Degree Of Endolymphatic Hydrops Research Articles

Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of autoimmune sensorineural hearing loss in a guinea pig model.

Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

Peak Width in Multifrequency Tympanometry and Endolymphatic Hydrops Revealed by Magnetic Resonance Imaging

To investigate the relationship between the peak width of the characteristic "M"-shaped peak of 2 kHz conductance tympanometry and the degree of endolymphatic hydrops in magnetic resonance imaging (MRI) after intratympanic or intravenous gadolinium administration. Prospective study. An academic university hospital. One hundred twenty-eight ears in which multifrequency tympanometry was performed and endolymphatic space size was evaluated by MRI. Forty-five patients were examined bilaterally and 38 patients were examined unilaterally. Endolymphatic space size was evaluated by MRI after intratympanic or intravenous gadolinium injection. Endolymphatic space size was classified into three groups: none, mild, and significant in the cochlea and in the vestibule. The relationship between the degree of endolymphatic hydrops and peak width of 2 kHz conductance tympanometry was investigated. The peak width in 94 ears in which significant endolymphatic hydrops was observed on MRI in the cochlea and/or the vestibule was 178.8 ± 102.7 daPa. The peak width in 21 ears in which mild but not significant endolymphatic hydrops was observed on MRI in the cochlea and/or the vestibule was 126.0 ± 77.1 daPa. The peak width in 13 ears with no endolymphatic hydrops in the cochlea and vestibule was 107.1 ± 84.1 daPa. The peak width in ears with significant endolymphatic hydrops was larger than that observed in ears with no endolymphatic hydrops. However, the peak width was not significantly different between cases of mild and absent endolymphatic hydrops. Large peak width in multifrequency tympanometry was associated with significant endolymphatic hydrops.

In Vivo Visualized Endolymphatic Hydrops and Inner Ear Functions in Patients With Electrocochleographically Confirmed Ménière’s Disease

To study the correlation between the degree of endolymphatic hydrops as detected in vivo by magnetic resonance (MR) imaging and the auditory and vestibular function in patients with definite Ménière's disease. Prospective observational study. Tertiary referral center for balance disorders. In this prospective study, 41 patients who fulfilled the criteria for definite unilateral Ménière's disease according to the American Association of Otolaryngology-Head and Neck Surgery and who showed a summating potential-to-action potential ratio of greater than 0.4 on electrocochleography were included. Intratympanic contrast-enhanced 3 Tesla MR imaging of the inner ear was performed using a 3D Inversion Recovery Turbo Spin Echo sequence. The degree of endolymphatic hydrops was graded on a Likert scale (0-3) in the cochlea and by vestibular endolymph space ratio in the vestibulum. The degree of hydrops was then analyzed with respect to its correlation with audiometric hearing levels, interaural amplitude ratios of vestibular evoked myogenic potentials, degree of horizontal semicircular canal paresis on caloric irrigation, and disease duration. The degree of hearing loss and the disease duration correlated significantly with cochlear hydrops (r = 0.85; r = 0.34). Sacculus dysfunction was significantly correlated with vestibular hydrops (r = -0.47). There was no significant correlation between horizontal semicircular canal paresis and vestibular hydrops. In patients with clinically and electrocochleographically confirmed definite Ménière's disease, the degree of MR morphological hydrops severity correlates significantly with impairment of hearing function and sacculus function.

Effect of standard-dose Betahistine on endolymphatic hydrops: an MRI pilot study

This study aimed to assess whether standard-dose Betahistine (48 mg daily) exerts an effect upon the degree of endolymphatic hydrops in patients with Menière's disease using a retrospective case series in the setting of a tertiary neurotology referral centre. In six patients with definite unilateral Menière's disease, the degree of cochlear and vestibular endolymphatic hydrops was assessed before and after treatment with a standard dose of Betahistine (48 mg daily), using high-resolution 3 T MR imaging after intratympanic contrast medium application. The treatment duration was 3-7 months (mean 5 months), and the patients were followed-up for 6-29 months (mean 11 months). In the study cohort, the standard dose of Betahistine did not have an MR morphologically measurable beneficial effect on the degree of endolymphatic hydrops. The results indicated no effect of standard-dose Betahistine on endolymphatic hydrops found on high-resolution MR imaging. Possible explanations are: (1) insufficient dosage or duration of treatment with betahistine, (2) insufficient resolution of the MR imaging technique, and (3) insufficient length of follow-up. Further studies addressing these issues are warranted.

Association Between Endolymphatic Hydrops as Revealed by Magnetic Resonance Imaging and Caloric Response

To investigate the association between the degree of endolymphatic hydrops (EH) revealed by magnetic resonance imaging (MRI) and a caloric response in the ear. Prospective diagnostic study. University hospital. Twenty-four patients with hearing loss and/or vertigo, who underwent MRI 1 day after an intratympanic gadolinium injection. MRI after intratympanic gadolinium injection and caloric testing with cool air stimulation (15°C, 6 l/min, 60 s). Association between the degree of EH and caloric responses. The degree of EH in the vestibule, in the cochlea, and in the ampulla of the lateral semicircular canal (LSC) was evaluated using MRI. The ratio of the diameter of the endolymphatic space to the diameter of the perilymphatic space was measured in the LSC ampulla. Canal paresis (CP, >25%) was present in 15 patients and absent (CP, <25%) in 9 patients. There was no significant difference between caloric response and the degree of EH in the vestibule, the cochlea, or the LSC ampulla. The period between the onset of clinical symptoms and examination tended to be longer in the group with CP compared with the group without CP. There was no significant association between the degree of EH and caloric response.

Progression of Endolymphatic Hydrops in Ménière's Disease as Evaluated by Magnetic Resonance Imaging

To evaluate the presence and the degree of endolymphatic hydrops (EHs) in patients with unilateral Ménière's disease (MD), as a function of duration of the disease, estimated using a 3-dimensional fluid-attenuated inversion recovery sequence in a 3-Tesla magnetic resonance imaging unit, after intratympanic gadolinium administration. A total of 32 patients (21 male and 11 female subjects, aged 25-78 yr; median, 56 yr) participated in the investigation. The duration of the disease ranged from 2 months to 10 years (median, 3 yr), with a prevalence of vertigo spells in the last 6 months ranging from 0.5 to 8 per month (median, 2.5). A 0.6-ml solution of gadobutrol (1 mmol/ml) diluted 1:7 in saline was injected in the affected ear through the inferior-posterior quadrant of the tympanic membrane, using a 22-gauge spinal needle. The patient was kept with the head rotated 45 degrees contralaterally for 30 minutes after each injection. Twenty-four hours later, a 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging was performed. Perilymphatic enhancement was evaluated in different portions of the labyrinth as a function of MD duration. Reduced or absence of enhancement of the vestibule occurred precociously and occurred in all subjects at long term. The prevalence of enhancement abnormalities in the cochlea and the semicircular canals was directly proportional to MD duration. At long term, the vestibule and the cochlea showed a more severe hydropic involvement compared with semicircular canals. A statistical significant correlation between enhancement abnormalities and MD duration was observed for most inner ear sites. The increased prevalence and severity of EH with the duration of MD indicates that hydrops is a progressive degenerative phenomenon. The frequent abnormality in the vestibule and, secondarily, in the cochlea is in line with some histopathologic investigations. It remains to be clarified whether hydropic changes are related to specific signs and symptoms of MD.

In vivo visualization of endolyphatic hydrops in patients with Meniere’s disease: correlation with audiovestibular function

Our objective is to determine whether the degree of endolymphatic hydrops as it is detected in vivo in patients with definite Meniere's disease correlates with audiovestibular function. In this prospective study, 37 patients with definite Meniere's disease according to AAO-HNS criteria were included. Intratympanic contrast enhanced temporal bone MRI was performed using a 3D FLAIR protocol. The degree of endolymphatic hydrops in the cochlea and the vestibulum was graded on a Likert scale (0-3). The degree of hydrops was then analyzed with respect to its correlation with audiometric hearing levels, electrocochleographic SP/AP ratios, interaural amplitude ratios of vestibular evoked myogenic potentials and degree of horizontal semicircular canal paresis on caloric irrigation. There was a significant correlation between the degree of hydrops on the one hand and the averaged hearing level at 0.25-1 and 0.5-3kHz and the vestibular evoked myogenic potential interaural amplitude ratio on the other hand. A trend toward a correlation was noticed between the hydrops and the caloric response, no correlation was noticed between the hydrops and the SP/AP ratio. The degree of endolymphatic hydrops correlates with a progressive loss of auditory and sacculus function in patients with Meniere`s disease.

Image diagnosis of endolymphatic hydrops with MRI

The first visualization of endolymphatic hydrops in patients with Ménière's disease was performed using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) imaging with a 3 Tesla MRI unit after gadolinium contrast agent (Gd) was injected intratympanically. The 3D-FLAIR MRI could differentiate the endolymphatic space from the perilymphatic space, but not from the surrounding bone. By optimizing the inversion time, the endolymphatic space, perilymphatic space and surrounding bone could be separately visualized on a single image using three-dimensional real inversion recovery (3D-real IR) MRI. Using 3D-FLAIR and 3D-real IR MRI, various degrees of endolymphatic hydrops were observed in the basal and upper turns of the cochlea and in the vestibular apparatus after intratympanic Gd injection. Recently, visualization of endolymphatic hydrops became possible 4 h after intravenous Gd injection in patients with Ménière's disease. We applied a heavily T(2)—weighted 3D-FLAIR technique to detect Gd more sensitively for evaluation of endolymphatic hydrops after an ordinary amount of Gd was administered intravenously. Thus, newly developed MRI techniques have contributed significantly to the evaluation of endolymphatic hydrops. The intravenous administration of an ordinary amount of Gd is routinely done clinically. The relationship between endolymphatic hydrops and clinical symptoms will be investigated widely using new techniques.

Relationship between endolymphatic hydrops and vestibular-evoked myogenic potential

Conclusion: Vestibular-evoked myogenic potential (VEMP) can be used to examine endolymphatic hydrops, especially in the vestibule. Objective: To investigate the relationship between the degree of endolymphatic hydrops revealed by magnetic resonance imaging (MRI) and VEMP. Methods: Gadolinium diluted with saline was injected intratympanically in 49 ears (40 patients). One day after the injection, the endolymphatic space in the vestibule and the cochlea was visualized by 3 Tesla MRI. A VEMP test was done, and VEMP was judged as absent when the VEMP was within the noise level. Results: VEMP was present in 21 ears and absent in 28 ears. Endolymphatic hydrops was significantly associated with the disappearance of VEMP. Endolymphatic hydrops in the vestibule had a stronger effect than endolymphatic hydrops in the cochlea. Five patients with extremely large vestibular hydrops showed no response of VEMP.

Relationship between the Degree of Endolymphatic Hydrops and Electrocochleography

The purpose of this study was to evaluate the relationship between the endolymphatic space image obtained using magnetic resonance imaging (MRI) and the results of electrocochleography. Electrocochleography recordings were obtained from 25 ears of 24 patients, who underwent MRI 1 day after the intratympanic injection of gadolinium diethylenetriamine pentaacetic acid bismethylamide. The average summating potential to action potential (SP/AP) ratio in patients with significant endolymphatic hydrops in the cochlea was 54 ± 17%. However, in some patients who had significant endolymphatic hydrops in the cochlea, the SP/AP ratio was not enlarged. This may imply that elevation of the SP/AP ratio is related to not only the degree of endolymphatic hydrops but also to the persistence of hydrops.

Clinical significance of endolymphatic imaging after intratympanic gadolinium injection

Conclusion: Using three-dimensional real inversion recovery (3D-real IR) and three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI), various degrees of endolymphatic hydrops were observed in the basal and upper turns of the cochlea and in the vestibular apparatus after intratympanic gadolinium (Gd) injection. MRI may contribute to our understanding of inner ear diseases and may be a useful addition to intratympanic drug therapy in the management of inner ear diseases. Objective: To evaluate 3D-real IR MRI and 3D-FLAIR MRI with clinical symptoms and signs in patients with inner ear disease. Patients and methods: Gd was diluted in saline and injected intratympanically in 73 patients with inner ear disease. The endolymphatic space was evaluated with 3-Tesla MRI at 1 day after the intratympanic Gd injection. Results: 3D-real IR MRI was generally better than 3D-FLAIR MRI in discriminating between the perilymphatic space and endolymphatic space in the cochlear turns and in the vestibular apparatus. However, when Gd concentration was insufficient in the perilymph, it was more difficult to visualize the Gd with 3D-real IR MRI than with 3D-FLAIR MRI. Endolymphatic hydrops was observed using MRI in patients with ‘probable’ Ménière's disease based on the criteria.

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.

Fixation-induced shrinkage of Reissner's membrane and its potential influence on the assessment of endolymph volume

The quantification of endolymph volume by histological techniques or by magnetic resonance (MR) microscopy requires the inner ear to be first treated with chemical fixatives. If the fixative induces soft-tissue shrinkage, it would tend to return a distended Reissner's membrane towards a straight position, since this membrane is anchored to bone at its medial and lateral edges. The goal of this study was to determine the degree of Reissner's membrane shrinkage induced by different fixation protocols to establish methods which minimize tissue shrinkage. Fragments of fresh Reissner's membrane were dissected from isolated cochleae in an artificial perilymph. Specimens were viewed with an inverted microscope during infusion of fixatives, and changes recorded on video tape. Size changes of the specimen were quantified, usually over a 20 min period. Heidenhain-Susa, a fixative which is widely used in histological studies of hydropic cochleae, caused substantial shrinkage of Reissner's membrane, decreasing the length of specimens by an average of 15.1%. Other fixation procedures induced far less shrinkage. The use of 3X/0 glutaraldehyde in Hanks' balanced salt solution produced a mean length decrease of only 0.3%. The inclusion in the fixation medium of 4.5`/0 mercuric chloride, corresponding to the concentration which is present in Heidenhain-Susa and which acts to increase the contrast of Reissner's membrane in MR microscopy, contributes significantly to specimen shrinkage. We can conclude that the degree of endolymphatic hydrops may be underestimated in specimens fixed with media containing high levels of mercuric chloride.

Time course of endolymph volume increase in experimental hydrops measured in vivo with an ionic volume marker

A new method has been developed to measure the cross-sectional area (CSA) of scala media in the living cochlea. The method has some advantages over histological methods, in which tissues may shrink or move during processing. In the present study, scala media CSA was measured in the second turn of guinea-pig cochleas in which endolymphatic hydrops was induced surgically. The area measurement method used an iontophoretic injection of a volume marker into scala media, during which the concentration of marker in endolymph was monitored with an ion-selective microelectrode. The measured marker concentration was inversely proportional to the CSA of endolymph.The marker we used was the anion arsenic hexafluoride (AsF − 6), which was almost ideal for the purpose as it was retained well in endolymph. Area was measured in normal animals and in hydropic animals at times from 4 days to 16 weeks after endolymphatic duct obstruction. The results showed that hydrops develops within days of ablation of the endolymphatic duct. The degree of hydrops was compared with electrophysiological measures of function, including the endocochlear potential, action potential thresholds and the amplitudes of the cochlear microphonic, summating potential and action potentials. In the initial stages of hydrops development, electrophysiological changes were small. In contrast, there were marked functional changes between 8 and 16 weeks, when endolymph volume was no longer increasing. These data support earlier studies which have shown that dysfunction in the hydropic cochlea does not correlate directly with the degree of endolymphatic hydrops. If the same is true for dysfunction in the ears of patients with Ménière's Disease, then it may not be possible to restore normal function simply by alleviating the hydrops. Furthermore, if dysfunction depends on factors other than the degree of hydrops, it may be possible to alleviate symptoms in ways other than by directly reducing hydrops.

一側性内リンパ水腫モルモットの台形方式回転検査成績に関する研究

Obliteration of the right endolymphatic sac was performed by Kimura's method in 57 guinea pigs with normal hearing and vestibular function. However, 43 animals exhibited postoperative cerebellopontile disturbance and labyrinthitis detected by gait test, ABR test and histological examination. The remaining 14 guinea pigs were evaluated periodically by the trapezoid rotation test. Two weeks after the operation, 11 of these 14 guinea pigs exhibited prolonged right beating nystagmus based on the labyrinthine preponderance of impaired side (Lpi). In addition, endolymphatic hydrops was histological detected in the labyrinth on the operation side. A positive relation was observed between the degree of endolymphatic hydrops and the degree of Lpi. Lpi at 4 weeks after the operation was markedly lower than that at 2 weeks (P = 0.05). Therefore, the degree of Lpi was thought to be influenced by the rate of hydrops development. These results corresponded with the clinical findings that the degree of Lpi increases prior to vertiginous episodes in Meniere's patients.

The effect of kanamycin on experimentally induced endolymphatic hydrops.

In guinea pigs with endolymphatic hydrops 6 months after operation the DC potential had decreased from +80 mV to +50 mV, while the sodium activity had increased. The twofold increase in Na+ activity could explain the increased degree of endolymphatic hydrops. The K+ activity and Cl- activity were unchanged. However, endolymphatic hydrops could be produced in kanamycin-induced deaf guinea pigs after obliteration of the endolymphatic sac and duct. The physiological data on DC potential, K+, and Na+ activity were similar to those for non-treated animals. When the animals were treated with kanamycin 6 months after the development of endolymphatic hydrops, there was no effect on the morphological and functional changes compared to controls. The data suggest that regulation of the inner ear fluid occurs independent of an intact auditory system. The effect of aminoglycoside treatment in Ménière's disease cannot be explained by an effect on endolymphatic hydrops formation.

実験的内リンパ水しゅに関する研究 その発現ひん度ならびに形態学的変化と機能との関連について

Endolymphatic hydrops were tried to produce in 33 guinea pigs by obliteration of the endolymphatic sac, and the following three points were investigated.1) The incidence of the spontaneous nystagmus.2) The relationship between the time course and the degree of endolymphatic hydrops.3) The relationship between the caloric response to cold water stimuli and the degree of endolymphatic hydrops.The results were as follows:1) By this procedure, endolymphatic hydrops were produced in 24 out of 33 guinea pigs (72.7%). The spontaneous nystagmus was noticed in 3 cases. However these spontaneous nystagmus seemed to be originated from other pathological changes. Namely, two cases were accompanied with labyrinthitis and one was labyrinthine bleeding.2) Endolymphatic hydrops were more remarkable in the postoperatively prolonged cases.3) The cases which showed severe endolymphatic hydrops had tendency of decreased caloric response to cold water stimuli.Although the spontaneous nystagmus was not noticed in these model animals, morphologically and functionally these results were very similar to the findings of the patients with Meniere's disease.

Changes of the action potential, the summating potential and cochlear microphonics in experimental endolymphatic hydrops.

The changes of the action potential (AP), the summating potential (SP) and cochlear microphonics (CM) were investigated in reference to the grade of endolymphatic hydrops produced by endolymphatic sac obliteration in guinea pigs. In a few cases with minimum endolymphatic hydrops, super-normal AP was obtained. With an increase of endolymphatic hydrops, CM responses were reduced although AP responses at intensive stimulation were maintained relatively well. It is thought that the polarity of positive SP, as observed in control, was influenced to deflect towards negative SP by an interaction between the increased degree of endolymphatic hydrops and the changes of the biochemical components of the inner ear fluids.