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The present study was to investigate the dynamics of endolymphatic hydrops (EH) and hearing function, and explore whether the hearing loss is caused by EH alone and whether the hearing function can be modulated by changes in the EH. The extent of EH visualized by gadolinium (Gd)-enhanced inner ear magnetic resonance imaging, hearing thresholds and the summating potential/action potential ratio (-SP/AP ratio) of electrocochleography (ECochG) were recorded prior to and following surgery in 22 patients with intractable Meniere's disease (MD) who underwent endolymphatic duct blockage (EDB). The difference value of the hearing threshold and -SP/AP ratio was significantly positively correlated with the difference value of the endolymph to vestibule-volume ratio (EVVR) and grading of cochlear hydrops between prior to and following surgery. Among patients with a decreased EVVR, the average hearing threshold and -SP/AP ratio was significantly decreased following surgery, as compared to that prior to surgery. Six out of seven patients with a hearing improvement (≥10-dB decline) and 4/5 patients with a negative conversion of EcochG showed downgrading of their hydrops in the cochlea and/or vestibule. By contrast, among patients with an increased EVVR, the average hearing threshold and -SP/AP ratio tended to increase following EDB, as compared with that prior to surgery. One out of two patients with a hearing deterioration (≥10-dB elevation) showed upgrading of her hydrops in both cochlea and vestibule. The present results showed the downgrading of cochlear and/or vestibular hydrops accompanied by the downregulation of the hearing threshold and -SP/AP ratio of EcochG, as well as the upgrading of cochlear and/or vestibular hydrops that tended to upregulate the hearing threshold and -SP/AP ratio of EcochG; this suggested that hearing loss is likely to be caused by hydrops and that the impaired hearing function be modulated by changes in the hydrops., Competing Interests: The authors have declared that no competing interests exist.

Conclusion: A new murine model for the study of Ménière's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure., Objective: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Ménière's disease., Materials and Methods: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac., Results: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine.

Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere's disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (Phex Hyp-Duk/Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk/Y mice and to test the hypotheses that (a) the Phex Hyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk/Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk/Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk/Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.

The objective of this report is to emphasize the clinical features of delayed endolymphatic hydrops in comparison with Ménière's disease. Four cases were selected from a series of 16 examined between the years 1993 and 2005, due to their unusual characteristics. A short clinical history and significant tests are presented for each of the four cases. The cases of delayed endolymphatic hydrops discussed in this article suggest that hydrops is the most important underlying pathology that causes the hearing loss and the vestibular symptoms both in the better ear and in the ear with severe hearing loss. They also suggest that this condition probably occurs in patients with congenitally sensitive ears that make them prone to the development of the late hydrops.

Objectives: To evaluate the efficacy of a new device, the Meniett, in the treatment of Meniere's disease. The device delivers pressure pulses to the middle ear through a ventilating tube in the tympanic membrane at a frequency of 6 Hz for 0.6 second. After rising to a pressure level of 1.2 kPa, the pressure oscillates between 0.4 and 1.2 kPa. It is believed that the pressure changes are conveyed to the inner ear, inducing a transport of fluids via the pressure outlets and thus reducing the endolymphatic hydrops., Study Design: A clinical, randomized, multicenter, double-blind, placebo-controlled study. A total of 40 patients were included that had active Meniere's disease according to American Academy of Otolaryngology-Head and Neck Surgery criteria, aged between 20 and 65 years, with a history of at least eight attacks during the past year. After insertion of the ventilation tube, the patients should have had attacks of vertigo for 2 months before entering the study., Outcome Measures: Primary study endpoints were change in frequency of vertigo, change of functionality profile, and change in patient perception of vertigo (visual analogue scale); secondary endpoints were perception of tinnitus, aural pressure, and hearing, as well as an audiologic evaluation of hearing before and after the treatment period., Results: The functionality level improved statistically significantly in the active group compared with the placebo group (p=0.0014), as did the visual analogue scale evaluation of vertigo (p=0.005). There was a trend toward a reduction of the frequency of vertiginous attacks that was not significant (p=0.090). With regard to the secondary endpoints, there was no statistical difference between active and placebo groups., Conclusion: Local overpressure treatment is a novel treatment that is noninvasive, nondestructive, and safe. It significantly reduces vestibular symptoms in patients with Meniere's disease. The Meniett was cleared by the Food and Drug Administration in 2000.

The term Meniere's disease is used to define either the classic triad of vestibular and cochlear symptoms and aural pressure from known or unknown causes or its clinical variants, vestibular and cochlear Meniere's disease. Some variants evolve after years into typical forms, whereas others do not. Some symptoms (positional vertigo) have been long underestimated in previous reports. The more we study our patients and correlate clinical findings and the natural history with pathologic studies on temporal bones and laboratory research, the more we will understand Meniere's disease and its causes. Some causes have already been identified as most probable. Extrinsic factors (inflammation, trauma, otosclerosis, autoimmunity, endocrine disorders, and such) interact with congenital (genetic) and developmental intrinsic factors (primary or secondary, acquired) into a multifactorial inheritance that is, to date, the best explanation for the basis of Meniere's disease. Endolymphatic hydrops is widely accepted as the pathologic substrate, but not all hydrops seems to be progressive or becomes clinically manifest. Endolymphatic hydrops is the result of a dysfunction in the mechanism of production/absorption of endolymph, which is mainly due to defective absorptive activity of the endolymphatic duct and sac. Hyperproduction of endolymph cannot be excluded in some cases. Ruptures of the labyrinthine membranes do not satisfactorily substantiate the multiform duration, recurrence, and repetitiveness of attacks of Meniere's disease, nor do they explain the entire complex of symptoms. It seems reasonable to explain symptoms of Meniere's disease on the basis of mechanical factors (as observed in temporal bone studies) associated with biologic and biochemical factors.

Until now, shunt catheters used in endolymphatic sac (ELS) and duct surgery have not been visible at computed tomography (CT) imaging. This report summarizes findings at postoperative CT in 50 patients who underwent endolymphatic system decompressive surgery with a new opaque shunt catheter placed at or into the endolymphatic duct (ELD). The catheter was visible in all 50 cases, and the best projection for visualization was the semicoronal view. The postoperative visualization of the opaque shunt catheter allows determination of the exact placement of the catheter (a) in the bony vestibular aqueduct (within the membranous ELD); (b) at the external aperture of the bony vestibular aqueduct (within or at the membranous ELD at its junction with the ELS); or (c) outside the bony vestibular aqueduct system or aperture but presumably within the membranous ELS. These objective findings may be used as a marker to help predict outcomes from this type of nondestructive inner ear surgery, as well as to determine exactly where the surgeon placed the shunt-tube catheter tip.

Rhizoma Alismatis Mixture (RAM), which can promote diuresis to eliminate wetness-evil and activate blood circulation, is a pure TCM preparation composed of Rhizoma Alismatis, Semen Plantaginis, Rhizoma Ligustici Wallichii and Herba Leonuri. After clinical observation, it showed that RAM can greatly case the inner ear edema of patients with Menière's disease and therefore improved their hearing threshold (63.7%). RAM can also diminish SP amplitude or reduce the SP/AP ratio on the cochleogram. As compared with glyceral test, there was no statistically significant difference, while the side effect of RAM group (5%) was lower than that of glyceral group (87.3%) significantly, therefore RAM test can replace glycerin test in the diagnosis of Menière's disease. The animal experiment results indicated that RAM did not affect stria vascularis permeation but it probably dehydrates the inner ear by changing the osmotic pressure between endolymphatic and perilymphatic or increasing the absorption of the endolymphatic sac.

The fistula sign without middle-ear lesion, also known as the Hennebert's sign, was observed in 7 (14%) subjects among 50 patients with unilateral Ménière's disease. The Hennebert's sign was obtained in 4 cases (57%) by negative pressure in the external auditory canal, by positive pressure in 2 cases and by both positive and negative pressures in 1 case. The Hennebert's sign is characterized by a few beats of horizontal nystagmus seen under Frenzel glasses. Caracteristically this nystagmus is of low frequency and amplitude. Most patients indicate simultaneous sensation of dizziness. The presence of Hennebert's sign seems to indicate in most cases the existence of an endolymphatic hydrops with contact of the saccular wall up to the internal face of the footplate (internal sacculostapedopexy). The test was also performed on the controlateral healthy ear used as a control. No Hennebert's sign was obtained on the healthy side. None of the patients showed any complication following the provocation of Hennebert's sign.

A patient with Ménière's disease is presented in whom several transtympanic electrocochleographic recordings were made during the course of the disease. Variations in the amplitude of the Summating Potential are related to clinical status. These findings lend support to the theory that the enhanced negative SP in Ménière's disease is produced by endolymphatic hydrops. The scientific evidence for this theory is discussed.

In this paper the current state of knowledge of the development in experimental endolymphatic hydrops (EEH) is summarized, with particular emphasis on calcium. An imbalanced Ca2+ homeostasis in the inner ear is demonstrated using EEH as an animal model for Meniere's disease. The possibility of a receptor-mediated Ca2+ transport across the epithelial layer, especially the light cells, and of 'chemical signal' as an initiating modulating factor in the disturbance of Ca2+ homeostasis was suggested. It is pointed out that melanin is capable of binding calcium and may act as a buffering system. Finally, the possible malfunction of the Ca-overloaded melanocytes on the inner ear function is discussed.

We have previously shown by chronic implantation of round window electrodes, that after the experimental induction of endolymphatic hydrops by surgical blockade of the endolymphatic canal, in the guinea pig, there is a low/mid-frequency fluctuant hearing loss, followed by a very high frequency loss and after a few months the audiogram is flat. This evolution reproduces exactly that observed in Meniere's patients. The aim of this study was to investigate the evolution of one aspect of vestibular function in parallel with audiogram changes. The nystagmic responses in the dark were tested every month during the 4 months which followed hydrops induction. There was considerable variation in the number of evoked saccades for different control animals and even between different recordings for the same control animal. However, in general, the number of saccades to right and left rotation was symmetrical for control animals, whereas for hydropic animals there was a period, within the first 2 months post-operation, when there was a reduction of saccades to the left (operated side) with sometimes an increase to the right. This asymmetry which occurred in the period of fluctuant hearing losses did not however appear synchronized with audiogram fluctuations. The nystagmic responses tended to become symmetrical over the 4 months post-operation. Oral administration of glycerol to animals whose nystagmus was asymmetric brought the vestibular response towards symmetry in 50% of the cases. Although episodes of vertigo, as known in Meniere's disease, were never observed in operated guinea pigs, these data indicate that they have some functional vestibular disturbance.

The inner ear possesses remarkably stable homeostatic mechanisms for the maintenance of the functional integrity of the inner ear end-organs. The inner ear fluid maintains its homeostasis by a variety of subtle regulatory mechanisms, both locally and systemically. Any disturbance in one of these mechanisms can induce the disruption of homeostasis expressed by ionic, osmotic, or metabolic imbalance between the compartments. This can be manifested as membrane displacement or abnormal functions of the inner ear, depending on the degree of the disturbance. Further studies are necessary to clarify these regulatory mechanisms of homeostasis and those conditions which alter homeostasis which can result in the abnormal functions. Further research along this line is essential in order to understand the etiology of endolymphatic hydrops and also to establish guidelines for possible normalization of this pathological status.

By means of human temporal bone slides we want to demonstrate that interruption of the so-called longitudinal endolymphcirculation causes a hydrops ahead of the block. This fact, proven by animal experiments, we observed in human specimens. Predominant locations are the anatomic narrows of the endolymphatic system: Isthmus of the endolymphatic duct, utriculoendolymphatic valve Bast, ductus reuniens. The different possible pathohistological data are: bony obliteration of the ductus endolymphaticus, embolic closure within the isthmic portion of the endolymphatic duct, blockage of the utriculoendolymphatic valve by the distended utricle or perilymphatic connective tissue strands, angled ductus reuniens in perilymphatic fibrosis.

Pigmented guinea pigs were chronically implanted with bilateral round-window electrodes. Endolymphatic hydrops was induced by obstruction of the endolymphatic duct on one side. At 1-5 months post-surgery, glycerol was orally administered to each animal and the acute effect on cochlear and eighth nerve responses was investigated. Doses from half to four times the clinical dose of glycerol failed to improve the CAP audiogram in operated ears and were often found to raise the thresholds. Glycerol was found to diminish the amplitude of the summating potential as well as that of the compound action potential. Similar effects were observed for the higher doses in the control ears, although no effect was seen when doses used were equal to or less than the clinical dose. Our data suggest that the cochlear conditions in the guinea pig model of hydrops differ notably from those seen in patients with Ménière's disease.

Fluctuation of hearing at low frequencies is one of the most characteristic findings in Meniere's disease and seems to be a phenomenon closely related to changes of endolymphatic pressure and volume. In the present study, pressure was applied to the external auditory canal of patients with Meniere's disease, and the effect on the bone conduction threshold was examined at times of depressed and improved hearing. In more than half of these cases, it was found that the pressure effect was marked at the time of improved hearing acuity, but not at the time of depressed hearing. This effect was also confirmed in more objective experiments with guinea pigs. It is concluded that the fluctuation of hearing in Meniere's disease seems to be a phenomenon accompanying the endolymphatic pressure change in the scala media.