Acoustic stimulation of the saccule gives rise to a vestibulocollic reflex, the output of which can be measured in the neck as inhibition of activity in the ipsilateral sternocleidomastoid muscle. This vestibular evoked myogenic potential has been promoted as a means of assessing integrity of saccular function. In this study, we test the hypothesis that the cochleosaccular hydrops of Ménière's syndrome leads to alterations in saccular motion that change the dynamics of the vestibular evoked myogenic potential.Prospective cohort study.Large specialty hospital, department of otolaryngology.Fourteen normal adult volunteers and 34 consecutive consenting adult patients with unilateral Ménière's disease by American Academy of Otolaryngology-Head and Neck Surgery diagnostic criteria.All subjects underwent vestibular evoked myogenic potential testing using ipsilateral broadband click and short tone-burst stimuli at 250, 500, 1,000, 2,000, and 4,000 Hz.Threshold, amplitude, and latency of vestibular evoked myogenic potential responses in normal and Ménière's affected and unaffected ears.Vestibular evoked myogenic potential was present in all ears tested. Normal subjects show a frequency-dependent vestibular evoked myogenic potential threshold, with best response ("frequency tuning") at 500 Hz. Compared with normal subjects and unaffected ears of Ménière's subjects, affected Ménière's ears had significantly increased vestibular evoked myogenic potential thresholds. Affected Ménière's ears showed threshold shifts at all frequencies and there was less tuning apparent at 500 Hz. Unaffected ears of Ménière's subjects also showed significantly elevated vestibular evoked myogenic potential thresholds compared with normal subjects. Analyses of vestibular evoked myogenic potential thresholds for effects of age, hearing loss, and audiometric configuration showed no significant differences.Ménière's ears display alterations in vestibular evoked myogenic potential threshold and tuning, supporting our hypothesis of altered saccular motion mechanics arising from hydropic distention. Unaffected ears of unilateral Ménière's subjects show similar changes, though to a lesser degree. This finding may be because of occult saccular hydrops in the asymptomatic ear or binaural interactions in the vestibular evoked myogenic potential otolith-cervical reflex arc.
Objective: The present study was undertaken to assess the sensitivity of vestibular evoked myogenic potentials testing to side-of-disease in Ménière’s disease patients and to test the hypothesis that information supplied by vestibular evoked myogenic potentials is complementary to that provided by a conventional vestibular test battery. Study Design: Prospective cohort study. Setting: Large specialty hospital, department of otolaryngology. Subjects: Twenty consenting adults (9 men and 11 women) with unilateral Ménière’s disease by American Academy of Otolaryngology–Head and Neck Surgery diagnostic criteria. Interventions: All subjects underwent bilateral vestibular evoked myogenic potentials testing using ipsilateral broadband click and short-toneburst stimuli at 250, 500, and 1,000 Hz. All subjects also underwent electronystagmography and sinusoidal vertical axis rotation testing. Main Outcome Measures: Accuracy of side-of-disease assignment by vestibular evoked myogenic potentials, caloric asymmetry, and multivariate analysis. Results: Side-of-disease assignment was most accurate using caloric asymmetry with a 5% interaural difference criterion, achieving 85% correct assignment. The next best method was vestibular evoked myogenic potentials using 250-Hz toneburst stimuli, achieving 80% correct assignment. The least accurate method was caloric asymmetry using a traditional 30% interaural difference limen, achieving 55% correct assignment. Comparison of 5% interaural difference criterion and vestibular evoked myogenic potentials using 250-Hz toneburst stimuli showed discordant results, but in no case did both 5% interaural difference criterion and vestibular evoked myogenic potentials using 250-Hz toneburst stimuli make an incorrect assignment. Conclusion: Vestibular evoked myogenic potentials threshold was shown to be highly sensitive to side-of-disease in unilateral Ménière’s disease. We observed instances of discordance in side-of-disease assignment by caloric asymmetry and vestibular evoked myogenic potential methods but no case in which both methods were incorrect. This supports the hypothesis that vestibular evoked myogenic potentials supplies information complementary to that provided by other components of the vestibular test battery.
Common causes of hearing loss in humans - exposure to loud noise or ototoxic drugs and aging - often damage sensory hair cells, reflected as elevated thresholds on the clinical audiogram. Recent studies in animal models suggest, however, that well before this overt hearing loss can be seen, a more insidious, but likely more common, process is taking place that permanently interrupts synaptic communication between sensory inner hair cells and subsets of cochlear nerve fibers. The silencing of affected neurons alters auditory information processing, whether accompanied by threshold elevations or not, and is a likely contributor to a variety of perceptual abnormalities, including speech-in-noise difficulties, tinnitus and hyperacusis. Work described here will review structural and functional manifestations of this cochlear synaptopathy and will consider possible mechanisms underlying its appearance and progression in ears with and without traditional ‘hearing loss’ arising from several common causes in humans.
Abstract Objectives: Proteins in perilymph may alter the delivery profile of implantable intracochlear drug delivery systems through biofouling. Knowledge of protein composition will help anticipate interactions with delivered agents. Study Design: Analysis of mouse perilymph. Methods: Protein composition of perilymph and cerebrospinal fluid (CSF) was analyzed using a capillary liquid chromatography‐mass spectrometry‐based iTRAQ quantitative proteomics approach. We searched against a mouse subset of the Uniprot FASTA protein database. We sampled perilymph from the apex of the mouse cochlea to minimize CSF contamination. Results: More than 50 explicit protein isoforms were identified with very high confidence. iTRAQ reporter ions allowed determination of relative molar amounts of proteins between perilymph and CSF. Protein in perilymph was almost three times more concentrated than in CSF. More than one‐third of the proteins in perilymph comprised protease inhibitors, with serpins being the predominant group. Apolipoproteins constituted 16%. Fifteen percent of the proteins were enzymes. Albumin was the most abundant single protein (14%). Proteins with relatively high perilymph/CSF ratios included broad‐spectrum protease inhibitors and apolipoproteins. Discussion: Some proteins found in perilymph, such as albumin and HMW kininogen, have been implicated in biofouling through adsorption to device materials. The relatively large quantities of apolipoprotein and albumin may serve as a reservoir for acidic and lipophillic drugs. Alpha‐2‐glycoprotein can bind basic drugs. Conclusions: Perilymph is similar in protein composition to CSF, though amounts are 2.8 times higher. Protease inhibitors comprise the largest category of proteins. Laryngoscope, 2009
Dynamic regulation of the expression of surface AMPA receptors (AMPARs) is a key mechanism to modulate synaptic strength and efficacy in the CNS and also to regulate auditory sensitivity. Here we address the role of surface AMPAR expression in excitotoxicity by blocking clathrin-mediated AMPAR endocytosis in auditory neurons. We used a membrane-permeable, dynamin-derived, myristoylated peptide (myr-Dyn) to inhibit surface AMPAR endocytosis induced by glutamate receptor agonists in culture and by noise exposure in vivo. Myr-Dyn infused into the mouse cochlea induced excitotoxic responses to acoustic stimuli that were normally not excitotoxic. These included vacuolization in the nerve terminals and spiral ganglion as well as irreversible auditory brain stem response threshold shifts. In cultured spiral ganglion neuronal cells, blockade of the reduction of surface AMPARs exacerbated neuronal death by incubation with N-methyl-d-aspartate and AMPA. This excitotoxic neuronal death could be prevented by calpeptin, a calpain-specific inhibitor. These results suggest that the reduction of surface AMPAR by endocytosis during excitatory stimulation plays an important role in limiting the excitotoxic damage to the neuron.
Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.
