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Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.

ABSTRACT: Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation.Between 30 and 50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes.Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes.Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1?, TNF-?, and Tnfrsf1a/b) and ion homeostasis genes (Scnn1?, Aqp3, and Gjb3). Upregulation of tissue remodeling genes (TGF-?, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds.Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss.

SUBMITTER: Zhang H

PROVIDER: S-EPMC4884452 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.

Zhang Hongzheng H Stark Gemaine G Reiss Lina L

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 20150801 7

<h4>Hypothesis</h4>Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation.<h4>Background</h4>Between 30 and 50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes.<h4>Methods</h4>Guinea pigs were i ...[more]

PMID: 25970030

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Project description:The use of neonatal hearing screening has enabled the identification of congenital unilateral sensorineural hearing loss (USNHL) immediately after birth, and today there are several intervention options available to minimize potential adverse effects of this disease, including cochlear implantation. This study aims to analyze the characteristics of the inner ear of a homogeneous group of congenital non-syndromic USNHL to highlight the features of the inner ear, which can help in clinical, surgical, and rehabilitative decision-making. A retrospective chart review was carried out at a tertiary referral center. Systematic diagnostic work-up and rigorous inclusion-exclusion criteria were applied to 126 children with unilateral hearing impairment, leading to a selection of 39 strictly congenital and non-syndromic USNHL cases, undergoing computed tomography (CT) and magnetic resonance (MR) imaging studies. The frequency and type of malformations of the inner ear in USNHL and unaffected contralateral ears were assessed, with an in-depth analysis of the deficiency of the cochlear nerve (CND), the internal auditory canal (IAC) and the cochlear aperture (CA). Inner ear anomalies were found in 18 out of 39 (46%) of the USNHL patients. In 1 subject, the anomalies were bilateral, and the CND resulted in the predominant identified defect (78% of our abnormal case series), frequently associated with CA stenosis. Only 3 out of 14 children with CND presented stenosis of the IAC. CND and CA stenosis (and to a much lesser extent IAC stenosis) are a frequent association within congenital and non-syndromic USNHL that could represent a distinct pathological entity affecting otherwise healthy infants. In the context of a diagnostic work-up, the evaluation with CT and MRI measurements should take place in a shared decision-making setting with thorough counseling. Both imaging techniques have proven useful in differentiating the cases that will most likely benefit from the cochlear implant, from those with potentially poor implant performance.

Project description:ObjectiveFitting cochlear implants, especially the precise determination of electrical hearing thresholds, is a time-consuming and complex task for patients as well as audiologists. Aim of the study was to develop a method that enables cochlear implant (CI) patients to determine their electrical hearing thresholds precisely and independently. Applicability and impact of this method on speech perception in noise at soft speech levels were evaluated.MethodAn adaptive psychoacoustic procedure for precise hearing threshold determination (precT) was implemented using MatLab (MathWorks) and a graphical user interface was created. Sound signals were calibrated with a CIC4-Implant-Decoder. Study design: A prospective study including 15 experienced adult cochlear implant users was conducted. Electrical hearing thresholds were determined using the automated precT procedure (auto-precT). Speech perception in noise at 50 dB SPL presentation levels was measured for three conditions: (P1) T-levels kept at the previously established T-levels; (P2) T-levels set to the hearing thresholds determined using auto-precT application; (P3) T-levels set 10 cu below the values determined with auto-precT.ResultsAll subjects were able to perform the auto-precT application independently. T-levels were altered on average by an absolute value of 10.5 cu using auto-precT. Median speech reception thresholds were significantly improved from 2.5 dB SNR (P1) to 1.6 dB SNR (P2, p = 0.02). Speech perception was lowest using the globally lowered T-levels, median 2.9 dB SNR (P3, not significant compared to P1 and P2).ConclusionThe applicability of the developed auto-precT application was confirmed in the present clinical study. Patients benefited from adjusting previously established T-levels to the threshold levels determined by the auto-precT application. The integration of the application in the clinical fitting routine as well as a remote fitting software approach is recommended. Furthermore, future possibilities of auto-precT include the implementation of the application on tablets or smart phones.

Project description:ImportanceCochlear implantation is highly effective at improving hearing outcomes, but results have been limited to groupwise analysis. That is, limited data are available for individual patients that report comparisons of preoperative aided speech recognition and postimplantation speech recognition.ObjectiveTo assess changes in preoperative aided vs postoperative speech recognition scores for individual patients receiving cochlear implants when considering the measurement error for each speech recognition test.Design, setting, and participantsThis cross-sectional study used a prospectively maintained database of patients who received cochlear implants between January 1, 2012, and December 31, 2017, at a tertiary, university-based referral center. Adults with bilateral sensorineural hearing loss undergoing cochlear implantation with 6- or 12-month postoperative measures using 1 or more speech recognition tests were studied.ExposuresCochlear implantation.Main outcomes and measuresPostoperative word recognition (consonant-nucleus-consonant word test), sentence recognition (AzBio sentences in quiet), and sentence recognition in noise (AzBio sentences in +10-dB signal-to-noise ratio) scores, and association of each speech recognition score change with aided preoperative score to each test's measurement error.ResultsAnalysis of data from a total of 470 implants from 323 patients included 253 male (53.8%) patients; the mean (SD) age was 61.2 (18.3) years. Most patients had statistically significant improvement in all speech recognition tests postoperatively beyond measurement error, including 262 (84.8%) for word recognition, 226 (87.6%) for sentence recognition, and 33 (78.6%) for sentence recognition in noise. A small number of patients had equivalent preoperative and postoperative scores, including 45 (14.5%) for word recognition, 28 (10.9%) for sentence recognition, and 9 (21.4%) for sentence recognition in noise. Four patients (1.6%) had significantly poorer scores in sentence recognition after implantation. The associations between age at implantation and change in speech recognition scores were -0.12 (95% CI, -0.23 to -0.01) for word recognition, -0.22 (95% CI, -0.34 to -0.10) for sentence recognition, and -0.10 (95% CI, -0.39 to 0.21) for sentence recognition in noise. Patients with no significant improvement were similarly distributed between all preoperative aided speech scores for word recognition (range, 0%-58%) and sentence recognition (range, 0%-56%) testing.Conclusions and relevanceIn this cross-sectional study, with respect to preoperative aided speech recognition, postoperative cochlear implant outcomes for individual patients were largely encouraging. However, improvements in scores for individual patients remained highly variable, which may not be adequately represented in groupwise analyses and reporting of mean scores. Presenting individual patient data from a large sample of individuals with cochlear implants provides a better understanding of individual differences in speech recognition outcomes and contributes to more complete interpretations of successful outcomes after cochlear implantation.

Project description:Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 h of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and were not correlated with threshold shifts at any frequency. As in the previous study in a normal-hearing model, stria vascularis capillary changes were associated with immediate hearing loss after implantation, while little to no hair cell loss was observed even in cochlear regions with threshold shifts as large as 40-50 dB. These findings again support a role of lateral wall blood flow changes, rather than hair cell loss, in hearing loss after surgical trauma, and implicate the endocochlear potential as a factor in implantation-induced hearing loss. Further, the analysis of the hair cell ribbons and post-synaptic receptors suggest that delayed hearing loss may be linked to synapse or peripheral nerve loss due to stimulation excitotoxicity or inflammation. Further research is needed to separate these potential mechanisms of delayed hearing loss.

Project description:BackgroundIn order to preserve residual hearing in patients with sensorineural hearing loss (SNHL) who receive a cochlear implant (CI), insertion trauma to the delicate structures of the cochlea needs to be minimized. The surgical approach comprises the conventional mastoidectomy-posterior tympanotomy (MPT) to arrive at the middle ear, followed by either a cochleostomy (CO) or the round window (RW) approach. Both techniques have their benefits and disadvantages. Another important aspect in structure preservation is the design of the electrode array. Two different designs are used: a "straight" lateral wall lying electrode array (LW) or a "pre-curved" perimodiolar lying electrode array (PM). Interestingly, until now, the best surgical approach and design of the implant is uncertain. Our hypothesis is that there is a difference in hearing preservation outcomes between the four possible treatment options.MethodsWe designed a monocenter, multi-arm, randomized controlled trial to compare insertion trauma between four groups of patients, with each group having a unique combination of an electrode array type (LW or PM) and surgical approach (RW or CO). In total, 48 patients will be randomized into one of these four intervention groups. Our primary objective is the comparison of postoperative hearing preservation between these four groups. Secondly, we aim to assess structure preservation (i.e., scalar translocation, with basilar membrane disruption or tip fold-over of array) for each group. Thirdly, we will compare objective outcomes of hearing and structure preservation by way of electrocochleography (ECochG).DiscussionCochlear implantation by way of a cochleostomy or round window approach, using different electrode array types, is the standard medical care for patients with severe to profound bilateral sensorineural hearing loss, as it is a relatively simple and low-risk procedure that greatly benefits patients. However, loss of residual hearing remains a problem. This trial is the first randomized controlled trial that evaluates the effect of cochlear insertion trauma of several CI treatment options on hearing preservation.Trial registrationNetherlands Trial Register (NTR) NL8586 . Registered on 4 May 2020. Retrospectively registered; 3/48 participants were included before registration.

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Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.

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Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.

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