CI were enrolled. Pure-tone thresholds, the cervical/ocular vestibular-evoked myogenic potential (cVEMP/oVEMP), and video head impulse test (vHIT) were all evaluated in the 24 pediatric patients with preoperative normal VF before and at 1 and 12 months after surgery. The relationship between changes in hearing and VF was analyzed preoperatively and at 1 and 12 months postoperatively. RESULTS: There were no significant differences on VF preservation and hearing preservation (HP) at both 1 and 12 months post-CI (p > 0.05). At 1 month post-CI, the correlations of the variations in vestibulo-ocular reflex (VOR) gains of horizontal semicircular canal (HSC) and posterior semicircular canal (PSC) and the shift in 250 Hz threshold were negatively correlated (r = - 0.41, p = 0.04 and r = - 0.43, p = 0.04, respectively). At 12 months post-CI, the shift in 250 Hz threshold negatively correlated to the variations in VOR gain of superior semicircular canal (SSC) (r = - 0.43, p = 0.04); the HP positively correlated to the variation in oVEMP-amplitude ratio (AR) (r = 0.41, p = 0.04). CONCLUSION: Our study confirmed that there were partial correlations between VF preservation and HP both in the short- and long-terms after atraumatic CI surgery, especially with the 250 Hz threshold. Regarding the variation of PSC function, the correlation with hearing status was variable with time after atraumatic CI surgery. Minimally invasive techniques for HP are successful and effective for the preservation of VF in pediatric patients both in the short- and long-terms.

Long-Term Auditory and Speech Outcomes of Cochlear Implantation in Children With Cochlear Nerve Aplasia.

OBJECTIVES: In this study, we aimed to (1) review the long-term outcomes of cochlear implantation in children with cochlear nerve aplasia and (2) compare the development of their auditory and speech abilities to children with normal-sized cochlear nerves. DESIGN: This is a retrospective case-control study. Patients who underwent unilateral cochlear implant (CI) surgery in a tertiary referral center from September 2012 to December 2018 were reviewed. The study group included 55 children with cochlear nerve aplasia diagnosed using preoperative images. The control group included 35 children with normal-sized cochlear nerves. The control group did not differ from the study group in terms of age at implantation, pre-implantation auditory and speech abilities, or the electrode array type. Cochlear implantation outcomes were assessed using a test battery, including the Categories of Auditory Performance (CAP) score, the Speech Intelligibility Rating (SIR) score, behavioral audiometry, and closed- or open-set speech recognition tests. The development of auditory and speech abilities was compared between the two groups using Generalized Linear Mixed-effect Models. RESULTS: The mean duration of CI usage was 4.5 years (SD = 1.5, range = 2.0 to 9.5) in the study group. The CAP scores, SIR scores, and aided hearing thresholds improved significantly post-implantation in the study group, but were significantly poorer than those in the control group. Generalized Linear Mixed-effect Models showed that the development of CAP and SIR scores was significantly slower in the study group than in the control group. Overall, 27 (49%) children with cochlear nerve aplasia had some degree of open-set speech perception skills, but the monosyllabic and bisyllabic word recognition rates were significantly lower than those in the control group. CONCLUSION: For children with cochlear nerve aplasia, auditory perception and speech intelligibility continued to improve in the long-term follow-up, but this progress was significantly slower than in children with normal-sized cochlear nerves. Most children with cochlear nerve aplasia could obtain the ability of common phrase perception and understanding simple spoken language with consistent CI usage and auditory rehabilitation.

Reverberation Degrades Pitch Perception but Not Mandarin Tone and Vowel Recognition of Cochlear Implant Users.

OBJECTIVES: The primary goal of this study was to investigate the effects of reverberation on Mandarin tone and vowel recognition of cochlear implant (CI) users and normal-hearing (NH) listeners. To understand the performance of Mandarin tone recognition, this study also measured participants' pitch perception and the availability of temporal envelope cues in reverberation. DESIGN: Fifteen CI users and nine NH listeners, all Mandarin speakers, were asked to recognize Mandarin single-vowels produced in four lexical tones and rank harmonic complex tones in pitch with different reverberation times (RTs) from 0 to 1 second. Virtual acoustic techniques were used to simulate rooms with different degrees of reverberation. Vowel duration and correlation between amplitude envelope and fundamental frequency (F0) contour were analyzed for different tones as a function of the RT. RESULTS: Vowel durations of different tones significantly increased with longer RTs. Amplitude-F0 correlation remained similar for the falling Tone 4 but greatly decreased for the other tones in reverberation. NH listeners had robust pitch-ranking, tone recognition, and vowel recognition performance as the RT increased. Reverberation significantly degraded CI users' pitch-ranking thresholds but did not significantly affect the overall scores of tone and vowel recognition with CIs. Detailed analyses of tone confusion matrices showed that CI users reduced the flat Tone-1 responses but increased the falling Tone-4 responses in reverberation, possibly due to the falling amplitude envelope of late reflections after the original vowel segment. CI users' tone recognition scores were not correlated with their pitch-ranking thresholds. CONCLUSIONS: NH listeners can reliably recognize Mandarin tones in reverberation using salient pitch cues from spectral and temporal fine structures. However, CI users have poorer pitch perception using F0-related amplitude modulations that are reduced in reverberation. Reverberation distorts speech amplitude envelopes, which affect the distribution of tone responses but not the accuracy of tone recognition with CIs. Recognition of vowels with stationary formant trajectories is not affected by reverberation for both NH listeners and CI users, regardless of the available spectral resolution. Future studies should test how the relatively stable vowel and tone recognition may contribute to sentence recognition in reverberation of Mandarin-speaking CI users.

Prediction of the Functional Status of the Cochlear Nerve in Individual Cochlear Implant Users Using Machine Learning and Electrophysiological Measures.

OBJECTIVES: This study aimed to create an objective predictive model for assessing the functional status of the cochlear nerve (CN) in individual cochlear implant (CI) users. DESIGN: Study participants included 23 children with cochlear nerve deficiency (CND), 29 children with normal-sized CNs (NSCNs), and 20 adults with various etiologies of hearing loss. Eight participants were bilateral CI users and were tested in both ears. As a result, a total of 80 ears were tested in this study. All participants used Cochlear Nucleus CIs in their test ears. For each participant, the CN refractory recovery function and input/output (I/O) function were measured using electrophysiological measures of the electrically evoked compound action potential (eCAP) at three electrode sites across the electrode array. Refractory recovery time constants were estimated using statistical modeling with an exponential decay function. Slopes of I/O functions were estimated using linear regression. The eCAP parameters used as input variables in the predictive model were absolute refractory recovery time estimated based on the refractory recovery function, eCAP threshold, slope of the eCAP I/O function, and negative-peak (i.e., N1) latency. The output variable of the predictive model was CN index, an indicator for the functional status of the CN. Predictive models were created by performing linear regression, support vector machine regression, and logistic regression with eCAP parameters from children with CND and the children with NSCNs. One-way analysis of variance with post hoc analysis with Tukey's honest significant difference criterion was used to compare study variables among study groups. RESULTS: All three machine learning algorithms created two distinct distributions of CN indices for children with CND and children with NSCNs. Variations in CN index when calculated using different machine learning techniques were observed for adult CI users. Regardless of these variations, CN indices calculated using all three techniques in adult CI users were significantly correlated with Consonant-Nucleus-Consonant word and AzBio sentence scores measured in quiet. The five oldest CI users had smaller CN indices than the five youngest CI users in this study. CONCLUSIONS: The functional status of the CN for individual CI users was estimated by our newly developed analytical models. Model predictions of CN function for individual adult CI users were positively and significantly correlated with speech perception performance. The models presented in this study may be useful for understanding and/or predicting CI outcomes for individual patients.

The Effect of Pulse Polarity on Neural Response of the Electrically Stimulated Cochlear Nerve in Children With Cochlear Nerve Deficiency and Children With Normal-Sized Cochlear Nerves.

OBJECTIVE: This study aimed to (1) investigate the effect of pulse polarity on neural response of the electrically stimulated cochlear nerve in children with cochlear nerve deficiency (CND) and children with normal-sized cochlear nerves and (2) compare the size of the pulse polarity effect between these two subject groups. DESIGN: The experimental and control group included 31 children with CND and 31 children with normal-sized cochlear nerves, respectively. For each study participant, evoked compound action potential (eCAP) input/output (I/O) functions for anodic-leading and cathodic-leading biphasic stimuli were measured at three electrode locations across the electrode array. The dependent variables of interest included the eCAP amplitude measured at the maximum comfortable level of the anodic stimulus, the lowest level that could evoke an eCAP (i.e., the eCAP threshold), the slope of the eCAP I/O function estimated based on linear regression, the negative-peak (i.e., N1) latency of the eCAP, as well as the size of the pulse polarity effect on these eCAP measurements. Generalized linear mixed effect models were used to compare the eCAP amplitude, the eCAP threshold, the slope of the eCAP I/O function, and the N1 latency evoked by the anodic-leading stimulus with those measured for the cathodic-leading stimulus for children with CND and children with normal-sized cochlear nerves. Generalized linear mixed effect models were also used to compare the size of the pulse polarity effect on the eCAP between these two study groups. The one-tailed Spearman correlation test was used to assess the potential correlation between the pulse phase duration and the difference in N1 latency measured for different pulse polarities. RESULTS: Compared with children who had normal-sized cochlear nerves, children with CND had reduced eCAP amplitudes, elevated eCAP thresholds, flatter eCAP I/O functions, and prolonged N1 latencies. The anodic-leading stimulus led to higher eCAP amplitudes, lower eCAP thresholds, and shorter N1 latencies than the cathodic-leading stimulus in both study groups. Steeper eCAP I/O functions were recorded for the anodic-leading stimulus than those measured for the cathodic-leading stimulus in children with CND, but not in children with normal-sized cochlear nerves. Group differences in the size of the pulse polarity effect on the eCAP amplitude, the eCAP threshold, or the N1 latency were not statistically significant. CONCLUSIONS: Similar to the normal-sized cochlear nerve, the hypoplastic cochlear nerve is more sensitive to the anodic-leading than to the cathodic-leading stimulus. Results of this study do not provide sufficient evidence for proving the idea that the pulse polarity effect can provide an indication for local neural health.

Effect of Increasing Pulse Phase Duration on Neural Responsiveness of the Electrically Stimulated Cochlear Nerve.

OBJECTIVES: The aim of this study is to (1) investigate the effects of increasing the pulse phase duration (PPD) on the neural response of the electrically stimulated cochlear nerve (CN) in children with CN deficiency (CND) and (2) compare the results from the CND population to those measured in children with normal-sized CNs. DESIGN: Study participants included 30 children with CND and 30 children with normal-sized CNs. All participants used a Cochlear Nucleus device in the test ear. For each subject, electrically evoked compound action potential (eCAP) input/output (I/O) functions evoked by single biphasic pulses with different PPDs were recorded at three electrode locations across the electrode array. PPD durations tested in this study included 50, 62, 75, and 88 µsec/phase. For each electrode tested for each study participant, the amount of electrical charge corresponding to the maximum comfortable level measured for the 88 µsec PPD was used as the upper limit of stimulation. The eCAP amplitude measured at the highest electrical charge level, the eCAP threshold (i.e., the lowest level that evoked an eCAP), and the slope of the eCAP I/O function were measured. Generalized linear mixed effect models with study group, electrode location, and PPD as the fixed effects and subject as the random effect were used to compare these dependent variables measured at different electrode locations and PPDs between children with CND and children with normal-sized CNs. RESULTS: Children with CND had smaller eCAP amplitudes, higher eCAP thresholds, and smaller slopes of the eCAP I/O function than children with normal-sized CNs. Children with CND who had fewer electrodes with a measurable eCAP showed smaller eCAP amplitudes and flatter eCAP I/O functions than children with CND who had more electrodes with eCAPs. Increasing the PPD did not show a statistically significant effect on any of these three eCAP parameters in the two subject groups tested in this study. CONCLUSIONS: For the same amount of electrical charge, increasing the PPD from 50 to 88 µsec for a biphasic pulse with a 7 µsec interphase gap did not significantly affect CN responsiveness to electrical stimulation in human cochlear implant users. Further studies with different electrical pulse configurations are warranted to determine whether evaluating the eCAP sensitivity to changes in the PPD can be used as a testing paradigm to estimate neural survival of the CN for individual cochlear implant users.

The Effects of GJB2 or SLC26A4 Gene Mutations on Neural Response of the Electrically Stimulated Auditory Nerve in Children.

OBJECTIVES: This study aimed to (1) investigate the effect of GJB2 and SLC26A4 gene mutations on auditory nerve function in pediatric cochlear implant users and (2) compare their results with those measured in implanted children with idiopathic hearing loss. DESIGN: Participants included 20 children with biallelic GJB2 mutations, 16 children with biallelic SLC26A4 mutations, and 19 children with idiopathic hearing loss. All subjects except for two in the SLC26A4 group had concurrent Mondini malformation and enlarged vestibular aqueduct. All subjects used Cochlear Nucleus devices in their test ears. For each subject, electrophysiological measures of the electrically evoked compound action potential (eCAP) were recorded using both anodic- and cathodic-leading biphasic pulses. Dependent variables (DVs) of interest included slope of eCAP input/output (I/O) function, the eCAP threshold, and eCAP amplitude measured at the maximum comfortable level (C level) of the anodic-leading stimulus (i.e., the anodic C level). Slopes of eCAP I/O functions were estimated using statistical modeling with a linear regression function. These DVs were measured at three electrode locations across the electrode array. Generalized linear mixed effect models were used to evaluate the effects of study group, stimulus polarity, and electrode location on each DV. RESULTS: Steeper slopes of eCAP I/O function, lower eCAP thresholds, and larger eCAP amplitude at the anodic C level were measured for the anodic-leading stimulus compared with the cathodic-leading stimulus in all subject groups. Children with GJB2 mutations showed steeper slopes of eCAP I/O function and larger eCAP amplitudes at the anodic C level than children with SLC26A4 mutations and children with idiopathic hearing loss for both the anodic- and cathodic-leading stimuli. In addition, children with GJB2 mutations showed a smaller increase in eCAP amplitude when the stimulus changed from the cathodic-leading pulse to the anodic-leading pulse (i.e., smaller polarity effect) than children with idiopathic hearing loss. There was no statistically significant difference in slope of eCAP I/O function, eCAP amplitude at the anodic C level, or the size of polarity effect on all three DVs between children with SLC26A4 mutations and children with idiopathic hearing loss. These results suggested that better auditory nerve function was associated with GJB2 but not with SLC26A4 mutations when compared with idiopathic hearing loss. In addition, significant effects of electrode location were observed for slope of eCAP I/O function and the eCAP threshold. CONCLUSIONS: GJB2 and SLC26A4 gene mutations did not alter polarity sensitivity of auditory nerve fibers to electrical stimulation. The anodic-leading stimulus was generally more effective in activating auditory nerve fibers than the cathodic-leading stimulus, despite the presence of GJB2 or SLC26A4 mutations. Patients with GJB2 mutations appeared to have better functional status of the auditory nerve than patients with SLC26A4 mutations who had concurrent Mondini malformation and enlarged vestibular aqueduct and patients with idiopathic hearing loss.

The Effect of Interphase Gap on Neural Response of the Electrically Stimulated Cochlear Nerve in Children With Cochlear Nerve Deficiency and Children With Normal-Sized Cochlear Nerves.

OBJECTIVES: This study aimed to compare the effects of increasing the interphase gap (IPG) on the neural response of the electrically stimulated cochlear nerve (CN) between children with CN deficiency (CND) and children with normal-sized CNs. DESIGN: Study participants included 30 children with CND and 30 children with normal-sized CNs. All subjects were implanted with a Cochlear Nucleus device with the internal electrode array 24RE[CA] in the test ear. The stimulus was a charge-balanced, cathodic leading, biphasic pulse with a pulse-phase duration of 50 µsec. For each subject, the electrically evoked compound action potential (eCAP) input/output (I/O) function was measured for 6 IPGs (i.e., 7, 14, 21, 28, 35, and 42 µsec) at 3 electrode locations across the electrode array. For each subject and each testing electrode, the highest stimulation used to measure the eCAP I/O function was the maximum comfortable level measured with an IPG of 42 µsec. Dependent variables (DVs) were the maximum eCAP amplitude, the eCAP threshold, and the slope of the eCAP I/O function estimated using both linear and sigmoidal regression functions. For each DV, the size of the IPG effect was defined as the proportional change relative to the result measured for the 7 µsec IPG at the basal electrode location. Generalized linear mixed effect models with subject group, electrode location, and IPG duration as the fixed effects and subject as the random effect were used to compare these DVs and the size of the IPG effect on these DVs. RESULTS: Children with CND showed smaller maximum eCAP amplitudes, higher eCAP thresholds, and smaller slopes of eCAP I/O function estimated using either linear or sigmoidal regression function than children with normal-sized CNs. Increasing the IPG duration resulted in larger maximum eCAP amplitudes, lower eCAP thresholds and larger slopes of eCAP I/O function estimated using sigmoidal regression function at all three electrode locations in both study groups. Compared with children with normal-sized CNs, children with CND showed larger IPG effects on both the maximum eCAP amplitude and the slope of the eCAP I/O function estimated using either linear or sigmoidal regression function, and a smaller IPG effect on the eCAP threshold than those measured in children with normal-sized CNs. CONCLUSIONS: Increasing the IPG increases responsiveness of the electrically stimulated CN in both children with CND and children with normal-sized CNs. The maximum eCAP amplitude and the slope of the eCAP I/O function measured in human listeners with poorer CN survival are more sensitive to changes in the IPG. In contrast, the eCAP threshold in listeners with poorer CN survival is less sensitive to increases in the IPG. Further studies are warranted to identify the best parameters of eCAP results for predicting CN survival before this eCAP testing paradigm can be used as a clinical tool for evaluating neural health for individual cochlear implant patients.

Recommendations for Measuring the Electrically Evoked Compound Action Potential in Children With Cochlear Nerve Deficiency.

OBJECTIVES: This study reports a method for measuring the electrically evoked compound action potential (eCAP) in children with cochlear nerve deficiency (CND). DESIGN: This method was developed based on experience with 50 children with CND who were Cochlear Nucleus cochlear implant users. RESULTS: This method includes three recommended steps conducted with recommended stimulating and recording parameters: initial screen, pulse phase duration optimization, and eCAP threshold determination (i.e., identifying the lowest stimulation level that can evoke an eCAP). Compared with the manufacturer-default parameters, the recommended parameters used in this method yielded a higher success rate for measuring the eCAP in children with CND. CONCLUSIONS: The eCAP can be measured successfully in children with CND using recommended parameters. This specific method is suitable for measuring the eCAP in children with CND in clinical settings. However, it is not suitable for intraoperative eCAP recordings due to the extensive testing time required.

Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation.

Aims: This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods: A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results: A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion: A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

Responsiveness of the Electrically Stimulated Cochlear Nerve in Children With Cochlear Nerve Deficiency.

OBJECTIVES: This study aimed to (1) investigate the responsiveness of the cochlear nerve (CN) to a single biphasic-electrical pulse in implanted children with cochlear nerve deficiency (CND) and (2) compare their results with those measured in implanted children with normal-size CNs. DESIGN: Participants included 23 children with CND (CND1 to CND23) and 18 children with normal-size CNs (S1 to S18). All subjects except for CND1 used Cochlear Nucleus cochlear implants with contour electrode arrays in their test ears. CND1 was implanted with a Cochlear Nucleus Freedom cochlear implant with a straight electrode array in the test ear. For each subject, the CN input/output (I/O) function and the refractory recovery function were measured using electrophysiological measures of the electrically evoked compound action potential (eCAP) at multiple electrode sites across the electrode array. Dependent variables included eCAP threshold, the maximum eCAP amplitude, slope of the I/O function, and time-constants of the refractory recovery function. Slopes of I/O functions were estimated using statistical modeling with a sigmoidal function. Recovery time-constants, including measures of the absolute refractory period and the relative refractory period, were estimated using statistical modeling with an exponential decay function. Generalized linear mixed-effect models were used to evaluate the effects of electrode site on the dependent variables measured in children with CND and to compare results of these dependent variables between subject groups. RESULTS: The eCAP was recorded at all test electrodes in children with normal-size CNs. In contrast, the eCAP could not be recorded at any electrode site in 4 children with CND. For all other children with CND, the percentage of electrodes with measurable eCAPs decreased as the stimulating site moved in a basal-to-apical direction. For children with CND, the stimulating site had a significant effect on the slope of the I/O functions and the relative refractory period but showed no significant effect on eCAP threshold and the maximum eCAP amplitude. Children with CND had significantly higher eCAP thresholds, smaller maximum eCAP amplitudes, flatter slopes of I/O functions, and longer absolute refractory periods than children with normal-size CNs. There was no significant difference in the relative refractory period measured in these two subject groups. CONCLUSIONS: In children with CND, the functional status of the CN varied along the length of the cochlea. Compared with children with normal-size CNs, children with CND showed reduced CN responsiveness to electrical stimuli. The prolonged CN absolute refractory period in children with CND might account for, at least partially, the observed benefit of using relatively slow pulse rate in these patients.

Prevalence of Mutations in Deafness-Causing Genes in Cochlear Implanted Patients with Profound Nonsyndromic Sensorineural Hearing Loss in Shandong Province, China.

The mutations of GJB2, SLC26A4, and mtDNA12SrRNA are the most common inherited causes of nonsyndromic sensorineural hearing loss (NSHL) in China, yet previous genetic screenings were mainly carried on patients with moderate-to-profound impairment. We aimed to detect the mutation frequencies in NSHL population within a more specified range of severity. Patients with profound NSHL who had undergone cochlear implantation in the Shandong Provincial Hospital (Shandong, China) were recruited. The majority (n = 472) were between 0.7 and 6 years old, and the remaining (n = 63) were between 6 and 70 years old. In total, 115 mutation alleles of the three genes were screened with SNP scan assay. Of the patients, 19.44% (104/535) were found to have GJB2 mutations, and the most common allele was c.235delC, followed by c.299_300delAT and c.109G>A. SLC26A4 mutations were detected in 13.46% patients (72/535), and the most common allele was c.919-2A>G (IVS7-2A>G), followed by c.1174A>T and c.2168A>G. Seven patients (1.31%) carried mutations in mtDNA12SrRNA, with the alleles of m.1555A>G and m.1494C>T. We found the allele frequency of c.109G>A (GJB2) was relatively lower in the profound NSHL population in comparison to the moderate-to-profound ones, and the c.1174A>T (SLC26A4) relatively higher. It suggests those mutations may be connected with the degree of deafness, which needs more observations and analyses to support.

Relationship between electrically evoked compound action potential thresholds and behavioral T-levels in implanted children with cochlear nerve deficiency.

It is challenging to program children with cochlear nerve deficiency (CND) due to limited auditory and speech abilities or concurrent neurological deficits. Electrically evoked compound action potential (ECAP) thresholds have been widely used by many audiologists to help cochlear implant programming for children who cannot cooperate with behavioral testing. However, the relationship between ECAP thresholds and behavioral levels of cochlear nerve in children with CND remains unclear. This study aimed to investigate how well ECAP thresholds are related to behavioral thresholds in the MAP for children with CND. This study included 29 children with CND who underwent cochlear implantation. For each participant, ECAP thresholds and behavioral T-levels were measured at three electrode locations across the electrode array post-activation. The relationship between ECAP thresholds and behavioral T-levels was analyzed using Pearson's correlation coefficient. The results showed that ECAP thresholds were significantly correlated with behavioral T-levels at the basal, middle, and apical electrodes. ECAP thresholds were equal to or higher than the behavioral T-levels for all tested electrodes, and fell within MAP's dynamic range for approximately 90% of the tested electrodes. Moreover, the contour of the ECAP thresholds was similar to the contour of T-levels across electrodes for most participants. ECAP thresholds can help audiologists select stimulation levels more efficiently for children with CND who cannot provide sufficient behavioral response.

Systematic Hearing Performance Evaluation Process for Adolescents with Cochlear Implantation at Early Ages.

Cochlear implant (CI) provision is the most effective clinical treatment to restore hearing performance in individuals with profound sensorineural hearing loss (SNHL). It has been successful in providing improved speech perception outcomes, especially in quiet environments. However, speech perception performance within complex environments, lexical tone recognition, and music perception have been shown to only improve with newer fine structure coding strategies or related techniques. Therefore, the methods used to assess hearing performance in noisy environments, lexical tone recognition, and music perception are of vital importance. These assessments must reflect the postoperative outcomes and also provide guidance for the programming, rehabilitation, and application of new coding strategies. In this study, hearing performance in simple and complex situations was evaluated before and after upgrading to a fine structure strategy. The participants were a cohort of Mandarin-speaking adolescents, who were experienced CI users. The comprehensive clinical workflow involved assessments of speech in quiet conditions, speech in noisy conditions, lexical tone recognition, and music perception. This battery of tests is explained in detail, from the coding strategy to the test methods, including the test process, environment, device, material, and order. The details that require special attention are discussed, such as the position of the participants, the angle of the loudspeaker, the intensity of the sound, the noise type, the practice test, and the way of answering questions. Each test step, method, and material for speech, lexical tone, and music perception is presented in detail. Finally, the clinical results are discussed.

Distribution of gentamicin in inner ear after local administration via a chitosan glycerophosphate hydrogel delivery system.

OBJECTIVES: We examined the distribution of gentamicin sulfate in the inner ear after delivery via a chitosan glycerophosphate (CGP) hydrogel system and examined the change in morphology of the hair cells so as to determine how gentamicin affected the function of the inner ear. METHODS: A matrix of CGP hydrogel loaded with gentamicin conjugated with Texas Red (GTTR) was injected into the round window niche of the left ear of C57/BL6 mice. The mice were painlessly killed on day 1 or day 7 after injection. Confocal fluorescence microscopy was used to locate the gentamicin in the cochlear and vestibular systems. RESULTS: In the vestibule, the intensity of GTTR staining in the hair cells of the macula of the saccule on day 1 was significantly stronger than that on day 7, and the number of hair cell bundles on top of the cuticular plate on day 7 was obviously decreased in comparison to that on day 1. In the cochlea, the intensity of GTTR staining in the basal turn was significantly stronger than that in the medial turn on both day 1 and day 7. Negligible fluorescence was observed in the apical turn on both day 1 and day 7. Less-intense GTTR staining was detected on day 7 than on day 1 in both the basal turn and the medial turn. There was some outer hair cell loss in the basal turn on day 7, and no hair cell loss in the medial and apical turns at any time point. CONCLUSIONS: Gentamicin is distributed in the inner ear via the CGP hydrogel delivery system in a time-dependent and basal-to-apical manner. This finding implies that the vestibule and the basal turn may retain more gentamicin for a longer period than do other sites in the inner ear. These two characteristics may account for the high-frequency hearing loss and vestibular dysfunction seen with use of this system to deliver gentamicin into the inner ear.

Apoptosis-inducing factor is involved in gentamicin-induced vestibular hair cell death.

AIM: Vestibular hair cell loss in response to different stimuli may be attributable to the occurrence of apoptosis, in which apoptosis-inducing factor (AIF) is an important regulator mediating apoptotic process independent of caspases. This study was designed to investigate the possible involvement of AIF in gentamicin (GM)-induced vestibular hair cell death. METHODS: Vestibular organs from postnatal day 3 or 4 rats were maintained in tissue culture and were exposed to 2 mg/ml GM for up to 72 h. Vestibular hair cell viability was quantified by MTT assay. Apoptosis was determined by flow cytometry. AIF activation was examined by RT-PCR. The expressions of the mitochondrial protein and cytoplasm protein of AIF were detected by Western blot. RESULTS: GM could significantly inhibit the cell viability of vestibular hair cells in a dose- and time-dependent manner. The number of apoptotic cells treated with GM was higher than that of cells not treated with GM. RT-PCR showed upregulation of AIF mRNA under GM. Western blot showed that AIF from mitochondria was decreased, whereas AIF from cytoplasm was increased after GM exposure. CONCLUSIONS: AIF participates in GM-induced apoptosis of vestibular hair cells.

Relationship Between the Ability to Detect Frequency Changes or Temporal Gaps and Speech Perception Performance in Post-lingual Cochlear Implant Users.

Previous studies, using modulation stimuli, on the relative effects of frequency resolution and time resolution on CI users' speech perception failed to reach a consistent conclusion. In this study, frequency change detection and temporal gap detection were used to investigate the frequency resolution and time resolution of CI users, respectively. Psychophysical and neurophysiological methods were used to simultaneously investigate the effects of frequency and time resolution on speech perception in post-lingual cochlear implant (CI) users. We investigated the effects of psychophysical results [frequency change detection threshold (FCDT), gap detection threshold (GDT)], and acoustic change complex (ACC) responses (evoked threshold, latency, or amplitude of ACC induced by frequency change or temporal gap) on speech perception [recognition rate of monosyllabic words, disyllabic words, sentences in quiet, and sentence recognition threshold (SRT) in noise]. Thirty-one adult post-lingual CI users of Mandarin Chinese were enrolled in the study. The stimuli used to induce ACCs to frequency changes were 800-ms pure tones (fundamental frequency was 1,000 Hz); the frequency change occurred at the midpoint of the tones, with six percentages of frequency changes (0, 2, 5, 10, 20, and 50%). Temporal silences with different durations (0, 5, 10, 20, 50, and 100 ms) were inserted in the middle of the 800-ms white noise to induce ACCs evoked by temporal gaps. The FCDT and GDT were obtained by two 2-alternative forced-choice procedures. The results showed no significant correlation between the CI hearing threshold and speech perception in the study participants. In the multiple regression analysis of the influence of simultaneous psychophysical measures and ACC responses on speech perception, GDT significantly predicted every speech perception index, and the ACC amplitude evoked by the temporal gap significantly predicted the recognition of disyllabic words in quiet and SRT in noise. We conclude that when the ability to detect frequency changes and the temporal gap is considered simultaneously, the ability to detect frequency changes may have no significant effect on speech perception, but the ability to detect temporal gaps could significantly predict speech perception.

Value of Preoperative Imaging Results in Predicting Cochlear Nerve Function in Children Diagnosed With Cochlear Nerve Aplasia Based on Imaging Results.

This study aimed to assess the function of the cochlear nerve using electrically evoked compound action potentials (ECAPs) for children with cochlear implants who were diagnosed with cochlear nerve aplasia and to analyze the correlation between preimplantation imaging results and ECAP responses. Thirty-five children diagnosed with cochlear nerve aplasia based on magnetic resonance imaging (MRI) were included. Preimplantation MRI and high-resolution computed tomography (HRCT) images were reconstructed, and the width of the bone cochlear nerve canal (BCNC), the diameter of the vestibulocochlear nerve (VCN), and the diameter of the facial nerve (FN) were measured. ECAP input/output (I/O) functions were measured at three electrode locations along the electrode array for each participant. The relationship between ECAP responses (including ECAP threshold, ECAP maximum amplitude, and slope of ECAP I/O function) and sizes of the BCNC and VCN was analyzed using Pearson's correlation coefficients. Our analysis revealed that ECAP responses varied greatly among individual participants. Overall, ECAP thresholds gradually increased, while maximum amplitudes and ECAP I/O function slopes gradually decreased, as the electrode location moved from the basal to the apical direction in the cochlea. ECAP responses exhibited no significant correlations with BCNC width or VCN diameter. The ratio of the VCN to FN diameters was significantly correlated with the slope of the ECAP I/O function and the maximum amplitude. BCNC width could not predict the function of the cochlear nerve. Compared with the absolute size of the VCN, the size of the VCN relative to the FN may represent an indicator for predicting the functional status of the cochlear nerve in children diagnosed with cochlear nerve aplasia based on imaging results.

Minimally invasive surgical techniques in vestibular function preservation in patients with cochlear implants.

Background: Cochlear implantation (CI) is an effective and successful method of treating individuals with severe-to-profound sensorineural hearing loss (SNHL). Coupled with it's great clinical effectiveness, there is a risk of vestibular damage. With recent advances in surgical approach, modified electrode arrays and other surgical techniques, the potential of hearing preservation (HP) has emerged, in order to preserve the inner ear function. These techniques may also lead to less vestibular damage. However, a systematic study on this at different follow-ups after CI surgery has not been documented before. Aims: To investigate changes of vestibular function systematically in recipients at short and long follow-ups after a minimally invasive CI surgery. Methods: In this retrospective study, 72 patients (72 ears) with minimally invasive CI were recruited. All participants selected had bilateral SNHL and pre-operative residual hearing (RH) and underwent unilateral CI. They were treated to comprehensive care. All patients underwent vestibular function tests 5 days prior to CI. During the post-operative period, follow-up tests were performed at 1, 3, 6, 9, and 12 months. The contemporaneous results of caloric, cervical vestibular-evoked myogenic potential (cVEMP), ocular vestibular-evoked myogenic potential (oVEMP), and video head impulse (vHIT) tests were followed together longitudinally. Results: On the implanted side, the percent fail rate of caloric test was significantly higher than that of vHIT at 1, 3, and 9 months post-operatively (p < 0.05); the percent fail rate of oVEMP was higher than vHIT of superior semicircular canal (SSC), posterior semicircular canal (PSC), or horizontal semicircular canal (HSC) at 1, 3, and 9 months (p < 0.05); at 3 and 9 months, the percent fail rate of cVEMP was higher than that of SSC and PSC (p < 0.05). There were no significant differences in the percent fail rates among all tests at 6 and 12 months post-CI (p > 0.05). The percent fail rates showed decreased trends in caloric (p = 0.319) and HSC tested by vHIT (p = 0.328) from 1-3 to 6-12 months post-operatively. There was no significant difference in cVEMP between 1-3 and 6-12 months (p = 0.597). No significant differences on percent fail rates of cVEMP and oVEMP between short- and long-terms post-CI were found in the same subjects (p > 0.05). Before surgery, the abnormal cVEMP and oVEMP response rates were both lower in patients with enlarged vestibular aqueduct (EVA) than patients with a normal cochlea (p = 0.001, 0.018, respectively). Conclusion: The short- and long-term impacts on the vestibular function from minimally invasive CI surgery was explored. Most of the vestibular functions can be preserved with no damage discrepancy among the otolith and three semicircular canal functions at 12 months post-CI. Interestingly, a similar pattern of changes in vestibular function was found during the early and the later stages of recovery after surgery.