The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study.

Pathogenic variations in the OTOF gene are a common cause of hearing loss. To refine the natural history and genotype-phenotype correlations of OTOF-related auditory neuropathy spectrum disorders (ANSD), audiograms and distortion product otoacoustic emissions (DPOAEs) were collected from a diverse cohort of individuals diagnosed with OTOF-related ANSD by comprehensive genetic testing and also reported in the literature. Comparative analysis was undertaken to define genotype-phenotype relationships using a Monte Carlo algorithm. 67 audiograms and 25 DPOAEs from 49 unique individuals positive for OTOF-related ANSD were collected. 51 unique OTOF pathogenic variants were identified of which 21 were missense and 30 were loss of function (LoF; nonsense, splice-site, copy number variants, and indels). There was a statistically significant difference in low, middle, and high frequency hearing thresholds between missense/missense and LoF/missense genotypes as compared to LoF/LoF genotypes (average hearing threshold for low, middle and high frequencies 70.9, 76.0, and 73.4 dB vs 88.5, 95.6, and 94.7 dB) via Tukey's test with age as a co-variate (P = 0.0180, 0.0327, and 0.0347, respectively). Hearing declined during adolescence with missense/missense and LoF/missense genotypes, with an annual mid-frequency threshold deterioration of 0.87 dB/year and 1.87 dB/year, respectively. 8.5% of frequencies measured via DPOAE were lost per year in individuals with serial tests. Audioprofiling of OTOF-related ANSD suggests significantly worse hearing with LoF/LoF genotypes. The unique pattern of variably progressive OTOF-related autosomal recessive ANSD may be amenable to gene therapy in selected clinical scenarios.

Evaluation of speech recognition of cochlear implant recipients using a personal digital adaptive radio frequency system.

BACKGROUND: Previous research supports the use of frequency modulation (FM) systems for improving speech recognition in noise of individuals with cochlear implants (CIs). However, at this time, there is no published research on the potential speech recognition benefit of new digital adaptive wireless radio transmission systems. PURPOSE: The goal of this study was to compare speech recognition in quiet and in noise of CI recipients while using traditional, fixed-gain analog FM systems, adaptive analog FM systems, and adaptive digital wireless radio frequency transmission systems. RESEARCH DESIGN: A three-way repeated-measures design was used to examine performance differences among devices, among speech recognition conditions in quiet and in increasing levels of background noise, and between users of Advanced Bionics and Cochlear CIs. STUDY SAMPLE: Seventeen users of Advanced Bionics Harmony CI sound processors and 20 users of Cochlear Nucleus 5 sound processors were included in the study. DATA COLLECTION AND ANALYSIS: Participants were tested in a total of 32 speech-recognition-in noise-test conditions, which included one no-FM and three device conditions (fixed-gain FM, adaptive FM, and adaptive digital) at the following signal levels: 64 dBA speech (at the location of the participant) in quiet and 64 dBA speech with competing noise at 50, 55, 60, 65, 70, 75, and 80 dBA noise levels. RESULTS: No significant differences were detected between the users of Advanced Bionics and Cochlear CIs. All of the radio frequency system conditions (i.e., fixed-gain FM, adaptive FM, and adaptive digital) outperformed the no-FM conditions in test situations with competing noise. Specifically, in conditions with 70, 75, and 80 dBA of competing noise, the adaptive digital system provided better performance than the fixed-gain and adaptive FM systems. The adaptive FM system did provide better performance than the fixed-gain FM system at 70 and 75 dBA of competing noise. At the lower noise levels of 50, 55, 60, and 65 dBA, no significant differences were detected across the three systems, and no significant differences were found across the quiet conditions. In all conditions, performance became poorer as the competing noise level increased. CONCLUSIONS: In high levels of noise, the adaptive digital system provides superior performance when compared to adaptive analog FM and fixed-gain FM systems.

Worldwide trends in bilateral cochlear implantation.

OBJECTIVES/HYPOTHESIS: The goal of this study is to ascertain worldwide experience with bilateral cochlear implantation (BCI) with regard to patient demographics, trends in provision of BCI to adult and child patient populations, differences and similarities in BCI candidacy criteria, diagnostic requirements, and treatment approaches among clinicians in high-volume cochlear implant centers. STUDY DESIGN: Retrospective/prospective. METHODS: : An electronic survey consisting of 59 mainly multiple-choice questions was developed for online completion. It examined the implant experience and clinical opinion of expert cochlear implant (CI) centers worldwide on the indications, motivations, and contraindications for adult and pediatric, simultaneous and sequential BCI candidacy. Centers were chosen to complete the survey based on their known reputation as a center of excellence. Patient demographics were queried for two time periods to elucidate trends: 2006 and prior, and for the year 2007. RESULTS: Seventy-one percent (25/35) of the CI clinics approached completed the survey. Collectively, these 25 clinics represent experience with approximately 23,200 CI users globally, representing 15% of the total estimated CI population worldwide. The total number of BCI surgeries reflected in their experience (2,880) represents 36% of the estimated number worldwide as of December 2007. Cumulatively to the end of 2007, 70% of all BCI surgeries have occurred in children, with the 3- to 10-year-old age group having the highest representation (33% of all BCIs), followed in order by adults (30%), children under 3 years of age (26%), and children between 11 and 18 years of age (11%). Seventy-two percent of all BCI surgeries were performed sequentially (70% of children, 76% of adults). Children <3 years of age represent the only age group of all patients in which simultaneous surgeries predominate (58% simultaneous). For all other age groups, sequential surgeries far outnumber simultaneous (3-10 years, 84% sequential; 11-18 years, 94% sequential; adults, 76% sequential). Prior to January 2007, 68% of BCIs were performed in children. This increased to 79% for the year 2007 (P < .001). With regard to children only, a change is apparent over time in terms of the age group making up the majority of pediatric BCI surgeries performed. Prior to 2007, children 3 to 10 years of age made up 50% of the children undergoing BCI, whereas those <3 years made up only 33%. In 2007 this shifted more toward the younger age group (47% for those <3 years and 40% for 3-10-year-olds; P < .001). United States clinics had a higher proportion of adult BCI patients (59% children, 41% adults) than the non-United States clinics (78% children, 22% adults; P < .001). The majority of responders do not hold to a minimum or maximum age by which they limit BCI. CONCLUSIONS: Worldwide experience with BCI is now quite extensive and provides a useful base for evaluating clinical outcomes across patient categories and for providing further support during the patient/parent counseling process.

Importance of age and postimplantation experience on speech perception measures in children with sequential bilateral cochlear implants.

OBJECTIVES: Clinical trials in which children received bilateral cochlear implants in sequential operations were conducted to analyze the extent to which bilateral implantation offers benefits on a number of measures. The present investigation was particularly focused on measuring the effects of age at implantation and experience after activation of the second implant on speech perception performance. STUDY DESIGN: Thirty children aged 3 to 13 years were recipients of 2 cochlear implants, received in sequential operations, a minimum of 6 months apart. All children received their first implant before 5 years of age and had acquired speech perception capabilities with the first device. They were divided into 3 age groups on the basis of age at time of second ear implantation: Group I, 3 to 5 years; Group II, 5.1 to 8 years; and Group III, 8.1 to 13 years. Speech perception measures in quiet included the Multisyllabic Lexical Neighborhood Test (MLNT) for Group I, the Lexical Neighborhood Test (LNT) for Groups II and III, and the Hearing In Noise Test for Children (HINT-C) sentences in quiet for Group III. Speech perception in noise was assessed using the Children's Realistic Intelligibility and Speech Perception (CRISP) test. Testing was performed preoperatively and again postactivation of the second implant at 3, 6, and 12 months (CRISP at 3 and 9 mo) in both the unilateral and bilateral conditions in a repeated-measures study design. Two-way repeated-measures analysis of variance was used to analyze statistical significance among device configurations and performance over time. SETTING: US Multicenter. RESULTS: Results for speech perception in quiet show that children implanted sequentially acquire open-set speech perception in the second ear relatively quickly (within 6 mo). However, children younger than 8 years do so more rapidly and to a higher level of speech perception ability at 12 months than older children (mean second ear MLNT/LNT scores at 12 months: Group I, 83.9%; range, 71-96%; Group II, 59.5%; range, 40-88%; Group III, 32%; range, 12-56%). The second-ear mean HINT-C score for Group III children remained far less than that of the first ear even after 12 months of device use (44 versus 89%; t, 6.48; p<0.001; critical value, 0.025). Speech intelligibility for spondees in noise was significantly better under bilateral conditions than with either ear alone when all children were analyzed as a single group and for Group III children. At the 9-month test interval, performance in the bilateral configuration was significantly better for all noise conditions (13.2% better for noise at first cochlear implant, 6.8% better for the noise front and noise at second cochlear implant conditions, t=2.32, p=0.024, critical level=0.05 for noise front; t=3.75, p<0.0001, critical level=0.05 for noise at first implant; t=2.73, p = 0.008, critical level=0.05 for noise at second implant side). The bilateral benefit in noise increased with time from 3 to 9 months after activation of the second implant. This bilateral advantage is greatest when noise is directed toward the first implanted ear, indicating that the head shadow effect is the most effective binaural mechanism. The bilateral condition produced small improvements in speech perception in quiet and for individual Group I and Group II patient results in noise that, in view of the relatively small number of subjects tested, do not reach statistical significance. CONCLUSION: Sequential bilateral cochlear implantation in children of diverse ages has the potential to improve speech perception abilities in the second implanted ear and to provide access to the use of binaural mechanisms such as the head shadow effect. The improvement unfolds over time and continues to grow during the 6 to 12 months after activation of the second implant. Younger children in this study achieved higher open-set speech perception scores in the second ear, but older children still demonstrate bilateral benefit in noise. Determining the long-term impact and cost-effectiveness that results from such potential capabilities in bilaterally implanted children requires additional study with larger groups of subjects and more prolonged monitoring.