Vestibular rehabilitation improves spontaneous nystagmus normalization in patients with acute unilateral vestibulopathy.

Introduction: Spontaneous nystagmus (SN) can be observed after acute unilateral vestibulopathy (AUVP). The slow phase eye velocity of the SN progressively decreases in darkness as the result of rebalanced neurophysiological activity between both vestibular nuclei, a process that can take several months. Although this compensatory process can occur spontaneously, there is poor evidence that vestibular rehabilitation (VR) can facilitate the process. Methods: We documented the natural time course of SN reduction in patients with AUVP, as well as the effects of VR by means of a unilateral rotation paradigm. In a retrospective study (Study 1: n = 126 AUVP patients), we compared the time course of the SN reduction in patients with VR (n = 33) and without VR (n = 93). In a prospective study (Study 2: n = 42 AUVP patients), we compared the effects of early VR (n = 22; initiated within the first two weeks of symptoms onset) or late VR (n = 20; initiated after the second week of symptoms onset) on the time course of the SN reduction. Results: Study 1 showed shorter median time of SN normalization in patients with VR compared to patients without VR (14 days and 90 days, respectively). Study 2 showed that AUVP patients with early and late VR had a similar median time of SN normalization. The SN slow phase eye velocity was significantly decreased as early as the end of the first VR session in both groups, and kept decreasing at each subsequent VR session. In the early VR group, 38% of the patients had slow phase eye velocity below 2°/s after the first VR session, 100% after the fifth session. Similar findings were observed in the late VR group. Discussion: Taken together, these results indicate that VR with a unidirectional rotation paradigm speeds up the normalization of SN. This effect seems independent of the time between symptoms onset and commencement of VR, but early intervention is recommended to speed up the SN reduction.

Two conditions to fully recover dynamic canal function in unilateral peripheral vestibular hypofunction patients.

BACKGROUND: The crucial role of early vestibular rehabilitation (VR) to recover a dynamic semicircular canal function was recently highlighted in patients with unilateral vestibular hypofunction (UVH). However, wide inter-individual differences were observed, suggesting that parameters other than early rehabilitation are involved. OBJECTIVE: The aim of the study was to determine to what extent the degree of vestibular loss assessed by the angular vestibulo-ocular reflex (aVOR) gain could be an additional parameter interfering with rehabilitation in the recovery process. And to examine whether different VR protocols have the same effectiveness with regard to the aVOR recovery. METHODS: The aVOR gain and the percentage of compensatory saccades were recorded in 81 UVH patients with the passive head impulse test before and after early VR (first two weeks after vertigo onset: N = 43) or late VR (third to sixth week after onset: N = 38) performed twice a week for four weeks. VR was performed either with the unidirectional rotation paradigm or gaze stability exercises. Supplementary outcomes were the dizziness handicap inventory (DHI) score, and the static and dynamic subjective visual vertical. RESULTS: The cluster analysis differentiated two distinct populations of UVH patients with pre-rehab aVOR gain values on the hypofunction side below 0.20 (N = 42) or above 0.20 (N = 39). The mean gain values were respectively 0.07±0.05 and 0.34±0.12 for the lateral canal (p < 0.0001), 0.09±0.06 and 0.44±0.19 for the anterior canal (p < 0.0001). Patients with aVOR gains above 0.20 and early rehab fully recovered dynamic horizontal canal function (0.84±0.14) and showed very few compensatory saccades (18.7% ±20.1%) while those with gains below 0.20 and late rehab did not improve their aVOR gain value (0.16±0.09) and showed compensatory saccades only (82.9% ±23.7%). Similar results were found for the anterior canal function. Recovery of the dynamic function of the lateral canal was found with both VR protocols while it was observed with the gaze stability exercises only for the anterior canal. All the patients reduced their DHI score, normalized their static SVV, and exhibited uncompensated dynamic SVV. CONCLUSIONS: Early rehab is a necessary but not sufficient condition to fully recover dynamic canal function. The degree of vestibular loss plays a crucial role too, and to be effective rehabilitation protocols must be carried out in the plane of the semicircular canals.

Posture Deficits and Recovery After Unilateral Vestibular Loss: Early Rehabilitation and Degree of Hypofunction Matter.

Postural instability and balance impairment are disabling symptoms in patients with acute unilateral peripheral vestibular hypofunction (UVH). Vestibular rehabilitation (VR) is known to improve the vestibular compensation process, but (1) its effect on posture recovery remains poorly understood, (2) little is known about when VR must be done, and (3) whether the degree of vestibular loss matters is uncertain. We analyzed posture control under static (stable support) and dynamic (unstable support) postural tasks performed in different visual conditions [eye open (EO); eyes closed (EC); and optokinetic stimulation] using dynamic posturography. Non-linear analyses of the postural performance (wavelet transform, diffusion analysis, and fractal analysis) were performed in two groups of patients with UVH subjected to the same VR program based on the unidirectional rotation paradigm and performed either early (first 2 weeks) or later (fifth to the sixth week) after vertigo attack. Distribution of the angular horizontal vestibulo-ocular reflex (aVOR) gain values recorded on the hypofunction side before rehabilitation differentiated two distinct sub-groups (cluster analysis) with aVOR gains below or above 0.20. The postural performance of the four sub-groups of patients with UVH (early rehabilitation with aVOR gain <0.20: n = 25 or gain >0.20: n = 19; late rehabilitation with aVOR gain <0.20: n = 15 or gain >0.20: n = 10) tested before VR showed significantly altered postural parameters compared with healthy controls. Greater instability, higher energy to control posture, larger sway without feedback corrections, and lower time of automatic control of posture were observed in static conditions. The four sub-groups recovered near-normal postural performance after VR in the EO and EC conditions, but still exhibited altered postural performance with optokinetic stimulation. In dynamic posturography conditions and before VR, the percentage of patients able to perform the postural tasks with EC and optokinetic stimulation was significantly lower in the two sub-groups with aVOR gain <0.20. After VR, the improvement of the postural parameters depended on the stage of rehabilitation and the degree of vestibular hypofunction. The best balance function recovery was found in the sub-group with early VR and pre-rehabilitation aVOR gain above 0.20, the worst in the sub-group with late rehabilitation and aVOR gain below 0.20. These differences were seen when the vestibular input remains the main sensory cue to control balance, that is, on unstable support without vision or altered visual motion cues. These findings extend to dynamic balance recovery the crucial roles of early rehabilitation and degree of vestibular hypofunction which we have already highlighted for vestibulo-ocular reflex recovery.

Good Clinical Approach: Delphi Consensus for the Use of Betahistine in Menière's Disease.

Menière's disease is a disorder of the inner ear that causes vertigo, tinnitus, fullness, and hearing loss. Several pharmacological treatments are available, but none of them has shown significant results. Betahistine has been largely used but its effect on the main symptoms of Menière's disease remains unclear. In order to improve clinical appropriateness and to reduce the heterogeneity of the therapeutic approaches for Menière's disease, we proposed a European Consensus Conference on Betahistine's prescription. A group of European experts in vestibular disorders completed a questionnaire, prepared by opinion leaders, on the use of betahistine in Menière's disease. The Delphi method was used as an iterative investigation method in order to increase and establish the consensus. While betahistine was considered useful to reduce the number of the vertigo attacks during the intercritical phase of the disease, its use during attacks was considered helpful only when associated with other drugs. Betahistine was not considered useful for preventing hearing loss. The experts support the use of betahistine during the intercritical phase of the disease to reduce the number and severity of vertigo episodes. They also defined the parameters for a good clinical approach to evaluate the efficacy of betahistine treatment for Menière's disease.

How Eye Movements Stabilize Posture in Patients With Bilateral Vestibular Hypofunction.

Chronic patients with bilateral vestibular hypofunction (BVH) complain of oscillopsia and great instability particularly when vision is excluded and on irregular surfaces. The real nature of the visual input substituting to the missing vestibular afferents and improving posture control remains however under debate. Is retinal slip involved? Do eye movements play a substantial role? The present study tends to answer this question in BVH patients by investigating their posture stability during quiet standing in four different visual conditions: total darkness, fixation of a stable space-fixed target, and pursuit of a visual target under goggles delivering visual input rate at flicker frequency inducing either slow eye movements (4.5 Hz) or saccades (1.2 Hz). Twenty one chronic BVH patients attested by both the caloric and head impulse test were examined by means of static posturography, and compared to a control group made of 21 sex-and age-matched healthy participants. The posturography data were analyzed using non-linear computation of the center of foot pressure (CoP) by means of the wavelet transform (Power Spectral Density in the visual frequency part, Postural Instability Index) and the fractional Brownian-motion analysis (stabilogram-diffusion analysis, Hausdorff fractal dimension). Results showed that posture stability was significantly deteriorated in darkness in the BVH patients compared to the healthy controls. Strong improvement of BVH patients' posture stability was observed during fixation of a visual target, pursuit with slow eye movements, and saccades, whereas the postural performance of the control group was less affected by the different visual conditions. It is concluded that BVH patients improve their posture stability by (1) using extraocular signals from eye movements (efference copy, muscle re-afferences) much more than the healthy participants, and (2) shifting more systematically than the controls to a more automatic mode of posture control when they are in dual-task conditions associating the postural task and a concomitant visuo- motor task.

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.

Betahistine Treatment in a Cat Model of Vestibular Pathology: Pharmacokinetic and Pharmacodynamic Approaches.

This study is a pharmacokinetic (PK) and pharmacodynamics (PD) approach using betahistine doses levels in unilateral vestibular neurectomized cats (UVN) comparable to those used in humans for treating patients with Menière's disease. The aim is to investigate for the first time oral betahistine administration (0.2 and 2 mg/kg/day) with plasma concentrations of betahistine and its major metabolite 2-pyridylacetic acid (2-PAA) (N = 9 cats), the time course of posture recovery (N = 13 cats), and the regulation of the enzyme synthesizing histamine (histidine decarboxylase: HDC) in the tuberomammillary nuclei (TMN) of UVN treated animals (N = the same 13 cats plus 4 negative control cats). In addition the effect of co-administration of the lower betahistine dose (0.2 mg/kg/day) and selegiline (1 mg/kg/day), an inhibitor of the monamine oxidase B (MAOBi) implicated in betahistine catabolism was investigated. The PK parameters were the peak concentration (Cmax), the time when the maximum concentration is reached (Tmax) for both betahistine and 2-PAA and the area under the curve (AUC). The PD approach consisted at quantifying the surface support area, which is a good estimation of posture recovery. The plasma concentration-time-profiles of betahistine and 2-PAA in cats were characterized by early Cmax-values followed by a phase of rapid decrease of plasma concentrations and a final long lasting low level of plasma concentrations. Co administration of selegiline and betahistine increased values of Cmax and AUC up to 146- and 180-fold, respectively. The lowest dose of betahistine (0.2 mg/kg) has no effects on postural function recovery but induced an acute symptomatic effect characterized by a fast balance improvement (4-6 days). The higher dose (2 mg/kg) and the co-administration treatment induced both this acute effect plus a significant acceleration of the recovery process. The histaminergic activity of the neurons in the TMN was significantly increased under treatment with the 2 mg/kg betahistine daily dose, but not with the lower dose alone or in combination with selegiline. The results show for the first time that faster balance recovery in UVN treated cats is accompanied with high plasma concentrations of betahistine and 2-PAA, and upregulation of HDC immunopositive neurons in the TMN. The higher betahistine dose gives results similar to those obtained with the lower dose when co-administrated with an inhibitor of betahistine metabolism, selegiline. From a clinical point of view, the study provides new perspectives for Menière's disease treatment, regarding the daily betahistine dose that should be necessary for fast and slow metabolizers.

Vestibular compensation: the neuro-otologist's best friend.

Why vestibular compensation (VC) after an acute unilateral vestibular loss is the neuro-otologist's best friend is the question at the heart of this paper. The different plasticity mechanisms underlying VC are first reviewed, and the authors present thereafter the dual concept of vestibulo-centric versus distributed learning processes to explain the compensation of deficits resulting from the static versus dynamic vestibular imbalance. The main challenges for the plastic events occurring in the vestibular nuclei (VN) during a post-lesion critical period are neural protection, structural reorganization and rebalance of VN activity on both sides. Data from animal models show that modulation of the ipsilesional VN activity by the contralateral drive substitutes for the normal push-pull mechanism. On the other hand, sensory and behavioural substitutions are the main mechanisms implicated in the recovery of the dynamic functions. These newly elaborated sensorimotor reorganizations are vicarious idiosyncratic strategies implicating the VN and multisensory brain regions. Imaging studies in unilateral vestibular loss patients show the implication of a large neuronal network (VN, commissural pathways, vestibulo-cerebellum, thalamus, temporoparietal cortex, hippocampus, somatosensory and visual cortical areas). Changes in gray matter volume in these multisensory brain regions are structural changes supporting the sensory substitution mechanisms of VC. Finally, the authors summarize the two ways to improve VC in humans (neuropharmacology and vestibular rehabilitation therapy), and they conclude that VC would follow a "top-down" strategy in patients with acute vestibular lesions. Future challenges to understand VC are proposed.

Comparative analysis of pharmacological treatments with N-acetyl-DL-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.

Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only.

Plasticity of the histamine H3 receptors after acute vestibular lesion in the adult cat.

After unilateral vestibular neurectomy (UVN) many molecular and neurochemical mechanisms underlie the neurophysiological reorganizations occurring in the vestibular nuclei (VN) complex, as well as the behavioral recovery process. As a key regulator, the histaminergic system appears to be a likely candidate because drugs interfering with histamine (HA) neurotransmission facilitate behavioral recovery after vestibular lesion. This study aimed at analyzing the post-lesion changes of the histaminergic system by quantifying binding to histamine H3 receptors (H3R; mediating namely histamine autoinhibition) using a histamine H3 receptor agonist ([(3)H]N-α-methylhistamine). Experiments were done in brain sections of control cats (N = 6) and cats submitted to UVN and killed 1 (N = 6) or 3 (N = 6) weeks after the lesion. UVN induced a bilateral decrease in binding density of the agonist [(3)H]N-α-methylhistamine to H3R in the tuberomammillary nuclei (TMN) at 1 week post-lesion, with a predominant down-regulation in the ipsilateral TMN. The bilateral decrease remained at the 3 weeks survival time and became symmetric. Concerning brainstem structures, binding density in the VN, the prepositus hypoglossi, the subdivisions of the inferior olive decreased unilaterally on the ipsilateral side at 1 week and bilaterally 3 weeks after UVN. Similar changes were observed in the subdivisions of the solitary nucleus only 1 week after the lesion. These findings indicate vestibular lesion induces plasticity of the histamine H3R, which could contribute to vestibular function recovery.

Interaction between Vestibular Compensation Mechanisms and Vestibular Rehabilitation Therapy: 10 Recommendations for Optimal Functional Recovery.

This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation), which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalog of results but to provide clinicians with an understandable view on when and how to perform VR therapy, and why VR may benefit from basic knowledge and may influence the recovery process. With this perspective, 10 major recommendations are proposed as ways to identify an optimal functional recovery. Among them are the crucial role of active and early VR therapy, coincidental with a post-lesion sensitive period for neuronal network remodeling, the instructive role that VR therapy may play in this functional reorganization, the need for progression in the VR therapy protocol, which is based mainly on adaptation processes, the necessity to take into account the sensorimotor, cognitive, and emotional profile of the patient to propose individual or "à la carte" VR therapies, and the importance of motivational and ecologic contexts. More than 10 general principles are very likely, but these principles seem crucial for the fast recovery of vestibular loss patients to ensure good quality of life.

Betahistine treatment in managing vertigo and improving vestibular compensation: clarification.

Betahistine dihydrochloride (betahistine) is currently used in the management of vertigo and vestibular pathologies with different aetiologies. The main goal of this review is to clarify the mechanisms of action of this drug, responsible for the symptomatic relief of vertigo and the improvement of vestibular compensation. The review starts with a brief summary recalling the role of histamine as a neuromodulator/neurotransmitter in the control of the vestibular functions, and the role of the histaminergic system in vestibular compensation. Then are presented data recorded in animal models demonstrating that betahistine efficacy can be explained by mechanisms targeting the histamine receptors (HRs) at three different levels: the vascular tree, with an increase of cochlear and vestibular blood flow involving the H1R; the central nervous system, with an increase of histamine turnover implicating the H3R, and the peripheral labyrinth, with a decrease of vestibular input implying the H3R/H4R. Clinical data from vestibular loss patients show the impact of betahistine treatment for the long-term control of vertigo, improvement of balance and quality of life that can be explained by these mechanisms of action. However, two conditions, at least, are required for reaching the betahistine therapeutic effect: the dose and the duration of treatment. Experimental and clinical data supporting these requirements are exposed in the last part of this review.

Static and dynamic posture control in postlingual cochlear implanted patients: effects of dual-tasking, visual and auditory inputs suppression.

Posture control is based on central integration of multisensory inputs, and on internal representation of body orientation in space. This multisensory feedback regulates posture control and continuously updates the internal model of body's position which in turn forwards motor commands adapted to the environmental context and constraints. The peripheral localization of the vestibular system, close to the cochlea, makes vestibular damage possible following cochlear implant (CI) surgery. Impaired vestibular function in CI patients, if any, may have a strong impact on posture stability. The simple postural task of quiet standing is generally paired with cognitive activity in most day life conditions, leading therefore to competition for attentional resources in dual-tasking, and increased risk of fall particularly in patients with impaired vestibular function. This study was aimed at evaluating the effects of postlingual cochlear implantation on posture control in adult deaf patients. Possible impairment of vestibular function was assessed by comparing the postural performance of patients to that of age-matched healthy subjects during a simple postural task performed in static (stable platform) and dynamic (platform in translation) conditions, and during dual-tasking with a visual or auditory memory task. Postural tests were done in eyes open (EO) and eyes closed (EC) conditions, with the CI activated (ON) or not (OFF). Results showed that the postural performance of the CI patients strongly differed from the controls, mainly in the EC condition. The CI patients showed significantly reduced limits of stability and increased postural instability in static conditions. In dynamic conditions, they spent considerably more energy to maintain equilibrium, and their head was stabilized neither in space nor on trunk: they behaved dynamically without vision like an inverted pendulum while the controls showed a whole body rigidification strategy. Hearing (prosthesis on) as well as dual-tasking did not really improve the dynamic postural performance of the CI patients. We conclude that CI patients become strongly visual dependent mainly in challenging postural conditions, a result they have to be awarded of particularly when getting older.

Postural performance of vestibular loss patients under increased postural threat.

The effects of increasing postural task difficulty on balance control was investigated in 9 compensated vestibular loss patients whose results were compared to 11 healthy adults. Subjects were tested in static (stable support) and dynamic (sinusoidal translation of the support) conditions, both at floor level and at height (62 cm above the floor), and with and without vision, to create an additional postural threat. Wavelet analysis of the center of foot pressure displacement and motion analysis of the body segments were used to evaluate the postural performance. Evaluation questionnaires were used to examine the compensation level of the patients (DHI test), their general anxiety level (SAST), fear of height (subjective scale), and workload (NASA TLX test). (Vestibular loss patients rely more on vision and spend more energy maintaining balance than controls, but they use the same postural strategy as normals in both static and dynamic conditions.) Questionnaire data all showed differences in behavior and perceptions between the controls and the patients. However, at height and without vision, a whole body strategy leading to rigid posture replaces the head stabilization strategy found for standing at floor level. The effects of height on postural control can be attributable to an increase in postural threat and attention changes resulting from modifications in perception.

Neurogenic potential of the vestibular nuclei and behavioural recovery time course in the adult cat are governed by the nature of the vestibular damage.

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.

[Discovering a new functional neurogenic zone: the vestibular nuclei of the brainstem]. / Une nouvelle zone de neurogenèse fonctionnelle: les noyaux vestibulaires du tronc cérébral.

The adult mammal brain is mostly considered as non-neurogenic, except in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus, where ongoing neurogenesis occurs. However, anti-neurogenic influences can be removed in pathological conditions or after specific injury. That is what happens in a model of unilateral vestibular neurectomy (UVN) that mimics human pathology in adult cats. We showed for the first time that a UVN promoted an intense reactive cell proliferation in the deafferented vestibular nuclei located in the brainstem. The new cells survived up to one month, differentiated into glial cells - microglia or astrocytes - or GABAergic neurons, so highlighting a GABAergic neurogenesis. Surprisingly, we further showed that post-UVN reactive cell proliferation contributed successfully to fine restoration of vestibular posturo-locomotor functions. In conclusion, these pioneering studies bring new pieces of a promising puzzle in both stem cell and vestibular therapy domains.

Betahistine treatment improves the recovery of static symptoms in patients with unilateral vestibular loss.

Vestibular loss induces a combination of postural, oculomotor, and perceptive symptoms that are compensated over time. The aim of this study was to analyze the influence of betahistine dihydrochloride on vestibular compensation. A randomized, double-blind, placebo-controlled study was performed in Menière's disease patients who underwent a curative unilateral vestibular neurotomy (UVN). The effects of betahistine treatment were investigated on a broad spectrum of vestibular-induced changes resulting from vestibular loss: body sway, head orientation, ocular cyclotorsion, spontaneous nystagmus, verticality perception, and self-evaluation of the postural stability. The time course of the recovery was compared in 16 patients who received either a placebo or betahistine (24 mg b.i.d.) from 3 days up to 3 months after UVN. Patients were examined before (day -1) and after UVN (days 7, 30, and 90). Results indicate that betahistine reduces the time to recovery by 1 month or more depending on the tested functions. Betahistine was effective as soon as 4 days after treatment administration, and the effect remained during the whole compensation period (up to 3 months). The observed clinical effects may be attributed to an action of betahistine in rebalancing the neuronal activity between contralateral vestibular nuclei.

Changes in TNFα, NFκB and MnSOD protein in the vestibular nuclei after unilateral vestibular deafferentation.

BACKGROUND: Unilateral vestibular deafferentation results in strong microglial and astroglial activation in the vestibular nuclei (VN) that could be due to an inflammatory response. This study was aimed at determining if markers of inflammation are upregulated in the VN after chemical unilateral labyrinthectomy (UL) in the rat, and if the inflammatory response, if any, induces the expression of neuroprotective factors that could promote the plasticity mechanisms involved in the vestibular compensation process. The expressions of inflammatory and neuroprotective factors after chemical or mechanical UL were also compared to verify that the inflammatory response was not due to the toxicity of sodium arsanilate. METHODS: Immunohistological investigations combined the labeling of tumor necrosis factor α (TNFα), as a marker of the VN inflammatory response, and of nuclear transcription factor κB (NFκB) and manganese superoxide dismutase (MnSOD), as markers of neuroprotection that could be expressed in the VN because of inflammation. Immunoreactivity (Ir) of the VN cells was quantified in the VN complex of rats. Behavioral investigations were performed to assess the functional recovery process, including both static (support surface) and dynamic (air-righting and landing reflexes) postural tests. RESULTS: Chemical UL (arsanilate transtympanic injection) induced a significant increase in the number of TNFα-Ir cells in the medial and inferior VN on both sides. These changes were detectable as early as 4 h after vestibular lesion, persisted at 1 day, and regained nearly normal values at 3 days. The early increase in TNFα expression was followed by a slightly delayed upregulation of NFκB 8 h after chemical UL, peaking at 1 day, and regaining control values 3 days later. By contrast, upregulation of MnSOD was more strongly delayed (1 day), with a peak at 3 days, and a return to control values at 15 days. Similar changes of TNFα, NFκB, and MnSOD expression were found in rats submitted to mechanical UL. Behavioral observations showed strong posturo-locomotor deficits early after chemical UL (1 day) and a complete functional recovery 6 weeks later. CONCLUSIONS: Our results suggest that the upregulation of inflammatory and neuroprotective factors after vestibular deafferentation in the VN may constitute a favorable neuronal environment for the vestibular compensation process.

Tell me your vestibular deficit, and i'll tell you how you'll compensate.

Most patients with unilateral vestibular loss exhibit a similar static and dynamic vestibular syndrome consisting of vestibulo-ocular, posturolocomotor, and perceptive deficits. This vestibular syndrome recovers more or less completely and more or less rapidly over time. One open question is whether recovery mechanisms differ according to vestibular pathology and/or patients. It is reported here (1) data from three different cat models of unilateral vestibular loss reproducing vestibular pathology with sudden (unilateral vestibular neurectomy [UVN] model), gradual (unilateral labyrinthectomy [UL] model), or reversible (tetrodotoxine [TTX]) model) loss of vestibular function, and (2) clinical observations in a population of unilateral vestibular loss patients suffering the same pathology (Menière's disease). Animal models show that time courses and mechanisms of recovery depend on the type of vestibular deafferentation, and clinical findings show that Menière's patients compensate their postural and perceptive deficits using different vicarious processes. Taken together, results point to a more complex picture of compensation after unilateral vestibular loss, which cannot be reduced either to a common recovery mechanism or to a single process identical for all individuals. These findings should guide physiotherapists in treatment and rehabilitation for vestibular deficits.