Gene mutations as a non-invasive measure of adult cochlear implant performance: Variable outcomes in patients with select TMPRSS3 mutations.

BACKGROUND: The cochlear implant (CI) has proven to be a successful treatment for patients with severe-to-profound sensorineural hearing loss, however outcome variance exists. We sought to evaluate particular mutations discovered in previously established sensory and neural partition genes and compare post-operative CI outcomes. MATERIALS AND METHODS: Utilizing a prospective cohort study design, blood samples collected from adult patients with non-syndromic hearing loss undergoing CI were tested for 54 genes of interest with high-throughput sequencing. Patients were categorized as having a pathogenic variant in the sensory partition, pathogenic variant in the neural partition, pathogenic variant in both sensory and neural partition, or with no variant identified. Speech perception performance was assessed pre- and 12 months post-operatively. Performance measures were compared to genetic mutation and variant status utilizing a Wilcoxon rank sum test, with P<0.05 considered statistically significant. RESULTS: Thirty-six cochlear implant patients underwent genetic testing and speech understanding measurements. Of the 54 genes that were interrogated, three patients (8.3%) demonstrated a pathogenic mutation in the neural partition (within TMPRSS3 genes), one patient (2.8%) demonstrated a pathogenic mutation in the sensory partition (within the POU4F3 genes). In addition, 3 patients (8.3%) had an isolated neural partition variance of unknown significance (VUS), 5 patients (13.9%) had an isolated sensory partition VUS, 1 patient (2.8%) had a variant in both neural and sensory partition, and 23 patients (63.9%) had no mutation or variant identified. There was no statistically significant difference in speech perception scores between patients with sensory or neural partition pathogenic mutations or VUS. Variable performance was found within patients with TMPRSS3 gene mutations. CONCLUSION: The impact of genetic mutations on post-operative outcomes in CI patients was heterogenous. Future research and dissemination of mutations and subsequent CI performance is warranted to elucidate exact mutations within target genes providing the best non-invasive prognostic capability.

Predicting Reduced Tinnitus Burden After Cochlear Implantation in Adults.

OBJECTIVE: Explore patient characteristics associated with tinnitus improvement after cochlear implantation. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral. PATIENTS: Adults with bilateral severe-to-profound hearing loss and tinnitus. INTERVENTIONS: Unilateral cochlear implantation. RESULTS: From 1996 to 2018, 358 patients endorsed pre-implant tinnitus and had ascertainable tinnitus status at 1-year. Clinically significant improvement in Tinnitus Handicap Inventory (THI) (reduction by at least 7-points) was observed in 262 (73.2%) patients, of whom 155 (59.2%) reported complete resolution. Of the 24 characteristics explored, four were identified as independent predictors of improved tinnitus in logistic regression models. In a multivariable model including identified independent predictors, each 10-percentage point increase in baseline hearing in noise test was associated with an 14% reduction in odds of tinnitus resolution or clinically significant improvement (odds ratio [OR] 0.86, 95% confidence limits [CL] 0.77, 0.96) and preoperative use of a hearing aid in the contralateral ear was associated with a 72% reduction (OR 0.28; 95% CL 0.11, 0.73). Each 10-point increase in baseline Hearing Handicap Inventory for Adults (HHI) score was associated with a 28% increase in odds of tinnitus improvement (OR 1.28; 95% CL 1.07, 1.54). Higher baseline burden of tinnitus was associated with higher odds of tinnitus improvement (OR 1.21 per 10-point THI increase, 95% CL 1.04, 1.40). CONCLUSIONS: Worse residual hearing and higher baseline hearing and tinnitus handicap are associated with higher odds of tinnitus improvement. Expectations of patients seeking reduced tinnitus burden following cochlear implantation should be managed by counselling regarding odds of tinnitus improvement compared to those with similar residual hearing and tinnitus burden.

Association of Speech Processor Technology and Speech Recognition Outcomes in Adult Cochlear Implant Users.

OBJECTIVE: Determine association of advancements in speech processor technology with improvements in speech recognition outcomes. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: Adult unilateral cochlear implant (CI) recipients. INTERVENTION: Increasing novelty of speech processor defined by year of market availability. MAIN OUTCOME MEASURES: Consonant-Nucleus-Consonant (CNC) and Hearing in Noise Test (HINT) in quiet. RESULTS: From 1991 to 2016, 1,111 CNC scores and 1,121 HINT scores were collected from 351 patients who had complete data. Mean post-implantation CNC score was 53.8% and increased with more recent era of implantation (p < 0.001, analysis of variance [ANOVA]). Median HINT score was 87.0% and did not significantly vary with implantation era (p = 0.06, ANOVA). Multivariable generalized linear models were fitted to estimate the effect of speech processor novelty on CNC and HINT scores, each accounting for clustering of scores within patients and characteristics known to influence speech recognition outcomes. Each 5-year increment in speech processor novelty was independently associated with an increase in CNC score by 2.85% (95% confidence limits [CL] 0.26, 5.44%) and was not associated with change in HINT scores (p = 0.30). CONCLUSION: Newer speech processors are associated with improved CNC scores independent of the year of device implantation and expanding candidacy criteria. The lack of association with HINT scores can be attributed to a ceiling effect, suggesting that HINT in quiet may not be an informative test of speech recognition in the modern CI recipient. The implications of these findings with respect to appropriate interval of speech processor upgrades are discussed.

The Benefit of a Wireless Contralateral Routing of Signals (CROS) Microphone in Unilateral Cochlear Implant Recipients.

OBJECTIVE: Assess speech outcomes in unilateral cochlear implant (CI) recipients after addition of a wireless contralateral routing of signals (CROS) microphone. STUDY DESIGN: Prospective cohort study. SETTING: Ambulatory. PATIENTS: Sixteen adult unilateral CI users with nonserviceable hearing on the contralateral side were recruited. Those with AzBio sentence scores of 40 to 80% or Hearing in Noise Test - Quiet (HINT-Q) scores of 60 to 90% with a CI alone were eligible participants. INTERVENTION: Speech testing was carried out with the CROS on and off. MAIN OUTCOME MEASURE: Speech recognition. RESULTS: In the consonant-nucleus-consonant test presented in quiet from the front, word scores were 64.4 (CI) and 63.8% (CI + CROS) (p = 0.72), and phoneme scores were 80.2 (CI) and 80.8% (CI + CROS) (p = 0.65). In AzBio sentence testing in quiet, with the signals projected from the contralateral, front, or ipsilateral to the CI, speech perception with the CI alone was 60.8, 75.9, and 79.1%. With the addition of the CROS microphone, using the same speaker arrangement, speech perception was 69.8 (p < 0.05), 71.8 (p = 0.05), and 71.8 (p < 0.05). In AzBio sentence testing in noise, speech perception with the CI alone was 18.6, 45.3, and 56.3% when signals were projected from contralateral, front, and ipsilateral sides to the CI. The addition of the CROS microphone led to speech perception of 45.3 (p < 0.05), 45.3 (p = 0.86), and 51.4% (p = 0.27) in the same paradigm. CONCLUSIONS: Addition of a wireless CROS microphone to a unilateral CI recipient can improve users' perception of speech in both quiet and noise if speech signals come from the deaf ear, mitigating the head shadow effect.

Isolated Second Implant Adaptation Period in Sequential Cochlear Implantation in Adults.

OBJECTIVE: To determine if depriving the use of the first cochlear implant (CI1) impacts adaptation to a sequential implant (CI2). STUDY DESIGN: Prospective cohort. SETTING: Academic center. PATIENTS: Sixteen unilateral cochlear implant recipients undergoing contralateral implantation (sequential bilateral) were matched according to age, etiology, duration of deafness, device age, and delay between implants. INTERVENTION: During a 4-week adaptation period after CI2 activation, patients underwent deprivation of CI1 or were permitted continued use of it. MAIN OUTCOME MEASURES: Speech perception scores and subjective quality of life outcomes before CI2 and at 1, 3, 6, and 12-months following activation. RESULTS: Maximal CI2 speech perception scores in quiet were achieved by 1-month postactivation for the "deprivation" group (71.3% for hearing in noise test [HINT], p = 0.767 for change beyond 1-mo) compared with 6-months for the "continued use" group (67.9% for HINT, p = 0.064 for change beyond 6-mo). The "deprivation" group experienced a temporary drop in CI1 scores (67.9% for HINT in quiet at 1-mo versus 78.4% pre-CI2, p = 0.009) recovering to 77.3% by 3-months; unchanged from baseline levels (p = 1.0). A binaural advantage over the better hearing ear was present for HINT sentences with noise (72.4% versus 58.8% for "deprivation", p = 0.001; 71.5% versus 52.7% for "continued use," p = 0.01). Missing data precluded a meaningful analysis of subjective quality of life outcome scales. CONCLUSION: Bilateral cochlear implantation improves speech perception compared with one implant. A period of deprivation from CI1 shortens time to maximum speech perception by CI2 without long-term consequences on the performance of CI1.

The Role of Preoperative Steroids for Hearing Preservation Cochlear Implantation: Results of a Randomized Controlled Trial.

OBJECTIVES: To determine whether preoperative steroids can improve hearing outcomes in cochlear implantation (CI). METHODS: This is a randomized controlled trial involving 30 postlingual deaf CI patients. Subjects had preoperative thresholds of better than or equal to 80 dB at 125 and 250 Hz, and better than or equal to 90 dB at 500 and 1,000 Hz. The subjects were randomized to a control group, an oral steroid group (receiving 1 mg/kg/day of prednisolone for 6 days prior to surgery), or a transtympanic steroid group (receiving a single dose of 0.5 mL of 10 mg/mL dexamethasone at 24 h prior to surgery). RESULTS: The subjects receiving transtympanic steroids had a significant decrease in the pure tone average over 3 months compared to the control and oral steroid group, which persisted over 12 months (p < 0.05). CONCLUSION: A single dose of preoperative transtympanic steroids prior to CI appears to have a beneficial effect, at least in the short term, with minimal effects seen in the longer term.

Towards a Unified Testing Framework for Single-Sided Deafness Studies: A Consensus Paper.

BACKGROUND: While hearing aids for a contralateral routing of signals (CROS-HA) and bone conduction devices have been the traditional treatment for single-sided deafness (SSD) and asymmetric hearing loss (AHL), in recent years, cochlear implants (CIs) have increasingly become a viable treatment choice, particularly in countries where regulatory approval and reimbursement schemes are in place. Part of the reason for this shift is that the CI is the only device capable of restoring bilateral input to the auditory system and hence of possibly reinstating binaural hearing. Although several studies have independently shown that the CI is a safe and effective treatment for SSD and AHL, clinical outcome measures in those studies and across CI centers vary greatly. Only with a consistent use of defined and agreed-upon outcome measures across centers can high-level evidence be generated to assess the safety and efficacy of CIs and alternative treatments in recipients with SSD and AHL. METHODS: This paper presents a comparative study design and minimum outcome measures for the assessment of current treatment options in patients with SSD/AHL. The protocol was developed, discussed, and eventually agreed upon by expert panels that convened at the 2015 APSCI conference in Beijing, China, and at the CI 2016 conference in Toronto, Canada. RESULTS: A longitudinal study design comparing CROS-HA, BCD, and CI treatments is proposed. The recommended outcome measures include (1) speech in noise testing, using the same set of 3 spatial configurations to compare binaural benefits such as summation, squelch, and head shadow across devices; (2) localization testing, using stimuli that rove in both level and spectral content; (3) questionnaires to collect quality of life measures and the frequency of device use; and (4) questionnaires for assessing the impact of tinnitus before and after treatment, if applicable. CONCLUSION: A protocol for the assessment of treatment options and outcomes in recipients with SSD and AHL is presented. The proposed set of minimum outcome measures aims at harmonizing assessment methods across centers and thus at generating a growing body of high-level evidence for those treatment options.

The role of a new contralateral routing of signal microphone in established unilateral cochlear implant recipients.

OBJECTIVES/HYPOTHESIS: To investigate whether a contralateral routing of signal (CROS) microphone combined with a unilateral cochlear implant (CI) results in hearing improvement after a prolonged trial period. STUDY DESIGN: A prospective experimental trial was undertaken on a group of 10 postlingually deafened adults who are experienced CI users. METHODS: Participants completed audiometric testing and validated questionnaires with their unilateral CI alone, followed by addition of a CROS microphone (CI-CROS). This was worn daily for the 2-week trial, after which hearing performance was reevaluated using the same measures. Objective tests included AzBio sentences in quiet and noise and consonant-vowel nucleus-consonant (CNC) words. Subjective measures included the Abbreviated Profile of Hearing Aid Benefit (APHAB); Speech, Spatial, Qualities of Hearing Index (SSQ); Hearing Implant Sound Quality Index; an institutional questionnaire; and a daily log sheet. RESULTS: There is statistically significant enhanced speech discrimination with the CI-CROS when speech is presented on the CROS side. However, scores are markedly diminished when background noise is introduced, particularly to the CROS side. Subjective results indicate lower satisfaction scores for the global and ease of communication subdomains of the APHAB with the CI-CROS, but increased scores on the spatial hearing subdomain of the SSQ (P < 0.05). CONCLUSION: The CI-CROS provides significant benefit in certain situations, particularly speech recognition in quiet. CI-CROS performance with background noise is poor, leading to low satisfaction scores. Further refinement of the device may yield a useful tool for unilateral CI users in the future.

Management of single-sided deafness with the bone-anchored hearing aid.

OBJECTIVES: The benefits of the bone-anchored hearing aid (BAHA) for rehabilitation of conductive and mixed hearing loss are well established. Recently, the BAHA was used to rehabilitate patients with single-sided deafness (SSD). In this study, the benefits of the BAHA in SSD are presented. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Twenty-one consecutive adult patients with SSD underwent single-stage BAHA implantation on the side of deafness. Testing in sound field was performed using the hearing-in-noise test (HINT) in both unaided and aided conditions. Speech and noise signals were delivered through two speakers oriented in two test paradigms. The outcomes were expressed as signal-to-noise (S/N) ratios. Subjective benefit analyses were determined through two questionnaires: the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Glasgow Hearing Aid Benefit Profile (GHABP). RESULTS: All subjects demonstrated significant improvement in speech reception thresholds with the HINT using the BAHA, especially with the 90/270 speaker paradigm, in which the mean improvement over the unaided condition was 5.5 dB SPL (range, 2.0-11.0 dB; P=0.00001). Qualitative subjective outcome measures demonstrated additional benefits. CONCLUSION: In SSD patients, the BAHA provides significant subjective benefits and improves speech understanding in noise.