The natural history and genotype-phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis.

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype-phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.

Musical Emotion Categorization with Vocoders of Varying Temporal and Spectral Content.

While previous research investigating music emotion perception of cochlear implant (CI) users observed that temporal cues informing tempo largely convey emotional arousal (relaxing/stimulating), it remains unclear how other properties of the temporal content may contribute to the transmission of arousal features. Moreover, while detailed spectral information related to pitch and harmony in music - often not well perceived by CI users- reportedly conveys emotional valence (positive, negative), it remains unclear how the quality of spectral content contributes to valence perception. Therefore, the current study used vocoders to vary temporal and spectral content of music and tested music emotion categorization (joy, fear, serenity, sadness) in 23 normal-hearing participants. Vocoders were varied with two carriers (sinewave or noise; primarily modulating temporal information), and two filter orders (low or high; primarily modulating spectral information). Results indicated that emotion categorization was above-chance in vocoded excerpts but poorer than in a non-vocoded control condition. Among vocoded conditions, better temporal content (sinewave carriers) improved emotion categorization with a large effect while better spectral content (high filter order) improved it with a small effect. Arousal features were comparably transmitted in non-vocoded and vocoded conditions, indicating that lower temporal content successfully conveyed emotional arousal. Valence feature transmission steeply declined in vocoded conditions, revealing that valence perception was difficult for both lower and higher spectral content. The reliance on arousal information for emotion categorization of vocoded music suggests that efforts to refine temporal cues in the CI user signal may immediately benefit their music emotion perception.

Age-related High-frequency Hearing Loss Is Not Associated With Horizontal Semicircular Canal Function.

OBJECTIVE: Investigate the association between age-related hearing loss and reduced peripheral vestibular function using paired assessments of high-frequency hearing and horizontal semicircular canal (HSC) function. We hypothesized that age-related high-frequency hearing loss would be correlated with reduced HSC function and, therefore, useful to predict age-related vestibular hypofunction. DESIGN: We conducted a single center, retrospective cross-sectional study in a tertiary/academic referral hospital. This study included 185 patients who were diagnosed with a cerebellopontine angle (CPA) tumor and referred to the academic hospital to evaluate treatment options. Data collected included pure-tone audiometry, caloric reflex test, video head-impulse test (vHIT), and medical history. High-frequency hearing loss was quantified by the high Fletcher index (hFI), and horizontal semicircular canal (HSC) function were quantified by the caloric reflex test and vHIT. RESULTS: We observed a significant association between age and high-frequency hearing loss that was significantly worse in men compared with women. In contrast, we observed no significant association between age and HSC function assessed by either the caloric reflex test or vHIT. We observed associations between HSC function and sex, with male sex predicting reduced HSC function by caloric reflex testing but enhanced HSC function by vHIT. High-frequency hearing loss did not predict HSC hypofunction. CONCLUSIONS: We found no evidence indicating age-related decline in HSC function or an association between age-related high-frequency hearing loss and age-related decline in HSC function. We did observe sex-specific differences in HSC function. Our study highlights the need for sex-specific normative values for identifying age-related reduced peripheral vestibular function and for future work linking comprehensive assessments of inner ear function with tests of balance and stability to understand the complex interactions underlying hearing loss and imbalance, especially in the elderly.

Changes in Tinnitus by Cochlear Implantation: A Parametric Study of the Effect of Single-Electrode Stimulation.

INTRODUCTION: While cochlear implantation may have a positive effect on tinnitus, it is not effective in reducing tinnitus in all patients. This may be due to different patients requiring different strategies of electrical stimulation in order to obtain a positive effect on tinnitus. It is, therefore, important to identify the most effective stimulation strategies to reduce tinnitus. The simplest possible strategy is stimulation by only one electrode. In this study, we investigated tinnitus suppression by electrical stimulation via a single electrode of the cochlear implant. METHODS: We performed a listening experiment in 19 adult participants, who had received a unilateral cochlear implant (CI) because of severe bilateral hearing loss. All of these patients had indicated that they suffered from tinnitus. During a 300-s interval, patients listened to blocks of single-electrode stimulation and rated the loudness of the stimulus and any effects on their tinnitus. The 300-s interval included a block of single-electrode stimulation (duration 120 s). In consecutive intervals, the stimulus differed in its cochlear location (basal or apical), its pulse rate (720 or 725 Hz, 1,200 Hz, and 2,400 or 2,320 Hz), and amplitude (just above threshold or equivalent to moderate loudness). Thus, 2 × 3 × 2 = 12 stimulus conditions were tested in each participant, and each condition was presented only once. During the experiment, the participants promptly rated the loudness of the stimuli and the loudness of their tinnitus on a Visual Analogue Scale (10-point VAS). RESULTS: Significantly more tinnitus reduction was observed with stimuli at a moderate intensity level (30%) compared to stimuli at near-threshold level (18%) (χ2 [1, N = 222] = 14.115, p < 0.01). No significant differences in tinnitus levels resulted from the different pulse rates and stimulation sites. Eight participants reported an increase of tinnitus loudness under at least one stimulus condition. Changes in tinnitus loudness were generally minor, and never exceeded 3 points on the VAS. The overall effect of cochlear implantation on tinnitus, that is, the effect with full-array stimulation, was not correlated with the effectiveness of the single-electrode stimulation on tinnitus. CONCLUSION: In conclusion, the effect of single-electrode stimulation on tinnitus is relatively insignificant in comparison to the effect of full-array stimulation. However, in some individual cases, sustained single-electrode stimulation may be beneficial for tinnitus management.

The Relation Between Tinnitus and a Neurovascular Conflict of the Cochleovestibular Nerve on Magnetic Resonance Imaging.

INTRODUCTION: Magnetic resonance (MR) imaging is often used in diagnostic evaluation of tinnitus patients. Incidental findings like a neurovascular conflict (NVC) in the cerebellopontine angle are often found; however, the diagnostic value of this finding remains unclear. The aim of this study is to investigate whether the type or degree of compression of the vestibulocochlear nerve is of diagnostic value in patients with a NVC. METHODS: A retrospective study was performed in 111 tinnitus patients with available MR imaging between 2013 and 2015. Clinical and audiometric variables were gathered and MR imaging was reevaluated by two neuroradiologists. NVCs were analyzed using a grading system based on previous research by Sirikci et al. RESULTS:: In total, 220 ears were available for assessment. In patients with unilateral tinnitus a loop compression and an indentation of the cochleovestibular nerve were more frequent than in patients with bilateral tinnitus. However, there was no significant difference in distribution of the type of compression between tinnitus and nontinnitus ears. Patient with unilateral tinnitus had a significantly higher degree of hearing loss in the symptomatic ear, compared with the asymptomatic ear and with the bilateral tinnitus group. Also, it was found that the degree of hearing loss did not differ between the various types of compression. CONCLUSION: This study did not find a diagnostic value of specific types of compression in patients with a NVC. Although the distribution of NVC classification was different in patients with unilateral and bilateral tinnitus, there was no definite relation between the type of NVC and the presence of ipsilateral tinnitus. Also, the degree of hearing loss was not related to specific types of NVC.

An auditory brainstem implant for treatment of unilateral tinnitus: protocol for an interventional pilot study.

INTRODUCTION: Tinnitus may have a very severe impact on the quality of life. Unfortunately, for many patients, a satisfactory treatment modality is lacking. The auditory brainstem implant (ABI) was originally indicated for hearing restoration in patients with non-functional cochlear nerves, for example, in neurofibromatosis type II. In analogy to a cochlear implant (CI), it has been demonstrated that an ABI may reduce tinnitus as a beneficial side effect. For tinnitus treatment, an ABI may have an advantage over a CI, as cochlear implantation can harm inner ear structures due to its invasiveness, while an ABI is presumed to not damage anatomical structures. This is the first study to implant an ABI to investigate its effect on intractable tinnitus. METHODS AND ANALYSIS: In this pilot study, 10 adults having incapacitating unilateral intractable tinnitus and ipsilateral severe hearing loss will have an ABI implanted. The ABI is switched on 6 weeks after implantation, followed by several fitting sessions aimed at finding an optimal stimulation strategy. The primary outcome will be the change in Tinnitus Functioning Index. Secondary outcomes will be tinnitus burden and quality of life (using Tinnitus Handicap Inventory and Hospital Anxiety and Depression Scale questionnaires), tinnitus characteristics (using Visual Analogue Scale, a tinnitus analysis), safety, audiometric and vestibular function. The end point is set at 1 year after implantation. Follow-up will continue until 5 years after implantation. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Institutional Review Board of the University Medical Centre Groningen, The Netherlands (METc 2015/479). The trial is registered at www.clinicialtrials.gov and will be updated if amendments are made. Results of this study will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02630589. TRIAL STATUS: Inclusion of first patient in November 2017. Data collection is in progress. Trial is open for further inclusion. The trial ends at 5 years after inclusion of the last patient.

No Difference in Behavioral and Self-Reported Outcomes for Simultaneous and Sequential Bilateral Cochlear Implantation: Evidence From a Multicenter Randomized Controlled Trial.

Objective: The primary aim of this study was to longitudinally compare the behavioral and self-reported outcomes of simultaneous bilateral cochlear implantation (simBiCI) and sequential BiCI (seqBiCI) in adults with severe-to-profound postlingual sensorineural hearing loss. Design: This study is a multicenter randomized controlled trial with a 4-year follow-up period after the first moment of implantation. Participants were allocated by randomization to receive bilateral cochlear implants (CIs) either, simultaneously (simBiCI group) or sequentially with an inter-implant interval of 2 years (UCI/seqBiCI group). All sequential patients where encouraged to use their hearing aid on the non-implanted ear over of the first 2 years. Patients were followed-up on an annual basis. The primary outcome was speech perception in noise coming from a source directly in front of the patient. Other behavioral outcome measures were speech intelligibility-in-noise from spatially separated sources, localization and speech perception in quiet. Self-reported outcome measures encompassed questionnaires on quality of life, quality of hearing and tinnitus. All outcome measures were analyzed longitudinally using a linear or logistic regression analysis with an autoregressive residual covariance matrix (generalized estimating equations type). Results: Nineteen participants were randomly allocated to the simBiCI group and 19 participants to the UCI/seqBiCI group. Three participants in the UCI/seqBiCI group did not proceed with their second implantation and were therefore unavailable for follow-up. Both study groups performed equally well on speech perception in noise from a source directly in front of the patient longitudinally. During all 4 years of follow-up the UCI/seqBiCI group performed significantly worse compared to the simBiCI group on spatial speech perception in noise in the best performance situation (8.70 dB [3.96 - 13.44], p < 0.001) and localization abilities (largest difference 60 degrees configuration: -44.45% [-52.15 - -36.74], p < 0.0001). Furthermore, during all years of follow-up, the UCI/seqBiCI group performed significantly worse on quality of hearing and quality of life questionnaires. The years of unilateral CI use were the reason for the inferior results in the UCI/SeqBiCI group. One year after receiving CI2, the UCI/seqBiCI group performance did not statistically differ from the performance of the simBiCI group on all these outcomes. Furthermore, no longitudinal differences were seen in tinnitus burden prevalence between groups. Finally, the complications that occurred during this trial were infection, dysfunction of CI, facial nerve palsy, tinnitus and vertigo. Conclusion: This randomized controlled trial on bilaterally severely hearing impaired participants found a significantly worse longitudinal performance of UCI/seqBiCI compared to simBiCI on multiple behavioral and self-reported outcomes regarding speech perception in noise and localization abilities. This difference is associated with the inferior performance of the UCI/seqBiCI participants during the years of unilateral CI use. After receiving the second CI however, the performance of the UCI/seqBiCI group did not significantly differ from the simBiCI group. Trial Registration: Dutch Trial Register NTR1722.

De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment.

ATP2B2 encodes the PMCA2 Ca2+ pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca2+ from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been reported as a modifier, or in a digenic mechanism with CDH23 for hearing impairment in humans. Whole exome sequencing in hearing impaired index cases of Dutch and Polish origins revealed five novel heterozygous (predicted to be) loss-of-function variants of ATP2B2. Two variants, c.1963G>T (p.Glu655*) and c.955delG (p.Ala319fs), occurred de novo. Three variants c.397+1G>A (p.?), c.1998C>A (p.Cys666*), and c.2329C>T (p.Arg777*), were identified in families with an autosomal dominant inheritance pattern of hearing impairment. After normal newborn hearing screening, a rapidly progressive high-frequency hearing impairment was diagnosed at the age of about 3-6 years. Subjects had no balance complaints and vestibular testing did not yield abnormalities. There was no evidence for retrocochlear pathology or structural inner ear abnormalities. Although a digenic inheritance pattern of hearing impairment has been reported for heterozygous missense variants of ATP2B2 and CDH23, our findings indicate a monogenic cause of hearing impairment in cases with loss-of-function variants of ATP2B2.

Musician effect on perception of spectro-temporally degraded speech, vocal emotion, and music in young adolescents.

In adult normal-hearing musicians, perception of music, vocal emotion, and speech in noise has been previously shown to be better than non-musicians, sometimes even with spectro-temporally degraded stimuli. In this study, melodic contour identification, vocal emotion identification, and speech understanding in noise were measured in young adolescent normal-hearing musicians and non-musicians listening to unprocessed or degraded signals. Different from adults, there was no musician effect for vocal emotion identification or speech in noise. Melodic contour identification with degraded signals was significantly better in musicians, suggesting potential benefits from music training for young cochlear-implant users, who experience similar spectro-temporal signal degradations.

Comparison of Two Music Training Approaches on Music and Speech Perception in Cochlear Implant Users.

In normal-hearing (NH) adults, long-term music training may benefit music and speech perception, even when listening to spectro-temporally degraded signals as experienced by cochlear implant (CI) users. In this study, we compared two different music training approaches in CI users and their effects on speech and music perception, as it remains unclear which approach to music training might be best. The approaches differed in terms of music exercises and social interaction. For the pitch/timbre group, melodic contour identification (MCI) training was performed using computer software. For the music therapy group, training involved face-to-face group exercises (rhythm perception, musical speech perception, music perception, singing, vocal emotion identification, and music improvisation). For the control group, training involved group nonmusic activities (e.g., writing, cooking, and woodworking). Training consisted of weekly 2-hr sessions over a 6-week period. Speech intelligibility in quiet and noise, vocal emotion identification, MCI, and quality of life (QoL) were measured before and after training. The different training approaches appeared to offer different benefits for music and speech perception. Training effects were observed within-domain (better MCI performance for the pitch/timbre group), with little cross-domain transfer of music training (emotion identification significantly improved for the music therapy group). While training had no significant effect on QoL, the music therapy group reported better perceptual skills across training sessions. These results suggest that more extensive and intensive training approaches that combine pitch training with the social aspects of music therapy may further benefit CI users.

A Prospective Study of the Effect of Cochlear Implantation on Tinnitus.

Previous studies have shown diverse and sometimes even contrary results concerning the effect of cochlear implantation on tinnitus and the factors that can influence this effect. The aim of this prospective questionnaire study was to determine the effects of cochlear implantation on tinnitus and explore which factors can influence the effect of cochlear implantation on tinnitus. Forty-four of the patients implanted in our hospital returned 2 questionnaire packages, i.e., one before the cochlear implantation and one 6 months after implantation. Before implantation, 66% of the patients experienced tinnitus. This study shows that cochlear implantation could help to reduce tinnitus and the tinnitus handicap in at least 28% of the patients with preoperative tinnitus. In 72% of the patients the tinnitus remained after implantation. None of the patients developed tinnitus after implantation. A shorter duration of tinnitus prior to implantation, a more fluctuating type of tinnitus, a higher tinnitus handicap prior to implantation, and a round-window surgical approach might have a positive influence on the effect of cochlear implantation on tinnitus, but further research is necessary to confirm these findings.

Tinnitus after Simultaneous and Sequential Bilateral Cochlear Implantation.

IMPORTANCE: There is an ongoing global discussion on whether or not bilateral cochlear implantation should be standard care for bilateral deafness. Contrary to unilateral cochlear implantation, however, little is known about the effect of bilateral cochlear implantation on tinnitus. OBJECTIVE: To investigate tinnitus outcomes 1 year after bilateral cochlear implantation. Secondarily, to compare tinnitus outcomes between simultaneous and sequential bilateral cochlear implantation and to investigate long-term follow-up (3 years). STUDY DESIGN: This study is a secondary analysis as part of a multicenter randomized controlled trial. METHODS: Thirty-eight postlingually deafened adults were included in the original trial, in which the presence of tinnitus was not an inclusion criterion. All participants received cochlear implants (CIs) because of profound hearing loss. Nineteen participants received bilateral CIs simultaneously and 19 participants received bilateral CIs sequentially with an inter-implant interval of 2 years. The prevalence and severity of tinnitus before and after simultaneous and sequential bilateral cochlear implantation were measured preoperatively and each year after implantation with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ). RESULTS: The prevalence of preoperative tinnitus was 42% (16/38). One year after bilateral implantation, there was a median difference of -8 (inter-quartile range (IQR): -28 to 4) in THI score and -9 (IQR: -17 to -9) in TQ score in the participants with preoperative tinnitus. Induction of tinnitus occurred in five participants, all in the simultaneous group, in the year after bilateral implantation. Although the preoperative and also the postoperative median THI and TQ scores were higher in the simultaneous group, the median difference scores were equal in both groups. In the simultaneous group, tinnitus scores fluctuated in the 3 years after implantation. In the sequential group, four patients had an additional benefit of the second CI: a total suppression of tinnitus compared with their unilateral situation. CONCLUSION: While bilateral cochlear implantation can have a positive effect on preoperative tinnitus complaints, the induction of (temporary or permanent) tinnitus was also reported. CLINICAL TRIAL REGISTRATION: Dutch Trial Register NTR1722.

Guidelines in CHARGE syndrome and the missing link: Cranial imaging.

"CHARGE syndrome" is a complex syndrome with high and extremely variable comorbidity. As a result, clinicians may struggle to provide accurate and comprehensive care, and this has led to the publication of several clinical surveillance guidelines and recommendations for CHARGE syndrome, based on both single case observations and cohort studies. Here we perform a structured literature review to examine all the existing advice. Our findings provide additional support for the validity of the recently published Trider checklist. We also identified a gap in literature when reviewing all guidelines and recommendations, and we propose a guideline for neuroradiological evaluation of patients with CHARGE syndrome. This is of importance, as patients with CHARGE are at risk for peri-anesthetic complications, making recurrent imaging procedures under anesthesia a particular risk in clinical practice. However, comprehensive cranial imaging is also of tremendous value for timely diagnosis, proper treatment of symptoms and for further research into CHARGE syndrome. We hope the guideline for neuroradiological evaluation will help clinicians provide efficient and comprehensive care for individuals with CHARGE syndrome.

Objective and Subjective Measures of Simultaneous vs Sequential Bilateral Cochlear Implants in Adults: A Randomized Clinical Trial.

Importance: To date, no randomized clinical trial on the comparison between simultaneous and sequential bilateral cochlear implants (BiCIs) has been performed. Objective: To investigate the hearing capabilities and the self-reported benefits of simultaneous BiCIs compared with those of sequential BiCIs. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted between January 12, 2010, and September 2, 2012, at 5 tertiary referral centers among 40 participants eligible for BiCIs. Main inclusion criteria were postlingual severe to profound hearing loss, age 18 to 70 years, and a maximum duration of 10 years without hearing aid use in both ears. Data analysis was conducted from May 24 to June 12, 2016. Interventions: The simultaneous BiCI group received 2 cochlear implants during 1 surgical procedure. The sequential BiCI group received 2 cochlear implants with an interval of 2 years between implants. Main Outcomes and Measures: First, the results 1 year after receiving simultaneous BiCIs were compared with the results 1 year after receiving sequential BiCIs. Second, the results of 3 years of follow-up for both groups were compared separately. The primary outcome measure was speech intelligibility in noise from straight ahead. Secondary outcome measures were speech intelligibility in noise from spatially separated sources, speech intelligibility in silence, localization capabilities, and self-reported benefits assessed with various hearing and quality of life questionnaires. Results: Nineteen participants were randomized to receive simultaneous BiCIs (11 women and 8 men; median age, 52 years [interquartile range, 36-63 years]), and another 19 participants were randomized to undergo sequential BiCIs (8 women and 11 men; median age, 54 years [interquartile range, 43-64 years]). Three patients did not receive a second cochlear implant and were unavailable for follow-up. Comparable results were found 1 year after simultaneous or sequential BiCIs for speech intelligibility in noise from straight ahead (difference, 0.9 dB [95% CI, -3.1 to 4.4 dB]) and all secondary outcome measures except for localization with a 30° angle between loudspeakers (difference, -10% [95% CI, -20.1% to 0.0%]). In the sequential BiCI group, all participants performed significantly better after the BiCIs on speech intelligibility in noise from spatially separated sources and on all localization tests, which was consistent with most of the participants' self-reported hearing capabilities. Speech intelligibility-in-noise results improved in the simultaneous BiCI group up to 3 years following the BiCIs. Conclusions and Relevance: This study shows comparable objective and subjective hearing results 1 year after receiving simultaneous BiCIs and sequential BiCIs with an interval of 2 years between implants. It also shows a significant benefit of sequential BiCIs over a unilateral cochlear implant. Until 3 years after receiving simultaneous BiCIs, speech intelligibility in noise significantly improved compared with previous years. Trial Registration: trialregister.nl Identifier: NTR1722.

Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.

INTRODUCTION: In tinnitus treatment, there is a tendency to shift from a "one size fits all" to a more individual, patient-tailored approach. Insight in the heterogeneity of the tinnitus spectrum might improve the management of tinnitus patients in terms of choice of treatment and identification of patients with severe mental distress. The goal of this study was to identify subgroups in a large group of tinnitus patients. METHODS: Data were collected from patients with severe tinnitus complaints visiting our tertiary referral tinnitus care group at the University Medical Center Groningen. Patient-reported and physician-reported variables were collected during their visit to our clinic. Cluster analyses were used to characterize subgroups. For the selection of the right variables to enter in the cluster analysis, two approaches were used: (1) variable reduction with principle component analysis and (2) variable selection based on expert opinion. RESULTS: Various variables of 1,783 tinnitus patients were included in the analyses. Cluster analysis (1) included 976 patients and resulted in a four-cluster solution. The effect of external influences was the most discriminative between the groups, or clusters, of patients. The "silhouette measure" of the cluster outcome was low (0.2), indicating a "no substantial" cluster structure. Cluster analysis (2) included 761 patients and resulted in a three-cluster solution, comparable to the first analysis. Again, a "no substantial" cluster structure was found (0.2). CONCLUSION: Two cluster analyses on a large database of tinnitus patients revealed that clusters of patients are mostly formed by a different response of external influences on their disease. However, both cluster outcomes based on this dataset showed a poor stability, suggesting that our tinnitus population comprises a continuum rather than a number of clearly defined subgroups.

Effect of Direct Stimulation of the Cochleovestibular Nerve on Tinnitus: A Long-Term Follow-Up Study.

OBJECTIVE: Tinnitus is a common entity that may lead to severe impairment in quality of life. An adequate treatment modality for severe tinnitus is currently lacking. Neurostimulation of the auditory tract may serve as a promising adjunct in tinnitus treatment. The aim is to investigate the effect of direct stimulation on the cochleovestibular nerve for intractable tinnitus. METHODS: This study was conducted at the University Medical Center Groningen, The Netherlands. We studied 10 patients with severe, unilateral, intractable tinnitus, who were implanted with a cuff electrode around the cochleovestibular nerve between 2001 and 2013. All patients had preoperative ipsilateral hearing loss. Tinnitus Handicap Inventory (THI) scores and audiometric values were collected. Treatment success was determined based on the self-assessment of satisfactory usage by each patient. RESULTS: The mean preoperative tinnitus duration was 8.0 ± 5.9 years. The preoperative THI score was 71 ± 18 points. During mean follow-up of 49 months, the mean THI reduction was 24 ± 26 points (P = 0.02). Treatment was regarded successful in 6 patients (60%). In these patients, tinnitus did not disappear, but transformed into a more bearable sound. In 4 patients, transient complications occurred, and 1 patient experienced permanent vertigo postoperatively. Furthermore, hearing deterioration was a result of implantation in 86% of the patients. CONCLUSIONS: Direct neurostimulation resulted in treatment success in a small majority of the patients, with a significant decrease in THI score. However, because of a high risk of additional hearing damage, this technique seems not viable for patients with moderate hearing loss.

Microvascular decompression of the cochleovestibular nerve for treatment of tinnitus and vertigo: a systematic review and meta-analysis of individual patient data.

OBJECTIVE Microvascular decompression (MVD) is regarded as a valid treatment modality in neurovascular conflicts (NVCs) causing, for example, trigeminal neuralgia and hemifacial spasms. An NVC of the cochleovestibular nerve might cause tinnitus and/or vertigo; however, general acceptance of MVD for this indication is lacking. The aim of this study was to investigate the effectiveness, safety, and prognostic factors for success of MVD of the cochleovestibular nerve. METHODS A systematic review and meta-analysis of individual patient data (IPD) were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Individual Patient Data (PRISMA-IPD) guidelines. By a comprehensive search (conducted in January 2016) in MEDLINE, EMBASE, and Google Scholar, eligible studies were identified. The collected outcome was a global measurement of improvement of 1) tinnitus, 2) vertigo, and 3) tinnitus combined with vertigo. For the meta-analysis, IPD were collected from the papers and/or from the authors. IPD were analyzed with logistic regression analysis while accounting for study clustering. RESULTS Thirty-five studies (572 patients) were included. The level of evidence provided by these studies was low. In 28% of patients with tinnitus and 32% of patients with vertigo, complete relief following MVD was reported. Patients with both tinnitus and vertigo had complete relief in 62% of cases. In 11% of patients, ≥ 1 complications were reported. Meta-analysis of IPD (165 patients) demonstrated that patients with both tinnitus and vertigo had a higher chance of success (OR 3.8, 95% CI 1.45-10.10) than patients with tinnitus alone. No other variables were significantly related to success. CONCLUSIONS Due to low success rates, MVD cannot be considered as a standard treatment method for tinnitus or vertigo. Moreover, a substantial complication rate was found. However, patients with combined symptoms had a higher chance of success. When combined symptoms occur, it is more likely that an NVC is the underlying pathology and MVD might be appropriate. Due to the low level of evidence in the included studies, this conclusion must be taken with caution. Further validation is necessary to evaluate whether patients with combined symptoms are indeed better candidates for MVD.

Stable benefits of bilateral over unilateral cochlear implantation after two years: A randomized controlled trial.

OBJECTIVES/HYPOTHESIS: To investigate hearing capabilities and self-reported benefits of simultaneous bilateral cochlear implantation (BiCI) compared with unilateral cochlear implantation (UCI) after a 2-year follow-up and to evaluate the learning effect of cochlear implantees over time. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Thirty-eight postlingually deafened adults were included in this study and randomly allocated to either UCI or simultaneous BiCI. Our primary outcome was speech intelligibility in noise, with speech and noise coming from straight ahead (Utrecht-Sentence Test with Adaptive Randomized Roving levels). Secondary outcomes were speech intelligibility in noise with spatially separated sources, speech intelligibility in silence (Dutch phoneme test), localization capabilities and self-reported benefits assessed with different quality of hearing and quality of life (QoL) questionnaires. This article describes the results after 2 years of follow-up. RESULTS: We found comparable results for the UCI and simultaneous BiCI group, when speech and noise were both presented from straight ahead. Patients in the BiCI group performed significantly better than patients in the UCI group, when speech and noise came from different directions (P = .01). Furthermore, their localization capabilities were significantly better. These results were consistent with patients' self-reported hearing capabilities, but not with the questionnaires regarding QoL. We found no significant differences on any of the subjective and objective reported outcomes between the 1-year and 2-year follow-up. CONCLUSIONS: This study demonstrates important benefits of simultaneous BiCI compared with UCI that remain stable over time. Bilaterally implanted patients benefit significantly in difficult everyday listening situations such as when speech and noise come from different directions. Furthermore, bilaterally implanted patients are able to localize sounds, which is impossible for unilaterally implanted patients. LEVEL OF EVIDENCE: 1b Laryngoscope, 127:1161-1168, 2017.

Development of a Squelch Effect in Adult Patients After Simultaneous Bilateral Cochlear Implantation.

OBJECTIVES: To investigate whether a squelch effect occurs in the first 3 years after simultaneous bilateral cochlear implantation and to investigate whether this effect increases during follow-up. STUDY DESIGN: Prospective study as part of a multicenter randomized controlled trial that compares simultaneous bilateral cochlear implantation to sequential and unilateral cochlear implantation. SETTING: Tertiary referral center. PATIENTS: Nineteen postlingually deafened adults. INTERVENTION: Simultaneous bilateral cochlear implantation. MAIN OUTCOME MEASURE: The squelch effect, measured yearly with a speech-intelligibility-in-noise test with spatially separated sources. Bilateral results were compared to unilateral results in which the cochlear implant at the noise side was turned off. The squelch effect was investigated for the patients' best performing ear and for the left and right ears separately. RESULTS: In 13 individual patients, a squelch effect was present after 1 year. This number increased during follow-up years. On group level, a squelch effect was present in patients' best performing ear after 2 and 3 years (1.9 dB). A squelch effect was present in both ears after 3 years (AS: 1.7 dB, AD: 1.3 dB). CONCLUSION: Patients who underwent simultaneous bilateral cochlear implantation developed a measurable benefit from the squelch effect after 2 years in their best performing ear and after 3 years in both ears. These observations suggest that the brain learns to use interaural differences to segregate sound from noise after simultaneous bilateral cochlear implantation. The squelch effect increased over time which suggests a growth in cortical integration and differentiation of inputs from bilateral CIs due to brain plasticity. TRIAL REGISTRATION: Dutch Trial Register NTR1722. LEVEL OF EVIDENCE: 1b.

Benefits of simultaneous bilateral cochlear implantation on verbal reasoning skills in prelingually deaf children.

BACKGROUND: Impaired auditory speech perception abilities in deaf children with hearing aids compromised their verbal intelligence enormously. The availability of unilateral cochlear implantation (CI) auditory speech perception and spoken vocabulary enabled them to reach near ageappropriate levels. This holds especially for children in spoken language environments. However, speech perception in complex listening situations and the acquisition of complex verbal skills remains difficult. Bilateral CI was expected to enhance the acquisition of verbal intelligence by improved understanding of speech in noise. METHODS: This study examined the effect of bilateral CI on verbal intelligence of 49 deaf children (3;5-8;0 years). Relations between speech perception in noise, auditory short-term memory and verbal intelligence were analysed with multiple linear regressions. In addition, the interaction of educational setting, mainstream or special, on these relations was analysed. RESULTS: Children with bilateral CI obtained higher scores on verbal intelligence. Significant associations were present between speech perception in noise, auditory short-term memory and verbal intelligence. CONCLUSION: Children with simultaneous bilateral CIs showed better speech perception in noise than children with unilateral CIs, which mediated by the auditory short-term memory capacity, enhanced the ability to acquire more complex verbal skills for BICI children in mainstream education.