Auditory Brainstem Response Audiometry Research Articles

Long-Term Follow-Up After Translabyrinthine IAC Tumor Removal With Simultaneous Cochlear Implantation.

To evaluate the long-term hearing outcome after translabyrinthine resection of tumors within the internal auditory canal (IAC) with simultaneous cochlear implantation (CI). Prospective study. Tertiary referral center. Thirty-seven patients with tumors of the IAC undergoing translabyrinthine tumor surgery as a first-line therapy. Intraoperatively, electrically evoked auditory brainstem response audiometry (eABR) was performed in all patients to assess cochlear nerve (CN) integrity. In case of preserved CN function after tumor removal, CI was subsequently performed. Postoperatively, patients were regularly followed up to evaluate pure-tone hearing as well as speech recognition with a monosyllabic word comprehension test. Postoperative hearing thresholds and word recognition scores. Of 37 included patients, 22 (59.46%) had positive eABR responses after tumor removal. Twenty-one of these underwent simultaneous CI directly after tumor surgery and were followed-up for 24.24 ± 19.83 months after surgery. Hearing of these patients significantly improved from 73.87 ± 21.40 dB preoperatively to a mean pure-tone average of 41.56 ± 18.87 dB 1 year (p = 0.0008) and 34.58 ± 2.92 dB 3 years after surgery (p = 0.0157). Speech recognition significantly recovered from 13.33 ± 25.41% to 58.93 ± 27.61% 1 year (p = 0.0012) and 51.67 ± 28.58% 3 years postoperatively (p = 0.0164). Regardless of tumor histopathology, CI is an effective option to restore patients' hearing after translabyrinthine tumor surgery. After CI, patients hearing can be restored over a long-term period of a minimum of 3 years post-surgery. Furthermore, eABR proves to be a practical tool to evaluate CN function and screen for patients eligible for CI.

Auditory brainstem response audiometry in tauopathy mouse model of human Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which changes in hearing sensitivity precede cognitive decline. Despite a well-known link between dementia and hearing loss, few AD model mouse lines have hearing characterized. We screened for hearing loss using auditory brainstem responses (ABR) in young (3-4 months) and aging (9-10 months) mice with a P301S tauopathy (PS19 mice). Compared to wild types, aging PS19 mice did not show accelerated hearing loss but did show latency differences in centrally generated ABR waveform components. These results suggest that tauopathy causes mild central auditory dysfunction in the absence of overt hearing loss.

"To implant or not to implant": electrically evoked auditory brainstem response audiometry for decision-making in vestibular schwannoma resection with CI.

Vestibular schwannomas (VS) are often associated with debilitating hearing loss. Therefore, preservation and rehabilitation of hearing have become major therapeutic goals of VS management. Recently, cochlear implantation (CI) has been established as an effective treatment option for VS-associated hearing loss. Nevertheless, the integrity and proper function of the cochlear nerve must be evaluated before conducting CI to ensure optimal CI outcomes. Various methods to determine cochlear nerve integrity and functionality have emerged in the last few years. Of these, the use of electrically evoked auditory brainstem response audiometry (eABR) in particular has been proven to be ameaningful tool for monitoring cochlear nerve health during VS surgery. Here, the cochlear nerve can be electrically stimulated using an intracochlear test electrode before, during, and after tumor extirpation. Subsequently, the resulting brainstem responses can be measured and interpreted accordingly to obtain direct information on the cochlear nerve function. This allows for continuous monitoring of cochlear nerve function throughout the course of VS surgery and aids in the decision-making for CI candidacy. Finally, in the case of preserved brainstem responses, CI can be performed instantly after VS extirpation. This simultaneous approach offers several advantages over two-staged procedures and has been shown to be an efficient and safe procedure for restoring hearing after VS removal.

4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2/HO-1 signalling pathway.

Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI-OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH-DA. Real-time PCR quantified inflammatory cytokines TNF-α, IL-6 and IL-1β. Network Pharmacology and RNA sequencing (RNA-seq) analysis of the potential mechanism of 4-OI resistance to cisplatin-induced ferroptosis. The expressions of ferroptosis-related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO-1, GCLC and NQO1) were tested by real-time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin-induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4-OI exhibited anti-inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin-induced cell loss. In the present study, we show that 4-OI inhibits cisplatin-induced ferroptosis possibly through activation of the NRF2/HO-1 signalling pathway, thereby exerting a protective effect against cisplatin-induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin-induced hearing loss.

Evaluation of the auditory brainstem response test in patients with type 2 diabetes mellitus.

Hearing loss is an unknown complication of diabetes mellitus (DM). The aim of this study was to evaluate hearing function using auditory brainstem response (ABR) in diabetic patients. The present case-control study was performed on thirty diabetic patients as a case group and thirty healthy individuals as a control group. Baseline demographic information, HbA1c level, and duration of diabetes were obtained from all diabetic patients. In all subjects, the ABR and pure-tone audiometry (PTA) tests were performed and the results were analyzed using the t-test and logistic regression. The absolute latency of I was significantly lower in diabetes patients. The absolute latency of III and the interpeak latencies (IPL) I-III were significantly higher in diabetic patients. No significant relationship was noticed in the absolute latency of V and the IPL I-V among diabetic patients in the right and left ears (P>0.05). The results of this study suggested that diabetes may cause central auditory dysfunction manifested on the absolute latency of III, the IPL I-III and III-V.

Comparison of ASSR and frequency specificity ABR induced by NB CE-Chirp for prediction of behavioral hearing thresholds in children with conductive hearing loss

BackgroundElectrophysiological tests are often used to evaluate hearing loss in infants and young children with conductive hearing loss, no matter to quantify or characterize. However, there are advantages and disadvantages associated with the various electrophysiological tests that are currently available. Therefore, there is no gold standard test. This study aimed to compare the value of narrow-band (NB) CE-Chirp-induced auditory steady-state response (ASSR) and auditory brainstem response (ABR) for assessing hearing thresholds in children with conductive hearing loss. We hope to identify an effective electrophysiological testing method to evaluate conductive hearing loss and provide a reference for clinical hearing assessment of infants with conductive hearing loss. Subjectsand Methods: We selected 27 children (41 ears) aged 3–6 years with otitis media with effusion (OME). Within 1 day, they underwent behavioral audiometry and NB CE-Chirp-induced ASSR and ABR tests in sequence. Pearson's correlation analysis was performed to compare behavioral audiometry thresholds and ASSR and ABR response thresholds at 500, 1000, 2000, and 4000 Hz. ResultsThe behavioral audiometry thresholds of all children were strongly correlated with the response thresholds of the two electrophysiological tests, with correlation coefficients of 0.659, 0.605, 0.723, and 0.857 for ASSR, and 0.587, 0.684, 0.753, and 0.802 for ABR. The proportion of children with a difference of ≤10 dB between ASSR and behavioral audiometry thresholds or between ABR and behavioral audiometry thresholds was not high, especially in the low frequencies. ABR results were superior to ASSR results in terms of predicting actual hearing levels. At 0.5, 1, 2, and 4 kHz, the average differences between the behavioral hearing thresholds and ASSR thresholds in the 41 ears were 5.6, 5.7, 2, and 5.6 dB, respectively. The average differences between behavioral hearing thresholds and ABR thresholds was −5.6, −1.4, −6.8, and 3.2 dB, respectively. The hearing loss configuration of the ASSR exhibited a peaked pattern, similar to behavioral audiometry, whereas the ABR exhibited an ascending pattern. The time to perform the single-ear ASSR test was 5.9 min, whereas the ABR test took 17.0 min. ConclusionASSR and ABR induced by the NB CE-Chirp correlated well with behavioral audiometry in children with conductive hearing loss. The NB CE-Chirp ASSR has advantages in terms of testing time and hearing configuration evaluation, whereas ABR has better reliability than ASSR. However, the stability of ASSR and ABR induced by the NB CE-Chirp is poor, and the thresholds obtained cannot replace behavioral audiometry in evaluating the true hearing of children with conductive hearing loss. However, ASSR and ABR can be used as auxiliary tests for cross-validation.

Magnetic resonance spectroscopy and auditory brain-stem response audiometry as predictors of bilirubin-induced neurologic dysfunction in full-term jaundiced neonates

The purpose of this research was to define the functions of MRS and ABR as predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy and/or exchange transfusion). This prospective cohort study was done at the NICU of Tanta University Hospitals over a 2-year duration. Fifty-six full-term neonates with pathological unconjugated hyperbilirubinemia were divided according to MRS and ABR findings into 2 groups: group (1) included 26 cases with mild acute bilirubin encephalopathy (BIND-M score 1–4). Group (2) included 30 cases with neonatal hyperbilirubinemia only. In addition, 20 healthy neonates with similar ages were employed as the controls. When compared to group 2 and the control group, group 1’s peak-area ratios of NAA/Cr and NAA/Cho were found to be significantly reduced (P < 0.05). As compared to group 2 and the control group, group 1’s Lac/Cr ratio was significantly greater (P < 0.05), but the differences were not significant for group 2 when compared to the control group. Waves III and V peak latencies, I–III, and I–V interpeak intervals were significantly prolonged in group 1 in comparison to group 2 and controls (P < 0.05) with no significant difference between group 2 and control group. Conclusion: When the symptoms of ABE are mild and MRI does not show any evident abnormalities, MRS and ABR are helpful in differentiating individuals with ABE from patients with neonatal hyperbilirubinemia. Trial registration: ClinicalTrials.gov, Identifier: NCT06018012.What is Known:• MRS can be used as a diagnostic and prognostic tool for the differential diagnosis of patients with acute bilirubin encephalopathy, from patients with neonatal hyperbilirubinemiaWhat is New:• ABR is a useful diagnostic and prognostic tool in the care and management of neonates with significantly raised bilirubin. It can be used as early predictor of acute bilirubin encephalopathy in the earliest stage of auditory damage caused by bilirubin.

Comparative study of Automated Auditory Brainstem Response (AABR) and Brainstem Evoked Response Audiometry (BERA) for Hearing Loss Detection in High Risk Infants delivered in Dhulikhel Hospital

Background &amp; Objective: Brainstem evoked response audiometry (BERA) is most specific and sensitive test for brain stem dysfunction. It is most important objective method for evaluating peripheral auditory system in neonates, infants, sedated and comatose patients and other person who doesn’t understand the language. Objective of the study was to evaluate correlation BERA with other audiological tests in different types of hearing loss. Material and Methods: This was a hospital based retrospective observational analytic study that used a cross-sectional approach. The sampling used was consecutive sampling until the minimum size fulfilled from 1st September 2021 to 30th September 2022. All high-risk infants aged 0–3 months who suffer from asphyxia, sepsis, LBW, premature, and hyperbilirubinemia, the baby was stable and transportable, the patient’s parents were willing to participate were taken. Results: Out of 46 high risk infants of 0 - 3 months, male:female ratio of 1.7:1 with mean age of 31 days, the most common high risk factor was low birth weight and hyperbilirubinemia i.e 23(50%). 64% of infants were pass in AABR 2nd test in comparison to 71% pass in BERA test. Conclusion: There was no difference between AABR and BERA results for HL detection in high-risk infants at NICU.

Predicting Behavioral Threshold at 6 and 8 kHz for Children and Adults Based on the Auditory Brainstem Response.

Common clinical application of auditory brainstem response (ABR) testing is limited to 0.25-4 kHz. Prior research has demonstrated associations between ABR and behavioral thresholds for tone burst stimuli > 4 kHz in adults, but there are no comparable data for children. The ability to predict behavioral thresholds > 4 kHz clinically based on the ABR would provide valuable audiologic information for individuals who are unable to provide behavioral thresholds. This study included children with hearing loss and children with normal hearing to determine the association between ABR and behavioral thresholds at 6 and 8 kHz. ABR and behavioral thresholds were obtained for children ages 4.7-16.7 years (M = 10.5, SD = 3.4) with sensorineural hearing loss (n = 24) or normal hearing sensitivity (n = 16) and for adults ages 18.4-54.4 years (M = 32.7, SD = 10.4) with sensorineural hearing loss (n = 13) or normal hearing sensitivity (n = 11). Thresholds obtained for 6 and 8 kHz using ABR and conventional audiometry were compared. Differences between ABR and behavioral thresholds averaged 5-6 dB for both children and adults for both test frequencies, with differences of ≤ 20 dB in all instances. Linear mixed modeling for data from participants with hearing loss suggested that ABR threshold is a good predictor of behavioral threshold at 6 and 8 kHz for both children and adults. Test specificity was 100%; no participants with behavioral thresholds ≤ 20 dB HL had ABR thresholds > 25 dB nHL. Initial evidence suggests that ABR testing at 6 and 8 kHz is reliable for estimating behavioral threshold in listeners with hearing loss and accurately identifies normal hearing sensitivity. The results of this study contribute to efforts to improve outcomes for vulnerable populations by reducing barriers to clinical implementation of ABR testing at > 4 kHz.

Salidroside Attenuates Cisplatin-Induced Ototoxicity: An Experimental Study In Vitro and In Vivo

Oxidative damage to hair cells is the major cause of ototoxicity induced by cisplatin (cis)-based chemotherapy. In this study, we aimed to assess how salidroside (SAL) protected cochlear explants (CEs) and HEI-OC1 cell lines against cis-induced ototoxicity and reduced relative hearing loss in mouse models. Furthermore, the protective mechanism of the Nrf2/ARE pathway was investigated. Cell Counting Kit-8 was used to measure the viability of HEI-OC1 cells. Flow cytometry and the TUNEL assay were used to evaluate cell apoptosis. Flow cytometry was used to measure intracellular reactive oxygen species (ROS). Immunofluorescence staining determined the changes in mitochondrial membrane potential (ΔΨm). Western blot was used to measure the levels of caspase-3 and Nrf-2. An analysis of Nrf2 and target gene levels of expression was conducted using qRT-PCR. Hearing was monitored using auditory brainstem response audiometry. In cochlear explants, SAL inhibits cis-induced apoptosis of HEI-OC1 cells and decreased hair cell apoptosis. SAL inhibited cis-induced apoptosis by lowering intracellular ROS, preserving mitochondrial function, and reducing caspase-3 expression. Moreover, auditory cells were protected from the toxic effects of cis by the Nrf2-ARE pathway after treatment with SAL. In Vivo, SAL could protect against cis-induced hearing loss, and the use of the PLGA-poloxamer nanohydrogel as a carrier increased the protection efficiency of SAL. Through its ability to reduce oxidative stress, SAL could protect auditory cell lines from cis-induced apoptosis In Vitro and attenuate cis-induced hearing loss In Vivo. Nano-based drug delivery can improve the protection efficiency of SAL. Further research should be conducted on the antioxidant capacity of SAL and its use in ototoxicity.

Functional Outcome After Simultaneous Vestibular Schwannoma Resection and Cochlear Implantation With Intraoperative Cochlear Nerve Monitoring.

Electrically evoked auditory brainstem response audiometry has emerged as a suitable option to intraoperatively assess cochlear nerve function during vestibular schwannoma resection. This study aimed to analyze the functional outcome and implant usage of patients with preserved auditory nerve responses after simultaneous translabyrinthine schwannoma resection and cochlear implantation. Prospective study. Tertiary referral center. Patients with unilateral sporadic vestibular schwannoma underwent translabyrinthine tumor resection. Intraoperatively, electrically evoked auditory brainstem response audiometry was performed before and after tumor removal. Cochlear implantation was carried out if positive responses were detected after tumor removal indicating cochlear nerve function. Postoperatively, patients were biannually followed-up to assess aided sound field audiometry and word recognition as well as implant usage. Overall, 26 patients with vestibular schwannoma underwent translabyrinthine schwannoma resection. Out of these patients, 15 had positive cochlear nerve responses after tumor removal and concurrently received a cochlear implant. In 13 patients with histologically confirmed vestibular schwannoma, hearing improved by 23.7 ± 33.2 decibels and word recognition by 25.0 ± 42.4% over a mean follow-up period of 18 months. Overall, 12 included patients were regular cochlear implant users. Patients with vestibular schwannoma can benefit substantially from cochlear implantation. Intraoperative assessment of cochlear nerve function using electrically evoked auditory brainstem response audiometry can help to better identify individuals eligible for simultaneous vestibular schwannoma resection and cochlear implantation.

The Sensitivity and Specificity of DPOAE (Distortion Product Otoacoustic Emission) Compared with ABR (Auditory Brain Stem Response Audiometry) in Neonatal Hearing Screening

The Sensitivity and Specificity of DPOAE (Distortion Product Otoacoustic Emission) Compared with ABR (Auditory Brain Stem Response Audiometry) in Neonatal Hearing Screening

Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy.

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses.

QOL-23. Expanded protocols for hearing loss related cisplatin-based therapy in childhood cancer patients.

Abstract BACKGROUND: Most children who require cisplatin chemotherapy incur hearing loss. The basal end of the cochlea, corresponding to high frequency sound perception, is typically affected first, with progression along the basilar membrane and to lower frequencies over time. Typical audiologic protocols for children are often restricted to the speech frequencies (500-4000Hz). However, reliable responses to higher frequencies can be obtained using specialized electrophysiologic measures or adapted behavioral test procedures, which may lead to earlier identification of hearing loss during ototoxicity monitoring. METHODS: Auditory Brainstem Response (ABR) and behavioral threshold assessments were completed for patients during cisplatin treatment at Cincinnati Children’s Hospital between 2017 and 2021. High frequency ABR protocols were established to include 6000 and 8000 Hz and behavioral testing protocols were expanded to include frequencies 8000 through 16000 Hz. Hearing loss was defined as &amp;gt;20 dB eHL at any frequency. The typical and high frequency protocols were compared to determine if higher frequency measurement provides a more sensitive means to detect the onset of hearing loss. RESULTS: One-hundred and fifty-three patients receiving cisplatin were assessed audiometrically. For patients who required ABR evaluations, 38% were identified with hearing loss when using the typical test protocol, where 79% of the patients were identified with hearing loss when using the high frequency protocol. For patients who were able to complete behavioral audiometric evaluations, 42% were identified with hearing loss with the typical protocol while 84% were identified with the high frequency protocol. CONCLUSIONS: The addition of higher frequencies to audiologic evaluation protocols for both ABR and behavioral audiometry significantly increases sensitivity to detect hearing loss during ototoxicity monitoring of cisplatin treatment and is a feasible strategy in pediatric cancer patients. Audiologically, the increased sensitivity to detect hearing loss may lead to earlier intervention regarding hearing and communication for the patient/family.

Difference in Thresholds Between Auditory Brainstem Response Test and Pure Tone Audiometry by Frequency

Background and Objectives There is no clear standard for the difference in the thresholds of auditory brainstem response (ABR) and pure tone audiometry (PTA) when using ABR to evaluate the reliability of PTA. Therefore, we assessed the difference in the thresholds of ABR and PTA for each frequency. Consequently, we present here the actual difference values between the two tests that can be used as a reference in the clinic.Subjects and Method We retrospectively assessed the audiometry results of 129 ears. Ears in which the hearing thresholds of each frequency continuously declined were classified as the downward group. We compared the average of differences between the two tests by frequency. The differences were compared for each hearing level from 50 dB or higher.Results For all ears, the appropriate range of difference value was ±5 dB at 2 kHz. At 1 kHz, the ABR threshold was 10 dB higher than PTA, and it was 10 dB less than PTA at 4 kHz. In the downward group, the difference value increased by 10 dB at 1 kHz and 4 kHz. In the subgroups at each hearing level, the difference value showed similar results (p&lt;0.05).Conclusion The difference in the threshold, regardless of the severity or tendency of hearing loss, was the smallest at 2 kHz and the range was ±5 dB. ABR was 10 dB higher at 1 kHz and and 10 dB lower at 4 kHz than PTA. In the downward group, the difference at 1 kHz and 4 kHz increased by 10 dB each.

Long-Term Effects of Aircraft Noise Exposure on Vascular Oxidative Stress, Endothelial Function and Blood Pressure: No Evidence for Adaptation or Tolerance Development.

Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance mechanisms in mice in response to chronic noise exposure. C57BL/6J mice were exposed to aircraft noise for 0, 4, 7, 14 and 28d at a mean sound pressure level of 72 dB(A) and peak levels of 85 dB(A). Chronic aircraft noise exposure up to 28d caused persistent endothelial dysfunction and elevation of blood pressure. Likewise, reactive oxygen species (ROS) formation as determined by dihydroethidium (DHE) staining and HPLC-based measurement of superoxide formation in the aorta/heart/brain was time-dependently increased by noise. Oxidative burst in the whole blood showed a maximum at 4d or 7d of noise exposure. Increased superoxide formation in the brain was mirrored by a downregulation of neuronal nitric oxide synthase (Nos3) and transcription factor Foxo3 genes, whereas Vcam1 mRNA, a marker for inflammation was upregulated in all noise exposure groups. Induction of a pronounced hearing loss in the mice was excluded by auditory brainstem response audiometry. Endothelial dysfunction and inflammation were present during the entire 28d of aircraft noise exposure. ROS formation gradually increases with ongoing exposure without significant adaptation or tolerance in mice in response to chronic noise stress at moderate levels. These data further illustrate health side effects of long-term noise exposure and further strengthen a consequent implementation of the WHO noise guidelines in order to prevent the development of noise-related future cardiovascular disease.

Biallelic p.V37I variant in GJB2 is associated with increasing incidence of hearing loss with age

PurposeThis study aimed to quantitatively assess the incidence of hearing loss in relation to age in individuals with biallelic p.V37I variant in GJB2. MethodsPopulation screening of the biallelic p.V37I variant was performed in 30,122 individuals aged between 0 and 97 years in Shanghai. Hearing thresholds of the biallelic p.V37I individuals and the controls were determined by click auditory brainstem response or pure tone audiometry. ResultsBiallelic p.V37I was detected in 0.528% (159/30,122) of the subjects. Of the biallelic p.V37I newborns, 43.91% (18/41) passed their distortion-product otoacoustic emissions–based newborn hearing screening or had hearing thresholds lower than 20 decible above normal hearing level. The older newborns had elevated hearing thresholds, with increasing incidence of 9.52%, 23.08%, 59.38%, and 80.00% for moderate or higher grade of hearing loss in age groups of 7 to 15 years, 20 to 40 years, 40 to 60 years, and 60 to 85 years, respectively. Their hearing deteriorated at a rate of 0.40 dB hearing level per year on average; males were more susceptible, and deterioration occurred preferentially at higher sound frequencies. ConclusionThe biallelic p.V37I variant is associated with steadily progressive hearing loss with increasing incidence over the course of life. Most of the biallelic p.V37I individuals may develop significant hearing loss in adulthood and, can benefit from early diagnosis and intervention through wide-spread genetic screening.

Targeting Autophagy Induction as A possible Protective Mechanism by Verapamil Compared to Rapamycin (Sirolimus) Against Gentamicin -Induced Ototoxicity in Guinea Pigs

Background: Ototoxicity is a harmful feature of the cochlea or auditory nerve and sometimes vestibularapparatus. Gentamicin is known to cause irreversible bilateral ototoxicity. Autophagy induction hasbeen proposed as a target for prevention of gentamicin ototoxicity. Aim of the work: to investigate thepossible protective effect of autophagy induction by verapamil compared to rapamycin. Methods: Thisexperiment was conducted on 32 male guinea pigs. At the beginning each animal’s hearing status wasassessed using auditory brainstem response (ABR) audiometry. Then, they were divided into 4 equalgroups: Group 1: control group, Group 2: untreated gentamicin-induced ototoxicity group. Group 3:gentamicin-induced ototoxicity treated concomitantly with rapamycin. Group 4: gentamicin-inducedototoxicity treated concomitantly with verapamil. At the end of the experiment, ABR was repeatedthen the animals were sacrificed, and blood samples were obtained for assaying of reduced glutathioneand malondialdehyde levels. The left cochlea was processed for scanning electron microscope, whilethe right cochlea was processed for histopathology and LC3-II immunohistochemistry. Results:Verapamil revealed superiority compared to rapamycin proved by significant improvement in ABR,histopathological results, in addition to its antioxidant effect. Conclusion: verapamil could be suggestedas a potential therapeutic approach to decrease gentamicin ototoxicity.

Tinnitus development is associated with synaptopathy of inner hair cells in Mongolian gerbils.

Human hearing loss (HL) is often accompanied by comorbidities like tinnitus, which is affecting up to 15% of the adult population. Rodent animal studies could show that tinnitus may not only be a result of apparent HL due to cochlear hair cell damage but can also be a consequence of synaptopathy at the inner hair cells (IHCs) already induced by moderate sound traumata. Here, we investigate synaptopathy previously shown in mice in our animal model, the Mongolian gerbil, and relate it to behavioral signs of tinnitus. Tinnitus was induced by a mild monaural acoustic trauma leading to monaural noise induced HL in the animals, quantified by auditory brainstem response (ABR) audiometry. Behavioral signs of tinnitus percepts were detected by measurement of prepulse inhibition of the acoustic startle response in a gap-noise paradigm. Fourteen days after trauma, the cochleae of both ears were isolated, and IHC synapses were counted within several spectral regions of the cochlea. Behavioral signs of tinnitus were only found in animals with IHC synaptopathy, independent of type of HL. On the other hand, animals with apparent HL but without behavioral signs of tinnitus showed a reduction in amplitudes of ABR waves I&II but no significant changes in the number of synapses at the IHC. We conclude-in line with the literature-that HL is caused by damage to the IHC or by other reasons but that the development of tinnitus, at least in our animal model, is closely linked to synaptopathy at the IHC.

The use of melatonin for auditory brainstem response audiometry in children with comorbidities.

In this study, the efficacy and feasibility of melatonin in young children with and without comorbidities, undergoing auditory brainstem response audiometry (ABR) was evaluated. The aim of this study was primarily to evaluate the use of melatonin for ABR investigations in children with comorbidities. Second, the efficacy of melatonin was evaluated based on several factors like sleep-onset latency, sleep duration, frequency of awakenings as well as adverse events. Click-induced ABR tests were performed at the outpatient clinic between January, 2018 and August, 2020. Investigations were considered successful when binaural testing was completed. A dose of melatonin depending on age, 5mg for children younger than 6years and 10mg if older than 6years, was administered after placement of electrodes. 131 children were included in this study. 87% of all ABR investigations were performed successfully. Comorbidities such as neurodevelopmental disorders or developmental delays were present in 70% of all children. There was no significant difference in age (p = 0.36) or gender (p = 0.97) between the success and failed group. In addition, comorbidities were equally distributed between both groups. Mean sleep duration was 38 (SD 21) min and sleep-onset latency was 28 (SD 20) min No adverse events were documented. Melatonin is effective for ABR examinations in infants and children with and without comorbidities. Furthermore, it allows for sequential testing in those at risk for progressive hearing loss. Clear instructions to caregivers and expertise of audiologists are a prerequisite for optimal outcomes.