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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.

Background: High signal intensity in the endolymphatic duct (ED) is occasionally observed on magnetic resonance imaging (MRI) in ears that have otological disorders., Objective: The signal intensity (SI) in the ED on post-contrast MRI was investigated in subjects with various otological disorders, and the meaning of high SI in the ED was evaluated., Material and Methods: 392 patients with otological disorders and 21 controls without otological symptoms underwent 3 T MRI. The SIs of the ED and the cerebellum were measured, the SI ratio (SIR) was calculated, and ears with SIR ≥4 were identified., Results: A high SIR was identified in the ED of 3.7% of ears affected by definite Meniere's disease (dMD), 100% of ears affected by large vestibular aqueduct syndrome (LVAS), and 7.1% of ears with no otological symptoms. On the whole, a significant relationship was found between the existence of vestibular or cochlear EH and the SIR in the ED., Conclusion: The MRI finding of high SI in the ED may indicate the mechanism of inner ear disturbances in ears with otological disorders, especially in those with LVAS, and it may suggest an underlying disorder in some ears in which otological symptoms are not apparent.

Objectives: The goal of this study was to characterize the signal intensity (SI) pattern in the endolymphatic duct/sac from T2-weighted spin echo magnetic resonance (MR) images and T2*-weighted 3-dimensional (3-D) constructive interference in steady state (CISS) MR images that were obtained from a homogenous group of patients with an enlarged vestibular aqueduct (EVA) associated with SLC264 (PDS) mutations., Study Design: A retrospective study., Setting: Tertiary referral center., Patients: Eleven subjects (22 ears), with at least 1 SLC26A4 mutation and bilateral EVA confirmed by temporal bone computed tomography, were enrolled., Intervention: The MR images of 22 ears were reviewed retrospectively., Main Outcome Measures: The SI of the endolymphatic sac (ES) from 2 sequences were compared and reviewed. The presence of anomalies of the vestibule were also evaluated. In addition, the caloric test results were also reviewed to characterize the vestibular function in a subset of our cohort (12 ears)., Results: T2*-weighted 3-D CISS MR images revealed a more variable SI in the enlarged endolymphatic system than did the T2-weighted images. There was a hierarchy for the order of SI loss from the endolymphatic system on the T2*-weighted 3-D CISS MR images. There were 3 cases where the SI loss from the intraosseous ES, on the T2*-weighted 3-D CISS images, was associated with an abnormal caloric response., Conclusion: The SI of the ES observed on T2*-weighted 3-D CISS images of EVA patients, with SLC26A4 mutations, showed a distinctive pattern, and the results from this study suggest a potential role for the MR imaging in providing physicians with better information about the functional status of the inner ear.

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.

The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid- and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-beta receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED.

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.

Certain peripheral vertigos undoubtedly do not raise from neuro-sensorial structures but rather of the secretory structures and can be called "endolymphatic". They deserve to be individualized because concerning different pathogenic mechanisms and certainly are relevant for a specific treatment. We hope that in the next years new investigation tools will allow to explore in a noninvasive way the endolymphatic contents and dysfunctions of these structures.

An in vivo tracer was used to determine if the reticular lamina and/or the cell membranes abutting the endolymphatic space are temporarily disrupted after intense noise exposure (4-kHz OBN, 108-dB SPL, 1.75 h). Using a double-barreled micropipette, the endolymphatic potential (EP) was recorded and artificial endolymph containing 10% carbon particles was injected into the endolymphatic space either 0 days or 28 days post-exposure. The cochleae were fixed 30-45 min post-injection, then dehydrated, embedded in plastic and dissected as flat preparations. Damage in the organ of Corti (OC) was quantified, the location of carbon was determined, and some OC segments were then sectioned radially. EP averaged 72+/-5 mV in five controls. These cochleae had carbon tracer in the endolymphatic space only. Four of five noise-exposed chinchillas examined 3-4 h post-exposure had a low EP (30+/-6 mV). The cochleae from these 0-day animals had several focal lesions in which nearly all outer hair cells had just degenerated. At these lesions, carbon was attached to cell membranes and debris between the reticular lamina and basilar membrane. By transmission electron microscopy, discontinuities were found in the apical membranes of sensory and supporting cells. Carbon particles were found in the cytoplasm of these cells. Four of five animals examined at 28 days had an average EP of 70+/-11 mV. The cochleae from these animals had multiple lesions in the basal turn, all of which were healed by phalangeal scars or squamous epithelial cells. In these cochleae, no carbon was found within the OC. Acute disruption of the reticular lamina and the apical membranes of sensory and supporting cells from noise appears to be a major mechanism to account for degeneration in the cochlea that spreads or continues for days to weeks post-exposure., (Copyright 2002 Elsevier Science B.V.)

Our previous studies have suggested a close relationship between vasopressin and endolymphatic hydrops, or the increased volume of endolymph in the inner ear. Endolymphatic hydrops is also thought to occur in Ménière's disease patients. In the kidney collecting duct, vasopressin induces the expression of aquaporin-2 (AQP2), resulting in increased water reabsorption. We explored the possibility, using a quantitative PCR method, that vasopressin regulates the expression of AQP2 mRNA in the rat inner ear, as it does in the kidney. The levels of AQP2 mRNA in the cochlea and endolymphatic sac were significantly higher in rats treated with vasopressin than the levels in control animals. We speculate that over-expression of AQP2 may be involved in the formation of endolymphatic hydrops.

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.

The effects of isosorbide on distortion-product otoacoustic emissions (DPOAEs) and endocochlear DC potential (EP) were examined in experimentally induced endolymphatic hydropic ears and untreated control ears using 20 albino guinea pigs. DPOAEs and EP in the hydropic ears decreased after obliteration of the endolymphatic duct and sac. The administration of isosorbide restored DPOAEs to the normal level, whereas EP was further reduced. In control ears there was no significant change in DPOAEs and EP after the administration of isosorbide. The results obtained in the present study indicate that the effect of isosorbide on DPOAEs is different from that on EP, and the recovery of DPOAEs in hydropic ears is not a secondary phenomenon due to the recovery of EP.

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.

The endolymphatic sac (ELS) has been shown to respond rapidly to sudden disruptions in fluid balance such as labyrinthectomy or systemic administration of hyperosmolar agents. The present study was designed to determine the ELS response to slower changes in fluid dynamics by occluding the endolymphatic duct (ELD), thereby interrupting the longitudinal flow of endolymph to the ELS. Morphologic studies and autoradiographic techniques were used to evaluate the effects of ELD obstruction on the structure and function of the ELS after 48 hours. There were no significant changes in cellular morphology and a slight decrease in the incorporation of radiolabeled glucose when compared with normal ELS cells. We conclude that it is rapid change in fluid balance that triggers the ELS response, which is not seen with disruption of longitudinal flow.

Electrocochleography has been widely used in human and animal studies of endolymphatic hydrops. A variety of response patterns have been reported in normal and hydropic ears. Recent clinical studies have focused almost exclusively on the amplitude ratio of the summating potential (SP) and action potential (AP) derived from alternating polarity click responses. In this report normal response patterns are described with a tympanic membrane electrode employing condensation, rarefaction and alternating polarity clicks and tone burst stimulation. A variety of response abnormalities are described in patients with suspected endolymphatic hydrops. The exclusive use of alternating polarity clicks is not adequate to reveal the nature of these abnormalities.

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.

Three to four months after unilateral surgical ablation of the endolymphatic duct and sac, endolymphatic and perilymphatic pressures were measured in both the normal and hydropic ears of 11 guinea pigs. In normal ears, endolymphatic pressure always approximated perilymphatic pressure. Endolymphatic pressure exceeded perilymphatic pressure in all ears with hydrops, except one in which these pressures were equal. The effect of postural inversion on inner ear pressures were studied in both normal and hydropic inner ears. Normal ears showed endolymphatic and perilymphatic pressure to rise equally during this maneuver. In hydropic ears, the difference between endolymphatic and perilymphatic pressure was notably reduced from measurements obtained in the prone position. This study indicates that an alteration in pressure regulation within the inner ear may be important in the pathogenesis and manifestation of experimental endolymphatic hydrops in the guinea pig. Physiologic mechanisms and clinical implications of these results are described.

The endocochlear potential (EP) was measured in 38 guinea pigs with experimentally induced endolymphatic hydrops at the 3rd, 6th, 12th and 24th postoperative weeks, and the effects of furosemide (FUR, 50 or 80 mg/kg) on the EP were examined. A time-related reduction of the EP from the normal value and increased susceptibility to FUR were disclosed in the hydropic animals. Furthermore, 24-week animals given 80 mg/kg FUR showed a significantly slower recovery rate of the EP than the other groups, indicating impairment of the strial function progressive with post-operative time. The negative component of the EP was considered to be unimpaired until at least 12 weeks after the surgery.

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.

The effect of transient local anoxia (10 to 120 min) upon the endolymphatic potential (abbr. EP) was observed in 30 normal guinea pigs. The recovery of the EP was complete in the animal subjected to 10 min anoxia and almost complete in 20 min anoxia. When the duration of anoxia was 30 min or longer, the recovery of the potential was incomplete, and the longer the duration of anoxia, the lower the level of the EP after reoxygenation. These results were discussed in relation to the possible role of a transient anoxia upon sudden deafness.

The present study was designed to examine the effects of cochleostomy on the development of endolymphatic hydrops in the rabbit. Fistulization of the cochlear partition and simultaneous obstruction of the endolymphatic duct was performed in one group of animals (n = 13). Rabbits in two other groups underwent either cochleostomy (n = 6) or endolymphatic duct obstruction (n = 6) alone. Animals were terminated at 1-, 4-, and 6-week intervals and the cochleas were examined with the light microscope to document the presence or absence of hydrops, or were evaluated with the scanning electron microscope to assess sensory-cell damage. Hydrops was observed in 67% of the animals in the combined duct-obstruction/cochleostomy group, in 100% of the duct-obstruction alone group, and in 0% of the cochleostomy alone group. Widespread sensory-cell degeneration was observed with the scanning electron microscope in the combined and the cochleostomy alone groups.

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.

Fistulization at various parts of the membranous labyrinth has been currently in use as one of the treatments for the symptoms of Meniere's disease. The present report concerns our experience with membranous fistulae in experimental animal ears with and without manifestation of endolymphatic hydrops. The materials presented are mostly new; however, our previous data are also incorporated in order to bring this issue into better perspective. The first part describes the nonproduction aspect of endolymphatic hydrops in the rat, chinchilla, and squirrel monkey after obliteration of the endolymphatic duct in relation to the occurrence of spontaneous fistulae. The second part describes surgical fistulization of the vestibular membranous labyrinth and cochlear duct in order to prevent or control development of endolymphatic hydrops in the guinea pig, the species in which hydrops can be produced consistently. These results are tabulated and analyzed in terms of the pathological consequences that can be expected in performing fistulization of the membranous labyrinths in animals as well as in humans.

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.