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Objectives: The increase of bilateral cochlear implantation (CI) in recent years has made it essential to comprehend the effects of CI on otolith function. This study aimed to investigate the development of gross motor and otolith function in patients with inner ear malformations (IEMs) using vestibular-evoked myogenic potentials (VEMPs)., Materials and Methods: Overall, 78 patients with sensorineural hearing loss (SNHL) (age 5.7 ± 4.1 years) were divided into two groups based on the presence (IEM group, n = 39) or absence (control group, n = 39) of IEMs. VEMP testing was performed both before and 1-3 months after CI, and the evaluation of gross motor development was carried out., Results: The mean ages for achieving head control and independent walking were delayed in the IEM group compared with the control group (p = 0.02). The preoperative cervical VEMP (cVEMP) and ocular VEMP (oVEMP) response rates were higher in the control group (60% and 86.95%) than in the IEM group (57.69% and 74.35%) (p < 0.05). Additionally, abnormal cVEMP was associated with delayed acquisition of independent walking (p = 0.017). Saccular and utricular functions after CI were lost by 40% and 31.75%, respectively, in patients who elicited preoperative VEMPs waveform (n = 25)., Conclusions: Among SNHL patients, balance development is more delayed in patients of IEMs than in patients without IEMs. The cVEMP and oVEMP waveforms differed greatly between the two groups. The otolith-vestibular nerve conduction pathway can be affected by CI, potentially leading to otolith function impairment. Therefore, it is essential to assess otolith and balance functions before CI, and this evaluation should be considered an integral part of clinical practice., (© 2024 John Wiley & Sons Ltd.)

Objectives: To evaluate the differences between audio-vestibular function testing and inner ear gadolinium magnetic resonance imaging (MRI) in distinguishing definite Ménière disease (DMD) and probable Ménière disease (PMD), and to provide a reference for early clinical diagnosis and intervention., Methods: A total of 116 patients diagnosed with DMD (n = 80) and PMD (n = 36) were enrolled. The differences in the results of pure tone audiometry, caloric test, and tympanic injection of gadolinium for contrast-enhanced MRI between the two groups were compared and analyzed. Parameters that could differentiate between the two conditions were identified, and the sensitivity and specificity and the area under the curve (AUC) of individual and combined indices in the differential diagnosis of DMD and PMD were evaluated., Results: The hearing threshold and hearing asymmetry rate of the DMD group were significantly higher than those of the PMD group (p < 0.001), 98.8% and 30.6%, respectively. The abnormal rates of canal paresis (CP) and severity of endolymphatic hydrops in the DMD group were higher than those in the PMD group (p < 0.05). When combined with high-frequency hearing thresholds, hearing asymmetry, hearing curve type, endolymphatic hydrops, and abnormal CP, the diagnostic accuracy of DMD was improved compared to using high-frequency alone (p < 0.05)., Conclusion: This study showed that PMD and DMD may represent two different stages in the development of MD disease. The comprehensive assessment of audio-vestibular function testing and inner ear MRI proves beneficial for early diagnosis, potentially contributing to the preservation of inner ear function., Competing Interests: Conflict of interest statement: The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024, Otology & Neurotology, Inc.)

The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited. Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (P SV ) and scala tympani (P ST ) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (P DIFF ) across the basilar membrane - known to be closely related to the hearing sensation - was calculated as the complex difference between P SV and P ST . With air conduction stimulation, both P SV and P ST increased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for P ST compared to P SV . The P DIFF , in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement. With bone conduction, the average within-specimen effects were less than 5 dB for either P SV , P ST, or P DIFF . The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction. This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

An explosion is a process that rapidly releases a huge amount of energy in the form of heat, kinetic energy, and high-pressure shock waves. Since the organ of hearing is most susceptible to pressure changes, damage to the sound-conducting or sound-receiving systems is inevitable in case of an explosive injury. This article examines the mechanism of formation of explosive injuries of the middle and inner ear in children and adolescents, the features of diagnosis and tactics of surgical reconstructive treatment of explosive ear injuries based on the data available in the scientific literature and their own experience.

Competing Interests: I have no commercial associations, contractual relations, or proprietary considerations that might pose a conflict of interest related or unrelated with the submitted manuscript, and have had no involvements that might raise the question of bias in the work reported or in the conclusions, implications, or opinions stated. The authors disclose no conflicts of interest.

Competing Interests: The authors disclose no conflicts of interest.

Noise-induced hearing loss (NIHL) results from a complex interplay of damage to the sensory cells of the inner ear, dysfunction of its lateral wall, axonal retraction of type 1C spiral ganglion neurons, and activation of the immune response. We use RiboTag and single-cell RNA sequencing to survey the cell-type-specific molecular landscape of the mouse inner ear before and after noise trauma. We identify induction of the transcription factors STAT3 and IRF7 and immune-related genes across all cell-types. Yet, cell-type-specific transcriptomic changes dominate the response. The ATF3/ATF4 stress-response pathway is robustly induced in the type 1A noise-resilient neurons, potassium transport genes are downregulated in the lateral wall, mRNA metabolism genes are downregulated in outer hair cells, and deafness-associated genes are downregulated in most cell types. This transcriptomic resource is available via the Gene Expression Analysis Resource (gEAR; https://umgear.org/NIHL) and provides a blueprint for the rational development of drugs to prevent and treat NIHL., Competing Interests: Declaration of interests K.S.S., J.B.S., G.P., A.T.P., and J.B. are employees of Decibel Therapeutics. The data presented in this manuscript are registered for pending U.S. Provisional Patent Application, number: 63/151,249, title: “System and Methods for Cell Type-Specific Atlas for the Inner Ear Transcriptional Response to Acoustic Trauma,” and UMB docket number: RH-2021-073., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Otological diseases including Meniere's disease (MD) involve endolymphatic hydrops (EH), which can be visualized by magnetic resonance imaging (MRI) with gadolinium contrast agents, but the temporal changes of contrast in the inner ear have not been evaluated., Objectives: We investigated the permeability of the blood-perilymph barrier (BPB) in ears with EH to evaluate the severity of the inner ear disturbances., Materials and Methods: The study included 32 ears from 16 patients with EH or related diseases who underwent MRI. The permeability of the BPB was assessed by the signal-intensity ratio (SIR) at four-time points: before and at 10 min, 4 h, and 24 h after administration of gadolinium for assessing EH., Results: Cochlear EH was found in 25 of the 32 ears, and vestibular EH in 11. The rate of EH was significantly higher in symptomatic ears; however, the existence of EH was not related to SIR values. Nevertheless, SIR values in the basal turn were significantly higher 4 and 24 h after injection of gadolinium in patients aged ≥50 years., Conclusion and Significance: Higher SIR values observed in older patients with EH indicate severe disturbances of the BPB in the cochlea, which may account for intractable inner ear disturbances in older patients.

Osteogenesis imperfecta (OI or brittle bone disease) is a group of genetic disorders of the connective tissues caused mainly by mutations in the genes encoding collagen type I. Clinical manifestations of OI include skeletal fragility, bone deformities, and severe functional disabilities, such as hearing loss. Progressive hearing loss, usually beginning in childhood, affects approximately 70% of people with OI with more than half of the cases involving the inner ear. There is no cure for OI nor a treatment to ameliorate its corresponding hearing loss, and very little is known about the properties of OI ears. In this study, we investigate the morphology of the otic capsule and the cochlea in the inner ear of the oim mouse model of OI. High-resolution 3D images of 8-week old oim and WT inner ears were acquired using synchrotron microtomography. Volumetric morphometric measurements were conducted for the otic capsule, its intracortical canal network and osteocyte lacunae, and for the cochlear spiral ducts. Our results show that the morphology of the cochlea is preserved in the oim ears at 8 weeks of age but the otic capsule has a greater cortical thickness and altered intracortical bone porosity, with a larger number and volume density of highly branched canals in the oim otic capsule. These results portray a state of compromised bone quality in the otic capsule of the oim mice that may contribute to their hearing loss., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a neurodegenerative disease due to mutations in TUBB4A. Patients suffer from extrapyramidal movements, spasticity, ataxia, and cognitive deficits. Magnetic resonance imaging features are hypomyelination and atrophy of the striatum and cerebellum. A correlation between the mutations and their cellular, tissue and organic effects is largely missing. The effects of these mutations on sensory functions have not been described so far. We have previously reported a rat carrying a TUBB4A (A302T) mutation and sharing most of the clinical and radiological signs with H-ABC patients. Here, for the first time, we did a comparative study of the hearing function in an H-ABC patient and in this mutant model. By analyzing hearing function, we found that there are no significant differences in the auditory brainstem response (ABR) thresholds between mutant rats and WT controls. Nevertheless, ABRs show longer latencies in central waves (II-IV) that in some cases disappear when compared to WT. The patient also shows abnormal AEPs presenting only Waves I and II. Distortion product of otoacoustic emissions and immunohistochemistry in the rat show that the peripheral hearing function and morphology of the organ of Corti are normal. We conclude that the tubulin mutation severely impairs the central hearing pathway most probably by progressive central white matter degeneration. Hearing function might be affected in a significant fraction of patients with H-ABC; therefore, screening for auditory function should be done on patients with tubulinopathies to evaluate hearing support therapies., (© 2020 Wiley Periodicals LLC.)

The purpose of this study was to use a murine model to determine if melatonin can protect the inner ear from radiation-induced damage. A total of 81 4-week-old Balb/c mice were randomly divided into five groups: control group; 50 mg/kg melatonin group; 5 mg/kg melatonin+radiotherapy group; 50 mg/kg melatonin+radiotherapy group; radiotherapy group. The radiotherapy groups received 16 Gy irradiation and melatonin was administered by intraperitoneal injection 30 min before radiotherapy. On days 3 and 7 after irradiation the function of outer hair cells was determined by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) testing, pathological changes of inner ear cells were observed by light microscopy, and the expression of prestin mRNA was determined. ABR thresholds were increased and wave I latencies were extended after radiotherapy; however, the increases were lower in the groups that received melatonin (P < 0.05). DPOAEs showed radiotherapy-induced hearing loss at 8-12 kHz, and hearing loss was greater on day 7 than day 3. However, hearing loss was less in the melatonin groups (P < 0.05). Histopathological examination showed irradiation resulted in breaks and distortion of the cochlear basement membrane, disruption of the stria vascularis, and swelling of outer hair cells. Melatonin reduced these changes. Radiotherapy upregulated prestin mRNA expression. Radiotherapy-induced upregulation of prestin was decreased in the melatonin groups (P < 0.05), and the decrease was greater in the 50 mg/kg melatonin group (P < 0.05). Melatonin protects against radiation-induced cochlear damage by reducing damage to outer hair cells., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of synaptopathy represent promising future therapies. Minimally invasive endoscopic ear surgery offers a viable approach to aid in delivery of pharmacologic compounds, cells, or viral vectors to the inner ear for all of these techniques., Competing Interests: Disclosure Consultant, Boston Pharmaceuticals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Blast-induced hearing loss is an acoustic trauma commonly caused by high-energy explosions of improvised explosive devices, and the auditory system may be affected by blast damage. This study aims to evaluate the protective effect of tympanic membrane perforation (TMP) on the inner ear against blast injury., Methods: In this study, 43 adult patients who had suffered blast injury were divided into three subgroups: intact tympanic membranes in both ears, unilateral TMP, and bilateral TMP. Each patient underwent a comprehensive audiogram, including bone conduction, in the audiology department., Results: Evaluation was performed on 43 (100%) males with a mean age of 31.44±8.01 years (range, 18-52 years). When the type of hearing loss was evaluated separately for each ear, sensorineural hearing loss (SNHL) was observed in 31 (36%), high-frequency SNHL in 26 (30.2%), conductive hearing loss in eight (9.3%), and mixed type hearing loss in 21 (24.4%) ears. TMP was detected in 21 (48.8%) of 43 blast-injured patients, on the right side in four (9.3%) patients, on the left side in seven (16.3%), and bilateral in 10 (23.3%). When the type of acoustic trauma was evaluated, 15 (34.9%) patients were observed to have suffered from the explosion of an IED, 12 (30.2%) from weapon explosion, six (14%) were a vehicle bomb explosion, three (7%) were projectile missile explosion, three (7%) were mortar explosion, two (4.7%) were mine explosion, and two (4.7%) were exposed to the explosion in an armored vehicle (Table 1)., Conclusion: No significant difference was observed in the majority of the frequencies whether the tympanic membrane was perforated or not in the blast-injured patients and it was concluded that tympanic membrane perforation caused by blast injury had no protective effect on the inner ear.

Hearing impairment is a reported complication of sickle cell disease, yet inner ear pathology is not fully understood. The study purpose was to examine the patterns of inner ear involvement in patients with sickle cell disease by magnetic resonance imaging (MRI) and to assess its association with auditory functions. A cross-sectional study included 22 children with sickle cell disease examined for inner ear pathology by audiogram, MRI inner ear and transcranial Doppler (TCD) with revision of their hospital records for transfusion, chelation and hydroxyurea (HU) therapy. Abnormal MRI in the form of intrinsic T1 hyperintensity within the lumen of inner ear structures and cochlear neuropathy was found in five (22.7%) patients; left middle cerebral artery (MCA) flow velocity was higher in patients with abnormal MRI (83.4 ± 5.3 cm/sec) compared to normal MRI (68.2 ± 11.1 cm/sec) ( p  = 0.015), however, none of the patients had TCD of >170 cm/sec. There was no significant difference between patients with normal and abnormal MRI as regards hearing level and speech audiometry. Sensorineural hearing loss (SNHL) was present in two (9.1%) and conductive hearing loss (CHL) in two (9.1%) patients. There was a significant negative correlation between right ear mean hearing level and right MCA flow velocity and significant negative correlation between left ear mean hearing level and basilar artery (BA) flow velocity. We concluded that inner ear pathology is not uncommon in asymptomatic patients with sickle cell anemia, yet it did not correlate with hearing impairment and may occur with normal TCD results.

The present study was to investigate the dynamics of endolymphatic hydrops (EH) and hearing function, and explore whether the hearing loss is caused by EH alone and whether the hearing function can be modulated by changes in the EH. The extent of EH visualized by gadolinium (Gd)-enhanced inner ear magnetic resonance imaging, hearing thresholds and the summating potential/action potential ratio (-SP/AP ratio) of electrocochleography (ECochG) were recorded prior to and following surgery in 22 patients with intractable Meniere's disease (MD) who underwent endolymphatic duct blockage (EDB). The difference value of the hearing threshold and -SP/AP ratio was significantly positively correlated with the difference value of the endolymph to vestibule-volume ratio (EVVR) and grading of cochlear hydrops between prior to and following surgery. Among patients with a decreased EVVR, the average hearing threshold and -SP/AP ratio was significantly decreased following surgery, as compared to that prior to surgery. Six out of seven patients with a hearing improvement (≥10-dB decline) and 4/5 patients with a negative conversion of EcochG showed downgrading of their hydrops in the cochlea and/or vestibule. By contrast, among patients with an increased EVVR, the average hearing threshold and -SP/AP ratio tended to increase following EDB, as compared with that prior to surgery. One out of two patients with a hearing deterioration (≥10-dB elevation) showed upgrading of her hydrops in both cochlea and vestibule. The present results showed the downgrading of cochlear and/or vestibular hydrops accompanied by the downregulation of the hearing threshold and -SP/AP ratio of EcochG, as well as the upgrading of cochlear and/or vestibular hydrops that tended to upregulate the hearing threshold and -SP/AP ratio of EcochG; this suggested that hearing loss is likely to be caused by hydrops and that the impaired hearing function be modulated by changes in the hydrops., Competing Interests: The authors have declared that no competing interests exist.

Transient vestibular organ deafferentation, such that is caused by traumatic tissue injury, is presently addressed by corticosteroid therapy. However, restoration of neurophysiological properties is rarely achieved. Here, it was hypothesized that the tissue-protective attributes of α1-antityrpsin (AAT) may promote restoration of neuronal function. Inner ear injury was inflicted by unilateral labyrinthotomy in wild-type mice and in mice overexpressing human AAT. A 2-week-long assessment of vestibular signs followed. All animals responded with peak vestibular dysfunction scores within 4 h after local trauma. While wild-type animals displayed partial or no recovery across 7 days post-injury, AAT-rich group exhibited early recovery: from behavioral score 9-out-of-9 at peak to 4.8 ± 0.44 (mean ± SD) within 8 h from injury, a time when wild-type mice scored 8.6 ± 0.54 (p < 0.0001), and from vestibular score 15-out-of-15 to 7.8 ± 2.2 within 24 h, when wild-type mice scored 13.0 ± 2.0 (p < 0.01). Thus, recovery and functional normalisation of an injured vestibular compartment is achievable without corticosteroid therapy; expedited tissue repair processes appear to result from elevated circulating AAT levels. This study lays the foundation for exploring the molecular and cellular mediators of AAT within the repair processes of the delicate microscopic structures of the vestibular end organ., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Background: numerous researches on the pathological mechanism of Enlarged Vestibular Aqueduct (EVA) syndrome mainly focuses on the genetic characteristics of SLC26A4 gene and the function of its encoding protein, Pendrin. One of the limitations with these explanations is that it does not explain why cerebrospinal fluid pressure can affect clinical manifestations., Objectives: To establish a new approach to explain the clinical manifestations of EVA syndrome with biomechanical method., Material and Methods: 108 cases of EVA syndrome who received cochlear implantation were analyzed retrospectively. A cochlear model was built to reflect the differences of the structure in EVA syndrome with or without Mondini malformation. The CFD software was used to simulate and display the differences in mechanical pathogenic factors to which the model was subjected., Results: EVA syndrome patients with Mondini malformation suffer more mechanical damage from the cerebrospinal fluid pressure due to their structural reason and their symptoms appear earlier and progress faster., Conclusions: Biomechanics is an important aspect of pathological mechanism of EVA syndrome, and it provides a new angle for clinical decision-making.

Inner and middle ear disorders are the leading cause of hearing loss, and are said to be among the greatest risk factors of dementia. The use of regenerative medicine for the treatment of inner ear disorders may offer a potential alternative to cochlear implants for hearing recovery. In this paper, we reviewed recent research and clinical applications in middle and inner ear regeneration and cell therapy. Recently, the mechanism of inner ear regeneration has gradually been elucidated. "Inner ear stem cells," which may be considered the precursors of various cells in the inner ear, have been discovered in the cochlea and vestibule. Research indicates that cells such as hair cells, neurons, and spiral ligaments may form promising targets for inner ear regenerative therapies by the transplantation of stem cells, including mesenchymal stem cells. In addition, it is necessary to develop tests for the clinical monitoring of cell transplantation. Real-time imaging techniques and hearing rehabilitation techniques are also being investigated, and cell therapy has found clinical application in cochlear implant techniques.

Objective: Subjects implanted with a Direct Acoustic Cochlear Implant (DACI) show improvements in their bone conduction (BC) thresholds after surgery. We hypothesised that a new pathway for BC sound is created via the DACI. The aim of this study was to investigate the contribution of this pathway to the cochlear response via measurements of the promontory and round window membrane (RWM) velocities while stimulating with a conventional bone conductor. Design: This study was a cadaver head study with a repeated measures study design. Study Sample: Eight ears of five fresh-frozen cadaveric whole heads were investigated in this trial. Results: After DACI implantation the promontory and RWM velocities did not change significantly in the frequency range 0.5-2 kHz when the DACI was switched off. Conclusions: No significant changes in the relative vibration magnitude of the RWM after DACI implantation were observed. The improvements in BC thresholds seen in patients implanted with a DACI very likely have their origin in the changed impedance at the oval window after DACI surgery leading to a more efficient contribution from the inner ear components to BC sound.

Background: Individuals with superior semi-circular canal syndrome often describe vestibular symptoms elicited by loud sounds, as well as other pressure-induced symptoms. They also often report other symptoms, including autophony, hyperacusis, cognitive dysfunction, spatial disorientation, anxiety and migraine headaches. Symptoms occur due to the presence of a 'third window' created by the dehiscence of the superior semi-circular canal. This case report describes a minimally invasive technique to provide soft reinforcement of the round window., Case Report: Our patient underwent a permeatal procedure whereby the tympanic membrane was raised to allow inspection of the middle ear. The round window niche was identified and the round window membrane was reinforced with fat. The mucosa of the bony meatus leading to the round window was then disrupted before the application of a double layer of perichondrium to allow further reinforcement., Conclusion: The case provides support for the use of 'soft reinforcement' as a simple and effective technique to treat the symptoms of superior canal dehiscence syndrome.

Objective: The deficits in the cochlea which is at the one end of the ear sound transfer system, may effect middle ear functions. Wideband typanometry (WBT) is frequently used to evaluate these transfer functions which play a crucial role in setting the impedance matching between the external ear and the cochlea. To this end, the aim of this study was to investigate the ear transfer functions in inner ear malformations via WBT, and to question whether these functions change depending on the types of inner ear malformation., Methods: This prospective case-control study was conducted in a university hospital. One hundered-fifty-seven ears (aged 3-37 years) under the groups of cochlear hypoplasia, incomplete partition I, incomplete partition II, cochlear aplasia and complete labyrinthine aplasia were evaluated. In the control group, 30 ears with normal hearing were enrolled and WBT was carried out. Tympanometric peak pressure, equivalent middle ear volume, static admittance, tympanogram width, resonance frequency, average wideband tympanometry and absorbance measurements were analyzed., Results: The inner ear malformation groups demonstrated statistically significant differences than the control group and from each other in terms of traditional tympanometric parameters and WBT test parameters (p<0.05). The most remarkable difference was between the group of complete labyrinthine aplasia and the control group, most probably because of complete labyrinthine aplasia's structural effects. However, on some parameters, incomplete partition II and the control group showed similarities. In absorbance measurements, there was significant difference between all patient groups and the control group, especially at high frequencies (p<0.05). The largest difference was between the control group and the group of complete labyrinthine aplasia which has revealed the lowest absorbance values (p<0.05). In averaged-wideband tympanogram analysis, all patient groups obtained a lower amplitude peak than the control group; complete labyrinthine aplasia group had the flattest peaked amplitude, while the incomplete partition II group had a near-normal curve., Conclusion: The results of the study revealed the distinctive effects of inner ear malformations in middle ear transfer functions. It is concluded that the absence of inner ear structures causes negative effects on energy absorbance and the other transfer functions of the middle ear. WBT may provide additional information on diagnosis of patients with inner ear malformations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Otitis media with effusion (OME) is the most common cause of hearing impairment among children in developed nations. Middle ear (ME) fluid accumulation leads to progressive hearing impairment, usually of the conductive type. In some cases, mixed hearing loss associated with OME has been noted. It was reported that effusion in the ME has a negative impact on the vestibular system of the inner ear., Objectives: The aim of this random-sample cohort study was to evaluate postural stability and the influence of ME drainage on vestibulospinal reflexes in children with OME, and to determine whether disturbances in the vestibular organ correlate with a sensorineural component in OME-related hearing loss., Material and Methods: The study group consisted of 53 children with bilateral OME who were treated with bilateral ME drainage. The study group was divided into subgroups according to hearing loss. The control group consisted of 29 healthy children. Vestibular function and hearing evaluation were performed before and 4 weeks after drainage., Results: A comparison of the stabilograms of the study group and the control group revealed elevated parameters in most of the tests. In the subgroup with mixed hearing loss, either before or after ME drainage, elevated stabilogram parameters were found in all tests. Posturography revealed vestibular system disturbances before and after ME drainage in the subgroup with mixed hearing loss, especially before ME drainage. The stabilogram parameters in the subgroup with conductive hearing loss after ME drainage were better in most tests in comparison to those before the procedure., Conclusions: The presence of effusion in the ME has a negative effect on the inner ear. We highlight the importance of monitoring the condition of the vestibular system in all children with OME, especially in cases with mixed hearing loss and more advanced clinical stages of the disease.

Objective: Because of their high metabolic activity and low-resting oxygen tension, the organs of the inner ear are vulnerable to hypoxia, a condition that occurs repetitively in obstructive sleep apnea-hypopnea syndrome (OSAHS). The present study aimed to investigate the inner ear function of patients with OSAHS., Methods: A total of 58 patients with OSAHS (116 ears) and 20 adults without OSAHS were enrolled in the present study. The clinical features, such as air-conduction thresholds, auditory brainstem response (ABR, 11 times/s and 51 times/s stimulation rates), and distorted products otoacoustic emission (DPOAE), were evaluated and compared between these two groups., Results: Air-conduction thresholds at 4 kHz and 8 kHz were higher in patients with OSAHS compared with controls (P < 0.001). At the rate of 11 times per second, biauricular wave I latencies and wave V latencies in the OSAHS group were longer than those in the control group (1.51 ± 0.13 vs. 1.33 ± 0.07 ms, P < 0.001; 5.65 ± 0.23 vs. 5.53 ± 0.23 ms, P = 0.0016). At the rate of 51 times per second, biauricular wave I latencies and wave V latencies in the OSAHS group were longer than those in the control group (1.64 ± 0.12 vs. 1.44 ± 0.06 ms, P = 0.0001; 5.92 ± 0.26 vs. 5.80 ± 0.18 ms, P = 0.0077). However, there was no significant difference in the wave I and wave V interval between these two groups (P = 0.10). DPOAE amplitude was significantly reduced in OSAHS patients, although no hearing loss was observed., Conclusion: High-frequency hearing loss was detected in adults with severe OSAHS, and wave I latencies and wave V latencies of ABR were prolonged.

Purpose: To investigate and compare the effect of endoscopic and microscopic type 1 tympanoplasty on the cochlear function, to determine if they have a different impact on the inner ear function., Methods: 72 ears treated by transcanal endoscopic type 1 tympanoplasty and 84 ears treated by microscopic type 1 tympanoplasty in 3 tertiary referral centers were enrolled in the study. Microscopic type 1 tympanoplasty were performed by transcanal or retroauricular approach. Only patients with mobile and intact ossicular chain were involved in the study. A retrospective chart review was performed. Main outcome measures were: (1) change in bone conduction thresholds at 250, 500, 1000, 2000, 4000 Hz; (2) change in bone conduction Pure Tone Audiometry; (3) correlation of audiometric outcomes with surgical technique, graft type and graft position., Results: A mild postoperative bone conduction threshold shift was observed at 2000 Hz and 4000 Hz in both groups, without significant differences between the two groups. No statistically significant modifications in bone conduction were observed at any frequencies in patients operated by transcanal endoscopic approach compared with those who underwent transcanal or retroauricular microscopic type 1 tympanoplasty. Moreover, neither the placement nor the type of the graft seemed to influence the cochlear function preservation., Conclusions: The endoscopic and the microscopic approaches have a similar impact on the bone conduction threshold during type 1 tympanoplasty. In particular, the one-handed manipulation of the ossicular chain during the endoscopic technique did not show an increased risk of inner ear damage.

Objective: Our aim was to elucidate relationships between results from the caloric test (c-test), video Head Impulse Test (vHIT) and inner ear gadolinium-enhanced MRI (ieMRI) in patients with endolymphatic hydrops (EH), especially patients with Ménière's disease (MD)., Methods: We managed 1789 successive patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to December 2018. After providing informed consent for vertigo/dizziness examinations, 281 patients were hospitalized to check their inner ear function for proper diagnosis and treatment. Then 76 participants underwent the c-test, vHIT and ieMRI. Among these 76 cases, 20 were diagnosed with MD (20/76; 26.3%) and 56 were non-MD (56/76; 73.7%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. The MD group included 15 unilateral and 5 bilateral cases. The non-MD group included 22 benign paroxysmal positional vertigo, 10 vestibular neuritis, 8 sudden deafness with vertigo, 6 orthostatic dysregulation, 4 vestibular neuropathy and 6 others. Results in these examinations in the side of an active lesioned inner ear were representative in each peripheral case., Results: Twenty-nine of the 76 patients (38.1%) showed discrepant results between the c-test (outside of normal range) and vHIT (within normal range). Twenty-two of 76 patients (28.9%) had a positive EH sign on ieMRI. The c-test/vHIT discrepancy percentage in MD (14/20; 70.0%) was significantly higher than that in non-MD (15/56; 26.8%) (p=0.00179). The positive EH sign in ieMRI percentage in MD (15/20; 75.0%) was significantly higher than that in non-MD (7/56; 12.5%) (p=0.0015). There was a significant positive relationship between the c-test/vHIT discrepancy and the positive EH sign (p=0.00058) in all 76 cases combined. However, there was no significant relationship between c-test/vHIT discrepancy and positive EH sign (p=0.13) in the 20 MD cases. Considering the 15 unilateral and 5 bilateral MD cases, the c-test/vHIT discrepancy was observed in 14 of the 25 affected ears. Positive signs of vestibular EH herniation into the cupula in the lateral semicircular canal was seen in 14 of the 25 MD ears. There was significant relationship between the c-test/vHIT discrepancy and EH herniation (p=0.0012) in MD ears., Conclusion: The present results suggest that patients with MD could have inner ear EH significantly more often than those with non-MD. In cases with MD, a positive EH sign on ieMRI did not always indicate a c-test/vHIT discrepancy; both findings may occur due to herniation of vestibular EH adjacent to the lateral semicircular canal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this study was to test whether hearing function is impaired in women with premature ovarian failure. Thirty (30) women with premature ovarian failure (POF), 30 women in menopause and 30 healthy controls were recruited in this study. Pure tone audiometric (PTA), transiently evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) of the study participants were analysed. At PTA, 6 and 8 kHz were lower in menopause group compared with both women with POF and controls. At TEOAE 3 and 4 kHz and at DPOAE 1, 2, 4 and 6 kHz were lower in menopause group compared with the controls. At DPOAE 6 kHz was lower in the POF group compared with the controls. Women with POF comparing to menopause group at TEOAE 3, 4 kHz and at DPOAE 4 and 6 kHz were lower in the menopause group. Inner ear function of both women in menopause and women with POF was declined compared to the healthy controls. Clinically, evaluation of hearing status may be considered in women with POF.Impact statement What is already known on this subject: Premature ovarian failure (POF) affects 1%-2% of women, and it adversely effects on health status (such as cardiovascular, psychological and cognitive disorders). Previous studies suggested that a lack of oestrogen might play a role in hearing disorders in women. However, we do not know POF's adversely effect on cochlea and hearing. What the results of this study add : The present study demonstrates that lower serum oestrogen has a negative effect hearing in women with POF at DPOAE 6 kHz. What the implications are of these findings for clinical practice and/or further research: The women with POF must be evaluated for hearing status.

Objectives: Petrous bone cholesteatoma is a rare pathologic entity and may be a difficult surgical challenge because of potential involvement of the facial nerve, carotid artery, dura mater, otic capsule and superior petrosal or lateral sinus. The objective of this article is to present the endoscope-assisted surgery for petrous bone cholesteatoma., Materials and Methods: Eight patients (nine ears) who underwent endoscope-assisted petrous bone surgery for cholesteatoma. Pure tone audiogram, magnetic resonance imaging were performed at preoperatively, and at approximately 12 months postoperatively., Results: Endoscope assisted surgery was performed in 8 patients and 9 ears. Of these patients, 6 were male and 2 were females. Median age was 19,5 (range 7-52) years. Hearing was able to preserved in 8 ears (8/9). Recurrence disease was observed one ear in long term follow up (1/9). In another one patient, cholesteatoma pearl was removed in the office., Conclusion: Endoscope-assisted surgery can allow removal of cholesteatoma of petrous apex with preserving hearing. It also provides to remove the cholesteatoma via transmastoid approach for perilabyrinthine space as "minimally invasive surgery" instead of middle fossa approach that is standard surgical procedure. In apical and peri-labyrinthine cholesteatomas, endoscopes allow to preserve hearing with middle fossa approach instead of trans-otic/ trans-labyrinthine/trans-cochlear approach.

Current cochlear implant (CI) systems provide substantial benefits for patients with severe hearing loss. However, they do not allow for 24/7 hearing, mainly due to the external parts that cannot be worn in all everyday situations. One of the key missing parts for a totally implantable CI (TICI) is the microphone, which thus far has not been implantable. The goal of the current project was to develop a concept for a packaging technology for state-of-the-art microelectromechanical systems (MEMS) microphones that record the liquid-borne sound inside the inner ear (cochlea) as a microphone signal input for a TICI. The packaging concept incorporates requirements, such as biocompatibility, long-term hermeticity, a high sensing performance and a form factor that allows sensing inside the human cochlea and full integration into the existing CI electrode array. The present paper (1) describes the sensor packaging concept and the corresponding numerical and experimental design verification process and (2) gives insight into new engineering solutions for sensor packaging. Overall, a packaging concept was developed that enables MEMS microphone technology to be used for a TICI system., Competing Interests: The authors declare no conflict of interest.

Acoustic overstimulation (AOS) is defined as the stressful overexposure to high-intensity sounds. AOS is a precipitating factor that leads to a glutamate (GLU)-induced Type I auditory neural excitotoxicity and an activation of an immune/inflammatory/oxidative stress response within the inner ear, often resulting in cochlear hearing loss. The dendrites of the Type I auditory neural neurons that innervate the inner hair cells (IHCs), and respond to the IHC release of the excitatory neurotransmitter GLU, are themselves directly innervated by the dynorphin (DYN)-bearing axon terminals of the descending brain stem lateral olivocochlear (LOC) system. DYNs are known to increase GLU availability, potentiate GLU excitotoxicity, and induce superoxide production. DYNs also increase the production of proinflammatory cytokines by modulating immune/inflammatory signal transduction pathways. Evidence is provided supporting the possibility that the GLU-mediated Type I auditory neural dendritic swelling, inflammation, excitotoxicity, and cochlear hearing loss that follow AOS may be part of a brain stem-activated, DYN-mediated cascade of inflammatory events subsequent to a LOC release of DYNs into the cochlea. In support of a DYN-mediated cascade of events are established investigations linking DYNs to the immune/inflammatory/excitotoxic response in other neural systems.

Objectives: The ASSR is used widely as an objective measurement of hearing in clinical settings because of its high frequency specificity. The recruitment phenomenon is generally detected using subjective evaluations which require direct communication with the patient. If the recruitment phenomenon can be detected with ASSR, it would facilitate diagnosis in patients with developmental disorders and infants., Subjects and Methods: We examined 2 groups of subjects: 10 subjects with unilateral hearing impairment in whom the recruitment phenomenon was detected by the alternate binaural loudness balance test and 12 normal subjects. We compared the relationships between the ASSR response and the stimulus sound pressure level in the 2 groups using the 80-Hz ASSR., Results: The amplitude of ASSR was significantly higher in the impaired ear in hearing-impaired subjects compared to a normal ear in normal subjects. The latency of ASSR was significantly shorter in the impaired ear in hearing-impaired subjects than in the normal ear in the normal subjects., Conclusion: This study showed that the recruitment phenomenon caused the higher amplitude and the shorter latency observed in hearing-impaired subjects in the 80-Hz auditory steady-state response (ASSR) in comparison with normal subjects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Presbycusis or age-related hearing loss (ARHL) is the most common sensory deficit in the human population. A substantial component of the etiology stems from pathological changes in sensory and non-sensory cells in the cochlea. Using a non-obese diabetic (NOD) mouse model, we have characterized changes in both hair cells and spiral ganglion neurons that may be relevant for early signs of age-related hearing loss (ARHL). We demonstrate that hair cell loss is preceded by, or in parallel with altered primary auditory neuron functions, and latent neurite retraction at the hair cell-auditory neuron synapse. The results were observed first in afferent inner hair cell synapse of type I neurites, followed by type II neuronal cell-body degeneration. Reduced membrane excitability and loss of postsynaptic densities were some of the inaugural events before any outward manifestation of hair bundle disarray and hair cell loss. We have identified profound alterations in type I neuronal membrane properties, including a reduction in membrane input resistance, prolonged action potential latency, and a decrease in membrane excitability. The resting membrane potential of aging type I neurons in the NOD, ARHL model, was significantly hyperpolarized, and analyses of the underlying membrane conductance showed a significant increase in K + currents. We propose that attempts to alleviate some forms of ARHL should include early targeted primary latent neural degeneration for effective positive outcomes.

Objectives: Distortion product otoacoustic emissions (DPOAEs) are a time-efficient, non-invasive means of assessing the integrity of active inner ear mechanics. Unfortunately, the presence of even relatively minor conductive hearing loss (CHL) has been suggested to reduce the clinical utility of DPOAEs significantly. The primary aims of this study were to systematically evaluate the impact of CHL on DPOAE amplitude and to determine if ear-specific primary tone level manipulations can be used to mitigate CHL impact and recover DPOAE measurability., Methods: For 30 young adults (57 ears) with normal hearing, DPOAEs were obtained for f 2  = 1-6 kHz. Observed DPOAE amplitudes were used to generate ear- and frequency-specific models with the primary tone levels, L 1 and L 2, as inputs and predicted DPOAE amplitude, L DP , as output. These models were then used to simulate the effect of CHL (0-15 dB), as well as L 1 manipulations (0-15 dB), on DPOAE measurability., Results: Mean L DP for every CHL condition was significantly different from that for all other conditions (p = <.001), with a mean L DP attenuation of 8.7 dB for every 5 dB increase in CHL. Mean DPOAE measurability in response to a standard clinical stimulation paradigm of L 1 /L 2  = 65/55 (dB SPL) was determined to be 99%, 84%, 37%, and 9% in the presence of 0, 5, 10, and 15 dB CHL, respectively. In the presence of 10 dB CHL, altering L 1 resulted in an approximately 25% increase in DPOAE responses., Conclusion: Subclinical CHL loss is sufficient to significantly impair DPOAE measurability in a meaningful proportion of otherwise healthy ears. However, through strategic alteration of primary tone levels, the clinician can mitigate CHL impact and at least partially recover DPOAE measurability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dizziness is one of the most common hemodialysis-associated symptoms, and has been thought to be caused by cerebral edema or intravascular hypovolemia. However, the possibility of a peripheral vestibular disturbance due to hemodialysis has not been addressed as a cause of hemodialysis-associated dizziness. In the present study, we propose a new hypothesis accounting for hemodialysis-associated dizziness, i.e., the decrease in serum osmolality due to rapid removal of urea during dialysis causes inner ear fluid dyshomeostasis, leading to density difference between perilymph and endolymph., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

SLC26A4 gene mutations lead to Pendred syndrome and non-syndromic hearing loss (DFNB4). The mouse model is well used to study the pathology of Pendred syndrome, however, mice with different Slc26a4 mutations exhibit different phenotypes, and these mice have severe deafness and inner ear malformations that are not imitated less severely Human phenotype. In this study, we generated a knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation to mimic the most common mutation found in human. Some L236P mice were observed to have significant vestibular dysfunction including torticollis and circling, the giant otoconia and destruction of the otoconial membrane was observed in L236P mice. Unlike other profoundly deafness in Slc26a4 mouse model, L236P mice present mild to profound hearing loss, consistent with the hearing threshold, inner ear hair cells also lost from slight to significant. Together, these data demonstrate that the L236P mouse phenotype is more similar to the human phenotype and should be used as a tool for further research into the human Pendred syndrome., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inner ear anomalies diagnosed using a radiological study are detected in almost 30% of cases with congenital or prelingual-onset sensorineural hearing loss. Inner ear anomalies can be isolated or occur along with a part of a syndrome involving other systems. Although astonishing progress has been made in research aimed at revealing the genetic causes of hearing loss in the past few decades, only a few genes have been linked to inner ear anomalies. The aim of this review is to discuss the known genetic causes of inner ear anomalies. Identifying the genetic causes of inner ear anomalies is important for guiding clinical care that includes empowered reproductive decisions provided to the affected individuals. Furthermore, understanding the molecular underpinnings of the development of the inner ear in humans is important to develop novel treatment strategies for people with hearing loss.

Objective: To discuss the benefit of using transmastoid slotted labyrinthotomy approach (TSLA) and customized electrode for common cavity deformity (CCD) patients, and to evaluate the audiological outcomes. Methods: A retrospective analysis of the intraoperative monitoring data and postoperative auditory outcomes of 10 CCD cases who received cochlear implantation in Beijing Tongren Hospital,Capital Medical University from April 2016 to December 2017, was conducted using TSLA and customized electrod as a test group.At the same time, 10 cases of age and gender matched children with severe or severe sensorineural hearing loss and normal inner ear structures were recorded as a control group. Four questionnaires were collected from the two groupspre-operative, 6 months and 1 year after start-up. The Wilcoxon signed rank sum test was used to compare the scores of different time points. Rank sum test of two independent samples was used to compare the scores between different groups. Results: None of the patients exhibited CSF leakage or facial paralysis after operation. The average impedance of 8 CCD children in the experimental group was below 5 kΩ. The total extraction rate of auditory neural response telemetry (ART) of all stimulating electrodes was 55% (33/60), and the amplitude of the electricity induced complex action potential (ECAP) of electrodes at different positions ranged from 50.69 to 170.3 μV.The average surgical time of the TSLA group was 46.4 min, shorter than the traditional approach.There was significant difference between the scores of pre-operative, 6 months and 1 year after start-up for the TSLA group(categories of auditory performance,CAP: 2.0 (2.0,3.0) vs . 4.0 (3.8,4.0) , Z= -3.109, P= 0.002; speech intelligibility rating,SIR: 2.0 (2.0,2.3) vs . 3.0 (2.8,4.0) , Z= -2.952, P= 0.003; meaningful use of speech scale,MUSS: 4.0 (3.3,6.0) vs . 9.0 (6.0,11.8) , Z= -3.421, P= 0.001; meaningful auditory integration scale, MAIS or infant-toddler and meaningful auditory integration scale, IT-MAIS: 5.5 (3.8,9.0) vs . 15.5 (10.8,18.5) , Z= -3.522, P= 0.000 for the latter two).In addition, The scores of the TSLA group were significantly worse than the control group at 6 months and 1 year after start-up.The high-resolution CT scan showed good adhesion of the electrodes without displacementone week and one year after surgery. Conclusions: For CCD patients, TSLA and customized electrode is recommended due to lower surgical difficulty and post-operative risk, shortened surgical time; Intraoperative ART monitoring can be used to determine the integrity of the auditory pathway. Children with common cavity deformity have a longer period of auditory rehabilitation, and the individual differences in speech rehabilitation are significantly different, which is significantly worse than those with normal structure.

Background: Inner ear hemorrhage is increasingly recognized as a cochlear lesion that can cause profound sudden sensorineural hearing loss (SSNHL). Objectives: To investigate changes of cochlear and vestibular function and to compare therapeutic recovery from profound SSNHL induced by different etiologies. Material and methods: Eighty patients with profound SSNHL (≥90 dB) were divided into an inner ear hemorrhage group and a non-inner ear hemorrhage group by MRI. Statistical analysis was performed to compare the therapeutic effects from vertigo and hearing loss and the outcomes of follow-up in the two groups. Results: There were significant differences between the two groups in terms of the overall 14-day therapeutic response rate (20 vs. 48%), the incidence of imbalance (26.7 vs. 6%), the incidence of semicircular canal dysfunction on the affected side (60 vs. 20%), the incidence of abnormal C-VEMP and O-VEMP on the affected side (63.3 vs. 38%; and 60 vs. 30%, respectively), the average hearing threshold (74.2 ± 10.7 vs. 53.6 ± 11.4 dB), and the word recognition score (65.5 ± 21.7 vs. 83.5 ± 24.5%) at a 12-month follow-up. Conclusions and significance: A higher percentage of patients with profound SSNHL induced by inner ear hemorrhage were associated with vertigo and had a poor prognosis.

Objective: To identify audiologic and otologic outcomes in previously healthy non-HIV patients with cryptococcal meningoencephalitis (CM)., Study Design: Retrospective case review of a subset of patients recruited in a prospective observational study following previously healthy individuals who developed CM., Setting: Tertiary referral center, National Institutes of Health Clinical Center., Patients: Previously healthy adult patients with CM without immune suppressive therapy before disease onset., Interventions: Diagnostic evaluations included audiometry, acoustic immittance, otoacoustic emissions, and auditory brainstem response studies, in addition to neurotologic assessment., Results: Twenty-nine patients (58 years) underwent audiologic evaluation between 6 months and 3.5 years after CM diagnosis; 21 patients were seen for longitudinal assessment with an average duration of follow up of 20.3 months. Nearly three-quarters (73%) of the cohort presented with hearing loss, most commonly (90%) sensorineural in origin. The most frequent degree of loss was mild and then moderate, although some patients had severe or profound impairment. Hearing loss improved (43%) or remained stable (38%) in most cases. Ears with internal auditory canal enhancement on magnetic resonance imaging (MRI) had significantly more hearing loss than those without enhancement, although a similar finding was not observed with gyral enhancement or the presence of ependymitis or ventricular volume expansion. Hearing loss was not associated with reduced cerebrospinal fluid (CSF) glucose, CSF total protein, cryptococcal antigen, or total cell count., Conclusions: Hearing loss is a common manifestation of cryptococcal meningitis in previously healthy patients and may involve a cochlear or neural site of lesion, or both. Routine surveillance of hearing in patients is recommended, regardless of symptomatology, to ensure early and appropriate intervention and care.

Objectives: This study aimed to assess the clinical benefit of device therapy on controlling the symptoms of Meniere's disease (MD)., Materials and Methods: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Internet, and Wanfang Data before January 13, 2018. We selected randomized controlled clinical trials, case-controlled studies, and cohort studies that dealt with outcomes of device therapy for the treatment of MD., Results: Sixteen trials met our inclusion criteria. The use of device therapy resulted in improved vertigo control, which was described as a reduction in the number of vertigo days by month (weighted mean difference [WMD]: 3.15, 95% confidence interval [CI]: 2.00-4.31), in the number of vertigo episodes by month (WMD: 7.37, 95% CI: 2.40-12.35), and in the vertigo visual analog score (WMD: 41.51, 95% CI: 34.68-48.34). In addition, the overall complete vertigo control (class A) rate was 50% (95% CI: 37%-64%). The device therapy also reduced the number of sick days by month (WMD: 4.56, 95% CI: 2.15-6.97), and the functional level improved (WMD: 2.66, 95% CI: 2.15-3.17). The electrocochleographic parameters decreased. The device therapy proved beneficial for hearing changes (WMD: 3.19, 95% CI: 0.66-5.71). No publication bias was found in the funnel plot and the results of Egger's test., Conclusion: This study showed that the device therapy might reduce vertigo attacks and sick days in patients with MD. Additionally, the function level and hearing level may improve after the device therapy. In addition, the decrease in electrocochleographic parameters showed that inner ear electrophysiology improved after device therapy.

Objectives:: The purpose of this study was to investigate the correlation between grades of endolymphatic hydrops (ELH) and clinical characteristics and determine the detailed clinical characteristics of Ménière's disease (MD) patients with evidence of hydrops based on magnetic resonance imaging (MRI)., Methods:: One hundred ninety-eight MD patients (396 ears) with MRI evidence of hydrops were included. ELH grades were evaluated using the Nakashima grading standard. Correlations between the extent of ELH and clinical features were evaluated. Detailed clinical characteristics were analyzed to assess the clinical diagnostic criteria., Results:: Of 198 patients, ELH was observed in 100% of cases on the clinically affected side and 8.6% of cases on the asymptomatic side. In addition, 98.5% of ELH was classified as moderate or significant grade. Low-frequency hearing loss was significantly correlated with the extent of both vestibular and cochlear hydrops, whereas the vertigo attack frequency showed no significant correlation with ELH grades. The disease duration of MD with bilateral ELH was longer than that with unilateral ELH. The clinical characteristics were variant and did not completely fit the proposed diagnostic criteria., Conclusions:: MRI findings have relevance to the clinical severity, to a certain extent, but not vestibular symptoms. The proposed diagnostic criteria based on clinical characteristics may be partially effective; analysis of the detailed clinical characteristics of MD was meaningful. Diagnosis of MD based on both MRI and clinical symptoms could facilitate an early diagnosis.

Objectives: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menière's disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at long-term follow-up., Study Design: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires., Setting: Outpatient hospital clinic setting., Patients: Adult patients with definite unilateral refractory Menière's disease, who previously received intratympanic treatment in a comparative trial., Intervention: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL)., Outcome Measures: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability., Results: Forty six of the 60 original trial patients (77%) completed the survey, 24 from the gentamicin and 22 from the methylprednisolone group. Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p < 0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone = 5 and gentamicin = 3) required further injections for relapse after completing the original trial., Conclusion: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up.

Hearing loss is the most common human sensory deficit. Its correction has been the goal of several gene-therapy based studies exploring a variety of interventions. Although these studies report varying degrees of success, all treatments have targeted developing inner ears in neonatal mice, a time point in the structural maturation of the cochlea prior to 26 weeks gestational age in humans. It is unclear whether cochlear gene therapy can salvage hearing in the mature organ of Corti. Herein, we report the first study to test gene therapy in an adult murine model of human deafness. Using a single intracochlear injection of an artificial microRNA carried in an AAV vector, we show that RNAi-mediated gene silencing can slow progression of hearing loss, improve inner hair cell survival, and prevent stereocilia bundle degeneration in the mature Beethoven mouse, a model of human TMC1 deafness. The ability to study gene therapy in mature murine ears constitutes a significant step toward its translation to human subjects., (Copyright © 2019 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

The performance of cochlear implant (CI) listeners is limited by several factors among which the lack of spatial selectivity of the electrical stimulation. Recently, many studies have explored the use of multipolar strategies where several electrodes are stimulated simultaneously to focus the electrical field in a restricted region of the cochlea., Objective: These strategies are based on several assumptions concerning the electrical properties of the inner ear that need validation. The first, often implicit, assumption is that the medium is purely resistive and that the current waveforms produced by several electrodes sum linearly. The second assumption relates to the estimation of the contribution of each electrode to the overall electrical field. These individual contributions are usually obtained by stimulating each electrode and measuring the resulting voltage with the other inactive electrodes (i.e. the impedance matrix). However, measuring the voltage on active electrodes (i.e. the diagonal of the matrix) is not straightforward because of the polarization of the electrode-fluid interface. In existing multipolar strategies, the diagonal terms of the matrix are therefore inferred using linear extrapolation from measurements made at neighboring electrodes., Approach: In experiment 1, several impedance measurements were carried out in vitro and in eight CI users using sinusoidal and pulsatile waveforms to test the resistivity and linearity hypotheses. In experiment 2, we used an equivalent electrical model including a constant phase element in order to isolate the polarization component of the contact impedance., Main Results: In experiment 1, high-resolution voltage recordings (1.1 MHz sampling) showed the resistivity assumption to be valid at 46.4 kHz, the highest frequency tested. However, these measures also revealed the presence of parasitic capacitive effects at high frequency that could be deleterious to multipolar strategies. Experiment 2 showed that the electrical model provides a better account of the high-resolution impedance measurements than previous approaches in the CI field that used resistor-capacitance circuit models., Significance: These results validate the main hypotheses underlying the use of multipolar stimulation but also suggest possible modifications to their implementation, including the use of an impedance model and the modification of the electrical pulse waveform.

Introduction: Sound is integral to communication and connects us to the world through speech and music. Cochlear hair cells are essential for converting sounds into neural impulses. However, these cells are highly susceptible to damage from an array of factors, resulting in degeneration and ultimately irreversible hearing loss in humans. Since the discovery of hair cell regeneration in birds, there have been tremendous efforts to identify therapies that could promote hair cell regeneration in mammals., Areas Covered: Here, we will review recent studies describing spontaneous hair cell regeneration and direct cellular reprograming as well as other factors that mediate mammalian hair cell regeneration., Expert Opinion: Numerous combinatorial approaches have successfully reprogrammed non-sensory supporting cells to form hair cells, albeit with limited efficacy and maturation. Studies on epigenetic regulation and transcriptional network of hair cell progenitors may accelerate discovery of more promising reprogramming regimens.

Objective: To evaluate resonance frequency (RF) values via dehydration effects in the inner ear caused by the glycerol test, which is used as a diagnostic method for Ménière's disease (MD)., Methods: Twenty adult patients with unilateral MD were included in the study. Before, and then at 1, 2, and 3 h after administration of glycerol (1 g/kg), pure-tone hearing levels (125-8,000 kHz) and multifrequency tympanometry tests were performed. As a control, the RF values of the ears of 25 healthy subjects (i.e., 50 ears) were compared to the affected and unaffected ears in the 20 MD patients., Results: There was a significant difference between the RF values of affected and healthy ears before glycerol administration (p = 0.047). The RF values before and after glycerol administration into affected ears were compared. The average RF values decreased significantly from 748.0 ± 402.1 to 808.0 ± 410.1 Hz at 1 h after glycerol intake, and this value increased during the subsequent hours. There were no statistically significant differences between the pure-tone levels before and 1 h after glycerol administration, but a significant decrease was observed at 3 h., Conclusion: We suggest that MD has different inner-ear dynamics and normal RF values when compared to healthy ears. Furthermore, decreased inner ear pressure causes reduction of the mass effect and a stiffening of the annular ligament. We conclude that pre- and post-RF tests should be added to the test battery for diagnosis of MD., (© 2019 S. Karger AG, Basel.)

Aim: To study ultrastructural changes in stria's vascularis cells of inner ear and determine possible ways of correction., Material and Methods: The work was carried out on male guinea pigs. After completion of the experiment, stria vascularis of inner ear was subjected to electron microscopic examination., Results and Discussion: In the control group (receiving gentamycin sulfate in an ototoxic dose), signs of blood flow disturbance were revealed, as well as ultrastructural changes in stria's vascularis cells (expansion of intercellular space, deformation of organelles, thinning of glycocalyx, blebbing). Also, fragmented cells were found. These changes are characteristics for apoptosis. In experimental group (receiving gentamycin sulfate and melaxen), degenerative changes were less pronounced. An increase of cell's secretory activity was observed., Conclusion: Changes in stria's vascularis cells by using melaxen are less pronounced. Increase of cell's secretory activity in stria vascularis is a compensatory reaction and saves auditory function.