Vestibular End Organs Research Articles

Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear

The retinoblastoma family of pocket proteins (pRBs), composed of Rb1, p107, and p130 are negative regulators of cell-cycle progression. The deletion of any individual pRB in the auditory system triggers hair cells’ (HCs) and supporting cells’ (SCs) proliferation to different extents. Nevertheless, accessing their combined role in the inner ear through conditional or complete knockout methods is limited by the early mortality of the triple knockout. In quiescent cells, hyperphosphorylation and inactivation of the pRBs are maintained through the activity of the Cyclin-D1-cdk4/6 complex. Cyclin D1 (CycD1) is expressed in the embryonic and neonatal inner ear. In the mature organ of Corti (OC), CycD1 expression is significantly downregulated, paralleling the OC mitotic quiescence. Earlier studies showed that CycD1 overexpression leads to cell-cycle reactivation in cultures of inner ear explants. Here, we characterize a Cre-activated, Doxycycline (Dox)-controlled, conditional CycD1 overexpression model, which when bred to a tetracycline-controlled transcriptional activator and the Atoh1-cre mouse lines, allow for transient CycD1 overexpression and pRBs’ downregulation in the inner ear in a reversible fashion. Analyses of postnatal mice’s inner ears at various time points revealed the presence of supernumerary cells throughout the length of the cochlea and in the vestibular end-organs. Notably, most supernumerary cells were observed in the inner hair cells’ (IHCs) region, expressed myosin VIIa (M7a), and showed no signs of apoptosis at any of the time points analyzed. Auditory and vestibular phenotypes were similar between the different genotypes and treatment groups. The fact that no significant differences were observed in auditory and vestibular function supports the notion that the supernumerary cells detected in the adult mice cochlea and macular end-organs may not impair auditory functions.

Human Temporal Bone Study of Vestibular Histopathology in Cochlear Implant Patients With Cochlear Hydrops.

Endolymphatic hydrops (EH) associated with cochlear implantation are associated with vestibular dysfunction. Vestibular dysfunction is a known risk after cochlear implantation (CI). CI has been shown to cause cochlear hydrops due to fibrosis surrounding the ductus reuniens. However, the association of cochlear hydrops with vestibular hydrops and the relationship to vestibular symptoms remain unknown. Histopathological analysis and clinical evaluation of the vestibular end organs of 17 human temporal bones (HTB)s exhibiting cochlear hydrops from 15 CI recipients. Eight of 15 patients with cochlear hydrops due to CI had complaints of dizziness, vertigo, or imbalance following CI. In all 17 HTBs with cochlear hydrops, there was fibrosis, atrophy, or obstruction of the ductus reuniens, and all had straight electrode CI via cochleostomy. In one of the eight reporting postoperative dizziness, labyrinthitis ossificans was deemed causative. Six of the seven remaining patients had EH of both the saccule and utricle. Fifteen of 17 HTBs (88.2%) had saccular EH. In contrast, 8 of 17 HTBs (47.0%) in 7 patients had utricular EH, of which 6 patients had postoperative vertigo spells. It seems that hydrops of the utricle closely corresponds to postoperative vertigo spells and vestibular complaints. Implantation of the CI, when complicated by ductus reuniens fibrosis, may cause both cochlear hydrops and vestibular endolymphatic hydrops. Hydrops of the vestibular periphery when involving the utricle seems to be more likely associated with disabling vertigo symptoms. This study supports the round window technique of insertion rather than cochleostomy.

The Distribution and Prevalence of Macrophages in the Cochlea Following Cochlear Implantation in the Human: An Immunohistochemical Study Using Anti-Iba1 Antibody.

Cochlear implantation may cause an increase in the number of macrophages in the human cochlea similar to previous findings in the vestibular endorgans. Macrophages play a key role in both an inflammatory response and homeostatic maintenance. Recently, an increase in the prevalence of macrophages was demonstrated in the human vestibular endorgans after implantation. However, the prevalence of macrophages in the cochlea after implantation is unclear. The aim of this study was to compare the distribution and prevalence of macrophages in implanted human cochleae and the contralateral unimplanted ears. The prevalence of macrophages in the cochlea in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy using anti-Iba1 immunostaining. The densities of macrophages in the osseous spiral lamina (OSL) and Rosenthal's canal (RC) in implanted cochleae were compared with the contralateral unimplanted ears. The distribution of macrophage morphology (amoeboid, transitional, and ramified) was also compared. There were activated and phagocytosing macrophages within the fibrotic sheath surrounding the electrode track and within fibrous tissue with lymphocytic infiltration in implanted ears. The densities of macrophages in OSL and RC in implanted ears were significantly greater than in unimplanted ears in some areas. There was also a difference in the prevalence of macrophage phenotype between the OSL and RC. An increase in the density of macrophages in the cochlea after cochlear implantation was demonstrated. Both phagocytosis and anti-inflammatory activity of macrophages were suggested by the distribution and prevalence of macrophages in the implanted cochlea.

Histopathological changes to the peripheral vestibular system following meningitic labyrinthitis.

ObjectiveWhile cochlear ossification is a common sequalae of meningitic labyrinthitis, less is known about the effects of meningitis on peripheral vestibular end organs. Herein, we investigate histopathologic changes in the peripheral vestibular system and cochlea in patients with a history of meningitic labyrinthitis.MethodsTemporal bone (TB) specimens from patients with a history of meningitis were evaluated and compared to age‐matched controls. Specimens were evaluated by light microscopy and assessed for qualitative changes, including the presence of vestibular and/or cochlear endolymphatic hydrops, presence and location of inflammatory cells, new bone formation, and labyrinthitis ossificans; and quantitative changes, including Scarpa's ganglion neuron (ScGN) and spiral ganglion neuron (SGN) counts.ResultsFifteen TB from 10 individuals met inclusion and exclusion criteria. Presence of inflammatory cells and fibrous tissue was found in 5 TB. Of these, evidence of labyrinthitis ossificans was found in 2 TB. In the peripheral vestibular system, mild to severe degeneration of the vestibular membranous labyrinth was identified in 60% of cases (n = 9 TBs). There was a 21.2% decrease (range, 3%‐64%) in the mean total count of ScGN in patients with meningitis, compared to age‐matched controls. In the cochlea, there was a 45% decrease (range, 25.3%‐80.9%) in the mean total count of SGN compared to age‐matched controls (n = 14 TBs).ConclusionsOtopathologic analysis of TB from patients with a history of meningitic labyrinthitis demonstrated distinct peripheral vestibular changes. Future research may help to delineate potential mechanisms for the observed otopathologic changes following meningitis.Level of EvidenceN/A

Interactions between Auditory and Vestibular Modalities during Stimulation with a Combined Vestibular and Cochlear Prosthesis

Background: A combined vestibular and cochlear prosthesis may restore hearing and balance to patients who have lost both. To do so, the device should activate each sensory system independently. Objectives: In this study, we quantify auditory and vestibular interactions during interleaved stimulation with a combined 16-channel cochlear and 6-channel vestibular prosthesis in human subjects with both hearing and vestibular loss. Methods: Three human subjects were implanted with a combined vestibular and cochlear implant. All subjects had severe-to-profound deafness in the implanted ear. We provided combined stimulation of the cochlear and vestibular arrays and looked for interactions between these separate inputs. Our main outcome measures were electrically evoked slow-phase eye velocities during nystagmus elicited by brief trains of biphasic pulse stimulation of the vestibular end organs with and without concurrent stimulation of the cochlea, and Likert scale assessments of perceived loudness and pitch during stimulation of the cochlea, with and without concurrent stimulation of the vestibular ampullae. Results: All subjects had no auditory sensation resulting from semicircular canal stimulation alone, and no sensation of motion or slow-phase eye movement resulting from cochlear stimulation alone. However, interleaved cochlear stimulation did produce changes in the slow-phase eye velocities elicited by electrical stimulation. Similarly, interleaved semicircular canal stimulation did elicit changes in the perceived pitch and loudness resulting from stimulation at multiple sites in the cochlea. Conclusions: There are significant interactions between different sensory modalities during stimulation with a combined vestibular and cochlear prosthesis. Such interactions present potential challenges for stimulation strategies to simultaneously restore auditory and vestibular function with such an implant.

Exposure to blast shock waves via the ear canal induces deficits in vestibular afferent function in rats

The ears are air-filled structures that are directly impacted during blast exposure. In addition to hearing loss and tinnitus, blast victims often complain of vertigo, dizziness and unsteady posture, suggesting that blast exposure induces damage to the vestibular end organs in the inner ear. However, the underlying mechanisms remain to be elucidated. In this report, single vestibular afferent activity and the vestibulo-ocular reflex (VOR) were investigated before and after exposure to blast shock waves (∼20 PSI) delivered into the left external ear canals of anesthetized rats. Single vestibular afferent activity was recorded from the superior branch of the left vestibular nerves of the blast-treated and control rats one day after blast exposure. Blast exposure reduced the spontaneous discharge rates of the otolith and canal afferents. Blast exposure also reduced the sensitivity of irregular canal afferents to sinusoidal head rotation at 0.5–2Hz. Blast exposure, however, resulted in few changes in the VOR responses to sinusoidal head rotation and translation. To the best of our knowledge, this is the first study that reports blast exposure-induced damage to vestibular afferents in an animal model. These results provide insights that may be helpful in developing biomarkers for early diagnosis of blast-induced vestibular deficits in military and civilian populations.

Autoimmune Vestibulocerebellar Syndromes.

Autoimmune disorders affecting the vestibular end organs, vestibular pathways, vestibular nuclei, and vestibulocerebellum are often underrecognized as a cause of chronic dizziness and ataxia. Autoantibodies specific for cell-surface, synaptic, and intracellular neural antigens serve as biomarkers of these disorders. This article describes the epidemiology, clinical presentation, diagnostic considerations, imaging findings, treatment, and prognosis of autoimmune disorders, in which the vestibulocerebellar syndrome is the main or presenting clinical presentation. Antibodies specific for intracellular antigenic targets described in the article are PCA-1 (Purkinje cell cytoplasmic antibody type 1, also known as anti-Yo), ANNA-1 (antinuclear neuronal antibody type 1, also known as anti-Hu), ANNA-2 (antinuclear neuronal antibody type 2, also known as anti-Ri), Ma1/2 (anti-Kelch-like 11/12 antibody), Kelch-like 11, amphiphysin, CV2 (collapsin response 2, also known as collapsin response mediator protein-5 [CRMP5]), VGCC (voltage-gated calcium channel), GAD65 (glutamic acid decarboxylase 65-kDa isoform), AP3B2 (adaptor protein 3B2, also known as anti-Nb), MAP1B (microtubule-associated protein 1B antibody, also known as anti-PCA-2), and neurochondrin antibodies. Antibodies targeting cell-surface or synaptic antigenic targets described in the article include DNER (delta/notchlike epidermal growth factor related receptor; antigen to anti-Tr), CASPR2 (contactin-associated proteinlike 2), septin-5, Homer-3, and mGluR1 (metabotropic glutamate receptor 1). The vestibulocerebellar presentation is largely indistinguishable among these conditions and is characterized by subacute onset of cerebellar symptoms over weeks to months. The diagnosis of autoimmune vestibulocerebellar syndromes is based on a combination of clinical and serological features, with a limited role for neuroimaging. Subtle eye movement abnormalities can be an early feature in many of these disorders, and therefore a meticulous vestibulo-ocular examination is essential for early and correct identification. Cancer occurrence and its type are variable and depend on the autoantibody detected and other cancer risk factors. Treatment comprises immunotherapy and cancer-directed therapy. Acute immunotherapies such as intravenous immunoglobulin, plasma exchange, and steroids are used in the initial phase, and the use of long-term immunosuppression such as rituximab may be necessary in relapsing cases. Outcomes are better if immunotherapy is started early. The neurologic prognosis depends on multiple factors.

Stabilization of Gaze during Early Xenopus Development by Swimming-Related Utricular Signals.

Locomotor maturation requires concurrent gaze stabilization improvement for maintaining visual acuity [1, 2]. The capacity to stabilize gaze, in particular in small aquatic vertebrates where coordinated locomotor activity appears very early, is determined by assembly and functional maturation of inner ear structures and associated sensory-motor circuitries [3-7]. Whereas utriculo-ocular reflexes become functional immediately after hatching [8, 9], semicircular canal-dependent vestibulo-ocular reflexes (VORs) appear later [10]. Thus, small semicircular canals are unable to detect swimming-related head oscillations, despite the fact that corresponding acceleration components are well-suited to trigger an angular VOR [11]. This leaves the utricle as the sole vestibular origin for swimming-related compensatory eye movements [12, 13]. We report a remarkable ontogenetic plasticity of swimming-related head kinematics and vestibular end organ recruitment in Xenopus tadpoles with beneficial consequences for gaze-stabilization. Swimming of older larvae generates sinusoidal head undulations with small, similar curvature angles on the left and right side that optimally activate horizontal semicircular canals. Young larvae swimming causes left-right head undulations with narrow curvatures and strong, bilaterally dissimilar centripetal acceleration components well suited to activate utricular hair cells and to substitute the absent semicircular canal function at this stage. The capacity of utricular signals to supplant semicircular canal function was confirmed by recordings of eye movements and extraocular motoneurons during off-center rotations in control and semicircular canal-deficient tadpoles. Strong alternating curvature angles and thus linear acceleration profiles during swimming in young larvae therefore represents a technically elegant solution to compensate for the incapacity of small semicircular canals to detect angular acceleration components.

Efficient viral transduction in mouse inner ear hair cells with utricle injection and AAV9-PHP.B

Viral delivery of exogenous coding sequences into the inner ear has the potential for therapeutic benefit for patients suffering genetic or acquired hearing loss. To devise improved strategies for viral delivery, we investigated two injection techniques, round window membrane injection or a novel utricle injection method, for their ability to safely and efficiently transduce sensory hair cells and neurons of the mouse inner ear. In addition, we evaluated three synthetic AAV vectors (Anc80L65, AAV9-PHP.B, AAV2.7m8) encoding enhanced green fluorescent protein (eGFP) and three promoters (Cmv, Synapsin, Gfap) for their ability to transduce and drive expression in desired cell types. We found the utricle injection method with AAV9-PHP.B and a Cmv promoter was the most efficient combination for driving robust eGFP expression in both inner and outer hair cells. We found eGFP expression levels rose over 3–5 days post-injection, a viral dose of 1.5 × 109 gc yielded half maximal eGFP expression and that the utricle injection method yielded transduced hair cells even when delivered as late as postnatal day 16. Sensory transduction and auditory thresholds were unaltered in injected mice relative to uninjected wild-type controls. Vestibular end organs were also transduced without affecting balance behavior. The Synapsin promoter and the Gfap promoter drove strong eGFP expression in inner ear neurons and supporting cells, respectively. We conclude the AAV9-PHP.B vector and the utricle injection method are well-suited for delivery of exogenous gene constructs into inner ears of mouse models of auditory and vestibular dysfunction.

Comparison between ocular-evoked and cervical-evoked myogenic potentials in adults with unilateral sensorineural hearing loss

Background The cochlea and the vestibule share the continuous membranous labyrinth of the inner ear. Moreover, there is great similarity between the cochlear and vestibular hair cell ultrastructures and the common arterial blood supply of the cochlea and vestibular end organs via the same end artery, so vestibular involvement in cochlear damage may occur. Aim The aim was to measure the effect of unilateral sensorineural hearing loss on both cervical vestibular-evoked myogenic potentials (cVEMP) and ocular vestibular-evoked myogenic potentials (oVEMP) and to compare between them in different degrees of hearing loss with or without vertigo. Patients and methods This is a cross-sectional study carried out on 40 adults with different degrees of unilateral sensorineural hearing loss. The other normal ear was used as a control for diseased ear with unilateral sensorineural hearing loss, cVEMP, and oVEMP recorded using air-conducted acoustic stimulus. Results cVEMP and oVEMP were abnormal and absent in 45 and 47.5% of ears, respectively. Moreover, there is no significant relation between the degree of SNHL, cVEMP, and oVEMP response in affected ears. There is a significant association and agreement between cVEMP and oVEMP in unilateral sensorineural hearing loss. There was a significant relation between vertigo and VEMP. Conclusion SNHL affects VEMPs response rate and other parameters, and the functions of vestibular organs are not associated with disease severity. cVEMP and oVEMP were affected equally in unilateral sensorineural hearing loss. Hearing loss may be associated with vestibular dysfunction even when there is no history of dizziness.

How sacculo-collic function assessed by cervical vestibular evoked myogenic Potentials correlates with the quality of postural control in hearing impaired children?

ObjectiveFunctional integrity of vestibular end organs is essential for gaze stabilization, dynamic visual acuity, postural control and spatial orientation. Some authors hypothesized on the importance of saccules for postural control and motor development in children, including achievements such as standing up and walking. The purpose of this article was to observe how saccular dysfunction assessed by cervical Vestibular Evoked Myogenic Potentials (cVEMPs) correlates with the quality of postural control in non-syndromic deaf children. MethodSeventy-six non-syndromic hearing-impaired children were retrospectively included. Sacculo-collic pathway was assessed with cVEMPs elicited in bone conduction. The response was quoted “normal” if a reproducible wave P13–N23 of at least 50μV in amplitude was present, if not, it was quoted “absent”. The sample was divided in 3 groups depending on the presence of the sacculo-collic responses: normal bilateral group (Group 1), normal unilateral (Group 2) and absent bilaterally group (Group 3). Motor assessment was achieved with Movement Assessment Battery for Children, second edition (MABC-2). Postural control (PC) was assessed using the dynamic Balance Quest platform. The scores obtained with MABC-2, and the postural parameters recorded on the Balance Quest platform (sway of Centre of Pressure and spectral power index) were analyzed and compared throughout the groups. ResultsGroup 1 (normal bilateral) showed the best scores regarding motor abilities and postural stability within available normative data. Group 3 (absent bilateral) had the lowest motor and postural control skills. A good correlation between the scores obtained by MABC-2 motor test and dynamic posturography (Balance Quest) was observed. ConclusionsThe presence of at least one sacculo-collic response would predict satisfactory static and dynamic motor and postural control skills in non-syndromic hearing-impaired children. MABC-2 and Dynamic Posturography Balance Quest appears reliable and comparable tools for PC assessment in hearing impaired children. In the light of these results, it appears that in young children candidates for uni- or bilateral CI whose walking is not yet acquired, should receive a vestibular assessment before surgery to avoid the risk of bilateral sacculo-collic function impairment.

Development of a conversion model between mechanical and electrical vestibular stimuli.

The vestibular end-organs encode for linear and angular head accelerations in space contributing to our internal representation of self-motion. Activation of the vestibular system with transmastoid electrical current has recently grown in popularity; however, a direct relationship between electrically evoked and mechanically evoked vestibular responses remains elusive in humans. We have developed and tested a mechanical-to-electrical vestibular stimulus conversion model incorporating physiological activation of primary vestibular afferents identified in nonhuman primates. We compared ocular torsional responses between mechanical (chair rotation) and model-derived electrical (binaural-bipolar) stimuli in separate experiments for an angular velocity step change (±10 deg/s over 1 s, ±4-mA peak amplitude; n = 10) and multisine angular velocities (±10 deg/s, 9.7 mA peak to peak, 0.05-1 Hz; n = 5), respectively. Perception of whole body rotation (n = 18) to our step-change stimuli was also evaluated. Ocular torsional slow-phase velocity responses between stimulation types were similar (paired two one-sided tests of equivalence: multiple P < 0.002; one-sample t test: P = 0.178) and correlated (Pearson's coefficient: multiple P < 0.001). Bootstrap analysis of perceived angular velocity likewise showed similarity in perceptual decay dynamics. These data suggest that central processing between stimuli was similar, and our vestibular stimulus conversion model with a conversion factor of ∼0.4 mA per deg/s for an angular velocity step change can generate electrical stimuli that replicates dynamic vestibular activation elicited by mechanical whole body rotations. This proposed vestibular conversion model represents an initial framework for using electrical stimuli to generate mechanically equivalent activation of primary vestibular afferents for use in biomedical applications and immersive reality technologies.NEW & NOTEWORTHY With the growing popularity of electrical vestibular stimulation in biomedical and immersive reality applications, a direct conversion model between electrical and mechanical vestibular stimuli is needed. We developed a model to generate electrical stimuli mimicking the physiological activation of vestibular afferents evoked by mechanical rotations. Ocular and perceptual responses evoked by mechanical and model-derived electrical stimuli were similar, thus providing a critical first step toward generation of electrically induced vestibular responses that have a realistic mechanical equivalent.

Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear

Expression patterns of transcription factors leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), transforming growth factor-β-activated kinase-1 (TAK1), SRY (sex-determining region Y)-box 2 (SOX2), and GATA binding protein 3 (GATA3) in the developing human fetal inner ear were studied between the gestation weeks 9 and 12. Further development of cochlear apex between gestational weeks 11 and 16 (GW11 and GW16) was examined using transmission electron microscopy. LGR5 was evident in the apical poles of the sensory epithelium of the cochlear duct and the vestibular end organs at GW11. Immunostaining was limited to hair cells of the organ of Corti by GW12. TAK1 was immune positive in inner hair cells of the organ of Corti by GW12 and colocalized with p75 neurotrophic receptor expression. Expression for SOX2 was confined primarily to the supporting cells of utricle at the earliest stage examined at GW9. Intense expression for GATA3 was presented in the cochlear sensory epithelium and spiral ganglia at GW9. Expression of GATA3 was present along the midline of both the utricle and saccule in the zone corresponding to the striolar reversal zone where the hair cell phenotype switches from type I to type II. The spatiotemporal gradient of the development of the organ of Corti was also evident with the apex of the cochlea forming by GW16. It seems that highly specific staining patterns of several transcriptions factors are critical in guiding the genesis of the inner ear over development. Our findings suggest that the spatiotemporal gradient in cochlear development extends at least until gestational week 16.

Revision surgery after triple semicircular canal plugging and morphologic changes of vestibular organ

This study aims to investigate the causes of vertigo relapse in patients with Meniere’s disease (MD) who had undergone triple semicircular canal plugging (TSCP) and explore the morphologic changes of vestibular organ through revision surgery. Eleven intractable MD patients who underwent TSCP initially and experienced episodic vertigo recurrence later, were enrolled. All patients accepted revision surgery, including seven cases who underwent labyrinthectomy and four cases who underwent repeat TSCP. Pure tone test, caloric test and video-head impulse test (v-HIT) were used to evaluate audiological and vestibular functions. Specimens of canal plugging materials and vestibular end organs were collected from patients who underwent labyrinthectomy during revision surgery. Mineralization and other histological characteristics of canal plugging materials were evaluated by von Kossa staining. Incomplete occlusion or ossification was observed in the semicircular canals (SCs) of all eleven patients, with all three SCs affected in three, the superior SC in five patients, the horizontal SC in two and the posterior SC in one. The results of v-HIT were in accordance with findings discovered intraoperatively. Few mineralized nodules and multiple cavities were found in the von Kossa-stained canal plugging materials. Incomplete occlusion or ossification of SCs was the principal cause of vertigo recurrence in MD patients who underwent TSCP. v-HIT was helpful in determining the responsible SCs.

Vestibular Compensation after Vestibular Dysfunction Induced by Arsanilic Acid in Mice.

When vestibular function is lost, vestibular compensation works for the reacquisition of body balance. For the study of vestibular dysfunction and vestibular compensation, surgical or chemical labyrinthectomy has been performed in various animal species. In the present study, we performed chemical labyrinthectomy using arsanilic acid in mice and investigated the time course of vestibular compensation through behavioral observations and histological studies. The surgical procedures required only paracentesis and storage of 50 µL of p-arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies.

Are Meniere’s disease patients with otolith organ impairment more likely to have balance dysfunction?

Background: Patients with Meniere’s disease (MD) may present with peripheral vestibular end organ dysfunction and balance dysfunction.Objective: This study aimed to compare the results of vestibular evoked myogenic potential (VEMP) tests with those of the sensory organization test (SOT) in patients with MD to determine whether they are correlated.Material and methods: In total, 132 patients with unilateral MD were evaluated using an audiometric test, the SOT, a caloric test and VEMP tests.Results: Cervical VEMP and ocular VEMP tests were conducted in 132 patients with MD, and the response rates of the affected side were lower than those of the unaffected side. The composite score, C5ES, and C6ES of the SOT were significantly decreased in patients with no VEMP responses compared to those with VEMP responses.Conclusions and significance: MD patients with no VEMP responses are more likely to develop balance impairment than those with VEMP responses. MD patients with otolith organ impairment may therefore have balance disorders, and should exercise caution to prevent falls and subsequent injuries.

Localization of melatonin and its receptors (melatonin 1a and 1b receptors) in the mouse inner ear

Background: In the inner ear, evidence has been gathered indicating that melatonin plays important roles in inner ear physiology and pathophysiology. However, no attempt has been made previously to investigate the localization or expression of melatonin and its receptors in the whole inner ear.Aims/objectives: To analyze the presence of melatonin and its receptors in the normal mouse inner ear.Material and methods: C57BL6/J mice were used in this study. The localizations of melatonin, MT1a and MT1b in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion and endolymphatic sac (ES), were studied by immunohistochemistry.Results: The organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory cells, vestibular dark and transitional cells, and ES epithelial cells showed an immunofluorescence reaction to melatonin, MT1a and MT1b.Conclusion and significance: The present findings show that melatonin and its receptors (MT1a and MT1b) are present in the inner ear, thus supporting the hypothesis that melatonin plays a physiological role in the inner ear.

Density of Macrophages Immunostained With Anti-iba1 Antibody in the Vestibular Endorgans After Cochlear Implantation in the Human.

Cochlear implantation may result in an increase in the density of macrophages in vestibular endorgans in the human. Vestibular symptoms are a common complication of cochlear implantation. In a previous study, we demonstrated histological evidence of a foreign-body response caused by silicon and platinum in the human cochlea following cochlear implantation. The objective of the current study was to seek evidence of a possible immune response in vestibular endorgans after cochlear implantation. The density of macrophages immunostained with anti-Iba1 antibody in the vestibular endorgans (lateral and posterior semicircular canals, utricle and saccule) in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy. The densities of macrophages in the neuroepithelium, subepithelial stroma, and among dendritic processes in the mid-stromal zone in four vestibular endorgans in the implanted and the opposite unimplanted ears were compared. The distributions of macrophage morphology (amoeboid, transitional and ramified) were also compared. The densities of macrophages in implanted ears in four vestibular endorgans were significantly greater than that in opposite unimplanted ears except in the subepithelial zone of the utricle and posterior semicircular canal. In contrast to the neuroepithelium, the subepithelial distribution of amoeboid macrophages in implanted ears was significantly less than in unimplanted ears. An increase in the density of macrophages in four vestibular endorgans after implantation was demonstrated. The transition among phenotype of macrophages suggested possible migration of amoeboid macrophages from the subepithelial stroma into the neuroepithelium.

Audiological and Vestibular Findings in Subjects with MELAS Syndrome.

The mitochondrial DNA (mtDNA) point mutation m.3243A>G is known to express the following two syndromes among others: maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Sensorineural hearing loss (SNHL) is the most frequent symptom in individuals harboring the m.3243A>G mutation. However, dysfunction of the vestibular organs has been scarcely examined. Therefore, the present study aimed to study the impact of the m.3243A>G mutation on the inner ear. A total of 8 subjects harboring the blood-verified m.3243A>G mutation underwent thorough audiological and vestibular examinations, including tone and speech audiometry, video head impulse test (vHIT), ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP), and full otoneurological examination. The subjects also answered a Dizziness Handicap Inventory (DHI) questionnaire. SNHL was identified in all the 8 subjects, with a mean pure-tone average-4 (PTA-4) of 59 dB. Speech discrimination score (n=7) ranged from 24% to 100% (mean 74%), and vHIT (n=42) detected pathology in nine lateral semicircular canals (SCCs), five posterior SCCs, and one anterior SCC, whereas three measurements were inconclusive. All oVEMPs (n=14 ears) were absent, nine cVEMPs were absent, and two were inconclusive. Based on the DHI scores, 6 subjects reported none to mild dizziness, 1 reported moderate, and 1 reported severe dizziness. Our study population had pathological findings from every audiological and vestibular end organs. The results indicated that the pathological findings originated from within the end organs themselves and not within the superior and inferior vestibular or cochlear nerve.

Is Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome (CANVAS) a Vestibular Ganglionopathy?

CANVAS is an acronym for cerebellar ataxia, neuropathy and vestibular areflexia syndrome. Limited autopsy data has suggested that CANVAS is caused by a focal dorsal root ganglionopathy that damages Scarpa's (vestibular) ganglion, but spares the Spiral (hearing) ganglion. If the vestibular areflexia of CANVAS is in fact due to ganglionopathy, then there should be global reduction of all vestibular responses. With this hypothesis in mind, a retrospective review of 5 subjects who met the clinical criteria for CANVAS was performed. Recent advances in vestibular testing have made it possible to quantify responses from all 5 vestibular end organs in the inner ear. Results of the Video head impulse test (VHIT), video oculography, caloric test and vestibular evoked myogenic potential (VEMP) were examined to determine if all 5 end organs are nonfunctional in CANVAS. Severe reduction of function of the six semicircular canals and ocular VEMPs were observed. Only the cervical VEMPs were present and reproducible, consistent with either partial sparing of the inferior vestibular ganglia, specific embryologic resistance of the saccule to the degeneration or a mechanism for cervical VEMPs that does not require an intact vestibular ganglion. Our results suggest that Scarpa´s ganglia dysfunction could be the mechanism for loss of semicircular canal and utricular function in CANVAS patients, but the preservation of the cervical VEMP response is unexplained.