Study on gene therapy for DPOAE and ABR threshold changes in adult Otof-/- mice / 临床耳鼻咽喉头颈外科杂志

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear / 神经科学通报·英文版

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.

Osteoporosis bilateral del yunque, hallazgos otopatológicos / Case report: Bilateral incus osteoporosis, otopathological findings / Relato de caso: Osteoporose bilateral da bigorna, achados otopatológicos

La osteoporosis es una enfermedad sistémica esquelética, cuyas manifestaciones más comunes son las fracturas vertebrales y de cadera. En relación con el oído, se han realizado algunos estudios controversiales que sugieren el aumento de riesgo de pérdida auditiva en pacientes con osteoporosis, mientras otros indican que no hay relación alguna con esta enfermedad. Se realizó un reporte de caso donde se describen los hallazgos en el oído medio y oído interno, tras la valoración bajo microscopía de luz, en un espécimen de hueso temporal con antecedente de osteoporosis. Se evidencia desmineralización, porosidad y disminución cualitativa del tejido óseo, así como disminución del espacio incudomaleolar.

Osteoporosis is a skeletal systemic disease, commonly known for its affection on hips and spine. In relation to the ear, several controversial studies have documented an increased risk for hearing loss in patients with osteoporosis, while others do not find any association with these disorders. A case report was carried out which describes the findings in the middle ear and inner ear, after evaluation under light microscopy, in a temporary bone specimen with a history of osteoporosis. Demineralization, porosity and qualitative diminished bone tissue are found, as well as a decrease in the incudomallear joint.

A osteoporose é uma doença esquelética sistêmica, cujas manifestações mais comuns são as fraturas vertebrais e de quadril. Em relação ao ouvido, foram realizados alguns estudos controversos que sugerem um risco aumentado de perda auditiva em pacientes com osteoporose, enquanto outros indicam que não há relação com essa doença. Foi feito um relato de caso descrevendo os achados em ouvido médio e ouvido interno, após avaliação sob microscopia de luz, em espécime de osso temporal com histórico de osteoporose. Há evidências de desmineralização, porosidade e diminuição qualitativa do tecido ósseo, bem como diminuição do espaço incudomaleolar.

El buceo recreativo y la otorrinolaringología: ¿qué sabemos y deberíamos saber? / Recreational diving and otolaryngology: what do we know and should we know?

El buceo recreativo es una práctica cada vez más popular en la población mundial, sin embargo, no está exenta de riesgos. A medida que transcurre una inmersión, el buzo es susceptible a una serie de cambios de presión que afectan las distintas cavidades que contienen aire dentro del cuerpo humano, tales como el oído, cavidades paranasales y los pulmones. Existe un gran espectro de patologías asociadas al buceo, explicándose la mayoría de ellas por el barotrauma asociado, cuya gravedad depende de la magnitud del daño asociado, pudiendo presentar desde manifestaciones a nivel local, así como también a nivel sistémico. Las patologías otológicas suelen ser las más frecuentes y el principal motivo de consulta en este tipo de pacientes. Sin embargo, las afecciones otoneurológicas, rinosinusales, de vía aérea y sistémicas pueden ser comunes dependiendo de cada perfil de buceo. Actualmente no existen recomendaciones locales sobre esta práctica, por lo que el conocimiento de la fisiología, fisiopatología y el tratamiento de las patologías otorrinolaringológicas asociadas deben ser conocidas a medida que este deporte se vuelve cada vez más popular. Se realizó una revisión de la literatura sobre las distintas afecciones otorrinolaringológicas con el fin de sistematizarlas y elaborar recomendaciones para establecer una práctica segura.

Recreational diving is an increasingly popular practice in the world; however, it is not without risks. As a dive progresses, the diver is susceptible to a series of pressure changes that affect the air-containing cavities, such as the ear, paranasal cavities, and lungs. There is a large spectrum of pathologies associated with diving, most of them being explained by associated barotrauma, the severity of which depends on the magnitude of the associated damage, could present local manifestations, as well as at systemic level. Otological pathologies are usually the most frequent and the main reason for consultation in this type of patients, however, otoneurological, rhinosinusal, airway and systemic conditions can be common depending on each diving profile. Currently there are no local recommendations on this practice, therefore, knowledge of the physiology, pathophysiology and treatment of associated otorhinolaryngological pathologies should be known as this sport becomes increasingly popular. A review of the literature on the different ear, nose and throat conditions was carried out in order to systematize them and develop recommendations to establish a safe practice.

Analysis of wideband tympanometry in Ménière's disease / Análise da timpanometria de banda larga na doença de Ménière

Abstract Introduction: Endolymphatic hydrops is the pathophysiological substrate of Ménière's disease. The changes in the inner ear, transmitted to the middle ear through changes in the ossicular chain mobility, can be quantified by wideband tympanometry, through the measurement of the acoustic absorbance at multiple frequencies, represented by the sound energy absorbed by the middle ear, even at its early stages. Studying the behavior of the middle ear through the absorbance in patients with endolymphatic hydrops under ambient pressure and under peak pressure can be useful for detecting Ménière's disease. Objective: To characterize acoustic absorbance behavior in subjects with symptomatic and asymptomatic Ménière's disease compared to controls, in order to verify the ability of wideband tympanometry to detect Ménière's disease. Methods: We carried out a cross-sectional study with a diagnostic approach comparing the findings of wideband tympanometry at ambient pressure and peak pressure between the ears of the control group (n = 30), the asymptomatic group (n = 21) and the symptomatic group (n = 9). Results: Different peak pressure values were found between the ears of the control group (0daPa), the asymptomatic group (−11 daPa) and the symptomatic group (−192 daPa), with p < 0.05 by the Kruskal-Wallis test, Mann Whitney test and Bonferroni correction. Different absorbance values were found between the ears of the symptomatic group and the asymptomatic group compared to the control group for low frequencies at ambient pressure and peak pressure, with p < 0.05 by the Kruskal-Wallis test, Mann Whitney test and Bonferroni correction. Conclusions: The Wideband Tympanometry test was capable of identifying the presence of Ménières disease, and to differentiate between asymptomatic and symptomatic patients, when comparing them with healthy individuals.

Resumo Introdução: A hidropsia endolinfática é o substrato fisiopatológico da doença de Ménière. As alterações desencadeadas na orelha interna, transmitidas à orelha média pelas modificações na mobilidade da cadeia ossicular, podem ser quantificadas pela timpanometria de banda larga, através da medida da absorvância acústica sob múltiplas frequências, representadas pela energia sonora absorvida pela orelha média, mesmo em estágios iniciais de sua instalação. Estudar o comportamento da orelha média através da absorvância em pacientes com hidropisia endolinfática sob pressão ambiente e sob o pico de pressão pode ser útil na detecção da doença de Ménière. Objetivo: Caracterizar o comportamento da absorvância em indivíduos com diagnóstico da doença de Ménière sintomáticos e assintomáticos, comparados com controles, a fim de verificar a capacidade da timpanometria de banda larga em detectar variações clínicas relacionadas a possível hidropisia endolinfática. Método: Foi realizado um estudo transversal, com enfoque diagnóstico, que comparou os achados da timpanometria de banda larga na pressão ambiente e no pico de pressão entre orelhas do grupo controle (n = 30), grupo assintomático (n = 21) e grupo sintomático (n = 9). Resultados: Foram encontrados valores do pico de pressão diferentes entre orelhas do grupo controle (0 daPa), do grupo assintomático (-11 daPa) e do grupo sintomático (-192 daPa), com p <0,05 pelos testes de Kruskal-Wallis, Mann Whitney e correção de Bonferroni. Foram encontrados valores de absorvância diferentes entre orelhas do grupo sintomático e do grupo assintomático em relação ao grupo controle para as frequências baixas na pressão ambiente e na pressão de pico, com p < 0,05 pelos testes de Kruskal-Wallis, Mann Whitney e correção de Bonferroni. Conclusão: A timpanometria de banda larga foi um teste capaz de identificar a presença da doença de Ménière e de diferenciar os pacientes assintomáticos e sintomáticos, comparando-os com indivíduos hígidos.

Preliminary observation on the differential expression of metformin in preventing noise-induced hearing loss in inner ear protein group of rats / 中华劳动卫生职业病杂志

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.

Inner ear hemorrhage : A cause of sensorineural hearing loss in leukemia

@#A 25-year-old male who was recently diagnosed with chronic myelogenous leukemia developed bilateral tinnitus and hearing loss. The hearing loss progressed rapidly but asymmetrically, with the right ear being subjectively worse than the left. Pneumatoscopy revealed bilaterally intact and mobile tympanic membranes and no visual evidence of middle ear pathology. Audiometry confirmed the presence of a profound hearing loss in the right ear and a moderate sensorineural hearing loss in the left ear. In relation to evaluating the cause of hearing loss, the radiologic interpretation of a contrast-enhanced cranial MRI performed to evaluate other neurological symptoms that predated the hearing loss only stated that the cerebellopontine angle cisterns were unremarkable. No mention was made about the status of the inner ears. When asked to comment on the inner ears in the MR study, the radiologist opined that the cranial MRI did not have the proper fine-cut imaging sequences necessary to evaluate this region adequately, and indicated the need for a dedicated MR study of the temporal bones. An independent review of the DICOM imaging data of the patient’s cranial MRI revealed the presence of three imaging sequences with information pertinent to the evaluation of the inner ears. These sequences are shown below, with a sequential narration of the descriptive imaging findings and their clinical significance that helps to arrive at a conclusive diagnosis.

Internal acoustic opening: different osseous landmarks and their clinical implications / Poro acústico interno: diferentes hitos óseos y sus implicaciones clínicas

SUMMARY: Internal acoustic opening is a space that opens to facies posterior of the petrous piece of temporal bone that goes inside facial nerve, vestibulocochlear nerve, intermedial nevre and labyrinthine artery. The purpose of this study is the assessment of internal acoustic opening from a morphometric perspective, determination of the shape of the hole and determination of the distance to some important anatomic formations. This study is conducted on 166 temporal bones with unknown sex formation which are part of the skull collection in NEU and KTO Karatay University, Anatomy Department. In this study, the vertical and diameter of internal acoustic meatus, its distance to the bottom and top sides of posterior surface of the petrous part, its distance to groove for superior sagittal sinus and its distance to apex were measured. Moreover, in this study internal acoustic opening spaces are categorized into six groups as round, oval, U-shaped, fissure, irregular and V shape. Digital caliper was used for internal acoustic meatus measurements. While the vertical horizontal diameters and distance to groove for superior sagittal sinus of internal acoustic opening on the right side are 4.12 mm, 6.83 mm and 19.64mm respectively, they are 4.56 mm, 7.10 mm and 21.06 mm on the left side respectively. We have observed in this study, 37.3 % of the internal acoustic opening as round, 34.3 % as oval, 6.6 % as U-shaped, 6.6 % as fissure, 12.7 % as irregular and 2.4 % as V-shaped. We believe that these measurements can provide guidance and help in surgical procedures.

RESUMEN: El poro acústico interno es un espacio que se abre en la cara posterior de la parte petrosa del hueso temporal, donde entran los nervios facial, intermedio y vestibulococlear, además de la arteria laberíntica. El propósito de este estudio fue la evaluación del poro acústico interno desde una perspectiva morfométrica, determinación de la forma del foramen y de la distancia a algunas formaciones anatómicas importantes. Este estudio se realizó en 166 huesos temporales de individuos de sexo desconocido que forman parte de la colección de cráneos del Departamento de Anatomía en NEU y KTO, Universidad de Karatay, Se midió la altura vertical y el diámetro del poro acústico interno, su distancia a los lados inferior y superior de la superficie posterior de la parte petrosa, su distancia al surco del seno sagital superior y su distancia al vértice. Además, el poro acústico interno se clasificó en seis grupos: redondos, ovalados, en forma de U, de fisura, irregulares y en forma de V. Se utilizó un calibrador digital para las mediciones del meato acústico interno. Mientras que los diámetros horizontales, verticales y la distancia al surco para el seno sagital superior del poro acústico interno en el lado derecho fue de 4,12 mm, 6,83 mm y 19,64 mm respectivamente, en el lado izquiedo fue de 4,56 mm, 7,10 mm y 21,06 mm, respectivamente. Hemos observado que en el 37,3 % de los casos el poro acústico interno era redondo, el 34,3 % ovalado, el 6,6 % en forma de U, el 6,6 % de fisura, el 12,7 % irregular y el 2,4 % en forma de V. Estas medidas pueden servir de guía y ayuda en los procedimientos quirúrgicos.

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

Análise das respostas do VEMP cervical e ocular em indivíduos hígidos / Analysis of cervical and ocular VEMP responses in healthy individuals / Análisis de las respuestas VEMP cervicales y oculares en individuos sanos

Introdução: os potenciais evocados miogênicos vestibulares (VEMP) são respostas eletrofisiológicas que conseguem fornecer informações dos órgãos otolíticos sáculo, utrículo e do nervo vestibular. O VEMP é um exame complementar à avaliação vestibular, consistindo num exame rápido, de fácil aplicação e objetivo. Objetivo: analisar os parâmetros de latência, amplitude, limiar e índice de assimetria das respostas do VEMP cervical (cVEMP) e ocular (oVEMP) de indivíduos sem queixas vestibulares. Métodos: estudo transversal realizado com 53 indivíduos de ambos os sexos, sem queixas auditivas e vestibulares. Resultados: encontrou-se simetria de respostas nas latências, amplitudes e limiares de respostas do exame cVEMP. Entretanto, verificou-se diferença entre orelhas da latência P15 do exame oVEMP, sendo maior à direita no sexo feminino. Conclusão: Encontrou-se simetria nas respostas de todos os parâmetros avaliados do cVEMP. Houve assimetria apenas na latência de P15 do oVEMP no sexo feminino. Os limiares de resposta encontrados nos exames cVEMP e oVEMP foram iguais ou maiores que 75 dBNA.

Introduction: Vestibular evoked myogenic potentials (VEMP) are electrophysiological responses that can provide information on the otolithic organs saccule, utricle and of the vestibular nerve. VEMP is a complementary exam to the vestibular assessment; it is a quick exam, easy to apply and objective. Purpose: to analyze the parameters of latency, amplitude, threshold and asymmetry index of the cervical (cVEMP) and ocular VEMP (oVEMP) responses of individuals without vestibular complaints. Methods: cross-sectional study carried out with 53 individuals of both genders without hearing and vestibular complaints. Results: response symmetry was found in the latencies, amplitudes and thresholds of cVEMP test responses. However, there was a difference between the ears of the P15 latency of the oVEMP exam, and this was greater on the right ear in females. Conclusion: symmetry was found in the responses of all cVEMP evaluated parameters. There was asymmetry in oVEMP P15 latency only in female patients. The response thresholds found in the cVEMP and oVEMP tests were equal or greater than 75 dBHL.

Introducción: los potenciales miogénicos evocados vestibulares (VEMP) son respuestas electrofisiológicas que pueden proporcionar información sobre los órganos otolíticos el sáculo, el utrículo y el nervio vestibular. El VEMP es un examen complementario a la evaluación vestibular; es un examen rápido, fácil de aplicar y objetivo. Objetivo: analizar los parámetros de latencia, amplitud, umbral e índice de asimetría de las respuestas VEMP cervical (cVEMP) y ocular (oVEMP) de individuos sin quejas vestibulares. Métodos: estudio transversal realizado con 53 individuos de ambos sexos, sin quejas auditivas y vestibulares. Resultados: Se encontró simetría de respuestas en las latencias, amplitudes y umbrales de respuestas en el examen cVEMP. Sin embargo, hubo una diferencia entre los oídos de la latencia P15 del examen oVEMP, siendo mayor a la derecha en el sexo femenino . Conclusión: se encontró simetría en las respuestas de todos los parámetros evaluados de cVEMP. Hubo asimetría solo en la latencia P15 de oVEMP en el sexo femenino. Los umbrales de respuesta encontrados en las pruebas cVEMP y oVEMP fueron iguales o superiores a 75 dBHL.

Disfunções metabólicas e vertigem: apresentação e revisão dos métodos diagnósticos / Metabolic dysfunctions and vertigo: presentation and review of diagnostic methods

Contexto: A tontura é um sintoma de alta prevalência e as labirintopatias de causas metabólicas destacam-se como uma das mais frequentes em nosso meio. Distúrbios do metabolismo glicêmico, disfunções tireoidianas e dislipidemias são as principais. Objetivos: Os objetivos deste estudo são descrever a porcentagem das principais disfunções metabólicas nos pacientes com vertigem e revisar os métodos diagnósticos. Desenho e local: Estudo observacional de pacientes atendidos no setor de Otoneurologia do Instituto Penido Burnier. Métodos: Avaliação de 506 pacientes com vertigem por meio da análise do hormônio tireoestimulante, glicemia de jejum, hemoglobina glicada, insulina de jejum, curvas glicoinsulinêmica de três horas, colesterol total e suas frações (lipoproteína de alta densidade [HDL] e lipoproteína de baixa densidade [LDL]) e triglicerídeos. Foi feita a comparação entre os sexos e com os dados encontrados na população geral. Resultados: Níveis de HDL, triglicerídeos e glicemia de jejum foram mais alterados no sexo masculino e o colesterol total foi mais elevado no sexo feminino. A elevação do HOMA (homeostatic model assessment) foi a alteração mais significante encontrada no grupo em estudo comparando com a população geral, entretanto as curvas glicoinsulinêmicas mostraram mais alterações em comparação ao HOMA. Discussão: A análise do HOMA e da curva glicoinsulinêmica mostrou que a porcentagem de alteração é diferente entre os métodos, não havendo concordância entre eles. O HOMA não substitui as curvas na investigação dos pacientes com vertigem e suspeita de distúrbios do metabolismo glicêmico. Conclusão: É alta a porcentagem das disfunções metabólicas na população com vertigem, justificando a investigação laboratorial neste grupo de pacientes.

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.

Prosper Menière: the man who located vertigo in the inner ear / Prosper Menière: o homem que localizou a vertigem na orelha interna

ABSTRACT Since the Greek Aellus Galenum (129 AD - c.200/c.216), vertigo was considered a problem attributed to a cerebral disorder, diagnosed as the manifestation of apoplectiform cerebral congestion. In the mid-19th century, the Frenchman Prosper Menière changed this concept by placing the origin of this symptom in the inner ear. The main objective of this historical note is to highlight who Menière was, his work, and some aspects of the disease that bears his name.

RESUMO Desde o grego Aellus Galenum (129 d.C. - c.200/c.216), a vertigem era considerada um problema atribuído a um distúrbio cerebral, diagnosticado como a manifestação de uma 'congestão cerebral apoplectiforme'. Em meados do século 19, o francês Prosper Menière mudou esse conceito, colocando a origem desse sintoma na orelha interna. O principal objetivo desta nota histórica é ressaltar quem foi Menière, seu trabalho e alguns aspectos da doença que leva seu nome.

A minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal: a step by step description / Abordagem retrosigmoide minimamente invasiva assistida por endoscopia para remoção de cistos aracnóides no conduto auditivo interno: descrição passo a passo

Abstract Introduction: Arachnoid cyst in the internal auditory canal is a quite rare pathology but due to its compressive action on the nerves in this district should be surgically removed. Several surgical techniques have been proposed but no surgeons have used the minimally assisted endoscope retrosigmoid approach for its removal. Objective: To investigate the feasibility of using a minimally invasive endoscope assisted retro-sigmoid approach for surgical removal of arachnoid cysts in the internal auditory canal. Methods: Minimally invasive endoscope assisted retrosigmoid approach allows to access to the internal auditory canal through a minimally invasive retrosigmoid approach that combines the use of a microscope and an endoscope. It is performed in six steps: soft tissue step, bone step, dura step, cerebellopontine angle step (performed using an endoscope and a microscope), microscope-endoscope assisted arachnoid cysts removal and closure. We tested minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal on two human cadaveric heads (specimens) of subjects affected from audio-vestibular disorders and with arachnoid cysts in the internal auditory canal confirmed by magnetic resonance imaging. Results: The mass was completely and successfully removed from the two specimens with no damage to the nerves and/or vessels in the surgical area. Conclusion: The results of our study are encouraging and support the feasibility of using minimally invasive endoscope assisted retrosigmoid approach for removal of arachnoid cysts in the internal auditory canal. While further clinical in-vivo studies are needed to confirm the accuracy and safety of using the minimally invasive endoscope assisted retrosigmoid approach for this specific surgery, our group has successfully used the minimally invasive endoscope assisted retrosigmoid approach in the treatment of microvascular compressive syndrome, schwannoma removal and vestibular nerve resection.

Resumo Introdução: O cisto aracnóide no conduto auditivo interno é uma doença bastante rara, mas, devido à sua ação compressiva sobre os nervos deste local, ele deve ser removido cirurgicamente. Várias técnicas cirúrgicas foram propostas, mas ninguém utilizou a abordagem retrosigmoide minimamente invasiva assistida por endoscopia para a sua remoção. Objetivo: Investigar a viabilidade do uso da abordagem retrosigmoide minimamente invasiva assistida por endoscopia para remoção cirúrgica de cistos aracnóides no conduto auditivo interno. Método: A abordagem retrosigmoide minimamente invasiva assistida por endoscopia permite o acesso ao conduto auditivo interno através de uma abordagem retrosigmóide minimamente invasiva que combina o uso de um microscópio e um endoscópio. É realizada em seis etapas: do tecido mole, óssea, dura-máter, do ângulo pontocerebelar (realizado com um endoscópio e um microscópio), remoção e fechamento assistidos por endoscópio-microscópico. Testamos a abordagem retrosigmoide minimamente invasiva assistida por endoscopia para remoção de cistos aracnóides no conduto auditivo interno em duas cabeças de cadáveres humanos (espécimes) de indivíduos afetados por distúrbios auditivos-vestibulares e com cistos aracnóides no conduto auditivo interno confirmado por imagem de ressonância magnética. Resultados: A lesão foi removida completamente e com sucesso nos dois espécimes sem dano aos nervos e/ou vasos na área cirúrgica. Conclusão: Os resultados do nosso estudo são encorajadores e apoiam a viabilidade do uso da abordagem retrosigmoide minimamente invasiva assistida por endoscopia para remoção de cistos aracnóides no conduto auditivo interno. Embora mais estudos clínicos in vivo sejam necessários para confirmar a precisão e a segurança do uso da abordagem retrosigmoide minimamente invasiva assistida por endoscopia para essa cirurgia específica, nosso grupo utilizou com sucesso a abordagem retrosigmoide minimamente invasiva assistida por endoscopia no tratamento da síndrome compressiva microvascular, remoção de schwannoma e ressecção do nervo vestibular.

Effects of Toluene on the Development of the Inner Ear and Lateral Line Sensory System of Zebrafish / 生物医学与环境科学（英文）

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.

Práctica experimental de disección y modelación 3D de oído medio e Interno para la construcción significativa de conocimiento en el área de anatomía humana / Experimental practice of dissection and 3D modeling of the middle and inner ear for the development of increased knowledge of human anatomy

La comprensión de la anatomía humana y especialmente de algunos órganos muy pequeños como es el oído medio e interno, resulta desafiante debido a su compleja estructura tridimensional. Construir conocimiento en la comprensión de la Anatomía del oído medio e interno humano, a partir del experimento de disección y modelación 3D. Con imágenes DICOM de una tomografía axial computarizada del oído humano convertidas a un modelo 3D (Mimics) y disecciones cadavéricas del hueso temporal, se diseñaron las estructuras óseas y blandas del oído externo, medio e interno mediante la implementación de software de modelado orgánico. Creación de un protocolo operativo estándar, modelado 3D de oído medio e interno e impresión 3D de las estructuras, diferenciando por color cada una de ellas. La experimentación, en este caso, la disección y modelación de las piezas anatómicas fue fundamental en la enseñanza y aprendizaje de esta área de las ciencias, permitiendo que se construya conocimiento a partir de la búsqueda de información, observación, análisis y reflexión. Los estudiantes manifestaron fascinación y aprendizaje profundo en la práctica realizada. La construcción de modelos explicativos en torno a la experimentación cualitativa permite comprender a profundidad los diferentes fenómenos. La actividad experimental, supera la demostración y facilita la confrontación de pensamiento, los estudiantes a través de esta actividad comprendieron a profundidad la anatomía del oído medio e interno, han adquirido destrezas quirúrgicas, han propuesto y analizado proyectos que les ha permitido participar eventos académicos, adquiriendo competencias como el uso comprensivo del conocimiento científico.

Understanding human anatomy, and especially some very small organs such as the middle and inner ear, is challenging due to their complex three-dimensional structure. To build knowledge in understanding of anatomy, of the human inner and middle ear, from the 3D modeling and dissection experiment. Using DICOM images from a computerized axial tomography of the human ear converted to a 3D model (Mimics) and cadaveric dissections of the temporal bone, the bony and soft structures of the external, middle, and internal ear were designed, using organic modeling software. A standard operating protocol, 3D modeling of the middle and inner ear and 3D printing of the structures was created, differentiating each one by color. In this case, the dissection and modeling of the anatomical pieces was fundamental in the teaching and learning of this area of science, allowing expanded knowledge from the search for information, observation, analysis and reflection. The students showed fascination and deep learning in the practice carried out. The construction of explanatory models around qualitative experimentation allows an in-depth understanding of the different phenomena. The experimental activity overcomes the demonstration and facilitates thought process. The students achieve and in depth understanding of the middle and inner ear anatomy, acquired surgical skills, proposed and analyzed projects that allowed them to participate in academic event. They have also acquired additional skills, such as the comprehensive use of scientific knowledge.

Laberintectomía quirúrgica e implante coclear simultáneo en paciente con enfermedad de Ménière bilateral / Simultaneous labyrinthectomy with cochlear implantation in a patient with bilateral Ménière's disease

Los pacientes con enfermedad de Ménière representan un desafío terapéutico para el médico tratante, especialmente cuando no responden al tratamiento médico conservador. Presentamos un caso de un paciente de 45 años con enfermedad de Ménière activa en oído izquierdo sometido a laberintectomía quirúrgica con implante coclear simultáneo en dicho oído. Se evaluaron resultados clínicos y audiométricos en un seguimiento de 9 meses posencendido del implante y el paciente presentó PTP de 21 dB, con 92% de discriminación a disílabos a 45 dB en el oído implantado, sin tinnitus ni síntomas vestibulares. La combinación de laberintectomía con implante coclear en un mismo tiempo quirúrgico, fue efectiva en controlar los síntomas vestibulares y audiológicos del paciente estudiado.

Patients with Méniére's disease represent a therapeutical problem for physicians, especially in those who do not respond to conservative approaches. We report the case of a 45-year-old male with bilateral Ménière's disease, active in the left ear, who underwent simultaneous cochlear implantation combined with labyrinthectomy surgery. Audiometric and clinical results were evaluated, 9 months after the activation of the implant the patient's PTA was 21 dB, with 92% disyllabic word's discrimination at 45 dB in the implanted ear, without tinnitus or vestibular symptoms. The combined surgical labyrinthectomy and cochlear implantation are efficient for the treatment of vestibular and audiological symptoms of the patient.

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.

Estenosis congénita aislada del conducto auditivo interno como causa de hipoacusia neurosensorial unilateral y paresia del nervio facial / Congenital internal auditory canal stenosis presenting with unilateral sensorineural hearing loss and facial nerve dysfunction

RESUMEN La estenosis del conducto auditivo interno con aplasia/hipoplasia del nervio cocleovestibular es una patología muy infrecuente. Suele ser unilateral y puede acompañarse de aplasia/hipoplasia del nervio facial y otras malformaciones del oído interno. Se presentan aquí dos casos clínicos de pacientes pediátricos con estenosis del conducto auditivo interno unilateral con compromiso del séptimo y octavo par craneal ipsilateral. Se describen las historias y evaluaciones clínicas, hallazgos audiovestibulares, hallazgos imagenológicos, tratamientos indicados y sus resultados.

ABSTRACT Congenital internal auditory canal stenosis associated with aplasia/hypoplasia of the cochleovestibular nerve is a very infrequent pathology. It is usually unilateral and may be accompanied by aplasia/hypoplasia of the facial nerve and other malformations of the inner ear. We hereby present two clinical cases of pediatric patients with congenital internal auditory canal stenosis, with involvement of the seventh and eighth ipsilateral cranial nerve. The medical histories and clinical evaluations, audiovestibular findings, imaging findings, treatments and their results are described.

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.