Comparison of the efficacy of the Epley maneuver and repeated Dix-Hallpike tests for eliminating positional nystagmus: A multicenter randomized study.

Background and objectives: Patients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix-Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week. Methods: This multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%. Results: Data for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin. Discussion: This study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living. Classification of evidence: This study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week. Registration number: UMIN000016421.

Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex.

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement.

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.

Rat Model of Ménière's Attack: Intratympanic Injection of Potassium Chloride Produces Direction-Changing Spontaneous Nystagmus and Hearing Fluctuations.

The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks.

Expression Analysis of Serotonin Receptors, Serotonin Transporter and l-Amino Acid Decarboxylase in the Mouse Sphenopalatine Ganglion by RT-PCR, Northern Blot Analysis and In Situ Hybridization.

The sphenopalatine ganglion (SPG) is a gathering of the cell bodies of parasympathetic fibers that dominate the nasal gland, lacrimal gland and cerebral blood vessels. The SPG controls nasal secretions, tears, and the dilation of cerebral blood vessels. However, it is unclear how serotonin regulates SPG functions. In this study, we investigated the expression of genes involved in the serotonergic system in the mouse SPG. We examined the mRNA expression levels of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3A, 5-HT3B, 5-HT4, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7 receptors, as well as serotonin transporter, tryptophan hydroxylases 1 and 2, and L-amino acid decarboxylase (AADC) by RT-PCR. It revealed that the 5-HT3A and 5-HT3B ionotropic receptors and AADC were likely to be highly expressed in the SPG, as measured by RT-PCR. We next performed in situ hybridization on the SPG to examine the expression of these three genes at the cellular level after validating the specificity of each cRNA probe by northern blotting. The 5-HT3A receptor, 5-HT3B receptor, and AADC were expressed in 96.5% ±â€¯1.0%, 29.7% ±â€¯10.7%, and 57.4% ±â€¯2.9% of neuronal cell bodies in the SPG, respectively, indicating that the 5-HT3A receptor was virtually expressed in all SPG neurons. Our results on the expression of these critical serotonin system genes in the parasympathetic SPG provide insight into the pathogenetics of rhinitis, conjunctivitis and headache. Furthermore, our findings suggest that targeting the 5-HT3A receptor might have therapeutic potential in the treatment of these ailments.

Change in endolymphatic hydrops 2 years after endolymphatic sac surgery evaluated by MRI.

OBJECTIVE: This study was performed to determine whether endolymphatic sac surgery improves vestibular and cochlear endolymphatic hydrops 2 years after sac surgery and to elucidate the relationship between the degree of improvement of endolymphatic hydrops and the changes in vertigo symptoms, the hearing level, and the summating potential/action potential ratio (-SP/AP ratio) by electrocochleography (ECochG) in patients with Ménière's disease (MD). METHODS: Twenty-one patients with unilateral MD who underwent sac surgery were included in this study. All patients underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI) before and 2 years after sac surgery. We evaluated the difference in vestibular and cochlear endolymphatic hydrops between before and after surgery in both ears and compared these findings with the frequency of vertigo attacks, hearing level, and ECochG findings. RESULTS: In affected ears, the presence of vestibular endolymphatic hydrops and the frequency of vertigo attacks significantly decreased after surgery. However, affected ears showed no significant improvement in the presence of cochlear endolymphatic hydrops or the -SP/AP ratio by ECochG; there was also no significant improvement or deterioration in the hearing level. CONCLUSION: The present findings suggest that sac surgery reduces vestibular endolymphatic hydrops and prevents aggravation of cochlear endolymphatic hydrops, and these changes lead to a reduction of vertigo attacks and suppress the progression of hearing impairment associated with vertigo attacks.

Visual Target Strategies in Infantile Nystagmus Patients With Horizontal Jerk Waveform.

The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.

Fibroblast growth factor 12 is expressed in spiral and vestibular ganglia and necessary for auditory and equilibrium function.

We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.

P2X2 Receptor Deficiency in Mouse Vestibular End Organs Attenuates Vestibular Function.

P2X2 receptors are ligand-gated cation channels activated by extracellular ATP that modulate neural transmission in various neuronal systems. Although the function and distribution of P2X2 receptors in the cochlea portion of the inner ear are well established, their physiological role in the vestibular portion is still not understood. Therefore, we investigated P2X2 receptor localization in the peripheral vestibular portion, and assessed their physiological function in vivo using P2X2 receptor knock out (P2X2-KO) mice. Histological analysis revealed that P2X2 receptors were localized on the epithelial surface of supporting and transitional cells of the vestibular end organs. To examine vestibular function in P2X2-KO mice, we conducted behavioral tests and tested the vestibulo-ocular reflex (VOR) during sinusoidal rotations. P2X2-KO mice exhibited significant motor balance impairment in the balance beam test. VOR gain in P2X2-KO mice was significantly reduced, with no decrease in the optokinetic response. In conclusion, we showed that P2X2 receptors are mainly localized in the supporting cells of the vestibular inner ear, and the loss of P2X2 receptors causes mild vestibular dysfunction. Taken together, our findings suggest that the P2X2 receptor plays a modulatory role in vestibular function.

Epiphycan is specifically expressed in cochlear supporting cells and is necessary for normal hearing.

The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function.

Three-dimensional analysis of linear vestibulo-ocular reflex in humans during eccentric rotation while facing downwards.

When participants undergo eccentric rotation (ER), i.e., they are rotated while displaced from the axis of rotation, they undergo both rotational stimulation and linear acceleration, which induces both the angular vestibulo-ocular reflex (aVOR) and linear VOR (lVOR). During ER, the lVOR induced by tangential linear acceleration enhances the eye movement induced by aVOR. In this study, we attempted to measure aVOR and lVOR separately, while participants underwent ER while facing the ground in a dark room. We analyzed three-dimensional eye movements using a video-oculography system. The participants sat on the ER chair either directly above the center of rotation, or with their head out, head in, right ear out, or left ear out against the center of rotation. Under these conditions, the rotational axis of the eye was perpendicular to the ground for rotational stimulation (aVOR), and the axis was parallel to the ground for linear stimulation (lVOR). Thus, measured eye movements could be separated into these two components. At 0.1 and 0.3 Hz rotation, we observed aVOR but not lVOR. However, when the stimulation frequency was above 0.5 Hz, we observed both aVOR and lVOR. These data indicate that lVOR is activated when the stimulation frequency is above 0.5 Hz. We conclude that it is possible to separately analyze aVOR and lVOR, and to simultaneously assess the function of aVOR and lVOR by analyzing eye movements induced when participants undergo ER above 0.5 Hz while facing the ground.

Assessment of endolymphatic hydrops and otolith function in patients with Ménière's disease.

Ménière's disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved. We used gadolinium-enhanced magnetic resonance imaging and measured cervical and ocular vestibular evoked myogenic potentials and the gain in the utricular induced linear vestibulo-ocular reflex to test the hypothesis that vestibular hydrops in Ménière's disease patients is associated with otolith organ dysfunction. We evaluated 21 patients diagnosed with unilateral definitive Ménière's disease using gadolinium magnetic resonance imaging to detect endolymphatic hydrops in the cochlea and vestibule. Cervical and ocular vestibular evoked myogenic potentials and the gain in utricular induced linear vestibulo-ocular reflex during eccentric rotation were measured to assess otolith organ function. For eccentric rotation, patients were rotated while displaced from the axis of rotation, while linear acceleration stimulated the utricle and induced the vestibulo-ocular reflex. Magnetic resonance imaging revealed vestibular hydrops in 14 of 20 patients (70%). Among the 14 patients, ten (71%) had abnormal cervical and three (21%) had abnormal ocular vestibular evoked myogenic potentials. Four patients (4/21, 19%) had abnormal linear vestibulo-ocular reflexes, three of whom also had abnormal ocular vestibular evoked myogenic potentials. Overall, 16 of 17 patients had normal linear vestibulo-ocular reflexes and normal ocular vestibular evoked myogenic potentials. Vestibular endolymphatic hydrops in Ménière's disease patients caused otolith organ dysfunction, mainly in the saccule. The number of Ménière's disease patients with abnormal ocular vestibular evoked myogenic potentials was low (19%), and they also had abnormal utricular induced linear vestibulo-ocular reflexes.

Functional Expression of an Osmosensitive Cation Channel, Transient Receptor Potential Vanilloid 4, in Rat Vestibular Ganglia.

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor.

Cisplatin-induced toxicity decreases the mouse vestibulo-ocular reflex.

Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0.5, 1.0 and 2.5Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16mg/kg, but not 8mg/kg, decreased the VOR gain at 2.5Hz compared with the vehicle control. Following 16mg/kg cisplatin treatment, the animals showed no change in the optokinetic nystagmus response, suggesting that no major changes in visual or oculomotor functions had occurred. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment.

Three-dimensional analysis of otolith-ocular reflex during eccentric rotation in humans.

When a participant is rotated while displaced from the axis of rotation (eccentric rotation, ER), both rotational stimulation and linear acceleration are applied to the participant. As linear acceleration stimulates the otolith, the vestibulo-ocular reflex (VOR) caused by the otolith (linear VOR; lVOR) would be induced during ER. Ten participants were rotated sinusoidally at a maximum angular velocity of 50°/s and at frequencies of 0.1, 0.3, 0.5, and 0.7Hz. The radius of rotation during ER was 90cm. The participants sat on a chair at three different positions: on the axis (center rotation, CR), at 90cm backward from the axis (nose-in ER, NI-ER) and at 90cm forward from the axis (nose-out ER, NO-ER). Their eye movements during rotation were recorded and analyzed three-dimensionally. The VOR gain during NI-ER was lower at 0.5 and 0.7Hz, and that during NO-ER was higher at 0.3, 0.5, and 0.7Hz than during CR. These results indicate that lVOR actually worked at 0.5 and 0.7Hz during ER and that the enhancement and decline of the VOR gain relative to the VOR gain during CR was seen in humans. Thus, we suggest that otolith function can be assessed via rotational testing of NI-ER and NO-ER.

High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of Eye Movements in Mice.

BACKGROUND: The mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum's role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult. METHODS: We developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye's angular velocity around the axis of eye rotation. RESULTS: When mice were rotated at 0.5 Hz and 2.5 Hz around the earth's vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz. CONCLUSIONS: To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.

New scoring system of an interview for the diagnosis of benign paroxysmal positional vertigo.

Conclusion This study investigated a novel instrument to diagnose benign paroxysmal positional vertigo (BPPV). Objective To develop a new scoring system of an interview for the diagnosis of BPPV. Methods The answers to questions on dizziness and/or vertigo (D/V) (571 patients) were analyzed and the questions for which the answers differed significantly between the patients with and without BPPV were selected. Results This study established an intensive questionnaire with a scoring system. It consists of the following questions: (1) Is rotary vertigo a characteristic of your D/V? (2) Is your D/V triggered when you roll your head over in a supine position? (3) Does your D/V disappear within 5 min? (4) Have you previously experienced hearing loss in one ear, or have you experienced hearing loss, tinnitus, or ear fullness with this D/V? One point each was given to an answer of 'yes' to questions (1) and (2). Two points were given to an answer of 'yes' to question (3). One point was subtracted upon an answer of 'yes' to question (4). When the total score was greater than two points, the patient was diagnosed with BPPV. The sensitivity of the diagnosis of BPPV by this scoring system was 81% and the specificity was 69%.

Gadolinium contrast-enhanced MRI reveals cystic lateral semicircular canal contents.

CONCLUSION: Contrast-enhanced magnetic resonance imaging (MRI) reveals variations in the endolymphatic morphology of the cystic lateral semicircular canal (CLSC) that correlate with inner ear function. This report is the first to suggest a relationship between the morphology and function of this common inner ear malformation in clinical cases. OBJECTIVES: This study investigated the radiological and functional findings of a common inner ear malformation using computed tomography (CT), gadolinium contrast-enhanced magnetic resonance imaging (MRI), caloric testing, and cervical and ocular vestibular evoked myogenic potential (VEMP) testing. METHOD: Four ears in three patients who were radiologically diagnosed with a CLSC and a normal cochlea on high-resolution CT and contrast-enhanced MRI were included. Semicircular canal and vestibular functions were analyzed using the caloric test and cervical and ocular VEMP testing. RESULTS: Unilateral and bilateral cystic canals were found in two and one patients, respectively. In the first patient, the malformed vestibule and cystic space were separate on imaging, and perilymph filled the cystic space. The functional test results were normal. In the second patient, endolymph filled both cystic spaces, and the functional responses were poor. In the third patient, endolymph filled the cystic space, and the ear did not respond during functional testing.

5-HT(3) receptor expression in the mouse vestibular ganglion.

The 5-hydroxytryptamine type 3 (5-HT3) receptor is a ligand-gated ion channel and a member of the Cys-loop family of receptors. Previous studies have shown 5-HT3 receptor expression in various neural cells of the central and peripheral nervous systems. Although the function and distribution of the 5-HT3 receptor has been well established, its role in the inner ear is still poorly understood. Moreover, no study has yet determined its localization and function in the peripheral vestibular nervous system. In the present study, we reveal mRNA expression of both 5-HT3A and 5-HT3B receptor subunits in the mouse vestibular ganglion (VG) by RT-PCR and in situ hybridization (ISH). We also show by ISH that 5-HT3 receptor mRNA is only expressed in the VG (superior and inferior division) in the peripheral vestibular nervous system. Moreover, we performed Ca(2+) imaging to determine whether functional 5-HT3 receptors are present in the mouse VG, using a selective 5-HT3 receptor agonist, SR57227A. In wild mice, 32% of VG neurons responded to the agonist, whereas there was no response in 5-HT3A receptor knockout mice. These results indicate that VG cells express functional 5-HT3 receptor channels and might play a modulatory role in the peripheral vestibular nervous system.

[Endolymphatic hydrops detected with inner ear gd contrast-enhanced MRI; comparison between administration routes or with ECochG or glycerol test].

OBJECTIVE: Gadolinium (Gd) contrast-enhanced MRI has recently been introduced to clinical practice to detect endolymphatic hydrops. However, since the image depends on the hardware, pulse sequence or the way of Gd administration, the protocol and the evaluating criteria for hydrops on MRI have not yet been standardized. In this study, we assessed the usefulness of the hydrops detection by MRI following the intratympanic or intravenous Gd administration methods, and compared these findings with the electrocochleography and glycerol test. METHODS: MRI was taken in 27 patients with Meniere's disease or delayed endolymphatic hydrops. All patients had frequent episodes of vertigo attacks which were clinically considered as of unilateral ear origin. Two types of Gd administration were used; injection into the tympanic cavity in 17 patients or intravenous injection in 10 patients. Axial 2D-FLAIR images were obtained with a 3.0T MRI unit, 24 and 4 h after intratympanic or intravenous administration, respectively. The endolymphatic space was detected as a low signal intensity area, while the surrounding perilymphatic space showed high intensity with Gd contrast. Those cases in which low signal areas corresponding to the cochlear duct could be clearly noticed, were classified as cochlear hydrops. When the greater part of the vestibule was occupied by a low signal area in more than half of the images, it was classified as vestibular hydrops. RESULTS: Endolymphatic hydrops was detected in 88% (15/17 cases) by the intratympanic Gd administration method, and 90% (9/10) by the intravenous method. In the contralateral ears, 20% (2/10) showed hydrops, detected by the intravenous method. ECochG and the glycerol test were difficult when the hearing of the patient was severely impaired. Positive results of EcochG and the glycerol test were obtained only in 15 and 6 cases, respectively. However, as far as the waves could be obtained, ECochG showed a high detection rate of 88% (15/17) in the affected ear. In those cases in which both MRI and EcochG could be obtained, including both ears, the results were matched in 78% (21/27ears). CONCLUSION: For the qualitative detection of hydrops, intratympanic and intravenous Gd administration methods were equivalent. Inner ear Gd contrast-enhanced MRI had higher efficacy in the detection of hydrops than the conventional tests.