L’angolo pontocerebellare (APC) è una regione anatomica ricca di elementi vascolonervosi, il che spiega la frequente manifestazione di diverse patologie attraverso il danneggiamento dei nervi cranici che vi circolano. La patologia dell’angolo pontocerebellare è estremamente varia ma dominata da patologie tumorali con, in ordine di frequenza, lo schwannoma vestibolare, il meningioma e la cisti epidermoide. La risonanza magnetica (RM) è l’esame diagnostico chiave per le patologie che colpiscono l’angolo pontocerebellare e il condotto uditivo interno (CUI). Le sequenze morfologiche consentono uno studio dettagliato dei diversi elementi della fossa posteriore e le sequenze funzionali sono un prezioso aiuto nella diagnosi eziologica delle lesioni. Nel caso di un acufene pulsatile, la RM può cercare prove a favore di un’anomalia vascolare della fossa posteriore o della base del cranio. L’emergere della RM 3 Tesla con sequenze tridimensionali (3D) fluid attenuated inversion recovery (FLAIR) tardive consente di ottenere maggiori informazioni sulla diagnosi positiva e sulla localizzazione dei diversi disturbi dell’orecchio interno. La TC resta indicata per le lesioni ossee dell’osso temporale e le situazioni di emergenza e a scopo anatomico prechirurgico. L’arteriografia è un esame invasivo utile prima di un intervento di radiologia interventistica.

Esistono molte vie d’accesso all’apice petroso. Ciò è spiegato dalla sua topografia profonda all’interno di un’anatomia complessa a causa del suo difficile accesso, ai confini di varie specialità (otologia, neurochirurgia e chirurgia cervicofacciale e rinosinusale), dalla varietà delle lesioni che vi si possono sviluppare e dalla necessità di adattamento ai vari contesti clinici (stato uditivo e facciale, precedenti…). Questo articolo si propone di presentarle sottolineando le vie d’accesso più rilevanti all’apice petroso, che il più delle volte sono transtemporali, transpetrose ed extradurali.

El ángulo pontocerebeloso (APC) es una región anatómica que contiene abundantes elementos vasculonerviosos, lo que explica que el modo de revelación frecuente de las diferentes patologías sea una afectación de los nervios craneales que circulan por él. La patología del ángulo pontocerebeloso es muy variada, pero está dominada por las patologías tumorales como, por orden de frecuencia, el schwannoma vestibular, el meningioma y el quiste epidermoide. La resonancia magnética (RM) es la exploración clave del diagnóstico de estas patologías que afectan al ángulo pontocerebeloso y al conducto auditivo interno (CAI). Las secuencias morfológicas permiten un estudio detallado de los diferentes elementos de la fosa posterior y las secuencias funcionales son una ayuda muy útil para el diagnóstico etiológico de las lesiones. En el caso de un acúfeno pulsátil, la RM permite buscar argumentos a favor de una anomalía vascular de la fosa posterior o de la base del cráneo. La aparición de la RM de 3 teslas con secuencias en tres dimensiones (3D) y recuperación de inversión atenuada por fluido (FLAIR, fluid attenuated inversion recovery) tardías permite obtener más informaciones sobre el diagnóstico positivo y sobre la localización de las distintas afectaciones del oído interno. La tomografía computarizada sigue estando indicada para las lesiones óseas del hueso temporal, las situaciones de urgencia y con un fin anatómico prequirúrgico. La arteriografía es una exploración invasiva que tiene interés antes un procedimiento de radiología intervencionista.

Évaluer un protocole de transparisation utilisant l’éthyle cinnamate, produit organique non toxique pour l’homme, et son intérêt dans l’étude par microscopie à feuille de lumière des dommages cochléaires post-implantatoires chez la gerbille de Mongolie. Les animaux bénéficiaient d’une implantation cochléaire droite en fenêtre ronde par voie rétro-auriculaire. Ils étaient ensuite euthanasiés 10 semaines après l’implantation. Les cochlées étaient préparées (porte électrodes en place) selon un protocole de 29 jours comprenant des étapes de fixation, microdissection, décalcification, perméabilisation, blocage, immunomarquage fluorescent, déshydratation et enfin transparisation en solution d’éthyle cinnamate. L’acquisition était effectuée en microscopie à feuille de lumière. Le logiciel Imaris était ensuite utilisé pour l’analyse tridimensionnelle. Les cochlées transparentes n’avaient pas subi de modification architecturale notable. Six cochlées étaient acquises en microscopie à feuille de lumière permettant une bonne visibilité de la cochlée entière. L’analyse tridimensionnelle en immunofluorescence de la cochlée permettait de mettre en évidence une résolution d’image suffisante pour l’analyse des cellules neuronales du ganglion spiral et l’évaluation de la réaction tissulaire fibrotique entourant le porte électrodes. Le protocole de transparisation par l’éthyle cinnamate était performant pour l’analyse en microscopie à feuille de lumière de la cochlée entière de gerbille de Mongolie avec l’implant laissé in situ. Cette technique était adaptée à l’étude dans un même échantillon, des dommages cellulaires et tissulaires post-implantatoires, sans présenter la toxicité des autres méthodes décrites à ce jour.

Objectives: To assess a clearing protocol using ethyl cinnamate, an organic substance which is non-toxic for humans, and its value in light-sheet microscopy study of post-implantation cochlear damage in the Mongolian gerbil. Material and methods: The animals underwent right cochlear implantation in the round window by a retroauricular approach. They were then euthanized 10 weeks after implantation (electrode array in place). The cochleae were prepared according to a 29-day protocol including steps of fixation, microdis-section, decalcification, permeabilization, blocking, fluorescent immunolabeling, dehydration and finally clearing in ethyl cinnamate solution. Acquisition of transparent cochleae was performed by light-sheet microscopy. Imaris software was then used for 3D analysis. Results: The transparent cochleae had not undergone any shrinkage or any significant architectural changes. Six cochleae were acquired by light-sheet microscopy, allowing good visibility of the whole cochlea. 3D immunofluorescence analysis of the cochlea provided sufficient image resolution for analy-sis of the spiral ganglion neurons and assessment of the fibrotic tissue reaction surrounding the electrode array. Conclusion: The ethyl cinnamate clearing protocol was effective for light-sheet microscopy analysis of the whole Mongolian gerbil cochlea with the implant left in situ. This technique is suitable for the study of post-implantation cell and tissue damage in the same sample, without the potential toxicity of other methods described to date. (c) 2022 Published by Elsevier Masson SAS.

Immunofluorescence on cleared intact cochlea allows detailed analysis of the cochlear ultrastructure, while avoiding the problems of dissection and serial sections. Protocols have been developed for mice and Mongolian gerbils. This technical note proposes a detailed and optimised immunofluorescence protocol in the Mongolian gerbil comprising significant quantitative and qualitative improvements. This protocol sequentially comprises: fixation (1 day), decalcification (6 days), pre-treatment (7.5hours), immunolabelling (42hours), dehydration and clearing (23hours), followed by mounting and laser scanning confocal microscopy acquisition. This protocol has been optimised in terms of duration (10 days versus 13 days) with a reduction of the number of steps, improvement of the specificity of immunolabelling and optimisation of the quality of the results obtained. This technical note provides a detailed description of this protocol.

Aim: To evaluate azimuthal sound-source localization performance under different conditions, with a view to optimizing a routine sound localization protocol. Material and method: Two groups of healthy, normal-hearing subjects were tested identically, except that one had to keep their head still while the other was allowed to turn it. Sound localization was tested without and then with a right ear plug (acute auditory asymmetry) for each of the following sound stimuli: pulsed narrow-band centered on 250 Hz, continuous narrowband centered on 2000 Hz, 4000 Hz and 8000 Hz, continuous 4000 Hz warble, pulsed white noise, and word ("lac" (lake)). Root mean square error was used to calculate sound-source localization accuracy. Results: With fixed head, localization was significantly disturbed by the earplug for all stimuli (P< 0.05). The most discriminating stimulus was continuous 4000 Hz narrow-band: area under the ROC curve (AUC), 0.99 [95% CI, 0.95-1.01] for screening and 0.85 [0.82-0.89] for diagnosis. With mobile head, localization was significantly better than with fixed head for 4000 and 8000 Hz stimuli (P< 0.05). The most discriminating stimulus was continuous 2000 Hz narrow-band: AUC, 0.90 [0.83-0.97] for screening and 0.75 [0.71-0.79] for diagnosis. In both conditions, pulsed noise (250 Hz narrow-band, white noise or word) was less difficult to localize than continuous noise. Conclusion: The test was more sensitive with the head immobile. Continuous narrow-band stimulation centered on 4000 Hz most effectively explored interaural level difference. Pulsed narrow-band stimulation centered on 250 Hz most effectively explored interaural time difference. Testing with mobile head, closer to real-life conditions, was most effective with continuous narrow-band stimulation centered on 2000 Hz. (C) 2019 Elsevier Masson SAS. All rights reserved.

L’objectif était d’évaluer les performances de localisation sonore spatiale azimutale dans différentes conditions pour l’optimisation d’un protocole de localisation sonore spatiale de routine. Deux groupes de sujets sains ont été testés de façon identique. Le premier groupe devait garder la tête fixe alors que le deuxième groupe était autorisé à tourner la tête. La localisation sonore spatiale était testée oreilles nues, puis avec un bouchon d’oreille droit (asymétrie auditive aiguë) pour chacun des stimuli sonores suivants : bande étroite centrée sur 250 Hz pulsé, bandes étroites centrées sur 2000 Hz, 4000 Hz et 8000 Hz continus, wobulé 4000 Hz continu, bruit blanc pulsé et mot (« lac »). L’erreur quadratique moyenne ou RMS Error (Root Mean Square Error) permettait de calculer la performance de localisation. Tête fixe, la localisation sonore était significativement perturbée après bouchon d’oreille pour l’ensemble des stimuli (p < 0,05). Le stimulus sonore le plus discriminant était en bande étroite 4000 Hz continu : aire sous la courbe ROC à 0,99 [0,95–1,01] en dépistage, à 0,85 [0,82–0,89] en diagnostic. Tête mobile, la localisation sonore était améliorée (par rapport à tête fixe) de façon significative pour les stimuli à 4000 et 8000 Hz (p < 0,05). Le stimulus sonore le plus discriminant tête mobile était en bande étroite 2000 Hz continu : aire sous la courbe ROC à 0,90 [0,83–0,97] en dépistage, à 0,75 [0,71–0,79] en diagnostic. Dans les deux conditions, les bruits pulsés (bande étroite 250 Hz, bruit blanc et mot) étaient moins difficiles à localiser que les bruits continus. Le test réalisé chez un sujet tête fixe est plus sensible. L’utilisation d’un bruit en bande étroite centré sur 4000 Hz et continu explore la différence d’intensité interaurale. Un bruit en bande étroite centré sur 250 Hz et pulsé permet d’explorer la différence de temps interaurale. Le test tête mobile, plus proche des conditions de vie réelle, est optimisé avec un bruit en bande étroite centré sur 2000 Hz et continu.

A new type of miniaturized implants for local controlled drug delivery to the inner ear is proposed: Hybrid Ear Cubes. They are composed of two main parts: (i) a cylinder, which is placed into a tiny hole (<0.4 mm) drilled into (or close to) the oval (or round) window, and (ii) a cuboid, which is placed into the middle ear. The drug is released at a pre-programmed rate into the perilymph: (i) via the cylindrical part of the implant, which is in direct contact with this liquid, and (ii) via diffusion from the cuboid through the oval/round window. Importantly, the cylindrical part assures a reliable fixation of the drug delivery system at the site of administration. Furthermore, the cuboid provides a relatively "large" drug reservoir, without expulsing perilymph from the cochlea. The required surgery is minimized compared to the placement of an intracochlear implant. In contrast to previously proposed Ear Cubes, which are mono-block systems, Hybrid Ear Cubes consist of two halves, which can: (i) be loaded with different drugs, (ii) be loaded with the same drug at different concentrations, and/or (iii) be based on two different matrix formers. This offers a substantially increased formulation flexibility. Different types of silicone-based Hybrid Ear Cubes were prepared, loaded with 10% dexamethasone in one half and 0-60% dexamethasone in the other half. Importantly, tiny drug crystals were homogeneously distributed throughout the respective implant halves. The observed drug release rates were very low (e.g., <0.5% after 2 months), which can be attributed to the type of drug and silicone as well as to the very small surface area exposed to the release medium. Importantly, no noteworthy implant swelling was observed.

La localisation sonore spatiale est primordiale pour le confort de vie. Elle permet de définir la position d’une source sonore dans les trois dimensions de l’espace (azimut, hauteur et distance). Elle repose sur trois types d’indices différents : deux indices binauraux (différence de temps interaurale et différence d’intensité interaurale) et 1’indice monaural spectral (fonction de transfert liée à la tête). Ces indices sont complémentaires et varient selon les caractéristiques acoustiques du son incident. L’objectif de cette mise au point est de réaliser une synthèse des connaissances actuelles sur les fondements physiques de la localisation sonore spatiale.

Sound source localization is paramount for comfort of life, determining the position of a sound source in 3 dimensions: azimuth, height and distance. It is based on 3 types of cue: 2 binaural (interaural time difference and interaural level difference) and 1 monaural spectral cue (head-related transfer function). These are complementary and vary according to the acoustic characteristics of the incident sound. The objective of this report is to update the current state of knowledge on the physical basis of spatial sound localization.