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.

[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.

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.

[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 !

Oscillatory neural responses evoked by natural vestibular stimuli in humans.

While there have been numerous studies of the vestibular system in mammals, less is known about the brain mechanisms of vestibular processing in humans. In particular, of the studies that have been carried out in humans over the last 30 years, none has investigated how vestibular stimulation (VS) affects cortical oscillations. Here we recorded high-density electroencephalography (EEG) in healthy human subjects and a group of bilateral vestibular loss patients (BVPs) undergoing transient and constant-velocity passive whole body yaw rotations, focusing our analyses on the modulation of cortical oscillations in response to natural VS. The present approach overcame significant technical challenges associated with combining natural VS with human electrophysiology and reveals that both transient and constant-velocity VS are associated with a prominent suppression of alpha power (8-13 Hz). Alpha band suppression was localized over bilateral temporo-parietal scalp regions, and these alpha modulations were significantly smaller in BVPs. We propose that suppression of oscillations in the alpha band over temporo-parietal scalp regions reflects cortical vestibular processing, potentially comparable with alpha and mu oscillations in the visual and sensorimotor systems, respectively, opening the door to the investigation of human cortical processing under various experimental conditions during natural VS.

[Spatial navigation : brief overview of the medicine and physiology Nobel prize 2014]. / Navigation spatiale : bref aperçu des travaux lauréats du prix Nobel de médecine et physiologie 2014.

Various cells of the thalamus, hippocampus, and the medial entorhinal cortex plays a crucial role in spatial navigation ability. The highlighting of these cells and the understanding of their functioning by John O'Keefe, May-Britt and Edvard Moser have earned them the Nobel Prize for Medicine and Physiology in 2014. The vision, olfaction, and the vestibular system contribute to this complex system. These observations may well explain why patients with vestibular disorder complain of spatial disorientation, often a source of deep anxiety.

Diverses cellules du thalamus, de l'hippocampe et du cortex entorhinal médial jouent un rôle crucial dans la capacité de navigation spatiale. La mise en évidence de ces cellules et la compréhension de leur fonctionnement par J. O'Keefe, M.-B. et E. Moser leur ont valu le prix Nobel de médecine et physiologie en 2014. La vision, l'olfaction et le système vestibulaire concourent à ce système complexe. Ces observations peuvent parfaitement expliquer pourquoi des patients souffrant d'un trouble vestibulaire se plaignent de désorientation spatiale, souvent source d'une profonde angoisse.

[Update on the evaluation and management of dizziness in older people]. / Prise en charge des vertiges chez la personne âgée.

This article provides an update on the evaluation and management of dizziness in older people. It is based on a recent literature review. Indeed, it is a frequent reason to consult a general practitioner. Its clinical presentation is not very specific and its treatment is often challenging. Although dizziness is often benign it can have serious physical, functional and psychological consequences. Thanks to a careful medical history and simple clinical examination tools, general practitioners can make a correct diagnosis and provide early multidisciplinary care that can greatly improve the quality of life of elderly people who suffer from dizziness.

L'objectif de cet article est de faire le point sur la prise en charge des vertiges chez la personne âgée, en se basant sur une synthèse de la littérature récente. Il s'agit en effet d'un motif de consultation fréquent en médecine générale, avec une clinique peu spécifique et qui reste difficile à traiter. Le vertige périphérique, bien que pathologie bénigne, peut avoir des répercussions fonctionnelles invalidantes, tant sur le plan physique que psychique. Grâce à une anamnèse précise et des outils relativement simples d'examen clinique, le médecin de premier recours pourra le plus souvent aboutir à un diagnostic adéquat et une prise en charge précoce multidisciplinaire permettra d'améliorer grandement la qualité de vie des patients âgés souffrant de vertiges.

[Vestibular and visual stimulation : simultaneous perception or not ?] / Stimulation vestibulaire et visuelle : perception simultanée ou pas ?

The human brain is able to consider that two sensory stimuli are synchronous while they activate the cortex with some delay because they follow different neurological pathways. This process is only possible if the time interval between the two stimuli does not exceed a certain limit, called "Temporal Binding Window" (TBW). Studies of this parameter, involving the vestibular perception, are difficult because subjects must be moved, which generates parasitic proprioceptive information. By cons, in patients equipped with a vestibular implant, it is possible to generate a vestibular perception selectively by electrical stimulation of the vestibular nerve. These patients are therefore an unique model to study the TBW between visual and vestibular perception.

Le cerveau humain est capable de considérer que deux stimuli sensoriels sont synchrones alors qu'ils activent le cortex avec un décalage temporel dû au fait qu'ils suivent des voies neurologiques différentes. Ce processus n'est possible que si l'intervalle de temps entre les deux stimuli ne dépasse pas un certain délai, qu'on appelle « Temporal Binding Window ¼ (TBW). Etudier ce paramètre en mettant en jeu la perception vestibulaire est difficile puisqu'il faut bouger le sujet et donc générer aussi des informations proprioceptives. Par contre, chez les patients porteurs d'un implant vestibulaire, il est possible de délivrer une perception vestibulaire de façon sélective par stimulation électrique du nerf vestibulaire. Ces patients représentent donc un modèle unique pour étudier le TBW entre les perceptions visuelle et vestibulaire.

Difficulties Faced by Patients Suffering from Total Bilateral Vestibular Loss.

A unilateral sudden loss of function generates intense and frightening symptoms urging patients to see a doctor. Generally, the symptoms and signs of the deficit are so obvious that doctors make the diagnosis quickly. The situation is quite different if the deficit is gradual and affects both sides. To better understand the difficulties faced by patients suffering from total bilateral vestibular loss, 19 subjects were interviewed in a semistructured talk. The discussion focused on five main topics: (1) symptoms, (2) the medical trajectory from the earliest symptoms to the diagnosis, (3) the prescribed treatments, (4) the impact of the disease on work, and (5) the impact on social functioning and recreational activities. The symptoms reported by patients are insidious, and they may suggest a neurological deficit or a cardiocirculatory or psychiatric disorder. The diagnosis is often made after several consultations with several doctors from different specialties. When the diagnosis is made, all kinds of treatment are undertaken, in particular vestibular rehabilitation. Indeed, most physicians believe that it can promote central compensation processes, even though it has been demonstrated that vestibular exercises are ineffective in most of these patients. Two thirds of our subjects were obliged to modify or even stop their professional activities due the bilateral vestibular loss. In some patients, the disability is such that they almost constantly require the presence of their spouse. In conclusion, the symptoms of bilateral vestibular loss are sometimes misleading. They are often not recognized by doctors. The deficit has an obvious impact on patients' social functioning and professional activities.

Perception of Discomfort Caused by a Unilateral Hearing Loss in People Suffering from a Total Bilateral Vestibular Loss.

The quality of life of patients suffering from a bilateral vestibular loss is severely altered. Patients mainly complain of oscillopsia, imbalance, and spatial disorientation. Up to now, there is no efficient treatment. Some teams around the world are working on the development of a vestibular implant for the restoration of the vestibular function based on the concept similar to that of a cochlear implant, stimulating the neural vestibular pathways through electrical pulses. There are different potential stimulation sites of the vestibular system, all raising the major concern about a potential hearing loss in the implanted ear. As this implant does not exist yet, patients cannot be informed of the risk of hearing loss due to the surgical intervention versus the benefits brought by the vestibular prosthesis. In order to better inform future vestibular implant candidates, we need to evaluate the handicap of patients with an actual unilateral hearing loss, and to compare it to the way that patients suffering from a bilateral vestibular loss perceive a potential unilateral hearing loss. For this, we used the HHIA questionnaire (Hearing Handicap Inventory for Adults) on 3 groups of participants, i.e. patients with a unilateral hearing loss, patients suffering from a bilateral vestibular loss but having normal hearing, and healthy subjects. The scores reported by patients with a unilateral hearing loss were much lower than those of the other 2 groups, indicating that people whose hearing is normal overstate the disability related to a unilateral hearing loss. Patients to whom a vestibular implant is proposed in order to correct their balance disorders may use this information to decide whether or not to choose an operation.

Vestibular Implants: 8 Years of Experience with Electrical Stimulation of the Vestibular Nerve in 11 Patients with Bilateral Vestibular Loss.

BACKGROUND: The concept of the vestibular implant is primarily to artificially restore the vestibular function in patients with a bilateral vestibular loss (BVL) by providing the central nervous system with motion information using electrical stimulation of the vestibular nerve. Our group initiated human trials about 10 years ago. METHODS: Between 2007 and 2013, 11 patients with a BVL received a vestibular implant prototype providing electrodes to stimulate the ampullary branches of the vestibular nerve. Eye movements were recorded and analyzed to assess the effects of the electrical stimulation. Perception induced by electrical stimulation was documented. RESULTS: Smooth, controlled eye movements were obtained in all patients showing that electrical stimulation successfully activated the vestibulo-ocular pathway. However, both the electrical dynamic range and the amplitude of the eye movements were variable from patient to patient. The axis of the response was consistent with the stimulated nerve branch in 17 out of the 24 tested electrodes. Furthermore, in at least 1 case, the elicited eye movements showed characteristics similar to those of compensatory eye movements observed during natural activities such as walking. Finally, diverse percepts were reported upon electrical stimulation (i.e., rotatory sensations, sound, tickling or pressure) with intensity increasing as the stimulation current increased. CONCLUSIONS: These results demonstrate that electrical stimulation is a safe and effective means to activate the vestibular system, even in a heterogeneous patient population with very different etiologies and disease durations. Successful tuning of this information could turn this vestibular implant prototype into a successful artificial balance organ.

Quality of life of patients with bilateral vestibulopathy.

OBJECTIVES: Currently, there is no evidence of an effective treatment for patients with bilateral vestibulopathy (BV). Their main complaints are oscillopsia and imbalance. Opinions about the impact of BV on their quality of life are controversial, and their handicap is not always recognized, even among otoneurologists. The aim of this study was to objectively assess the health status of BV patients in order to evaluate the need for pursuing efforts toward the development of new treatments. METHODS: The short-form health survey (SF-36), the dizziness handicap inventory (DHI), the short falls efficacy scale-international (short FES-I), and an oscillopsia severity questionnaire were submitted to 39 BV patients. The SF-36 scores were compared to the scores of a general Dutch population. The DHI scores were correlated to the oscillopsia severity scores. The short FES-I scores were compared to scores in an elderly population. Residual otolithic function was correlated to all scores, and hearing to SF-36 scores. RESULTS: Compared to the general Dutch population, the BV patients scored significantly worse on the "physical functioning", "role physical", "general health", "vitality", and "social functioning" SF-36 variables (p < 0.05). The DHI scores were strongly correlated with the oscillopsia severity scores (r = 0.75; p < 0.000001). The short FES-I scores indicated a slight to moderate increase in the patients' fear of falling. No significant score differences were found between BV patients with residual otolithic function and patients with complete BV. There was no correlation between hearing status and SF-36 scores. CONCLUSIONS: The results correlate with our clinical impression that BV has a strong negative impact on physical and social functioning, leading to a quality-of-life deterioration. There is a clear need for a therapeutic solution. Efforts toward the development of a vestibular implant are justified.

APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa.

The bone marrow constitutes a favorable environment for long-lived antibody-secreting plasma cells, providing blood-circulating antibody. Plasma cells are also present in mucosa-associated lymphoid tissue (MALT) to mediate local frontline immunity, but how plasma cell survival there is regulated is not known. Here we report that a proliferation-inducing ligand (APRIL) promoted survival of human upper and lower MALT plasma cells by upregulating expression of the antiapoptotic proteins bcl-2, bcl-xL, and mcl-1. The in situ localization of APRIL was consistent with such a prosurvival role in MALT. In upper MALT, tonsillar epithelium produced APRIL. Upon infection, APRIL production increased considerably when APRIL-secreting neutrophils recruited from the blood infiltrated the crypt epithelium. Heparan sulfate proteoglycans (HSPGs) retained secreted APRIL in the subepithelium of the infected zone to create APRIL-rich niches, wherein IgG-producing plasma cells accumulated. In lower MALT, neutrophils were the unique source of APRIL, giving rise to similar niches for IgA-producing plasmocytes in villi of lamina propria. Furthermore, we found that mucosal humoral immunity in APRIL-deficient mice is less persistent than in WT mice. Hence, production of APRIL by inflammation-recruited neutrophils may create plasma cell niches in MALT to sustain a local antibody production.

Mental transformation abilities in patients with unilateral and bilateral vestibular loss.

Vestibular information helps to establish a reliable gravitational frame of reference and contributes to the adequate perception of the location of one's own body in space. This information is likely to be required in spatial cognitive tasks. Indeed, previous studies suggest that the processing of vestibular information is involved in mental transformation tasks in healthy participants. In this study, we investigate whether patients with bilateral or unilateral vestibular loss show impaired ability to mentally transform images of bodies and body parts compared to a healthy, age-matched control group. An egocentric and an object-based mental transformation task were used. Moreover, spatial perception was assessed using a computerized version of the subjective visual vertical and the rod and frame test. Participants with bilateral vestibular loss showed impaired performance in mental transformation, especially in egocentric mental transformation, compared to participants with unilateral vestibular lesions and the control group. Performance of participants with unilateral vestibular lesions and the control group are comparable, and no differences were found between right- and left-sided labyrinthectomized patients. A control task showed no differences between the three groups. The findings from this study substantiate that central vestibular processes are involved in imagined spatial body transformations; but interestingly, only participants with bilateral vestibular loss are affected, whereas unilateral vestibular loss does not lead to a decline in spatial imagery.

Adaptation to steady-state electrical stimulation of the vestibular system in humans.

OBJECTIVES: Efforts are being made toward the development of a vestibular implant. If such a device is to mimic the physiology of the vestibular system, it must first be capable of restoring a baseline or "rest" activity in the vestibular pathways and then modulating it according to the direction and velocity of head movements. The aim of this study was to assess whether a human subject could adapt to continuous electrical stimulation of the vestibular system, and whether it was possible to elicit artificial smooth oscillatory eye movements via modulation of the stimulation. METHODS: One bilaterally deaf patient with bilateral vestibular loss received a custom-modified Med-E1 cochlear implant in which one electrode was implanted in the vicinity of the left posterior ampullary nerve. This electrode was activated with biphasic pulse trains of 400-micros phase duration delivered at a repetition rate of 200 pulses per second. The resulting eye movements were recorded with 2-dimensional binocular video-oculography. RESULTS: Successive "on-off" cycles of continuous electrical stimulation resulted in a progressively shorter duration of the nystagmic response. Once the adapted state was reached upon constant stimulation, amplitude or frequency modulations of electrical stimulation produced smooth oscillatory conjugated eye movements. CONCLUSIONS: Although this is a case study of one patient, the results suggest that humans can adapt to electrical stimulation of the vestibular system without too much discomfort. Once the subject is in the adapted state, the electrical stimulation can be modulated to artificially elicit smooth eye movements. Therefore, the major prerequisites for the feasibility of a vestibular implant for human use are fulfilled.

Eye movements in response to electrical stimulation of the lateral and superior ampullary nerves.

OBJECTIVES: Recently, we demonstrated that it was possible to elicit vertical eye movements in response to electrical stimulation of the posterior ampullary nerve. In order to develop a vestibular implant, a second site of stimulation is required to encode the horizontal movements. METHODS: Three patients with disabling Meniere's disease were included in the study. Before a labyrinthectomy via a standard transcanal approach was performed, their lateral and anterior ampullary nerves were surgically exposed under local anesthesia through a procedure we recently developed. The attic was opened, the incus and malleus head were removed, and a small well was drilled above the horizontal portion of the facial nerve canal to place an electrode. This electrode was used to deliver balanced biphasic trains of electrical pulses. RESULTS: The electrical stimuli elicited mainly horizontal nystagmus without simultaneous stimulation of the facial nerve. CONCLUSIONS: It is possible to stimulate electrically the lateral and superior ampullary nerves without simultaneous stimulation of the facial nerve. Because the nerves run close to each other, electrical stimulation provoked eye movements that were not purely horizontal, but also had some vertical components. Nevertheless, this site can be used to encode horizontal movements, because central adaptation may correct unnatural afferent vestibular cues delivered by a prosthetic sensor. The range of stimulus intensities that produced a response was broad enough for us to envision the possibility of encoding eye movements of various speeds.