Search

Two-nation-wide surveys of Meniere's disease have been carried out by the Vestibular Disorders Reserch Committee of Japan, supported by the Ministry of Health and Welfare of Japan. First survey has already been reported. In the second survey 1564 cases of definite and 1439 cases of presumed Meniere's disease were collected and their epidemiological and clinical features were analyzed. The second survey included the name, sex, age and other necessary items.Some items were compared with the results of the epidemiological and clinical surveys of the Meniere's Disease Reserch Committee of Japan reported in 1971.

Schuller projection films and CTs encompassing the lateral semicircular canal were obtained in 22 patients with unilateral Meniere's disease ; similar procedures were performed on 16 patients with unilateral chronic otitis media as controls. The distance between the posterior semicircular canal and the posterior petrous surface (P-P distance) was measured in the CTs, and the distance between the capsula ossea labyrinthi and the sigmoid plate (C-S distance) in the Schuller projections. The statistical differences between the affected ears and the non-affected ears were then calculated in both Meniere's disease and chronic otitis media. The correlation between the P-P distance and the C-S distance was also determined.1) In the affected ears in unilateral Meniere's disease, P-P and C-S distances was significantly shorter than in the non-affected ears. No correlation was found between the P-P distance and the C-S distance.2) The C-S distance was shortest in the affected ears of patients with chronic otitis media. The C-S distance appeared to be influenced by middle ear infection : apparent differences due to the radiological projection angle must be taken into consideration.3) The P-P distance appears to be more useful than the C-S distance for the evaluation of Meniere's disease.

Since the first reports of endolymphatic hydrops in Meniere's disease by Yamakawa and Hallpike & Cairns in 1938, various attempts have been made to induce endolymphatic hydrops experimentally in animals. We reviewed the literature from 1947 to 1990 on methods of inducing experimental endolympphatic hydrops and summarized these methods on the basis of Schuknecht's classification of human endolymphatic hydrops into progressive and non-progressive types. The progressive pattern of hydrops was induced experimentally in guinea pigs using the silver nitrate cauterization method developed in our department in 1981. This type of experimental endolymphatic hydrops has been found particularly suitable as an animal model of Meniere's disease, since endolymphatic hydrops in Meniere's disease is always of the progressive pattern.

The anti-diuretic hormone vasopressin has been shown to be important in regulating inner ear fluid. The diuretic hormone, CNP, and its receptor, ANP-B receptor, may also function in the regulation of inner ear fluid. To determine whether vasopressin directly affects the fluid level, we infused this hormone to rat and assay of V2-AVP receptor mRNA by semiquantitative RT-PCR demonstrated a significantly lower level of this transcript in vasopressin-infused animals than in saline-infused animals. The levels of CNP and ANP-B receptors mRNA, however, were the same in both groups of rats. Results suggest that high plasma levels of vasopressin may be a principal causal factor of endolymphatic hydrops in Meniere's disease, perhaps by down-regulating the number of vasopressin receptors.

Isosorbide was administered to guinea pigs with experimentally induced endolymphatic hydrops, and endolymphatic space cross sections were measured with a microscope, video camera, and computer arrangement. The results were then compared with those in control guinea pigs which had not received isosorbide. Decrease in endolymphatic hydrops was most pronounced in the saccule and the basal turn of the cochlea, where hydrops was reduced by 25-30%. The decrease became progressively smaller towards the apex. The utricular space was virtually unaffected.

In order to investigate the clinical factors relating to positive glycerol tests, 51 patients with Ménière's disease were subjected to a complete battery of audiometric examinations, including the short increment sensitivity index, Bekesy, alternate binaural loudness balance, speech discrimination and pure-tone audiometry tests, both before and after glycerol ingestion. The correlation between positive glycerol tests and vestibular response, cochlear symptoms, age at onset and disease duration was investigated. High ratios of positive tests were obtained in the following categories of patients with Ménière's disease: elderly patients with vertiginous attacks; patients with high-level hearing loss; nystagmus patients, and patients with fluctuating hearing loss.

Although mechanisms regulating inner ear fluid have not been yet elucidated, control of blood flow has been thought to be of great importance. Vasoactive intestinal polypeptide (VIP) was the first neuropeptide demonstrated in cerebrovascular nerves. To study the possible role of VIP in regulation of inner ear fluid, we investigated the presence of mRNA for VIP and VIP receptor in the rat inner ear using a reverse transcription-polymerase chain reaction (RT-PCR) method. A single band of the size expected for VIP and its receptor was detected in mRNA from the rat inner ear by using primers specific for VIP and the receptor. The nucleotide sequences of the subcloned RT-PCR products were identical to those of rat VIP and the rat lung VIP receptor. These results indicate that both VIP and VIP receptor are expressed in the inner ear of the rat and suggest that VIP may be implicated in regulation of fluid in the inner ear.

In Japan, the number of households who have pets has gradually increased, together with the number of people who have pet allergies. Many reports exist on pollen and mite allergy, but few on pet allergy. We conducted an epidemic study in 531 first-year junior high school students in Wakayama prefecture in 1999. Questionnaires covered allergy and measurement of total IgE antibody using CAP system (Pharmacia Co. Ltd.) and specific IgE antibody using MAST26 system (Hitachi chemical Co. Ltd.). Of 306 students having pets, 11 were allergic to dogs, 11 to cats, 8 to both, and 1 to rabbits. Clinical symptoms were various. No differences in symptoms were observed among allergens. Serum total IgE tended to increase in students who suffered from pet allergies. Positive rates of specific IgE antibodies were high in mites and Japanese cedar pollen (36.7% for mites and 37.0% for Japanese cedar pollen), and also in dogs and cats (15.4% for dogs and 18.2% for cats). Specific dog and cat IgE antibodies increased significantly (p = 0.033 for dog and for p < 0.0001 cat), but no significant correlation was found between the positive specific IgE antibody and history of pet keeping.

The main purpose of this study is to search for a viral etiology in Ménière’s disease by examining the presence or absence of herpes family virus DNA in the endolymphatic sac (ES) using the in situ hybridization method. This was a prospective study with the ES from 10 patients with Ménière’s disease and from 7 control cases without any pre-mortem ear diseases except a case of acoustic tumor. These 10 patients underwent the ES surgery. The presence of herpes family virus DNA, such as herpes simplex virus types 1 and 2 (HSV1&2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and human cytomegalovirus (CMV), was examined using the in situ hybridization method. Serum antibody titers against these viruses just before the ES surgery were studied in these patients. Of the 10 specimens from the patients with Ménière’s disease, 7 were positive for VZV, 4 for EBV, 1 for CMV and none for HSV1&2, although the serum antibody titers against these viruses did not show any significant elevation in these patients just before the ES surgery. This result suggests that the viral DNA in the ES is inactive and is present in a latent form. From the statistical analysis, it can be postulated that VZV infection in early childhood may reach the ES and play a role in the pathogenesis of Ménière’s disease (p = 0.0235). The double infection with both VZV and EBV tended to be another candidate for the pathogenesis of Ménière’s disease (p = 0.0557).

Autoimmune ear disease induced by type II collagen has been investigated by Yoo et al. In the present study, we investigated the effects of direct chronic infusion of type II collagen-specific monoclonal antibodies into guinea pig cochlea. Type II collagen fragment CB11 peptide-specific monoclonal antibodies (anti-CB11 Mabs) were infused directly into the scala tympani of guinea pigs with an Alzet mini-osmotic pump (anti-CB11 Mab group). As a control, normal mouse serum was infused by the same method (control group). To evaluate the auditory function, we recorded brain stem auditory-evoked potentials (BAEPs). In the anti-CB11 Mab group, 80% of the animals showed an increased hearing threshold of more than 25 dB at 7 days after infusion. The hearing threshold shift observed in the guinea pigs of the control group was minimal (15 dB or less). To detect the structural changes, we performed histopathologic studies using hematoxylin and eosin staining. Inflammatory cell migration was detected mainly in the scala tympani of the guinea pigs of both groups. In the anti-CB11 Mab group, endolymphatic hydrops was also observed. The results of this experiment suggest that type II collagen autoimmunity is responsible for the production of hearing loss and endolymphatic hydrops.

The posterior insula, central sulcus, and inferior parietal lobule including the intraparietal sulcus have been considered the vestibular cortex based on functional brain mapping in humans as well as experiments in lower primates. The same regions receive optokinetic, visual, and proprioceptive projections. We examined the cortical and subcortical projection of vestibular activity with visual and proprioceptive input eliminated during caloric stimulation (CS), using functional magnetic resonance imaging (fMRI). Single-shot gradient-echo echoplanar image (EPI) volumes were sensitive to BOLD contrast in oblique orientation. We adopted a pharmacokinetic model for analysis of imaging data from 10 subjects as a group. The insular gyrus, intraparietal sulcus, superior temporal gyrus, hippocampus, cingulate gyrus, and thalamus showed activation by CS. Cortical and subcortical activation during CS in the present study was observed within regions less precisely delineated by other methods. As intraparietal sulcus activation showed right hemispheric dominance, this region may have an oculomotor projection as well as the vestibular input.

We examined the sera of patients with Meniere's disease for the presence of antibodies against 8 inner ear antigens by enzyme-linked immunosorbent assay (ELISA). One hundred eight patients with Meniere's disease and 28 control subjects were studied. The antibodies against chicken type II collagen, bovine type II collagen, the cyanogen bromide cleaved peptide 11 (CB11) of each, type IX and XI collagens, C-Raf, and tubulin were measured by ELISA. The sensitivity of each antigen was between 37% and 60% individually, and was 91% when all 8 inner ear antigens were combined. These results showed that 91% of Meniere's disease sera have antibody activities to 1 or more of these inner ear antigens. The results suggest that performing ELISA for these 8 inner ear antigens was useful as a diagnostic tool for Meniere's disease. Further study is required for elucidating the role of these antigens in the pathogenesis of Meniere's disease, which might eventually result in better therapy.

In order to confirm the crossed-innervation between auditory cortex and the ear that receives monosyllabic sound, the auditory cortical response to monaural monosyllabic stimulation as detected by functional magnetic resonance imaging (fMRI) was investigated in six normal hearing subjects. Stimulus amplitude averaged 95 dBSPL at the distal end of the audio system. A series of 440 echo planar images was acquired during the acoustic stimulation within the four OFF-ON cycle paradigm. Five image series with 10 slices were collected within each OFF or On period. Each scanning session began with four baseline images before the OFF-ON paradigm. Monosyllabic sounds were presented monaurally duritng the ON period at a rate of one monosyllable/sec. Functional MRI data were analyzed with SPM99b software (Statistical Parametric Mapping). The background scanner noise averaged 97dBSPL. The selicon ear plug and headphone as acoustic shields attenuated the noise as much as 17dB. A broad and intense auditory cortical response was observed bilaterally in response to monaural monosyllable stimulation. Sound presentation to the right ear was followed by a larger response in the left auditory cortex than in the right, and left ear stimulation evoked a larger response in the right auditory cortex than in the left. This pattern was consistent in all subjects examined. The primary auditory cortex responded to monosyllabic words presented to the contralateral ear. The results confirmed the crossed-innervation between the auditory cortex and ear for listening to monosyllables. Functional MRI is a useful tool for investigating auditory cortex function, if the scanner noise is adequated controlled.

High resolution transverse axial CT encompassing the lateral semicircular canal was used to study the visualization of the vestibular aqueduct and to measure the minimum distance between the posterior semicircular canal and the posterior petrous surface (P-P distance) in Meniere's disease and chronic otitis media. The results indicate that the development of the bone between the posterior semicircular canal and the posterior petrous surface, which usually contains the endolymphatic sac, is significantly poorer in affected ears than in non-affected ears in unilateral Meniere's disease, and much poorer than in chronic otitis media.

C-type natriuretic peptide (CNP) is a member of the atrial natriuretic peptide family (ANP family). The family also includes ANP and brain natriuretic peptide (BNP). These peptides regulate the homeostasis of body fluid and blood pressure as a neuropeptide in the central nervous system as well as a cardiac hormone in the periphery. We have recently reported the expression of CNP mRNA in the inner ear. To assess the possible physiological role of CNP in the inner ear, we investigated the localization of CNP peptide in the rat inner ear by immunohistochemistry at the light and electron microscopic level. CNP-like immunoreactivity was widely distributed in the secretory and the neuronal portion of the inner ear, i.e. the spiral ligament, the dark cell region of the utriculus, the epithelium of the endolymphatic sac, the spiral ganglion cells and the vestibular ganglion cells. The results suggest that CNP may play a role in the homeostasis of the perilymph and endolymph and may also influence nerve activities in the inner ear.

The long-term results of endolymphatic sac (ES) shunt surgery in Ménière’s disease have been reported to be unsatisfactory compared to the short-term results, probably because of fibrosis and/or reclosure of the incised ES. To solve this problem, we tried to apply mitomycin C (MMC) intraoperatively to the incised ES as used in trabeculectomy for glaucoma. MMC has an antiproliferative effect as well as an antineoplastic effect. Thus, it is expected that MMC would have a benefit to prevent rapid fibrosis and/or reclosure of the ES. MMC did not show any ototoxicity in our animal study and we started a clinical trial after being approved by the Ethics Committee for Human Research at our university. Fourteen patients with Ménière’s disease underwent ES mastoid shunt surgery with intraoperative application of MMC and they were followed up more than 6 months. No patients experienced vertigo, although some complained of slight dizziness. Five patients out of 14 showed remarkable hearing improvement by more than 10 dB, accompanied with decrease of tinnitus.

Myelin protein P0 has been identified as an autoantigen in inner ear diseases. In order to study autoimmune hearing loss, we performed brain stem auditory-evoked potential (BAEP) studies on P0-sensitized mice. Two P0-sensitized mice showed hunched posture, poor coat, loss of body weight, and abnormal walking with a waddling gait. About 25% of the P0-sensitized mice developed hearing loss. In the BAEP study, peak latencies of waves I, III, and V and the interpeak latency I-III were prolonged in the P0-sensitized hearing loss group of mice. Hearing thresholds were elevated in this group of mice in comparison with the control mice. Inflammatory cell infiltration was observed in the cochlear nerve region, and a reduced number of spiral ganglion cells was also detected. These results suggest that P0-sensitized mice are a useful model for studying autoimmune inflammation of the peripheral portion of the auditory system.

To assess the possible physiological role of the atrial natriuretic peptide (ANP) family, we investigated the expression of mRNA of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and their receptors in rat inner ear using the reverse transcription-polymerase chain reaction method. ANP and CNP message bands were detected in the inner ear, but the BNP message band was not. Amplification products of the expected sizes of ANP-A, ANP-B, and ANP-C receptors were detected in the inner ear. These results suggest that natriuretic peptide family may influence the function of the inner ear through the ANP-A, ANP-B, and ANP-C receptors.

Laser Doppler flowmetry was used to assess cochlear blood flow (CoBF) in guinea pigs with experimental endolymphatic hydrops following intravenous infusion of 5 types of drugs: 50% glycerol, 70% isosorbide, 20% mannitol, 7% sodium bicarbonate, and 1% diphenidol. The magnitude of the CoBF changes following infusion tended to be smaller in the hydropic ears than in the normal control ears. A significant reduction in CoBF changes was observed in hydropic ears infused with isosorbide and sodium bicarbonate. These results suggest that the cochlear microvascular sensitivity to various stimuli such as drug infusion is reduced in hydropic ears. This may result from atrophy of the stria vascularis which is often observed in the hydropic ears of guinea pigs. Thus it seems likely that the same reaction occurs in the inner ear of patients with Ménière’s disease in whom atrophy of the stria vascularis is also presumed to exist in conjunction with extensive endolymphatic hydrops. Therefore, it seems probable that the function of the microvasculature of the stria vascularis is impaired in the inner ear of patients with Ménière’s disease, resulting in the slow progressive deterioration of the inner ear with time.

The cause of endolymphatic hydrops, a characteristic finding in Meniere's disease, is not known. To study the possible involvement of the neurohormones vasopressin and oxytocin in this condition, we investigated whether transcripts of the genes encoding the arginine vasopressin (AVP) and oxytocin receptors are expressed in the rat inner ear. Utilizing the reverse transcription-polymerase chain reaction (RT-PCR) method, primers specific for each receptor showed a single message band of the expected size in the rat inner ear. When the PCR products were cloned, the sequences were identical to those of the real-type (V2) AVP receptor and oxytocin receptor transcripts. The finding of vasopressin and oxytocin receptor mRNAs in the inner ear suggests that these neurohypophyseal hormones may have roles in the regulation of inner ear fluid. In particular, the presence of vasopressin receptor mRNA in the inner ear supports the hypothesis of a relationship between high plasma vasopressin levels and endolymphatic hydrops.

C-Type natriuretic peptide (CNP) is the third member of the natriuretic peptide family which plays an important role in body fluid homeostasis. To determine a possible role of CNP in regulation of an inner ear fluid, we investigated the expression of CNP and atrial natriuretic peptide B receptor (ANP-B receptor) mRNAs in rat inner ear using a reverse transcription polymerase chain reaction (RT-PCR) method. Amplification products with sizes expected for CNP and ANP-B were detected in the inner ear. After cloning and analysis, the sequences for PCR products were identical to those of CNP or ANP-B receptor in the brain. These results indicate that both CNP and ANP-B receptor are expressed in the inner ear of the rat and suggest that CNP may play a role in inner ear function (such as regulation of inner ear fluid) in an autocrine and/or paracrine manner.

Sera from patients with various inner-ear diseases, especially Meniere's disease, were investigated by Western blot against guinea pig inner-ear proteins. Of 45 patients, 24 (53%) with various inner-ear diseases had antibodies against inner-ear proteins, compared with 0 of 10 (0%) in control subjects without inner-ear diseases. Of the 10 proteins that showed a positive reaction with patient sera, the 28-kD band was unique in that it appeared only in the membranous fraction of the inner ear and was highly positive (28%) in reaction with Meniere's disease patient sera. The results in the present study with proteins extracted from guinea pig inner ear were consistent with our previous study using proteins from human inner ear, suggesting that the 28-kD protein may be a candidate for detecting autoimmune inner-ear disease.

We correlated the surgical findings and the findings of computerized tomographic scans of the temporal bone in 38 ears from 38 patients with Menière's disease (31 unilateral and 7 bilateral) treated by endolymphatic sac (ES) drainage surgery between 1986 and 1991. At surgery, the position and size of the ES were recorded. The position of the ES was classified as one of three types according to Arenberg's parameters (type I, type II and type III) and the size of the ES was classified as large, intermediate or small. Scans encompassing the lateral semicircular canal were used to measure the minimum distance between the posterior semicircular canal and the posterior petrous surface (P-P distance). The P-P distance in 23 type III cases was significantly shorter (2.25 mm) than in 13 type II cases (3.39 mm). The P-P distance in 9 large-sized ES cases was significantly longer (3.99 mm) than in 20 intermediate-sized ES cases (2.40 mm) and in 9 small-sized ES cases (1.92 mm). Significant correlations were found in patients with Menière's disease between a short P-P distance and type III ES position, and also between a short P-P distance and an intermediate or small-sized ES.

High resolution transverse axial computerized tomograph (CT) encompassing the lateral semicircular canal (LSC) was used to measure the size of the petrous bone in ears with bilateral (n = 13) and unilateral (n = 38) Menière's disease, and in ears with unilateral chronic otitis media (n = 25) as a control group. Measurements were made of the following 4 distances in the petrous bone; A: the distance between the posterior semicircular canal (PSC) and the posterior petrous surface (PPS) (P-P distance), B: the distance between the PSC and the LSC (P-L distance), C: the distance between the vestibule and the PPS (V-P distance), and D: the distance between the PSC and the anterior margin of the sigmoid sinus (P-S distance). The P-P and the V-P distances were significantly shorter in ears with Menière's disease, especially in ears with bilateral Menière's disease compared to the nonaffected ears in unilateral Menière's disease or ears with chronic otitis media. This tendency was clearer in the P-P distance than in the V-P distance. The P-L and P-S distances did not show any statistical difference between groups. The results indicate that bone development between the PSC and the PPS and between the vestibule and the PPS, which usually contains the endolymphatic duct and sac, is significantly poorer in ears with Menière's disease than in ears with chronic otitis media. Hypoplasia of the retrolabyrinthine region may be an important factor in the pathogenesis of endolymphatic hydrops.

A swimming test was used to evaluate vestibular function in guinea pigs. We first observed tracings of the swimming patterns of 20 healthy guinea pigs to establish the normal range. Then the same test was used in a group of 49 guinea pigs with endolymphatic hydrops induced by immunologic techniques. They did not show spontaneous nystagmus or body deviation while walking, but a total of 20 out of 49 animals displayed abnormal swimming patterns, with 8 swimming clockwise and 4 counterclockwise. This swimming test is easily able to detect mild vestibular dysfunction in guinea pigs, and can be repeated, so that we consider it useful for examining vestibular function in these animals.

The wide range in incidence rates reported for bilateral Meniere's disease results mainly from the lack of established clinical criteria for bilaterality, and from follow-ups of varying duration. In order to help determine a reasonable bilateral involvement rate, we examined histologic reports of temporal bones with endolymphatic hydrops. We reviewed the literature on temporal bone autopsies from 1938 to 1988, and selected 72 cases for histologic examination. Of the 72 cases, 67 (93%) showed endolymphatic hydrops, 2 (2.8%) showed collapse, and 3 (4.2%) showed membranous labyrinths of normal appearance. Twenty of the 67 endolymphatic hydrops cases (29.9%) displayed bilateral involvement, suggesting a rate of bilaterality in Meniere's disease of approximately 30%.

It is widely accepted that Meniere’s is an idiopathic disease involving the membranous inner ear. Disease which cause secondary endolymphatic hydrops (SEH) are differentiated from Meniere’s disease. Theoretically this idea is acceptable, but it is quite difficult to distinguish SEH from idiopathic endolymphatic hydrops (IEH). In other words, when symptoms similar to those of Meniere’s disease coexist with another definitive disease, we find difficulty in determining whether the symptoms are caused by the disease itself or whether they are truly those of Meniere’s disease. In this paper, we will discuss this controversial problem in diagnosing Meniere’s disease.

Endolymphatic hydrops in the temporal bones of Meniere’s disease patients was first described in 1938 by Yamakawa [1] and Hallpike and Cairns [2]. The first successful experimental induction of this condition was by Naito [3] and Kimura and Schuknecht [4], who, in separate studies, produced endolymphatic hydrops in guinea pigs through the obliteration of the endolymphatic duct or sac.

It has been well established by anatomic and tomographic reports [1, 2] that the endolymphatic sac (ELS) and vestibular aqueduct (VA), appear in great varieties of size, position, course, and form. These irregularities are particularly pronounced in Meniere’s disease, with tomographic studies revealing the VA to be filiform, stenotic, or nonvisualized in more than 50% of all Meniere’s cases [3, 4]. Such tomographic findings were used by Stahle and Wilbrand [4, 5] in the development of a system classifying the degree of peri-aqueductal pneumatization in Meniere’s disease into 3 grades: large cell pneumatization, small pneumatization, and non-pneumatization.

Steroids are less frequently used for the treatment of Meniere’s disease compared with their use for sudden deafness or facial paresis. Hauser [1] reported 2 cases of Meniere’s disease in which hearing was improved by the administration of steroids. McCabe [2], Hughes et al. [3, 4] and Shea [5] also reported the efficacy of steroids in cases of sensorineural hearing loss and/or Meniere’s disease with a suspected immunological origin. According to our 1970 and 1980 nationwide surveys [6, 7], incidences where otolaryngologists treated Meniere’s disease with steroids increased from 2% to 7%. It is true that steroids are one of the few drugs which have promising effects on certain types of Meniere’s disease. This study was made to examine the effects of steroids on endolymphatic hydrops experimentally induced in guinea pigs by an immunological technique [8].

Meniere's disease and vestibular Meniere's disease have episodic vertigo followed by remission in which the patients feel perfectly well. Recurrences may come at intervals varying from a few days to several years. The duration of attacks showed an irregular pattern producing both a longest period without a vertigo attack and a shortest period without a vertigo attack. In this presentation, clinical characteristics between Meniere's disease and vestibular Meniere's disease were studied by using the maximum and minimum intervals. The following results were obtained.1. Most patients with a 1-2 year history of Meniere's disease were found to have a maximum attack-free interval of within 6 months. Patients with a history of 2-5 years and 5-10 years were found to have maximum attack-free intervals of 2-5 years.2. The minimum attack-free interval of Meniere's disease was not influenced by the duration of the disease.3. The minimum attack-free interval of Meniere's disease was observed most often within 7 days. The minimum attack-free interval of vestibular Meniere's disease was observed most often over 7 days.4. Regarding bilaterality, sex and age of onset, there was no significant difference in patient with a history of over 2 years in maximum and minimum attack-free intervals of Meniere's disease.5. Patients with Meniere's disease can be divided into 3 groups; those with cochlear and vestibular symptoms starting at the same time, and those with the vestibular symptoms starting before or after cochlear symptoms: All 3 groups had the same tendency in terms of maximum and minimum attack-free intervals.6. For the prognosis of Meniere's disease, it is convinient to use the accumulated frequency of maximum intervals.

The elasticity of Reissner's membrane was investigated in guinea pigs with experimentally induced endolymphatic hydrops. Isosorbide, an osmotic diuretic, was administered to reduce the size of the endolymphatic space and thereby decrease pressure on the bulging Reissner's membrane. If elasticity is present, a consequent shortening of this membrane would be expected. Significant folding in the basal turn of the cochlea was observed, but careful measurement with a microscope, video camera, and computer arrangement revealed no contraction of Reissner's membrane in comparison with guinea pigs which had not received isosorbide. This indicates a lack of elasticity in the membrane following the occurrence of endolymphatic hydrops, suggesting irreversibility of the elongation process.

Five specimens of the endolymphatic sac taken from patients with Ménière's disease during epidural drainage surgery were examined under the electron microscope. The clinical history and histopathological findings are presented. The most common and prominent finding was perisaccular fibrosis of the endolymphatic sac which appears to disturb the free absorption of endolymph in the endolymph in the endolymphatic sac resulting in endolymphatic hydrops. Well-preserved epithelial cells of the endolymphatic sac could only be found in one of the specimens.

Irregularities in the appearance of the endolymphatic sac are often observed during operations on patients with Meniere's disease. This study attempts to clarify the nature of several of these irregular characteristics. Photographs were taken of the sacs of 46 patients with Meniere's disease during endolymphatic sac drainage, and they were classified into 3 groups according to the sac's position, size, color and vascularity. They were then compared with 12 photographs of the sacs of patients with acute mastoiditis or cholesteatoma. The patients with Meniere's disease were found to have endolymphatic sacs located lower and more anteriorly in the posterior semicircular canal, very close to the jugular bulb. The sacs were smaller, whiter, and less vascular than those of the patients without Meniere's disease.

Endolymph-perilymph shunts were produced in 20 guinea pigs with endolymphatic hydrops induced by the silver nitrate method. The shunt was created between the scala media and the scala tympani through the basilar membrane in the basal turn of the cochlea. At various intervals (3 hours-27 days), animals were sacrificed and prepared for pathological examination. In 10 of the 20 animals the shunt was visible, varying from a small fissure to 200 microns in width. In the other 10 animals the shunt had probably healed over, because fracture lines were often observed. In those examined 3 hours to 3 days after operation, there was slight membranous collapse. After 7 to 27 days however, the animals showed hydrops even if the shunt was still patent. Severe degenerative changes of Corti's organ and severe atrophy of the stria vascularis were observed adjacent to the shunt area. The temporal bone of a patient with otosclerosis and Meniere's disease was also studied. Otosclerosis had invaded the lateral wall of the cochlea inducing atrophy of the spiral ligament, stria vascularis and basilar membrane to create a natural endolymph-perilymph shunt between the scala media and the scala tympani. This structure resembled the shunt produced experimentally in guinea pigs. The patient had suffered from vertigo which later disappeared although hearing loss was severe. The shunt may have worked as a pressure-releasing fistula.