Changes in the Neurovascular Unit in Meniere's Disease.

ObjectivesTo analyze and summarize the clinical features and image characteristics of Meniere's Disease (MD) patients with Endolymphatic Hydrops (EH) confirmed by enhanced Magnetic Resonance Imaging (MRI). Methods252 MD patients with EH confirmed by MRI were enrolled. All patients met the diagnostic criteria for MD and underwent intravenous gadolinium injection. After 4 h, MR examinations were performed. The Nakashima grading standard was used to classify EH and evaluate its correlation with clinical features. ResultsDifferent degrees of EH were shown in all MD patients, and 157 of the 252 (62.3%) patients showed significant EH, 95 of the 252 (37.7%) patients showed mild EH. Only 89 (35.3%) met the diagnostic criteria for definite MD, and the remaining 163 (64.7%) patients met the diagnostic criteria for probable MD. Compared with patients with unilateral EH, the symptoms of the first affected ear of patients with bilateral EH were more serious. The degree of EH was related to the degree of hearing loss (p < 0.05). ConclusionMRI with intravenous gadolinium injection can provide a better assessment of EH in MD patients. The clinical features of MD patients with EH confirmed by enhanced MRI did not fully meet the existing diagnostic criteria for definite MD. Including the diagnosis of EH in the diagnostic criteria of MD can increase the diagnosis rate of MD. The degree and distribution of EH may be related to the degree of hearing loss. Level of evidence4.

Ménière's disease (MD) is characterized by the triad of fluctuating hearing loss, episodic vertigo and tinnitus, and by endolymphatic hydrops found on post-mortem examination. Increasing evidence suggests that oxidative stress is involved in the development of endolymphatic hydrops and that cellular damage and apoptotic cell death might contribute to the sensorineural hearing loss found in later stages of MD. While excess reactive oxygen species (ROS) are toxic, regulated ROS, however, play an important role in cellular signaling. The ability of a cell to counteract stressful conditions, known as cellular stress response, requires the activation of pro-survival pathways and the production of molecules with anti-oxidant, anti-apoptotic or pro-apoptotic activities. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include heat shock proteins (Hsps) as well as the thioredoxin/thioredoxin reductase system. In this study we tested the hypothesis that in MD patients measurable increases in markers of cellular stress response and oxidative stress in peripheral blood are present. This study also explores the hypothesis that changes in the redox status of glutathione, the major endogenous antioxidant, associated with abnormal expression and activity of carbonic anhydrase can contribute to increase oxidative stress and to disruption of systemic redox homeostasis which can be associated to possible alterations on vulnerable neurons such as spiral ganglion neurons and consequent cellular degeneration. We therefore evaluated systemic oxidative stress and cellular stress response in patients suffering from Meniere's disease (MD) and in age-matched healthy subjects. Systemic oxidative stress was estimated by measuring protein oxidation, such as protein carbonyls (PC) and 4-hydroxynonenal (HNE) in lymphocytes of MD patients, as well as ultraweak luminescence (UCL) as end-stable products of lipid oxidation in MD plasma and lymphocytes, as compared to age-matched controls, whereas heat shock proteins Hsp70 and thioredoxin (Trx) expression were measured in lymphocytes to evaluate the systemic cellular stress response. Increased levels of PC (P < 0.01) and HNE (P < 0.05) have been found in lymphocytes from MD patients with respect to control group. This was paralleled by a significant induction of Hsp70, and a decreased expression of Trx (P < 0.01), whereas a significant decrease in both plasma and lymphocyte ratio reduced glutathione GSH) vs. oxidized glutathione (GSSG) (P < 0.05) were also observed. In conclusion, patients affected by MD are under condition of systemic oxidative stress and the induction of vitagenes Hsp70 is a maintained response in counteracting the intracellular pro-oxidant status generated by decreased content of GSH as well as expression of Trx. The search for novel and more potent inducers of vitagenes will facilitate the development of pharmacological strategies to increase the intrinsic capacity of vulnerable ganglion cells to maximize antidegenerative mechanisms, such as stress response and thus cytoprotection.

P 74 Endolymphatic hydrops of the inner ear in patients with vestibular migraine and concurrent Meniere's disease – VOLT algorithm extension

Relationship between vestibular schwannoma and endolymphatic hydrops

Menière's disease (MD) is associated with endolymphatic hydrops (EH), which is an accumulation of excessive endolymphatic fluid in the inner ear. However, using temporal bone CT, lower visualization rates of the vestibular aqueduct (VA) in these patients have also been reported. In this retrospective single-center imaging study, we have included 25 healthy subjects and 47 patients having a definite, probable, or possible clinical diagnosis of MD that underwent temporal bone CT and inner ear MRI performed 4 h after contrast media administration. Two radiologists independently ranked the morphology of the VA in healthy subjects and in MD patients, using a three-level score (completely visible, discontinuous, and not visible). Each subject was then graded, based on both the VA's appearance and on EH presence. In healthy subjects, the VA was normal (grade 0) in 22/25 (88%) ears and discontinuous (grade I) in 3 healthy ears (12%). In the symptomatic ears of MD patients, we found 17/56 ears (30.3%) with VA grade 0, 15/56 ears (26.8%) with grade I, and 24/56 ears (42.8%) with grade II (p < 0.001). In MD patients, EH was observed in 46/94 ears (48.9%). A VA of grade 0 would eliminate the presence of EH with a negative predictive value of 88.6%, while a VA grade II would predict the presence of saccular hydrops with a positive predictive value of 93.1%. The evaluation by temporal bone CT of the VA can predict the presence of EH on MRI with a high positive predictive value. • The evaluation by temporal bone CT of the vestibular aqueduct can predict the presence of EH on MRI. • A vestibular aqueduct of grade 0 would eliminate the presence of EH on MRI with a negative predictive value of 88.6%. • A vestibular aqueduct grade II would predict the presence of endolymphatic hydrops on MRI with a positive predictive value of 93.1%.

Analysis of human temporal bone specimens of patients with Menière's disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens. MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD. Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN). Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52, p = 0.011), OC (14.93 vs 29.16, p = 0.014), and SGN (7.69 vs 18.85, p = 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88, p = 0.049) and CLU (7.80 vs 17.51, p = 0.0051) expression was significantly reduced in the SGN. The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.

The aims of the present study are to investigate the variations in clinical features, including medical history, hearing function, vestibular function, and degree of endolymphatic hydrops (EH), in Meniere's disease (MD) patients with and without drop attacks (DAs), and to examine the efficacy of intratympanic gentamicin (ITG) treatment in alleviating DAs. In total, 177 unilateral definite MD patients, including 16 patients with DAs and 161 patients without DAs, were enrolled. The results of hearing test, vestibular-evoked myogenic potentials (VEMPs), and magnetic resonance imaging (MRI) were analyzed. Thirteen patients with DAs received a single ITG treatment and were followed up. The disease course of MD in the DA group was significantly longer than that in the control group (p = 0.007). MD patients with DAs had significantly greater hearing loss and worse EH than MD patients without DAs (p < 0.05). However, there was no between-group difference in vestibular function. In the study, 92.31% of refractory definite MD patients with DAs achieved satisfactory control of DAs after ITG treatment. MD patients with DAs tend to suffer from severe hearing loss and a significant degree of EH in the inner ear. However, the vestibular function of MD patients with DAs may not be completely abolished, but be sensitive to stimulating signals. ITG treatment, which helps to decrease vestibular sensitivity, was an effective treatment to control DAs.

Objective: Intravenous contrast agent enhanced, high-resolution magnetic resonance imaging of the inner ear (iMRI) confirmed that patients with Menière's disease (MD) and vestibular migraine (VM) could present with endolymphatic hydrops (EH). The present study aimed to investigate EH characteristics and their interrelation to neurotologic testing in patients with VM, MD, or VM with concurrent MD (VM-MD).Methods: Sixty–two patients (45 females, aged 23–81 years) with definite or probable VM (n = 25, 19 definite), MD (n = 29, 17 definite), or showing characteristics of both diseases (n = 8) were included in this study. Diagnostic workup included neurotologic assessments including video-oculography (VOG) during caloric stimulation and head-impulse test (HIT), ocular and cervical vestibular evoked myogenic potentials (o/cVEMP), pure tone audiometry (PTA), as well as iMRI. EH's degree was assessed visually and via volumetric quantification using a probabilistic atlas-based segmentation of the bony labyrinth and volumetric local thresholding (VOLT).Results: Although a relevant number of VM patients reported varying auditory symptoms (13 of 25, 52.0%), EH in VM was only observed twice. In contrast, EH in VM-MD was prevalent (2/8, 25%) and in MD frequent [23/29, 79.3%; χ2(2) = 29.1, p < 0.001, φ = 0.7]. Location and laterality of EH and neurophysiological testing classifications were highly associated (Fisher exact test, p < 0.005). In MD, visual semi-quantitative grading and volumetric quantification correlated highly to each other (rS = 0.8, p < 0.005, two-sided) and to side differences in VOG during caloric irrigation (vestibular EH ipsilateral: rS = 0.6, p < 0.05, two-sided). In VM, correlations were less pronounced. VM-MD assumed an intermediate position between VM and MD.Conclusion: Cochlear and vestibular hydrops can occur in MD and VM patients with auditory symptoms; this suggests inner ear damage irrespective of the diagnosis of MD or VM. The EH grades often correlated with auditory symptoms such as hearing impairment and tinnitus. Further research is required to uncover whether migraine is one causative factor of EH or whether EH in VM patients with auditory symptoms suggests an additional pathology due to MD.

ObjectivesFew studies have addressed the benefits of cochlear implantation for the small group of patients with bilateral, end-stage Meniere's disease, or unilateral disease with contralateral hearing loss from another cause. Our retrospective study evaluates the effectiveness and post-operative performance in these Meniere's disease patients and discusses these findings relative to other post-lingually deafened adults.MethodsAmong 456 adults who received cochlear implants, we identified eight (1.7%) patients with Meniere's disease who met clinical indications for implantation and a control group of seven non-Meniere's patients of comparable age and deafness. Data gathered included demographics, auditory and vestibular symptoms pre-implantation, and clinical course after implantation, including audiometric scores (consonant-nucleus-consonant (CNC), hearing-in-noise testing (HINT), and AzBio score) and audiologic evaluations.ResultsComparing the Meniere's and non-Meniere's patients, pre- to post-implant scores averaged 15 and 16%–57 and 76% for CNC; and 4.5 and 40.5%–78 and 81% for AzBio and/or HINT tests, respectively; scores between groups did not statistically differ. Of note, five of eight patients had 0% word recognition scores pre-operatively. Fluctuations in CI performance were seen in five patients with Meniere's disease but not for those without the disease.ConclusionsAudiologic testing found a strong likelihood that CIs did benefit our subset of Meniere's patients with severe to profound sensorineural hearing loss. Fluctuations in hearing sensitivity (perhaps owing to physical changes relative to the implant array with the spiral ganglion neurons during an acute attack or changes in spiral ganglion neurons because of the hydropic state) can often be resolved by subsequent reprogramming.

Introduction Degenerative changes in the otolithic organs have been theorized to be caused by the mechanical obstruction to endolymphatic flow, possibly resulting in endolymphatic hydrops (ELH). Otolin-1 is an otoconial matrix protein that crosses the blood labyrinth barrier and has been found in the serum of healthy and diseased patients. Objective To measure the serum levels of Otolin-1 in Meniere disease (MD) patients and compared them with the healthy individuals. Methods This pilot, cross-sectional study was performed at our tertiary care referral center to compare the serum Otolin-1 levels of healthy individuals with those of MD patients. The blood samples were obtained during patients' visit to the vertigo clinic following remission of an acute episode. The data was analyzed using the Stata/SE version 12.0 (StataCorp. College Station, TX, USA). Comparison between the serum Otolin-1 levels in the two groups was performed using the unpaired t -test. A p -value of 0.05 was considered to be statistically significant. Results The participants were divided into two groups, with 31 MD patients, and 30 age and gender-matched members of the control group. The serum levels of Otolin-1 in MD patients (247.6, ± 44.2 pg/ml) were not found to be significantly different from those of the control group (236.2, ± 43.5 pg/ml) ( p = 0.31). Conclusion The current study reveals that the serum levels of Otolin-1 are not significantly different between the patients with MD in the interictal phase and the control group's healthy ones.

Meniere's disease (MD) patients can show normal head impulses despite poor caloric test results. This study aimed to investigate the discrepancy in the vestibulo-ocular reflex (VOR) in MD patients and whether endolymphatic hydrops (EH) influence the VOR. Prospective, cross-sectional observational study. Ninety MD patients were enrolled. Neuro-otological testing, including a video head impulse test (vHIT) of all semicircular canals (SCs), and gadolinium-enhanced inner ear magnetic resonance imaging were performed. The vestibular EH volume was quantitatively evaluated by processing magnetic resonance images. Abnormal vHIT results in MD patients were found most frequently in the posterior (44.4%) SCs, followed by the horizontal (13.3%) and anterior (10%) SCs. Canal paresis (CP) was assessed using the vHIT and the caloric test, and results were not significant when vHIT responses were assessed as CP only using the horizontal SC. The difference in the vestibular EH between the presence and absence of CP was not significant if assessed using the vHIT (P = .5591), but it was statistically different if assessed using the caloric test (P = .0467). The contradictory reaction of VOR in MD patients may result from the high specificity but low sensitivity of CP in the horizontal vHIT. EH volume in the vestibule affects the caloric response but does not affect the vHIT response. 2b Laryngoscope, 129:1660-1666, 2019.

The aim of this study was to assess the rate of endolymphatic hydrops (EH) on MRI and the rate of otolithic dysfunction with cVEMP and oVEMP, in patients with recurrent vertigo such as Menière's disease (MD), vestibular migraine (VM) and vestibular Menière's disease (vMD). In this retrospective study, we performed 3D-FLAIR sequences with delayed acquisition in 20 MD, 20 VM and 20 vMD patients. Each subject was then assessed for the presence of EH on MRI. All patients underwent pure-tone audiometry, cVEMP and oVEMP. In MD patients, EH was observed in 18 (90%) out of 20 patients while EH was observed in only 1 MV (5%) and 1 vMD (5%) patients. We found significant differences between groups for the presence of EH on MRI (p = 0.001). MD patients had significant higher PTA level (p < 0.001) and oVEMP impairment than MV and vMD (p = 0.08 and p = 0.06, respectively). However, no significant differences were observed for cVEMP impairment, either asymmetric ratio (p = 0.36) and 1000/500 ratio (p = 0.20). Concerning cVEMP, we observed no significant differences between VM, vMD and MD. However, we observed higher oVEMP impairment, PTA level and EH on MRI in MD patients. We believe that MRI could be used to differentiate MD from VM patients with cochlear symptoms. However, in cases of migraine associated with recurrent vertigo and without cochlear symptoms, we believe that MRI is not a useful tool to differentiate between VM and vMD.

Background Patients with Meniere’s disease (MD) receive treatment to reduce vertigo. Purpose To explore the fluctuation of vertigo symptoms and the changes in endolymphatic hydrops (EHs) in MD patients during long-term regular medication. Materials and methods We enrolled MD patients who had received two magnetic resonance imaging with intravenous contrast agents. Results Of the 42 patients in the study, 18(42.9%) had progressive EHs and 3(7.1%) had remission. The change value of the signal intensity ratio (SIR; cochlear perilymph/cerebellum) on the affected side (1.2) was larger than that on the healthy side (0.9), but there was no statistical difference. Among the 30 patients followed up, two patients had complete control of vertigo, two patients had substantial control, and three patients had worse control. The other 23 patients had insignificant control of vertigo symptoms before and after treatment. The correlation between the progression of cochlear and vestibular hydrops and the improvement of vertigo symptoms in MD patients was not significant. Conclusions and significance In treated patients with MD, EHs may progress or relieve over the long course of the disease. But there was no correlation between the development of EHs and changes in vertigo symptoms.

The exact pathomechanism of deafening in Meniere's disease (MD) is still unknown; intoxication of hair cells and neural damage from endolymphatic hydrops is discussed. In the literature, there are only a few reports on hearing outcome of MD patients after treatment with cochlear implantation (CI) whereby especially the comparison of MD vs. non-MD patients with CI differs. In this retrospective study, results in speech understanding [Freiburger Einsilber (FES65) and Hochmair-Schulz-Moser test in quiet (HSM) and in noise (HSM+10dB)] of 27 implanted MD patients were collected and compared to a matched standard CI cohort. Alternative diagnoses were excluded as far as possible by re-analyzing neuroradiologic imaging. After first fitting, MD patients showed significantly better results in FES and HSM testing compared to controls. At 1-year refitting, this effect could not be seen anymore. To conclude, cochlear implantation is a safe and effective treatment for deafness in MD patients. Results in speech understanding are at least equal compared to general CI recipients. To the best of our knowledge, this retrospective study examined the largest collective of CI users deafened by MD so far.

Aminoglycoside-Induced Degeneration of Adult Spiral Ganglion Neurons Involves Differential Modulation of Tyrosine Kinase B and p75 Neurotrophin Receptor Signaling