Polarized Secretion of APRIL by the Tonsil Epithelium Upon Toll-Like Receptor Stimulation.

In mucosa such as tonsil, antibody-producing plasmocytes (PCs) lie in sub-epithelium space, which is thought to provide a suitable environment for their survival. A proliferation inducing ligand (APRIL) is one key survival factor for PCs present in this area. According to in situ staining, apical epithelial cells produced APRIL, and the secreted product had to migrate all through the stratified surface epithelium to reach basal cells. A similar process also occurred in the less-organized crypt epithelium. Tonsil epithelial cells captured secreted APRIL, thanks to their surface expression of the APRIL coreceptor, either syndecan-1 or -4 depending on their differentiation stage. In the most basal epithelial cells, secreted APRIL accumulated inside secretory lamp-1+ vesicles in a polarized manner, facing the sub-epithelium. The tonsil epithelium upregulated APRIL production by apical cells and secretion by basal cells upon Toll-like receptor stimulation. Furthermore, LPS-stimulated epithelial cells sustained in vitro PC survival in a secreted APRIL-dependent manner. Taken together, our study shows that the tonsil epithelium responds to pathogen sensing by a polarized secretion of APRIL in the sub-epithelial space, wherein PCs reside.

[Surgical landmarks of the inferior laryngeal nerve : do they differ by ethnicity ?] / Les repères chirurgicaux du nerf laryngé inférieur diffèrent-ils selon les ethnies ?

For safe procedures, the surgeon performing thyroid gland surgeries must know precisely the anatomical relationships of the inferior laryngeal nerve with other cervical structures, in particular the inferior laryngeal artery and its branches. Classic descriptions of these relationships are based almost exclusively on the observation of Caucasian populations. However, this study shows that there are important differences between Caucasian and Sub-Saharian ethnic group, differences that any surgeon having the opportunity to operate in Africa should know to limit the risk of iatrogenic nerve damage and its morbid consequences.

Lors de chirurgies de la glande thyroïde, il est nécessaire que le chirurgien connaisse précisément les relations anatomiques du nerf laryngé inférieur avec d'autres structures cervicales, en particulier l'artère thyroïdienne inférieure et ses branches. Les descriptions classiques de ces relations sont basées quasi exclusivement sur l'observation de populations caucasiennes. Or, cette étude montre qu'existent d'importantes différences entre les ethnies caucasiennes d'une part et celles d'Afrique subsaharienne d'autre part, différences que tout chirurgien ayant l'occasion d'opérer en Afrique devrait connaître pour limiter le risque de lésion iatrogène du nerf et ses conséquences morbides.

Restoring the High-Frequency Dynamic Visual Acuity with a Vestibular Implant Prototype in Humans.

INTRODUCTION: The vestibular implant could become a clinically useful device in the near future. This study investigated the feasibility of restoring the high-frequency dynamic visual acuity (DVA) with a vestibular implant, using the functional Head Impulse Test (fHIT). METHODS: A 72-year-old female, with bilateral vestibulopathy and fitted with a modified cochlear implant incorporating three vestibular electrodes (MED-EL, Innsbruck, Austria), was available for this study. Electrical stimulation was delivered with the electrode close to the lateral ampullary nerve in the left ear. The high-frequency DVA in the horizontal plane was tested with the fHIT. After training, the patient underwent six trials of fHIT, each with a different setting of the vestibular implant: (1) System OFF before stimulation; (2) System ON, baseline stimulation; (3) System ON, reversed stimulation; (4) System ON, positive stimulation; (5) System OFF, without delay after stimulation offset; and (6) System OFF, 25 min delay after stimulation offset. The percentage of correct fHIT scores for right and left head impulses were compared between trials. RESULTS: Vestibular implant stimulation improved the high-frequency DVA compared to no stimulation. This improvement was significant for "System ON, baseline stimulation" (p = 0.02) and "System ON, positive stimulation" (p < 0.001). fHIT scores changed from 19 to 44% (no stimulation) to maximum 75-94% (System ON, positive stimulation). CONCLUSION: The vestibular implant seems capable of improving the high-frequency DVA. This functional benefit of the vestibular implant illustrates again the feasibility of this device for clinical use in the near future.

Cervical myogenic potentials and controlled postural responses elicited by a prototype vestibular implant.

Gaze stabilization and postural control are two key functions of the vestibular system. In consequence, oscillopsia and chronic imbalance are the two main complaints of patients presenting with a severe bilateral vestibular function loss. The vestibular implant is emerging as a promising treatment for this group of patients whose quality of life is significantly impaired. Although the final aim of the vestibular implant should be to restore vestibular function as a whole, until now the research has focused mainly on the restoration of the vestibulo-ocular reflex to improve gaze stabilization. In this study, we aimed to explore whether the vestibulo-collic and vestibulo-spinal pathways could be activated and controlled with the electrical stimuli provided by our vestibular implant prototype. This was first explored and demonstrated with recordings of electrically elicited cervical vestibular evoked myogenic potentials (ecVEMPs). ecVEMPs with characteristics similar to the classical acoustically elicited cervical vestibular evoked myogenic potentials (cVEMPs) were successfully evoked in five out of the eight tested patients. Amplitudes of the electrically elicited N-P complex varied, ranging from 44 to 120 µV. Mean latencies of the N and P waves were of 9.71(± 1.17) ms and 17.24 ms (± 1.74), respectively. We also evaluated the possibility of generating controlled postural responses using a stepping test. Here, we showed that controlled and consistent whole-body postural responses can be effectively obtained with rapid changes in the "baseline" (constant rate and amplitude) electrical activity delivered by the vestibular implant in two out of the three tested subjects. Furthermore, obtained amplitude of body rotations was significantly correlated with the intensity of stimulation and direction of body rotations correlated with the side of the delivered stimulus (implanted side). Altogether, these data suggest that the vestibular implant could also be used to improve postural control in patients with bilateral vestibulopathy.

A New and Faster Test to Assess Vestibular Perception.

Objective: Clinical vestibular testing mainly consists of testing reflexes, but does not routinely include testing for perceptual symptoms. The objective of this study was to investigate a new and faster test for vestibular perception, and to compare its results with previous studies. Methods: Fifty-five healthy subjects with no prior vestibular complaints were included and divided into three age groups. Vestibular perceptual thresholds were measured using a hydraulic platform in the dark. The platform delivered 12 different movements: six translations (forward, backward, right, left, up, and down) and six rotations/tilt (yaw left, yaw right, pitch forward, pitch backward, roll left, and roll right). The subject had to report the correct type and direction of movements. Thresholds were determined by a double confirmation of the lowest threshold. General trends in thresholds like relative interrelationship and the influence of age were analyzed and compared with values reported previously. Results: Mean thresholds of age groups ranged between 0.092 and 0.221 m/s2 for translations, and between 0.188 and 2.255°/s2 for rotations. The absolute values differed from previous reports, but the relative interrelationship of thresholds between type and direction of motion remained. An association between age and vestibular thresholds was found, similar to previous reports. Conclusion: This new and faster test for vestibular perception showed comparable patterns in perceptual thresholds when compared to more research oriented, lengthy tests. This might pave the way for establishing vestibular perception testing protocols useful for the clinic.

Drafting a Surgical Procedure Using a Computational Anatomy Driven Approach for Precise, Robust, and Safe Vestibular Neuroprosthesis Placement-When One Size Does Not Fit All.

OBJECTIVE: To design and evaluate a new vestibular implant and surgical procedure that should reach correct electrode placement in 95% of patients in silico. DESIGN: Computational anatomy driven implant and surgery design study. SETTING: Tertiary referral center. PARTICIPANTS: The population comprised 81 patients that had undergone a CT scan of the Mastoid region in the Maastricht University Medical Center. The population was subdivided in a vestibular implant eligible group (28) and a control group (53) without known vestibular loss. INTERVENTIONS: Canal lengths and relationships between landmarks were calculated for every patient. The relationships in group-anatomy were used to model a fenestration site on all three semicircular canals. Each patient's simulated individual distance from the fenestration site to the ampulla was calculated and compared with the populations average to determine if placement would be successful. MAIN OUTCOME MEASURES: Lengths of the semicircular canals, distances from fenestration site to ampulla (intralabyrinthine electrode length), and rate of successful electrode placement (robustness). RESULTS: The canal lengths for the lateral, posterior, and superior canal were respectively 12.1 mm ±â€Š1.07, 18.8 mm ±â€Š1.62, and 17.5 mm ±â€Š1.23, the distances from electrode fenestration site to the ampulla were respectively 3.73 mm ±â€Š0.53, 9.02 mm ±â€Š0.90, and 5.31 mm ±â€Š0.73 and electrode insertions were successful for each respective semicircular canal in 92.6%, 66.7%, and 86.4% of insertions in silico. The implant electrode was subsequently revised to include two more electrodes per lead, resulting in a robustness of 100%. CONCLUSIONS: The computational anatomy approach can be used to design and test surgical procedures. With small changes in electrode design, the proposed surgical procedure's target robustness was reached.

Milestones in the development of a vestibular implant.

PURPOSE OF REVIEW: Bilateral vestibular deficits exist and their prevalence is more important than believed by the medical community. Their severe impact has inspired several teams to develop technical solutions in an attempt to rehabilitate patients. A particularly promising pathway is the vestibular implant. This article describes the main milestones in this field, mainly focusing on work conducted in human patients. RECENT FINDINGS: There have been substantial research efforts, first in animals and more recently in humans, toward the development of vestibular implants. Humans have demonstrated surprising adaptation capabilities to the artificial vestibular signal. Today, the possibility of restoring vestibular reflexes, particularly the vestibulo-ocular reflex, and even achieving useful function in close-to-reality tasks (i.e. improving visual abilities while walking) have been demonstrated in humans. SUMMARY: The vestibular implant opens new perspectives, not only as an effective therapeutic tool, but also pushes us to go beyond current knowledge and well-established clinical concepts.

[A crazy patient or an additional weird experience vestibular in origin ?] / Une histoire de fou ou encore un trouble bizarre d'origine vestibulaire ?

We present a patient suffering from persistence of images after cessation of the visual stimulus, a phenomenon called palinopsia. As none of classical causes existed in this patient, we hypothethized that the phenomenon is related to the particular dysfunction of his right inner ear associating a canalar deficit with a preserved otolithic function. In such a situation, the vestibular inputs are slower than normal. Therefore, palinopsia could result from an abnormal temporal integration of visual and vestibular informations.

Nous présentons un patient souffrant de la persistance des images après la cessation du stimulus visuel, un phénomène appelé « palinopsie ¼. Comme aucune des causes classiques n'existait chez ce patient, nous avons émis l'hypothèse que le phénomène soit lié au dysfonctionnement particulier de son oreille interne droite associant un déficit canalaire à une fonction otolithique préservée. Dans une telle situation, les entrées vestibulaires sont plus lentes que la normale. Par conséquent, les épisodes de palinopsie pourraient résulter d'une intégration temporelle anormale des informations visuelles et vestibulaires.

Palinopsia Following Acute Unilateral Partial Vestibular Deafferentation: A Case Report.

Palinopsia is defined as the persistence or reappearance of images after cessation of the visual stimulus. One patient presented episodes of palinopsia after the functional loss of the 3 semicircular canals of the right ear while the otolithic function was preserved. None of classical causes was identified in this patient, intoxications, brain tumors, migraines, psychiatric disorders, etc. For a movement to be perceived as a single event, central processes of temporal integration are necessary to correct the shift between the rapid vestibular information, and the slow visual information. However, it has been shown on animal models that vestibular inputs are slower than normal in case of peripheral deafferentation limited to the canalar function with preservation of the otolithic function, which is the case in this patient. Therefore, we hypothesize that episodes of palinopsia he presents result from the fact that temporal integration processes do not take into account the slower than normal vestibular information due to the peripheral disorder and continue to slow it down. Thus, the patient keeps the visual image in memory until the late arrival of the vestibular information.

European Position Statement on Diagnosis, and Treatment of Meniere's Disease.

Meniere Disease keeps challenges in its diagnosis and treatment since was defined by Prosper Meniere at the beginning of 19th Century. Several classifications and definition were made until now and speculations still exist on its etiology. As the etiology remains speculative the treatment models remain in discussion also. The European Academy of Otology and Neurotology Vertigo Guidelines Study Group intended to work on the diagnosis and treatment of Meniere's disease and created the European Positional Statement Document also by resuming the consensus studies on it. The new techniques on diagnosis are emphasized as well as the treatment models for each stage of the disease are clarified by disregarding the dilemmas on its treatment. The conservative, noninvasive and invasive therapeutic models are highlighted.

Optimization of 3D-Visualization of Micro-Anatomical Structures of the Human Inner Ear in Osmium Tetroxide Contrast Enhanced Micro-CT Scans.

Introduction: Knowledge of the neuro-anatomical architecture of the inner ear contributes to the improvement and development of cochlear and vestibular implants. The present knowledge is mainly based on two-dimensional images (histology) or derived models that simplify the complexity of this architecture. This study investigated the feasibility of visualizing relevant neuro-anatomical structures of the inner ear in a dynamic three-dimensional reproduction, using a combination of staining, micro-CT imaging and an image processing algorithm. Methods: Four fresh cadaveric temporal bones were postfixed with osmium tetroxide (OsO4) and decalcified with EDTA. Micro-CT was used for scanning at 10 µm (4 scans) and 5.5 µm (1 scan) voxel resolution. A new image processing algorithm was developed and the scans were visualized in open source software. Results: OsO4 enhanced the contrast in all scans and the visualization was substantially improved by the image processing algorithm. The three-dimensional renderings provided detailed visualization of the whole inner ear. Details were visible up to the size of individual neurons, nerve crossings and the specific neuro-anatomical structures such as the tunnel of Corti. Conclusion: The combination of OsO4, micro-CT and the proposed image processing algorithm provides an accurate and detailed visualization of the three-dimensional micro-anatomy of the human inner ear.

Full Spectrum of Reported Symptoms of Bilateral Vestibulopathy Needs Further Investigation-A Systematic Review.

OBJECTIVE: To systematically review the symptoms reported by patients with bilateral vestibulopathy (BV) in clinical studies and case reports. This would serve as the first step in establishing a validated patient-reported outcome measures (PROM) for BV. METHODS: A search on symptoms reported by patients with BV was performed in PubMed, and all publications covering these symptoms were included. Exclusion criteria comprised reviews and insufficient details about the frequency of occurrence of symptoms. RESULTS: 1,442 articles were retrieved. 88 studies were included (41 clinical studies, 47 case reports). In consensus, 68 descriptions of symptoms were classified into 6 common and generic symptoms. Frequency of symptoms in clinical studies and case reports were reviewed, respectively; imbalance (91 and 86%), chronic dizziness (58 and 62%), oscillopsia (50 and 70%), and recurrent vertigo (33 and 67%). BV could be accompanied by hearing loss (33 and 43%) and tinnitus (15 and 36%). 15 clinical studies and 10 case reports reported symptoms beyond vestibular and hearing deficits such as limited social activities, depression, concentration, and memory impairment and reduced quality of life in general. CONCLUSION: The literature on BV symptomatology mainly focuses on classic symptoms such as imbalance and oscillopsia, while only few report additional symptoms such as cognitive memory impairment and performing dual tasks. In fact, none of the reviewed clinical studies and case reports provided a comprehensive overview of BV symptoms. To develop a validated PROM, qualitative research using semi-structured and unstructured interviews is needed to explore the full spectrum of BV symptoms.

Characterization of Cochlear, Vestibular and Cochlear-Vestibular Electrically Evoked Compound Action Potentials in Patients with a Vestibulo-Cochlear Implant.

The peripheral vestibular system is critical for the execution of activities of daily life as it provides movement and orientation information to motor and sensory systems. Patients with bilateral vestibular hypofunction experience a significant decrease in quality of life and have currently no viable treatment option. Vestibular implants could eventually restore vestibular function. Most vestibular implant prototypes to date are modified cochlear implants to fast-track development. These use various objective measurements, such as the electrically evoked compound action potential (eCAP), to supplement behavioral information. We investigated whether eCAPs could be recorded in patients with a vestibulo-cochlear implant. Specifically, eCAPs were successfully recorded for cochlear and vestibular setups, as well as for mixed cochlear-vestibular setups. Similarities and slight differences were found for the recordings of the three setups. These findings demonstrated the feasibility of eCAP recording with a vestibulo-cochlear implant. They could be used in the short term to reduce current spread and avoid activation of non-targeted neurons. More research is warranted to better understand the neural origin of vestibular eCAPs and to utilize them for clinical applications.

The Video Head Impulse Test to Assess the Efficacy of Vestibular Implants in Humans.

The purpose of this study was to evaluate whether it is possible to restore the high-frequency angular vestibulo-ocular reflex (aVOR) in patients suffering from a severe bilateral vestibulopathy (BV) and implanted with a vestibular implant prototype. Three patients (S1-3) participated in the study. They received a prototype vestibular implant with one to three electrode branches implanted in the proximity of the ampullary branches of the vestibular nerve. Five electrodes were available for electrical stimulation: one implanted in proximity of the left posterior ampullary nerve in S1, one in the left lateral and another one in the superior ampullary nerves in S2, and one in the right lateral and another one in the superior ampullary nerves in S3. The high-frequency aVOR was assessed using the video head impulse test (EyeSeeCam; EyeSeeTec, Munich, Germany), while motion-modulated electrical stimulation was delivered via one of the implanted vestibular electrodes at a time. aVOR gains were compared to control measurements obtained in the same patients when the device was not activated. In three out of the five tested electrodes the aVOR gain increased monotonically with increased stimulation strength when head impulses were delivered in the plane of the implanted canal. In these cases, gains ranging from 0.4 to values above 1 were measured. A "reversed" aVOR could also be generated when inversed stimulation paradigms were used. In most cases, the gain for excitatory head impulses was superior to that recorded for inhibitory head impulses, consistent with unilateral vestibular stimulation. Improvements of aVOR gain were generally accompanied by a concomitant decrease of corrective saccades, providing additional evidence of an effective aVOR. High inter-electrode and inter-subject variability were observed. These results, together with previous research, demonstrate that it is possible to restore the aVOR in a broad frequency range using motion-modulated electrical stimulation of the vestibular afferents. This provides additional encouraging evidence of the possibility of achieving a useful rehabilitation alternative for patients with BV in the near future.

[Equilibrium management]. / Gestion de l'équilibre.

Balance requires the modulation and integration of multiple sensory information, among which the vestibular apparatus of the inner ear plays an essential role. The management of all informations is assumed by a system whose adaptive capacities are much faster than we thought until recently, as demonstrated by the experiments carried out in human during the development of a vestibular implant designed to restore the lost function. While these adaptive capacities have the advantage of allowing all kinds of activities, they also have the disadvantage of producing various sensations, sometimes very strange. Enormous progress has been made recently in the investigation of vestibular disorders. However, given the complexity of the system, it must be admitted that many elements remain to be discovered. In the meantime, let us avoid considering the 'bizarre' phenomena that some patients report as the expression of a psychological disorder !

L'équilibre nécessite la mise en jeu de multiples informations sensorielles parmi lesquelles l'appareil vestibulaire de l'oreille interne joue un rôle essentiel. La gestion de toutes les informations est assumée par un système dont les capacités d'adaptation sont encore beaucoup plus rapides qu'on ne pouvait le penser, comme le démontrent les expériences menées chez l'homme au cours du développement d'un implant vestibulaire destiné à restituer la fonction perdue. Si ces capacités d'adaptation ont l'avantage de permettre toutes sortes d'activités, elles ont aussi l'inconvénient de produire diverses sensations, parfois très étranges. D'énormes progrès ont été réalisés récemment dans l'investigation des troubles vestibulaires. Toutefois, vu la complexité du système, il faut bien admettre que bien des éléments restent à découvrir. D'ici là, évitons de considérer les phénomènes « bizarres ¼ que rapportent quelques patients comme l'expression d'une affection psychologique !

The vestibular implant: A probe in orbit around the human balance system.

The primary goal of the vestibular implant is to restore the vestibular function in patients with a disabling bilateral vestibular loss for whom there is currently no available treatment. The prototype developed by our team is a hybrid system consisting of a modified cochlear implant incorporating additional vestibular electrodes. Therefore, in addition of delivering sound information it is also capable of delivering motion information to the central nervous system using electrical stimulation. To date, thirteen patients have been implanted with such vestibular implant prototypes. For ethical reasons, only deaf ears were implanted and all patients experienced a clinical benefit from the hearing rehabilitation. The recent demonstration of partial restoration of the vestibulo-ocular and the vestibulo-collic reflexes in implanted patients suggests that gaze stabilization and postural control, fundamental functions of the balance system, can be artificially restored using a vestibular implant. This allows us to glimpse a useful clinical application in a near future. In parallel, we show how the vestibular implant provides a unique opportunity to explore the integration of the vestibular sensory input into the multisensory, multimodal balance system in humans, since it is able to selectively stimulate the vestibular system.