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Background: Systemic sclerosis (SSc) is a disease of a very heterogeneous clinical picture and immunological profile with progression rate that varies between individuals. Although hearing deterioration is not a complaint that comes to the fore in SSc patients, as it is not life-threatening compared to many other more severe symptoms of this disease, it can significantly impair the quality of life. Medical literature concerning this problem is rather scarce., Materials and Methods: In this article we systematically reviewed the medical publications concerning hearing impairment in patients with systemic sclerosis to evaluate current understanding of this complex problem. Following PRISMA guidelines a total of 19 papers were found and analysed including 11 original studies and 8 case reports., Results: Although it seems that hearing impairment in SSc patients is relatively more common than in the general population, based on the analysis of available literature, no firm conclusions regarding its frequency and pathomechanism can be drawn yet. Microangiopathy leading to damage to the sensory cells of the inner ear is suspected to be the main mechanism of hearing loss, although damage to the higher levels of the auditory pathway appears to be underestimated due to incomplete audiological diagnosis., Conclusion: Undoubtedly, the reason for the difficulty in such an evaluation are the complex and still not fully elucidated pathomechanism of SSc, the individually variable dynamics of the disease and the unique heterogeneity of symptoms. Nevertheless, further studies in larger and appropriately selected groups of patients, focused more on the dynamics of microangiopathy and not solely on clinical symptoms could provide answers to many key questions in this regard., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sieśkiewicz, Rębacz and Sieśkiewicz.)

Objective Because of the anatomically close relationship between the cochlea and the vestibular organs, cochlear function disorders may be accompanied by vestibular disorders. This study aimed to evaluate vestibular functions in patients with idiopathic sudden sensorineural hearing loss using VEMP, caloric test, and VNG test battery and its relation to prognosis. Materials and Methods For this study, 42 patients aged 18–55 years with idiopathic sudden sensorineural hearing loss and 30 volunteers who had no hearing and balance problems were included. Audiometry, cVEMP, oVEMP, caloric tests, and VNG tests were performed. Moreover, the effects of age, sex, time of admission, degree and configuration of hearing loss, accompanying vertigo, tinnitus, and ear fullness on improvement in hearing were evaluated. Results Of the 42 patients in the study group, 26 (56.52%) were male, 20 (43.48%) were female, and the mean age was 41.54 ± 12.23 years. Of the 30 individuals in the control group, 19 (63.3%) were male, 11 (36.7%) were female, and the mean age was 39.53 ± 13.03 years. There was no significant difference in the incidence of sudden sensorineural hearing loss in terms of sex and age, and the prognosis was better for female patients. Early admission to treatment was a factor of good prognosis; profound hearing loss, bilateral hearing loss and vertigo were factors of poor prognosis. Prognosis was better in patients with rising type audiogram configuration, while the prognosis was worse in patients with flat, descending and total hearing loss. Tinnitus and ear fullness had no effect on the prognosis. No anomalies were observed in VNG findings. Moreover, abnormal caloric response was higher in patients with profound hearing loss and total hearing configuration. Shortening was observed in cVEMP / oVEMP P1 and N1 latency after treatment. Furthermore, there was an improvement in abnormal responses after treatment. Conclusion In this study, vestibular function was affected in patients with idiopathic sudden sensorineural hearing loss. The present study can help the development of a clinical strategy in the evaluation of the vestibular system in idiopathic SSNHL, patient follow-up, patient information, and the implementation of vestibular rehabilitation. Note that additional studies involving larger patients series are required.

Despite the low overall prevalence of individual rare diseases, cochlear dysfunction leading to hearing loss represents a symptom in a large proportion. The aim of this work was to provide a clear overview of rare cochlear diseases, taking into account the embryonic development of the cochlea and the systematic presentation of the different disorders. Although rapid biotechnological and bioinformatic advances may facilitate the diagnosis of a rare disease, an interdisciplinary exchange is often required to raise the suspicion of a rare disease. It is important to recognize that the phenotype of rare inner ear diseases can vary greatly not only in non-syndromic but also in syndromic hearing disorders. Finally, it becomes clear that the phenotype of the individual rare diseases cannot be determined exclusively by classical genetics even in monogenetic disorders.Auch wenn die einzelnen Krankheitsbilder selten sind, stellen seltene Erkrankungen der Cochlea in ihrer Gänze eine doch gehäufte Entität dar, die zu Hörstörungen führt. Ein/Das Ziel des vorliegenden Referates war es, unter Berücksichtigung der Embryonalentwicklung der Hörschnecke und einer systematischen Zusammenfassung eine übersichtliche Darstellung der seltenen cochleären Erkrankungen zu ermöglichen. Auch wenn rapide biotechnologische und bioinformatische Fortschritte die Diagnose einer seltenen Erkrankung erleichtern, so kann oft nur im interdisziplinären Austausch der Verdacht einer seltenen Erkrankung erhoben werden. Trotz gleicher zugrunde liegender Mutationen kann der Phänotyp nicht nur bei den genetisch bedingten Hörstörungen sondern auch bei den syndromalen Erkrankungen stark variieren. Schließlich wird deutlich, dass der Phänotyp der einzelnen seltenen Erkrankungen nicht ausschließlich durch die klassische Genetik bestimmt werden kann.

Objectives This paper attempts to create a new classification type of cochlear hypoplasia (CH)-type malformation taking into consideration of vestibular section and internal auditory canal (IAC). Materials and methods Preoperative computed-tomography (CT) scans of cochlear implant (CI) candidates (N=31) from various clinics across the world with CH type malformation were taken for analysis. CT dataset were loaded into 3D-slicer freeware for three-dimensional (3D) segmentation of the inner-ear by capturing complete inner-ear structures from the entire dataset. Cochlear size in terms of diameter of available cochlear basal turn and length of cochlear lumen was measured from the dataset. In addition, structural connection between IAC and cochlear portions was scrutinized, which is highly relevant to the proposed CH classification in this study. Results CH group-I has the normal presence of IAC leading to cochlear and vestibular portions, whereas CH group-II is like CH group-I but with some degree of disruption in vestibular portion. In CH group-III, a disconnection between IAC and the cochlear portion irrespective of other features. Within all these three CH groups, the basal turn diameter varied between 3.1 mm and 9.6 mm, and the corresponding cochlear lumen length varied between 3 mm and 21 mm for the CI electrode array placement. Conclusion A new classification of CH mainly based on the IAC connecting the cochlear and vestibular portions is presented in this study. CI electrode array length could be selected based on the length of the cochlear lumen, which can be observed from the 3D image.

Cochlear synaptopathy is the noise-induced or age-related loss of ribbon synapses between inner hair cells (IHCs) and auditory-nerve fibers (ANFs), first reported in CBA/CaJ mice. Recordings from single ANFs in anesthetized, noise-exposed guinea pigs suggested that neurons with low spontaneous rates (SRs) and high thresholds are more vulnerable than low-threshold, high-SR fibers. However, there is extensive postexposure regeneration of ANFs in guinea pigs but not in mice. Here, we exposed CBA/CaJ mice to octave-band noise and recorded sound-evoked and spontaneous activity from single ANFs at least 2 wk later. Confocal analysis of cochleae immunostained for pre- and postsynaptic markers confirmed the expected loss of 40%–50% of ANF synapses in the basal half of the cochlea; however, our data were not consistent with a selective loss of low-SR fibers. Rather they suggested a loss of both SR groups in synaptopathic regions. Single-fiber thresholds and frequency tuning recovered to pre-exposure levels; however, response to tone bursts showed increased peak and steady-state firing rates, as well as decreased jitter in first-spike latencies. This apparent gain-of-function increased the robustness of tone-burst responses in the presence of continuous masking noise. This study suggests that the nature of noise-induced synaptic damage varies between different species and that, in mouse, the noise-induced hyperexcitability seen in central auditory circuits is also observed at the level of the auditory nerve. NEW & NOTEWORTHY Noise-induced damage to synapses between inner hair cells and auditory-nerve fibers (ANFs) can occur without permanent hair cell damage, resulting in pathophysiology that “hides” behind normal thresholds. Prior single-fiber neurophysiology in guinea pig suggested that noise selectively targets high-threshold ANFs. Here, we show that the lingering pathophysiology differs in mouse, with both ANF groups affected and a paradoxical gain-of-function in surviving low-threshold fibers, including increased onset rate, decreased onset jitter, and reduced maskability.

Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions, this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results showed that ZIKV can robustly infect proliferating sensory progenitors, as well as post-mitotic hair cells and supporting cells. Virus neutralization using ZIKV-117 antibody blocked cochlear infection. AXL is a cell surface molecule known to enhance the attachment of flavivirus to host cells. While Axl mRNA is widely expressed in embryonic cochlear tissues susceptible to ZIKV infection, it is selectively downregulated in the post-mitotic sensory organ by E15.5, even though these cells remain infectible. These findings may offer insights into which target cells could potentially contribute to hearing loss resulting from fetal exposure to ZIKV in humans.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.

Postoperative inflammation and the formation of fibrotic tissue around the intracochlear electrode array are often held responsible for negative outcomes in cochlear implant recipients. Here we test the effectiveness of intracochlear delivery of dexamethasone via a drug-eluting electrode array in reducing fibrotic tissue formation, assessed via measurement of both monopolar and four-point electrode impedance. Adult guinea pigs were bilaterally implanted with a dexamethasone-eluting array (left ear) and a standard non-eluting array (right ear). Arrays were electrically stimulated daily for 4 weeks, commencing 1 week after implantation, and impedance measured both before and after stimulation. Histological assessment of the tissue was made at the end of the 5-week period. The dexamethasone-eluting array did not reduce monopolar (MP1 + 2) electrode impedance over the course of 5 weeks, and no significant difference was observed in fibrotic tissue, new bone growth, or spiral ganglion neuron density between array types. However, four-point impedance, which provides an indication of the local environment at the neural-tissue interface, was significantly lower in the presence of dexamethasone. A strong relationship was seen between four-point and monopolar impedance for individual electrode arrays, with the exception of the standard array after daily electrical stimulation. This group instead showed a significant correlation between the final four-point impedance measure and percentage of fibrous tissue and new bone growth. In conclusion, this study demonstrated that dexamethasone influences four-point electrode impedance as well as the relationship between fibrotic tissue and impedance, and that both outcomes are shaped by daily electrical stimulation. These results suggest a change occurs at the local tissue-electrode interface in the presence of sustained, intracochlear release of dexamethasone.

Purpose of review Increasing awareness and prevalence of disorders in hearing and balance have placed emphasis on treatment strategies. With the rapid evolution in molecular, gene, and nanotechnology, alternate delivery methods have advanced intracochlear drug delivery. This review aims to raise awareness of recent developments in technologies to augment current clinical practices. Recent findings Intracochlear drug delivery research has expanded with the familiarity and accessibility to cochlear implantation. Various therapeutics are closely studied for both safety and efficacy as well as biologic effect. Agents including neurotrophins, antiapoptotics, cell therapy, gene therapy, and anti-inflammatory drugs are on the forefront of preclinical research. Cochlear implant electrode modification and drug administration at the time of implantation is a major focus of research. Improvements in study design have focused on overcoming barriers including elucidating the role of the blood-perilymph barrier. Summary Inner ear drug delivery methods include systemic, intratympanic, and intracochlear administration. Therapeutic technologies aim to overcome delivery barriers and to improve overall biologic effect while minimizing toxicity. Precision of drug application through intratympanic and intracochlear administration with minimal trauma is the future of inner ear drug development.

Purpose: Sudden sensorineural hearing loss (SSNHL) has similarities to conditions with vascular etiologies such as myocardial infarction and cerebral stroke. Thus, it could be considered as an early sign of a vascular disease and not only a specific local condition. Chronic hypoperfusion in the brain districts leads to a chronic ischemic damage, called cerebral small vessel disease (CSVD), detectable with brain magnetic resonance imaging (MRI). Methods: The authors used CSVD to establish the presence of vascular risk factors in individuals with SSNHL and used the Fazekas score scale to classify them. Results: Our study showed that individuals with SSNHL aged between 48 and 60 years have 26% more probability to have a Fazekas score higher than 1 compared to the general population. Individuals younger than 28 years showed a statistically significant negative correlation to have a Fazekas score higher than 0. The higher is the Fazekas score, the less is the probability of hearing recovery. The medium hearing-recovery probability is 46%. This decreases by 16% for every increase of score in the Fazekas scale. In the present study, the recovery probability decreased from 80% in individuals younger than 48 years with a score of 0 to 14% in individuals with a Fazekas scores of 3 and 4. Conclusions: The authors assessed a higher prevalence of CSVD compared to the general population in patients aged between 48 and 60 years with SSNHL. Moreover, they assessed that the presence of CSVD is related to a decreased probability of recovery, as it has already been demonstrated for stroke.

ObjectiveTo examine when cochlear fibrosis occurs following a translabyrinthine approach for vestibular schwannoma resection, and to determine the safest time window for potential cochlear implantation in cases with a preserved cochlear nerve.MethodsThis study retrospectively reviewed the post-operative magnetic resonance imaging scans of patients undergoing a translabyrinthine approach for vestibular schwannoma resection, assessing the fluid signal within the cochlea. Cochleae were graded based on the Isaacsonet al. system (from grade 0 – no obstruction, to grade 4 – complete obliteration).ResultsThirty-nine patients fulfilled the inclusion criteria. The cochleae showed no evidence of obliteration in: 75 per cent of patients at six months, 38.5 per cent at one year and 27 per cent beyond one year. Most changes happened between 6 and 12 months after vestibular schwannoma resection, with cases of an unobstructed cochlear decreasing dramatically, from 75 per cent to 38.5 per cent, within this time.ConclusionThe progress of cochlear obliteration that occurred between 6 and 12 months following vestibular schwannoma resection indicates that the first 6 months provides a safer time window for cochlear patency.

Introduction The investigation of amplitudes of otoacoustic emissions in congenital hypothyroidism can provide information on cochlear function with more sensibility, when compared to other methods of auditory evaluation. Aim To investigate cochlear function through the amplitude of distortion product otoacoustic emissions in individuals with congenital hypothyroidism and to correlate with clinical aspects. Methods An exploratory, analytical, cross-sectional study with a convenience sample, composed of 50 individuals with congenital hypothyroidism and a group of 42 individuals without the disease, mean age of 8.4 (±3.1) years. The subjects of the research were evaluated by means of tonal and speech audiometry, immittance and distortion product otoacoustic emissions (DPOAEs). Continuous variables were described as mean or median and standard deviation. The Spearman test evaluated the correlations between the variables. Results Otoacoustic emission amplitudes were significantly reduced in the exposed group, with congenital hypothyroidism, when compared to the group of individuals without the disease, especially in the medium frequencies. The Spearman test showed a slight correlation between the amplitude values of the otoacoustic emissions of some frequencies and the variables: disease time, diagnostic age, irregular serum free thyroxine hormone levels and thyroid stimulating hormone, especially in the condition of less treatment, whose correlation was negative. Conclusion There was a correlation between the levels of signal amplitudes of otoacoustic emissions with clinical conditions and hormonal follow-up, suggesting probable subclinical auditory impairment in this population, as well as influence of some clinical aspects of congenital hypothyroidism on auditory function.

Demografischer Wandel und verandertes Freizeitverhalten lassen in den nachsten 20–30 Jahren eine rapide Zunahme von Horstorungen erwarten. Damit steigt das Risiko, an altersbedingtem Sprachdiskriminationsverlust, Tinnitus, Hyperakusis oder, wie neueste Studien postulieren, an Demenz zu erkranken. Es verdichten sich Hinweise darauf, dass bei Mensch und Tier der Verlust spezifischer Horfasern an verschiedenen Horstorungen beteiligt ist. Dieser Horfaserverlust kann durch cochleare Synaptopathie oder Deafferenzierung verursacht werden und fuhrt nicht zwangslaufig zu klinisch messbaren Horschwellenabweichungen. Tierexperimentell wurde belegt, dass eine verminderte Hornervaktivitat nach akustischem Trauma oder durch Alter zentral uber eine disproportional erhohte und schnellere akustisch evozierte Stammhirnantwort kompensiert werden kann. Die Analyse der uberschwelligen Amplituden von auditorisch evozierten Hirnstammpotenzialen und deren Latenz in Kombination mit nichtinvasiven bildgebenden Techniken wie die Magnetresonanztomographie konnen helfen die zentrale Kompensationsfahigkeit von Probanden zu identifizieren und definierten Hordefiziten zuzuordnen.

BACKGROUND: Experiments show that the extent of ongoing fibrotic change within the cochlea can be determined by the volume and pattern of bleeding within the first 24 h following cochlear implantation. Tissue-type plasminogen activator (tPA) is effective at reducing thrombus volume when administered both within and external to the systemic circulation. AIMS/OBJECTIVES: To determine if tPA delivered into the scala tympani immediately following implantation will reduce thrombus volume within the lower basal turn of the cochlea. MATERIALS AND METHODS: Guinea pigs were implanted with either 'soft' or 'hard' arrays and administered tPA or saline via an intra-cochlear infusion immediately after implantation. Hearing was checked prior to, and 2 weeks after implantation. Cochleae were then harvested and imaged. RESULTS: Animals implanted with 'soft' arrays had 4.2% less tissue response compared with animals implanted with 'hard' arrays. In animals receiving 'soft' arrays, tPA reduced the volume of tissue response (measured by the percentage of the lower basal turn of the scala tympani occupied by tissue response) compared with saline. CONCLUSIONS AND SIGNIFICANCE: tPA may be effective in reducing the overall volume of tissue response in routine 'soft' cochlear implantation and may have a greater effect in the event of significant surgical trauma.

OBJECTIVES/HYPOTHESIS To investigate the prevalence and course of cochlear obliteration according to microsurgical approach to inform clinical decision making regarding optimal timing of cochlear implantation. STUDY DESIGN Retrospective radiologic review and chart review. METHODS Patients who underwent microsurgical resection of vestibular schwannoma (VS) with a minimum of two available postoperative magnetic resonance imaging (MRI) scans were analyzed. The prevalence and timing of cochlear and labyrinthine obliteration was classified using relevant MRI sequences. RESULTS MRI studies in 60 patients were analyzed: 20 translabyrinthine (TL), 20 retrosigmoid, and 20 middle fossa (MF) cases. The first and last postoperative MRI was obtained a median of 3.4 months (interquartile range (IQR), 3.0-3.7 months) and 35 months (IQR, 27-83 months) after surgery, respectively. At the time of the first postoperative MRI, 21 (35%) patients had partial basal turn obliteration, and none of the patients had complete basal turn obliteration. At the time of the last postoperative MRI, six (10%) patients had partial basal turn obliteration and 17 (28%) patients had complete basal turn obliteration. The pattern of partial or complete basal turn obliteration differed significantly among all three surgical approaches (P

Cisplatin is a potent chemotherapeutic compound for which ototoxicity is a significant side effect. Cisplatin has shown sensitivity to circadian time, in that cisplatin is most effective as an anti-tumor compound, and least nephrotoxic, when given in the active (dark) period of the light-dark cycle in rodents. The objective of the study was to determine the sensitivity of cisplatin ototoxicity to circadian time. Fifty-seven Fischer 344/NHsd rats were exposed to 12 mg/kg cisplatin by intra-peritoneal injection at one of six time points on a 12 h light-12 h dark cycle: 2, 6, or 10 h after light onset or 2, 6, or 10 h after light offset. Cochlear injury was evaluated using auditory brainstem response threshold shifts and postmortem outer hair cell counts. All animals experienced threshold shift in the highest frequencies tested (30 and 40 kHz). The animals exposed to cisplatin at 6 h after light onset (the inactive period) had significantly higher mid-frequency threshold shifts and outer hair cell losses than the groups exposed during the dark hours. The results indicate that cisplatin is less likely to cause ototoxicity in the Fischer 344/NHsd rat when given during the active period. This finding is consistent with the lower nephrotoxicity that has been detected in cisplatin-exposed animals treated during the dark hours, and the magnitude of differences in threshold shifts between the light and dark exposure indicates that circadian timing has a significant impact on susceptibility to cisplatin ototoxicity.

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1–2 synapses per inner hair cell of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

No cochlear otosclerosis in infants with congenital bilateral SNHL has been reported.We report an infant male with bilateral cochlear otosclerosis, suggesting that cochlear otosclerosis may be a congenital disease and to further analyze the etiology of and genetic expression in congenital bilateral cochlear otosclerosis. We also describe the clinical characteristics and experience of patients with bilateral cochlear otosclerosis treated with cochlear implants (CIs).Seven patients, including an infant, who were diagnosed with cochlear otosclerosis underwent CI surgery. Their medical records, audiological and radiological results, surgical procedures, and CI outcomes were collected and reviewed.The median age at hearing loss was 38 years, ranging from 0 to 47 years. The child had bilateral hearing loss at birth and received a CI at 1 year of age. He also had growth retardation and was diagnosed with 3q+/3p- syndrome. All patients (8 ears) had better postoperative auditory performance than that preoperatively.Although cochlear otosclerosis often starts at middle age and progresses slowly, it may be a congenital disease that is related to chromosome abnormality. This disease presents with SNHL or MHL, and treatment with a CI is beneficial.

Incomplete partition type III (IP-III) is a relatively rare inner ear malformation that has been associated with a POU3F4 gene mutation. The IP-III anomaly is mainly characterized by incomplete separation of the modiolus of the cochlea from the internal auditory canal. We describe a 71-year-old woman with profound sensorineural hearing loss diagnosed with an IP-III of the cochlea that underwent cochlear implantation. Via targeted sequencing with a non-syndromic gene panel, we identified a heterozygous c.934G > C p. (Ala31Pro) pathogenic variant in the POU3F4 gene that has not been reported previously. IP-III of the cochlea is challenging for cochlear implant surgery for two main reasons: liquor cerebrospinalis gusher and electrode misplacement. Surgically, it may be better to opt for a shorter array because it is less likely for misplacement with the electrode in a false route. Secondly, the surgeon has to consider the insertion angles of cochlear access very strictly to avoid misplacement along the inner ear canal. Genetic results in well describes genotype-phenotype correlations are a strong clinical tool and as in this case guided surgical planning and robotic execution.

[ES] El hámster GASH/Sal es un modelo de epilepsia audiógena que sufre hipoacusia neurosensorial. En el presente estudio, se ha cuantificado las principales células auditivas, así como la expresión de los genes implicados en la estructura y funcionalidad de los estereocilios cocleares (Cdh23, Pcdh15 y Gpr98) en el primer eslabón de la vía auditiva del GASH/Sal, el órgano de Corti. Para ello, se han extraído y preparado las espiras de la cóclea para su posterior tinción y análisis cuantitativo en imágenes obtenidas con microscopía de epifluorescencia. Los resultados muestran una falta de correlación entre el número de células ciliadas internas y las células ciliadas externas y de Deiters, pero no se han encontrado diferencias numéricas significativas entre las tres filas de células ciliadas externas. El análisis de expresión génica, mediante RT-qPCR, mostró una menor expresión de los genes Cdh23 y Pcdh15 en la cóclea del hámster GASH/Sal, mientras que Gpr98 no mostró diferencias comparado con el hámster control. Las características morfológicas de la cóclea del GASH/Sal difieren de lo descrito en otras especies de roedores que, junto con las alteraciones en la expresión de genes cocleares, podrían explicar la hipoacusia congénita del GASH/Sal, abriendo nuevas líneas de investigación.

Bilateral sensorineural deafness and unilateral cochlear ossification have rarely been described in patients with chronic myeloid leukemia (CML). A 21-year-old man presented to a hospital with right-sided sudden hearing loss and tinnitus. He was diagnosed with CML. Five days later, sudden hearing loss appeared in the other ear. Abnormality of the right-sided inner ear structure was revealed by preoperative magnetic resonance imaging; honeycomb-like cochlear ossification was observed during cochlear implant surgery in the right ear. The patient’s auditory performance exhibited significant improvement after bilateral cochlear implantation in our hospital. Hematological disorders must be considered in patients with sensorineural hearing loss. Cochlear implantation is feasible in patients with CML who exhibit sensorineural deafness, but cochlear ossification should be carefully evaluated by means of preoperative imaging examinations.

Background: Essential tremor (ET) is the most common adult movement disorder, characterized by several motor and increasingly well recognized non-motor symptoms. Sensory deficits, such as hearing impairment and olfactory dysfunction, are amongst them. This review analyzes the available evidence of these sensory deficits and their possible mechanistic basis in patients with ET. Method: A PubMed literature search on the topic was performed in the May 2019 database. Results: Nineteen articles on hearing impairment and olfactory dysfunction in ET patients were identified. The prevalence of hearing impairment is higher in ET patients than healthy controls or Parkinson disease. Cochlear pathologies are suggested as the underlying cause, but there is still a lack of information about retrocochlear pathologies and central auditory processing. Reports on olfactory dysfunction have conflicting results. The presence of mild olfactory dysfunction in ET was suggested. Conflicting results may be due to the lack of consideration of the disease’s heterogeneity, but according to recent data, most studies do not find prominent evidence of olfactory loss in ET. Conclusion: Although there is increasing interest in studies on non-motor symptoms in ET, there are few studies on sensory deficits, which are of particularly high prevalence. More studies are needed on to investigate the basis of non-motor symptoms, including sensory deficits.

Immune-related adverse events have been described in 86%-96% of high-risk melanoma patients treated with immune checkpoint inhibitors (ICI), while in 17%-59% of cases these are classified as severe or even life-threatening. The most common immune-related adverse events include diarrhea, fatigue, hypothyroidism, and hepatitis. Bilateral uveitis and unspecific vertigo have been described in 1% of cases, respectively, in the pivotal studies of ICIs, but the affection of the vestibule-cochlear system has not been reported before. In this case series, we present 3-stage IV melanoma patients with sudden onset of otovestibular dysfunction (hearing loss and vestibulopathy), partly combined with uveitis because of ICIs. We describe detailed diagnostic work-up and therapeutic interventions and discuss possible pathogenic mechanisms of this rare and disabling event.

OBJECTIVES: To assess the incidence and onset of cochlear obliteration after translabyrinthine and retrosigmoid vestibular schwannoma surgery. MATERIALS AND METHODS: We retrospectively identified a consecutive series of eighty ears in eighty vestibular schwannoma patients who were treated via a translabyrinthine or retrosigmoid approach by a single neuro-otological surgical team in a tertiary referral center from May 2011 to January 2018. Postoperative, high- resolution T2-weighted turbo spin echo three-dimensional magnetic resonance (MR) images of the posterior fossa were evaluated at the level of the membranous labyrinth and internal auditory canal. Perilymphatic patency of the vestibule, basal, and apical cochlear turns were scored and classified as patent, hypointense, partially obliterated, or completely obliterated. RESULTS: Twenty-five vestibular schwannomas were treated with surgery via a translabyrinthine approach, and fifty-five were treated using a retrosigmoid approach; of these, 8% and 65%, respectively, showed no signs of perilymphatic alterations in the basal or apical turns, while 84% and 20%, respectively, showed partial or complete obliteration in the basal or apical turns with a mean postoperative interval of 127 and 140 days, respectively. All the patients who underwent multiple MR scans and had a completely patent perilymphatic system on the first postoperative scan remained patent during subsequent scans; 16% of the patients showed worsened perilymphatic appearance. The onset of cochlear obliteration occurred within 2-7 months in most translabyrinthine patients. CONCLUSION: These findings may support the need for simultaneous cochlear electrode or dummy implantation in translabyrinthine surgery. Second-stage implantation could be feasible in cases where a retrosigmoid approach is used; however, the implantation should be considered within the initial months to avoid cochlear obliteration. Findings on the first postoperative MR could indicate the need for intensified MR follow-up and may even predict the occurrence of cochlear obliteration. ispartof: JOURNAL OF INTERNATIONAL ADVANCED OTOLOGY vol:16 issue:1 pages:53-57 ispartof: location:Turkey status: published

Objectives To analyze the clinical characteristics of cochlear fistulas (CFs) and propose a new fistula classification system with regard to the cochlea. Materials and methods A retrospective chart review was conducted between January 2008 and December 2015 to identify patients who had undergone surgery for cholesteatoma with an associated CF. The following data were collected: preoperative symptoms, findings of temporal bone computed tomography (TBCT), fistula stage, cholesteatoma classification, surgical technique, and pre- and postoperative pure-tone audiometry. Results We analyzed a total of 159 patients, out of which 9 (5.7%) were diagnosed with a CF. The average duration of the chronic otitis media was 19.8 years. Cholesteatomas that induced CF rarely existed in the nonaggressive state; recurrent otorrhea was observed in all but one of our subjects. All the patients with CF had a distinct origin of cholesteatoma that developed from the retraction of posterior pars tensa; further, 88.9% cholesteatomas extended to and filled the sinus tympani. Preoperative audiometry revealed total hearing loss in 4 (44.4%) patients. Further, five patients with residual hearing before surgery had stage I fistulas, and the bone conduction thresholds remained stable after surgery. Conclusion Cochlear fistulas were often detected in patients with (1) a history of chronic otitis media (exceeding 10 years), (2) frequently recurring otorrhea, and (3) pars tensa cholesteatomas that extended to the posterior mesotympanum and filled the sinus tympani. Such patients can suffer from potentially severe and irreparable sensorineural hearing loss.

Molecular mechanisms governing the development of the mammalian cochlea, the hearing organ, remain largely unknown. Through genome sequencing in 3 subjects from 2 families with nonsyndromic cochlear aplasia, we identified homozygous 221-kb and 338-kb deletions in a noncoding region on chromosome 8 with an approximately 200-kb overlapping section. Genomic location of the overlapping deleted region started from approximately 350 kb downstream of GDF6, which codes for growth and differentiation factor 6. Otic lineage cells differentiated from induced pluripotent stem cells derived from an affected individual showed reduced expression of GDF6 compared with control cells. Knockout of Gdf6 in a mouse model resulted in cochlear aplasia, closely resembling the human phenotype. We conclude that GDF6 plays a necessary role in early cochlear development controlled by cis-regulatory elements located within an approximately 500-kb region of the genome in humans and that its disruption leads to deafness due to cochlear aplasia.

Objective: The primary aim of this study was to investigate whether scores for a speech-in-noise test were associated with the results of two electrophysiological techniques mainly targeting low sp...

[ES]El objetivo de esta tesis es evaluar experimentalmente la audicion de los usuarios de implantes cocleares con una estrategia de procesamiento binaural de sonidos inspirada en el reflejo olivococlear medial, denominada "estrategia MOC". La tesis describe cuatro estudios dirigidos a comparar la inteligibilidad del habla en ruido, la localizacion de fuentes sonoras y el esfuerzo auditivo con procesadores de sonido estandar y con diversos procesadores MOC disenados para reflejar de forma mas o menos realista el tiempo de activacion del reflejo olivococlear medial natural y sus efectos sobre la comprension coclear humana.

To evaluate prestin as a biomarker for the identification of early ototoxicity.Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system.The mean serum prestin levels were 377.0 ± 135.3, 411.3 ± 73.1, 512.6 ± 106.0, 455.0 ± 74.2 and 555.3 ± 47.9 pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (p = 0.031) and prestin levels of Control-LAG-HAG groups (p = 0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (p = 0.028 and p = 0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8 kHz than control groups (p 0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (p 0.05).Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.

Objective Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. Materials and methods House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly, anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST-1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic cell death was measured using flow cytometric analysis of annexin-V/7-amino-actinomycin (7-AAD) and cell cycle tests. Results LIPO or CDDP inhibited cell viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1 cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and 750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively. Conclusion LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP at anti-tumoral doses.

To describe the vestibular function in patients with superficial siderosis of the central nervous system (SSCN).Retrospective analysis.Tertiary referral center.Ten consecutive patients with SSCN. This study is the largest case series of SSCN in which detailed neuro-otological findings, including electronystagmography recording, video head impulse test (vHIT), and posturography, were described.Audiological and neuro-otological examinations, including pure-tone audiometry, distortion product otoacoustic emissions, speech audiometry, auditory brainstem responses, electronystagmography recording, vHIT, and posturography.Pure-tone average, DP level, maximum speech discrimination score, interpeak latency between auditory brainstem responses waves I and V, eye tracking test, examination of optokinetic nystagmus, caloric response, visual suppression, vestibulo-ocular reflex gains, total center of pressure path length, and Romberg's ratio.Audiological examinations suggested that the sensorineural hearing loss was of a cochlear etiology in 3 ears, a retrocochlear etiology in 11 ears, and a combined cochlear and retrocochlear etiology in 6 ears. Neuro-otological examinations revealed that eight out of nine patients had cerebellar disorders, while all patients also had peripheral vestibular dysfunction.In addition to cerebellar disorders, SSCN patients suffer from severe peripheral vestibular dysfunction, which can exacerbate the patient's imbalance. When otolaryngologists encounter patients with distinctly progressive sensorineural hearing loss and imbalance, they should include SSCN in the differential diagnosis and perform neuro-otological examinations, including an electronystagmography recording and vHIT and brain magnetic resonance imaging.

Cochlear synaptopathy, i.e. the loss of auditory-nerve connections with cochlear hair cells, is seen in aging, noise damage, and other types of acquired sensorineural hearing loss. Because the subset of auditory-nerve fibers with high thresholds and low spontaneous rates (SRs) is disproportionately affected, audiometric thresholds are relatively insensitive to this primary neural degeneration. Although suprathreshold amplitudes of wave I of the auditory brainstem response (ABR) are attenuated in synaptopathic mice, there is not yet a robust diagnostic in humans. The middle-ear muscle reflex (MEMR) might be a sensitive metric (Valero et al., 2016), because low-SR fibers may be important drivers of the MEMR (Liberman and Kiang, 1984; Kobler et al., 1992). Here, to test the hypothesis that narrowband reflex elicitors can identify synaptopathic cochlear regions, we measured reflex growth functions in unanesthetized mice with varying degrees of noise-induced synaptopathy and in unexposed controls. To separate effects of the MEMR from those of the medial olivocochlear reflex, the other sound-evoked cochlear feedback loop, we used a mutant mouse strain with deletion of the acetylcholine receptor required for olivocochlear function. We demonstrate that the MEMR is normal when activated from non-synaptopathic cochlear regions, is greatly weakened in synaptopathic regions, and is a more sensitive indicator of moderate synaptopathy than the suprathreshold amplitude of ABR wave I.

An auditory brainstem implant (ABI) is an option for auditory rehabilitation in patients with totally ossified cochleae who cannot receive a conventional cochlear implant.To evaluate the outcomes in audiometry and speech perception tests after the implantation of an ABI via the extended retrolabyrinthine approach in patients with postmeningitis hearing loss.Ten patients, including children and adults, with postmeningitis hearing loss and bilateral totally ossified cochleae received an ABI in a tertiary center from 2009 to 2015. The extended retrolabyrinthine approach was performed in all the patients by the same surgeons. A statistical analysis compared pure tonal averages and speech perception tests before and at least 12 months after the ABI activation.Eight patients (80%) showed improvements in tonal audiometry and the word and vowel perception tests after an average follow-up of 3.3 years. Two patients recognized up to 40% of the closed-set sentences without lip-reading. Two patients had no auditory response.The ABI improved hearing performance in audiometry and speech perception tests in cases of postmeningitis hearing loss. The extended retrolabyrinthine approach is a safe surgical option for patients with postmeningitis hearing loss and bilateral totally ossified cochleae.