The effect of glycerol on the guinea-pig hydropic ear.

The aim of this paper was to investigate the effect of glycerol on experimental endolymphatic hydrops in guinea-pigs. The right endolymphatic sac and duct were obliterated through an extradural posterior fossa approach. Some animals received a 3 g/kg dose of glycerol for a period of 7 days, whereas others received the same dose for 30 days. The activity of glycerol was studied by investigating the volumetric changes in the scala media determined with a computerized planimeter. Glycerol induced a significant reduction of the hydrops showing its effectiveness and suggesting a strial metabolic response.     

The effect of glycerol on short-term experimental endolymphatic hydrops

The aim of this paper was to evaluate the effect of one month of treatment with different dosages of glycerol on experimental endolymphatic hydrops produced by obliteration of endolymphatic sac and duct through an extradural approach. Forty-two guinea pigs were used. The animals, divided into six groups, received 0.5-2 gr/kg body weight of the drug per day for one month. The activity of glycerol was determined by statistical analysis of volumetric changes of scala media. Glycerol demonstrated the effect of reducing endolymphatic hydrops. The decrease in hydrops was influenced by the dosage suggesting a stria metabolic response.     

Vestibular evoked myogenic potentials and glycerol testing

OBJECTIVES/HYPOTHESIS: The objective was to evaluate dizziness as the first symptom of endolymphatic hydrops, which could provide valuable information on the initial stages of endolymphatic hydrops development. STUDY DESIGN: The present investigation was specifically designed to establish whether a combination of the traditional glycerol test and the vestibular evoked myogenic potential (VEMP) glycerol test is capable of diagnosing endolymphatic hydrops early and to identify potential Meniere's disease. The study was limited to patients who complained of dizziness as their only vestibular symptom. METHODS: Thirty-eight consecutive patients with dizziness who had received no treatment were investigated. Each patient underwent glycerol testing measured with both conventional pure-tone audiometry and vestibular evoked myogenic potential testing. For the vestibular evoked myogenic potential glycerol test, an increase of more than 20% in both latency and amplitude after glycerol intake was considered an improvement.RESULTS In one patient, the reappearance of the vestibular evoked myogenic potentials was observed. In another six patients, there was an increase in the vestibular evoked myogenic potential amplitudes, unilaterally in four cases and bilaterally in two. One patient showed a bilateral improvement in amplitude and an unilateral amelioration in latency. CONCLUSION: The assumption of saccular dilation as a sign of early Meniere's disease was not supported by the literature, which considered saccular hydrops as the final progression of the dilation of the endolymphatic compartments into the cochlea. These data seem to indicate that in our patients a saccular dysfunction rather than an early saccular hydrops has been documented, confirming vestibular evoked myogenic potential testing as an intriguing diagnostic option for a lesion of this structure. The vestibular evoked myogenic potential glycerol test proved capable of identifying dysfunctions of the saccule that were not otherwise detectable by the routine methods. Therefore, the vestibular evoked myogenic potential glycerol test should be considered as an additional method of diagnosis in patients with vertigo or dizziness.     

Distortion-product otoacoustic emissions and glycerol testing in endolymphatic hydrops

OBJECTIVES/HYPOTHESIS: Aural fullness is a frequent symptom of endolymphatic hydrops. Its evaluation may provide valuable information on the initial stage of development of endolymphatic hydrops. STUDY DESIGN: The present investigation was specifically designed to ascertain the ability of the glycerol test, combined with pure tone audiometry and distortion product otoacoustic emissions (DPOAEs) testing, to diagnose endolymphatic hydrops early and to identify patients who may evolve toward Meniere's disease. For these purposes, patients who complained about aural fullness as their only audiologic symptom were selected. METHODS: This investigation consisted of 19 consecutive patients with unilateral or bilateral aural fullness who received no treatment. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with both DPOAEs. For the traditional pure-tone glycerol test, a hearing improvement of at least 10 dB, at the lower two or three frequencies (125, 250, and 500 Hz), was judged as a positive result. For the DPOAE glycerol test, a smaller positive difference (5 dB) for at least three frequencies was interpreted as an ameliorative fluctuation. RESULTS: The outcomes of the glycerol tests (24 ears examined) showed variable patterns. Seven ears showed no significant changes of either the pure-tone audiogram or DPOAE. In seven other ears, the comparison of the traditional glycerol test and the DPOAE glycerol test indicated an improvement in both measures. Another seven ears showed negative glycerol tests, whereas DPOAE responses gradually recovered reaching levels significantly higher than those recorded before glycerol administration. The three remaining ears showed contrasting results. CONCLUSIONS: Patients with aural fullness in the absence of other associated symptoms may potentially be in the initial stages of Meniere's disease. This notion is confirmed by the present findings showing a high rate (58%) of positive glycerol tests in the selected patients. The importance of DPOAE testing is supported by their ability to detect minimal dysfunction, possibly representing endolymphatic hydrops that goes undetected by routine pure-tone audiometry.     

Protective effect of edaravone against endolymphatic hydrops

CONCLUSION: Our findings suggest that edaravone prevented the production of reactive oxygen species (ROS). Edaravone also delayed the formation of endolymphatic hydrops in guinea pigs, but had no effect on endolymphatic hydrops. OBJECTIVE: To analyse the protective effect of a free radical scavenger, edaravone, on endolymphatic hydrops. MATERIALS AND METHODS: Guinea pigs were subjected to surgical obliteration of the endolymphatic duct (ED). For the detection of ROS, group 1 received intraperitoneal injections of edaravone (3 mg/kg/day) for 2 days, group 2 received edaravone for 2 weeks, group 3 saline for 2 days, and group 4 saline for 2 weeks. ROS production by the organ of Corti and stria vascularis was examined by using dihydrotetramethylrosamine. For the morphological analysis, guinea pigs were divided into five groups, i.e. 2 or 4 weeks after ED obliteration, 2 weeks with edaravone, first or last 2 weeks with edaravone and sacrificed 4 weeks after ED obliteration. Increases in the ratios of the cross-sectional area of scala media were analysed quantitatively to assess the degree of endolymphatic hydrops among the above-mentioned five groups of the hydropic cochlea. RESULTS: ROS was detected both in the organ of Corti and in the lateral wall of cochleae 2 days after ED obliteration. Edaravone prevented the production of ROS and also attenuated the formation of endolymphatic hydrops in the acute hydrops group.     

Vestibular evoked myogenic potentials and distortion-product otoacoustic emissions combined with glycerol testing in endolymphatic hydrops: their value in early diagnosis

The present investigation was specifically designed to evaluate the ability of the glycerol test combined with pure tone audiometry, distortion-product otoacoustic emissions (DPOAEs), and vestibular evoked myogenic potentials (VEMPs) to diagnose endolymphatic hydrops early and to identify cases that may evolve toward Meniere's disease. This investigation consisted of 29 consecutive patients with mild dizziness or vertigo who received no treatment. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with both DPOAEs and VEMPs. It is interesting to note that in 7 and 8 of the 29 cases, the VEMPs and DPOAEs, respectively, showed an improvement after glycerol administration that had not been shown on traditional audiometry. A further element worthy of consideration emerges from an analysis of the VEMP results compared to the DPOAE results that divided the patients into 4 groups. The first group had a postglycerol improvement with both methods, which would seem to suggest hydrops in both the anterior and posterior parts of the labyrinth. In the second and third groups, there was an improvement only either with VEMPs or DPOAEs, and this finding seems to indicate that only one endolymphatic compartment might be involved. In the last group, all patients had a positive glycerol test with positive DPOAEs on one side and with positive VEMPs on the other. Although endolymphatic hydrops can only be proven after death, a combination of VEMPs and DPOAEs with the glycerol test may permit early diagnosis of endolymphatic hydrops. These results clearly imply that these methods should be permanently included in the diagnostic protocol of patients with vestibular and audiological symptoms.     

Postural control and glycerol test in Ménière's disease.

Ménière's disease is a clinical disorder, characterized by fluctuating hearing loss, recurrent spontaneous episodic vertigo, tinnitus and aural fullness, which may be defined as the idiopathic syndrome of endolymphatic hydrops. The most important test for diagnosis of Ménière's disease is the glycerol test. This is a simple and rapid method and several authors have confirmed its efficiency for identifying endolymphatic hydrops. This test provides information on the cochlear response to the osmotic changes produced by glycerol in the inner ear, whereas modifications in the vestibular labyrinth are usually not evaluated. The aim of this study was to evaluate the effects of glycerol on postural control during attacks of Ménière's disease, and to correlate this data with data on cochlear function. After the glycerol test, an improvement in postural control was recorded in 70% of patients, with all patients reporting a recovery of vertigo. The impairment of postural control during endolymphatic hydrops could be related to a pressure increase in the labyrinth, which interferes with the normal dynamics of the endolymph, and a rapid functional recovery could occur during an osmotic depletion. Dynamic posturography improves the sensitivity of the glycerol test and may therefore be useful in the diagnosis and staging of Ménière's disease.     

Clinical electrocochleography in Menière's disease

Transtympanic electrocochleography (ECochG) was performed on 137 definite Menière ears, 29 normal ears and 383 ears with other diseases. The average SP/AP amplitude ratio (SP/AP) was significantly larger than that of normal subjects in the following four disease groups whose causes are thought to be endolymphatic hydrops: 1) definite Menière's disease, 2) suspected Menière's disease, 3) delayed endolymphatic hydrops and 4) labyrinthine syphilis. The SP amplitude could not provide any information for a differential diagnosis of endolymphatic hydrops from normal subjects nor from other sensorineural deafness . The upper 99% confidence limit of normal SP/AP using a 100dBSPL click was 0.37 for 29 subjects. In patients with Menière's disease the relationship between SP/AP and clinical data such as pure tone threshold, audiogram pattern, results of glycerol test and duration of illness from the first vertiginous attack to the test were investigated. In patients with severe hearing loss, the number of those showing SP/AP of greater than 0.37 was much higher than in patients with less severe hearing loss. There were no relationship, however, between SP/AP and duration of illness, or audiogram pattern, or glycerol test. ECochG was recorded before and after intravenous administration of 50 gr of glycerol (10% solution, 500ml), and a significant decrease of SP/AP was found in 21 Menière ears. However, there were no change of SP/AP after oral administration of 50 gr of glycerol (50% solution, 100ml) and isosorbide (70% solution, 2.0gr/kg of body weight). After endolymphatic sac surgery a decrease of SP/AP of 10% or more was found in 5 ears, an increase of SP/AP in 3 ears, and no change of SP/AP in 3 ears. In the patients showing no change of SP/AP after the surgery, numerical values of vertigo by AAOHNS were higher than in patients showing an increase or a decrease of SP/AP. The results demonstrate the usefulness of ECochG in diagnosis of endolymphatic hydrops and indicate a possibility of monitoring the state of hydrops after administration of glycerol and endolymphatic sac surgery.     

Vestibular evoked myogenic potentials in ipsilateral delayed endolymphatic hydrops

We recorded vestibular evoked myogenic potentials (VEMPs) in 12 patients diagnosed as having ipsilateral delayed endolymphatic hydrops (DEH). Seventy-five percent (9/12) of the patients showed decreased or absent VEMPs in the affected ears. Almost all patients had normal VEMPs in the unaffected ears. In addition, in 4 patients, VEMPs were recorded before and 3 h after oral glycerol administration (1.3 g/kg body weight). VEMPs improved after glycerol administration in 2 of the 3 patients whose VEMPs had been abnormal in the affected ears before glycerol administration. None of the 4 patients presented significant changes in VEMPs in the unaffected ears after glycerol administration. Improvement of VEMPs after glycerol administration confirmed the existence of endolymphatic hydrops in patients with ipsilateral DEH. In conclusion, VEMPs are useful to evaluate the function of otolith organs in patients with ipsilateral DEH, and the glycerol test using VEMPs may be useful to detect endolymphatic hydrops in ipsilateral DEH.     

Postural Control and Glycerol Test in Me´nie`re's Disease

Ménière's disease is a clinical disorder, characterized by fluctuating hearing loss, recurrent spontaneous episodic vertigo, tinnitus and aural fullness, which may be defined as the idiopathic syndrome of endolymphatic hydrops. The most important test for diagnosis of Ménière's disease is the glycerol test. This is a simple and rapid method and several authors have confirmed its efficiency for identifying endolymphatic hydrops. This test provides information on the cochlear response to the osmotic changes produced by glycerol in the inner ear, whereas modifications in the vestibular labyrinth are usually not evaluated. The aim of this study was to evaluate the effects of glycerol on postural control during attacks of Ménière's disease, and to correlate this data with data on cochlear function. After the glycerol test, an improvement in postural control was recorded in 70% of patients, with all patients reporting a recovery of vertigo. The impairment of postural control during endolymphatic hydrops could be related to a pressure increase in the labyrinth, which interferes with the normal dynamics of the endolymph, and a rapid functional recovery could occur during an osmotic depletion. Dynamic posturography improves the sensitivity of the glycerol test and may therefore be useful in the diagnosis and staging of Me´nie &#164 re's disease.     

Auditory dehydration testing: glycerol versus urea

Auditory dehydration testing with oral hyperosmolar substances is commonly used in the evaluation of patients with suspected endolymphatic hydrops. Endolymphatic hydrops is assumed to be temporarily reduced in some cases, resulting in an improvement in hearing. Unfortunately, ingestion of glycerol, the most frequently used oral agent, often causes severe headache, vomiting, or both. Urea has recently been used as an alternative. A study of patients with Meniere's disease was designed to compare the effectiveness of glycerol versus urea in inducing a temporary improvement in hearing thresholds. Three hundred patients received either glycerol or urea. Fifty-seven percent of the glycerol patients had positive hearing results compared with 77% of the urea patients. Temporary hearing improvements following urea ingestion may not be caused by a rise in serum osmolality alone, since this occurs with glycerol but not with urea.     

Comparison between electrocochleography and glycerol test in the diagnosis of Meniere's disease

Electrocochleography (ECoG) and glycerol test were performed in 51 Meniere ears. The positive rate of both tests was compared. The positive rate of ECoG and glycerol test was 63% and 51%, respectively. The ears with positive result of both tests and of either test were 15 of 51 ears (29%) and 43 of 51 ears (84%), respectively. The positive rate of ECoG was higher in ears with a moderate to severe hearing loss at high frequencies, while the positive rate of glycerol test was higher in ears with a moderate to severe hearing loss at low frequencies. The present study has demonstrated that ECoG is different in selectivity of detection of the endolymphatic hydrops from glycerol test and that the combination of both tests increases the detection rate of the endolymphatic hydrops in Meniere's disease.     

Glycerol-induced changes in the cochlear responses of the guinea pig hydropic ear

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.     

Early diagnosis of endolymphatic hydrops with distortion. Product otoacoustic emissions

The present investigation was specifically designed to evaluate the ability of the glycerol test combined with pure-tone audiometry, distortion-product otoacoustic emissions (DPOAEs) to diagnose endolymphatic hydrops early and to identify patients who may evolve toward Meniere's disease. This investigation consisted of 43 consecutive patients with daily episodes of tinnitus with duration exceeding few hours or with continuous tinnitus who received no treatment. These were the unique symptoms reported by the patients. Each patient underwent glycerol testing measured with conventional pure tone audiometry and with distortion product otoacoustic emissions (DPOAEs). For the traditional pure-tone glycerol test a hearing improvement of at least 10 dB, at the lower two or three frequencies (125,250 and 500 Hz) was judged as positive result. For the DPOAEs glycerol testing, a smaller positive difference (5 dB) for at least three frequencies was interpreted as a significant fluctuation. Twenty four patients showed negative glycerol test both with pure tone audiometry and DPOAEs. In 7 cases the improvement was concurrently observed. In 9 patients post-glycerol changes appeared only in the DPOAEs outcomes. Finally the remaining three patients had two different patterns. Two had different ameliorations of the DPOAEs and pure-audiometry on the left and right sides respectively, and in the last one only post-glycerol, audiograms recovered. The present study re-confirms the potentiality of DPOAEs associated with glycerol test in diagnosing endolymphatic hydrops precociously. The possibility of these patients degenerating into Meniere's disease should not be underestimated.     

Otoadmittance changes following glycerol dehydration in Meniere's disease

Otoadmittance studies were undertaken in 76 patients with Meniere's disease and 8 control subjects undergoing glycerol dehydration. Baseline otoadmittance values were significantly higher in ears with fluctuant hydrops compared to the non-fluctuant ears (p less than 0.01), suggesting that there is a pathophysiological difference between these clinical Meniere's groups. Significant maximum conductance changes were seen in 53.4% of hydroptic ears, and were associated with subjective audiometric threshold shifts in 23.2%. Similar changes were not seen in the control ears. These findings provide further clinical evidence to support an underlying physical basis for the auditory symptoms of endolymphatic hydrops and the effects of glycerol dehydration on the inner ear. Objective otoadmittance changes appear to be a more sensitive indicator of reversible hydrops than conventional audiometry. Possible mechanisms to explain the somewhat paradoxical increase in the resistance to the flow of sound energy through the cochlea following reduction of the endolymphatic hydrops by glycerol dehydration are discussed.     

Triple semicircular canal occlusion in guinea pigs with endolymphatic hydrops.

HYPOTHESIS: Triple semicircular canal occlusion will eliminate rotatory stimulation to the vestibular peripheral system (as it blocks endolymphatic fluid movement) and therefore release rotatory vertigo attack. This surgery is safe in ears with endolymphatic hydrops. BACKGROUND: Semicircular canal occlusion has been used as an alternative treatment of intractable benign paroxysmal positional vertigo with varied success. Triple semicircular canal occlusion in animal models blocks the responses of the semicircular canals to rotation and spares cochleae and the otolithic apparatus. This result suggests that triple semicircular canal occlusion is a prospective method in vertigo management for patients with Ménière's disease. However, the effectiveness and safety of triple semicircular canal occlusion has not been fully evaluated in ears with endolymphatic hydrops. METHODS: Endolymphatic hydrops was established in 20 guinea pigs by endolymphatic sac obliteration. Triple semicircular canal occlusion was performed in 12 of them 120 days after endolymphatic hydrops surgery, whereas 8 others were killed for morphologic observation to confirm endolymphatic hydrops. Auditory and vestibular functions were monitored from the time before endolymphatic hydrops until 1 month after triple semicircular canal occlusion. Endolymphatic hydrops and canal occlusion were confirmed by morphologic observation. RESULTS: Successful establishment of endolymphatic hydrops was indicated by mild elevation of the auditory brainstem response threshold and tentative asymmetry in nystagmus. Endolymphatic hydrops was confirmed by cochlear morphology in all eight animals that were killed 120 days after endolymphatic hydrops surgery. After triple semicircular canal occlusion, all 12 animals showed spontaneous nystagmus with a slow component toward the side that had been operated on, head tilt, rotated walking, and tentative asymmetry in rotatory nystagmus. The static symptoms disappeared within 1 month after triple semicircular canal occlusion. Caloric nystagmus was only slightly reduced after endolymphatic hydrops as compared with the contralateral ears but could not be elicited at all after triple semicircular canal occlusion. No significant elevation in auditory brainstem response threshold was found after triple semicircular canal occlusion. The canal occlusion and endolymphatic hydrops were confirmed in all surgical ears. CONCLUSION: Triple semicircular canal occlusion is effective for eliminating the response of semicircular canals to rotation and caloric stimulation and is safe in ears with endolymphatic hydrops. Also, the static compensation to the disequilibrium is quick and complete. These results suggest that triple semicircular canal occlusion should be an option for controlling rotatory vertigo in Ménière's disease.     

Clinical study of elderly patients with Meniere's and related diseases

In order to study the characteristics of elderly patients (70 or over at onset) with endolymphatic hydrops disorders, we selected six patients with Meniere's disease (MD), five patients with delayed endolymphatic hydrops (DEH), and two patients with syphilis of the labyrinth (SL) from 7112 patients who had visited the Neurotological Clinic of the Toyama Medical and Pharmaceutical University Hospital during 1979-1998. Clinical features were characterized as follows: (1) Since 1990, the proportion of elderly patients increased as lifespans lengthened. (2) A narrow fluctuation in hearing, low positive rate on glycerol test, high positive rate of dominant-SP in EcochG, and the moderate abnormal rate of the oculomotor system tests were found. (3) The prognosis was relatively good. From these neurotological observations, it could be concluded that elderly patients with endolymphatic hydrops disorders were characterized by the multipathological finding of the endolymphatic hydrops and the complications of CNS disorders.     

Glycerol-induced changes in the cochlear responses of the guinea pig hydropic ear

Summary 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.     

Endolymphatic hydrops precipitated by haemodialysis

We report a case of endolymphatic hydrops preceded by haemodialysis in the contralateral ear of a patient with known Menière's disease, and discuss the possible mechanism. It is suggested that the sudden decrease of plasma osmolality during haemodialysis acts as a reverse glycerol test. The audiometric and electrophysiological recordings pre- and post-dialysis and the induction of the Menière's triad of symptoms during dialysis, were strongly indicative of the presence of endolymphatic hydrops.     

Endolymphatic hydrops in asymptomatic ears in unilateral Ménière's disease

OBJECTIVES/HYPOTHESIS: The aim of our study was the objective assessment of endolymphatic hydrops in asymptomatic ears in unilateral Ménière's disease with a noninvasive electrophysiological test and investigation of significant clinical signs. The null hypothesis was that there would be no signs of endolymphatic hydrops in the asymptomatic ear. STUDY DESIGN: Prospective study using the traveling wave velocity test for endolymphatic hydrops. METHODS: The traveling wave velocity test was used in conjunction with standard audiological tests to investigate both ears of 181 Ménière's patients attending the Medical Research Council Institute of Hearing Research in Southampton, United Kingdom. The test uses derived auditory brainstem responses to estimate the velocity of the cochlear traveling wave that is altered in endolymphatic hydrops. Ménière's disease was assessed using Arenberg's five staging criteria. Significant correlations were evaluated using standard statistical methods. RESULTS: Of 100 patients with clinically unilateral Ménière's disease, 27% showed evidence of endolymphatic hydrops in their asymptomatic ear. There was a significant correlation between signs of hydrops and the mean air-conduction threshold at 500 Hz. CONCLUSIONS: We recommend that a full assessment of incipient disease in the asymptomatic ear in unilateral Ménière's disease should be undertaken before offering any treatment options to patients. Any suspicion of early disease in the asymptomatic ear in unilateral Ménière's disease should lead to full electrophysiological assessment to assess the evidence of endolymphatic hydrops in that ear.