Innovative approaches for managing patients with chronic vestibular disorders: follow-up indicators and predictive markers for studying the vestibular error signal.

Introduction: Despite significant advancements in understanding the biochemical, anatomical, and functional impacts of vestibular lesions, developing standardized and effective rehabilitation strategies for patients unresponsive to conventional therapies remains a challenge. Chronic vestibular disorders, characterized by permanent or recurrent imbalances and blurred vision or oscillopsia, present significant complexity in non-pharmacological management. The complex interaction between peripheral vestibular damage and its impact on the central nervous system (CNS) raises questions about neuroplasticity and vestibular compensation capacity. Although fundamental research has examined the consequences of lesions on the vestibular system, the effect of a chronic peripheral vestibular error signal (VES) on the CNS remains underexplored. The VES refers to the discrepancy between sensory expectations and perceptions of the vestibular system has been clarified through recent engineering studies. This deeper understanding of VES is crucial not only for vestibular physiology and pathology but also for designing effective measures and methods of vestibular rehabilitation, shedding light on the importance of compensation mechanisms and sensory integration. Methods: This retrospective study, targeting patients with chronic unilateral peripheral vestibulopathy unresponsive to standard treatments, sought to exclude any interference from pre-existing conditions. Participants were evaluated before and after a integrative vestibular exploratory and rehabilitation program through questionnaires, posturographic tests, and videonystagmography. Results: The results indicate significant improvements in postural stability and quality of life, demonstrating positive modulation of the CNS and an improvement of vestibular compensation. Discussion: Successful vestibular rehabilitation likely requires a multifaceted approach that incorporates the latest insights into neuroplasticity and sensory integration, tailored to the specific needs and clinical progression of each patient. Focusing on compensating for the VES and enhancing sensory-perceptual-motor integration, this approach aims not just to tailor interventions but also to reinforce coherence among the vestibular, visual, and neurological systems, thereby improving the quality of life for individuals with chronic vestibular disorders.

Prevalence of vestibular disease in France: analysis of prescription data from a national health insurance database.

Vestibular problems are frequent reasons for primary care consultations. However, there is considerable uncertainty about the prevalence and cost of vestibular disorders. Despite ambiguous effectiveness data, the histamine analogue betahistine is widely and almost exclusively used for treatment of vertigo. Prescription of betahistine can, therefore, be used as a proxy estimate for prevalence. We used openly available claims data from the French health insurance data warehouse, defining annual prevalence of vestibular disease as the number of people who received at least one betahistine prescription that year. Dosage and pack size of each prescribed formulation were extracted to calculate the sum of betahistine in mg and the Defined Daily Dose (DDD) for age and sex strata and in total. To estimate the relative impact of one landmark trial, the BEMED study, we compared prescriptions from the years 2014/2015 to prescriptions in 2019/2022. A total of 735,121 (2014), 694,705 (2015), 614,431 (2019), and 562,476 (2022) persons filled in a prescription of betahistine. Patients were predominantly older and female. Average amount dispensed per year and per person increased from 4422.54 mg during the pre-BEMED period to 4736.90 mg during the post-BEMED period. DDD decreased from 130 Mio per year in 2014/2015 to 116 Mio per year in 2019/2022. Total costs for betahistine decreased by 42% from 21,615,037 Euro in 2014 to 12,894,249 Euro in 2022. Vestibular disease is frequent in France and has a relevant impact on population health. Despite conflicting clinical evidence, betahistine continues to be prescribed widely in medical practice.

Histaminergic System and Vestibular Function in Normal and Pathological Conditions.

Most neurotransmitter systems are represented in the central and peripheral vestibular system and are thereby involved both in normal vestibular signal processing and the pathophysiology of vestibular disorders. However, there is a special relationship between the vestibular system and the histaminergic system. The purpose of this review is to document how the histaminergic system interferes with normal and pathological vestibular function. In particular, we will discuss neurobiological mechanisms such as neuroinflammation that involve histamine to modulate and allow restoration of balance function in the situation of a vestibular insult. These adaptive mechanisms represent targets of histaminergic pharmacological compounds capable of restoring vestibular function in pathological situations. The clinical use of drugs targeting the histaminergic system in various vestibular disorders is critically discussed.

Statistical Associations between Vestibular Pathologies and Hypothyroidism: A Retrospective Study.

The association between vestibular pathologies and thyroid hormone disorders has been known for several decades. However, very little information is available on the types of vestibular symptoms that may be affected by altered thyroid hormone levels. The aim of this study was to provide patient data in order to identify statistical associations between vestibular pathologies and thyroid hormone disorders. A retrospective review of the records of 422 patients seen for physiotherapy treatment of vertigo was carried out. Statistical analysis of the data was performed using logistic regression, providing Chi2 and Odds Ratio statistics. Our results show that hypothyroidism statistically significantly increases the expression of certain symptoms, such as vestibular instability and gait disorders, in vestibular pathologies such as Menière's disease or central vertigo. By analyzing patient data, our study provides new evidence of dependence between altered thyroid status and the expression of vestibular pathologies.

Cellular and Molecular Mechanisms of Vestibular Ageing.

While age-related auditory deficits and cochlear alterations are well described, those affecting the vestibular sensory organs and more broadly the central vestibular pathways are much less documented. Although there is inter-individual heterogeneity in the phenomenon of vestibular ageing, common tissue alterations, such as losses of sensory hair cells or primary and secondary neurons during the ageing process, can be noted. In this review, we document the cellular and molecular processes that occur during ageing in the peripheral and central vestibular system and relate them to the impact of age-related vestibular deficits based on current knowledge.

[Animal models of balance pathologies: New tools to study peripheral vestibulopathies]. / Les vestibulopathies périphériques - De nouveaux modèles d'étude.

The different types of peripheral vestibulopathies (PVs) or peripheral vestibular disorders (PVDs) are essentially diagnosed on the basis of their clinical expression. The heterogeneity of vestibular symptoms makes it difficult to stratify patients for therapeutic management. Animal models of PVs are a good mean to search for clinical evaluation criteria allowing to objectively analyze the kinetics of expression of the vertigo syndrome and to evaluate the benefits of therapeutic strategies, whether they are pharmacological or rehabilitative. The question of the predictability of these animal models is therefore crucial for the identification of behavioral and biological biomarkers that could then be used in the human clinic. In this review, we propose an overview of the different animal models of PVs, and discuss their relevance for the understanding of the underlying pathophysiological mechanisms and the development of new and more targeted therapeutic approaches.

Title: Les vestibulopathies périphériques - De nouveaux modèles d'étude. Abstract: Les vestibulopathies périphériques (VP) ou désordres vestibulaires périphériques (DVP) sont diagnostiqués surtout selon leur expression clinique, mais l'hétérogénéité des symptômes vestibulaires rend difficile la stratification des patients pour leur prise en charge thérapeutique. Les modèles animaux constituent un moyen d'identifier des critères d'évaluation clinique afin d'analyser la cinétique d'expression du syndrome vertigineux et d'évaluer les bénéfices des stratégies thérapeutiques, qu'elles soient pharmacologiques ou rééducatives. La question de la prédictibilité de ces modèles est donc cruciale pour l'identification de biomarqueurs comportementaux et biologiques qui pourraient être exploités en clinique. Dans cette revue, nous proposons un état des lieux des différents modèles animaux de VP, et discutons de leur pertinence pour la compréhension des mécanismes physiopathologiques impliqués et le développement de nouvelles approches thérapeutiques plus ciblées.

Identification of Follow-Up Markers for Rehabilitation Management in Patients with Vestibular Schwannoma.

This study delves into the absence of prognostic or predictive markers to guide rehabilitation in patients afflicted with vestibular schwannomas. The objective is to analyze the reweighting of subjective and instrumental indicators following surgery, at 7 days and 1 month postoperatively. This retrospective cohort encompasses 32 patients who underwent unilateral vestibular schwannoma surgery at the Marseille University Hospital between 2014 and 2019. Variations in 54 indicators and their adherence to available norms are calculated. After 1 month, one-third of patients do not regain the norm for all indicators. However, the rates of variation unveil specific responses linked to a preoperative error signal, stemming from years of tumor adaptation. This adaptation is reflected in a postoperative visual or proprioceptive preference for certain patients. Further studies are needed to clarify error signals according to lesion types. The approach based on variations in normative indicators appears relevant for post-surgical monitoring and physiotherapy.

Vestibular Disorders and Hormonal Dysregulations: State of the Art and Clinical Perspectives.

The interaction between endocrine and vestibular systems remains poorly documented so far, despite numerous observations in humans and animals revealing direct links between the two systems. For example, dizziness or vestibular instabilities often accompany the menstrual cycle and are highly associated with the pre-menopause period, while sex hormones, together with their specific receptors, are expressed at key places of the vestibular sensory network. Similarly, other hormones may be associated with vestibular disorders either as causal/inductive factors or as correlates of the pathology. This review was carried out according to the PRISMA method, covering the last two decades and using the MEDLINE and COCHRANE databases in order to identify studies associating the terms vestibular system and/or vestibular pathologies and hormones. Our literature search identified 646 articles, 67 of which referred directly to vestibular dysfunction associated with hormonal variations. While we noted specific hormonal profiles depending on the pathology considered, very few clinical studies attempted to establish a direct link between the expression of the vestibular syndrome and the level of circulating hormones. This review also proposes different approaches to shed new light on the link between hormones and vestibular disorders, and to improve both the diagnosis and the therapeutic management of dizzy patients.

What Predictability for Animal Models of Peripheral Vestibular Disorders?

The different clinical entities grouped under the term peripheral vestibulopathies (PVs) or peripheral vestibular disorders (PVDs) are distinguished mainly based on their symptoms/clinical expression. Today, there are very few commonly accepted functional and biological biomarkers that can confirm or refute whether a vestibular disorder belongs to a precise classification. Consequently, there is currently a severe lack of reliable and commonly accepted clinical endpoints, either to precisely follow the course of the vertigo syndrome of vestibular origin or to assess the benefits of therapeutic approaches, whether they are pharmacological or re-educational. Animal models of PV are a good means to identify biomarkers that could subsequently be exploited in human clinical practice. The question of their predictability is therefore crucial. Ten years ago, we had already raised this question. We revisit this concept today in order to take into account the animal models of peripheral vestibular pathology that have emerged over the last decade, and the new technological approaches available for the behavioral assessment of vestibular syndrome in animals and its progression over time. The questions we address in this review are the following: are animal models of PV predictive of the different types and stages of vestibular pathologies, and if so, to what extent? Are the benefits of the pharmacological or reeducational therapeutic approaches achieved on these different models of PV (in particular the effects of attenuation of the acute vertigo, or acceleration of central compensation) predictive of those expected in the vertiginous patient, and if so, to what extent?

Vertigoheel improves central vestibular compensation after unilateral peripheral vestibulopathy in rats.

The aim of this study was to assess the effect of Vertigoheel on central vestibular compensation and cognitive deficits in rats subjected to peripheral vestibular loss. Young adult male Long Evans rats were subjected to bilateral vestibular insults through irreversible sequential ototoxic destructions of the vestibular sensory organs. Vestibular syndrome characteristics were monitored at several time points over days and weeks following the sequential insults, using a combination of behavioral assessment paradigms allowing appreciation of patterns of change in static and dynamic deficits, together with spatial navigation, learning, and memory processes. Vertigoheel administered intraperitoneally significantly improved maximum body velocity and not moving time relative to its vehicle control on days 2 and 3 and on day 2, respectively, after unilateral vestibular lesion (UVL). It also significantly improved postural control relative to its vehicle 1 day after UVL. Conversely, Vertigoheel did not display any significant effect vs. vehicle on the severity of the syndrome, nor on the time course of other examined parameters, such as distance moved, mean body velocity, meander, and rearing. Spatial cognition testing using Y- and T-maze and eight-radial arm maze did not show any statistically significant difference between Vertigoheel and vehicle groups. However, Vertigoheel potentially enhanced the speed of learning in sham animals. Evaluating Vertigoheel's effect on thigmotaxis during the open-field video tracking test revealed no significant difference between Vertigoheel and its vehicle control groups suggesting that Vertigoheel does not seem to induce sedative or anxiolytic effects that could negatively affect vestibular and memory function. Present observations reveal that Vertigoheel improves central vestibular compensation following the unilateral peripheral vestibular loss as demonstrated by improvement of specific symptoms.

Effect of Fluoxetine and Acacetin on Central Vestibular Compensation in an Animal Model of Unilateral Peripheral Vestibulopathy.

Damage to the peripheral vestibular system is known to generate a syndrome characterized by postural, locomotor, oculomotor, perceptual and cognitive deficits. Current pharmacological therapeutic solutions for these pathologies lack specificity and efficacy. Recently, we demonstrated that apamin, a specific SK channel blocker, significantly reduced posturo-locomotor and oculomotor deficits in the cat and the rat. The aim of the present study was to test the antivertigo potential of compounds belonging to the SK antagonists family, such as Acacetin and Fluoxetine. Young rats were subjected to unilateral ototoxic lesions of the vestibular organ using transtympanic administration of arsanilic acid (TTA) to evoke unilateral vestibular loss (UVL). Vestibular syndrome was monitored using behavioural evaluation allowing appreciation of the evolution of static and dynamic posturo-locomotor deficits. A significant effect of the TTA insult was only found on the distance moved, the mean body velocity and the not moving time. From day 2 to week 2 after TTA, the distance moved and the mean body velocity were significantly decreased, while the not moving time was significantly increased. Acacetin does not evoke any significant change in the vestibular posturo-locomotor parameters' kinetics. Administration of Fluoxetine two weeks before TTA and over three weeks after TTA (preventive group) does not evoke any significant change in the vestibular posturo-locomotor parameters' kinetics. Administration of Fluoxetine from three weeks after TTA significantly delayed the functional recovery. This study demonstrates that Acacetin or Fluoxetine in TTA vestibulo-injured rats does not bring any significant benefit on the posture and locomotor balance deficits.

Microglial Dynamics Modulate Vestibular Compensation in a Rodent Model of Vestibulopathy and Condition the Expression of Plasticity Mechanisms in the Deafferented Vestibular Nuclei.

Unilateral vestibular loss (UVL) induces a vestibular syndrome composed of posturo-locomotor, oculomotor, vegetative, and perceptivo-cognitive symptoms. With time, these functional deficits progressively disappear due to a phenomenon called vestibular compensation, known to be supported by the expression in the deafferented vestibular nuclei (VNs) of various adaptative plasticity mechanisms. UVL is known to induce a neuroinflammatory response within the VNs, thought to be caused by the structural alteration of primary vestibular afferents. The acute inflammatory response, expressed in the deafferented VNs was recently proven to be crucial for the expression of the endogenous plasticity supporting functional recovery. Neuroinflammation is supported by reactive microglial cells, known to have various phenotypes with adverse effects on brain tissue. Here, we used markers of pro-inflammatory and anti-inflammatory phenotypes of reactive microglia to study microglial dynamics following a unilateral vestibular neurectomy (UVN) in the adult rat. In addition, to highlight the role of acute inflammation in vestibular compensation and its underlying mechanisms, we enhanced the inflammatory state of the deafferented VNs using systemic injections of lipopolysaccharide (LPS) during the acute phase after a UVN. We observed that the UVN induced the expression of both M1 proinflammatory and M2 anti-inflammatory microglial phenotypes in the deafferented VNs. The acute LPS treatment exacerbated the inflammatory reaction and increased the M1 phenotype while decreasing M2 expression. These effects were associated with impaired postlesional plasticity in the deafferented VNs and exacerbated functional deficits. These results highlight the importance of a homeostatic inflammatory level in the expression of the adaptative plasticity mechanisms underlying vestibular compensation. Understanding the rules that govern neuroinflammation would provide therapeutic leads in neuropathologies associated with these processes.

Characterization of Thyroid Hormones Antivertigo Effects in a Rat Model of Excitotoxically-Induced Vestibulopathy.

Impaired vestibular function induces disabling symptoms such as postural imbalance, impaired locomotion, vestibulo-ocular reflex alteration, impaired cognitive functions such as spatial disorientation, and vegetative deficits. These symptoms show up in sudden attacks in patients with Ménière or neuritis and may lead to emergency hospitalizations. To date, however, there is no curative solution to these pathologies and the effectiveness of treatments used to reduce symptoms in the management of patients is discussed. Thus, elucidating the biological mechanisms correlated to the expression kinetics of the vestibular syndrome is useful for the development of potential therapeutic candidates with a view to relieving patients and limiting emergency hospitalizations. Recently, a robust antivertigo effect of thyroxine (T4) was demonstrated in a rodent model of impaired vestibular function induced by unilateral surgical section of the vestibular nerve. The aim of the present study was to assess thyroid hormones L-T4 and triiodothyronine (T3) as well as the bioactive thyroid hormone metabolite TRIAC on a rodent model of acute unilateral vestibulopathy more representative of clinical vestibular pathology. To this end, a partial and transient unilateral suppression of peripheral vestibular inputs was induced by an excitotoxic lesion caused by transtympanic injection of kainic acid (TTK) into the inner ear of adult rats. Vestibular syndrome and functional recovery were studied by semi-quantitative and quantitative assessments of relevant posturo-locomotor parameters. In contrast to the effect previously demonstrated in the complete and irreversible vestibular injury model, administration of thyroxine in the TTK rodent model did not display significant antivertigo effect. However, it is noteworthy that administration of thyroxine showed trends to prevent posturo-locomotor alterations. Furthermore, the results of the current study suggested that a single dose of thyroxine is sufficient to induce the same effects on vestibular syndrome observed with sub-chronic administration, and that reducing the T4 dose may more efficiently prevent the appearance of vestibular deficits induced by the excitotoxic type lesion. Finally, comparison of the antivertigo effect of T4 in different vestibulopathy models enables us to determine the therapeutic indication in which thyroxine could be a potential therapeutic candidate.

Hormones and Vestibular Disorders: The Quest for Biomarkers.

The vestibular system exerts control over various functions through neural pathways that are not yet fully mapped. Functional dysregulations or tissue lesions at different levels of the peripheral and the central vestibular networks can alter these different functions, causing a wide variety of symptoms, ranging from posturo-locomotor alterations to psychiatric syndromes such as PPPD, including the deregulation of the main biological functions. These different symptoms differ by their expression kinetics (they each appear and regress with their own kinetics) by the targets affected (muscles, organs, and brain areas) and by the sensitivity specific to each individual. Vestibular pathologies thus cover a mosaic of distinct effects, and they involve various effectors-which constitute the many markers of their different types and stages. It is therefore crucial, to predict the onset of a vertigo syndrome, to follow its temporal course, or to monitor the impact of therapeutic approaches, and to have specific and reliable biomarkers. Hormonal variations are among the possible sources of biomarkers for neurotology. We know that specific hormonal profiles can promote the appearance of vestibular disorders. We also know that the expression of vertigo syndrome is accompanied by measurable hormonal variations. The link between endocrine deregulation and vestibular alterations therefore no longer needs to be proven. However, there are still few data on their precise correlations with the vertigo syndrome. This study was undertaken with the aim to deliver an extensive review of the hormonal alterations linked to vestibular disorders. A review of the literature covering the last two decades was carried out using the MEDLINE and COCHRANE databases in order to identify studies associating the terms vestibular system or vestibular pathologies and hormones. Bibliographic data provides several outcomes in terms of therapeutic innovation in the diagnosis and therapeutic follow-up of vestibular pathologies.

A Perspective for Ménière's Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2.

Ménière's disease is a chronic illness characterized by intermittent episodes of vertigo associated with fluctuating sensorineural hearing loss, tinnitus and aural pressure. This pathology strongly correlates with a dilatation of the fluid compartment of the endolymph, so-called hydrops. Dexamethasone is one of the therapeutic approaches recommended when conventional antivertigo treatments have failed. Several mechanisms of actions have been hypothesized for the mode of action of dexamethasone, such as the anti-inflammatory effect or as a regulator of inner ear water homeostasis. However, none of them have been experimentally confirmed so far. Aquaporins (AQPs) are transmembrane water channels and are hence central in the regulation of transcellular water fluxes. In the present study, we investigated the hypothesis that dexamethasone could impact water fluxes in the inner ear by targeting AQP2. We addressed this question through molecular dynamics simulations approaches and managed to demonstrate a direct interaction between AQP2 and dexamethasone and its significant impact on the channel water permeability. Through compartmentalization of sodium and potassium ions, a significant effect of Na+ upon AQP2 water permeability was highlighted as well. The molecular mechanisms involved in dexamethasone binding and in its regulatory action upon AQP2 function are described.

L-Thyroxine Improves Vestibular Compensation in a Rat Model of Acute Peripheral Vestibulopathy: Cellular and Behavioral Aspects.

Unilateral vestibular lesions induce a vestibular syndrome, which recovers over time due to vestibular compensation. The therapeutic effect of L-Thyroxine (L-T4) on vestibular compensation was investigated by behavioral testing and immunohistochemical analysis in a rat model of unilateral vestibular neurectomy (UVN). We demonstrated that a short-term L-T4 treatment reduced the vestibular syndrome and significantly promoted vestibular compensation. Thyroid hormone receptors (TRα and TRß) and type II iodothyronine deiodinase (DIO2) were present in the vestibular nuclei (VN), supporting a local action of L-T4. We confirmed the T4-induced metabolic effects by demonstrating an increase in the number of cytochrome oxidase-labeled neurons in the VN three days after the lesion. L-T4 treatment modulated glial reaction by decreasing both microglia and oligodendrocytes in the deafferented VN three days after UVN and increased cell proliferation. Survival of newly generated cells in the deafferented vestibular nuclei was not affected, but microglial rather than neuronal differentiation was favored by L-T4 treatment.

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei.

Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

SK Channels Modulation Accelerates Equilibrium Recovery in Unilateral Vestibular Neurectomized Rats.

We have previously reported in a feline model of acute peripheral vestibulopathy (APV) that the sudden, unilateral, and irreversible loss of vestibular inputs induces selective overexpression of small conductance calcium-activated potassium (SK) channels in the brain stem vestibular nuclei. Pharmacological blockade of these ion channels by the selective antagonist apamin significantly alleviated the evoked vestibular syndrome and accelerated vestibular compensation. In this follow-up study, we aimed at testing, using a behavioral approach, whether the antivertigo (AV) effect resulting from the antagonization of SK channels was species-dependent or whether it could be reproduced in a rodent APV model, whether other SK channel antagonists reproduced similar functional effects on the vestibular syndrome expression, and whether administration of SK agonist could also alter the vestibular syndrome. We also compared the AV effects of apamin and acetyl-DL-leucine, a reference AV compound used in human clinic. We demonstrate that the AV effect of apamin is also found in a rodent model of APV. Other SK antagonists also produce a trend of AV effect when administrated during the acute phase of the vertigo syndrome. Conversely, the vertigo syndrome is worsened upon administration of SK channel agonist. It is noteworthy that the AV effect of apamin is superior to that of acetyl-DL-leucine. Taken together, these data reinforce SK channels as a pharmacological target for modulating the manifestation of the vertigo syndrome during APV.

Breaking a dogma: acute anti-inflammatory treatment alters both post-lesional functional recovery and endogenous adaptive plasticity mechanisms in a rodent model of acute peripheral vestibulopathy.

BACKGROUND: Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained spinning vertigo, spontaneous ocular nystagmus and oscillopsia, perceptual-cognitive, posturo-locomotor, and vegetative disorders. We assessed the effectiveness of acute corticotherapy, and the functional role of acute inflammation observed after sudden unilateral vestibular loss. METHODS: We used the rodent model of unilateral vestibular neurectomy, mimicking the syndrome observed in patients with APV. We treated the animals during the acute phase of the vestibular syndrome, either with placebo or methylprednisolone, an anti-inflammatory corticosteroid. At the cellular level, impacts of methylprednisolone on endogenous plasticity mechanisms were assessed through analysis of cell proliferation and survival, glial reactions, neuron's membrane excitability, and stress marker. At the behavioral level, vestibular and posturo-locomotor functions' recovery were assessed with appropriate qualitative and quantitative evaluations. RESULTS: We observed that acute treatment with methylprednisolone significantly decreases glial reactions, cell proliferation and survival. In addition, stress and excitability markers were significantly impacted by the treatment. Besides, vestibular syndrome's intensity was enhanced, and vestibular compensation delayed under acute methylprednisolone treatment. CONCLUSIONS: We show here, for the first time, that acute anti-inflammatory treatment alters the expression of the adaptive plasticity mechanisms in the deafferented vestibular nuclei and generates enhanced and prolonged vestibular and postural deficits. These results strongly suggest a beneficial role for acute endogenous neuroinflammation in vestibular compensation. They open the way to a change in dogma for the treatment and therapeutic management of vestibular patients.

Proceedings of the GDR Vertige 2019 annual meeting devoted to endolymphatic hydrops.

The GDR Vertige is a federative research group gathering the different components of the French neuro-otology community. The annual meeting of the GDR Vertige is an opportunity for interactive exchanges between scientists, clinicians and industrialists, on basic issues related to vestibular function, as well as translational questions regarding the management of vestibular disorders. For its fifth edition, the annual meeting of the GDR Vertige, which took place in September 2019 in Marseille (France), was devoted to one of the most peculiar phenomena of neuro-otology: endolymphatic hydrops. For two days, international scientists and clinicians presented the most recent advances regarding the biophysical correlates of endolymphatic hydrops, the genetic and endocrine tableaux that favor its manifestation, new methods of clinical imaging, and current and upcoming therapeutic strategies to overcome the associated clinical manifestations. This special issue of the Journal of Vestibular Research aims at providing the proceedings of this meeting.