The effect of a first-generation H1-antihistamine on postural control: a preliminary study in healthy volunteers.

First-generation H1-antihistamines are known to cause fatigue and drowsiness, due to their poor receptor selectivity and their high penetration rate of the blood-brain barrier. However, little is known about the effects of first-generation H1-antihistamines on postural stability. The purpose of this study was to evaluate the effects of d-chlorpheniramine on postural stability using posturography with and without foam rubber. A double-blind study with three parallel groups was conducted. Twenty-seven healthy young volunteers (mean age 21.9 years) were recruited and orally administered d-chlorpheniramine, 2 or 4 mg, or placebo. Postural sway was measured every hour up to 8 h after administration. Two-legged stance tasks were performed by each subject in four conditions: eyes open or eyes closed and with or without foam rubber. Inter-group comparisons showed that the group receiving 4-mg d-chlorpheniramine showed significantly larger sway in the eyes open with foam rubber condition (visual and vestibular information available, somatosensory information reduced). Inter-subject analysis in the 4-mg d-chlorpheniramine group showed that the effect of d-chlorpheniramine on postural control was variable. Our results suggest that among the three main sensory systems responsible for postural control (visual, vestibular, and somatosensory), d-chlorpheniramine may have a larger effect on the visual and/or vestibular systems in susceptible individuals.

Ocular vestibular evoked myogenic potentials in response to air-conducted sound and bone-conducted vibration in vestibular schwannoma.

OBJECTIVE: To clarify the origin and pathways of ocular vestibular evoked myogenic potentials (oVEMPs) to air-conducted sound (ACS), we compared the results of oVEMPs with ACS, with oVEMPs with bone-conducted vibration (BCV), cervical VEMPs (cVEMPs) with ACS, and the caloric test in patients with unilateral vestibular schwannoma (VS). STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Forty-five patients with untreated unilateral VS. MAIN OUTCOME MEASURE: Each patient underwent vestibular tests, including oVEMPs to ACS, oVEMPs to BCV, cVEMPs to ACS, and caloric tests. The correlations among these tests were evaluated. RESULTS: Of the 45 patients recruited, 28 patients (63%) showed reduced or absent oVEMPs to ACS solely on the affected side. There were no significant differences in abnormal response ratios among oVEMPs to ACS, oVEMPs to BCV, cVEMPs to ACS, or the caloric test. The results of oVEMPs to ACS had a significant correlation with those of oVEMPs to BCV and the caloric test (p < 0.05) but not with those of cVEMPs to ACS (p > 0.05). CONCLUSION: These findings support the hypothesis that oVEMP in response to ACS are predominantly mediated by the superior vestibular nerve and probably reflect the function of the utricle.

Evidence for the utricular origin of the vestibular short-latency-evoked potential (VsEP) to bone-conducted vibration in guinea pig.

Previous studies have shown that the vestibular short-latency-evoked potential (VsEP) in response to the brief head acceleration stimulus is a compound action potential of neurons innervating the otolith organs. However, due to the lack of direct evidence, it is currently unclear whether the VsEP is primarily generated by the activity of utricular or saccular afferent neurons, or some mixture of the two. Here, we investigated the origin of the VsEP evoked by brief bone-conducted vibration pulses in guinea pigs, using selective destruction of the cochlea, semicircular canals (SCCs), saccule, or utricle, along with neural blockade with tetrodotoxin (TTX) application, and mechanical displacements of the surgically exposed utricular macula. To access each end organ, either a dorsal or a ventral surgical approach was used. TTX application abolished the VsEP, supporting the neurogenic origin of the response. Selective cochlear, SCCs, or saccular destruction had no significant effect on VsEP amplitude, whereas utricular destruction abolished the VsEP completely. Displacement of the utricular membrane changed the VsEP amplitude in a non-monotonic fashion. These results suggest that the VsEP evoked by BCV in guinea pigs represents almost entirely a utricular response. Furthermore, it suggests that displacements of the utricular macula may alter its response to bone-conduction stimuli.

The effect of systemic administration of desmopressin on cochlear function in guinea pigs.

CONCLUSIONS: Systemic desmopressin (dDAVP) administration in guinea pigs for up to 2 weeks induced only minor or no significant changes in cochlear sensitivity, suggesting that other factors may be required to induce the cochlear dysfunction that is usually associated with endolymphatic hydrops. OBJECTIVES: To investigate the effects of chronic systemic administration of dDAVP, a synthetic analog of vasopressin, on cochlear sensitivity in guinea pigs. METHODS: dDAVP was administered subcutaneously via a mini-osmotic pump, at a rate of 0.2 ng/kg/min (low-dose group) or 2.0 ng/kg/min (high-dose group) for up to 2 weeks. Cochlear responses (compound action potentials) and distortion product otoacoustic emissions (DPOAEs) were measured. Example specimens were scanned using X-ray micro-tomography (micro-CT). RESULTS: Compared with the control group, the low-dose dDAVP group showed a significant threshold increase in response to a 2 kHz tone-burst after 2 weeks of treatment, and also a decrease in the amplitude of the DPOAE after 1 week of treatment. However, individual results were variable and the high-dose dDAVP group showed no significant change compared to the control group. In the micro-CT images, two of four ears in the low-dose group showed mild hydrops, but no hydrops was found in the three ears sampled from the high-dose group.

Effect of vestibular dysfunction on the development of gross motor function in children with profound hearing loss.

OBJECTIVE: To evaluate the function of the superior and inferior vestibular nerve systems in children with profound sensorineural hearing loss, and to assess the influence of dysfunction of each vestibular nerve system on the development of gross motor function. STUDY DESIGN: Retrospective study. SETTING: A tertiary referral center. METHODS: Eighty-nine children (age range: 20-97 months) with profound sensorineural hearing loss who were due to undergo cochlear implant surgery were recruited. Function of the superior vestibular nerve system was evaluated by the damped rotation test and the caloric test, whereas functions of the inferior vestibular nerve systems were evaluated by the vestibular evoked myogenic potential (VEMP) test. Gross motor development was assessed using the age of acquisition of head control and independent walking. RESULTS: Among the children able to complete the vestibular function tests, abnormalities were found in 20% (16 of 84 children) in the damped rotation test, 41% (31 of 75 children) in the caloric test and 42% (26 of 62 children) in the VEMP test. Children who showed abnormal responses in the vestibular function tests showed significantly delayed acquisition of head control (p < 0.05) and independent walking (p < 0.05) in comparison with children with normal responses. The children who showed abnormal responses in all 3 vestibular tests showed the greatest delay in acquisition of gross motor function in comparison with the other groups. CONCLUSIONS: Children with profound hearing loss tend to have dysfunction in the superior as well as the inferior vestibular nerve systems. Both the superior and inferior vestibular nerve systems are important for the development of gross motor function in children.

Diagnostic usefulness of multifrequency tympanometry for Ménière's disease.

Multifrequency tympanometry (MFT) is the measurement of the impedance of the middle ear transmission system at a wide range of frequencies from 200 Hz to 2 kHz. A potential use of MFT as a new diagnostic tool for detecting endolymphatic hydrops has recently been reported. However, its clinical usefulness for diagnosing Ménière's disease (MD) remains unclear. To evaluate the clinical usefulness of MFT as a new qualitative and diagnostic test for MD, we performed MFT in 70 patients with unilateral or bilateral MD and in 29 normal control subjects. The width of double peaks in the admittance tympanograms (Y width) at 2 kHz and the resonance frequency (RF) were analyzed, and receiver operating characteristic (ROC) curves were constructed. The Y width in MD-affected ears was significantly greater than that in control ears (p < 0.001). The RF in MD-affected ears was significantly lower than that in control ears (p < 0.01). Neither the Y width nor RF had a significant relationship with hearing levels or the results of caloric and vestibular myogenic potential testings. The area under the ROC curve was 0.71 for the Y width and 0.66 for the RF. At the optimal cutoff points, the sensitivity and specificity of the Y width were 47.3 and 86.8%, respectively, and those of the RF were 41.3 and 84.2%, respectively. These results indicated that MFT is significantly associated with the presence of MD, but its diagnostic accuracy is only modest. MFT is a simple, noninvasive test, which should be considered as a complementary test in the diagnosis of MD.

Effect of severity of vestibular dysfunction on postural instability in idiopathic bilateral vestibulopathy.

CONCLUSIONS: Foam posturography reveals that idiopathic bilateral vestibulopathy (IBV) significantly affects postural stability. Instability was more severe in patients with damage to both of the vestibular nerve systems. Residual function in the spared vestibular nerve system might contribute to postural stability in IBV. OBJECTIVE: Postural stability was assessed using foam posturography in patients with IBV according to whether the inferior, superior or both of the vestibular nerve systems were affected. METHODS: Two-legged stance tasks were performed by patients with IBV (n = 29) in four conditions: eyes open with and without foam rubber, and eyes closed with and without foam rubber. We examined six variables: the velocity of movement of the center of pressure (COP), the envelopment area traced by the movement of the COP, Romberg's ratio of velocity and area, and the foam ratios of velocity and area. RESULTS: The presence of IBV was significantly positively related to all the variables in adjusting for the subjects' gender and age (p < 0.001). Five of the 29 patients (17%) with IBV required assistance to prevent falling with eyes closed/foam rubber. Four of these five patients showed bilateral canal paresis in caloric testing and bilaterally no responses in cervical vestibular evoked myogenic potential testing.

Changes in cochlear function during acute endolymphatic hydrops development in guinea pigs.

Previous studies have injected artificial endolymph into scala media in anaesthetized guinea pigs as an acute model of endolymphatic hydrops. Here, we have injected artificial endolymph into scala media in guinea pigs at rates of 40-80 nl/min, whilst monitoring Compound Action Potential (CAP) thresholds, the Summating Potential (SP)/CAP ratio, Cochlear Microphonic (CM) distortion, low-frequency modulated Distortion Product Otoacoustic Emissions (DPOAEs), and the Endocochlear Potential (EP). We found that abrupt recovery of CAP thresholds, SP/CAP ratio, and CM and DPOAE asymmetric distortion could occur several times during a single injection of less than 3 µl, suggesting that endolymph pressure could periodically decrease while the injection was ongoing. Larger volumes are thought to produce a rupture of the membranous labyrinth, however, our results suggest that multiple injections, each larger than 3 µl and within 40 min of each other, cause multiple pressure-related changes, which are difficult to be explained on the basis of a simple labyrinth rupture. We have also examined the morphological changes of the temporal bones ex vivo using X-ray micro-tomography. Both the functional changes and the micro-CT images suggest ruptures of the membranous labyrinth may not always be responsible for abrupt changes in inner ear function. Our results provide a new insight into the changes in cochlear function occurring during acute hydrops development, which compares well to the clinical findings observed in Ménière's Disease. We suggest that hydrops development may be a continual process, yet cause discontinuous functional changes due to mechanisms other than a simple rupture of the membranous labyrinth.

Clinical characteristics of inferior vestibular neuritis.

CONCLUSIONS: Inferior vestibular neuritis (IVN) is a relatively minor subtype of vestibular neuritis (VN) and its clinical characteristics are unique. OBJECTIVES: To clarify clinical characteristics of IVN in comparison with conventional VN. METHODS: This was a retrospective case series review. Caloric responses and cervical vestibular evoked myogenic potential (cVEMP) responses were measured in 71 patients with VN. The patients were classified into three groups: (1) IVN group, who showed only asymmetrical cVEMP responses; (2) superior VN (SVN) group, who showed only asymmetrical caloric responses; (3) total VN (TVN) group, who showed asymmetrical responses in both tests. The clinical records of time course of subjective symptoms (duration of attack, duration of hospitalization, and time to remission) were reviewed and other profiles (age, sex, affected side, acute symptoms, and sequelae) were evaluated. RESULTS: Of the 71 patients with VN, 13 (18%) were classified as having IVN. The mean age and time to remission of patients with IVN (44.2 ± 4.8 years, 0.9 ± 0.5 months) were significantly lower and shorter, respectively, than those of patients with TVN (57.3 ± 2.5 years, 4.9 ± 4.7 months). There were no significant differences in other symptoms and profiles among the three groups. No patients with IVN showed benign paroxysmal positional vertigo as a sequela.

Different effects of head tilt on ocular vestibular-evoked myogenic potentials in response to bone-conducted vibration and air-conducted sound.

The ocular vestibular-evoked myogenic potentials (oVEMPs) in response to air-conducted sound (ACS) and bone-conducted vibration (BCV) have recently been used to assess otolith-ocular pathways in humans. Although the oVEMPs to BCV are considered to reflect the function of the utricle and superior vestibular pathway, the pathway of the oVEMPs to ACS remains controversial. In this study, we compared the effect of different head positions in the roll plane on oVEMPs in response to BCV and ACS in 20 normal subjects. Head tilt in the roll plane significantly increased the asymmetry ratio of oVEMPs to BCV (p < 0.01) but did not affect the asymmetry ratio of oVEMPs to ACS. Head tilt did not affect the latencies of oVEMPs to either BCV or ACS. Rotation of the body in the yaw plane while keeping the head straight ahead did not affect the asymmetry of oVEMPs to BCV (p > 0.6). These results suggest that oVEMPs to BCV reflect the activity of a different population of vestibular afferents to those which are active during oVEMPs to ACS.

Bilateral vestibulopathy with dissociated deficits in the superior and inferior vestibular systems.

OBJECTIVES: The aim of this study was to reveal the clinical characteristics of dissociated bilateral vestibulopathy (BV) affecting the superior vestibular nerve system on one side and the inferior vestibular nerve system on the other side. It is probable that BV does not always show bilateral deficits of the same vestibular nerve system. METHODS: In a retrospective study of 2,752 consecutive new patients, 1,560 patients had undergone both caloric testing and cervical vestibular evoked myogenic potential testing. All 1,560 patients had also undergone a battery of tests including standardized neurologic, neuro-otologic, neuro-ophthalmologic, and audiological examinations. RESULTS: Forty-three patients (2.8% of 1,560 patients) were given a diagnosis of dissociated BV. Among them, 10 patients (23%) had Meniere's disease and 6 patients (14%) had vestibular neuritis. Eighteen patients (42%) did not have any identifiable disease involving the peripheral vestibule, and 9 patients (21%) could be regarded as having a novel subtype of idiopathic BV. CONCLUSIONS: Although dissociated BV might be induced by some of the same causes that provoke bilateral vestibular dysfunction, a definite proportion of the patients did not have any identifiable causes of dissociated vestibular dysfunction. Idiopathic cases could be categorized into a novel subtype of idiopathic BV.

Assessment of postural stability using foam posturography at the chronic stage after acute unilateral peripheral vestibular dysfunction.

OBJECTIVE: To investigate the utility of foam posturography for assessing equilibrium at the chronic stage after acute unilateral peripheral vestibulopathy. METHODS: Thirty-four consecutive patients (16 patients at the chronic stage) with acute unilateral peripheral vestibulopathy and absent caloric responses unilaterally were recruited, along with 66 healthy control subjects. Two-legged stance tasks were performed in 4 conditions: with eyes open or closed, with or without using foam rubber. We adopted 6 parameters: the movement velocity of the center of pressure, the envelopment area traced by the movement of the center of pressure with eyes closed/foam rubber, Romberg's ratios of velocity and area with foam rubber, and the foam ratios (the ratio of a parameter measured with and without foam rubber) of velocity and area with eyes closed. RESULTS: All 6 parameters were significantly higher in the patients in the acute/subacute stage (<3 mo) than in the control subjects (p < 0.0001). Five parameters, excluding the foam ratio of the area with eyes closed, were still significantly higher in the patients at the chronic stage (>3 mo) than in the control subjects (p < 0.01). CONCLUSION: Foam posturography is useful for assessing equilibrium even at the chronic stage after acute unilateral peripheral vestibulopathy.

Developmental changes in the expression of Κv1 potassium channels in rat vestibular ganglion cells.

The primary afferent neurons of the vestibular ganglion convey sensory information from hair cells in the semicircular canals and otolith organs to the vestibular nuclei, the adjacent brainstem and the cerebellum. The intrinsic firing properties of vestibular ganglion cells (VGCs) are heterogeneous and have been classified into phasic, intermediate and tonic firing types on the basis of their response to injected depolarizing currents. A previous study from our group showed that the proportion of phasic discharging VGCs decreased during the first postnatal weeks. Moreover, α-dendrotoxin (α-DTX), a Kv1 potassium channels antagonist, turned neuron phasic firing to tonic, thus suggesting that these channels play an important role in the developmental changes of VGCs firing patterns. Here, by using immunohistochemistry, Western blotting and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we explored the change in the expression of α-DTX-sensitive K(+) channels, Kv1.1, Kv1.2 and Kv1.6 in rat VGCs during early postnatal periods. We showed that expression of Kv1.6 protein is down-regulated together with expression of Kv1.6 mRNA after postnatal day 7 in rat VGCs whereas expression of Kv1.1 and Kv1.2 proteins did not change during the same developmental period. Our results suggest that down-regulation of the Kv1.6 protein and mRNA may be associated with maturation of excitable properties of primary vestibular neurons.

The mitochondrial A3243G mutation involves the peripheral vestibule as well as the cochlea.

OBJECTIVES/HYPOTHESIS: To evaluate vestibular function in patients with the mitochondrial A3243G mutation. STUDY DESIGN: Data from patients with the A3243G mutation attending an academic tertiary referral center were prospectively recorded. METHODS: The clinical histories of 13 unrelated patients with the mitochondrial A3243G mutation (six mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; and seven maternally inherited diabetes and deafness) were recorded, in particular their history of vestibular symptoms. Vestibular examinations including caloric testing and vestibular evoked myogenic potentials in response to air-conducted sound (ACS-VEMPs) were performed. In seven patients who showed abnormal ACS-VEMP, VEMP in response to galvanic stimuli (galvanic-VEMP) were also recorded. RESULTS: Eleven of the 13 patients had vestibular symptoms. The age of onset of vestibular symptoms was significantly later than the ages of onset of hearing loss and diabetes mellitus (P < .05). Ten of the 13 patients showed abnormal caloric responses, whereas 12 patients showed abnormal ACS-VEMPs on one or both sides. All of the seven patients who underwent galvanic-VEMP testing showed normal responses. CONCLUSIONS: The A3243G mutation is associated with vestibular dysfunction involving both the superior and inferior vestibular nerve systems. Furthermore, our results from galvanic-VEMP testing suggests that a labyrinthine lesion is primarily responsible for the symptoms of vestibular dysfunction.

Responsiveness of rat vestibular ganglion neurons to exogenous neurotrophic factors during postnatal development in dissociated cultures.

We examined the responsiveness of rat vestibular ganglion neurons (VGNs) to exogenous neurotrophic factors, BDNF, NT-3, and GDNF, during postnatal development in dissociated cultures. VGNs were obtained from postnatal days (P) 1, 3, 7, and 14. After two days in culture, the survival of VGNs in control cultures without any exogenous neurotrophic factors was greater in younger (P1 or 3) rats than older (P7 or 14) rats. None of the three neurotrophic factors used facilitated survival of VGNs from older rats while only BDNF facilitated survival of VGNs from younger rats. BDNF was also effective both for increasing neurite sprouting in VGNs from younger rats and for neurite extension in VGNs from each of the postnatal ages. VGNs from P1 rats showed responsiveness to all three neurotrophic factors in their neurite sprouting. Developmental changes of VGNs in their responsiveness to exogenous neurotrophic factors should be considered in treating or preventing neuronal degeneration caused by peripheral vestibular lesions.

The ocular vestibular-evoked myogenic potential to air-conducted sound; probable superior vestibular nerve origin.

OBJECTIVE: Intense air-conducted sound (ACS) elicits an ocular vestibular-evoked myogenic potential (oVEMP), and it has been suggested that it does so by stimulating saccular receptors and afferents in the inferior vestibular nerve and so activating a crossed sacculo-ocular pathway. Bone conducted vibration (BCV) also elicits an oVEMP probably by activating utricular receptors and a crossed utriculo-ocular pathway. Are there two separate pathways mediating oVEMPs for ACS and BCV? If saccular receptors and afferents are primarily responsible for the oVEMP to ACS, then the oVEMP to ACS should be normal in patients with reduced or absent utricular function--unilateral superior vestibular neuritis (SVN). If utricular receptors and afferents are primarily responsible for oVEMP n10, then oVEMP to ACS should be reduced or absent in SVN patients, and in these patients there should be a close relationship between the size of the oVEMP n10 to BCV and to ACS. METHODS: The n10 component of the oVEMP to 500 Hz BCV and to 500 Hz ACS was recorded in 10 patients with unilateral SVN but who had saccular and inferior vestibular nerve function preserved, as shown by their normal cVEMP responses to ACS. RESULTS: In SVN patients with normal saccular and inferior vestibular nerve function, the oVEMP n10 in response to ACS was reduced or absent. Across SVN patients there was a very close correspondence between the size of oVEMP n10 for ACS and for BCV. CONCLUSIONS: The n10 component of the oVEMP to ACS is probably mediated predominantly by the superior vestibular nerve and so most likely by utricular receptors and afferents. SIGNIFICANCE: The n10 component of the oVEMP to either ACS or BCV probably indicates mainly superior vestibular nerve function.

Cephalic tetanus presenting as acute vertigo with bilateral vestibulopathy.

Cephalic tetanus is a rare form of tetanus, defined by paralysis of more than one cranial nerve. The seventh cranial nerve is the most frequently involved. We report a 58-year-old man with cephalic tetanus and bilateral vestibulopathy. The patient's initial symptoms were rotatory vertigo and hypertension. He then developed trismus and cranial nerve palsies of the fifth and seventh nerves. The caloric test and vestibular evoked mygenic potentials in response to air-conducted clicks revealed absent responses on both sides, although audiometry and auditory brainstem responses were normal in both ears. To the best of our knowledge, this is the first report of involvement of the eighth cranial nerve in cephalic tetanus.

Effect of the canalith repositioning procedure on subjective visual horizontal in patients with posterior canal benign paroxysmal positional vertigo.

CONCLUSION: Substantial numbers of patients with posterior canal benign paroxysmal positional vertigo (p-BPPV) have signs of utricular dysfunction at baseline. This improves after performing the canalith repositioning procedure. OBJECTIVE: To evaluate the changes of subjective visual horizontal (SVH) in patients with p-BPPV before and after treatment with the canalith repositioning procedure. METHODS: Twenty-six patients with p-BPPV were treated with the canalith repositioning procedure, Epley's maneuver, according to the affected side. Baseline SVH measurements were taken before performing the Dix-Hallpike maneuver and Epley's maneuver, for comparison with measurements taken just after Epley's maneuver, and 2 weeks after Epley's maneuver. RESULTS: Among 26 patients with p-BPPV, 11 (42%) showed abnormal deviation of SVH at baseline. Just after performing Epley's maneuver, the number of patients who showed an abnormal deviation of SVH decreased significantly to 15% (4 of 26 patients; p < 0.05). Two weeks after performing Epley's maneuver, only two patients (8%) showed an abnormal deviation of SVH (p < 0.001).

Functional ligand-gated purinergic receptors (P2X) in rat vestibular ganglion neurons.

The expression of purinergic receptors (P2X) on rat vestibular ganglion neurons (VGNs) was examined using whole-cell patch-clamp recordings. An application of adenosine 5'-triphosphate (ATP; 100microM) evoked inward currents in VGNs at a holding potential of -60mV. The decay time constant of the ATP-evoked currents was 2-4s, which is in between the values for rapidly desensitizing subgroups (P2X1 and P2X3) and slowly desensitizing subgroups (P2X2, P2X4, etc.), suggesting the heterogeneous expression of P2X receptors. A dose-response experiment showed an EC(50) of 11.0microM and a Hill's coefficient of 0.82. Suramin (100microM) reversibly inhibited the ATP-evoked inward currents. Alpha, beta-methylene ATP (100microM), a P2X-specific agonist, also evoked inward currents but less extensively than ATP. An application of adenosine 5'-dihosphate (ADP; 100microM) evoked similar, but much smaller, currents. The current-voltage relationship of the ATP-evoked conductance showed pronounced inward rectification with a reversal potential more positive than 0mV, suggesting non-selective cation conductance. However, the channel was not permeable to a large cation (N-methyl-d-glucamine) and acidification (pH 6.3) had little effect on the ATP-evoked conductance. RT-PCR confirmed the expression of five subtypes (P2X2-P2X6) in VGNs. The physiological role of P2X receptors includes the modulation of excitability at the synapses between hair cells and dendrites and/or trophic support (or also neuromodulation) from supporting cells surrounding the VGNs.