cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

The clinical and imaging presentations of the stapical footplate hernia related to inner ear malformation / 中华放射学杂志

Objective:To summarize the clinical and imaging presentations of stapical footplate hernia related to inner ear malformation (SFH-Re-IEM).Methods:The clinical and imaging data of 19 patients (24 ears) with SFH-Re-IEM from Shandong Provincial ENT Hospital between June 2014 to June 2022 were retrospectively analyzed. The clinical presentations and headache and the high resolution CT (HRCT) and MRI findings including associated inner ear malformation (IEM) type, internal auditory canal (IAC) malformation, bony defect of the stapical footplate, the extent, margin, density and signal of the herniation cysts, the density and signal of ipsilateral intratympanic, cochlear osseous labyrinthitis were recorded.Results:Among 19 SFH-Re-IEM patients, including 14 males and 5 females, 3 (1, 12) years old. All of the affected ears presented sensorineural or mixed hearing loss, 1 ear for moderate, 7 ears for severe and 16 ears for extremely severe. Besides this, the vertigo in 1 case, otalgia and ear fullness in 2 cases were found, and the others were detected accidentally. Among 24 ears with SFH-Re-IEM, 9 ears (37.5%) consisting with incomplete partition type Ⅰ, 3 ears (12.5%) with common cavity, 7 ears (29.2%) with cochlear aplasia, 3 ears (12.5%) with cochlear dysplasia type Ⅱ, and 2 ears (8.3%) with Mondini deformity were found respectively. Four ears (16.7%) were associated with IAC enlargement and the bony defect of IAC fundus, 19 ears (79.2%) were accompanied with dysplasia in the IAC fundus. In all the 24 ears with SFH-Re-IEM, the focal bony defect of the affected stapical footplate and the hemispherical soft-tissue-density herniating cysts protruding into the tympanium were presented on HRCT, and the herniating cysts presenting the cerebrospinal fluid-like signal with the well-defined margin and the ipsilateral normal tympanium were shown on the MRI hydrographic sequence. Two ears underwent the perilymphaticum gadolinium based on MRI, which demonstrated the hypersignal gadolinium in the perilymphatic space entered into the herniating cysts. Two ears were accompanied with the cochlear osseous labyrinthitis.Conclusion:The ears with IEM-Re-SFH usually present the serious hearing loss. The ipsilateral severe IEM, focal bony defect of the stapical footplate and perilymph herniating are characteristic imaging appearances.

Audio-vestibular and radiological analysis in Meniere's disease

Abstract Objective: Intravenous gadolinium-enhanced inner ear magnetic resonance imaging (IV Gd-enhanced inner ear MRI) is a new technique for diagnosing Meniere's disease (MD). Vestibular tests have also long been used forMD, but which tests should be included in the oto-neurological test battery remains controversial. The evaluation method to be used to confirm the clinical diagnosis in MD is not clear. This study aimed to examine the results of vestibular tests and IV Gd-enhanced inner ear MRI in individuals diagnosed with unilateral definite Meniere's disease. Methods: IV Gd-enhanced inner ear MRI (Endolymphatic Hydrops [EH] and Perilymphatic Enhancement [PE]), conventional audiometry (0.25-8kHz), video Head Impulse Test (vHIT), cervical Vestibular Evoked Myogenic Potential (cVEMP), air caloric test, and dizziness handicap inventory were applied to 16 adult patients diagnosed with unilateral definite MD. Results: Among the patients with definite MD, EH (cochlear and/or vestibular) was identified in 93.7% and 68.7% of the symptomatic and the asymptomatic ears, respectively. There was a positive correlation between the hearing thresholds at 2, 4, 6 and 8 kHz and the degree of cochlear EH (p < 0.05). PE (cochlear and/or vestibular) was observed in 37.5% of the asymptomatic and symptomatic ears. The sensitivity of the vestibular test battery (vHIT, cVEMP, and caloric test) was 100% and its specificity was 50%, while the sensitivity of the IV Gd-enhanced inner ear MRI (EH and PE together) was 93.8% and the specificity was 81.3%. Conclusion: MRI had higher sensitivity and specificity than the vestibular test battery. PE or vHIT alone was not considered to be reliable in the diagnosis of MD. In suspected MD, the clinical history, hearing tests, and IV Gd-enhanced inner ear MRI are sufficient for diagnosis. If MRI technique is not possible, vestibular tests (caloric test and cVEMP, not vHIT) can provide reliable results when evaluated together.

Auditory and Vestibular Functioning in Individuals with Type-2 Diabetes Mellitus: A Systematic Review

Abstract Introduction Diabetes mellitus is a metabolic disease associated with a rise in the level of blood glucose. Individuals with diabetes mellitus are more likely to develop hearing loss, tinnitus, and dizziness due to macro- and microvascular complications. The extent to which auditory and vestibular functions are impaired in individuals with type-2 diabetes mellitus is still under debate. Objective To systematically review studies focusing on auditory and vestibular functions in individuals with type-2 diabetes mellitus. Data Synthesis A search was conducted in the PubMed, MedlinePlus, Ingenta Connect and Google Scholar databases for articles published until June 2019. A total of 15,980 articles were primarily retrieved, 33 of which were shortlisted based on the inclusion criteria set by the investigators for the systematic review. Out of 33 full-length articles, 26 evaluated the functioning of the auditory system, while 7 evaluated the functioning of the vestibular system. Most studies related to auditory functioning reported a significant effect of type-2 diabetes mellitus on the peripheral auditory system, whereas studies on vestibular functioning reported no significant effect of diabetes mellitus on the functioning of the peripheral vestibular end-organ. Conclusion Overall, the results of various audiological and peripheral vestibular tests reveal distinctive peripheral and/or central auditory and vestibular end-organ impairments in individuals with type-2 diabetes mellitus.

Sordera neurosensorial congénita con malformación de oído interno ligada al X en una familia mexicana / Congenital sensorineural deafness X-linked, with inner ear malformation in a Mexican family

Introducción. Las sorderas o hipoacusias prelinguales son de etiología genética entre el 60 y el 68% de los casos; de estos, del 20 al 40% son malformaciones del oído interno. De los casos de hipoacusia no sindrómica ligada al X se han descrito siete tipos. De las malformaciones de oído interno, la partición coclear incompleta tipo III es la menos frecuente.Objetivo. Presentar el reporte clínico-genético de una familia mexicana, con indi-viduos varones afectados por sordera neurosensorial congénita con malformación de oído interno. Material y Métodos. Se realizó estudio de una familia en la que nueve miembros presentaban sordera. Se estudiaron cuatro de ellos y una madre sin manifestaciones, a través del estudio clínico general por médico genetista, el estudio audiológico (otos-copía y audiometría) por médico audiólogo y el estudio de tomografía computada (TC) por médico radiólogo.Resultados. Los pacientes estudiados presentaron sordera neurosensorial congéni-ta, de severa a profunda bilateral. A través de la TC, se evidenció malformación de oído interno. Tres pacientes presentaron partición coclear incompleta tipo III y un paciente partición incompleta tipo I. Debido al estudio clínico y al árbol genealógico, se definió diagnóstico de hipoacusia neurosensorial no sindrómica ligada al X. La TC de la madre sin manifestaciones no presentó evidencia de malformaciones en oído interno (MOI).Conclusión. El estudio de imagen es fundamental para definir presencia o no de MOI en todos los pacientes con hipoacusia y así poder guiar la terapéutica y el aseso-ramiento genético, así como realizar los estudios moleculares más adecuados

Introduction. The pre-lingual deafness or hearing loss are of genetic cause in be-tween 60% and 68% of cases, among these, between 20% and 40% are malforma-tion of the inner ear. From the non-syndromic hearing loss cases that are linked to the X chromosome, seven types have been described. Among these inner ear malforma-tions, incomplete cochlear partition type III is the less frequent.Objective. Present the clinical genetical report of a Mexican family, with male in-dividuals affected by congenital neurosensory deafness with inner ear malformation.Materials and methodology. A study on a family in which nine members were affected by deafness was done. Four of them, plus a mother without manifestation, were studied through a general clinical study by a geneticist, an audiological study (otoscopy and audiometry) by an audiologist, and a computed tomography (CT) scan by a radiologist.Results. The studied patients presented congenital neurosensory deafness, from se-vere to deep bilateral. Via the CT, the inner ear malformation was made clear. Three of the patients presented incomplete cochlear partition type III and one patient in-complete cochlear partition type I. Due to the clinical study and the family tree, it was diagnosed non-syndromic neurosensory deafness linked to X. The CT of the mother without manifestation did not show evidence of inner ear malformations.Conclusion. The study by image is fundamental to define whether there is or not a presence of inner ear malformations in any patient with heading loss to be able to guide the therapeutics and the genetic counseling, as well as to make more accurate molecular studies

Disección anatómica del oído medio y el oído interno / Middle and inner ear anatomical dissection / Dissecção anatómica do ouvido médio e do ouvido interno

RESUMEN Introducción: El oído medio y el oído interno presentan una compleja constitución anatómica; La disección como método de enseñanza proporciona una comprensión óptima de la configuración tridimensional de sus estructuras debido a su carácter práctico y realista. Se propone un protocolo de disección aislada del oído medio e interno que ofrece una visión amplia de sus estructuras e incorpora esquemas didácticos. Metodología: En tres cadáveres humanos en estado de conservación se delimitaron dos cuadrángulos en la cara _ superior del hueso temporal mediante referentes anatómicos para extraer una estructura paralelepípeda correspondiente a la porción petrosa del hueso temporal, sobre la cual se realizó disección. Resultados: Se creó un protocolo de disección siguiendo esta secuencia: Extracción parcial de la porción petrosa del hueso temporal, visualización del oído medio, exposición de la membrana timpánica y visualización del oído interno. Conclusión: Esta herramienta pedagógica es aplicable al proceso de enseñanza y constituye un recurso cuyo carácter didáctico resulta potencialmente útil para los estudiantes facilitando el aprendizaje activo de los aspectos teóricos y prácticos del oído.

ABSTRACT Introduction: The middle and the inner ear have a complex anatomical constitution. As a traditional teaching method, the dissection provides an optimal knowledge of the three-dimensional configuration of its structures due to its practical and realistic qualities. It proposes a protocol of isolated dissection of the middle and the inner ear offering a broad vision of its structures and incorporates didactic schemes. Materials and Method: We delimited two quadrants in the upper face of the temporal bone of three conserved human corpses by employing anatomical referents to extract a parallelepiped structure that corresponds to the petrous portion of the temporal bone. On this portion, the dissection was performed. Results: we created a dissection protocol following this sequence: The petrous portion of the temporal bone partial removal, middle ear visualization, tympanic membrane exposure and inner ear visualization. Conclusion: This pedagogical instrument is applicable to the process of education and constitutes a resource whose didactic character results potentially useful for the students facilitating the active learning of the theoretical and practical issues of the ear anatomy

RESUMO Introdução: O ouvido médio e interior apresentam uma constituição anatómica complexa; a dissecação como método de ensino proporciona uma compreensão óptima da configuração tridimensional das suas estruturas devido ao seu carácter prático e realista. É proposto um protocolo de dissecção isolada do ouvido médio e interno, que oferece uma visão ampla das suas estruturas e incorpora diagramas didácticos. Metodologia: Em três cadáveres humanos conservados, dois quadrantes foram delimitados na face superior do osso temporal por meio de referências anatómicas, a fim de extrair uma estrutura paralelepipédica correspondente à porção petrosa do osso temporal, sobre a qual foi realizada a dissecação. Resultados: Foi criado um protocolo de dissecação seguindo esta sequência: extracção parcial da porção petrosa do osso temporal, visualização do ouvido médio, exposição da membrana timpánica e visualização do ouvido interno. Conclusão: Esta ferramenta pedagógica é aplicável ao processo de ensino e constitui um recurso cujo carácter didáctico é potencialmente útil para os estudantes, facilitando a aprendizagem activa dos aspectos teóricos e práticos do ouvido.

Histology and immunocytochemical localization of glial fibrillary acidic protein in the inner ear of Scincella tsinlingensis / Histología y localización inmunocitoquímica de la proteína ácida fibrilar glial en el oído interno de Scincella tsinlingensis

SUMMARY: The microstructure of inner ear in Scincella tsinlingensis was observed by light microscopy and the expression of glial fibrillary acidic protein (GFAP) in membranous labyrinth among the juvenile age group, subadult age group and adult age group were also detected by methods of immunohistochemistry. The inner ear in S. tsinlingensis resembled those in other Scincid lizards in their anatomy and histology. Large and elongate cochlear duct was slightly bowed or arched laterally. There was no hint of limbic modifications and the limbic lip was absent in cochlear recess. The basilar papilla elongated anteroventrally possessed specialized tectorial sallets. GFAP staining was significantly distributed in supporting cells of the sensory epithelia of cochlear duct, while the utricular macula and canal ampullae showed immunopositive for the GFAP antibody, with weaker staining in the saccular macula. The membranous inner ear of three different age groups revealed the similar pattern of GFAP expression, which suggested that the distribution of supporting cells were independent of age in S. tsinlingensis.

RESUMEN: La microestructura del oído interno en Scincella tsinlingensis fue analizada mediante microscopía óptica y por otra parte, fue cuantificada la expresión de la proteína ácida fibrilar glial (GFAP) en el laberinto membranoso, entre los grupos de edad juvenil, subadulto y adulto, utilizándose métodos inmunohistoquímicos. El oído interno de S. tsinlingensis se asemejaba al de otros lagartos Scincid tanto en su anatomía como en su histología. El conducto coclear mayor estaba ligeramente arqueado o arqueado lateralmente. No había indicios de modificaciones límbicas y no se evidenció el labio en el receso coclear. La papila basilar alargada anteroventralmente poseía sallets tectoriales especializados. La tinción de GFAP se distribuyó significativamente en las células del epitelio sensorial del conducto coclear, mientras que la mácula utricular y la ampolla del canal mostraron inmunopositividad para el anticuerpo GFAP, con una tinción más débil en la mácula sacular. El oído interno membranoso de los tres grupos de edad diferentes reveló un patrón similar de expresión de GFAP, lo que sugiere que la distribución de las células de soporte son independiente de la edad en S. tsinlingensis.

Frequency of Inner Ear Anomalies Among Cochlear Implant Candidates: A Case Study in the Northwest of Iran

@#Introduction: Globally hearing impairment occurs in about 1 to 2 per 1000 live births. The etiology of severe sensorineural hearing loos (SNHL) is complex and multifactorial. Congenital inner ear abnormality is a major cause of hearing loss in children and cochlear implantation (CI) is a proper treatment in these children. Preoperative CT scan of the temporal bones are used to evaluate inner ear malformations in CI candidates. The frequency of internal ear malformations reported on temporal scan could varied from 20% to 30%. The aim of this study was to evaluate the frequency of inner ear malformations in CT scan of cochlear implant candidates . Methods: In a retrospective cross-sectional descriptive study, 201 infants (105 boys and 96 girls ) with the mean age of 20.5 ± 14.01 month with severe SNHL who are CI candidates were examined by temporal bone imaging with multi-slice CT from March 2014 to March 2015 in CI center of Tabriz University. Results : CT revealed abnormalities of the inner ear in 26 (13%) of infants that most of them with 10 (38.5%) was enlarged vestibular aqueduct (EVA). Also, 31 infants (15.4%) had abnormalities in outer, middle ear or in mastoid aeration. Conclusion: Temporal bone imaging with CT is an essential method and could be suggested as a proper first step for evaluating inner ear malformations in CI candidates.

Comparação das respostas do VEMP cervical e ocular em indivíduos com e sem doenças otoneurológicas / Comparison of cervical and ocular VEMP responses in individuals with and without otoneurological diseases / Comparación de respuestas VEMP cervicales y oculares en individuos con y sin enfermedades otoneurológicas

Introdução: a avaliação vestibular é realizada tradicionalmente por meio da prova calórica para avaliação do labirinto em indivíduos com tonturas, porém este exame não avalia toda a via vestibular. Os potenciais evocados miogênicos vestibulares (VEMP) consistem em um exame de rápida execução, considerado método de escolha para avaliação dos órgãos otolíticos e do nervo vestibular. Objetivo: analisar as respostas do exame VEMP cervical (cVEMP) e ocular (oVEMP) em indivíduos com doenças vestibulares e compará-las àquelas obtidas em indivíduos de mesma faixa etária e sexo sem queixas de tontura pregressas e atuais. Métodos: Estudo observacional, transversal e analítico. Os participantes foram divididos em dois grupos: grupo com tontura (GT), composto por indivíduos com diversas doenças vestibulares e o grupo sem queixa de tontura (GC). Ambos os grupos foram submetidos à meatoscopia, ao VEMP cervical e ocular. Resultados: A amostra foi composta por 45 indivíduos com a idade entre 23 e 68 anos, sendo 27 indivíduos do grupo GC e 18 do grupo GT. No exame cVEMP as latências, amplitudes, índice de assimetria e o índice de assimetria corrigido foram iguais no GT quando comparado com o GC. No exame oVEMP encontrou-se a amplitude esquerda maior e a latência N10 menor estatisticamente no grupo GT quando comparado ao grupo GC. Dentre as doenças do grupo GT os indivíduos com deiscência de canal superior tiveram valores maiores na amplitude esquerda, o que pode ter interferido nos resultados. Conclusão: Não foram evidenciadas diferenças nas respostas do cVEMP entre os grupos neste estudo. Encontrou-se aumento da amplitude esquerda e o valor menor da latência N10 direita no grupo com tontura na análise do exame oVEMP. Acredita-se que a heterogeneidade de doenças vestibulares no grupo com tontura e o reduzido número de participantes em ambos os grupos tenham contribuído para esse desfecho.

Introduction: The vestibular assessment is traditionally carried out with the caloric test to evaluate the labyrinth in individuals with dizziness. However, this examination does not evaluate the entire vestibular pathway. The vestibular evoked myogenic potentials (VEMP) are a quick test, considered a choice method to assess the otolith organs and the vestibular nerve. Purpose: To analyze the responses of the cervical (cVEMP) and ocular VEMP (oVEMP) examinations in individuals with vestibular diseases and compare them with the results obtained in individuals of the same age group and gender without previous and current complaints of dizziness. Methods: In this observational, cross-sectional, analytical study, the participants were divided into two groups: the dizziness group (DG), composed of individuals with several vestibular diseases, and the group without complaints of dizziness (CG). Both groups underwent meatoscopy, and cervical and ocular VEMP. Results: The sample comprised 45 individuals aged 23 to 68 years ­ 27 individuals in the CG and 18 in the DG. In the cVEMP exam, the latencies, amplitudes, asymmetry index, and the corrected asymmetry index were the same in the GT when compared to the GC. In the cVEMP examination, the latencies, amplitudes, asymmetry index, and corrected asymmetry index were equal in the DG when compared with the CG. In the oVEMP examination, the left amplitude was statistically greater and the N10 latency, smaller in the DG when compared with the CG. Of the diseases in the DG, individuals with superior canal dehiscence had higher left amplitude values, which may have interfered with the results.Conclusion: There were no differences in cVEMP responses between the groups in this study. An increase in the left amplitude and the lower value in the right N10 latency were found in the DG in the analysis of the oVEMP examination. It is believed that the heterogeneity of vestibular diseases in the DG and the small number of participants in both groups have contributed to this outcome.

Introducción: La evaluación vestibular se lleva a cabo tradicionalmente a través de la prueba calórica para evaluar el laberinto en individuos con mareos, sin embargo, este examen no evalúa toda la vía vestibular. Los potenciales miogénicos evocados vestibulares (VEMP) consisten en una prueba de funcionamiento rápido, considerada el método de elección para evaluar los órganos otolíticos y el nervio vestibular. Objetivo: Analizar las respuestas del examen VEMP cervical y ocular en individuos con enfermedades vestibulares y compararlas con las obtenidas en individuos del mismo grupo de edad y sexo sin quejas de mareos previas y actuales. Métodos:Estudio observacional, transversal y analítico. Los participantes se dividieron en dos grupos: grupo con mareos (GT), compuesto por individuos con varias enfermedades vestibulares y el grupo sin quejas de mareos (CG). Ambos grupos se sometieron a meatoscopia, VEMP cervical y ocular. Resultados: La muestra consistió en 45 individuos con edades comprendidas entre 23 y 68 años, 27 individuos del grupo GC y 18 del grupo GT. En el examen cVEMP, las latencias, amplitudes, índice de asimetría y el índice de asimetría corregido fueron los mismos en el GT en comparación con el CG. En el examen oVEMP, la amplitud izquierda fue mayor y la latencia N10 fue estadísticamente menor en el grupo GT en comparación con el grupo CG. Entre las enfermedades en el grupo GT, los individuos con dehiscencia del canal superior tenían valores más altos en la amplitud izquierda, lo que puede haber interferido con los resultados. Conclusión: No hubo diferencias en las respuestas de cVEMP entre los grupos en este estudio. Se encontró un aumento en la amplitud izquierda y un valor más bajo de la latencia N10 derecha en el grupo con mareos en el análisis del examen oVEMP. Se cree que la heterogeneidad de las enfermedades vestibulares en el grupo de mareos y el pequeño número de participantes en ambos grupos contribuyeron a este resultado.

Use of scanning electron microscopy in the cochlea of guinea pigs / Microscopia eletrônica de varredura em cócleas de cobaias

Abstract Introduction: The use of electron microscopy in the study of the inner ear has allowed us to observe minute details of the hair cells, especially in ototoxicity studies; however, the preparation of this material is a difficult and delicate task. In an attempt to simplify the handling of these materials, two agents, toluidine blue and ethylenediamine tetra-acetic acid were tested, in addition to the elimination of osmium tetroxide during the preparation of albino guinea pig cochleae. We also tested the applicability of these methodologies in an ototoxicity protocol. Objective: To verify the quality of the images obtained with and without the use of ethylenediamine tetra-acetic acid, toluidine blue and osmium tetroxide in the preparation of cochleae of albino guinea pigs for the scanning electron microscopy. Methods: Three groups of cochleae were used. In Group 1, 10 cochleae were prepared with the usual methodology, dissecting the optical capsule without decalcification and using osmium tetroxide as a post-fixative agent. In Group 2, we prepared 10 cochleae decalcified with ethylenediamine tetra-acetic acid, injecting toluidine blue in the endolymphatic space to facilitate the identification of the organ of Corti. In Group 3, we used 4 cochleae of guinea pigs that received 3 doses of cisplatin (7.5 mg/kg, D1-D5-D6), two prepared according to the methodology used in Group 1 and two with that used in Group 2. Scanning electron microscopy images were obtained from the organ of Corti region of the basal turn of each cochlea. Results: The organ of Corti was more easily identified with the use of toluidine blue. The dissection of the cochlea was more accurate in the decalcified cochleae. The quality of the images and the preservation of the organ of Corti obtained with the two methodologies were similar. Conclusion: The proposed modifications resulted in images of similar quality as those observed using the traditional methodology.

Resumo Introdução: O emprego da microscopia eletrônica no estudo da orelha interna permitiu observar detalhes minuciosos das células ciliadas especialmente em estudos de ototoxicidade. Entretanto, o preparo desse material é trabalhoso e delicado. Para simplificar a manipulação desses materiais, testou-se o uso de dois agentes, azul de toluidina e ácido etilenodiamino tetra-acético, além da retirada do tetróxido de ósmio na preparação de cócleas de cobaias albinas. Testamos também a aplicabilidade dessas metodologias em um protocolo de ototoxicidade. Objetivo: Verificar a qualidade das imagens obtidas com e sem o uso de ácido etilenodiamino tetra-acético, azul de toluidina e tetróxido de ósmio na preparação de cócleas de cobaias albinas para a microscopia eletrônica de varredura. Método: Foram utilizados três grupos de cócleas. No Grupo 1 preparou-se 10 cócleas com a metodologia usual, dissecando a cápsula ótica sem descalcificac¸ão e utilizando tetróxido de ósmio como pós-fixador. No Grupo 2 preparamos 10 cócleas descalcificadas com ácido etilenodiamino tetra-acético, injetando azul de toluidina no espac¸o endolinfático para facilitar a identificação do órgão de Corti. No Grupo 3 utilizamos 4 cócleas de cobaias que receberam 3 doses de cisplatina (7,5 mg/kg, D1-D5-D6), duas preparadas com a metodologia do Grupo 1 e duas com a do Grupo 2. Foram obtidas imagens da microscopia eletrônica de varredura da região do órgão de Corti do giro basal de cada cóclea. Resultados: O órgão de Corti foi mais facilmente identificado com o azul de touidina. A dissecção da cóclea foi mais precisa nas cócleas descalcificadas A qualidade das imagens e a preservac¸ão do órgão de Corti obtidas com as duas metodologias foi similar. Conclusão: As modificações propostas resultaram em imagens de qualidade similar as observadas com o uso da metodologia tradicional.

Application value of magnetic resonance hydrography of the inner ear in cochlear implantation

SUMMARY OBJECTIVE This study aims to investigate the application value of magnetic resonance (MR) hydrography of the inner ear in cochlear implantation. METHODS 146 patients were enrolled. MR hydrography and spiral CT examinations for the intracranial auditory canal were performed before surgery, and all imaging results were statistically analyzed in order to explore the application value of MR hydrography of the inner ear in cochlear implantation. RESULTS 146 patients (292 ears) were examined. Among these patients, 13 were diagnosed with abnormal vestibular aqueducts (20 ears) by MR hydrography, while five were diagnosed with this disease by CT; 15 patients were diagnosed with inner ear malformation (19 ears) by MR hydrography, while 11 were diagnosed by CT (four were misdiagnosed); five patients were diagnosed with internal acoustic canal stenosis (eight ears) by MR hydrography, while two were diagnosed by CT (three were misdiagnosed); and four patients were diagnosed with cochlear fibrosis (five ears) by MR hydrography, while four were diagnosed by CT (four ears). The correct rate of diagnosis was 77.40% (113/146) based on CT, while the rate was 93.84% (137/146) based on MR hydrography. CONCLUSIONS MR hydrography imaging technique can be applied to the preoperative evaluation of cochlear implantation, providing accurate and reliable anatomic information on the inner membranous labyrinth and nerves in the internal acoustic canal and an accurate basis for the diagnosis of cochlear fibrosis and nerve development. This has a guiding significance for the selection of treatment schemes.

RESUMO OBJETIVO Este estudo visa investigar o valor da aplicação da hidrografia por ressonância magnética (RM) do ouvido interno no implante coclear. MÉTODOS Cento e quarenta e seis pacientes foram inscritos. Os exames da hidrografia por RM e do CT espiral para o canal auditivo intracraniano foram executados antes da cirurgia, e todos os resultados da imagem foram analisados estatisticamente, a fim de explorar o valor da aplicação da hidrografia por RM do ouvido interno no implante coclear. RESULTADOS Centro e quarenta e seis pacientes (292 ouvidos) foram examinados. Dentre esses pacientes, 13 foram diagnosticados com aquedutos vestibulares anormais (20 ouvidos) pela hidrografia por RM, enquanto cinco pacientes foram diagnosticados com esta doença pelo CT; 15 pacientes foram diagnosticados com malformação do ouvido interno (19 ouvidos) pela hidrografia por RM, enquanto 11 pacientes foram diagnosticados por CT (quatro foram diagnosticados erroneamente); cinco pacientes foram diagnosticados com estenose de canal acústico interno (oito ouvidos) pela hidrografia por RM, enquanto dois pacientes foram diagnosticados por CT (três foram diagnosticados erroneamente); e quatro pacientes foram diagnosticados com fibrose coclear (cinco ouvidos) pela hidrografia por RM, enquanto quatro foram diagnosticados por CT (quatro ouvidos). A taxa correta de diagnóstico foi de 77,40% (113/146) com base no CT, enquanto a taxa foi de 93,84% (137/146) com base na hidrografia por RM. CONCLUSÕES A técnica de imagem da hidrografia por RM pode ser aplicada à avaliação pré-operatória do implante coclear, que pode fornecer informações anatômicas precisas e confiáveis sobre o labirinto membranoso interno e os nervos no canal acústico interno, além de uma base exata para o diagnóstico da fibrose coclear e do desenvolvimento do nervo. Isso tem um significado orientador para a seleção de esquemas de tratamento.

Video head impulse test (v-hit) em indivíduos com diabetes mellitus tipo 1 / Video head impulse test (v-hit) in individuals with type 1 diabetes mellitus

RESUMO Objetivo Verificar a função dos canais semicirculares do labirinto de indivíduos com diabetes tipo 1, submetidos ao Video Head Impulse Test (v-HIT), e compará-los com indivíduos sem diabetes. Métodos Estudo transversal, observacional, analítico, realizado com uma amostra de conveniência, formada por 35 indivíduos diabéticos e 100 não diabéticos. Todos os participantes foram submetidos à avaliação vestibular por meio do v-HIT. Resultados A casuística foi composta por 135 participantes, divididos em dois grupos. O grupo de estudo foi composto por indivíduos com diabetes tipo 1, totalizando 21 mulheres e 14 homens. A idade variou entre 18 e 71 anos, com média de 35,37 anos e desvio padrão de 10,98. O grupo sem diabetes foi composto por 77 mulheres e 23 homens. A idade variou entre 20 e 83 anos, com média de 46,44 e desvio padrão de 19,82. Os grupos foram pareados entre si, com relação à idade (p=0,098) e sexo (p=0,052). Os pacientes diabéticos apresentaram ganho diminuído nos canais semicirculares posteriores e anterior esquerdo. A velocidade apresentou diferença significativa nos canais lateral esquerdo, anterior direito e posterior esquerdo no grupo com diabetes mellitus tipo 1, porém não apresentou correlação com o ganho dos canais semicirculares. Conclusão Os participantes com diabetes mellitus tipo 1 apresentaram um ganho diminuído nos canais semicirculares posteriores e no canal anterior esquerdo quando comparados com indivíduos não diabéticos.

ABSTRACT Purpose To verify the function of the labyrinth semicircular channels of type 1 diabetes individuals submitted to the Video Head Impulse Test (v-HIT) and to compare them with individuals without diabetes. Methods Cross-sectional, observational, analytical study conducted with a convenience sample of 35 diabetic and 100 non-diabetic individuals. All participants were submitted to vestibular evaluation using v-HIT. Results The sample consisted of 135 participants divided into two groups. The study group was composed of individuals with type 1 diabetes, totaling 21 women and 14 men. The age range was between 18 and 71 years, with a mean of 35.37 years and standard deviation of 10.98. The group without diabetes was composed of 77 women and 23 men. The age range was between 20 to 83 years, with a mean of 46.44 and standard deviation of 19.82. The groups were matched for age (p=0.098) and gender (p=0.052). Diabetic patients showed decreased gain in the posterior and left anterior semicircular canals. Velocity showed a significant difference in the left lateral, anterior right and posterior left canals in the group with DM1, however velocity did not show correlation with the gain of the semicircular canals. Conclusion participants with type 1 diabetes mellitus showed a decreased gain in the posterior semicircular canals and in the left anterior canal when compared to non-diabetic individuals.

Hipoacusia Neurosensorial súbita y COVID 19 / Sudden Sensirineural Hearing Loss (SSHL) and COVID 19

La enfermedad por COVID 19 es una infección viral causada por el agente etiológico SARS Cov 2; presenta una gama de características clínicas incluyendo síntomas neurológicos, afectando neuronas, células gliales y nervios; formando parte del grupo de etiología de la hipoacusia neurosensorial. Se realiza este reporte de caso de hipoacusia súbita neurosensorial unilateral acompañada de tinnitus en paciente con antecedente de SARSCov2 Positivo, describiendo los principales hallazgos otológicos y audiológicos en el proceso de evaluación diagnóstico. La afectación por el virus nCoV-19 tiene incidencia en la pérdida auditiva, como se describe en estudios de casos reportados internacionales.

COVID 19 disease is a viral infection caused by the etiologic agent SARS Cov 2; presents a range of clinical features including neurological symptoms, affecting neurons, glial cells, and nerves; forming part of the etiology group of sensorineural hearing loss. This case report of sudden unilateral sensorineural hearing loss accompanied by tinnitus is made in a patient with a history of SARSCov2 Positive, describing the main otological and audiological findings in the diagnostic evaluation process. The involvement by the nCoV-19 virus has an incidence on hearing loss, as described in international reported case studies.

The Study Of Hrct And Mri Temporal Bone Findings In Pediatric Patients With Congenital Sensorineural Hearing Loss

Introduction -The incidence of Congenital Sensorineural hearing loss (SNHL) is approximately 1: 1000 live births. SNHLis either due to disorders of the inner ear or cochleovestibular cranial nerve. Radiological evaluation is necessary to detect or rule out causes of SNHL. Also, the treatment of SNHLis predominantly determined by the etiology of hearing loss. Aim & objective-Radiological assessment of various congenital inner ear malformations in pediatric age group patients with sensorineural hearing loss in a tertiary care centre.Material & Methods-This is a prospective study conducted between 1 January 2018 and 1 June 2019 in Department of Radiodiagnosis, SAIMS, Indore & included all paediatric patients (93 children), who came for HRCTand MRI temporal bone imaging with the clinical diagnosis of congenital sensorineural hearing loss (SNHL) / for evaluating congenital sensorineural hearing loss (SNHL).Results-In our study out of 93 paediatric patients , no significant radiological abnormality were detected in 68 patients (73.11%), however, 25 patients (26.88%) had various congenital anomalies of the inner ear and vestibulocochlear nerve. Most commonly affected organ was cochlea. Among these 25 patients only cochlea was involved in 7(28%), both Cochlea and semicircular canal in 4(16%), and Cochlea and vestibular aqueduct in 1 patient(4%). Isolated vestibular aqueduct dilatation was found in 8 (32%) patients. Isolated semicircular canal involvement and cochleovestibular nerve abnormality were seen in 3 (12%) and 2 (8%) patients respectively.Conclusion-In this study, imaging has helped us to detect various inner ear malformations in children with congenital sensorineural hearing loss. It is helpful for preoperative planning and preparation for cochlear implant in a tertiary care centre

Cerebrospinal fluid otorrhea secondary to congenital inner ear dysplasia: diagnosis and management of 18 cases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Objective: To describe the characteristics of the clinical presentation, diagnosis, surgical methods, and outcomes of patients with otogenic cerebrospinal fluid (CSF) leakage secondary to congenital inner ear dysplasia. Methods: A retrospective review was performed of 18 patients with otogenic CSF leakage secondary to inner ear dysplasia who underwent surgery in our group from 2007 to 2017 and had a follow-up of at least 4 months. The average length of follow-up was three years. The characteristics of the clinical presentations of all patients, such as self-reported symptoms, radiographic findings, surgical approaches and methods of repair, position of the leakage during surgery, and postoperative course, including the success rate of surgery, are presented. Results: The patients presented mostly with typical symptoms of meningitis, severe hearing impairment, and CSF otorrhea or rhinorrhea. All 18 patients had at least one previous episode of meningitis accompanied by a severe hearing impairment. The preoperative audiograms of 17 patients showed profound sensorineural hearing loss, and one patient had conductive hearing loss. Twelve patients presented with an initial onset of otorrhea, and two had accompanying rhinorrhea. Six patients complained of rhinorrhea, two of whom were misdiagnosed with CSF rhinorrhea and underwent transnasal endoscopy at another hospital. High-resolution computed tomography (HRCT) images can reveal developments in the inner ear, such as expansion of a vestibular cyst, unclear structure of the semicircular canal or cochlea, or signs of effusion in the middle ear or mastoid, which strongly suggest the possibility of CSF otorrhea. The children in the study suffered more severe dysplasia than adults. All 18 patients had CSF leakage identified during surgery. The most common defect sites were in the stapes footplates (55.6%), and 38.9% of patients had a leak around the oval window. One patient had a return of CSF otorrhea during the postoperative period, which did not re-occur following a second repair. Conclusions: CSF otorrhea due to congenital inner ear dysplasia is more severe in children than in adults. The most common symptoms were meningitis, hearing impairment, and CSF otorrhea or rhinorrhea. HRCT has high diagnostic accuracy for this disease. The most common fistula site was around the oval window, including the stapes footplates and the annular ligament.

In vitro culture of mammalian inner ear hair cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory function in vertebrates depends on the transduction of sound vibrations into electrical signals by inner ear hair cells. In general, hearing loss resulting from hair cell damage is irreversible because the human ear has been considered to be incapable of regenerating or repairing these sensory elements following severe injury. Therefore, regeneration and protection of inner ear hair cells have become an exciting, rapidly evolving field of research during the last decade. However, mammalian auditory hair cells are few in number, experimentally inaccessible, and barely proliferate postnatally in vitro. Various in vitro primary culture systems of inner ear hair cells have been established by different groups, although many challenges remain unresolved. Here, we briefly explain the structure of the inner ear, summarize the published methods of in vitro hair cell cultures, and propose a feasible protocol for culturing these cells, which gave satisfactory results in our study. A better understanding of in vitro hair cell cultures will substantially facilitate research involving auditory functions, drug development, and the isolation of critical molecules involved in hair cell biology.

Bone morphogenetic proteins and inner ear development / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.

Clinical study of inner ear hemorrhage-associated sudden deafness and vertigo / 中华耳鼻咽喉头颈外科杂志

Objective@#To analyze the clinical features and possible pathogenesis of sudden deafenss and vertigo induced by inner ear hemorrhage.@*Methods@#Clinical data of 30 patients with inner ear hemorrhage, from the first affiliated hospital of Sun Yat-sen university during Jan 2016 to May 2017, were retrospectively analyzed.@*Results@#Vergito and profound deafness were seen in all patients. The duration of vertigo ranged from 24 hours to three days in 11 cases, three to 14 days in the remaining 19 cases. Simultaneous occurrence of vergito and deafenss were seen in 24 patients. Semicircular canal hypofunction and abnormal cervical vestibular evoked myogenic potentials(C-VEMP)/ocular vestibular evoked myogenic potentials(O-VEMP) were detected in all cases. Ten patients had benign paroxysmal positional vertigo(BPPV) simultaneously. Hearing recovered in 20% of the cohort posttreatment. Dizziness and balance disturbance disappeared 1 to 2 months after therapy in 16 cases. Long term (6 months) follow up revealed poor hearing outcome and vestibular rehabilitation.@*Conclusion@#Vestibular vertigo and profound sensorineural hearing loss, with unsatisfactory clinical prognosis, constituted the characters of inner ear hemorrhage-associated sudden deafness.

Intratympanic Gentamicin Versus Labyrinthectomy: Inner Ear Sensitivity to Gentamicin and Impact on the Contralateral Labyrinth

OBJECTIVES: To investigate the impact of labyrinthectomy and intratympanic (IT) gentamicin injections on the contralateral labyrinth, we also assessed the response of each individual semicircular canal to each IT gentamicin application. METHODS: We performed a pilot observational study on tertiary, referral, academic settings. Thirteen patients with unilateral vestibular pathology were organized into two groups, group I (seven patients) receiving IT gentamicin and group II undergoing labyrinthectomy (six patients). All patients underwent six-canal video-head-impulse test in predetermined time intervals. Patients receiving gentamicin were additionally tested 3 to 5 days after every sequential injection, until all ipsilateral canals were ablated, to determine the order of response to gentamicin. We recorded the vestibular-ocular reflex gains and the presence of covert/overt saccades for each canal. RESULTS: The posttreatment ipsilateral gains were abnormal. No patient from the gentamicin group developed abnormal contralateral responses, while patients undergoing labyrinthectomy had abnormal contralateral responses from at least one canal, even several months posttreatment. Finally, the lateral semicircular canal was the first one to be affected by IT gentamicin followed by the posterior canal: the superior canal was ablated last. CONCLUSION: In our study, labyrinthectomy had an impact on the responses recorded from the contralateral ear, while IT gentamicin ablated the ipsilateral labyrinthine function without affecting the contralateral responses, possibly because of a milder, more gradual impact. We also show for the first time the order that IT gentamicin application affects the semicircular canals, with the lateral being the first to be affected.

Analysis of Inner Ear Anomalies in Unilateral Congenital Aural Atresia Combined With Microtia

OBJECTIVES: The aim of this study was to analyze the incidence of inner ear anomalies in patients with unilateral congenital aural atresia (CAA) combined with microtia. METHODS: We retrospectively reviewed 61 patients with unilateral CAA combined with microtia who underwent high-resolution temporal bone computed tomography (TBCT) and hearing examination. Inner ear anomalies were analyzed using TBCT and evaluated according to the Jahrsdoerfer grading system, Marx classification, and extent of inferior displacement of the mastoid tegmen. RESULTS: Inner ear anomalies were observed in 14 patients (23.0%). Lateral semicircular canal (LSCC) dysplasia was the most common inner ear anomaly, with an incidence of 16.4%. The incidence was significantly higher on the pathologic side than on the unaffected side (P=0.002). All vascular anomalies were observed in the high-riding jugular bulb, with an incidence of 24.6%. The incidence was significantly higher on the pathologic side than on the unaffected side (P<0.001). LSCC dysplasia was significantly more common in patients with a lower Jahrsdoerfer score (odds ratio, 0.66; P=0.004). CONCLUSION: The incidence of inner ear anomalies was relatively high in patients with unilateral CAA combined with microtia; LSCC dysplasia was the most common anomaly and the probability of coexistence was higher in patients with a lower Jahrsdoerfer score.