Inner Ear Fluid Research Articles

Immunohistochemical localisation of aquaporin 2 and vasopressin type 2 receptor in the human endolymphatic sac.

This study aimed to determine the distribution and subcellular localisation of aquaporin 2 and vasopressin type 2 receptor in the human endolymphatic sac. Ten samples of human endolymphatic sac were collected during acoustic neurinoma removal using the translabyrinthine approach. Immunohistochemistry and immunofluorescence were performed using aquaporin 2 and vasopressin type 2 receptor monoclonal antibodies. Confocal microscopy demonstrated that vasopressin type 2 receptor labelling was expressed in both the apical and basolateral plasma membranes, and in the cytoplasm of the endolymphatic sac epithelium, whereas aquaporin 2 was strongly expressed at the basolateral site of the endolymphatic sac epithelium, in both the intraosseous and extraosseous parts of the endolymphatic sac. Both aquaporin 2 and vasopressin type 2 receptor were detected in the epithelial cells of the human endolymphatic sac, suggesting that this channel may be involved in inner-ear fluid homeostasis. However, strong basolateral expression of aquaporin 2 in endolymphatic sac epithelium suggested that the function of aquaporin 2 may differ between the endolymphatic sac and kidney.

Bone-conduction hyperacusis induced by superior canal dehiscence in human: the underlying mechanism

Our ability to hear through bone conduction (BC) has long been recognized, but the underlying mechanism is poorly understood. Why certain perturbations affect BC hearing is also unclear. An example is BC hyperacusis (hypersensitive BC hearing)—an unnerving symptom experienced by patients with superior canal dehiscence (SCD). We measured BC-evoked sound pressures in scala vestibuli (PSV) and scala tympani (PST) at the basal cochlea in cadaveric human ears, and estimated hearing by the cochlear input drive (PDIFF = PSV – PST) before and after creating an SCD. Consistent with clinical audiograms, SCD increased BC-driven PDIFF below 1 kHz. However, SCD affected the individual scalae pressures in unexpected ways: SCD increased PSV below 1 kHz, but had little effect on PST. These new findings are inconsistent with the inner-ear compression mechanism that some have used to explain BC hyperacusis. We developed a computational BC model based on the inner-ear fluid-inertia mechanism, and the simulated effects of SCD were similar to the experimental findings. This experimental-modeling study suggests that (1) inner-ear fluid inertia is an important mechanism for BC hearing, and (2) SCD facilitates the flow of sound volume velocity through the cochlear partition at low frequencies, resulting in BC hyperacusis.

Refining non-invasive techniques to measure intracranial pressure: comparing evoked and spontaneous tympanic membrane displacements

Objective: Tympanic membrane displacements (TMDs) are used to non-invasively gauge inner-ear fluid pressure. Inner-ear fluid pressure equalizes with intracranial pressure (ICP) via the cochlear aqueduct and therefore TMDs can indirectly evaluate ICP. We studied the relationship between two TMD modalities, evoked and spontaneous. Evoked TMD is a reflex response to an auditory stimulus and the established stapes-footplate mechanism explains how evoked TMDs change with ICP. Spontaneous TMD refers to a pulsatile TMD waveform expressed in the form of pulse amplitudes (TMD-PAs), the origins of which are poorly understood. We investigated whether both modalities respond similarly to an ICP change, suggesting a common mechanism. Approach: ICP was manipulated in 20 healthy volunteers by a postural change from sitting (lower ICP) to supine (higher ICP). Differences between paired sitting and supine TMD results generated ΔEvoked and ΔSpontaneous values. Main results: Evoked TMDs became more inward on lying supine while spontaneous TMDs became more outward. There was no evidence of a correlation between ΔEvoked and ΔSpontaneous (Right ears: r = −0.38, p = 0.10, 95% CI −0.75 to 0.21; Left ears: r = 0.34, p = 0.16, 95% CI −0.17 to 0.75). Significance: This suggests the stapes-footplate mechanism is not the primary mechanism explaining how spontaneous TMDs respond to changing ICP.

Noninvasive detection of alarming intracranial pressure changes by auditory monitoring in early management of brain injury: a prospective invasive versus noninvasive study

BackgroundIn brain-injured patients intracranial pressure (ICP) is monitored invasively by a ventricular or intraparenchymal transducer. The procedure requires specific expertise and exposes the patient to complications such as malposition, hemorrhage or infection. As inner-ear fluid compartments are connected to the cerebrospinal fluid space, ICP changes elicit subtle changes in the physiology of the inner ear. Notably, we previously demonstrated that the phase of cochlear microphonic potential (CM) generated by sound stimuli rotates with ICP. The aim of our study was to validate the monitoring of CM as a noninvasive method to follow ICP.MethodsNon-invasive measure of CM-phase was compared to ICP recorded invasively in a prospective series of patients with acute brain injury managed in a neuro-intensive care unit. The study focused on patients with varying ICP and normal middle-ear function.ResultsIn the 24 patients with less than 4 days of endotracheal ventilation and whose ICP fluctuated (50-hour data), we demonstrated close correlation between CM-phase rotation and ICP (average 1.26 degrees/mmHg). As a binary classifier, CM phase changes of 7–10 degrees signaled 7.5-mmHg ICP increases with a sensitivity of 83% and 19% fallout.ConclusionReference methods to measure ICP require the surgical placement of a pressure transducer. Noninvasive CM-based monitoring of ICP might be beneficial to early management of brain-injured patients with initially preserved consciousness and to the diagnosis of neurological conditions, whenever invasive monitoring cannot be performed.Trial registrationClinicalTrials.gov NCT01685476, registered on 30 August 2012.

A dual wedge microneedle for sampling of perilymph solution via round window membrane.

Precision medicine for inner-ear disease is hampered by the absence of a methodology to sample inner-ear fluid atraumatically. The round window membrane (RWM) is an attractive portal for accessing cochlear fluids as it heals spontaneously. In this study, we report on the development of a microneedle for perilymph sampling that minimizes the size of RWM perforation, facilitates quick aspiration, and provides precise volume control. Here, considering the mechanical anisotropy of the RWM and hydrodynamics through a microneedle, a 31G stainless steel pipe was machined into wedge-shaped design via electrical discharge machining. The sharpness of the needle was evaluated via a surface profilometer. Guinea pig RWM was penetrated in vitro, and 1 μL of perilymph was sampled and analyzed via UV-vis spectroscopy. The prototype wedge shaped needle was successfully fabricated with the tip curvature of 4.5 μm and the surface roughness of 3.66 μm in root mean square. The needle created oval perforation with minor and major diameter of 143 and 344 μm (n = 6). The sampling duration and standard deviation of aspirated volume were 3 s and 6.8 % respectively. The protein concentration was 1.74 mg/mL. The prototype needle facilitated precise perforation of RWMs and rapid aspiration of cochlear fluid with precise volume control. The needle design is promising and requires testing in human cadaveric temporal bone and further optimization to become clinically viable.

Human middle-ear model with compound eardrum and airway branching in mastoid air cells.

An acoustical/mechanical model of normal adult human middle-ear function is described for forward and reverse transmission. The eardrum model included one component bound along the manubrium and another bound by the tympanic cleft. Eardrum components were coupled by a time-delayed impedance. The acoustics of the middle-ear cleft was represented by an acoustical transmission-line model for the tympanic cavity, aditus, antrum, and mastoid air cell system with variable amounts of excess viscothermal loss. Model parameters were fitted to published measurements of energy reflectance (0.25-13 kHz), equivalent input impedance at the eardrum (0.25-11 kHz), temporal-bone pressure in scala vestibuli and scala tympani (0.1-11 kHz), and reverse middle-ear impedance (0.25-8 kHz). Inner-ear fluid motion included cochlear and physiological third-window pathways. The two-component eardrum with time delay helped fit intracochlear pressure responses. A multi-modal representation of the eardrum and high-frequency modeling of the middle-ear cleft helped fit ear-canal responses. Input reactance at the eardrum was small at high frequencies due to multiple modal resonances. The model predicted the middle-ear efficiency between ear canal and cochlea, and the cochlear pressures at threshold.

Large vestibular aqueduct syndrome and endolymphatic hydrops: two presentations of a common primary inner-ear dysfunction?

To present the theory that large vestibular aqueduct syndrome (i.e. the recognised existence of an enlarged vestibular aqueduct with progressive sensorineural hearing loss) and endolymphatic hydrops are due to a common primary dysfunction of inner-ear fluid homeostasis. Case report and review of the world literature concerning large vestibular aqueduct syndrome and endolymphatic hydrops. We report a family in which one sibling suffered from large vestibular aqueduct syndrome while the other had classic Ménière's disease. This suggests that large vestibular aqueduct syndrome and endolymphatic hydrops, in some cases, may be due to a common primary dysfunction of inner-ear fluid homeostasis. To our knowledge, this is the first report in the world literature to postulate that variation in the relative compliance of inner-ear membranes could be the factor that determines the manifestation of the disorder as either endolymphatic hydrops or large vestibular aqueduct syndrome.

Comment on “When an Air-Bone Gap is not a Sign of a Middle-Ear Conductive Loss” By Sohmer et al.

Comment on “When an Air-Bone Gap is not a Sign of a Middle-Ear Conductive Loss” By Sohmer et al.

Stria vascularis and vestibular dark cells: characterisation of main structures responsible for inner-ear homeostasis, and their pathophysiological relations

The regulation of inner-ear fluid homeostasis, with its parameters volume, concentration, osmolarity and pressure, is the basis for adequate response to stimulation. Many structures are involved in the complex process of inner-ear homeostasis. The stria vascularis and vestibular dark cells are the two main structures responsible for endolymph secretion, and possess many similarities. The characteristics of these structures are the basis for regulation of inner-ear homeostasis, while impaired function is related to various diseases. Their distinct morphology and function are described, and related to current knowledge of associated inner-ear diseases. Further research on the distinct function and regulation of these structures is necessary in order to develop future clinical interventions.

Three‐Dimensional Fluid‐Attenuated Inversion Recovery Magnetic Resonance Imaging Findings in Patients with Sudden Sensorineural Hearing Loss

To evaluate the inner ear in sudden sensorineural hearing loss (SNHL) using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) at 3 Tesla (T). 3D-FLAIR MRI has recently been developed to detect high concentrations of protein or hemorrhage. Application of this method to sudden SNHL has not been described. We used 3D-FLAIR at 3 T with and without gadolinium enhancement to evaluate eight patients with sudden SNHL. In four of eight ears with idiopathic sudden SNHL, high precontrast signals were observed within the inner ear on 3D-FLAIR. The high-signal areas observed on 3D-FLAIR were not detected by T1- or T2-weighted MRI in any of these patients. In one of these four ears, significant gadolinium enhancement was observed on 3D-FLAIR. Half the patients with sudden SNHL examined had high signals in the SNHL-affected ear on 3D-FLAIR at 3 T. High precontrast signals in the inner-ear fluid space may reflect minor hemorrhage, or an increased concentration of protein that had passed through blood vessels with increased permeability, or had originated from disrupted cells in the inner ear. Gadolinium enhancement in one ear suggested the breakdown of the blood-labyrinth barrier. 3D-FLAIR MRI should contribute markedly to the elucidation of pathologic conditions in the inner ears of patients with idiopathic sudden SNHL.

Relationship between inner-ear fluid pressure and semicircular canal afferent nerve discharge.

The present study was designed to determine (1) the transcupular fluid pressure (deltaP) generated across the semicircular canal cupula in response to sinusoidal head rotation, (2) the translabyrinthine dilational pressure (P0) generated across the membranous labyrinth in response to an increase in endolymph fluid volume (hydrops), (3) afferent nerve discharge patterns generated by these distinct pressure stimuli and, (4) threshold values of deltaP and P0 required to elicit afferent neural responses. The experimental model was the oyster toadfish, Opsanus tau. Micromechanical indentation of the horizontal canal (HC) duct and utricular vestibule was used to simulate sinusoidal head rotation and fluid volume injection. Single-unit neural spike trains and endolymph pressure within the ampulla, on both sides of the cupula, were recorded simultaneously. deltaP averaged 0.013 Pa per 1 degrees/s of sinusoidal angular head velocity and P0 averaged 0.2 Pa per 1 nL of endolymph volume injection. The most responsive afferents had a threshold sensitivity to deltaP of 10(-3) Pa and to P0 of 5 x 10(-2) Pa based on a discharge modulation criterion of 1 impulse/s per cycle for 2 Hz pressure stimuli. Neural sensitivity to AP was expected on the basis of transverse cupular and hair bundle deflections. Analysis of mechanics of the end organ, neuronal projections into the crista, and individual neural firing patterns indicates that P0 sensitivity resulted from pressure-induced distension of the ampulla that led to a nonuniform cupular deformation pattern and hair bundle deflections. This explanation is consistent with predictions of a finite element model of the end organ. Results have implications regarding the role of deltaP in angular motion transduction and the role of P0 under transient hydropic conditions.

Fonética y fonología actual del español By Francesco D'Introno (review)

BOOK NOTICES Fonética y fonología actual del español. By Francesco D'Introno, Enrique del Teso, and Rosemary Weston. Madrid: Cátedra, 1995. Pp. 478. This thorough and technical treatise, in Spanish, is on the phonetics and phonology ofSpanish as well as on contemporary phonological theory generally. The first chapter, 'La fonética en los estudios del lenguaje' (11-137), runs the gamut from a review ofNewtonian physics through acoustic, auditory, and articulatory phonetics. Details along the way include the geometry of vector quantities (14, n. 1), kinds of sound spectrogram equipment (59-62), chemistry of different inner-ear fluids (66), and much more. Equal thoroughness is granted to the treatment of acoustic and articulatory phonetics in spite ofthe latter's perhaps greater accessibility to the general reader's intuition . The second chapter, 'Fonemas y alófonos del espa ñol' (139-313), includes not only presentation of the structuralist phonemic inventory but also detailed treatments of topics such as secondary stress (169-73) and glide fortition (241-58). The chapter generally follows Tomás Navarro Tomás's Manual de pronunciación española (12th edn., Madrid: CSIC, 1965), both in theoretical approach and in the choice of dialect for description, namely educated Madrilenian speech. The third and final chapter, 'Fonología generativa ', devotes subsections to SPE (315-48), autosegmental (348-84), CV (384-96), lexical (397-99), and 'nonderivational' (i.e. optimality theory , 442-61) phonologies. It also includes up-to-date surveys of work on Spanish syllable structure (400-10) and stress (41 1-36). Intonation is reviewed briefly (131-35, 436-42). The SPE framework and its successor theories are each introduced organically , i.e. with clear rationales as to what existing theoretical inadequacies they were intended to remedy. Ch. 3 differs from Chs. 1 and 2 in giving more frequent citations of sources in the literature, and—especially after the SPE section—the discussion is more about current phonological theory than about that theory as applied to Spanish. While linguists such as James Harris and William Cressey have produced entire treatments of Spanish phonology ostensibly in the SPE framework, no such broad studies for this language have yet appeared under the successor theories. The text is supported graphically by diagrams, spectrograms, and tables. The bibliography (463-68) cites some 115 titles. Self-reference includes a subject index (469-71) and a finely-dissected table of contents (473-78). Although highly technical in subject matter, the book is written with clarity and consideration for the neophyte reader. Invisible phenomena are explained by analogies to familiar experiences: the vibration of complex sound waves is compared to a column of elastic balls bouncing one on top ofanother; autosegmental tiers are imagined like notebook pages radiating at different angles from their spiral binding; and so on. My only complaint is about the fatigue of reading closely-spaced lines of 11-point type on an off-white stock. A larger print and/or a brighter white paper would have been easier on the eyes. [Steven Lee Hartman, Southern Illinois University, Carbondale .] More Englishes: New studies in varieties of English 1988-1994. By Manfred Görlach. (Varieties of English around the world, G13.) Amsterdam & Philadelphia : John Benjamins, 1995. Pp. 276. $49.00. Manfred Görlach's editorship of the journal English World-Wide (EWW) and the series Varieties of English around the world as well as his own research have made him a prominent name within English studies. This collection brings together eight of his more recent articles, several of which have appeared elsewhere in slightly different form: Four are reprinted outright, with three from his own tenure at EWW. The 'reprinted' nature of this fine volume raises the question of who can really afford to buy such a relatively expensive book when many of the individual articles may be found elsewhere. But concerns of this nature are usually offset by the convenience of having the articles collected in one accessible source, and this is certainly the case here. All things considered, this collection of papers will interest researchers whose work falls across the areas ofsociolinguistics, applied linguistics, creóle studies, and dialectology. The book is divided into eight chapters...

Cytomegalovirus antibodies in endolymphatic sac biopsies of patients with endolymphatic hydrops and Ménière's disease.

Numerous viruses have been implicated as ototropic and as a contributing or initiating factor in inner-ear disorders. These ototropic viruses (mumps, CMV, herpes simplex virus, varicella-zoster, and the coxsackie virus) can cause damage or death to various hair cells, resulting in hearing loss and balance disorders. CMV infections are classified as two major types: the first is clinically seen at birth and is systemic in nature, and the second is not clinically apparent at birth and is termed asymptomatic or subclinical. Importantly, both types of CMV infections have reported otologic sequelae and involvement with the property of neurotropism.'.2 Thirty to fifly percent of patients with symptomatic CMV have reported hearing whereas a substantially lower number (7-13%) of patients who are asymptomatic have reported hearing I o s s , ~ , ~ * ' presumably related to the CMV infection. Recent speculations suggest that CMV infections may not be solely associated with congenital infections, but also with the reactivation of latent virus or with primary infections later in life, or as a primary or secondary trigger mechanism. However, definitive evidence of a viral etiology of Menitre's disease is lacking. Menitre's disease may be secondary to dysfunction of the ELS. The main function of the ELS is to act as a resorptive site for endolymph and is the main defensive mechanism for the inner ear. It is an important site for endolymph absorption,* regulation of the inner ear and inner-ear fluid dynamic^.'^*'^ Recent evidence indicates that dysfunction of the ELS and its inability to resorb endolymph resulting in ELH, may be a contributing factor, but not the only factor in the development of Menikre's disease. Studies involving immunohistochemical

Longitudinal non-invasive perilymphatic pressure measurement in patients with Ménière's disease.

The homeostasis of inner-ear fluids is essential for the functions of hearing and equilibrium. Inner-ear disorders, such as Ménière's disease, are affected by inner-ear pressure. The displacement of the human tympanic membrane can be studied by means of the MMS-10 Tympanic Displacement Analyser (Marchbanks Measurement Systems Ltd., UK) and is thought to be a measure for perilymphatic pressure variations. This measurement was performed in 18 patients with Ménière's disease (20 affected ears) at regular intervals, in order to investigate possible pressure variations in relation to the following symptoms: hearing loss, vertigo, tinnitus and pressure sensation. Symptoms changed independently; changes in symptoms were not significantly related to changes in perilymphatic pressure, as measured by means of the MMS-10 analyser.

The significance for postoperative hearing of preserving the labyrinth in acoustic neurinoma surgery.

Among 186 patients with preoperative hearing, a total of 189 acoustic neurinomas were removed through a lateral suboccipital approach with anatomical preservation of the cochlear nerve. Functional hearing was preserved in 92 (49%) of these patients; despite anatomical preservation of the cochlear nerve, deafness was the result in 51% of the series. Many factors have been considered to cause hearing loss in patients whose cochlear nerve was intact after surgery; these include nerve retraction, nerve or cochlear ischemia, overheating and vibration damage to the nerve, and opening of the labyrinth. To evaluate the significance of injury to the labyrinth in postoperative hearing loss, a prospective study was undertaken. High-resolution computerized tomography studies through the inner ear with bone algorithm were performed pre- and postoperatively. The postoperative status of the labyrinth was classified into three patterns: intact, fenestrated, and widely opened. Injury to the labyrinth occurred in 30% of the cases. The most frequently injured labyrinth structures were the crus commune of the posterior and superior semicircular canals (52%), the posterior semicircular canal (23%), the vestibule (21%), and the superior semicircular canal (4%). A statistically significant relationship was found between injury to the labyrinth and deafness, elevated thresholds, and lower discrimination values at pure-tone audiograms and speech audiometry (p < 0.0001). The degree of the injury (comparison between fenestration and wide opening of the labyrinth) was also significantly related to postoperative deafness (p < 0.0001). Disturbance of the inner-ear fluids was considered to be the cause of the hearing loss. In 12 patients labyrinth injury was not associated with deafness. This finding may support the existence of mechanisms of cochlear protection. The homeostatic function of the endolymphatic sac was considered to play an important role in recovery of damaged hearing in these 12 cases.

Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity.

This review critically evaluates the literature on aminoglycoside pharmacokinetics in order to answer the question how fluid and tissue levels of the drugs relate to the development of ototoxic and nephrotoxic side effects. We will summarize the evidence that: (1) aminoglycosides do not accumulate in inner-ear fluids; (2) aminoglycoside levels in fluids do not correlate with the ototoxic potential of a drug, and (3) selective toxicity cannot be explained by selective tissue penetration of the drugs. We suggest that studies of drug disposition at the cellular level after chronic aminoglycoside treatment be conducted to establish whether a cell-specific uptake contributes to the selective toxicity of the aminoglycoside antibiotics. A sequence of biochemical events that may lead to the development of toxicity at the molecular level is briefly described.

The effect of furosemide on sodium and potassium concentrations in guinea-pig perilymph.

To observe the effects of furosemide on electrolyte concentrations in inner-ear fluids, experiments were performed on 286 normal guinea-pigs. Intravenous injection of furosemide (15 mg/kg) induced increases of Na concentration in scala tympani perilymph, scala vestibuli perilymph, and cerebrospinal fluid (CSF). K concentrations in both perilymphs and CSF were also increased by furosemide. The increased Na concentrations are thought to be due to the dehydration of body fluids induced by the diuretic action of furosemide. The increase of K concentrations in perilymphs could be attributable to either a characteristic action of furosemide on the electrolyte transport in the inner ear or a secondary change caused by a rise of K concentration in the endolymph.

Potentiation of cochlear injury by noise and ototoxic antibiotics in guinea pigs

Guinea pigs were exposed to 8-kHz octave band noise, eight hours daily for one week, while receiving kanamycin 200 mg/kg daily. Other groups of animals received kanamycin alone, noise exposure alone, or both treatments separated in time. Two weeks after kanamycin treatment, injury to the cochlea was assessed in terms of reduction in the microphonic potential (CM) recorded at the round window and hair cell loss as evaluated in surface preparations. Pathological changes were greatest when noise exposure was concurrent with kanamycin treatment or preceded it by only one week. Noise exposure alone and other sequences, with and without an intervening week of rest, produced lesser degrees of injury. The results are compatible with the hypothesis that noise exposure affects the hemato-labyrinthine barrier, causing a more rapid accumulation of the antibiotic in the inner-ear fluids and tissues or a reduced rate of clearance from them. [Supported by NIH-NIEHS contract NO 1-ES-2-2110 and NIH Program Project Grant 05785.]

A rapid protein test for inner ear fluid analysis.

A rapid protein test for inner ear fluid analysis.

Chemical evaluation of inner ear fluid as a diagnostic aid.

Biochemical analyses have been made of the inner-ear fluids of patients with otosclerosis, Meniere's disease, and acoustic neurinoma. Unconta-minated samples of perilymph removed from the vestibule of otosclerotic ears show normal values for K, Na, and protein. For Meniere's disease, fluid from the vestibule shows normal values for endolymph and from the scala tympani of the basal turn, normal values for perilymph. For patients with acoustic neurinoma, the fluid removed from the vestibule and from the horizontal canal shows very high protein values even for those patients having normal protein values in the cerebrospinal fluid. Biochemical analysis of inner-ear fluid is a useful aid for difficult diagnostic problems.